FOOD AND DRUG ADMINISTRATION + + + + + MEDICAL DEVICES ADVISORY COMMITTEE + + + + + GENERAL AND PLASTIC SURGERY DEVICES PANEL + + + + + MEETING

+ + + + + Wednesday, March 1, 2000 + + + + +

The Gaithersburg Avenue,

meeting

was

held Two

in

the

Ballroom, Village Dr.

Holiday

Inn,

Montgomery at 8:00

Gaithersburg,

Maryland,

a.m.,

thomas V. Whalen, Chairman, presiding. PRESENT: THOMAS V. WHALEN, M.D.., Chairman JOSEPH V. BOYKIN, JR., M.D., Voting Member PHYLLIS CHANG, M.D., Voting Member KAREN Member NEAL R. GROSS
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BANDEEN-ROCHE,

Ph.D.,

Temporary

Voting

PRESENT (Continued): BRENT Member BOYD BURKHARDT, M.D., Temporary Voting Member NANCY A. DUBLER, LLB., Temporary Voting Member STEPHEN LI, Ph.D., Temporary Voting Member MICHAEL J. MORYKWAS, Ph.D., Temporary Voting Member JOHN S. ROBINSON, M.D., Temporary Voting Member MAXINE F. BRINKMAN, R.N., Consumer BLUMENSTEIN, Ph.D., Temporary Voting

Representative CINDY DOMECUS, Industry Representative DAVID KRAUSE, Ph.D., Executive Secretary

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C-O-N-T-E-N-T-S PAGE Conflict of Interest and Temporary Voting Member Deputization Statement................6 Introductions, Dr. Thomas Whalen .................10 FDA Modernization Act, Phil Phillips .............14 Welcoming Remarks, Stephen P. Rhodes .............27 Public Comment: Kristine Kitchen ...........................33 Patricia Faussett ..........................34 Dr. Kathleen A. Melez ......................41 Jennifer Gardner ...........................43 Dr. Tanya Aya Atagi ........................47 Dr. Norman Anderson ........................51 Dr. Fritz Barton ...........................59 Dr. Gwendolyn Lewis ........................62 Dr. Cheston M. Berlin, Jr. .................69 Melinda Cloud ..............................77 Dr. Howard W. Ory ..........................83 Patricia Brent, Accompanied by Catherine Brent ................................90 Ann Peterson Angus .........................96 Maura McGinn ..............................105 Karen Duhala ..............................111 Nicole Cummings ...........................120 Anne Lowder ...............................130 Lynda Roth ................................139 Lisa LaCivita .............................161 Susan Sherr ...............................164 Sybil Niden Goldrich ......................167 Cynthia Pearson ...........................180 Ron Hayton ................................193 Margaret S. Volpe .........................201 Anne Stansell .............................209 Dr. C. Lin Puckett ........................213 Elizabeth Mullen (via statement) ..........223 NEAL R. GROSS
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C-O-N-T-E-N-T-S (Continued) PAGE Public Comment (Continued): Dr. David B. Sarwer .......................237 Pierre Blais ..............................248 Diane Griffith ............................263 Dr. Anne S. Kasper.........................267 Carol Sherman .............................273 Regulation of Saline Filled Breast Prostheses, Dr. Celia Witten ..........................277 Considerations on Imaging Patients with Breast Implants, Dr. Wendie Berg .......................286 Mentor Corporation Presentation: Introduction, Anthony Gette ...............310 Preclinical Data, Bobby Purkait ...........314 Clinical Studies, Pamela L. Powell ........324 Clinical Safety, Bruce L. Cummingham ......328 Clinical Effectiveness, Rebecca Anderson . .350 Conclusion, Bobby Purkait .................361 FDA Presentation: Lead Review, Dr. David Berkowitz ..........428 Clinical Review, Dr. Sahar Dawisha ........433 Statistical Review, Phyllis Silverman . . . . .450 FDA Questions to Panel, David Berkowitz .........460 Panel Discussants: Mechanical Testing, Dr. Stephen Li ........463 Clinical, Dr. Boyd Burkhardt ..............492 Statistical, Dr. Brent Blumenstein ........504 Public Comment: Lale Goddard ..............................563 NEAL R. GROSS
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C-O-N-T-E-N-T-S (Continued) PAGE Public Comment (Continued): Rosmary A. Locke ..........................570 Dr. Diana Zuckerman .......................575 Jill McClure ..............................585 Sponsor Summation ...............................593

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P-R-O-C-E-E-D-I-N-G-S (8:06 a.m.) DR. KRAUSE: Good morning, everyone. I'd

like to get the meeting started, please. could please take a seat. Thank you.

If everyone

We're ready to begin the 56th meeting of the General and Plastic Surgery Devices Panel. My name

is David Krause, and I'm the Executive Secretary of the panel. I'm also a biologist and reviewer in the

Plastic and Reconstructive Surgery Devices Branch. I'd like to remind everyone that you're requested to please sign in on the attendance sheets, which are available at the tables by the door. You may

also pick up an agenda, a panel roster, and information about the meeting at that same table. The information includes about how to find out about future meetings of the panel and other

panels. Before turning the meeting over to Dr.

Whalen, I'm required to read two statements into the record: the deputization of temporary voting members NEAL R. GROSS
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statement and the conflict of interest statement. The first statement is the appointment to temporary voting status. Pursuant to the authority

granted under the Medical Devices Advisory Committee charter, dated October 27th, 1990, and as amended

August 18th, 1999, I appoint the following individuals as voting members of the General and Plastic Surgery Devices Panel for this meeting on March 1st, 2000: Karen Bandeen-Roche; Brent Blumenstein; Boyd Burkhardt; Nancy Dubler; Stephen Li; Michael Morykwas; and John Robinson. For the record, these individuals are

special government employees and consultants to this panel or other panels under the Medical Device Advisory Committee. They have undergone the customary conflict

of interest review and have reviewed the material to be considered at this meeting, and this is signed by Dr. David W. Feigal, Jr., the Director of Center for

NEAL R. GROSS
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Devices and Radiological Health. The following is the conflict of interest statement. The conflict of following issues announcement associated addresses with this

interest

meeting and is made a part of the record to preclude even the appearance of an impropriety. To determine if any conflict existed, the agency reviewed the submitted agenda and all financial interests reported by the committee participants. conflict of interest statutes prohibit The

special

government employees from participating in matters that could affect their or their employees' financial

interests. However, the agency has determined that

participation of certain members and consultants, the need for whose services outweighs the potential

conflict of interest involved, is in the best interest of the government. A waiver has been granted for Dr. Stephen Li and his interests in a firm at issue that could potentially be affected by the committee's

NEAL R. GROSS
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deliberations.

The waiver allows this individual to

participate fully in the panel's deliberations. A copy of his waiver may be obtained from the agency's Freedom of Information Office, Room 12A-15 of the Parklawn Building. We would like to know for the record that the agency took into consideration certain matters

regarding Drs. Burkhardt, Chang, Li, and Morykwas. Dr. Li reported a current interest in a firm at issue, but in matters not related to the

panel's agenda.

Therefore, the agency has determined

that he may participate fully in the deliberation. Drs. Burkhardt, Chang and Morykwas

reported past related involvements with firms at issue. Since these are past involvements and there are no continuing financial interests, the agency has

determined that these panelists may participate fully in the deliberations. The agency would also like to note for the record that Dr. Wendie Berg, who is making a

presentation today, has acknowledged a previous related financial interest with a firm at issue. NEAL R. GROSS
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Dr. Berg

serves

as

a

consultant

to

the

Radiological

Devices

Panel, as well as all panels of the Medical Advisory Committee. In the event that the discussions involve any other products or firms not already on the agenda for which an FDA participant has a financial interest, the participant should excuse him or herself from such involvement, and the exclusion will be noted for the record. With respect to all other participants, we ask in the interest of fairness that all persons making statements or presentations disclose any current or previous financial involvement with any firm whose

products they may wish to comment upon. Okay. This concludes the required

statements, and I would like now to turn this meeting over to Dr. Whalen, the Chair. CHAIRMAN WHALEN: Good Whalen. morning. Thank you, Dr. Krause. My name is Dr. Thomas

I'm head of the Division of Pediatric Surgery

at Robert Wood Johnson Medical School in Camden, New Jersey, and also the Program Director of the general NEAL R. GROSS
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surgical residency there. Today the panel will be making

recommendations to the Food and Drug Administration on a pre-market approval application, but the next item of business is for those of us on the panel to introduce ourselves. These are the panel members who are giving

of their time to help the FDA in these matters, and the FDA staff themselves, who will introduce themselves sitting here at the table. I would ask that each person introduce him or herself, stating his or her specialty, position

title, institution, and his or her status on the panel today as voting member, industry or consumer

representative, or deputized voting member. And Chang. DR. CHANG: I'm Phyllis Chang, an I would start to my left with Dr.

associate professor in the Section of Plastic Surgery, Department of Surgery and Division of Hand and

Microsurgery, Department of Orthopedic Surgery at the University of Iowa. I am a voting panel member. I am Michael Morykwas. I'm

DR. MORYKWAS:

NEAL R. GROSS
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an

assistant

professor

of

surgical

sciences

in

the

Department of Plastic and Reconstructive Surgery at the Wake Forest University School of Medicine. MS. DUBLER: I'm Nancy Dubler. I'm

Director of the Division of Bioethics at Montifiore Medical Center and a professor of bioethnics at the Albert Einstein College of Medicine in the Bronx. a temporary voting member today. DR. rheumatologist, ROBINSON: professor I'm of John Robinson, at a I'm

medicine

Loyola I'm a

University Medical Center in Chicago, Illinois. deputized voting member today. MS. BRINKMAN: I'm Maxine Brinkman.

I'm

Director of Women's Services, Mercy Medical Center, North Iowa. I represent Department of Consumer

Affairs, and I am a nonvoting member. MS. I'm Senior Vice DOMECUS: My name of is Cindy Domecus. and

President

Clinical

Research

Regulatory Affairs for Conceptus, and I'm the industry representative on the panel today. CHAIRMAN WHALEN: DR. WITTEN: Dr. Witten. I'm

I'm Dr. Celia Witten.

NEAL R. GROSS
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the Division Director of DGRD in ODE in CDRH and FDA. DR. Hospital for LI: Stephen Surgery Li, in senior New scientist, in the

Special

York

Department of Biomechanics and Biomolecular Design, and I'm a temporary voting member. DR. BLUMENSTEIN: I'm a biostatistician. I'm Brent Blumenstein.

I have worked for the American I'm deputized. I'm a

College of Surgeons Oncology Group. DR. BOYKIN:

My name is Joe Boykin.

permanent voting member, a plastic and reconstructive surgeon from Columbia Retreat Hospital, where I'm also the Director of the Wound Healing Center and Burn

Program. DR. BANDEEN-ROCHE: I'm Karen Bandeen-

Roche, associate professor of biostatistics at Johns Hopkins University in Baltimore. I'm a temporary

voting member. DR. BURKHARDT: I'm Boyd Burkhardt. I am

a practitioner in plastic surgery in Tucson, Arizona, and I'm a temporary voting member. DR. KRAUSE: Executive Secretary. NEAL R. GROSS
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I'm David Krause, the panel

CHAIRMAN WHALEN:

Thank you.

I'd like to note for the record that the voting members do constitute a quorum as required by 21 Code of Federal Regulations, Part 14. I'd like to next introduce Mr. Phil

Phillips, the Deputy Director of the Office of Device Evaluation, who will tell us a little bit about the least burdensome provisions of the FDA Modernization Act. Mr. Phillips. MR. PHILLIPS: Mr. Chairman and members of I'm the Deputy Director

the panel, I am Phil Phillips.

for Science and Regulatory Policy in the Office of Device Evaluation. Excuse morning. our low tech presentation this

I was thinking that I should have put a Power

Point presentation on and gone along with the rest, but nevertheless, I hope that you'll find this to be a very informative presentation. The signed into FDA Modernization back in Act of of 1997 1997 was by

effect

November

President Clinton.

Some individuals think that it is NEAL R. GROSS

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www.nealrgross.com

perhaps

one in

of

the

most

significant of FDA

pieces

of

legislation

the

history

certainly

since

President Ford signed in the medical device amendments back in 1976. I would encourage anyone who is interested on the panel to learn more about the FDA Modernization Act. You can go to our Web site, and you will find

that there's a lot of information on the law, as well as the steps that the agency has taken to actually implement the law. Today I'm going to be talking about two provisions that are included in the law, and it deals with the terms "least burdensome." I'm going to be I'm going to

going through the actual statute itself.

go through some of the actual mechanisms that we have in implementing the law. The terms "least burdensome" apply in It's

actually two different sections of the FD&C Act.

Section 513(a) and Section 513(i), and let's look at each one of them very briefly. Under Section 513(a), and this is the one that perhaps will have the most effect on panel

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deliberations because it applies to pre-market approval applications. Secretary What the law now tells us is that the consider in conjunction with the

shall

applicant the least burdensome appropriate means of evaluating device effectiveness that would have a

reasonable likelihood in resulting in approval. Now, burdensome, requirements applications. The burdensome" second is place in that the terms "least is and as keep this it in mind this to to the is the least

applies applies

effectiveness approval

pre-market

apply

Section

513(l).

This

probably not going to be something that the panels will be as involved in as with pre-market to approval pre-market

applications

because

this

applies

notification or 510(k) submissions. Yes, indeed, there are some 510(k)'s that go before advisory committees, but it is somewhat

unusual.

It's more likely that as members of the panel

you may receive a homework assignment that deals with a particular pre-market notification submission, and this would be an important part of the statute that would NEAL R. GROSS
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apply to those activities. Specifically, such requests, to and this this is says that for in making

requests

additional of

information

determine

substantial

equivalence

devices, that the Secretary shall consider the least burdensome means of demonstrating substantial So

equivalence and request information accordingly.

the terms "least burdensome" apply in two different parts of the statute. It's important for everyone to recognize that even though the Congress has told us to consider the least burdensome means of getting devices to

market, that the FDA Modernization Act did not change the standard for pre-market clearance and approval. That is, when we deal with pre-market approval

applications, it's still reasonable assurance of safety and effectiveness, and when we deal with pre-market notifications, your 510(k) submissions, it's still

substantial equivalence. As far as

The terms have not changed. the implementation of these

procedures, it actually started back in January of last year. There was an open public meeting that we had. NEAL R. GROSS
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We had a lot of people from the industry that was present. There were consumer groups present. There

were professional societies present.

It was a half a

day's session that we devoted strictly to the terms least burdensome and have been trying to interpret

those so that we know exactly how to apply them in our day-to-day activities. Since then we have had internal

communications inside the agency.

We have also had

scientific reviewer training similar to what is going on today, but of course in a little bit more detail because we had much, much more time. There was also a guidance document that was drafted by the agency. It's called the evidence That

models for the least burdensome means to market.

did appear in the Federal Register back in September of last year. I handouts. have included it. It's in your

It's also shown here, the actual Web address

so that you'll be able to access that if there's a need for you to access that particular document. It was a subject of a comment period, and NEAL R. GROSS
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that

comment

period in

closed the

November of

30th

of

1999. the

Currently

we're

process

evaluating

different comments that came into the agency on that particular draft guidance document. In addition to the FDA guidance document, there was also a least burdensome industry task force that was convened, and they gave a proposal to the agency back in March of 1999. That agency proposal was

incorporated as Appendix D in the FDA guidance document that I just mentioned. So it was subject to the same We

comment period, which closed November 30th of 1999.

were also looking at the comments on this particular aspect of our proposal. We have formulated what I will call an interim FDA definition. The importance to the term We do not have

"interim" is that this is not final.

final guidance out, but this is an operating definition that we've told our reviewers inside our organization and you as panel members that would be, I think, a reasonable attempt of trying to interpret exactly what the terms "least burdensome" means. What we said is that least burdensome is a NEAL R. GROSS
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successful means of addressing a pre-market issue that involves the smallest investment of time, effort and money on the part of the submitter and FDA. Now, keep in mind successful means that the applicant has met for the a statutory PMA or criteria: substantial

reasonable

assurance

equivalence for a 510(k). Some have suggested that in order for us to take the least burdensome approach, that we have to actually have a cultural change within our

organization.

Well, I don't know whether we need to

change the entire culture, but clearly we all need to recognize that there can be multiple approaches to

satisfying regulatory requirements.

There is no one

way to address any particular scientific issue. Likewise, collaborate and also we need to in communicate the interest and of

compromise

public health and some of the decisions that we make. We need to understand not just the letter of the law, but also the spirit of the law, and we need to also factor issues such as time, effort and money as

considerations as part of our decision making as a NEAL R. GROSS
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result of the least burdensome provisions. Least burdensome does not mean that we

need to in any way compromise scientific integrity. Clearly, endeavors resources. agency, all I think are we all recognize by the that scientific of

affected

availability

Inside the agency and even outside the research organizations are affected

certainly by available resources. Also, good science does, in fact, include issues such as cost effectiveness. necessity regulatory scientific believe, for successful may, and in research, fact, Compromise is a and to lessening enhance That, put I

burden progress the

serve

advance that the

medicine. Congress

is

reason

this

particular provision into law. What are some of the mechanisms that we're suggesting today that may actually lessen regulatory burden? Well, I think that we all need to insure that

all regulatory decisions are made in accordance with relevant statutory criteria. you've been trained on Again, as panel members such as reasonable

issues

assurance of safety and effectiveness. NEAL R. GROSS
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That is the

www.nealrgross.com

statutory criteria that you would apply to pre-market approval applications, and that has not changed as a result of anything that the FDA Modernization Act has done. We need to use the tools provided by the FDA Modernization Act -- that's referred to as FDAMA. You may hear that on occasion -- as well as some of the process reengineering that has actually taken place within the center. Now, for example, we have exemptions for many of the simple Class I devices so that we're not even using resources in clearing these particular types of products. That means that we can divert our

resources and your time and efforts into looking at the more significant types of products that pose more risk for the American public. There's we are now also to collaborative meetings that have of with industry as we

required evaluation

approach

different

marketing

applications.

There are also opportunities for third

party review, that is, for certain types of devices. They can take 510(k) submissions and have them actually NEAL R. GROSS
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evaluated by recognized third parties outside of the agency that will make recommendations regarding the clearance of these products to the agency. These are important mechanisms that I

think can serve to streamline and lessen regulatory burden. We also need to factor in relevant,

publicly available information in our decision making. This is particularly Since you important, all are I think, for panel a

members.

experts,

you

have

tremendous amount of knowledge.

You have a lot of

information that's at your fingertips. That publicly available information is

something that we should use in our decision making so that we can learn and we can lessen regulatory burden as, in fact, the level of knowledge increases. We need to rely on nonclinical testing for decision making when possible. I mean I think it's one

thing that's important to recognize that when you deal with nonclinical testing, in many cases you can get much more precision in some of our findings than you can actually get from clinical trials. NEAL R. GROSS
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That's not to suggest that clinical trials are not very, very important. They are very important,

but I think there's a tremendous amount of information that we can learn from doing some simple, preclinical testing. In the world today, you'll find

particularly when we talk about issues such as global harmonization effort put that there's a tremendous for amount of

into

developing

standards

different

devices and different types of products and different types of scientific methods. We need to rely on conformance with

recognized standards as part of our decision making. It is a way that can lessen the burden, and it can certainly streamline our evaluation of different types of medical devices. When clinical data is needed, we need to consider alternatives to randomized control trials, and here specifically I can say we can rely on literature or nonactive controls. Now, again, there are certainly different situations where you need to have a randomized

NEAL R. GROSS
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controlled other

clinical

trial, where

but there

likewise, are

there

are

situations

other

viable

alternatives that will address the issues that we're trying to address with the same level of assurance as doing a randomized controlled trial. We also need to use surrogate endpoints where possible to demonstrate device effectiveness.

Oftentimes, as you realize, if you look at issues of effectiveness you can talk about long term types of information. If we can find appropriate surrogates,

sometimes it can shorten the duration of some of the trials at least for the purposes of clearing different devices to market. What's the bottom line to my remarks this morning? early Well, keep in mind that this is still a very at trying to interpret the least

process

burdensome provisions and trying to give guidance to our internal reviewers as well as to our advisory

committees. But what I would suggest is that we all factor the least burdensome concepts into all of our pre-market activities. This would include, for

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example,

guidance

development

and

use,

regulation

development, as well as panel review and recommendation types of activities, such as is occurring today. Above and beyond, I think we all need to remain open minded to alternative proposals for

satisfying regulatory requirements. it up.

I think I can sum

I think that what Congress was trying very much

to do by instructing us to take these least burdensome tactics is really trying to inject a degree of common sense into the regulatory process without in any way diminishing the level of safety and effectiveness that we assure the American public. That concludes my remarks, Mr. Chairman, unless you have any questions. CHAIRMAN WHALEN: Do any panel members

have questions of Mr. Phillips? (No response.) CHAIRMAN WHALEN: MR. PHILLIPS: Thank you, sir.

Thank you for your time. I would like to next

CHAIRMAN WHALEN:

introduce Mr. Stephen Rhodes, the Branch Chief of the Plastic and Reconstructive Surgery Devices Branch, who NEAL R. GROSS
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will make some introductory remarks to the panel. Mr. Rhodes. MR. RHODES: Thank you, Dr. Whalen. I am Stephen Rhodes, and the Reconstructive Food and Drug

And good morning. the Branch Chief of the

Plastic at

Surgery

Devices

Branch

here

Administration. Welcome, members of the panel, members of the public, and manufacturers to this important threeday meeting of the General and Plastic Surgery Panel, important because it's the first FDA panel meeting to make recommendations on the approvability of any saline filled breast implant, and you will vote on three premarket approval applications over the next two days. Just a word about the order of the PMAs coming before the panel. It's the order in which the

PMAs were received by the agency. Because saline filled of the high public in interest to in the

breast

implants,

addition

regular public comment periods for any PMA discussion, we will have three hours of public comment this morning on general issues related to saline filled breast

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implants, and two and a half hours on Friday morning for public comment on issues specific to insuring the patients are making informed decisions when considered saline filled breast implants. As a reminder, we will not be discussing silicon gel filled breast implants at this meeting, and I request that the panel members and members of the public limit their comments and discussion filled to the

products implants.

being

evaluated,

saline

breast

Panel commitment.

members,

we

appreciate

your

Members of the public who have requested

time to address the panel, we appreciate your comments, and, manufacturers, we appreciate your participation in presenting the safety and effectiveness data you have collected to the panel and in answering questions that the panel may have. Thank you for your attention, and I'll

turn it back to you. CHAIRMAN WHALEN: Thank you, Mr. Rhodes.

Do any panel members have questions of Mr. Rhodes? NEAL R. GROSS
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(No response.) CHAIRMAN WHALEN: We will then now proceed

with the open public hearing session of this meeting. All persons addressing the panel are asked to speak clearly into the microphone as the transcriptionist is dependent on this means of providing an accurate record of the meeting. At this time I would like to ask Dr.

Krause to give us some instructions for those who will be testifying before the panel. Dr. Krause. DR. KRAUSE: Okay. First and foremost, I

would like to thank all of those of you who contacted me and asked for time to speak. sacrifice to come here. I know that it's a big

Some of you have come a long

way, and we appreciate that. I'd like to give a few instructions before we starting having the speakers come up, requesting that all persons making statements during the open

public hearing of the meeting disclose whether they have financial interests in any medical device company or if their trip to this meeting has been paid for by NEAL R. GROSS
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someone else. Before panel, in making to your presentation your to the and I

addition

stating

name

affiliation, please address the following questions.

will read the questions into the record at this time so that a rereading by all of the presenters and later in the day will not be necessary. for all speakers. Question number one: has your travel These are the questions

and/or accommodations been paid for or will they be reimbursed by someone else? Question two: have financial ties, If so, please state who. please indicate whether you including or grants health or other

compensation societies.

with

industry

professional

Number three:

please indicate whether you

are a party to or witness in a pending lawsuit related to breast implants. And question four: do you derive a

portion of your income from surgical procedures using saline filled implants or from treating patients with complaints that the patients believe are related to NEAL R. GROSS
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saline filled implants? What we have done this morning is if

you're a speaker, you should have registered at the table outside. You will have been assigned a position What we're going to try to

in which you will testify.

do is get as many of you in in the morning as we can. Probably we will have to break for lunch around 12 to 12:15, and some of you may wind up testifying in the early afternoon immediately following lunch. A couple of things that have come up is all of the time for today is full. So we can't have We

anybody who has not preregistered testifying today.

just have so many people testifying, and we're going to be running late as it is. But there is some time available tomorrow morning, and I think there is some time also available Friday. If you would like to address the panel, you

can go to the registration desk outside and let the people at the desk know that you wish to testify

tomorrow.

Unfortunately, we can't give anyone who asks

to testify tomorrow very much time if a lot of people go up. NEAL R. GROSS
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So if we get, you know, say, three or four people who wish to testify, then we can give everybody about five minutes. If we have 15 people, then we need So it will have

to restrict that to about two minutes. to be flexible. Okay. back to the chair. CHAIRMAN WHALEN:

I'd like to now turn the meeting

Thank you, Dr. Krause.

As just alluded to, we will only have time for those individuals who have notified FDA of their request to present in the open session. We consumers. are going to begin with individual

Each of them will have five minutes to

address the panel, which I'm sure after you answer the four questions thoroughly will leave at least six or seven seconds to make your comments. (Laughter.) CHAIRMAN WHALEN: I would ask that each of

those presenting would pay attention to the timer light which is by the podium so that each and everyone who has been assigned a portion of time will have their just amount of time to speak to the panel. NEAL R. GROSS
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The

first

individual

consumer

then

to

address the panel is listed in the program as Ms. Kitchen. DR. KRAUSE: timer. A quick comment about the

You'll get a blinking light at about a minute,

and then a red light at five minutes. MS. KITCHEN: support of saline implants. Good morning. I'm here in

I think there are a lot of

good reasons why saline implants should be available. CHAIRMAN but -MS. KITCHEN: Oh, oh. -- just because you're WHALEN: Forgive my intrusion,

CHAIRMAN WHALEN:

the first one, even if there's negative answers to those questions, would you just say that at the outset? MS. KITCHEN: your questions are no. Okay. reasons people. why saline Okay. My answers to all of

I had no -- nothing to gain.

I think there are a lot of good implants should be available to

In my case, I was born with a deformity of

right chest, and 20 years ago, I had saline implants. I had breast augmentation surgery using saline implants NEAL R. GROSS
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to correct my deformity, and this surgery changed my life. It camouflaged my deformity and gave me a

greater confidence in myself. And I've had no problems with the implants over the course of 20 years and have lived a very healthy, happy life as a result. I encourage you to keep them on the

market, and as long as people are notified of the risks and the benefits, I believe they should stay on the market. Thank you. CHAIRMAN WHALEN: thank you.

Next is Ms. Faussett. MS. FAUSSETT: Good morning. In answer to

the questions, I received an honorarium of $200 to participate in the workshop yesterday, and I will use to help pay for my expenses of travel. The honorarium

has been paid by a nonprofit research center, CPR for Women and Families. Only a little more than two years ago I had a normal life, and I was a happy, healthy, highly organized and energetic young woman. NEAL R. GROSS
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I had graduated

from college with honors, had a career in management, married the man of my dreams, and I had four wonderful children. My youngest is now five. I had enjoyed a robust health all my life and I hadn't missed a day of work due to illness for over ten years. It was after breast feeding my

children that I decided to get implants, hoping that they would help to restore my pre-pregnancy shape. My highly respected plastic surgeon had

told me that my McGhan saline breast implants would last my entire life and go with me to my grave. The

risks he mainly discussed were of a local nature, such as infection, hematoma, a rupture, and I was led to believe that these were easy to remedy. What I didn't know was that the risks were far greater than I was ever told. In January 1998,

eight months after getting my implants, my world crash. My vision became disturbed. I couldn't concentrate and I was extremely not refresh me.

was unable to retain anything I read. tired and found that sleep did

Mentally it seemed as if a fog had descended upon my brain and clear thoughts and coordination became very NEAL R. GROSS
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difficult for me. I was constantly dizzy and started bumping into walls and had tingling sensations in my hands. My

hands were always cold, and I experienced joint pain among other unsettling symptoms. I was frightened by this sudden drastic change in my health. Nothing in my habits or life

style had changed with the exception of having received the implants. While downplayed recommended my my original a be second removed plastic plastic and I surgeon surgeon see a

symptoms, they

that

rheumatologist. Blood tests showed an autoimmune response starting as evidence by an elevated rheumatoid factor, as well as a lowered C3 complement and macrocytosis. I

also had a brain MRI which showed a mild degree of atrophy, quite unusual considering I was only 38 years old at the time and have no family history of these problems. I spent the last two years of my life

struggling to regain the precious health that I had. NEAL R. GROSS
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The most important step I've taken was to have my saline implants removed. There's no doubt that the

implants were harming me in a terrible way, as almost all symptoms have subsided. I thank God that I'm still recovering, but I'm gravely concerned for other women out there who are ill or who will become ill from their implants and who are not properly informed of these dangers. The ensued should after never I devastating was implanted be health with problems saline that

implants risks,

ever

considered

acceptable

especially since these are not life saving devices. Ask acceptable. my parents if the risks were

They had to drive over 2,000 miles to come Ask my husband. in unexpected

and help care for me while I was ill. He had to pay thousands of dollars

medical bills and lost me as a supporting partner in taking care of our family. Ask my children. They lost

their smiling, nurturing mother and instead were left with a sick woman who could no longer play with them, cook their favorite dinners, or help them with their homework. NEAL R. GROSS
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Ask me if I think the risks are worth it, and I will ask you if you would be willing to let your wife or daughter, health, mother loss of or sister loss suffer of and from

destroyed emotional

career,

income, medical Only

distress,

financial

distress,

system abuse all for the sake of breast implants. fools will call these risks acceptable.

The information my plastic surgeon gave me was not enough to indicate fully informed consent. He

never told me that I was risking the integrity of central nervous system or the functioning of my brain. He never discussed the seriousness of autoimmune

disease or the fact that they are incurable. If he had told me that neurologically I was at risk, I would have said, "No, thanks," and walked away. there any Nowhere in my research about implants was indication of the illnesses that I

experienced.

It was only after I became ill that my

plastic surgeon told me about the FDA booklet on breast implants. Prior to that I did not know it existed. You are mistaken if you think that women will be able to correctly evaluate the risks and make NEAL R. GROSS
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informed

decisions

about

getting

breast

implants.

Women go into the surgery with great anticipation of the benefits. They will not get the information they

need until long term studies are done which show how many women become ill and which women are most at risk. That research has not been done, and the manufacturers' research has not answered those questions. Two weeks ago my stepdaughter, who did not know what I went through, wrote to my husband and I asking for $6,000 for breast implants and informed us she knew all the risks, but upon questioning, she did not know the meaning of capsular contracture or she had never heard of autoimmune diseases. She did not know that the saline in her implants could grow mold and bacteria over time and She was not fully

cause serious infection in her body. informed.

She is now only because we informed her of those things, not her plastic surgeon, and she has since chosen not to get implants. The number one mission at the FDA is to protect consumers regarding unsafe medical products. NEAL R. GROSS
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As far as myself and thousands of other women are concerned, they have failed at this mission. Studies are needed to objectively measure how many women have experiences like mine. After long

term research is completed, if the FDA improves saline implants, they should all require mandatory disclosures of the kind of ill effects women have experienced from implants like me and warn them of the very serious nature of these problems that result in the loss of jobs, career, incomes, home, family, and well-being, including life itself. Please recommend that saline implants not be approved until more research has been done as to their long term safety. Thank you. I also have my implants if anyone would like to look at them. CHAIRMAN WHALEN: Thank you.

The next speaker is Dr. Melez. DR. MELEZ: My name is Kathleen Melez. I I an

am a breast cancer survivor and an implant survivor. am a physician practicing in Los Angeles,

NEAL R. GROSS
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immunologist to be training in infectious diseases. I paid all of my expenses to come here today. I have no association with pharmaceutical

industry, with medical societies.

I have no conflict

of interest with the manufacturers here today, although I have a lawsuit against Bristol Myers Squibb. I see breast implant patients only as part of my regular duties to take care of patients in

general medical clinics and urgent care facilities. Working on the West Side in Los Angeles, I have seen a number of breast implant patients, both saline and silicon implant patients over the years. Both patients have a variety of manifestations of

foreign body reactions.

I would like to mention two

problems I am trained to recognize. Breast implantations complain of general

malaise, arthralgias, myalgias, peripheral neuropathy. This reminds me. The experiments we did

in the laboratory as an immunologist, then we injected rats and mice subcutaneously, under the skin at the base of the tail with small particles, bacteria and oil, and this resulted in systemic illness. NEAL R. GROSS
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I expect the best implants have the same result with small particles, infections, and oil from the envelope causing systemic disease, probably the same way similar to sterile arthritis in artificial joints. The other issue I would like to touch upon is infections. addition infections infections to do The breast in not sterile tissue. infections occur at the the time milk of In

surgery, Such the

through longer

ducts. with

would

stay

and

fester

foreign body, the implant, in place. Not only the outside of the breast implant getting infected, but the saline itself can harbor

bacteria and fungi well described in the literature. In fact, normal saline bags for infusion have a limited shelf life. I would like to offer into evidence this normal saline bag. expiration date is This is produced by Baxter. September of this year. The My

understanding is that saline bags have a shelf life of 18 months. Do we expect to change saline breast I think

implants in every patient, in every 18 months? NEAL R. GROSS
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www.nealrgross.com

these devices are unsafe, and I think they should not be allowed to remain on the market or should not be licensed. Thank you. CHAIRMAN WHALEN: Thank you. Forgive

The next speaker is Dr. Atagi. me. Ms. Jennifer Gardner. MS. GARDNER: Good morning.

I

am

traveling to this meeting at my own expense.

I have no

financial ties to any health professional societies or health industry companies. I am not involved as a

witness or party to any pending lawsuits related to breast implants, and I derive none of my income from medical procedures or treatment of patients in relation to breast implants. My name is Jennifer Gardner, and I would like to thank you for giving me the opportunity to speak to all of you about my experience with breast reconstruction using saline filled breast implants. All my life up until my illness I have been health, fit, and very proud of my appearance. In

November 1997, I was diagnoses with advanced breast NEAL R. GROSS
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cancer.

Because of the severity of my diagnosis, there

was no doubt I would lose my entire breast. I also knew I had the option of

reconstructive surgery.

After one and a half years of

aggressive treatment, I started researching this next step with approval from my oncologist. I selected Dr.

Scott Spear at Georgetown University Medical Center. At my first meeting we discussed what my options were and what his recommendations were for my condition. Dr. Spear was extremely compassionate and explained to me the entire procedure and what risks were involved. In September of 1999, I had my surgery. I

had a tran flap procedure with an expander with a saline filled implant where my left breast had been removed. mastectomy I on also my chose right to have a subcutaneous with an

breast,

replaced

expander and a saline implant. I remained in the hospital for four days and recovered at home for the next three weeks. no complications during or after my operation. This dramatically. surgery has changed my life I had

It has given me back my self-esteem and NEAL R. GROSS

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www.nealrgross.com

sexuality.

I cannot look in the mirror and no longer

see what this cancer has taken away. I feel that it is vitally important that saline breast implants remain on the market for other women and give them the same chance to look normal and feel like themselves again. Just knowing that that

option was out there for me gave me hope that I could get back what I thought was lost forever. I am now 22 months in remission, and I feel happy, healthy, and desirable again. Thank you. CHAIRMAN WHALEN: Now, Dr. Atagi. DR. ATAGI: Good morning. I'm Dr. Tanya Thank you.

Atagi, a plastic surgery -- plastic and reconstructive surgery resident Fellow at the in St. Louis, Missouri. Washington University

My research funding stipend

and travel expenses are supported by the Washington University School of Medicine and the Division of

Plastic and Reconstructive Surgery. I'm not a member of the American Society of Plastic Surgery or a member of the American Society NEAL R. GROSS
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of Aesthetic Plastic Surgery, nor do I represent any of these implant manufacturers. I'm not a witness in or

involved in any lawsuits regarding breast implants. As a plastic surgery resident functioning essentially as a surgical assistant, I was involved in the use of breast prostheses and the care of patients with breast implants and was paid a stipend. my personal income is derived from breast None of implant

surgery or from treating patients with breast implants. My involvement in breast implant research stems from three primary I am a interests, plastic in perhaps I most am, and

obviously however, product because

because

surgeon. the

particularly development I began my

interested aspects medical of

device

breast as a

prostheses biomedical

career

engineer. I'm psychological also especially of breast interested implants in on the women

effects

undergoing both aesthetic and reconstructive plastic surgery procedures, I think, in part, because I am woman. I'm currently involved in several aspects NEAL R. GROSS
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of breast implant research, including the development of a physical breast model for use in testing breast prostheses and the use of digital three dimensional imagining technology, including noninvasive volumetric analysis and ultrasound evaluation of postoperative

changes, and finally, the use of objective measurement techniques breast. This past year I've also been designing a psychological patients, validated Psychological outcome study a of breast of augmentation reliable and to evaluate capsular contracture of the

incorporating

battery test normed

psychological data using

instruments. test

psychological

surveys to examine breast implant surgery patients has been somewhat scarce, especially in the area of

aesthetic surgery. Existing standardized health status and

psychological test instruments have been shown to be sensitive in the evaluation of women undergoing breast implant surgery. tests In are addition, becoming more rigorously and

established

available

incorporated into useful prospective studies, including NEAL R. GROSS
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those

designed

for

use

in

the

breast

implant

population. I have found in my experience that with preoperative and postoperative psychological

evaluations conducted for women undergoing both breast augmentation and reconstruction using other implant

types is in agreement with other more recent studies. Surveys of women receiving saline implants, including those using both validated test instruments and selfdesigned questionnaires show that preoperatively the vast majority of women who undergo breast implant

surgery, whether for augmentation or reconstruction, are generally physically healthy and psychologically stable with reasonable surgical expectations. They

have a positive view of their bodies and expect to derive psychosocial benefits from their implants. They are not, however, seeking to address serious psychosocial problems related to their breasts, and patients are typically not depressed and

psychologically unstable as earlier studies using nonstandardized, uncontrolled tests have suggested. Women undergoing implant surgery generally NEAL R. GROSS
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demonstrate levels of

mature anxiety

personalities. and are

They

harbor

low

self-directed.

After

undergoing implant surgery, patients are less concerned about potential implant problems as they incorporate the implants into their new body image and they exhibit significantly improved levels of self-esteem and

improved body image. Women derive statistically significant

benefits from their implants.

They record measurable

benefits and social comfort and express consistently high levels of satisfaction. Informal and show that 93 to formal satisfaction surveys

99 percent of patients expressing

levels of positive satisfaction even in the light of complications. The plastic surgery and psychiatric

communities understand the body image and self-esteem are all critical in the overall health status of the individual, and I'm confident that these groups are making concerted, often multi-disciplinary efforts to study and meet the needs of the individual as a whole. In fact, I believe you will hear from a NEAL R. GROSS
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psychologist

who

studies

these

issues

in

plastic

surgery patients later in the proceedings. In summary, as an engineer, I think there is convincing evidence that saline breast implants are durable, which you will undoubtedly hear more about later, and as a plastic to surgeon, women in I see tremendous and in

psychosocial

benefits

improving

restoring self-image. to decrease risks

I see earnest, ongoing efforts and complications and improve

techniques and, therefore, outcomes. And as a woman, I feel we are fortunate to have surgical enhancement and restoration incorporating saline implants as an option to us in the company of informed consent. Overall the very real psychosocial

benefits to women are exceptionally important in your consideration of saline implants. Thank you. CHAIRMAN WHALEN: Thank you, Dr. Atagi.

Next, Ms. Maura McGinn. Cynthia Scott. Who do we have next? Dr. Anderson,

NEAL R. GROSS
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please. DR. ANDERSON: good morning, Mr. Chairman. I answer all of the questions put forward in the negative, except for one. I do care for about Good morning, panel, and

62 saline breast implant patients at this time. My name is Norman Anderson. proprietary currently interest serve as in a saline breast I have no I --

implants. of the

full-time

member

associate professor of the Johns Hopkins University School of Medicine. As a internist, I do not directly implant devices into patients. the However, of I have some

familiarity

with

regulation

breast

implants

gleaned from 13 years of between the late 1970s and 1992, when I served variously as a consultant, panel member, and chair of the committee which I'm now

addressing. From that experience, I well recognize the importance and the pressures that each of you are

facing today. Because of that experience, I also began NEAL R. GROSS
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receiving referrals of patients with breast implant problems into my clinic in the mid-1980s. These

referrals have steadily expanded over the years, and I've now been privileged to participate in the care of approximately 1,000 breast implant recipients, but only 62 clear-cut saline devices. Because of the vast of these women

presented with problems, this sampling bias prevents me in giving you an accurate insight into the general outcome of saline implant usage. However, it has given

me an exposure to related complications on the dark side, and I would like to share these with you today. Now, these comments are also well known to the manufacturers, as I have the opportunity to raise each of these points in an open FDA meeting with the manufacturers in 1993, when they were advised that PMA was about to continue. It provide sound is and my fervent hope that they now the

reasonable

evidence

proving

safety of these devices.

To my mind, the first issue

to be resolved is the long term survival of saline implants. They share the same type of shell that NEAL R. GROSS
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silicone gel implants do. With silicone gel implant review, very few implant ruptures were seen in the first two or three years. failure. However, eight to ten, rapid increase in device Depending upon what series and who you

believe, 20 to 80 percent of all of those devices ruptured after ten years. There's also evidence that the shell,

silicone shell degrades in the body.

Again, this was

extensively reviewed in the FDA hearings in 1991 and two, and I only have to give you the anecdotal

experiences of plastic surgeons who had the implant tear as they try to lift it from the body, what's happening to these shell membranes over time. Now, with that, it's also known that the saline implants will deflate with a pinhole, whereas the silicone implant may require a larger rent or tear to have gel extrusion and collapse recognized. With all of that, there is a big concern that the saline implants will show a very high failure rate with time. From our point of view, you also

should recognize that folds on that shelf have been NEAL R. GROSS
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associated with shell failure over time. I saline implant regret that to we report have to you that every

studied

with

sonograph

shows folds.

Because of that, the characteristic of

the shell change with aging, we believe that saline breast highest implants failure carry rates the of potential any device to achieve the

ever

presented

before the FDA over time. The surgeons have generally replied to

this concern saying they're easy to replace: in, saline out.

saline

The worries here are gel bleed into

the device from the membrane, which has been discussed; fragmentation or leaching from the membrane; and

release of material of unknown hazards. Equally important is contracture. All of

us had hopes that the saline implant would minimize or avoid device contracture. We're seeing this in at It is

least half of the patients who we're following. of interest, and I want to share the

patient's

description.

Early on they complained a bit -CHAIRMAN WHALEN: Excuse me, Doctor. I'm

sorry, but I'll need to ask you to summarize, please. NEAL R. GROSS
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DR. ANDERSON:

Yes.

One of the patient's This

words were describing a slosh when they move.

goes on to a kind of contracture where they describe the breast as feeling like plastic bubble wrap. We see hernia when these things go

through, and then finally, they develop the painful breast. About 15 percent of the saline implants that we're following have breast implant pain, and this is the most pernicious and neglected symptom of the entire breast implant scenario. fibrocytis and frozen shoulder. In my view, PMA approval is being It can progress to

requested for devices that carry a high probability for rupture over time. They may have unknown outcome from They have very

the lechate or bleed into the saline.

characteristic and worrisome patterns of contracture. They do interfere with the detection of breast cancer. We just don't know the number, and the only way to solve these problems for many women is explantation and mastopexy, and that incurs many problems. Thank you. I have stood on the other

NEAL R. GROSS
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side.

It's easier to be on this side.

I wish you well

on your endeavor today. CHAIRMAN WHALEN: Dr. Anderson, would you

entertain a question from the panel? DR. ANDERSON: Yes, I would. Dr. Burkhardt.

CHAIRMAN WHALEN: DR. BURKHARDT:

Thank you, Dr. Anderson.

You brought up a couple of issues with which I was not familiar and just need some more

information, which I'm sure you have.

You indicated

that the saline implants has the same type of shell as the gel filled implants. don't understand. DR. ANDERSON: as the silicone. A generic characterization What do you mean by that? I

The manufacturers will talk to you

about slight differences in the catalyst and thickness, but in terms of what we believe the biologically

important degradation over time and the influence of folds on rupture we think are very similar. DR. BURKHARDT: And in regard to the back

bleed of gel in the saline implant -DR. ANDERSON: Yes, sir.

NEAL R. GROSS
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DR. BURKHARDT: to me, please? DR. implant hearings ANDERSON: on

-- would you explain that

In

the

1991-92 were

breast long,

silicon

gel,

there

theoretical discussions on whether or not all bleeding came from the gel inside, and the theory was quite elegantly put forward by presenters from the FDA that even the membrane of the silicone device could bleed a few molecules. DR. BURKHARDT: But you're speaking of a

patient who has previously had a silicone gel implant. Where does the gel come from is what I'm trying to figure out. DR. ANDERSON: And the answer is, to turn

it around, if you look at the capsular contracture around these devices -DR. BURKHARDT: We're talking about saline

filled devices now we're talking about? DR. ANDERSON: different sets. Yeah. We have removed six

They all show scar tissue and the

granulation reaction, microgranulomas that we see in association with silicone gel. NEAL R. GROSS
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DR. BURKHARDT: in the capsule? DR. ANDERSON:

Do they show silicone gel

I have never done the X-ray I think that job

defraction microscopy to prove it.

belongs with the manufacturers behind it. DR. BURKHARDT: DR. ANDERSON: So we don't know then? No. This is a -- I've

raised this as a concern, sir. DR. BURKHARDT: DR. ANDERSON: Thank you. Yeah. Thank you.

CHAIRMAN WHALEN:

Next listed is Dr. Fritz Barton. DR. BARTON: Good morning. Thank you for

the opportunity to be here.

I'm Dr. Fritz Barton,

clinical professor and past Chairman of the Division of Plastic Surgery at the University of Texas Southwestern Medical School. I've years and have been in clinical thousands practice of for 24

managed

patients

with

breast implants.

Therefore, a portion of my income is

derived from breast implant surgery. My travel expenses are paid for by the NEAL R. GROSS
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American

Society

for

Aesthetic

Plastic

Surgery,

of

which I am president. I have no financial ties to any implant manufacturer. I'm neither a witness nor a party to a I am here

pending lawsuit relating to breast implants.

today on behalf of the many thousands of our patients who tell us that breast implants have made a positive difference in their lives. An increasing number of women today are choosing breast augmentation to enhance their

appearance, nearly a million women in the past decade alone. But why is this procedure so popular? In my experience, most patients become

interested after talking to someone else who has had the surgery. Satisfied patients have created the

popularity of breast augmentation. The experience of my practice parallels

very closely the documented description of the typical breast augmentation patient. her early 30s. children. The average patient is in

Most often she is married and has

These women do not fit the stereotype so They are responsible, adult women NEAL R. GROSS

often portrayed.

(202) 234-4433

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www.nealrgross.com

with families, careers, and very normal lives. I've found that women seeking breast

augmentation have similar motivations to other cosmetic surgery patients. augmentation for The idea that women seek breast any reason other than their own

personal desire is not supported by the literature, nor by my clinical experience. Research has shown that the vast majority of patients who have breast augmentation would make the same choice again. The high satisfaction rate and the

determination that so many women undergo a surgery with the knowledge that it's not perfect suggests just how deeply the benefits are felt. Women obstacles to get have this to overcome from tremendous societal

procedure,

prejudice to a wealth of misinformation.

The fact that

so many seek it out speaks to their strong desire. I believe that the vast majority of

plastic surgeons try to do a thorough job of informing their patients about both the benefits and the risks of implant surgery. As a physician it is my

responsibility to help round out the decision making NEAL R. GROSS
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process. A woman's right to choose breast implants is parallel by her right to be fully informed both of the risks and of the benefits. surgery judging consultations, the part of As with all cosmetic the of evaluation the is

appropriateness

patient's

motivations and expectations. have inappropriate

Patients who are felt to or inappropriate against or the

motivation are

unreachable surgery.

expectations

counseled

Saline

filled

breast

implants

provide Given these

important psychological benefits to many women. the proven level of safety and efficacy of

devices, women should have the right to choose them either for breast reconstruction or for augmentation. Our responsibility as health professionals is to provide the information by which a patient can exercise her informed consent. for Aesthetic Plastic Surgery The American Society and its 2,800 Board

certified plastic surgeon members and candidates are committed to this process. Thank you very much. NEAL R. GROSS
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CHAIRMAN WHALEN:

Thank you, Dr. Barton.

Next listed is Dr. Gwendolyn Lewis. DR. LEWIS: I am Gwendolyn Lewis, and I'm

here as a volunteer to read testimony for three women who had implants who are too sick or poor to come. My answer to all four question is no. In all three testimonies the women were healthy, got implants, got sick, got their implants removed, and then got better. The first woman I'd read for is Karen

Decker, who's from Pennsylvania.

She writes: Five My

I am a 36 year old mother and wife. years ago I decided to have saline implants put in.

surgeon had very positive things to say about them and said they would last a lifetime unless I happened to get in a very bad car accident, and even if that did happen and they ended up rupturing, I would be

perfectly safe because they were filled with saline, not silicone. At the time I didn't even know they

weren't FDA approved. As soon as I had the implants put in, my NEAL R. GROSS
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breasts

became

very

sensitive,

but

my

doctors

kept

telling me not to worry, that it was just my hormones. About two years after this, I started

having memory problems to the point I couldn't remember things that had happened the night before. all the time. I went to a specialist, but all the I was tired

results came back normal.

I had sharp, jabbing pains I also had

constantly running through my breasts.

aches and pains that left me virtually unable to move my joints, and there was overwhelming heat on my own skin. Finally I went to the doctor again, and my ANA test revealed that I had lupus. It's been a little My right

over a month since I've been explanted.

breast has swelled up twice since then, and each time they had to put a large tube in it for a week to drain. I've been on antibiotics all month, and I still have two infections. The hole is still there,

and I have to put an antibacterial ointment on gauze and push it in with a Q-tip. My left breast is healing fine. NEAL R. GROSS
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The hot

skin I was having for months went completely away after explantation. I no longer get sharp, jabbing pains ANA is back normal. that's normal with I am the

through my breast, and my still tired, but I guess

infections. My memory problem is still there, but I hope in time that also changes around. This is from a 29 year old woman, Cheryl. I'm a 29 year old woman who got McGhan textured saline implants in 1996 for cosmetic reasons. later the problems started. About a year

Although I had not had

health problems in the past, in 1997, I developed a number of allergies. In January of 1999, I was rushed to the emergency room with severe abdominal pain. At the time

they diagnosed me with urinary and vaginal infections and sent me home, but the pain never got better, and the infections never went away. I had polyps and infections. my skin all over my body started to burn. burning inside my veins, and my Last April It felt like joints were

tremendously painful. NEAL R. GROSS
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I went to several doctors and my blood work all came back normal. In May I went for a

mammogram which came back fine, but within three weeks of the mammogram I felt horrible. I had extreme

burning and a sense of strong pressure in my chest, particularly around and behind my implants. My eyes

and mouth were extremely dry, and soon after I noticed my hair falling out in clumps. I was so fatigued that I couldn't even get myself something to eat and soon found myself out of work. with Emotionally this was difficult for me to deal because I've always been a health and active

person.

I rarely ever had a cold, even in the middle Now at 28 my body was falling apart. By July I was so weak that

of flu season.

It got worse.

I could barely get up to use the bathroom and get a drink. I was diagnosed with extremely dry eyes. Since

1998, my eyeglass prescription has changed three times. Before that my prescription changed only once in four years. It seems like I couldn't remember anything anymore. I would get up from the couch to go get a NEAL R. GROSS
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tissue, and by the time I had gotten to the restroom, I had no idea what I was doing or getting. I would often become cold, and nothing

seemed to be able to warm me up.

For instance, I

remember feeling like my feet were freezing and decided to put on a pair of socks and wrap a blanket around them. Two hours later, they still felt cold.

Even a heating blanket wouldn't warm me up. and pains were so awful. Last implants. August I decided to

My aches

remove

my

I just wanted to feel better.

When I was

explanted in September, I noticed some of my symptoms going away. My hands weren't swelling anymore. All of

my chest pains were gone, and although I am still really tired all the time, I began to be able to do more things for myself. I still have health problems, and I still can't work, and at the age of 29 I find myself with no income and no way to take care of myself. I thank God for my family, friends and my boyfriend who have been supporting me through this, NEAL R. GROSS
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both financially and emotionally. would be homeless.

Without their help I

I'm glad I'm getting better, but it's not quite quickly enough. I would have loved to have come

to this meeting, but my health prevents me from doing so. I see this as flashing to stop. CHAIRMAN WHALEN: ask you to do so. DR. LEWIS: CHAIRMAN minutes. DR. LEWIS: Thank you. Thank you. Dr. Lewis. Dr. Okay. WHALEN: That is your five I'm afraid I'll have to

CHAIRMAN WHALEN: I'm sorry.

Doctor,

Burkhardt would like to ask you a question if you don't mind. DR. BURKHARDT: DR. LEWIS: DR. Are you a physician?

No, I'm a sociologist. I see. Is it your

BURKHARDT:

position then that because of these tragic stories that other women should not be allowed to have this surgery? NEAL R. GROSS
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DR.

LEWIS:

I

think

they

should

be

investigated thoroughly. stories do point -DR. BURKHARDT:

Yes, I think these tragic

But

it's

your

position

that they should not be allowed to have this surgery at the present time. Is that what you're recommending to

the -- because that's what a negative vote on this committee would probably do. DR. LEWIS: Well, I think you're the

experts and will have to decide that. DR. BURKHARDT: DR. LEWIS: that. CHAIRMAN WHALEN: Thank you, Dr. Lewis. Not here. Thank you.

I'm not in a position to do

Next listed is Jean Pentolino. Dr. Cheston Berlin. DR. BERLIN: Cheston M. Berlin, Jr. Good morning.

My name is

I am Chief of the Section on

General Pediatrics in the Department of Pediatrics of the Pennsylvania State University College of Medicine at the Milton S. Hershey Medical Center. university professor of pharmacology at I am also the same

NEAL R. GROSS
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institution. In addition to my academic and clinical appointments, I am a member of the Academy for Breast Feeding Medicine, the International the American Lactation Society for

Consultants

Association,

Nutritional Sciences, the American Society for Clinical Nutrition, and I'm a Board member of the International Board of Lactation Consultant Examiners. I wish to emphasize that I am not

representing these organizations, but with to indicate my professional interest in pediatric nutrition,

especially in lactation. I'm also a member of the American Academy of Pediatrics and have served as Chair of the Committee on Drugs. At the present time I am Chair of the

Network Steering Committee of the National Institutes of Health and Pediatric Pharmacology Research Units. One of my research interests is in the transfer of drugs and chemicals in the human milk. I

may be the only person to make a presentation to you this morning on the only purpose that those of us in pediatrics see for the human breast, which is breast NEAL R. GROSS
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feeding. I am paying for my own transportation I have no with any

today from my university professorship fund. financial interest, nor have I consulted

manufacturer of saline implants. I have served as a consultant to the

pharmaceutical industry, including Pfizer and Merck, Ascent, and Mediva, and I participated in the clinical trial for Mediva. I am neither a witness nor a party to any litigation involving breast implants. I do no surgery

involving breast implants, and I do not care for women with complaints they believe are related to breast

implants. Because of my interest in the silicone

filled implants, I have served as a consultant with both industry and with women with silicone implants. A major thrust in pediatrics over the past 25 years has been to increase the incidence of breast feeding 75 percent by the year 2000. achieve that goal. We shall not

The best estimation is that now

approximately 60 percent of infants are discharged from NEAL R. GROSS
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the hospital, if indeed they stay long enough to be breast fed, and there is a 50 percent attrition rate over the following six months. We are very anxious to

change these numbers in a positive trend. One of the frequent reasons for not

starting or for cessation of breast feeding has been the need for a mother to take a medication. frequently will receive instructions that she She must

terminate breast feeding. A similar situation exists with regard to exposure to environmental chemicals, including the

issue of breast feeding in women with breast implants. The initial implants contained a silicone gel within the silicone based capsule. It has been estimated, as you've heard

this morning, that nearly one million women have had breast implants. bearing age. Many of these have been in the child

Concern has been raised over the exposure

of children to milk from mothers who have had silicone implants. There's only one report in the literature of

a group of offspring of mothers with breast implants who had esophageal dismodality (phonetic). NEAL R. GROSS
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This study

has been criticized on methodology background. There does not appear to be any secretion of silicone with related these compounds implants. from human milk from

mothers

Since

saline

filled

implants would not have the silicone gel interior, this would not even be a hypothetical concern. It emphasis toward is important that the we continue of our

increasing

incidence

breast

feeding in the United States.

My presentation here is

not meant as an endorsement for the cosmetic use of implants, nor for the licensing of these implants for this purpose, but to assert that there should be no concern on the panel's part over any possible medical effect on the offspring of women with implants who choose to breast feed, the so-called second generation effect. At the present time there is no scientific data that would prohibit breast feeding in women with these implants. pediatric I'm convinced that, along with my that breast feeding for

colleagues,

nutritional, immunological, and psychological reasons is the most important thing that we can offer our NEAL R. GROSS
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children. We need to make a substantial increase in the incidence of breast feeding at all infant ages in this country, and in order to do so we should not arbitrarily exclude a group of women from nursing

because of a hypothetical risk without confirmatory scientific data. There are many reasons for stopping breast feeding, including return to work, onset of maternal disease, need for pumping and storage facilities, and the institution of maternal drug therapy. would interfere with the duration All of these of milk, of

lactation. We should not add to this list any other reason without scientific support. There is no

scientific data to indicate that breast feeding with saline implants would be hazardous to nursing infants. Thank you. CHAIRMAN WHALEN: question, Doctor? DR. BERLIN: Yes, sir. I'm sorry. I seem to be Would you entertain a

DR. BURKHARDT:

NEAL R. GROSS
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the only one asking these questions here, but, Doctor, hypothetically antibodies if a woman either were the to develop systemic shell or

toward

silicone

something in the silicone shell, as an expert in breast feeding, would this be likely to be reflected in any way in the content or quality of the other's milk? DR. BERLIN: I do not think so, Dr.

Burkhardt, because of some of the other situations like women with lupus, who have a significant number of antibodies to many, many different tissues. They do

not have difficulty, should they wish to choose to nurse. DR. BURKHARDT: then. So the answer is negative

It would not be reflected in -DR. BERLIN: I do not think so. Thank you. Thank you, Dr. Berlin.

DR. BURKHARDT:

CHAIRMAN WHALEN: DR. BERLIN:

Is there a question there? Yes, Ms. Brinkman. My question is you talk

CHAIRMAN WHALEN: MS. BRINKMAN:

about the fact that we're not getting contamination of milk, but implants interfering with the ability to

NEAL R. GROSS
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breast feed, what has been your experience? DR. BERLIN: The experience with that is

that certainly the type of surgery that is done for the insertion of the implant might interfere with the

ability to nurse.

The two things that seem to be very

important in breast feeding in women with implants, regardless of their composition, is the site of the incision, particularly if any of the ducts under the nipple have been harmed or if one of the -- the fourth accessory nerve that innervates in the nipple, which comes across from the lateral side, if that's been transected. If that's the case, there may be

difficulty particularly with establishment of lactation because of the reflex of nipple to the brain in the mother. So that is a legitimate concern, but that

would not affect the infant other than the fact that the mother could not make the milk. MS. BRINKMAN: And is it your

understanding this appears to be a common place for the incision for some of the augmentation patients? DR. BERLIN: That is a common place is

NEAL R. GROSS
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right under the nipple? MS. BRINKMAN: DR. BERLIN: Yes.

Yes. Thank you. Thank you, Dr. Berlin. No. sequence, and

MS. BRINKMAN:

CHAIRMAN WHALEN:

Next is Ms. Karen Duhala. Well, we'll complete the

then we'll return to anyone who has shown up late. Ms. Melinda Cloud. MS. CLOUD: Good morning. My name is

Melinda Cloud, and I am from Grand Rapids, Michigan. And to answer your first question, since I am on disability, I could not afford to come here. So

after asking for some assistance so that I could give a presentation, I was told that my plane fare and room would be paid for by a nonprofit support group for women with implants, Command Trust Network. In answer to your other three questions, the answer is no. I am here today with an unpleasant and yet very necessary story to tell regarding my experiences with saline breast implants. Were it not considered

NEAL R. GROSS
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highly inappropriate, I would bear my chest to you right now, for seeing with your own eyes, it would have a greater impact than the words that I can tell you. To me they are not breasts, but two

containers of saline in silicone baggies held in place by skin. Were you to see them, you would see puckers

and indentations where the containers have shifted, where the solution has dissipated. Were you to touch them, it would feel like touching a plastic bag that moved beneath a sheath of skin. You could feel the solution slosh. You'd want

to take your hand away, and I wouldn't blame you. In adamantly physician. 1974, to I was a young model and was by a

advised

have

breast

augmentation

I nursed my baby for about a year, and he

said I was much to young to have such ptotic breasts. I also had many cysts in my breast, and the doctor told me that the solution to my problems was to have my breast replaced with silicone implants,

which would last a lifetime and permanently end my pain and discomfort. beginning of a I had no idea that this was the long period of pain, suffering and

NEAL R. GROSS
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decline. I ended up not have one surgery, but 12, most of them attempting to remedy severe capsular

contracture and deformity.

I started with silicone

implants and later replaced these with several sets of saline. I had an emergency surgery to deal with a hematoma where blood was literally spurting out of my breast. I had two more surgeries to deal with a near

deadly staph infection. In 1987, 13 years after my first surgery, I finally consulted specialists at the University of Michigan Medical center who assured me they would solve my problem once and for all, but they didn't. couldn't. I had several other surgeries, including getting my first set of saline implants in 1992. They They

told me my saline implants were the safest kind, but my worst problems started after this surgery. On July 18, 1995, I had my first set of saline implants put in, which were described as a new, greatly improved type of saline implant. NEAL R. GROSS
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I still had a

great deal of deformity from all the previous surgeries and the infection of '86. That was my most recent breast invasion and reconstruction. There needs to be another. My

doctor tells me I have to have these implants taken out of me because my health has severely declined since 1992. I stand before you now, a recipient of Social Security disability trying to live my life on $512 per month. I was granted disability status in

1997, when I could no longer hold down a full-time job or work to support myself. successful student in free lance I had been a relatively a highly as promising a crisis

writer, working

sculpting,

also

intervention counselor for a substance abuse facility. I lost my job because I kept getting sick. I had to quit college in order to survive. I had to

sit in a courtroom with a Social Security judge and listen to people talk about me as though I were one of the most inept human beings, an incapable member of society. for me. NEAL R. GROSS
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This was the most significantly tragic day

There is not a single insurance company who will insure me. of my saline implants. This entire mess has cost well over a I'm considered high risk because

quarter of a million dollars.

Why?

Because I, like

everyone else, believed saline solutions encased in silicone shells did not cause problems. I have to get up every day and face

chronic fatigue, wash up from night sweats, Reynault's syndrome, and moments of excruciating chest pain that has doctors sending me to the emergency room. My I've developed immune what system known has as been compromised. induced

is

chemically

asthma.

I have blood in my urine and no one knows why. I get sores on my skin that have episodes of severe

My muscles have weakened. don't really heal. I

depression, and I can't even pick up my grandchildren. I was once a very strong and health woman. I raised three children alone without the benefit of child support. Illness was not even a consideration.

Now I pray every day for God's help to keep my spirits up for I know full well that, plus the NEAL R. GROSS
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blessed love of my family and friends, this is all that keeps me going. There is little that you can do for me anymore. The damage has been done, but you can help I cannot get my breast implants out. My

other women.

insurance will not pay for it because it's elective, and they have to pop first or have a great leak, and then no one knows what will happen. I also cannot get

reconstructive surgery because I cannot afford it. You are not doing any women any favor by giving them a choice that could leave them financially destitute with no ability to have a failed implant removed, which is my situation today. I would like you to look into the answer of saline implants in place of silicone because there's no proof anywhere for anyone that that's the remedy, and for me it absolutely was not. Thank you for this honor and opportunity to testify before you. I'm going to try once again to Please do not recommend the

trust you to do your part.

approval of saline implants unless you are convinced that what happened to me won't happen to anyone else. NEAL R. GROSS
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Thank you. CHAIRMAN WHALEN: Thank you, Ms. Cloud.

The next listed speaker is Dr. Ory. DR. ORY: Good morning. I'm Howard Ory.

Currently I'm a private consultant in epidemiology. I'm an adjunct professor of epidemiology at the Emory University School of Public Health, and in a past life, I was Deputy Director of the Epidemiology Program at the Centers for Disease Control. My presentation today is very abbreviated from the written report that I submitted to you in collaboration with Dr. Jim Schlesselman. Both Jim and

I have consulted with 3M and defended in a breast implant litigation. and lodging today. I continue to be involved with lawsuits related things. to breast implants. Today I will do two 3M has paid for my transportation

I'll present a summary of our meta analyses of

the more than 20 published epidemiologic studies that examine the association of breast implants and

connective tissue diseases. Then I will present the conclusions of

NEAL R. GROSS
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three blue ribbon panels that have examined this issue. This table shows estimates of the relative risk of connective tissue disease among women with A

breast implants.

The values range from 0.3 to 1.2.

summary estimate of the relative risk of connective tissue disease is 0.7. The common next four tables examine the most the

connective

tissue

diseases

comprising

aggregate diseases in Table 3 there. Estimates of the relative risk of lupus range from zero to 2.3. relative risk os 0.7. Estimates of the relative risk of A summary estimate of the

rheumatoid arthritis range from .3 to 1.6. estimate is 1.1. Estimates of the relative

A summary

risk

of

scleroderma range from zero to 1.8. is 1.0. Estimates of the

A summary estimate

relative

risk

of

Sjogren's syndrome range from .2 to 1.5. estimate is 0.8.

A summary

An atypical connective -- that's definite NEAL R. GROSS
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connective

tissue

disease.

In

atypical

connective

tissue disease specific to breast implants has never been defined. Lacking a case definition, six studies

examine conditions that represent various aspects of atypical connective tissue diseases, such as chronic fatigue syndrome, fibromyalgia, undifferentiated

connective tissue diseases. relative risk is 0.8.

A summary estimate of the

Based on the data I just presented, we conclude that the 25 or so epidemiologic studies now at hand provide sufficient evidence to reassure women that breast implants tissue do not cause or autoimmune atypical disease, connective

connective

disease,

tissue disease. Slide off, please. Three blue ribbon -I'm now going to

switch to the three blue ribbon independent reviews, which were released in 1998 and 1999, presenting

scientific evidence concerning the possible association of breast implants and systemic disease. The

scientists on these panels were chosen because of their distinguished credentials and their lack of previous NEAL R. GROSS
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involvement in the issue. reach about the

The conclusions that they data are strikingly

epidemiologic

similar to each other and to our own. The independent review group and panel by the Ministry of Health in the U.K. concludes there's no epidemiologic evidence for any link between silicone gel implants and any established connective tissue

disease.

If there is a risk of connective tissue

disease, it's too small to be quantified. The IRG cannot justify further

epidemiologic studies to investigate this hypothesis. Good evidence for the existence of atypical connective tissue disease or undefined conditions, such as

silicone poisoning, is lacking. The National Science Panel, empaneled by Judge Sam Pointer, Federal District Judge Pointer, This

who's in charge of the multi-district litigation. panel concludes:

no association was evident between

breast implants and any of the individual connective tissue diseases, all definite connective tissue

diseases combined or the other autoimmune rheumatic conditions. NEAL R. GROSS
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The

material

presented

represents

an

analysis of the most rigorous and relevant scientific information currently available. It's our informed

opinion that a large majority of scientists in our respective disciplines would find merit in our reviews. Finally, essentially insufficient silicone concludes evidence the the to Institute same thing, an of that Medicine there's of

support with

association fine

breast

implants

the

connective

tissue diseases. of resources and

There's no justification for the use further epidemiologic exploration.

The committee finds no convincing evidence for atypical connective tissue disease, rheumatic disease or novel constellation of symptoms in women with silicone breast implants. In fact, epidemiologic evidence suggests

there is no novel syndrome. Ladies and gentlemen of the panel, based in part on the 25 studies that I presented to you, the three independent blue ribbon panels conclude that this issue is resolved. Breast implants do not cause

connective tissue disease. Thank you. NEAL R. GROSS
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DR. question?

BANDEEN-ROCHE:

Could

I

ask

a

CHAIRMAN WHALEN:

Please. Couldn't help noticing

DR. BANDEEN-ROCHE:

both in the printed literature and up there that the Hennekens study was notably sort of out of line with the others and that it had higher estimates of risk. understand that this could happen by random I

chance

alone, et cetera. So my question to you is: of anything about the Hennekens are you aware study that Was

systematically makes it different than the others? it a more or less representative population? better or worse done? I'd appreciate your comments on that. DR. ORY:

Was it

The Hennekens study relies of It was

self-reports of both implants and diagnoses.

conducted during the time of maximum media attention to this, and the authors themselves notes that there's a substantial likelihood of selection bias of the people who entered the study, driving the relative risks up. In fact, of the target population, only 25 NEAL R. GROSS
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percent of the target population entered the study. there is a substantial likelihood for selection bias. The other thing I didn't have time

So

to

present is that I've done the meta analyses both with and without Hennekens, as has Dr. Hulka of the National Science Panel, and essentially you come to the same conclusions. The relative risks of all the connective

tissue disease that you study hover around 1.0, with or without Hennekens. CHAIRMAN WHALEN: MS. BRINKMAN: Ms. Brinkman.

Is it my understanding that

these studies are done on silicone gel implants? DR. ORY: MS. They're done on both, and the -What percent of saline

BRINKMAN:

implants are included in these studies? DR. ORY: It's hard to tell. Most of the

studies didn't -- were unable to make that assessment. The best way I could give you of looking at them is that Dr. Hulka of the National Science Panel broke out silicone gel studies in her meta analysis and also showed a relative risk of about one. So I think you

can infer that the relative risk for saline implants NEAL R. GROSS
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would have to be one since the overall risk is near one. DR. BURKHARDT: DR. ORY: May I ask a question? Dr. Burkhardt.

Yes, sir.

DR. BURKHARDT: of one mean? DR. ORY:

What does a relative risk

A relative risk of one means

that the risk of the particular disease you're studying in women with implants is the same as in the controls, women without implants. CHAIRMAN WHALEN: MS. PATRICIA Is Ms. Brent available? Good morning, and

BRENT:

thank you very much for having me here. Patricia Brent.

My name is

This is my daughter, Catherine Brent.

I breast fed her while implanted with a saline/silicone implant. In answer to the questions, my travel has been paid for by my husband. this. Do I have financial ties? witness or party to a pending lawsuit? filed in 1991. I have not resolved it. NEAL R. GROSS
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He is not happy about

No.

Are you a It was

Yes.

Catherine is

also a party to a lawsuit. has not been resolved.

It was filed in 1995.

It

And do I derive a portion of my income? No. I am here to voice my concerns and the concerns of many other mothers about the saline portion of our mammary gland implants. I will be referring to

these as mammary gland implants because the function of the breast is to breast feed. My implants were put in in December of 1982. I was a healthy woman of child bearing years. I

had them put in because I had nursed my four older children. I had the surgery to make my breasts look It was a path down

the way they did before I nursed. vanity lane. I children. It was a sin. had -I had my

four

other

older

In 1982 I was implanted.

In 1984 I got

pregnant with Catherine. of 1985, and under

Catherine was born in January advice of my physician, my

pediatrician, and from what I knew, it was perfectly safe for me to breast feed. being told to young women. That is what is still

I disagree.

NEAL R. GROSS
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When I was explanted, my breast implants had grown black aspergillus niger fungus and bacteria. This was in the implant upon explantation. Black

aspergillus niger fungus and unknown microorganisms is not a good thing to have in a mammary gland, especially when you are breast feeding. I will now let Catherine read a letter. It was an E-mail actually that she sent to the "Oprah Winfrey Show." I did not watch this program.

Catherine watched this program.

This is Catherine's

response to the "Oprah Winfrey Show." MS. CATHERINE BRENT: According to your

show today, it was stated that breast implants were safe for pregnancy and breast feeding. I would like to

tell you that the doctor on your show lied because if he referred to the FDA, it is not known whether a mother's breast implants can have an effect on the fetus. I am a 14 year old girl who's suffering from chronic inflammatory demyelinating polyneuropathy, esophageal motility disorder and gastroesophageal We are

reflux disease.

My young sister is also sick. NEAL R. GROSS

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www.nealrgross.com

the

children

my

mother

had

after

she

got

breast

implants. safe.

She nursed us after she was told it was

Are four older siblings are in perfect health. I would just like to tell you to research

what you say before you air a lie. Thank you very much. I would like to be

on your show so I can tell my story, my sister's, my mother's, and all of the thousands of children sick from these unsafe implants. Thank you. Catherine.

And please go to the FDA Web site. MS. PATRICIA BRENT: I heard back from the

"Oprah Winfrey Show" approximately two months later. It was from their legal department. because I know that if the legal It broke my heart department gets

involved, I will not get the truth. told the truth. I am now going to

People will not be

show

you

my

breast

implants with the fungus, and I'm going to show you a baby bottle that has black fungus on it. know. I did not have this cultured. I do not

I do not know if

this is aspergillus niger as mine was, but I ask you to NEAL R. GROSS
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look at the two of these and tell me, tell me as a mother it is safe for me to breast feed with this in my body. I know I have had six children. professional at this. last five births. I am pregnant. eat. I am a

I had natural childbirth for my

I know what to do with my body when I know what not to

I know what to eat.

I know what medication to take and what not to

take, and I listen to my doctors. Doctors do not know. The average

pediatrician does not know that this fungus can be in the implant. Whether it comes through into the breast I feel that unequivocally

milk, I feel that it does.

this is what has harmed my child. There is no family history of this, and I will just pass this along. I have one thing to say, and this is from Cindy Morrissy, who has three girls. Hillary has scleroderma. Her daughter

Please listen to what she has

to say because she could not be here today because of her children. They are too ill.

We have to have confidence, confidence in NEAL R. GROSS
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the physicians.

How can we have confidence if you do You do not know. You do

not know the full picture?

not know what this does to a nursing child or via the placenta. You do not have these answers. Upholding medicine in its greatest,

grandest form is do no harm.

Please, please, as you

consider putting these on the market, do no harm. Cindy also says: acceptable risks. One

would need to greatly define the term "acceptable risk" because when I had those implants I was never told it could grow fungus and have this bacteria in it, and my child was given no acceptable risk. On Monday, the Supreme Court allowed a

case to go forward in -- it was from South Carolina. Please forgive me if I don't get this exactly right, but I know that it's about the fetus having rights, and my child had no informed consent. consent. That is absolutely wrong. Catherine and my daughter Christine were part of Dr. Jeremiah Levine's original study in 1992. Catherine and Christine both have the esophageal I had no informed

motility disorder and the reflux. NEAL R. GROSS
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None of my other

COURT REPORTERS AND TRANSCRIBERS 1323 RHODE ISLAND AVE., N.W. WASHINGTON, D.C. 20005-3701

www.nealrgross.com

children have it, and Catherine since that study has been diagnosed with the chronic inflammatory

demyelinating polyneuropathy. I will give this to you. CHAIRMAN WHALEN: Thank you, Ms. Brent. Thank you.

MS. PATRICIA BRENT: CHAIRMAN WHALEN:

Returning to some of the

other speakers who I believe have arrived, I'm told Ms. Angus is available. MS. ANGUS: Excuse me if I sniffle. That

last testimony really, really touched me. Anyway, rolling? Okay. My name is Annie. Canada. I'm from Vancouver, okay. Here we go. Are we

I've got what, five minutes?

That's it?

I think I might be the only Canadian up here, My travel and accommodation have not been I

down here.

paid for, nor will I be reimbursed by someone else.

do not have financial ties, including grants or other compensation, with industry or health professionals or societies. I am not a witness or a party to a pending

lawsuit related to breast implants, and I do not derive NEAL R. GROSS
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a portion of my income from surgical procedures using breast implants or from treating patients with

complaints about breast implants. In other words, I represent myself and all of the other Jane Does out there or all of the Annies, Carols, Lauras, Miriams, and whoever else you want to call them who are too ill or too broke to be here. I am giving this testimony with the hope that women will be spared the ill health that I have experienced as a result of being implanted with saline breast implants manufactured by Mentor. I am not No

seeking any monetary compensation for my suffering.

amount of money can compensate me for what I have lost. In the spring of 1995, my husband and I were looking into the possibility of having my breast augmentation. good health. I was 33 years old and was then in very My third child had been born a year

earlier, and my breasts were small and saggy. I consulted our family physician and

sought a second opinion from a well reputed plastic surgeon. I was concerned about the bad reputation of

silicone implants and did not want to do anything that NEAL R. GROSS
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would jeopardize my health. Both physicians assured us that saline

implants were completely safe.

I was told that with One was of

saline implants there were only two risks.

the implant rupturing, which is not a threat to one's health. The other possible negative side effect that I

became aware of were the ingredients that could be a partial loss of sensation in the breast area. I was given statistics, and the incidence of rupturing and lost feeling and became convinced that only a minority experience these effects, between .0 percent and four percent. Having thought that I was well informed, I consented to the surgery and signed a waiver declaring that I would not pursue litigation if there were any complications. This act of weighting one's rights is

in hindsight intentionally disempowering and needs to be readdressed. In augmentation June of 1995, I underwent a breast by a

with

saline

implants

performed

Canadian Board certified plastic surgeon. months, I realized that the numb

After a few in my

sensation

NEAL R. GROSS
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general breast area was not going away, and that I was hypersensitive in the areola and nipple area, which is a painful and irritating sensation. I was told by my plastic surgeon that it could take up to two years for the nerve endings to heal. I kept waiting, hoping that all of the sharp

pains in my breast were signs that the sensations were returning to what I had known prior to my surgery. Two years later I still could not stand for my breasts to be touched, and now that I have had the implants removed, my breasts still have about 30 percent of the feeling that they had originally had. It has been tragic for me to have to deal with this loss of feeling and lack of pleasure for the rest of my life. If appearance pleasure, I I had any idea my that improving to my feel of

would would

jeopardize never have

ability this

played

game

Russian roulette. One year after the implantation, it became obvious that I had developed capsular contracture. My

right breast was softer than the left one, which was as NEAL R. GROSS
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hard

as

a

softball.

I

had

followed

my

plastic

surgeon's instruction to massage my breasts daily to keep them soft, but it hadn't helped. Also, there were dense lumps all around the top of the left implant that were visible if I was to wear certain clothing, like this top that I'm

wearing now.

I couldn't even wear a top like this

before because you would see lumps sticking out on the top of my breast. Within a year of having an operation that was supposed to improve my appearance, I became very self-conscious about appearing to be deformed. The

head of plastic surgery at the University of British Columbia, by the way, has stated that up to 40 percent of implants may rupture or develop capsular

contraction, not .4 percent, not four percent, but 40 percent, and I've got it on a video that CBC did when they interviewed me on their show called "Marketplace." This means multiple surgeries for implant patients. How did this statistics grow from .4 percent Do we even know what I think not.

to 40 percent in three years?

accurate statistics are in this area? NEAL R. GROSS
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www.nealrgross.com

Now I'm going to tell you about my real troubles. I could live with the sacrifice of the loss I can live with my and my

of sensation in my breast.

husband's dissatisfaction over the appearance of my implanted breasts. health. Four months after the initial surgery, I became sick with flu-like illnesses that lasted for months on end. bronchitis and During that time I had pneumonia, extreme fatigue. I would start to But I could not live without my

recover, but then would get sick again only days later. Over the next year I felt exhausted all the time. I used to stay up until at least midnight

previously, but now I'd fall into bed with exhaustion by nine o'clock at night. Some days were worse than others, but not a day went by without a general feeling of fatigue and illness. Another symptom was sleep disturbance

since I would wake up two to three times a night soaking wet with perspiration. sweats. NEAL R. GROSS
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They call these night

In January of 1997, I became ill again with bronchitis-pneumonia for three months. On many

occasions, I had such sharp chest pain that I lost my breath and was unable to move. I also began to have

difficulty concentrating and often felt spaced out. Then in April morning. of 1997, I woke up one

I went to the wash room, and the toilet was Now, this wasn't a slight pink It was pure blood. I remember

filled with blood.

color, but it deep red.

being so horrified that this happened I jumped in my car. I was on my cell phone. I was sobbing all the

way to the doctor's office, and they said, "Oh, you've probably got a bladder infection." I had had a couple of bladder infections in the past. I had never peed pure blood before, and

it continued to happen after that. A week later, I went for an ultrasound for the lumps in my breast and chest pain. apparently showed nothing. any lumps in my The ultrasound

I had never previously had The doctor had no

breasts.

explanation, and I felt I had hit a brick wall with the medical establishment. NEAL R. GROSS
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In

the

summer

of

1997,

I

began

to

experience debilitating joint pain.

My left hand was

so stiff and was aching that I could not clinch my fingers. and arm. I felt like I had arthritis in my left hand I have no history of this disease on either

side of my family. I mean, I know I could go on forever.

I'll try to sum it up. removed in January of 1998. then. have

I had the saline implants I have not been sick since Otherwise I don't a very strong

I still have night sweats. anymore chest pain. I

have

constitution, which is what I had before, and the only thing I have to deal with now is the way I look, and it's taken me two years to have the confidence to date again because my husband left me. through this with me. I have three children, ages five, seven, and nine, and I am producing a video on body image to take to all of the high schools across North America. I also am the founder of the Women's He could not go

Investment Network.

So if you want any good stock

tips, just see me after. NEAL R. GROSS
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You consider myself

know, a

I'm

a

very

capable I

and went

I to

very

smart

woman.

university at the age of 16 and all the rest of it, and this was the most stupidest thing I ever did, was to do this because I believed the professionals, and

whatever. I have pages here that I wrote. I think

the media is afraid to say anything because of where their funding comes from, and I think the Internet is the best thing that ever happened to women in this situation because they can finally be heard without any filters, and that's why most of the people in this room have given their testimony, because they've gotten on the Internet. here today. And opportunity. CHAIRMAN WHALEN: Ms. McGinn. MS. McGINN: Good morning. My name is Thank you, Ms. Angus. I thank you very much for this They've become educated, and they're

Maura McGinn, and I'd like to thank you, Mr. Chairman, and the other members of the panel this morning for the NEAL R. GROSS
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opportunity to appear before you today. Let me start by answering the questions like everybody else you asked of the witnesses at

today's hearing.

First, I am a professional actor and

model who is appearing before you today representing only myself. Second, I have no financial or other

professional ties to any saline filled breast implant manufacturer or industry association. Third, I am paying personally for all

travel and other expenses related to my participating in this hearing. Fourth, I am not a party to any pending lawsuit relating to breast implants. And finally, I do not now, nor have I ever derived income of any kind from surgical procedures using breast implants or from treating patients with complaints implants. Why then am I here today? important that you hear from more Because it is than industry they believe that are related to breast

representatives who only have financial interests in NEAL R. GROSS
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the income and from researchers whose interest in the subject is merely academic. You also need to hear from people like me, breast cancer survivors whose lives have been and will continue to be affected directly and immediately by the recommendation you make. I want to assure you that while I am a professional actor, I am not acting this morning. My

words and the emotions that prompt them are quite real and sincere. I support fully any and every decision

that will add to the information available to patients about the benefits and risks of saline filled breast implants, in much the same way that I wanted to know everything possible about the efficacy of the different treatment options I had when my cancer was diagnosed. I also want to know everything there was to know about the different options available for reconstruction. I want to state this as clearly as it can be stated. Manufacturers of saline filled breast

implants must be required to do all the research needed to assure people like me about their safety. NEAL R. GROSS
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The fact

that these devices have already been implanted in my body does not diminish in any way my need to know that they are safe. Anyone who is either already using saline filled breast implants or who will be faced with the decision in the future about using them is not just entitled to this information, but should be guaranteed that it will be provided. My case may be instructive. Unlike other

breast cancer patients, I chose not to be reconstructed immediately. In fact, I waited six years before making

the decision to have additional surgery. Why did I wait so long? Well, part of the

reason was that I wanted to focus all of my emotional and intellectual energy on my treatment. Also, part of

the reason was, frankly, I was not sure I was going to be around. But at least -- I am thankfully. But at least an equal part of the reason was that I was not convinced about the safety of breast implants. At the time I was diagnosed with cancer,

silicone gel implants had become very controversial, and I did not want to wade into those troubled waters, NEAL R. GROSS
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given what I was hearing, what my doctor was telling me, and my own research. Six years later my research, combined with my doctor's advice and counsel, led me to my decision to use saline filled implants. Although the

information about saline filled implants was limited to and often more conjecture than fact, nothing I had read or heard and no experience that I have had so far has come close to convincing me that my decision was

incorrect. To the contrary, my decision to be

reconstructed has had a huge positive impact on my life. Because I am happier with the way I look, I am

also happier with who I am. I know that there are those who say that my appearance should not matter, and in some sense they are right, but they're also wrong. I know from

personal experience that for me at least, and I suspect millions of other women as well, how I look strongly affects how I feel and how I relate to others. A moment ago I said I support all efforts, like those being considered by this panel, that will NEAL R. GROSS
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add to the information available to patients about the benefits and risks of saline filled breast implants. Anything the FDA can do to add to the base of knowledge about these implants, including continuing to

vigorously implement the PMA process, should, indeed, must go forward. The manufacturers more are comprehensive to do the and research the more

required

widespread they are forced to disseminate the findings, the better. There's no justifiable excuse for this not

being the case. I also want to make it clear, however, that the ultimate decision about assuming the risk of using saline filled implants must continue to be left to people like me, the cancer survivors whose lives will be affect by whether or not they are

reconstructed. Unless there is incontrovertible evidence that saline filled implants are unsafe, breast cancer patients must continue to be allowed to obtain them. Make sure that all the research is done. Make sure

that the research is conducted properly, and please let NEAL R. GROSS
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us know about the suspected risks and concerns. But do not ever allow the decision about whether I can use them to be made by someone other than me. And that includes all of the members of this

panel, the FDA as a whole, the implant manufacturers, or anyone on Capitol Hill who knows -- who think they know more about my body than I do. Thank you. CHAIRMAN WHALEN: And Ms. Duhala. MS. gentlemen. DUHALA: Good morning, ladies and I Thank you.

My name is Karen.

I'm 38 years old.

have been happily married for 14 years and the mother of two children, a daughter who is eight and a son who is six years old, and I hold a full-time working

position. I am here today to share my experience regarding surgery. my own decision to have breast implant

I have personally paid for my travel expenses I do not have any

incurred to attend this hearing.

financial ties with breast implant manufacturers, and I have never been, nor am I currently involved as a NEAL R. GROSS
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witness in any lawsuits involving breast implants. I am, however, an office manager for a plastic surgeon, a solo practitioner in the Baltimore, Maryland area. I have been employed with the plastic

surgeon for the past six years, and being that he does perform breast augmentation, along with many other

cosmetic procedures, a portion of my salary is derived from breast augmentation surgery. I'm using my own personal vacation time today to cover the missed day at work. When originally reading about the hearing today regarding saline filled breast implants, I did, in fact, speak with many former patients to see if they would come and share their own experiences with you. Most declined because, quite frankly, I could not

guarantee their confidentiality. I, too, like my privacy, but with respect to the past silicone breast implant controversy, the fact that most people do not like to talk about their private lives and their private decisions in the public eye and the fact that I have had a very positive experience, and my decision has affected me in a

NEAL R. GROSS
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positive way, I thought it was important for me to come and to speak. When thinking about what I was going to say today, first I went through all the statistics and I read all of the articles on the studies back from the silicone breast implants and how far we've come, and then I redirected my focus onto patients that I came across through the practice with my six years of

employment, and I began jotting down their stories. And what I found is that I am one of the patients. I, too, fit the category of the patients

that we often see. Almost all of our patients have been

embarrassed by the way they look.

They feel guilty

about coming to a plastic surgeon and expressing how they feel. think. They worry about what other people will These are women who are in A

They're not vain.

their late 20s to the early 40-ish age bracket. large percentage are married with children.

They're

involved with schools and PTA and church organizations, civic organizations, and hold jobs. women who are making choices. NEAL R. GROSS
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They're educated

When consultations, some

meeting of the

with women

patients who make

in their

decisions after meeting with the doctor that I work for, they decide not to undergo breast augmentation, breast implant surgery. Other patients we elect to not do the

surgery on, and, yes, there are those many that do elect to have the surgery and do have. I had personally contemplated having breast enlargement for many, many years. humiliation go back as far as high school. a

Years of I can still

vividly remember the teasing by my friends and, oh, yes, by my family members, too; the feeling of

humiliation when wearing certain clothes, let alone a bathing suit. Please don't misunderstand me. I have

never lacked self-confidence, and I feel that for the most part I'm a well rounded individual, but I, too, was self-conscious about the way I felt and in the way I looked. I avoided certain places in certain

situations. Having the surgery has not changed my

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life,b ut it has given me a personal boost. when I walk, I walk with my back a

That is, bit I

little

straighter, and I hold my head up a little higher. feel better about myself.

I wish I could explain passionately what the impact has done for me, but I can't find the words. It's funny because my husband was dead set against my having this surgery. He thought I was crazy. When I was

making my decision, I was like many others. reluctant. say, what

I was worried about what my family would my friends would let say, what the my church of

affiliations

would

think,

alone

guilt

spending so much money on myself. Would I be giving the wrong message to my two young children about really what's important in life? Shouldn't I be saving my money for the braces

and the college education? But with all of that said, the most

important thing to me was it was my decision. my choice.

It was

As in primarily all aspects of my life thus far, I have made personal choices, and with almost NEAL R. GROSS
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all

of

my

choices,

there

are

associated

risks

and

responsibility. I though I'm made the choice I my to went AAA drive, through magazine and even

well

educated, I read

driver's on the

education

training;

driver tips.

I have even taken auto mechanics class to I still

learn how to check air pressure and my oil.

know the risk that any day I could be involved in an automobile accident. I made the choice to have children. There

were risks involved with childbirth and risks that my children would not be born so-called normal. the risks were known and presented to me. Some of

Others were

not, and although I received excellent prenatal care and followed my doctor's orders, no one could prevent nor no one could predict that my son would be born a bilateral cleft lip and palate baby. I smoke. I know the risks. I'm fully

aware that my smoking will some day cause my death more than likely. My point is that breast augmentation is a choice. Like almost everything else, surgical or

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nonsurgical,

there

are

choices,

risks

and

responsibilities. My personal experience was that I was well informed of the risks both of undergoing a surgical procedure using general anesthesia and the risk of I

breast implants themselves.

It was my choice.

accepted the risks, and I still accept the risks that there may be complications down the road. My choice to have breast augmentation was one of the best choices I have made personally in my life for my own self. I strongly feel that as long as

women are educated about the benefits and the risks, it should be a woman's choice. It is also my opinion that today, between the implant manufacturers, the ASPS, and the doctor's responsibility of his or her addressing the pros and cons to every surgical procedure they perform, breast implants or otherwise, that patients are well informed today. I sometimes feel like we -CHAIRMAN WHALEN: Excuse me. Could you

come to a conclusion, Ms. Duhala? NEAL R. GROSS
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MS. DUHALA:

I can.

-- that we as a practice scare patients, and I'll just sum it up. It was one of the best decisions. I would

like to share and I'm going to leave this with you. When our patients come to our practice, because some people were talking about breast feeding and the four percent of risks, the information that we give out, and I work for a Board certified plastic surgeon, it is noted that it is 20 to 40 percent of patients do run the risks of the capsular contracture, and it's all in this booklet. Also, there's an informed consent that we have. It's a four page informed consent about the

risks, and it does stress that for certain things as far as breast feeding children, there is no studies that shows that it is or is not dangerous, and that is written out. And that's the biggest thing. I feel that

the most important thing in making a decision to have any cosmetic surgery is to have a good doctor who will educate you and give you all of the information, and NEAL R. GROSS
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with the Internet today, I agree.

The information is

too available if the doctor is not willing to do that, but check your doctor out, and somewhat evaluate your doctor as your doctor is evaluating you. Thank you. CHAIRMAN WHALEN: Thank you.

I believe all of the individuals who had been scheduled have now had time at the podium, and before we proceed to the consumer groups, we'll take a ten minutes break. (Whereupon, the foregoing matter went off the record at 10:06 a.m. and went back on the record at 10:21 a.m.) DR. KRAUSE: If everybody could please

start getting back to your seats, we could go on with the meeting. Thank you. CHAIRMAN WHALEN: If everyone will please

take a seat, we'll try to resume, and we're going to be proceeding to the presentations of consumer groups and consumer information providers with the critical

distinction now being that ten minutes are allotted to each of the presenters, and I would remind each of the NEAL R. GROSS
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presenters to again please try to be as fastidious as the individuals were in terms of noting the time. When

the yellow light begins to flash, it is key that you begin to sum up, and if the red light flashes, then please come to a conclusion. If there were any of the individuals who had been previously identified who showed up late who would still like to address the panel, if you could please identify yourself to the FDA, then we will try to get you in if we can. The first listed consumer group, consumer information provider is Ms. Nicole Cummings from

Implantinfo.com MS. CUMMINGS: gentlemen. Good morning, ladies and

My name is Nicole, and like many of the

women that will speak before you this week, I, too, have breast implants. However, augmentation patient, in I addition think I to being a breast broader

bring

much

perspective to the issue before you. at www.implantinfo.com, and Implants also

I host a Web site as Web Breast Site by

known

Augmentation

Information

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Nicole, which I founded in early of 1998. I paid for all of my own travel and

accommodations to be here today, and I will not be reimbursed by anyone for any of my expenses. I am here on behalf of myself as a happy breast augmentation patient and on behalf of the tens of thousands of women that visit my Web site each month. I have no financial ties to the implant industry or to any health professional societies. not a witness in any lawsuits relating to I am

breast

implants. Thanks to the sponsorship with plastic

surgeons who sponsor my Web site, I've been able to allow my Web site to grow to the point where we serve up to over 16 million hits per month and to 160,000 unique visitors each month, all free to the countless women seeking information about breast augmentation. I launched the Web site about two years ago because I wanted to provide a community for women like myself to share their experiences. The only

information I could find on the Internet at the time NEAL R. GROSS
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were surgeon Web sites and society Web sites.

They I

were very helpful, but as a patient I wanted more. wanted to interact with other women.

Once the site was launched, women from all around the country immediately began to pose questions and answers on my form about breast implants. wanted to know the issues and the risks. The amount of ignorance that women came to the table with -- excuse me? Closer? Sure -- the They

amount of ignorance that women came to the table with was not surprising. However, the number of women that I had no idea how many women

came was very surprising.

felt the same way that I did. I believe that breast augmentation

patients now, however, are very different from years ago. Women are much more informed. They are actively

seeking this information and taking an active role in their own preoperative education. I think anyone who has done any research about breast augmentation knows that this surgery, like any other, poses risks. The reasons I am here today is

to discuss those risks, as well as the benefits of NEAL R. GROSS
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breast implants. I am also here to tell you that I believe women today choose know enough about those risks to decide to implants and to do so with proper

breast

informed consent. My Web site is currently the number one site on the Internet relating to breast augmentation. I believe that the amount of traffic on my Web site qualifies me to briefly speak about what women know and feel about saline breast implants. I've passed out a booklet to each of you that contains some of the stories that women have Emailed me and posted on my forum. I've received

thousands of them and just brought a few today to give you an idea of the type of knowledge that women have and what women have to say about implants and their experiences. Some of the stories listed on my Web site are in my experiences section, and some I have simply saved in my scrapbooks to remind me on a daily basis how important it is for women to be informed about this procedure. Some of the stories are just happy stories NEAL R. GROSS
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from happy patients, and some are from women who have had complications and still feel the surgery was well worth it. What these stories also reinforce for me in my own personal sentiment is that despite some of the imperfections device, that breast implants implants may have, like a any very

manmade

represent

positive thing and are able to change for the better the lives of millions of women. I would like to read some of those stories to you, and I will try and keep them brief. This story that I'm about to read is kind of funny, and this person E-mailed me telling me why she felt she wanted to have breast augmentation. Most women worry about diving into a pool and having their boobs fall out of a bathing suit. me on a hot, crowded day, I dove into a pool For at

Caesar's Palace in Las Vegas and had both my curves fall out of my bathing suit. could float? Well, as I was frantically grasping for the curves, hoping that none of the 500 people sitting NEAL R. GROSS
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Did you know those things

by the pool would notice, one thought went through my head. "That is it. I'm getting boobs."

That was just another day in the 32 years of my life where I resembled a 12 year old boy. changed my life? self. I am no Has it

No, but it has changed my self of longer self-conscious about my

appearance.

Okay.

Maybe once in a while, like any

normal person would be, but it's no longer a daily, terrible ordeal. Another woman wrote to me. I decided to get breast augmentation I was a 36 AA

because I was very out of proportion.

and had two bris breasts (phonetic) that were almost unbearable for me to look at. I was very self-

conscious, even with my own husband. I spent way too much time comparing myself to other women and never felt adequate as a woman myself. While the recovery was much more difficult than I expected, I had no complications, and my only regret is that I did not do it sooner. go through a full day without ever I can actually once comparing

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myself to anyone else or wishing I had something it seems I should have had in the first place. I feel complete, like a real woman. I am

not self-conscious at work or in my personal life, and I love to put on my clothes in the morning knowing that they will fit right. I did this for me and only me, and I am so very glad I took the time and money to do something that pleases me so much. I am not ashamed or

embarrassed in any way.

In fact, I'm proud of myself

for being strong enough to admit that I could look at myself, see something I wanted to change and change it. The next comments that I'm going to read are from a woman with saline implants telling another woman what she would want to tell her if she was considering having this surgery. If I could tell women anything about my experience with saline implants, I would tell them this is major surgery and not to be taken lightly or with a cavalier lifetime replaced. attitude. and that Expect they that they won't need last to a be

will

eventually

Know that just as natural breasts are seldom NEAL R. GROSS

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perfect, neither are implanted breasts. If you expect to see improvements rather than perfection, you will most likely be satisfied with your results. Now, this last story I'm going to read is a favorite of mine because I just think it's

hysterical. Women like myself are constantly asked why we're so vain. their teeth. Why do we choose vanity? They get braces. They People fix get dental

implants.

No one seems to care. This woman's response to this was: I was I

born legally blind in one eye, and it was crossed. got it straightened a little ten years ago. ever questioned that or said I was being vain.

Nobody It was

like it was okay for me to fix my eye so other people didn't have to be subjected to its ugliness. Most people acted like I had purposely

offended them with my cockeye and told me I really should have it fixed. I used to literally get beat up Growing up in the Bronx was

in school because of it. cruel.

Some people would say it was unique or even NEAL R. GROSS

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sexy, and that would make me feel better. Now, imagine if we were all allowed to walk about topless. People have been insulted if they

were forced to look at my breasts because they were so ugly. They would be begging me to fix them and telling I would have really gotten

me I should get implants.

my butt kicked on a daily basis. You just can't please them. I really

don't care what other people see as right or wrong. This is my life. So I will keep my cockeyes and my

implants, and I don't care what anyone else says or thinks. People really need to learn how to live and let live and stop being so rude and judgmental. just gets tiresome. As you can tell from some of the stories that I've read and those that are discussed on my Web site each day, women today are informed about the real risks and the issues surrounding breast implants. It

Visitors no longer come to my Web site just asking how much will the surgery cost. Instead they now are

asking about smooth, round, textured, anatomical, what NEAL R. GROSS
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is rippling, what is the contracture rate, what is the failure rate; they know what the issue are. Today women overwhelmingly know what they are talking about and know what it is they are

choosing, and I'm happy to be a part of that each day. I have enclosed in your booklet a printout of the index of questions on my form from a typical day so that you can see the types of questions that women are asking. In closing, I think that it's vital that I leave you here today with one general theme. It does

not and should not matter to you or anyone else why I wanted breast implants or why millions of women want to have breast implants. We are not here to judge whether

women should be entitled to want to improve on oneself, and it should not matter if it is for breast cancer reconstruction or simply to augment one's appearance. What is important is that women should be allowed with informed consent to have this surgery. What you may see as the failure of an implant, such as the potential for rippling, hardening, or the need for replacement, informed women see as acceptable risks in NEAL R. GROSS
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the

process

where

the

emotional

and

psychological

benefits outweigh the risks. Women know the risks about breast

implants, and to the extent that they do not, they can be and want to be well informed. If women know the

risks and are willing to take the risks, they should be allowed to do so, and I don't think anyone should take that away from them. I hope that what I've said here today has been helpful. Thank you. CHAIRMAN WHALEN: from the panel? (No response.) CHAIRMAN WHALEN: Thank you, Ms. Cummings. Are there any questions

Next, Ms. Lowder from the Toxic Discovery Network. MS. LOWDER: Good morning. Thank you for

this opportunity to speak to each one of you. I wish my experience had been like the last lady and the letters she read, but mine was not. In 1984, I chose to have saline breast implants put in NEAL R. GROSS
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in Charlotte, North Carolina, after my plastic surgeon told me unequivocally that they would last a lifetime, and I did question. implant surgery. Actually I had not been there for

I had been there due to an accident

and needed a scar revised, and he brought it up, and consequently I ended up -- it was my choice. But informed choice I think is one of the key components here. After I was implanted in 1984, in July of 1984, it didn't take but a few months and I was in the hospital in very serious condition, and that was the beginning of what has been a downward spiral for the last 23 years. I have been in the hospital for untold surgeries. implants I have gone through a hysterectomy. were removed in 1984 shortly after The the

discovered a chest wall tumor just above the left one, and they finally agreed with me that there was a

problem.

I was leaking a grayish-black matter, and

then the doctor got in there, he discovered that I had fungus and large black particulate matter. Now, I'm not saying that every implant has NEAL R. GROSS
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this kind of a problem.

I don't know, but I do know

and I can tell you that I experienced it, and what ensued, what happened after that was a nightmare. I ended up with a total hysterectomy the same day that they removed the implants. They

discovered that I was filled with tumors that I had not had before. I need to backtrack a little bit right now. I had been an Olympic contender ice skater. I was an equestrian. I I

was a dancer, ballerina. played the piano.

I was a very happily married woman I

with two very young boys, very active, healthy boys. had whatever in this world wants. and a family.

I had a loving home

That surgery on December 5th, 1984, where they removed the implants and the hysterectomy, was just obviously just prior to Christmas. morning, the two boys and I were On Christmas at the

waiting

Christmas tree for my husband to come downstairs, and he came down with one bag in his hand, and he said with regret that he was really sorry, but he just didn't want the responsibility anymore. NEAL R. GROSS
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He didn't want to be

married to somebody who was so sick.

So he left.

I have gone through countless surgeries. It's too many to even go through. I, in fact, go home

from here to have a couple more tumors removed from my abdominal area and for a third time a cell tumor out of my hand. The seizures, the MS-like condition can

only be handled where morphine -- I take 60 milligram os morphine daily just to get through. Fortunately my

boys are now grown, and they've been educated, and they're on their own, and I thank God for that because I don't think I could go through it again. My experience was not what you hear some of these women sharing about, oh, the wonderful side of implants, and maybe there is a wonderful side. address that. I can't

I didn't experience it, and the women I

talked to on almost a daily basis have not experienced it. I was not informed. would take to have doctors I don't know what it what the real

explain

problems can possibly be or what people can expect from implants, but what I do know is that it is an elective NEAL R. GROSS
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surgery, and until we have an assurance that people like myself are not going to go in expecting nothing but good things and come out with a total disaster, maybe it is chemical sensitivity. think we need more answers I don't know, but I we can just

before

unequivocally, indiscriminately open the doors and say anybody that wants an implant, come get it because there are too many that are unsuspecting like I was. Today I am in total financial ruin. lost my home. Excuse me. I was a commercial designer. Not too many I

I had to close my business that I loved.

people you talk to can honestly say they love what they do, and I did. I loved every moment of it, but the day

that I was -- pardon me -- driving from Sandy Springs in Georgia to Cumming, Georgia to meet with a builder on a major highway, I had a seizure. The neurologist

and my other doctors had been trying to convince me that it was time to back away from my career. Well, that day I had no choice. said that I thank God that my boys are grown. were robbed. When I They

They were robbed of a mom that was a NEAL R. GROSS

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happy, healthy, well adjusted person.

Instead what

they have to remember is a mom not knowing whether or not when they came home from school I was going to be in the hospital, whether I was going to be in bed or whether I would be able to cook dinner for them that night. When I say this has been a nightmare, it really has, and I don't think you people sitting up here want to open that can of worms or continue to allow it to be open until there is some recognition of what has and what is going on. There are too many people. same stories day after day after day. typically known as ANDS. I hear the

I have what is

It's like MS, along with a

whole host of other things, and they're too long to even go into. I wrote them all down, and I thought that sounds like a laundry list. There's no point in

getting up here and reading off to you what's wrong with me today. I hate it. That much I can tell you.

I came to know a woman by the name of Kathy Keithley Johnston with Toxic Discovery Network NEAL R. GROSS
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going on three years ago now.

She had started from

pure love in her heart a nonprofit organization to help women who were and had gone through situations like I've had, and she's been there, and she has continued to be there for me. As I close, I want to read a statement from Kathy who has had to close the doors of TDN, but before I do, one other thing I want to mention to you. I purposefully have not named the manufacturer of my particular implants. The reason you don't hear as many

of these stories as you could is because six years ago now the manufacturer that was involved with me decided to pay me while I was still involved in the global settlement, and my part in that was I had to sign an agreement, a contract not to disclose and not to repeat what was in the contract or anything about my story. had to remain silent. nightmare that I had I

I could not tell anybody the gone through or that this

manufacturer was paying me $3,300 a month, and they did for four years. They years ago now. stopped paying me in November two

My father, my brother, and my oldest NEAL R. GROSS

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son are helping me stay afloat.

That's a hell of a

note for somebody who was as proud as I've always been. I'm sharing that story with you because, about the manufacturer, for one reason. I was being paid to be quiet. I question why

I had saline implants.

I had the same saline implants that they've had a number of problems with, a lot of problems with. I'm not going to be their conscience. The

story will come out, but I'm not here today to try to run them into the ground. I'm here to talk to you, the

FDA, about a product that I don't think is safe. I just want to close with a comment from Kathy Johnston who has selflessly given of her time, their money, and her love. president and Medical Kathy is an R.N. and of Toxic Discovery

Director

Network, and she wanted me to read this quote, and her comment was, "I want it read loud and clear." The right to choose is meaningless without the right to know, and I think that's pretty poignant. And with that I thank you for giving me the time. CHAIRMAN WHALEN: Would you entertain a

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question, Ms. Lowder? DR. BURKHARDT: Hi. I have two questions.

The first is that you referred to the global settlement in relation to your saline implants. It was my

understanding that the global settlement had to do with the silicone gel implants, but you had saline implants, and you were part of the global settlement? MS. LOWDER: DR. that you've That is correct. The an second enormous question amount is of

BURKHARDT: had

obviously

difficulty for which I think any of us must feel great empathy and sympathy, but it was not really clear in your presentation to me why you related that to your implants. MS. LOWDER: tied together. tie it together. I saline have I silicone have -even in though my I had Because it has been directly

I have, and I apologize that I didn't

implants,

silicone

lymphatic

system, in my brain, in every tumor that has been removed that they have checked since 1994. silicone, and my first question was: NEAL R. GROSS
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I have

well, how can I

have silicone when I had saline implants? The answer to that is the outer casing is silicone. DR. BURKHARDT: MS. LOWDER: Thank you very much.

Thank you. The next speaker is Ms.

CHAIRMAN WHALEN:

Lynda Roth from the Coalition of Silicone Survivors, and I would remind each of the speakers to please answer for us the questions at the beginning of their presentation that have been posed by the FDA. MS. ROTH: Thank you. I came

I paid my own way to this meeting.

of my own volition, and sadly I will not be reimbursed. I have no financial ties to industry or any group or individual in the health professions. I

am included as a claimant in the current Dow Corning bankruptcy settlement. I did receive a settlement from That was from almost dying.

Mentor for a whole $1,519.

I derive no income from anything related to breast implants. In fact, it has cost me many

thousands of dollars to help others with the situation. Ladies and gentlemen on the panel, I'm a NEAL R. GROSS
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social worker with MSW and the leader of a support network for women with breast implants. I'm here today

to represent the many women who are unable to come. There absence. are numerous reasons for their

Among them, the inability to afford a trip;

illness; and their feelings that they could not speak eloquently enough to get their points across. Many are embarrassed that they made this medical decision only to become ill and become a burden to their families and friends. They hide their shame.

Some fear the legal repercussions of being public while legality still exists of these devices. I'm here today to tell you my experiences with these women and with saline filled breast implants. Our network has existed since 1990 and has about 5,500 members. About 25 percent of those women A

who have had only saline filled silicone implants.

few of these women do not have problems, but they are concerned. The vast majority have medical problems

caused by their implants. As saline filled implants become more

popular, the percentage of calls coming from women with NEAL R. GROSS
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these breast implants has mushroomed.

In the last

three years, our calls have consisted of more and more saline implantees, nearing 50 percent today. Our network provides information free of charge throughout the world to those who cannot afford to pay for it, and we do provide a newsletter that some people pay for. We are incorporated as a 501(c)(3)

nonprofit organization. Silicone is not biologically inert. may be chemically inert. It

The silicone in a shell

contains many chemicals which react when placed in a biological setting. Some of these chemicals are known

to be harmful to the body. I am sure you have a list of all the

contents of the shells of these devices. read about the harmful effects of each. inert devices. Biochemical reactions can

I urge you to They are not

and

do

occur.

When implants are removed, often scar tissue remains. Some of the harmful chemicals that slough off the shell will remain in the chest, causing further reactions. NEAL R. GROSS
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Foreign reactions. tissue

bodies

are

known

to

cause

The calcium deposits that form in scar cancerous tissues on mammograms.

resemble

Screening for cancer is much more difficult with any implant. Women who have had cancer are known to have a suppressed immune system. I am one such woman,

and although at the time the implant seemed like a great idea, it was probably the biggest mistake of my life. It almost cost my life. Women who have suppressed immune systems should not be exposed to products that are known immune system suppressants. The manufacturers of saline that

goes into these implants are on record as stating their solution is not meant for long term implantation into the human body. It is a dated solution, and one that

cannot be guaranteed to remain sterile. Generally the date is less than a year from the time of the implantation. Sterility is only

as good as the conditions of the operating room and the cleanliness of the medical persons involved. In addition, sterility is never 100

NEAL R. GROSS
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percent, even with the modern ways we have to sterilize medical devices. Implants are microporous. fluid with the body. They exchange

Anything in the implants can get

into the body and vice versa. We bodies. all have bacteria and fungi in our

This leads to the incubation of nightmarish

microbes that cause serious damage. Saline implants can and do rupture, often. Besides the risk of the original surgery, women are exposed to repeated surgeries for years to come. The

FDA reportedly has over 25,000 claims of injury from these saline filled devices. We have heard that our What have they done

government is here to protect us. about these claims?

Some of the most common problems reported to us are deflation of the implant, often within a few weeks after surgery; hard, painful breasts; shifting of the implant so that it has to be surgically moved back where it belongs; body aches, joint pains; loss of energy; unexplained rashes often on the chest and neck; burning, twitching and weakness of muscles; and shortNEAL R. GROSS
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term memory loss. Many all over their and women report significant hair loss and with

bodies,

including usually

eyebrows reverses

eyelashes,

this

problem

implant removal. Women necrosis. silicone. I would like to specifically address the studies that the manufacturers have conducted, the socalled five year studies. lack of informed consent. Product label inserts are not often given to the women. Women often have these implants placed First, I want to mention the also report skin and nipple to

Testing

often

reveals

antibodies

without hearing a word about the possible problems. They report being given papers to sign when they have been prepped for surgery and have been given a

sedative. the

They report being given papers to sign after before they are fully recovered from

surgery

anesthesia. I have heard from more than a dozen

symptomatic women in the last three years who have NEAL R. GROSS
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never been contacted by their plastic surgeon after implantation with saline implants, despite the fact that they were told they were in a study about the safety of these devices. These women's symptoms remain unreported. If I had heard from this many and other group leaders have heard from at least this many, how many others remain unreported? These women are all part of a study being done by McGhan or Mentor. The plastic surgeons that This

insert the implants are collecting the data.

greatly reduces or eliminates any scientific validity of the study. Another problem is that a study that only goes on for five years can hardly define risks that may take 20 to 30 years to discover, as in the case of asbestos. We know for a certainly that women with

silicone implants often do not show symptoms for at least six to eight years. more. What possible value can a biased study, one in which not all the plastic surgeons follow up NEAL R. GROSS
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For some it is 15 years or

with patients and that only goes for five years, have? This certainly calls into question the accuracy of the data of these studies that you will hear at this PMA meeting. These saline filled silicone implant

studies need to be followed by unbiased researchers for at least 20 years before we can know what damage they will do to many of the recipients. I have heard doctors joking about these studies, stating that they are a study in name only. I

seriously doubt that any of these doctors who make money from placing implants are going to come here and admit that these studies are not scientifically valid. A survey of all women implanted should be done to find out how many had problems and how many have reported these to their plastic surgeons. This

should not be done by manufacturers of implants or the plastic surgeons. studies and check The FDA should closely monitor these the accuracy of the information

regarding these. Women call our network with illnesses

after a few years after implantation stating that they NEAL R. GROSS
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have never heard from their plastic surgeons. they do finally call their surgeon

When of

complaining

symptoms, they are told that these symptoms could not possibly be from the implants. I have heard from one of these women again recently, and after four years she had not once heard from her California plastic surgeon, despite the fact that she was told she was enrolled in a study. She

finally called his office to report problems and was told that her problems were not of the type implants cause. I'm including the E-mail of one woman who contacted me less than three weeks ago. saline implants for four months and She had her was already

symptomatic.

When she contacted her plastic surgeon,

he told her it was not due to her implants. She has persisted, and he has removed

them, but with great reluctance. is an uncommon problem. women and other support

I do not believe this

From the reports I get from group leaders, this is an

extremely common situation. Those of us who speak out are called

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fanatical, practical,

hysterical intelligent,

women. and

I

am

a

serious, I am

educated

woman.

dedicated to informing people on this issue. If this meeting is not a serious effort to evaluate the safety of implants, but instead a rubber stamp to please the manufacturers by approving their products, then I ask that you make absolutely certain that all women are at least a week before the surgery given the important information about side effects. They need to be informed of the wealth of information available. They need to be given this without bias or

comments by the physician. Often concerns are just waved away with a sweep of the hand and a statement that "we don't have any problems with this." to me. My paternalistic group response members from report this same That's exactly what happened

their

plastic

surgeons.

Maryland is a good example of informed consent law. The state has an excellent policy of informed consent regarding implants, but unfortunately the doctors do not comply. NEAL R. GROSS
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There's an increasing problem with younger and younger women desiring on getting breast implants. The age range is from 13 to 17 years of age. Although

some few plastic surgeons refuse to implant women so young, most can and do take these young women,

children, as patients.

They are not yet old enough to

understand the lifetime of surgeries and problems that may occur, yet they are having implants placed in their body. Ethically and morally these women should not be candidates for surgery. Their parents need to Often these

be truly informed of all the problems.

young women's bodies are not finished with development. Yet they're being exposed to surgeries. You will hear about the social aspects, the self-esteem issues, the self-worth issues, and the feel good issues, Many, "about of myself the now" reports are just here the

today. opposite.

many

results

The emotional pains are tremendously high. Women commit suicide to escape the pain. Increasing The

numbers of women are being granted disability. NEAL R. GROSS
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www.nealrgross.com

taxpayers are paying for this. saline implants in the '70s,

I know women who had and they are on

disability. shoes.

I'm grateful often that I'm not in their

The last point is that women have to sign away their rights to ever sue the manufacturers of these devices now. They have to sign a waiver saying If they are

they will never sue if they get implants.

so safe, why are we having to sign away our rights to ever sue? The manufacturers know these devices are not safety. In conclusion, I thank the panel for your time, and hope that you will make the decision to require more study on saline implants before any

approval so that women of this country and, indeed, the world will benefit from this hearing. Thank you. CHAIRMAN WHALEN: question? MS. ROTH: Sure. Dr. Dubler. Would you entertain a

CHAIRMAN WHALEN:

NEAL R. GROSS
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MS. DUBLER: You said

Thank you for your testimony. that you were dedicated to

informing women, and I wonder what sorts of information do you think they should have. data on the package insert? Should they have the

Should they have the raw

data from some of the studies that have been conducted? How would you go about informing them? MS. ROTH: Maryland has an excellent I would ask

brochure that has quite a number of pages.

that you look into that and find out exactly what they have done, but in informed consent, information is no better than the doctor who is giving it out, and

regretfully, most doctors do not give informed consent to their patients. Now, the FDA has had currently understood risks of saline filled breast prostheses, which I have here, for years. There's a thing on the back that says These are not being

"signature," "date," "witness." filled out.

These doctors are not giving these to the

patients, and if they do give them anything, they wave it away and say, "Oh, this is just a formality. We

don't have any problems with these," which is exactly NEAL R. GROSS
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what happened to me. MS. DUBLER: So are you suggesting that

the materials be given out, that are given out by physicians, be composed by other people? MS. ROTH: plastic surgeons be Oh, absolutely, and that the informed that they are not to

discount this information because patients truly have a right to informed consent. And I do have a picture here that was sent to me by one woman. She wants it back, of a saline So I

breast implant that was removed from her body.

would like to give you this information and share this picture. CHAIRMAN WHALEN: The next speaker is Ms.

Eileen Swanson from Survivors of Salines. MS. SWANSON: Eileen Swanson, and I am Good morning. here to tell My name is you of my

experience with saline implants and the experiences of that of my support group members, Survivors of Salines. To answer your questions, because I am on disability and have low income, I accepted the offers of small donations for this trip from several other NEAL R. GROSS
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breast

implant

survivors.

I

also

received

an

honorarium to participate in the workshop yesterday from the National Center of Policy Research for Women and Families, a nonprofit research center. I have no financial ties with industry or health professional societies. I'm a claimant in the

Dow Corning bankruptcy, and the answer to four is I derive no income from surgical procedures using breast implants or from treating patients with complaints they believe are related to breast implants. My Web site and support group, Survivors of Salines, is entirely supported by me and the

information is provided free of charge. I was implanted with Mentor leaf valve

(phonetic), smooth shelled, saline breast implants in July of 1989 for reconstruction following Stage 2

breast cancer on the right and prophylaxis on the left. Other than my cancer diagnosis, I was healthy and

active. The right implant deflated in the recovery room before I even woke up. from there. NEAL R. GROSS
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It went straight downhill

Another

surgery

followed,

a

saline

only

tissue expander a few months later, then a new set of Mentor saline textured surface implants two months

after that. In the following months I suffered from local complications: infection on both sides, swollen

lymph node, pain, redness and swelling on both sides, rash and skin tags on my chest and under arms, burning chest pain which persists to this day, Baker III

contractures, and a cluster of lumps on the left mound which mammography indicated was a crease in the

implant.

The lumps were later biopsied and found to be

fibrocystic changes in my tissue. Systemic symptoms began suddenly the third week of April 1990 and included widespread, constant pain, morning stiffness, frequent cramps, diarrhea,

nausea and vomiting, ceca symptoms, severe headaches, bladder pain, frequency and incontinence, extreme neck pain attacks which leave me bedridden, abnormal

fatigue, difficulty in concentrating and short term memory loss, chemical sensitivity, and a sleep disorder which I was told was called fragmented sleep. NEAL R. GROSS
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I was explanted in May of 1991.

I had a

brief reprieve, but then my condition deteriorated. The scar tissue capsules imbedded with microscopic

fragments of silicone were left in my chest underneath the muscle. them now Doctors tell me that surgery to remove likely mean scraping my ribs and

would

possibly doing more harm than good. In implantation, September my of '93, four years I after

condition

worsened.

developed

numbness, paraesthesias, and burning pain in my legs and feet, arms and hands and face. stumble things, and fall easily, shuffle These caused me to my feet and drop

have

difficulty onset

breathing, inability

difficulty to speak,

swallowing,

sudden

disorientation and dizziness, and balance difficulties. You can imagine with all of these symptoms I've named so far what it's like to live on a daily basis. I lost my photography business in 1994

because I could not hold my camera, move the props or backdrops, or even remember the technical details of my trade. NEAL R. GROSS
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I lost my marriage, my health insurance, my home, and I live in the attic bedroom in my mother's home. active I'm on SSI and Medicaid now. Army wife, full-time I used to be an of three, a

mother

community volunteer. bicycling, hiking,

I enjoyed cross-country skiing, and bicycling, in addition to

working full time. Now I'm lucky if I can walk around the corner to church on a really good day. Board certified doctors have diagnosed

fibromyalgia, with all of the symptoms that are defined by the American College of Rheumatology criteria. My current neurologist says that despite normal EMG, she feels I clearly have a neurological problem in my legs, at least in my legs. My current rheumatologist states that he believes abnormal I have blood more work than fibromyalgia he says due to the

which

indicates

inflammation, such as elevated ANA, C reactive protein, retic count and CPK. From the time I was 39 years old, nearly ten years ago, my life has been an agonizing struggle NEAL R. GROSS
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to do the everyday things most people take for granted. I have adverse reactions to nearly all medications

we've tried, even herbs and homeopathic remedies and even food. So treatment and pain management remains an

extreme challenge. In 1998, I founded Survivors of Salines, which is an Internet saline implant support group, I

because I wanted to educate women about the risks.

have heard my story repeated in countless women who have written to me who have had saline implants. have similar symptoms and similar They in

difficulties

obtaining effective medical treatment. Women like me who have had only saline implants, never gel, tell me they're experiencing

deflations, rippling of the implant shell, infection, contractures, multiple surgeries, joint pain, fatigue, hair loss, irritable loss, bowel chest syndrome, pain, bladder pain,

tremors,

memory

sleep

disorders, and

fibromyalgia,

lupus,

neuropathy,

scleroderma,

allergic reaction to silicone. I'm sorry. Women who have replaced silicone gel

NEAL R. GROSS
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implants

with

saline

implants

report

that

their

conditions worsened after receiving the saline, often having violent reactions such as intense inflammatory response in the breast, along with the other symptoms they have already had. Most of these women tell me that their symptoms are debilitating, and many are on disability. Women seeking to be implanted often tell me that their doctors did not even advise them of the risk of local complications. shell is They are frequently not aware that the much less that it can shed

silicone,

microscopic fragments, and they are always shocked when I tell them that sterile saline has a shelf life after which time it has been shown to support microbial

growth. I am requesting that the pre-market

approval applications for saline filled silicone breast implants be denied because the following have not been accomplished: standardized testing for allergy to

silicone for all saline implant patients. Salastic (phonetic) allergy was documented in 11 percent of patients in a study of endolymphatic NEAL R. GROSS
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subarachnoid shunt failures in 1998. American Society of Plastic

According to the the silicone

Surgeons,

shell of the saline implants parallels the material that makes up other medical devices. Second, a national registry of saline

implanted women by a government agency, information from which to is made available numbers to of saline women implant

patients,

include

implanted,

symptoms experienced, and treatments available. The plastic surgeon is often the sole

source of information for a prospective implantee and may have little incentive to advise breast implant

patients of possible complications since they earn an average of $3,000 from an augmentation or a

reconstructive procedure. Instead of the current climate of denial, there should be early detection of breast implant

related symptoms, whatever they might be. And third, studies and tests involving This is

women who have saline implants and are sick. not a novel concept. new illness becomes

It happens all the time when a known, such as Legionnaire's

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Disease in 1976. new bacteria.

The CDC intervened and discovered a

In our case, it would seem to be common sense to test not only for reaction to the silicone shell, but also for bacteria and fungi which have been shown to grow and reproduce it is are in no FDA's risky longer sterile that they

saline, saline

even filled

though

the less

position because

implants

release only salt water when they rupture, and not silicone gel. I am asking you to protect future It never

generations of women in a way that I was not.

occurred to me that my doctor would place an object in my body that was not approved for use in the human body. There is no proof that saline breast

implants are safe, and isn't that what should have happened bodies? Breast implants are not life saving, nor do they restore function in any way. Please do not before they were ever placed in women's

allow women to continue being used as guinea pigs. NEAL R. GROSS
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Thank you. CHAIRMAN WHALEN: Our next Thank you. we're going to go

speaker,

slightly out of order and go back to an individual consumer. So this will be a five minute address And

maximally to us rather than a ten minute address. this will be Ms. Lisa LaCivita. MS. LaCIVITA: I'm sorry I Hi. Thank you. make it at

couldn't

my

predetermined time.

I'll be very brief.

My name is Lisa LaCivita, and I am a woman that chose to have breast augmentation, and in coming here I had none of my travel or accommodations paid for. I don't have any financial ties to the industry.

I'm not party or witness to any lawsuits involving implants. However, I am an anesthesia provider, and I do derive income from surgical procedures involving breast implantation. that. But I'm here as a consumer advocate for a women's choice to have breast implantation, and I I think that you should know

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really believe that whether it's for reasons of vanity or self-esteem or to correct gross disfigurement that results from necessary surgical procedures, that it should be a woman's choice to have breast implantation. It's determine the the responsibility of the of the that FDA we to are

safety

products

implanted with and the responsibility of the patient's surgeons to discuss the risks and the benefits of the surgical procedure. Then it's the responsibility of the

patient to make an informed choice and to give informed consent to proceed. I'm a nurse anesthetist that works in a cosmetic surgery center, and for the last ten years we've done about 250 cases a year, about 90 of which are breast augmentations with saline implants. that time, we have not had any difficulty During with

patients, and the data that you have is part -- we participated in the data that was contributed. But we haven't had any patients come back and ask that their implants be removed. The most

common risk or adverse event that we have seen has been NEAL R. GROSS
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mild capsular contracture, and even then patients may come back and have their implants removed, have a

capsulectomy, and then have the implants put back in, but none of them have chosen to have them removed and to remain so. So in conclusion, I'm just here to urge that you not take away a woman's right to make informed choices when considering breast implantation. Thank you very much. CHAIRMAN WHALEN: Thank you.

Returning then to the consumer group list, so back to ten minute presentations maximally, we have next Ms. Susan Sherr from the National Coalition of Cancer Survivors. MS. SHERR: Good morning. In response to

all four of your questions, the answer is no. My name is Susan Sherr, and I thank you for this opportunity to speak to you, to this committee this morning. I'm speaking today as a representative of the National Coalition for Cancer Survivorship, and I will correct that in the record, NCCS. NEAL R. GROSS
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It is the only

patient

led

organization

advocating

on

behalf

of

survivors of all types of cancer. But I also am speaking today as a 22 year breast cancer survivor and one who has had personal experience with both reconstructive surgery and with breast implants. I have previously testified before the FDA when silicone implants were being reviewed, and in

1998, on behalf of the Cancer Leadership Council before the IOM Committee reviewing the safety of silicone

implants. I mention this because NCCS' position and that of most of the major cancer organizations has essentially remained the same since 1991, and that is that evidence based science be the determinant in your reviews, questions, deliberations, and findings. There will be several organizations and

individuals testifying about the importance of options particularly for breast cancer survivors and on the topics of quality of life, mammography screening, and an informed consent. issues in my remarks. NEAL R. GROSS
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So I will not address these

Unfortunately, the silicone implant issue is one that has been contentious and litigious, and one that has pitted woman against woman, created a media frenzy that has led to fear and misinformation in the general public. We do not want to see this replicated

with saline implants. As an organization representing survivors of all types of cancer, all ages and both sexes, it is especially important to us that the FDA factor in the ramifications of faulty or non-science based decision making be it for a drug, a biologic, or a medical device. By manufacturers this of I mean drugs, the implications or for

other

biologics

devices

leading to the potential loss or reduced development of new products, thus affecting patients and their

treatment options. It should also be understood that although this hearing is about saline implants, and NCCS is primarily concerned with the outcome for cancer

survivors, we are also concerned that the process by which a decision is reached be thorough, thoughtful, NEAL R. GROSS
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balanced, and not subject to hype, emotion, or possible bad publicity that the FDA might receive. Unlike the environment when silicone gel PMAs were being considered, there is considerable

information and data available about the safety and efficacy conducted States, of saline filled Europe, rupture, implants. China, under and In the studies United over

throughout

contracture,

inflation,

inflation, texture, microbial growth, and even noise following surgery have been reviewed. We are appreciative of the role of the FDA in protecting all citizens of the United States from unsafe and harmful products, but we do not need the FDA to take a paternalistic position. informed are perfectly capable Women who are well of making good

decisions, and women who have already dealt with a diagnosis of breast cancer may be inclined to accept more risk than the average person. this right if nothing dangerous They should have or unexpected is

presented in the PMA data. It is also important that the FDA include the patient experience as a body of evidence when

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making its evaluation, both pro and con, and that the established, respected, and reasonable patient-consumer advocacy community be more involved in the process. Thank you. CHAIRMAN WHALEN: Thank you.

Next is Ms. Sybil Niden Goldrich of the Command Trust Network. MS. GOLDRICH: Good morning. Command

Trust Network has paid my way here. any grants from any industry people. been appointed by the federal

I do not receive I am -- I have court to

district

represent women on certain panels in MDL 926.

I am the

consumer representative to the Tort Claimants Committee on the Dow Corning bankruptcy. I get no money from performing surgical procedures. I'm grateful for this opportunity because we're at a very critical juncture in the long

unresolved debate over breast implants, and I'm going to repeat today some of the very same remarks I made to this panel 12 years ago when I first spoke. Unfortunately, the issues that I raise

NEAL R. GROSS
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today must again be addressed. I thought to myself, gee, I've last longer than a lot of implants. (Laughter.) MS. GOLDRICH: The FDA continues to be

caught in a situation where virtually all classes of implanted medical devices, including breast implants are sold to millions of Americans without full and open analysis of the risks versus the benefits. Last year 130,000 saline filled implants were sold in the United States. advocate for more than a I've been a consumer and have had the

decade

occasion to speak to many women with saline implants. Believe me when I say that a large percentage of them are surprised and even shocked to learn that the safety of saline implants has never been formally approved by the FDA. They are also keenly disappointed to learn that the manufacturers were under no obligation to

begin collecting safety data until 1993, 20 years after saline implants were first marketed. Much of the

industry data that will be presented to this panel, NEAL R. GROSS
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therefore, will be of very limited value.

It is not

possible to evaluate the long term risks of saline implants when the data is only on a short term basis. Moreover, the two findings from the PMA data that were released prior to this conference are disturbing in their face. In the first instance, I

refer to a recently published comment from Dr. Bruce Cunningham, who was the lead researcher on the studies. PMA

He has reported that the failure rate for At that saline

saline implants was five percent per year. rate, after five years, one in every four

implants will have failed. failed.

After ten, half will have

This was on the WebTV article. A woman who has double implants is

essentially guaranteed to have one of them fail within ten years. Of course, the failure rate between the We

five year mark and the ten year mark may be worse. don't know.

We don't know because there's no data

available from that time period. Secondly, I refer to an industry study

that was cited in last years Institute of Medicine NEAL R. GROSS
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report.

Based on an observational survey of 2,855

women who received saline implants during 1995 and 1996 from McGhan Medical Corporation, it appears that women with saline implants must return to the hospital at a much more alarming rate than women with silicone

implants. With silicone implants, one in four women need additional surgeries within the first five years, according to the Mayo Clinic. According to the McGhan

data, however, one in three breast cancer survivors had to return to the operating room within the first 12 months with all of the inevitable risks and expenses involved in those procedures. The McGhan study divided women into two categories: augmentation. post-mastectomy reconstruction and

Of the cancer survivors, 35.9 percent

suffered infections, deflation, contracture, or other problems that necessitated removal of their implants. For augmentation patients, the rate for

the same set of problems was 18.9 percent.

Although it

seems that one in four saline women need new surgery within the first five years after receiving --

NEAL R. GROSS
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altogether it seems that one in four will need new surgery within the first five years after receiving implants. In other words, the rate for saline implant

patients is approximately five times higher than for silicone implants. But we can't really know this for sure, again, because it's only a one year study. I urge the

panel to make every effort to consult with medical professionals and other knowledgeable experts to obtain all of the available evidence before making a final decision. Bioethical concerns are very important.

Because breast implants are under the category of a cosmetic rather than a life saving device, most women assume that the risks are minimal or nonexistent. They

had better be prepared to accept a higher risk in the case of a brain shunt or a heart valve, but not for breast enhancement. Therefore, I recommend that this panel,

the panel members, attempt to elicit the answers to the following questions: One, what is the threshold of safety that NEAL R. GROSS
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must

be

achieved

before

cosmetic

devices

are

made

available for general marketing? Two, cosmetic devices how does the safety standard for for life

differ

from

the

standard

saving devices? Parenthetically I might add: ever approved a medical device has the FDA

that is not a life

saving device when it has as high a failure rate as breast implants? Also, period be to how long should the surveillance to measure

enable

scientists

epidemiological results? My medical concerns. Slick advertising,

most women today are misled into believing that breast implants have been proven safe. It is important that

you make the following determinations. What saline implants is the rate at which women with

experience

capsular

contracture,

infections, loss of nipple sensation, skin numbness, skin rashes, or bacterial contamination? What is the rate at which saline implants deflate or rupture? NEAL R. GROSS
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What is the time period for these rates? What is the rate at which saline implants interfere with mammographic tests for breast cancer? Informed consent. Women who decide to

undergo implant surgery only after a limited knowledge of the risks, later many of them say, "If I'd only known, I would have said no," but then it's too late. Most patients are not unduly upset if unpleasant

information is provided at the outset. What upsets them far more is when any

level of truth is withheld and when only half truths are provided. I urge that the panel press hard to

resolve the following. What level of information is necessary to permit consumers to make an informed consent decision about breast implants? How will women be notified in detail about potential risks, complications, and the longevity of devices prior to implantation? Will the package labeling include specific data about the rates and time periods of all medical complications? NEAL R. GROSS
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Will

photographic

examples

of

medical

complications be made available to women to enable them to visualize the potential risks? Will the package inserts be provided in duplicate so one can be kept in the surgeon's files and the other be given to the patient? How will women be informed that their

implants may interfere with mammograms and self-exams for breast cancer? The last thing I want to approach are long term studies. The Institute of Medicine recommended

last year that a standardized system, some type of registry be set up to help collect even more extensive information about the frequency, causes, management of medical complications of breast implants. I asked for that in 1988. The following

questions fall fully on the FDA to address. Number one, should the FDA establish a

monitoring system by which the implanted devices are tracked and retrieved upon removal for further study? Should they be a chain of custody set of documents? NEAL R. GROSS
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Should the national

breast by

implants model

be

registered and

in

registry

number

serial

number? Should consumers be informed of the model number and serial number of their individual implants? Should they be issued a permanent wallet size card marked with all permanent information about their implants? privacy? If a certain model of implant is deemed defective, what's your recall procedure? to pay for the cost of the recall? Adequate information was not available to me when I got my breast implants after breast cancer. I've had persistent health problems after my surgery. I've had two implant replacement operations. The article I wrote for Ms. magazine in 1988 brought widespread public attention to this issue and ultimately led the FDA to the moratorium for the devices in 1992. reiterate now: What I said then and what I will the patient's interest is the only Who's going How does that protect their personal

valid interest in this equation and only it must be NEAL R. GROSS
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served.

A product that is merely not unsafe should not The American

be placed in the general marketplace.

public expects and deserves that the FDA approve only those products that can truly be called safe. Please don't fall off that very fine line that separates the two. Thank you. CHAIRMAN WHALEN: Question? Thank you.

Ms. Brinkman. Yes. Ms. Goldrich, you

MS. BRINKMAN: made some good points. So -MS. GOLDRICH: MS. BRINKMAN:

I can't write fast enough.

I spoke too fast. -- is there a possibility

that some of the lists of points that you would like the FDA to consider, such as labeling and other issues that you made, just a brief list of what those are? MS. GOLDRICH: I will be very happy to

supply them to the panel and whatever group the panel chooses to write these documents. early advisory committee on I did serve on an the informed

writing

consent documents, but that committee was manned by NEAL R. GROSS
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manufacturers and plastic surgeons, and at the very end of that committee process, it was decided that the support groups were not even to be listed as an

information source. I hope that we have gone well beyond that in the last 12 years and that we can get some really solid answers to my questions. you. CHAIRMAN WHALEN: DR. BURKHARDT: Dr. Burkhardt. Ms. Goldrich, I was I'll supply them to

listening as carefully as I could, but I think I missed some statistics that you reported from the Institute of Medicine Report. MS. GOLDRICH: those. DR. BURKHARDT: Did you say that 19 Yes. I have to go back to

percent of patients who had augmentation with saline implants had their implants removed within one year? MS. GOLDRICH: say that. DR. BURKHARDT: MS. GOLDRICH: And that's in the report? Yeah, it is. Yes, I did. I think I did

NEAL R. GROSS
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DR. BURKHARDT:

Thank you. Any other questions?

CHAIRMAN WHALEN: Yes, I'm sorry. MS. DUBLER: the package insert. MS. GOLDRICH: MS. you're DUBLER: that

You mentioned at one point

Yes. And the I wonder, package again, insert if is

suggesting

appropriate to go to all patients.

The struggle in

informed consent construction has been to alert the consumer, the patient, to the material risks and those on which the patient should focus. Do you think that the package insert will help that process or perhaps hinder it? MS. GOLDRICH: I find it interesting that

for many years I have asked for the manufacturers to package the product in such a way that the package insert is on the outside of the box rather than on the inside of the box. The box is opened in the operating room. It doesn't even do the doctor any good there. I do

believe that the package insert should be supplied to a NEAL R. GROSS
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patient. When you buy a bottle of medicine in the pharmacy, they give you this big, fat thing stuck to the side. we It's the package insert. have it, and we There's no reason should also have

shouldn't

supportive documents to explain that package insert, but to keep it from somebody makes that person think that you're keeping a secret. There product. duplicate. The can package be no secrets should about be made this in

insert

The doctor should be required to write that They change them

he has read this new package insert. all the time.

Whenever they lose a lawsuit they change

the -- they up the ante and change the package insert, and the patient should be given that package insert. Let her go home and read it at three What

o'clock in the morning when the questions some. am I doing? Am I safe? I think it's only reasonable. Should I do this?

Is this healthy for me?

The more

information you get, the better, and I don't think in the long run a lot makes it more confusing. NEAL R. GROSS
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I think

what happens is you see certain issues repeated over and over again, and then they're repeated, they hit home. People understand. Anything else? CHAIRMAN WHALEN: MS. GOLDRICH: CHAIRMAN Thank you.

Thank you. Next is Ms. Cynthia

WHALEN:

Pearson from the National Women's Health Network. MS. PEARSON: I'm Cynthia Pearson. I'm

the Executive Director of the National Women's Health Network. The network is an independent member

supported organization dedicated to using a science based analysis to safeguard women's health rights and interests. We companies, lawyers. And in answer to the four questions, we have no travel expenses. in industry or We have no ties with anyone societies. We're not accept no money from pharmaceutical or trial

medical

device

manufacturers,

professional

involved in any lawsuits and derive no income from NEAL R. GROSS
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clinical services. Some of the panel members and FDA staff remember that the FDA has been actively involved as a voice for women consumers throughout the long history of FDA's consideration of breast implants. for the For the regulatory status of two first decades we have these

nearly to

advocated

agency

classify

devices as requiring study, and then to require the manufacturers to provide data demonstrating the safety of these devices. We're pleased that the day has finally

arrived when this panel is meeting to evaluate data that have been collected on saline filled breast

implants and make a determination about their safety. We're also pleased to have the opportunity to speak here. Unfortunately we've been forced to

prepare this statement in something that's a vacuum, as you see that most of the public speakers are speaking in advance of the data presentation. Because of this we'll make our remarks in a way that just give our general impression, but hope to have some opportunity to participate tomorrow after NEAL R. GROSS
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data have been presented. We believe, based on what we know as of this morning, that saline filled implants have not yet been tested in an adequate way to demonstrate that they are safe for anyone. There's no long term data

available showing what happens to women with implants after five to ten years. This deficiency is particularly

frustrating in light of the fact that women have been using these devices for more than 30 years. has been based on their belief that the This use products

wouldn't be available if they weren't known to be safe. The women are out there, and we know as well as you do the deficiencies of retrospective

studies, but they were a potential source of collecting data on the long term effect, the effects of long term sue of implants, and the fact that this opportunity has been ignored makes us question whether for some reason the manufacturers don't want the answer to that

question. But the women want the answer to that

question, especially because of what we are beginning NEAL R. GROSS
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to know in a very scientifically valid way about the short term experience and safety record of the

implants. information

We've heard some reports this morning of PMA that have been discussed publicly that

don't sound so wonderful, you know, a steady, constant breakage rate, a reoperation rate. These are serious and painful health

problems, even setting aside the question of whether there are larger systemic effects. These Everyone on both complications sides of are the not contested. agrees,

issues

acknowledges that they occur, although the data that establish the frequency with which they occur are only beginning to be made public. Similarly, in addition to the hardening of breasts and infections, the breakage rate is a common problem; the need to undergo another surgery. This

means that women, if the average age of implants is still in the early 30s, although it may be dropping because of the growing popularity of implants inserted when women are teenagers. Women might require

reoperations every five years.

I'm just guessing, or

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every ten years for the rest of their life. This is a serious consideration that

individual women must weigh and face, but we believe that the panel has to also weigh and face as to whether a product with that kind of regular failure rate can be considered to be approved for certain groups of people. We are specifically concerned because of our long history of work on breast cancer issues and with the new in the '90s wave of breast cancer specific survivor groups about the affect of implants on women who receive them following mastectomy. It appears, based on what we know this morning, that relatively few of the women studied for the somewhat short term effects of saline implants, received their implants for reconstruction after

mastectomy. It's not improbable. There is a

biological plausibility to the question of whether or not breast cancer survivors may be at increased risk for some health problems caused by implants as compared to other women. There might be health problems. It's

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possible that there could be health problems that are specific to breast cancer survivors, but we won't know that question, the answer to those questions, unless the FDA and you give the advice to the FDA to require that the manufacturers look at that question, and the answer will take what it takes to answer any scientific and clinical question like this: trials with adequate

sample size to determine an effect. We heard results of meta analyses. We

heard a guesstimate of what percent of women were in those meta analyses and in a statement that we should infer that the women had no risk -- in this case it was of connective tissue disorder -- because the overall group had no risk, but we all know, even we in the consumer world, that if there weren't enough women with saline implants to answer that question, the fact that they don't affect the overall outcome doesn't prove that you've answered any question about the impact on their health. So I'm deeply troubled, and as our breast cancer specific groups -- I know that the agency has received a letter from Breast Cancer Action in San NEAL R. GROSS
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Francisco expressing this concern, that there is this possibility that any of these implants could be

approved for use in reconstruction after mastectomy without adequate studies. We are more than anything concerned with the lack of long term follow-up. It's been 15 years

since your predecessors on this panel first recommended to the FDA that the manufacturers conduct studies and provide sound data assuring the safety and

effectiveness of these devices. It's been 12 years since the FDA accepted that recommendation and informed the manufacturers that such data would be required, and it has been eight years sine this panel found the available data wanting and engaged other research bodies in trying to

stimulate needed research. There's absolutely no excuse for us not to have solid data on the long term effects of these devices in year 2000. Another concern we have is the loss to follow-up rate. We don't know what it is now. We

haven't seen the studies that you reviewed in advance NEAL R. GROSS
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and

will

be

presented

this

afternoon,

but

loss

to

follow-up, it's a frightening prospect for us out in the consumer world. If the loss to follow-up is higher than average in the type of trials you're used to seeing, we would wonder based on the anecdotal reports of women in support groups who say they've talked to this woman, that woman and another woman who either has never been followed up or who has had her surgeon assume that her reported complications are not related to her device. We would be worried about selective loss to follow-up, and we hope that the FDA would have -- the FDA staff will be able to report to us later this afternoon that as they've examined the case reports and the

manufacturer's submissions very carefully, that they've looked at and verified the procedures that have been used for follow-up. So we hope that you'll give that really serious attention this afternoon and tomorrow. And to wrap up, I'd just like to say as the representative of a consumer group that works on a multiplicity of women's health issues, we know that the NEAL R. GROSS
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term

"FDA

approved"

carries

great

weight

with

the

public.

These implants currently have the sort of aura

of approval just because they've been in existence and been used so widely for so long. But if the panel votes to recommend

approval for any of the saline filled breast implants being considered today, women will even more so believe that these devices have been proven to be safe. Women count on the FDA to protect their health, and we believe and urge you to consider that approving a device such as this, without long term safety data and without data that specifically

demonstrated safety in the populations in which it will certainly be used would be a betrayal of that trust

that women place in the FDA. We urge you to take these concerns into consideration as you evaluate whether the data before you are sufficient to warrant approval. Thank you. CHAIRMAN WHALEN: DR. question. BURKHARDT: Dr. Burkhardt? If you don't mind, a I

One thing I did not -- could not follow. NEAL R. GROSS

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www.nealrgross.com

was unable to follow your apparent criticism of the statistical studies, many of which we'll rely on

specifically in regard to meta analysis. Can you explain that to us? MS. PEARSON: Yes. Before the FDA acted

in the early 1980s -- excuse me -- the early 1990s to restrict access to silicone gel filled implants, they were by far the most common type of breast implant used. The meta analysis, like all of the

previously published studies for the most part included the general population of users identified in a variety of ways, but unless the study was -- a particular study was designed specifically to include women with saline filled implants, their study population would reflect the general population, which was more than three-

quarters women with silicone gel filled implants. Dr. Ory said that when he was asked what is the relative risk of I believe it was connective tissue disease after using -- in women with saline filled implants as compared to a woman with no implants at all, he said that the overall risk is close to one. NEAL R. GROSS
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The risk for women with silicone gel filled implants is close to one in those studies which separated them. So since those two risks are both one, we can infer that the relative risk for women using saline must be close to one. My point is if there weren't enough women with saline filled implants in those studies to come up with a population size that has the power to find a relative disorder, risk which of is something like connective in the tissue general

relatively

rare

population, the fact that the inclusion of some few number of women with saline filled implants did not change the grand total relative risk does not tell you

one way or another whether or not those women are affected by their implants. I believe, and I think you'll have your hands on more of the numbers to know specifically, and you'll have saline specific studies submitted by the manufacturer, but I believe that until now the majority of published studies don't have the sample size of users of saline filled implants to answer very questions at all. NEAL R. GROSS
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many

DR. reason one

BURKHARDT: suspect the

Can

you

think of

of

any

would

incidence

systemic

problems to be greater with the silicone implants -with the saline implants than with the gel implants? MS. PEARSON: Not necessarily, but as a

representative of a consumer organization, I believe that these devices should be held to the same standards that they would have been held to if they came to the

agency after the device amendment passed in 1976. The fact that they existed before '76

allowed the situation to emerge that we have now, where we have decades of use, and I believe that you would only ask that question if you had the opinion based on clinical experience in decades of use that you know something about saline filled implants. We would like the opinions that have been believed up until now to be verified by trials of the size and design that can get the answer to those

questions. DR. BURKHARDT: MS. PEARSON: Thank you.

Another question?

(No response.) NEAL R. GROSS
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MS. PEARSON:

Thank you very much. Thank you.

CHAIRMAN WHALEN:

Next we'll hear from Ms. Martha Murdock from the National Silicone/Saline Implant Foundation. MR. HAYTON: I'm Ron Hayton. Martha was

sick this morning so I got volunteered. We have no connection with the

manufacturers, no money except from my regular job. I'd like to discuss a few issues for the panel to consider when making recommendation for PMA -thank you. I would like to discuss a few issues for

the panel to consider when making recommendation for PMA approval of saline breast implants. Thank you for providing an opportunity to do so. First, I'd like to quote a couple of

paragraphs from a recent article published January 24th of this year, copyrighted by Healthion Web, M.D. I

chose this article because of these types of comments repeatedly. The article states regarding the advisory hearing, underlying the meetings are very clear

NEAL R. GROSS
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indications

that

the

FDA

is

in

favor

of

approving

saline filled implants, products that while available for a quarter of a century have never been approved by the agency. A decision to formally approve silicon gel implants which are more controversial than saline

implants will come later, but all indications are the FDA is favorably disposed to approving them as well. The article further states a recent letter sent by the FDA to a member of Congress declared that the agency feels that there is a need not only for saline implants, but also for silicone gel implants, at least for reconstruction follow breast cancer surgery. Saline adequate continues for to all be filled women, a breast the implants stated. for are not There silicone

letter

public

health

need

filled implants. The letter was sent to Representative

Thomas Bliley, Republican from Virginia, Chairman of the Commerce Committee which oversees FDA activities. As you see, the buzz is that the PMAs will be approved. The FDA implies that Congress wants

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implants to remain on the market because they are a medical necessity. They fill a public need, and women

should have the right to choose what she does with her body as long as she gives informed consent. I'm sure you'll hear these statements many times by those who wish to keep breast implants on the market. concepts, consider. It is my hope that what Congress wants is for the FDA to fulfill its duty to provide protection to the consumers that only safe, effective products will be marketed in the United States. increasingly implants is obvious much that higher failure in It has become for breast I am in agreement with most of these general but I think there are a few things to

rates

companies'

reports.

Recently published research indicates 25 to 30 percent women will need additional surgery in five years.

Putting that into perspective and relating it to human beings, that means of 150,000 women a year receiving breast implants, 45,000 women will have to endure

additional surgery with all of the risks and expenses involved with any surgery. NEAL R. GROSS
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I ask you as American consumers:

do we

wish to set a standard that a 30 percent failure rate of a product in five years is acceptable? standard that is acceptable to the FDA? In 1993, FDA Commissioner David Kessler Is this a

stated that a five percent failure rate was not a failure rate that the FDA could accept for this device. Dr. Laurie Brown, a FDA researcher, has done a comprehensive study on the rupture rate of

silicone implants.

It's been done for quite some time, I suspect that that is

but has not been published.

because she has found unbelievably high failure rates for these devices. I believe the FDA has an obligation to make this data available to the public and certainly to this panel. Although Dr. Brown's research reported

failure rates exclusively for silicone implants, one could easily conceive failure rates for saline implants would be the same or higher. Saline implants are manufactured with the same silicone bag or shell as silicone implants.

Additionally, they have valves that have been known to NEAL R. GROSS
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leak and fail at unbelievably high rates. And finally, because sometimes are under filled, the risk of crease fold failures is increased. Another paragraph from this article states that in the letter to Bliley, FDA said that it believes that women can evaluate risk versus the benefits of breast implants for their personal situation if they are well informed about the rate of infection and other local complications that can occur. The agency cited a study in the New

England Journal of Medicine published March 1997 that found infections occurred in 2.5 percent of the women undergoing implants; other local complications, All of repeat

including rupture, pain, and disfigurement. these may lead to medical interventions and

surgery, the letter stated. In the letter to Chairman Bliley, the FDA conveniently left out the information from the same study which stated that approximately 25 percent of the women studied required additional surgery in the first five years, and the reconstruction patients had higher complication rates than cosmetic patients. NEAL R. GROSS
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One thing you don't hear much about is the companies that have numerous problems with their

manufacturing processes.

It is evidenced by FDA Form

483 inspection reports for both Mentor and McGhan since the moratorium in 1992 for most breast implant

manufacturers prior to the moratorium. Inspection reports reveal quality control problems, the under reporting of complications, and the inability to validate manufacturing processes of these devices. In fact, the FDA had to resort to issuing a

consent decree against Mentor in 1998 just to get them to comply with the law as good manufacturing practices, and to insist the company validate its manufacturing processes. The bottom line is companies are having problems proving their devices are safe and effective. Former company employees have reported company data may be misleading and problems with devices are not

adequately addressed and corrected.

Could it be they

can't prove the products are safe and effective? A shed light thorough why investigation company data would is probably

onto

significantly

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different than published data regarding complications. I urge the panel members to review FDA 483s and their EIR reports for the past 15 years for each company submitting a PMA before recommending

approval. review.

I am providing you with samples for your

I'd like to briefly address the issues the manufacturers and breast implant advocates argue for PMA approval, along with my responses to these

statements. a copy of

Additionally, I'd like to provide you with Mentor's PR plan titled "Mentor v. the

World," which may give you an indication of where some of these myths may have originated. Myth number one, breast implants are

medically necessary. Response: medically necessary. functions. Myth two, breast implants fulfill a public need. I believe it could be argued that breast implants fulfill a public desire for reconstruction NEAL R. GROSS
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breast

implants

are

not

They are not required for body

patients, but there is not a public need for those who simply -- for cosmetic reasons. Surprisingly, only 15

to 20 percent of the women who have received breast implants do so for reconstruction. These people may be willing to take the risk for what they perceive as a benefit they may receive and are entitled to make their own choice, if and only if they are given all of the information. Would you choose a breast implant from a company who has been cited for repeated or if violation you knew of they good were

manufacturing

practices,

undergoing criminal investigation, or if you knew by having breast implants or if you've had breast implants many health insurance companies will deny you coverage? CHAIRMAN WHALEN: Mr. Hayton, I'll have to

ask you to come to a conclusion, please. MR. HAYTON: I thought I had ten minutes. Indeed, you do, but that

CHAIRMAN WHALEN: light is flashing. MR. HAYTON: Oh.

Well, I'll just leave it

at that then, and I'll give you the copies of PMA. CHAIRMAN WHALEN: Are there any questions?

NEAL R. GROSS
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No response.) CHAIRMAN WHALEN: We'll, just for planning

purposes, have one more speaker and then we'll break for lunch and reassemble after for the conclusion of the public speakers. Before lunch, we'll have Ms. Ann Fonffa from the Annie Appleseed Project. She's not here.

Ms. Margaret Volpe from Y-ME. MS. VOLPE: Thank you for allowing me to

present this statement to the advisory panel. My name is Margaret Volpe. I am a breast I have care my

cancer survivor and a breast implant recipient. no financial ties to manufacturers not being or

health for

providers,

and

I'm

reimbursed

appearance here today. I am a volunteer representing Y-ME

national breast cancer organization. Chicago and have chapters nationwide.

We are based in We believe that So we operate

no one should face breast cancer alone.

a 24 hour national 1-800 number, hot line in Spanish and in English, and provide peer support and

educational programs. NEAL R. GROSS
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Y-ME is committed to providing support and accurate information to empower individuals touched by breast cancer so that they can select the most

appropriate options for themselves in conjunction with their health care provider. When I was diagnosed with breast cancer in 1995, I faced the fears, anxiety and depression common to those diagnosed with a life threatening illness. Because of the size and location of my tumor, I had to have a mastectomy. I chose to have a tissue expander inserted into my chest when I had my mastectomy. This was

followed by an implant placed under the pectoral muscle in February 1996 once I'd completed chemotherapy. It was very important to me to have

reconstruction, not have to worry about how clothes would fit, to feel whole again, for my family and me not to be constantly reminded of my breast cancer, and to get on with my life. And I have had no problems or

complications with my implant since my surgery. Now, let me tell you why I selected an NEAL R. GROSS
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implant for my reconstruction.

Now, I know I have

ample tissue on my abdomen to be eligible for tram flap reconstruction. to endure the However, I knew I didn't want to have major abdominal surgery and painful

recovery period required for the surgery, and I also wanted to keep those muscles intact. I have several friends who did not have this option at all. They were told they were too thin

to have the needed tissue for the tram reconstruction. Even the latissimus dorsi, or back flap reconstruction, usually requires an implant. By doing nothing and settling on an

external prosthesis, my friends and I would be reminded daily of the mutilation to our breast. Each woman who

has had a mastectomy must be allowed to pursue the best option for her, including breast implants. At present, if a woman has had tram

reconstruction on one breast, she is unable to have a second tram reconstruction at a later date if she

should develop cancer in the other breast.

It is

imperative that we continue to have a choice, and for many of us, implants are the only option we have. NEAL R. GROSS
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Y-ME

and

I

believe

the

availability

of

saline implants is very important to women who face breast cancer. It is the only uncomplicated option

left for women who desire an implant as part of their breast 1992. It was very difficult for me to get the textured reverse, double lumen implant I received in 1996 because of FDA restrictions that required me to be in a clinical trial. I am on a patient registry. reconstruction after the FDA restriction in

In addition, the informed consent I signed in order to participate in the implant study was much more lengthy and detailed than the informed consent I signed to have the potentially deadly stem cell rescue in a clinical trial at Johns Hopkins. This panel must stick to the science when evaluating saline breast implants. Do not allow

yourselves to get diverted and sidetracked by special interests that may have litigation more on their minds than health issues. The National Academy of Sciences'

Institute of Medicine report has been issued, and the NEAL R. GROSS
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science is clear.

The IOM conducted an exhaustive and

definitive review of all existing research and found that there is no evidence that silicone breast implants cause cancer or disease. This report also found the same result for saline Science scientific emphasizes breast Panel implants. and The U.S. court's National

several

European

government W-ME

panels the

issued for a

similar wide

findings. range of

need

treatment

options as each woman, each woman must be able to choose the option that best fulfills her needs. One of W-ME's main messages to women and families seeking our help is to fully understand the risk and benefits of any medical choice, including the usual surgical risks. We have worked with FDA to

produce accurate information and used the FDA breast implant information booklet when counseling women. And when it comes to the implant itself, women should understand that no medical device lasts forever. knees and Shunts, heart pacemakers, even artificial joints have an expected life span and

possible local complications. NEAL R. GROSS
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And rupture and

women need

should for

be

aware

of

potential Adequate Doctors

the

replacement.

informed consent is a key part of the process.

should discuss the issues of risk and benefit in detail with their patients. Saline implants do have a silicone shell, but from the exhaustive research on silicone implants, pointed out by the IOM report, we also know that there is no convincing evidence that silicone produces an immunologic response. The IOM report states that such

diseases or conditions are no more common in women with breast implants than in women without breast implants. In closing, W-ME would like to work with FDA on informed consent and labeling issues that will be required if the FDA approves the PMAs. committee to act based on the science alone. Breast In the effort have to the cancer resume right is our to a devastating lives, select disease. cancer and I urge the

breast

survivors

appropriate

effective medical therapies or devices. Thank you very much. CHAIRMAN WHALEN: Thank you.

NEAL R. GROSS
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Ms. Volpe, I perhaps didn't hear it. you at the beginning identify any

Did

financial

relationships of your organization? MS. VOLPE: CHAIRMAN As I said, I'm a volunteer. And W-ME receives no

WHALEN:

funding from any manufacturers of implants? MS. VOLPE: I believe that they have

funding provided in the past by some, and our funding is public knowledge and can be -CHAIRMAN WHALEN: Right, but we do ask

each of the speakers to identify that so that if there can be any potential bias, those four questions need to be answered, and one of those would be if your

organization receives funding from any manufacturers. So that is, indeed, the case. MS. VOLPE: been. CHAIRMAN WHALEN: Are members? (No response.) CHAIRMAN WHALEN: Thank you. there any Thank you. questions of the panel I believe in the past it has

NEAL R. GROSS
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As lunch.

I

stated,

we're

going

to

break

for

I have right now about 12:05, and we'll take 45 So please reassemble at a time sufficient so

minutes.

that we can begin business at ten minutes to one. (Whereupon, at 12:03 p.m., the meeting was recessed for lunch, to reconvene at 12:50 p.m., the same day.)

NEAL R. GROSS
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A-F-T-E-R-N-O-O-N

S-E-S-S-I-O-N (12:56 p.m.)

CHAIRMAN WHALEN:

If everyone could take If everyone

their seats, please, we'll try to resume.

could please be seated, we'll resume the continuing public comments from consumer groups and consumer

information providers. And the next identified speaker if she's present is Ms. Stansell, who is here from the United Silicone Survivors of the World. MS. STANSELL: Mexico. The trip. question is who's paying for this I'm Anne Stansell from New

My husband and I are. Now, I need to explain something. We both

work only part time due to health reasons.

My trip all That's a

the way from New Mexico costs about $1,000.

lot of money for a couple that only makes about 24,000 in a year. I'm stating these figures to let you know

how very important it is for all of us to tell you that we are sick from breast implants. seriously as we do. NEAL R. GROSS
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So please take this

The answer to the next question is -- are you a party to a pending lawsuit? -- I am a claimant in the Dow bankruptcy court. Dow is offering a

settlement, which means I will probably end up getting $1.98, and my lawyer will get two thirds of that. The answer to the other questions is no. I'm speaking to you as a leader of a group of women in New Mexico in a similar situation. There

are some of their photographs so they can be here in a way. Ninety percent of the women in our group in New Mexico are cancer survivors. filled silicone shell breast implants. Many have saline None of us had

all the facts when we made the decision to get the breast implants. None of us realized we had a choice.

It was presented to me as all part of the treatments. need My doctor said, "You have cancer. radiation, and breast You

mastectomies,

implants."

There was no discussion.

No facts were presented to me

other than breast implants are perfectly safe and will last forever. This experience is commonly shared by

others in our group. NEAL R. GROSS
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If

they

should

ever

leak,

we'll

just

replace them, the doctor said, as if it's as easy as changing hair styles. No rupture often. one told me that breast implants No

No one told me about infections.

one warned me about other complications causing a need for 14 more surgeries or procedures. No one warned us No one

that saline would get rancid and grow fungus.

warned us about capsular contracture until a plastic surgeon pounded on our tender chests with both fists. If I had had all the facts, I would never have chosen breast implants, "chosen" being the key word. It should be presented to a cancer patient and

all others as a choice, and one can only make an intelligent choice if one has all the facts. Furthermore, the group of cancer surviving women I represent here before you wants me to tell you that breast implants are not medically necessary. did not need breast implants to get over We

cancer.

Implants are not life saving devices. damaging devices.

They are life

We have been robbed of our survival to NEAL R. GROSS
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live a healthy life to a mature old age.

We should

have been warned by the FDA that they knew nothing about the device being surgically implanted. there is some warning on a thing called I guess "package

insert." Now, think about it a moment. insert." "Package It I

It is wrapped inside the sterile package.

is not opened until the patient is under anesthesia. don't read well under anesthesia. In enough. closing, we need to know when

is

ASPRS (phonetic) tells us that 80,000 women of

child bearing age received saline filled silicone shell breast implants in 1999. Many will file Medwatch forms

of adverse reactions as many of us already have. What number is enough? Is it ten percent, 20 percent? take? Is it 50 percent? Even ten percent is too much. I clinical Check charge the the FDA to validate have now the When does it stop? What's it going to

trials

manufacturers patient

submitted. Check into

into

selected

follow-up.

patient intimidation by giving up their rights to sue. NEAL R. GROSS
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Thank you. I give the remainder of my time to Dr. Blais. CHAIRMAN WHALEN: (No response.) CHAIRMAN WHALEN: Thank you. I have been told that Are there any questions?

Is Dr. Blais here? he is not here. PARTICIPANT:

He's here. All right. While we see Ms. --

CHAIRMAN WHALEN:

if he'll arrive, are any of the following here?

unfortunately we had no timer, but it was about five minutes left -- Ms. Fonffa, Ms. Mullen, Ms. Williams. None of those are available? PARTICIPANT: Ma'am?

(Inaudible.) Yes. Actually that's We're

CHAIRMAN WHALEN:

going to be a little bit delayed from 12:50. following sequence, but you will be called. Is Dr. Puckett available? DR. PUCKETT: Good afternoon.

I'm Dr. Lin

Puckett, professor and head of the Division of Plastic Surgery at the University of Missouri Health Sciences NEAL R. GROSS
(202) 234-4433 COURT REPORTERS AND TRANSCRIBERS 1323 RHODE ISLAND AVE., N.W. WASHINGTON, D.C. 20005-3701 www.nealrgross.com

Center in Columbia, Missouri.

I'm also President of

the American Society of Plastic Surgeons. The Educational Foundation of the ASPS has received undirected research funds from both Mentor and McGhan. Both of These have been used for implant research. them are also exhibitors at our national

meeting, along with about 350 other exhibitors. My travel and hotel expenses are being I

paid by the American Society of Plastic Surgeons. have no ties to the manufacturers myself.

I'm not As

involved in any lawsuit involving breast implants.

a part of my broad based practice of plastic surgery in the academic environment, I perform breast implant

surgery both for reconstructive and cosmetic reasons. I, therefore, derive a portion of my income from this type of surgery. The ASPS represents 5,000 Board certified plastic surgeons in the United States and Canada. It

is the largest organization in the world of surgeons certified by the American Board of Plastic Surgery. Our members have provided care for most of the more than one and a half million women who have chosen NEAL R. GROSS
(202) 234-4433 COURT REPORTERS AND TRANSCRIBERS 1323 RHODE ISLAND AVE., N.W. WASHINGTON, D.C. 20005-3701 www.nealrgross.com

breast implant surgery over the past 30-plus years. As physicians, we know the women who have benefitted from breast implant surgery, but who may be uncomfortable speaking about this very personal subject in this public forum. We are their advocates.

The FDA determined in 1992 that there is public health need for silicone filled breast implants. Women's request for silicone or saline filled implants dropped off temporarily due to the concerns of the early 1990s. However, since 1995, we've seen a

resurgence of interest in and demand for breast implant surgery. The majority of breast implant procedures performed today is the silicone inflatable shell or saline filled breast implant due to the clinical study restrictions on silicone gel filled implants. Today

only three companies market the saline implant in the United States. Important research data has emerged in

recent years on both gel and saline filled implants. Because the outside envelope that is used for both gel filled and saline filled implants is a silicone

NEAL R. GROSS
(202) 234-4433 COURT REPORTERS AND TRANSCRIBERS 1323 RHODE ISLAND AVE., N.W. WASHINGTON, D.C. 20005-3701 www.nealrgross.com

elastomer shell, the study findings on gel implants to a great extent also apply to saline filled implants. In 1997, the prestigious Institute of

Medicine of the National Academy of Sciences undertook a major study of silicone breast implants funded in part by the FDA and referred to several times this morning. The IOM's key findings released in June of

'99 concluded that silicone implants do not cause major disease. to Breast feeding does not pose a health threat Silicone implants do not harm the

infants.

developing fetus.

Radiation does not hurt implants and

vice versa, and that breast implants have improved over time, reducing local complications. It further reported that implants do not weaken the immune system and that, in general, silicone as present breast implants is safe. The findings of this landmark study are reassuring for women and physicians. They confirm the

positive clinical experience of plastic surgeons over the years and the high level of satisfaction reported by women with implants. The study also recognizes the problems

NEAL R. GROSS
(202) 234-4433 COURT REPORTERS AND TRANSCRIBERS 1323 RHODE ISLAND AVE., N.W. WASHINGTON, D.C. 20005-3701 www.nealrgross.com

that can occur in women with implants. the possible need to replace

These include local

implants,

complications, and the potential need for additional surgery. These silicone implants. The latest data on these potential gel factors are relevant and for both filled

filled

implants

saline

problems specific to saline filled breast implants will be presented subsequently at this hearing. recent University of Minnesota Data from a multi-center,

retrospective study of 450 patients with saline filled breast implants with a minimum follow-up of ten years shows a deflation rate of 5.8 percent for implant

models currently in use.

This would be a failure rate

of less than one percent per year, and this is in contrast to the interpretation of these statistics

quoted earlier today. Deflation implant is generally with of a saline but filled breast risk

harmless

carries for

the

associated

additional

surgery

replacement.

While these risks are not insignificant, they must be NEAL R. GROSS
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viewed in the context of the patient's overall risk-tobenefit ratio. The consultation satisfaction with with Minnesota the saline FDA, filled study, found breast designed that in

patient is

implants

extremely high. of whom

Ninety-three percent of patients, most implants for cosmetic breast

received

enlargement, reported that they were satisfied or very satisfied with their surgery. Ninety-six percent said

they would make the same choice again. Extensive scientific studies today

document the safety of silicone implants and the high level of patient satisfaction. Much of the past

controversy surrounding breast implants has focused on claims of a link between silicone and autoimmune

diseases. While a saline filled breast implant

contains only sterile saltwater solution, its shell is made of a silicone elastomer. As recently as August of

'99, the FDA stated in the Federal Register that no definitive link between immunologic or connective

tissue disorders and saline filled breast implants has NEAL R. GROSS
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been found. Further, after comprehensive evaluation of the evidence for association of silicone breast

implants with human health conditions, the Institute of Medicine concluded in June of '99 that there is no definitive evidence linking breast implants to cancer, immunologic diseases, neurological problems, or other systemic diseases. What then constitutes the major risks Besides

associated with saline filled breast implants?

deflation, there is the risk of capsular contracture, tightening of the natural scar tissue that forms around the implant, and it can cause breast firmness. The occurrence of capsular contracture is unpredictable, and if severe may require corrective surgery. In the Minnesota study, only four percent of

patients rated their reconstructed or augmented breasts as hard, while 24.5 percent said their breasts were slightly or moderately firm. While the ideal of implant surgery is a soft, natural feeling breast, some degree of firmness may be well tolerated by the patients, as evidenced by NEAL R. GROSS
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the high rate of patient satisfaction recorded in that same Minnesota study. A concern associated with breast implants is the possibility that the devices may interfere with the early detection of breast cancer. Mammography of

the implanted breast requires special techniques and additional X-ray views. University of Southern However, recently published California study of breast

cancer diagnosis and survival among 3,182 women with breast implants in Los Angeles County showed the stage of cancer diagnosis was virtually identical to that of all breast cancer patients in L.A. County. In addition, the five year survival rate was consistent with rats established by the National Cancer Institute. There is no evidence that implants In fact, two major studies have

cause breast cancer.

shown a lower than expected incidence of breast cancer in women with breast implants. Plastic surgeons have seen first hand how a woman's quality of life can be tremendously improved by these devices. numerous stories Every plastic surgeon can provide about women whose self-confidence

NEAL R. GROSS
(202) 234-4433 COURT REPORTERS AND TRANSCRIBERS 1323 RHODE ISLAND AVE., N.W. WASHINGTON, D.C. 20005-3701 www.nealrgross.com

flourished after augmentation mammoplasty. We also know first hand of many mastectomy patients who have expressed that they have only felt themselves to be recovered from their breast cancer experience when their bodies were restored with breast reconstruction. The responsibility that our patients

bestow on us as plastic surgeons when we perform breast implant surgery is taken very seriously. We believe

that women should be fully informed of the potential risks and benefits of implants and should have the right to choose implants to restore their breasts

following cancer, trauma, or deformity, or to achieve a satisfying breast appearance through augmentation. Women implant surgery who are would often wish made to to have breast the Yet

feel

that

procedure is frivolous and poses unnecessary risk. studies have confirmed that most of these

women

experience improvements in self-esteem and body image and quality of life. We must also remember that there is no alternative currently available to breast implants.

NEAL R. GROSS
(202) 234-4433 COURT REPORTERS AND TRANSCRIBERS 1323 RHODE ISLAND AVE., N.W. WASHINGTON, D.C. 20005-3701 www.nealrgross.com

Autogenous procedures to reconstruct the breast require extensive surgery and may not be an option or are impractical for many patients. Autologous tissue

transfer for breast enlargement could not be justified. We believe that breast implants fill a

significant health need, and we will continue to work to insure that women have access to this procedure and the right to make their own informed choice to proceed or not. The research findings of the recent years have

significantly restored women's faith in breast implant safety and efficacy. Thank you. CHAIRMAN WHALEN: Are panelists? (No response.) CHAIRMAN WHALEN: DR. PUCKETT: Thank you, sir. there any Thank you, Dr. Puckett. questions from the

Thanks. Before proceeding to the

CHAIRMAN WHALEN:

next speaker, I'm told that one of the speakers who could not be here, Ms. Mullen from the Women's

Information Network against Breast Cancer, that Ms. NEAL R. GROSS
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Brinkman will read a statement that was submitted by her. MS. given this. part. This is from Elizabeth Mullen -CHAIRMAN WHALEN: know of any financial As you're starting, do arrangement that that BRINKMAN: Thank you. I was just

So this in no way reflects any bias on my

organization has? MS. BRINKMAN: is. So -CHAIRMAN WHALEN: MS. BRINKMAN: Thank you. I don't even know who she

I do not.

It's from Elizabeth Mullen, President, CEO of Women's Information Network Against Breast Cancer, written testimony. I very much appreciate the opportunity to submit my written testimony to you for consideration. I had hoped to be here today in person, but was unable to make the trip from California due to circumstances beyond my control. My remarks will adhere to the ten

minute oral testimony limit. NEAL R. GROSS
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I am founder, President and CEO of the national, nonprofit organization Women's Information

Network Against Breast Cancer.

The acronym is WINABC.

As such, I am representing WINABC for the purposes of this from testimony the and would not like of to an

communicate

perspective

only

advocate, but also as a breast cancer survivor who has had a mastectomy and immediate post reconstruction

latissimus dorsi with a saline filled breast implant, and finally as a woman who cares deeply about the issue being addressed today and throughout this week: the

availability of saline filled implants and a woman's right to choose. Oh, she goes on to say at the bottom, "And I have in no way been reimbursed for addressing this panel." She says her organization has received grants

from a few pharmaceutical companies, Glaxo Wellcome. "I am not a witness or party to a pending lawsuit, and my income is not derived from breast implants." My perspective as a breast cancer survivor and as a woman. I was diagnosed with breast cancer

nearly seven and a half years ago at the age of 33. NEAL R. GROSS
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Judging

from

the

size

of

my

tumor,

my

physicians

estimated that the malignancy had been there for seven to ten years. Breast cancer had not been on my I

physicians' radar screens, nor had it been on mine.

quite simply did not fit the profit of a woman with breast cancer, or so it seemed. Wrong assumptions had been made regarding my health status, and as a result, when I was finally diagnosed with breast cancer, my treatment options were limited. Due to the size and location of the tumor in

my breast and the size of my breast in relation to the size of the tumor, I opted for breast conserving

surgery.

I would have, in essence, ended up with a

partial mastectomy. Due to these factors, there was consensus that a mastectomy was my best surgical option. I was,

to say the least, fraught with sadness and fear over the prospect of losing my breast, facing chemotherapy, and the prospect of dying within two to three years. was overwhelmed, confused, and numb. I

Being

misdiagnosed for several years robbed me of some very NEAL R. GROSS
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important choices. I oncologist was in fortunate a plastic that and my surgical

called

reconstructive My first my

surgeon for my initial surgical consult. glimpse of hope in the painful days

following

diagnosis was learning that breast reconstruction was an option for me. The prospect for my waking up after When an

surgery without a breast was devastating to me. my plastic surgeon explained that I could

have

immediate breast reconstruction, my outlook began to improve, and I began to regain my strength of spirit. Because of many factors, I was not a good candidate for a tram flap reconstruction. So

reconstruction with an implant was my best option, my only option, as it turned out. I remember making love with my husband for the last time before my mastectomy and reconstruction. It was so bittersweet. surgery? What would it be like after

There were so many unknowns. I share this with you because the personal

and intimate perspectives of all women all too often NEAL R. GROSS
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get bypassed in forums such as this. Just as the science is critical, as you consider the efficacy of saline filled breast implants, so, too, is the conscience, body, mind, and spirit of individuals who choose to have surgery with implants, be it for cosmetic augmentation or breast

reconstruction. How do you quantify hope, self-esteem,

body image, sexuality?

How do you hope self-esteem and

a positive self-image impact of a 33 year old woman fighting for her life after breast cancer surgery, or as a teenage young lady with a chest defect following reconstruction to correct the anomaly, or a 50 year old woman who has never been comfortable with her AA size breast, who following breast augmentation experiences a new sense of womanhood? I urge you to keep this human and humane outlook in mind. I am blessed to be married to the one and only true love of my life, my high school sweetheart. I have known Ken since I was 16 years old. We always

knew that we would get married, and for years we had NEAL R. GROSS
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the name of our first child all picked out, Semantha Ann Mullen, SAM for short, SAM, a daughter we never knew. Because of my chemotherapy protocol, Ken and I Although

will never be able to have children together.

we never had been warned about it, chemotherapy threw me into permanent menopause. the matter. Choice, one word that means so much. a woman faces the diagnosis of breast cancer, When she I never had a choice in

experiences a range of feelings that often include loss of control and grief over the possible loss of a

breast. But the good news is women have choices, including important choices in breast reconstruction. Limiting these choices by limiting or eliminating the availability of saline filled breast implants would be a tragic and devastating blow to women. What's at stake here today and throughout this week is a woman's right to choose, and here is where my perspective shifts from that of an individual patient and a women who has experienced first hand the positive impact of breast reconstruction with an

NEAL R. GROSS
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implant to that of a woman's health advocate, working to insure equal access to quality health care for

individuals. My perspective as an advocate and CEO of WIN Against Breast Cancer: to fear." I founded the WIN Against Breast Cancer following my own experiences with breast cancer. The "knowledge is the antidote

WIN organization was established to provide patients with the information and resources that they need to make to make confident and informed health care

decisions. and men

We place particular focus on helping women understand their treatment options and

empowering individuals with the even knowledge about their choices and health care. Choice and knowledge, informed decision

making are at the core of WIN's organization, mission and goals. all WINABC strives to provide individuals from and socioeconomic backgrounds with

cultural

responsible, unbiased information about breast health, breast cancer, and personal health responsibility. WIN was also founded to be a catalyst for NEAL R. GROSS
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change in partnership and to serve as a conduit by which individuals and organizations can be linked to one another in areas of common interest and purpose. I will leave the science to the scientists and the clinicians, but I'd like to highlight a few key points regarding the great implant debate. The studied for 20 device. years and Breast have implants been have been

under

intense

scrutiny for a large portion of that time. The science is sound and ongoing. Product information. see first hand that with and have respect I have been able to first in hand the

experience been to made

improvements development

the filled

product breast

saline

implants over the years. I started off this portion of my remarks with a quote about knowledge, to another the saline important under breast

development consideration implants. education?

with by

respect this

devices filled

panel:

Is the improvement in provider and consumer The bottom line: we fear what we do not

know and understand. NEAL R. GROSS
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As hundreds of

an

advocate over the

who

has

worked dozens

with of

women

years

and

providers, I can report first hand that what I referred to is myth conceptions are oftentimes tragic barriers to women seeking life saving breast cancer screening and treatment services. I cannot count the times women have called our organization following a sound byte on the news about, quote, the dangers of implants or the, quote, deadly side effects of Tamoxifen or the, quote, long term, ineffectiveness of lumpectomies. Hype destroys hope. to disintegration of Misinformation leads Overstated?

health.

Unfortunately not. Women often fear the prospect of losing their breast to cancer more than chemotherapy or the disease itself. The fear is a barrier to women

examining herself or seeking screening and treatment services. Oftentimes and tragically, women will ignore

a palpable lump for years and present in the clinic with open sores on their breast in late stage disease because of the fear of losing a breast. NEAL R. GROSS
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Many

women

do

not

know

that

breast

reconstruction, immediate or delayed, is an option for them. When women fully understand their options, the and risks, and are and given access to peer

benefits support,

second

opinions,

culturally

sensitive,

linguistically appropriate, educational materials, they are more likely to make intelligent, competent

treatment decisions and more likely will comply with treatment. And when physicians are made aware of

these issues and barriers, they can more effectively communicate with their patients and improve outcomes. I will never forget the day when I was making rounds with a surgical oncologist. I was with

him as he delivered a breast cancer diagnosis to a Latino patient. The patient clearly needed a

mastectomy, but because of a variety of reasons refused surgery. On her second visit to the clinic to again discuss options, her surgeon called me in and told the patient that I had a mastectomy and reconstruction. We

showed her my reconstruction, explained the procedure. NEAL R. GROSS
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The unknown of surgical outcomes was now a known. could envision the end result of a

She

breast

reconstruction and knowledgeably and willingly agree to the surgery. Her She chose choice was over made fear real and and tangible. from

treatment

flight

treatment. life.

The choice, her right to choose, saved her

She was the rule, not the exception. In closing, I am going back to the

beginning of my remarks.

I was given my breast cancer The entire conversation

diagnosis over the telephone.

lasted no more than three minutes, three minutes frozen in time that forever changed my life. It's a time

frame that makes me uneasy not because of a bad memory, but because every three minutes another woman is

diagnosed with breast cancer. Every day women are seeking breast cancer treatment options that include reconstruction with

saline filled breast implants, often their best and only -- their only reconstructive option, an option that can result in a new lease on life at a time when life seems so fragile and precarious, a choice that NEAL R. GROSS
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means hope, healing, and vitality to the all too many women confronted with a diagnosis of breast cancer

every day in this country and around the world. I will close with a favorite scripture of mine. "Where there is no vision people perish." It is my sincere hope that your vision, insight ability and of wisdom saline will filled result breast in preserving and the the

implants

opportunity and right for women to choose whether or not to use these devices. Device? it's hard for me Funny. to As I look in the mirror, that my feminine

consider

silhouette is attributed to a device.

This device,

this implant has become a part of me, and I dare say has outlived my original prognosis of two to three years by several years, for which I'm grateful on many levels. Other women deserve that chance. Thank you. CHAIRMAN WHALEN: that. Before proceeding to the next speaker, if there's anybody from either FDA or Holiday Inn in the NEAL R. GROSS
(202) 234-4433 COURT REPORTERS AND TRANSCRIBERS 1323 RHODE ISLAND AVE., N.W. WASHINGTON, D.C. 20005-3701 www.nealrgross.com

Thank you for reading

room who has the password to the thermostat and could drop it a couple of degrees, I think we'd all be immensely appreciative. The other professional society that will be address -DR. BURKHARDT: chair. I have a question for the

May I ask a procedural question at this time? CHAIRMAN WHALEN: DR. BURKHARDT: Oh, procedural, yes. Yeah, a procedural

question. We've heard lots of stories, individual In our

stories for and against this whole thing.

training session last night, the new members had a training session with the FDA. that in our deliberations as My understanding was we sit here, we are

precluded by statute from considering these individual experiences and experiential reports. CHAIRMAN deflect to Dr. Witten. DR. WITTEN: In terms of when you make a WHALEN: FDA questions I'll

recommendation about reasonable assurance of safety and effectiveness of each of the PMAs, you are to consider NEAL R. GROSS
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the data in the PMA and your scientific knowledge. DR. BURKHARDT: DR. WITTEN: Period?

Yes. Thank you. The other professional

DR. BURKHARDT:

CHAIRMAN WHALEN:

society to address us this afternoon is the American Society for Aesthetic Plastic Surgery represented by Dr. David Sarwer. DR. SARWER: Dr. David Sarwer. Good afternoon. I'm assistant My name is of

professor

psychology and psychiatry in surgery at the University of Pennsylvania School of Medicine. I'm testifying today at the request of the American Society for Aesthetic Plastic Surgery which will reimburse me for my travel expenses to this

hearing. one from

I have in the past received two small grants, the American Society of Aesthetic Plastic

Surgery and one from the University of Pennsylvania Research Foundation to support of my research on the

psychological patients.

characteristics

breast

augmentation

However,

I

do

not

derive

any

salary

NEAL R. GROSS
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support from these grants.

I am not involved as a

witness or party to any pending lawsuit related to breast implants. Members of panel, I am here today to

present information relevant to your consideration of the safety and My efficacy comments of are saline from a filled breast

implants.

psychological

perspective and are based on my expensive -- extensive experience -(Laughter.) DR. SARWER: Not so most expensive -- in

the area of the psychology of cosmetic surgery. Over the last five years I have published 21 empirical papers, review articles, book chapters, and discussions on the psychological aspects of plastic surgery. There articles have appeared in both the Many of breast

plastic surgery and psychological literatures. these papers have focused on cosmetic

augmentation patients. In 1999, I served as a chairman of a

symposium on cosmetic surgery at the seventh annual Congress of Women's Health and Gender Based Medicine. NEAL R. GROSS
(202) 234-4433 COURT REPORTERS AND TRANSCRIBERS 1323 RHODE ISLAND AVE., N.W. WASHINGTON, D.C. 20005-3701 www.nealrgross.com

Finally, paper which is

I've

recently under

written

a

review review

currently

editorial

specifically focusing on the psychological aspects of cosmetic breast augmentation surgery. Therefore, I am uniquely qualified to

discuss the psychological issues related to cosmetic breast argumentation. The surgery means and popularity that many of breast augmentation obstetricianhealth care

internists, other women's

gynecologists,

professionals are increasingly called upon to provide appropriate procedure. As you are aware, breast augmentation advice and guidance concerning this

surgery has become increasingly common with women from a variety of age, racial and socioeconomic groups now seeking the surgery. Thus, sensitivity to the I believe that much of greater breast

psychological

issues

augmentation is required from the medical community at large. Over the past 40 years, numerous studies NEAL R. GROSS
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have investigated the psychological issues of breast augmentation patients. The majority of these studies

were conducted with women who received silicone gel filled breast implants. Nevertheless, studies which have with the exception the of

investigated

surgical

complications and satisfaction rates, it may be safe to assume that the psychological motivations of women who have received both silicone filled implants and saline filled implants are similar. Based on our published reviews of the

literature, my colleagues and I believe that there has been a lack of solid data on the psychological While

characteristics of breast augmentation patients.

a variety of studies have been undertaken, most of them have suffered from methodological problems that limit the confidence that can be placed in their conclusions. The results of more recent, more carefully controlled studies, which I will share with you

shortly, have provided important new data in this area. It is surprising to many people that the majority of women who seek breast augmentation are in NEAL R. GROSS
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middle

adulthood, the

married

and

have assumed

children. stereotype

This of

contradicts

frequently

candidates for cosmetic breast enlargement. The these women has and preoperative been psychological status of through both clinical

studied

interviews Clinical

formal

psychometric

assessments. generally

interview

investigations

have

suggested a high degree of psychopathology in breast augmentation patients. have a number of However, these investigations shortcomings which

methodological

raise serious questions about their validity. In contrast, studies that have used

standardized psychometric tests generally have found little evidence of psychopathology in these women.

Only one study has found greater symptoms of depression in breast augmentation candidates as compared to

controls. The methodologies used in some of these psychometric studies also have limitations. Intuitively many women seek breast

augmentation surgery because they are not satisfied with the appearance of their bodies and their breasts. NEAL R. GROSS
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While such concerns were often dismissed as trivial vanity years ago, research over the past several

decades has demonstrated the importance of appearance in everyday life. Not only are more physically

attractive individuals perceived more favorably than those who are less attractive. It also appears that

more attractive individuals receive preferential social treatment in both interpersonal and social situations. Given this knowledge, improving one's

appearance can be seen less as trivial vanity and more as a positive, health self-care strategy. This

research, however, only explains the outside view of physical appearance. It does not account for the

inside view the way a person views his or her own appearance. This internal perspective of physical

appearance can be understood through the psychological construct of body image which thoughts, encompasses feelings an and

individual's

perceptions,

behaviors about the body.

Body image, particularly

body image dissatisfaction, may be the most relevant construct by which to understand the motivation of

NEAL R. GROSS
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cosmetic augmentation candidates. Body image dissatisfaction is so prevalent in our society that researchers have labeled a

normative discontent. suggests that 56

One recent body image survey of American women report

percent

dissatisfaction with their overall appearance, and 34 percent size. Furthermore, body dissatisfaction in women appears decades, economic, to have increased that over the the past several report a dissatisfaction with their breast

suggesting and

recent of

occupational, women in this

political

advances

country have not helped improve their personal body images. My empirically colleagues body and I were the first to in

assess

image

dissatisfaction

prospective cosmetic surgery patients.

Across several

studies, we found that women who seek cosmetic surgery as compared to women who do not seek surgery report greater body imagine dissatisfaction with the specific body feature for which they are seeking surgery. We have also completed three studies of NEAL R. GROSS
(202) 234-4433 COURT REPORTERS AND TRANSCRIBERS 1323 RHODE ISLAND AVE., N.W. WASHINGTON, D.C. 20005-3701 www.nealrgross.com

breast

augmentation

patients.

These

studies

have

replicated our previous findings, suggesting that women who seek augmentation as compared, again, to women who do not seek surgery report greater dissatisfaction with their breasts. These specific studies on have the also provided of more this

information

nature

dissatisfaction.

For example, more than 50 percent of

augmentation patients reported that they avoided an undressing in front of others and that they camouflaged their preoperative breast appearance with special

brassiere or clothing. These upsetting experiences appear to have a negative effect on self-esteem. In the most recent

investigation from our group, women who sought breast augmentation reported more appearance related teasing and a greater use of psychotherapy than did controls. These results may suggest that a history of appearance related teasing may who be do another and do variable not seek that breast

distinguishes augmentation.

women

Further, the greater use of psychotherapy NEAL R. GROSS
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in these women suggest that they may be experiencing negative emotional consequences as a result of their breast dissatisfaction. Studies of the psychological consequences of breast augmentation have been largely anecdotal, though the reported satisfaction rates, as we already heard today, are encouragingly high. physical complications of In the absence of interview

surgery,

investigations have reported that the majority of women experience psychological benefits, including

improvements in body image and self-esteem following augmentation surgery. Two recent studies have provided even more convincing evidence of the psychological benefits of cosmetic surgery. that as compared Results from the first study found to preoperative levels, cosmetic

surgery of patients reported significant improvements in depressive symptoms and quality of life six months after surgery. Results from a preliminary investigation

have found similar improvements in body image, also six months postoperatively. Thus, there is now growing

NEAL R. GROSS
(202) 234-4433 COURT REPORTERS AND TRANSCRIBERS 1323 RHODE ISLAND AVE., N.W. WASHINGTON, D.C. 20005-3701 www.nealrgross.com

evidence

to

suggest

that

cosmetic

surgery,

such

as

breast augmentation, leads to improvement in at least three areas of psychological functioning: quality of life, and depressive symptoms. A recent investigation of women who had their silicone breast implants removed further body image,

underscores the psychological impact of an altered body image. Women who had their implants removed reported

less satisfaction with their appearance, fewer positive appearance related thoughts, and greater discrepancy between their ideal and post explantation breast size. Thus, it appears that removal of a breast implant, something which has occurred more frequently as a result of prior controversies over silicone

safety, may have a profound effect, negative effects, on psychological functioning. In conclusion, recent evidence supports

the view that women seek breast augmentation to reduce or eliminate their personal dissatisfaction with the size and shape of their breasts. of the importance this of physical should not Based on what we know appearance be viewed in as our a

society,

desire

NEAL R. GROSS
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manifestation of psychopathology, but as a positive mechanism image. Two recent studies suggest that cosmetic surgeries, measurable such as breast in augmentation, body image, result as well in as for improving one's appearance and body

improvements

depressive symptoms and quality of life.

Given that

the benefits of breast augmentation surgery are more in the psychological than physical realm, more research demonstrating the psychological benefits of the

procedure is clearly warranted. However, based on the current studies, it is reasonable to assume that the vast majority of women who choose breast augmentation surgery will enjoy

significant psychological benefits that would otherwise be unavailable to them. Thank you. CHAIRMAN WHALEN: Thank you.

I think the get the award for the best timing today because the last word was right when the red light came on. DR. SARWER: Yeah, but I also had that

NEAL R. GROSS
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slip of the tongue at the beginning. CHAIRMAN WHALEN: for Dr. Sarwer? (No response.) CHAIRMAN WHALEN: Just so the three Are there any questions

remaining individuals who are going to be talking to us know, we will be getting to them in time. We have one remaining consumer group to hear from. Dr. Blais, Pierre Blais is from the

Chemically Associated Neurological Disorders, and in view of Ms. Stansell's yielding of half of her time, would the timer please be set for 15 minutes? DR. BLAIS: Thank you very much.

I differ from the other speakers inasmuch as I am not a U.S. citizen. I'm here on invitation.

I'm not a member of the association, nor, for that matter, of any advocacy association. I do not derive income from the breast implant trades, neither through implantation,

explantation, health care, diagnostic, marketing, sale, or whatever. I am here at my own expense. NEAL R. GROSS
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I have never

received funding from any source with respect to this program. I'm a former Canadian official with a

position very similar to our colleagues here from the FDA. I had a similar role in Canada. I'm responsible

for what may be the largest breast implant or, for that matter, general deep, long term implant study ever

taken worldwide. day.

It has lasted now 25 years to this

The part I wish to report today is a very small segment of this study. It concerns 250 specimens

from a very large cohort of explanted devices collected between about 1989 to almost the present. Out of

these, there were only a few that were suitable for the type of study according to our protocol. The type of protocol that we had targeted was one where we would look for contamination in

implants that had not failed.

This is a minority of

implants that are removed, and they also included a review of the mechanical issues surrounding the

fabrication of implants. We have heard today about many things. NEAL R. GROSS
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We

have heard about how beneficial the implants can be psychologically, how beneficial they will be to cancer patients, the fact that they are liked by individuals who have had deformity and so on. could agree with it. very worthwhile. My mundane. interests, however, are much more This may be so I They're

I applaud the studies.

I'm a scientist, and I'm also a technologist.

I've studied those devices now for far in excess of 25 years. I go back to the '60s, and I have personal

direct recollection from the Joseph Kennedy hearings. Those of you who are my age will remember that. Now, what I wish to impress on you is that the mention of science in the study, the retrospective study is one thing, and that may be so, but the mention of science in the context of fabrication and

engineering of the implant is not here.

I have never

seen any evidence of intelligent engineering or science in the design, the fabrication or, for that matter, the post explantation analysis of these devices. articles of commerce of very low grade. technology. They are

They belong to

They do not belong to science. NEAL R. GROSS

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www.nealrgross.com

Those of you who still hold the view that these things are scientific need only look at a few. have some here. I

I won't bore you with that they are

like, except to mention the part that I wish to draw attention to. Virtually anything we have pulled out of patients over the last years that have not been

outright broken amongst the salines were all septic, septic to a level which is unprecedented in studies on scientific implants. with all types of They were visibly contaminated flora, something that by itself

should be a sobering thought for any physician who puts them in and who takes them out. What I want to draw your attention to is a very small segment of our study which has concerned saline implants. Two hundred and forty-two implants

that fall into a certain category, a subclass of saline implants, 74 that fulfill criteria of being "intact" in the surgical sense of the word, six of the users

reporting problems prior to removal, such as deflation, a few of them claiming systemic complications -- I'm not competent to discuss it -three users only

NEAL R. GROSS
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involved in litigation. Out of these 74, 12 were very old

implants, what we call the Jenny Mark I, which is a unique implant introduced in 1968 with a very coarse and, by the way, highly secure valve system. These are

the ones that habitually are removed without rupture. It's an interesting observation. The others, 62 of them, bearing the same type of valve, this is what we call a forward valve or an apex valve. Those of you familiar with the trade It is simply a hole

will know what this symbols is.

with a diaphragm at the bottom and a plug at the top to cap it. The secure. early ones, the Jenny, were quite

The second generation which was introduced in

'76 is not, nor is it designed to be, as best as I can figure out. intentionally contracture. This type of implant is designed to leak to It support is by a claim itself of an control of

engineering It is

misrepresentation.

It is not a single product.

made by nearly everyone in the trade. different manufacturers have made it. NEAL R. GROSS
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More than 18 The values all

www.nealrgross.com

share the same process, the same problem because they all come from the same place. They are a commodity.

They are an article of commerce marketed by a single manufacturer, sold to others. Now, the other part of importance in this sub-study is that not only were the values of this design not terribly good in terms of manufacturing, but they did not even fit. The parts were not mated

correctly.

To put it in very vulgar terms, it was like

having a cork on a wine bottle which is about five millimeters smaller than the hole, so that if you put the cork in the bottle, it falls to the bottom. Now, I ask you as a technologist, as a scientist, as a physician, as an administrator, as a layman, as a user, what would you think of a company that presents to you with an elaborate pre-market

submission claiming elaborate studies and good science and good engineering, who cannot manufacture an object to the right dimensions? have? Now, there are many things. I've made a What credibility will the PMA

formal submission, and I'm very grateful to Dr. Krause NEAL R. GROSS
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for accepting it. Unlike

It will be given to you. many others, it involves 20

recommendations on what the committee has no option but to consider if they ever find that one of the

submissions complies with the terms of the requirement. I'm not saying there are any. but there could be one. If such an implant ever appears in your files and you're required to give it assent as an approved product, then you have no option but to I have yet to find one,

consider implementing the 20 recommendations that are made there, and many of them are quite surprising. They're also very old because the same recommendations are culled out of meetings that took place incidental to classification panels in 1978 right through to about 1983 and were reiterated again in the late '80s when the gel implant issue arose. I'll just point to a few of them. wish to have further elaborations, I can If you do that

personally, if an invitation. One of the main issues that I have is that the FDA must address retrospectively warnings for users NEAL R. GROSS
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of the implants.

They are exposed to risks which have

never been made clear to them and have been denied. Yet they are undeniable in the light of laboratory findings. The disclosure called and other the issues up have of to do that with are to

clearing remote

issues as

possibilities,

risks

opposed

inevitable, time dependent certainties. These implants are literally replete with certainties. They are not probabilities. And then finally I have to deal with the issue of breast person feeding. who is In the light about of any

reasonable

briefed

breast

physiology and in the light of the laboratory findings that we are getting from saline implant, there is no basis in any science, any technology, not even in

psychology, that would justify breast feeding, and as surprising as it sounds, it has nothing to do with the offspring. It has to do with the very principle on why

implants are put in in the first place. If you attempt breast feeding with an

implant, you will have a good chance of bringing the NEAL R. GROSS
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breast back to its pre-implantation condition, breast involution. It's all over medical texts. The oriented absolute. risk. Now, the issue of the offspring is issue of the so-called breast selfishly feeding is

recommendation

against

It is a cosmetic issue and also one of

secondary, but it's just as important in the ethical sense because we now have implants that are not secure in terms of integrity, which are known to be colonized by a broad range of microorganisms which have access to the breast, and the breast is fully engorged and

responsible for distribution of milk precursor product to the implant. Therefore, the implant constitutes a

direct channel for transmission of an infective vector to the offspring. This concept is so old that you will

find it in European texts in 1965. Contrary to opinions expressed this

morning, the saline implant is not a 1968 discovery. It's a 1960 discovery, and to make it even more

embarrassing, it's a Canadian one at that. NEAL R. GROSS
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It is my

www.nealrgross.com

Breton who has foisted this on you. the gel implant.

It is older than

It's been known since the beginning

that they constituted a microbiological hazard that would preclude absolutely any recommendation for breast feeding. Finally, to conserve and try to establish a record of being timely, the issue of radiography must also be addressed. It is also transparently obvious

these devices, the very shell is structured and is radiopaque. As such, the uniqueness of the shell, its

structure and its peculiarities, preclude any form of meaningful radiodiagnostic oncology aspect. The

implant is not just a confusing factor.

It is capable

of generating both false positive and false negatives. Therefore, there should be an FDA recommendation with respect to deemphasizing any value of radiographic

assessment for tumors. Then cost. How and last why of did all, I have the issue of

Canada

governments

become

interested in breast implants?

It had nothing to do

with the health of the user, the offspring, the safety, or the cosmetic aspects, what we call efficacy. NEAL R. GROSS
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It had

to do with cost. Some of you know that Canada operates

under a medicare system.

In the early days of this

debate, which is the late '70s, I performed a study on health care cost, which is easy to do. It's only a

computer issue in Canada, as we have the record, and a very strong outcome came. Anyone implanted consumed four times our health care resources of a corresponded age adjusted individual. scared. Now, this has enormous implications. If I haven't done the study since. I'm

you do a macroeconomic analysis of this phenomenon, you will observe that both primary and secondary health care costs of some states and incidental to

Medicare/Medicaid, which does operate in some states, you find that it exceeds in some cases the actual promotion technology. Now, as a result of this, everyone, They studies, the cost of promoting the

whether or not they have implants, are affected.

are affected in the sense that third party insurers, NEAL R. GROSS
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HMOs, and everyone else who is in the health care funding business is looking at breast implants with much concern for good reasons, because they attract health care procedures,a nd they attract health care costs. One doesn't have to be the rocket

scientist to figure this out. Finally, the issue, the last issue, I made a small omission in disclosing conflict. a conflict. It may not be

I have consulted for everybody, the breast

implant industry, the breast implant professionals, the attorneys for defense, attorneys for plaintiffs, third party insurers, governments, you name it. I have done

it, but I have not derived a living from it. And finally, I do have an involvement as a witness, and it's a witness in Canada called a material witness incidental to a criminal investigation of the Canadian government surrounding wrongdoings in the

approval process of medical devices. Thank you very much. CHAIRMAN WHALEN: DR. BURKHARDT: Dr. Burkhardt

Is it Dr. Blais?

NEAL R. GROSS
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DR. BLAIS:

Yes, it is, sir. Thank you. things that I couldn't

DR. BURKHARDT: A understand. couple of

I'm just a little dense about this stuff, You said that you had removed

the thing that you said. 74 intact saline implants. DR. BLAIS:

They're out of a group -I'm not finished yet. I apologize. removed 74 intact

DR. BURKHARDT: DR. BLAIS: DR. implants.

I'm sorry. You

BURKHARDT:

Then you commented that the valve looked

like it had been made to leak, and I don't understand whether the implants you removed were intact or

deflated or what.

What was the relationship there? They were intact in the sense

DR. BLAIS:

of the word that you would use in your own operative report, Dr. Burkhardt. DR. BURKHARDT: DR. BLAIS: But were they deflated? They were fully inflated.

Many of them were even over inflated. DR. BURKHARDT: DR. BLAIS: So they had not leaked. However, this is not

Correct.

NEAL R. GROSS
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true -DR. BURKHARDT: question. That was the answer to my

I just wanted to understand that. Now, in terms of transmitting an infected

vector to the offspring, it's my understanding, and we have an expert here who might be able to help us, that about 95 percent of lactating mother's milk is

contaminated with staff epidermatis. organism in the milk, and this is

It's a normal the predominant

organism that is recovered from around implants. So it's not clear to me why you think that the implant itself is a vector in transmitting that. DR. BLAIS: Yes, it's three questions

actually that you have directed, and I'm familiar with the microbiology of the breast. limited to stapholocci. It In fact, it's not also propioni

includes

bactiacne and many other things, the natural flora of the contaminated functional breast. However, the organisms in those implants were not of this genus. They belonged to the

mycobacteria family for reasons I can't go into, but now I show you the diagram of this valve again, and I NEAL R. GROSS
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tell you that it is not secure. Even which puzzled us though for a the implants our were inflated, studies It would

time,

modeling

showed that the valve functioned as a pump.

take extracellular fluid occupying the intracapsular space and through the user's habitual movements, this would produce cyclic compression, and it drive fluid within the implant. Therefore, the implant leaked not just one way,b ut in both directions and -DR. BURKHARDT: DR. BLAIS: Thank you very much.

-- therefore, whatever is in

would get out into the breast. DR. BURKHARDT: DR. BLAIS: Thank you.

Thank you. Yes, Dr. Dubler.

CHAIRMAN WHALEN: MS. DUBLER:

On the very last page of your

handout, you have a comment on publication. DR. BLAIS: MS. DUBLER: Yes. And how difficult it is to

get these sorts of negative data published. DR. BLAIS: Yes.

NEAL R. GROSS
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MS. DUBLER:

Has the government of Canada

-- has your report in any way been submitted formally and accepted by any agency of the Canadian government? DR. BLAIS: No, Doctor. The report that You are

you have in your hand was finished yesterday.

privileged to have its first copy, or either cursed with having its first copy. MS. DUBLER: DR. BLAIS: Thank you. I have published many things.

I have not and deliberately avoided publication in this area as it has been painfully difficult to collect clinical material, and that could be the object of another presentation, but it has no place here. CHAIRMAN WHALEN: We have three Thank you. remaining individual

consumers who were segregated into this separate area this morning due to some time constraints. First, Ms. Diane Griffith. And these are five minute presentations, please. MS. GRIFFITH: a half. Mine may go about five and I timed this the

I hope you'll bear with me. NEAL R. GROSS

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best I could. Well, let's see. My name is Diane

Griffith, and my travel has not been paid by anyone else. I'm not Social Security disability and that's my

source of income. I organization. Corning have no financial ties with any

I am a party to the Dow Chemical/Dow and I don't perform surgical

lawsuit,

procedures. I'm making a statement on behalf of Dr. Arthur C. Sehalski (phonetic) of the University of

Southern Illinois.

He's a scientist, an immunologist

and could not be with us this afternoon. The statement is confined to issues of the structural integrity within the human body of the shell of prothesis known as silicone gel breast implants and saline filled breast implants. The statements quoted during the next five minutes come from two sources, namely, one, the 1999 National Academy press publication titled "Safety of Silicone published, Breast peer Implants," reviewed and, by two, Dr. the Eugene 1999 P.

paper

NEAL R. GROSS
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Goldberg and co-authors, titled "Silicone Gel Breast Implant Failure and Frequency of Additional Surgeries." Analysis examination of more of than 35 8,000 studies explants. reporting In the

executive summary of the Institute of Medicine's 1999 publication, the following statement appears in the second paragraph of page 3. "Precise frequencies of

the rupture of gel filled or the deflation of saline filled implants are not available. The properties of

these devices can affect rupture or deflation and have changed markedly over time, and particularly in the case of gel implants. reliably diagnose and It has not been possible to study rupture in an unbiased

cross-section of implanted women." Continuing, "rupture frequencies in the

past have been considerable, and the rupture rate of current models has yet to be measured over the relevant periods of time." Assuming the accuracy of the statement, of the sentence just quoted, and given the absence since this statement by the IOM committee was made of

evidence to the contrary, why is the advisory committee NEAL R. GROSS
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even now considering a pre-market approval application for saline inflatable breast prosthesis. It is not the labeling information

available to the prospective saline implant recipient that establishes or certifies safety. Labeling

information merely informs the prospective recipient of risks. What it does not do and cannot do is provide

substantial human based evidence on the duration of the integrity obvious? Are saline inflatable breast implanted of the sell within women. Is this not

women again to serve as a test population to determine safety, to determine rate of rupture? Doesn't the

evidence from the studies conducted at the University of Florida's Biomaterials Center and the Tampa Bay

Cranial-Facial and Plastic Surgery Center show a direct and suitable, significant correlation of implant

duration with percent shell failure? And don't the studies of Goldberg and coworkers credibly reveal a failure rate of 30 percent at five years, 50 percent at ten years, and 70 percent at 17 years? NEAL R. GROSS
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In

1993,

the

AMA

Council

on

Scientific

Affairs suggested that the shell failure rate was four to six percent, and is this not true that the FDA itself has stated that five percent rupture is "not a safety standard that the FDA can accept"? now changed its mind? We would hope not. Thank you. CHAIRMAN WHALEN: Thank you. Has the FDA

Next is Dr. Anne Kasper. DR. KASPER: My name is Anne Kasper, and

I've been an advocate social science researcher and public policy expert in women's health for more than 25 years. I'm currently a senior research scientist with

the Center for Research on Women and Gender at the University of Illinois at Chicago, which is a national center of excellence in women's health. I've conducted two studies of women with breast cancer, the most recent study completed in May of '99 and supported by the U.S. Agency for Health Care Research and Quality. I'm the co-editor of a book on breast

NEAL R. GROSS
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cancer forthcoming later this year. I've not received any travel money nor do I have financial and I ties not with any industry with or health implant

society,

am

associated

any

lawsuits, nor do I derive income from implants in any way. I'm pleased to present testimony to you today and thank you for the opportunity to do so. The

focus of my testimony will be on women's perceptions of the safety of breast implants following mastectomy and the importance or lack of importance breast implants have in their recovery from breast cancer. In my testimony I draw on the experiences of 53 women who participated in the two qualitative research studies for which I was the principal

investigator. Most of these women diagnosed with breast cancer had a choice of treatment between lumpectomy with radiation and mastectomy. have known that the science Although since 1985 we has demonstrated equal

survival with these two forms of treatment, individual women have their preferences. NEAL R. GROSS
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Many

of

the

women

in

my

studies

chose

mastectomy for several reasons.

One, they feared that

lumpectomy would leave cancer remaining in the breast. Two, they were afraid of the long term effects of radiation. Most important, however, their choice of mastectomy was made possible by the availability of breast implants and the assurances given them by their physicians. The women were assured by their physicians that breast implants are safe and effective. Indeed,

if any of the women had known at the time that neither silicone gel implants nor saline breast implants have never been approved by the FDA as safe and effective, they would be astonished. As these women weighed their choices

between lumpectomy and mastectomy, the issue of safety and effectiveness of implants did not enter their

equations.

Rather, like most Americans, they trusted

their doctors, and they assumed that some independent authority had tested and approved the devices their doctors would assert in their chests. NEAL R. GROSS
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In safe and

some,

the made

belief the

that

implants to

were a

effective

choice

undergo

mastectomy possible for most of these women.

Without

this belief, I contend that few of the women would have had mastectomies, and their treatment choices would have been severely limited. In a paper published in a peer reviewed journal, I discuss the effects of breast loss and

breast reconstruction for the women in the earlier of the two studies. their physicians The women in this study stated that promoted breast reconstruction as

important to the women's recovery from breast cancer and to a renewed sense of well-being. A majority of the women who underwent

mastectomy chose implants because they hoped to replace the breast lost to cancer, wanted to erase the memory and reminder of cancer, and believed that

reconstruction would make them feel whole and normal again. However, when the women were able to

reflect back on their experiences, the majority of them were not convinced that breast reconstruction had meet NEAL R. GROSS
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their hopes and expectations, nor the assurances of well-being promoted by their physicians. The women

found that reconstruction did not erase the reality of cancer, nor did it assure their return to normalcy. Neither Rather, did the the implant replace breast the was lost a breast. physical

reconstructed

approximation that had none of the sensory, sexual, or maternal capacities of the normal breast. Many of the women sensed that the sole purpose of the implanted breast was for it to appear to be what it was not. deception, deceived Many of the women had a sense of by their doctors, by their own

expectations, and by the implant itself. Breast reconstruction with implants should remain a choice for all women who have lost a breast to cancer. However, the FDA has an opportunity to end

another deception, that breast implants are safe and effective for women who have had breast cancer. I urge this panel to not approve saline inflatable breast implants until appropriate studies have determined whether or not these implants are safe in the short and the long term for women who have had NEAL R. GROSS
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breast cancer. Thank you. (Applause.) CHAIRMAN WHALEN: Thank you.

Are there any questions? DR. BURKHARDT: Yes, I have a question.

In terms of breast reconstruction not duplicating the real thing, we all know that's the case. Is that the

reason for your recommendation that we don't approve -DR. KASPER: No. I'm just telling you

that the women had a lot of faith in their implants. They had great hope as to what the implants would be for them, and that they were not a perfect replacement was a disappointment to them. Even though many of them

had been told by their doctors it wouldn't be perfect, it was for them, for many of them, it was far less than perfect. And the point I think I was trying to make was the risks associated with implants for many of them were not worth it because the satisfaction levels were not high. DR. BURKHARDT: NEAL R. GROSS
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So

is

it

your

recommendation then that until the implants can be made more perfect we not approve them? DR. KASPER: No. It's really more an

issue of safety and effectiveness.

I mentioned that

because this was what some of the women in my studies had told me about implants, and I think it simply behooves the FDA when dealing with women's lives to have the highest standard regardless of other issues, as well. DR. BURKHARDT: Thank you. I'm sorry. quite At the put end I think I together of your

DR. BANDEEN-ROCHE: just realized that that you I didn't

everything

said.

presentation, I thought I heard you say that implants should remain an option for women who had had their breast -DR. KASPER: I breast reconstruction. Breast reconstruction.

DR. BANDEEN-ROCHE: Thank you. DR. KASPER:

Should remain an option, yes. Thank you. Thank you.

DR. BANDEEN-ROCHE: CHAIRMAN WHALEN:

Thank you, Dr. Kasper.

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Next we'll hear from Ms. Carol Sherman. MS. SHERMAN: Hello. Although no less

passionate about my statement, this should only take about two minutes. First, I'd like to thank you for listening to me today. I feel it's important for the panel to

hear my very positive experience with the saline breast implant. A little over a year ago I was diagnosed with early breast cancer. diagnosis I had a Within two weeks of the mastectomy and immediate

reconstruction with a saline filled breast implant. The emotional trauma of going from a

totally health and fit person to someone who discovers they have this dreaded disease is overwhelming, to say the least. As you can imagine, there were many very

emotional thoughts going through my mind, mostly having to do with am I going to live. At the same time there was one good thing. I never had to envision myself with a deformity. I

never even had to think about myself without a breast, not for one day. NEAL R. GROSS
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I still remember my doctor's words.

"But

you can have immediate reconstruction and wake up from surgery with a breast." I took tremendous comfort in

those words, and I was informed of both the benefits and the risks at that time. Most importantly, I was luck enough to be able to take comfort in the good news that my cancer was caught early. I thought to myself, as long as I'm

healthy and free of the disease I don't care if one breast will be filled with a saline filled implant instead of breast tissue. What I did care about was whatever the filler, I still had a breast. beat this disease. I was lucky enough to I My

I didn't want a daily reminder.

didn't want to be ravaged with a missing breast. self-esteem could not have handled that.

A very important part of surviving this kind of emotional trauma for me was to keep things as normal as possible, to bring normalcy back to my life as quickly as I could. Within four weeks of my surgery, I put on a sports bra feeling comfortable and looking like I had NEAL R. GROSS
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perfectly normal breasts and went back to my regular and fairly rigorous workout schedule. From day one, I

have had absolutely no problems with my implant. About a month later, I attended a special family event where comfortable and feeling good about my appearance, I was able to wear a favorite formal gown. Maybe four to six weeks after that, wearing

another favorite stretch bathing suit to the pool was not even an issue for me. You couldn't tell that three

months prior I had had a mastectomy because I had reconstruction with a saline filled implant. I felt like me, normalcy. I know the most

important part of my emotional recovery was returning to all of the theaters of my life in my normal way. Thank God I had this option. I had the option to feel

whole, my body intact, with two breasts. I don't even want to think about where I would be emotionally if I didn't have that option. It's a personal decision. I feel very strongly that

all women like me should have the option to choose saline filled breast implants as long as they're fully informed of both the benefits and the risks. NEAL R. GROSS
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It's a

matter of emotional health. Thank you. CHAIRMAN WHALEN: Thank you, Ms. Sherman.

Are you at all involved with any practice or company that is involved with putting these devices in? MS. SHERMAN: No, I'm not. Are you involved in any

CHAIRMAN WHALEN:

lawsuit that involves breast prosthesis? MS. SHERMAN: No, I'm not. Thank you.

CHAIRMAN WHALEN:

That being done, we will now proceed with the presentation by Dr. Celia Witten, Director of the Division of General and Restorative Devices, to discuss the regulation of saline filled breast prostheses. DR. WITTEN: Thank you. Thanks for your

patience during my effort to enter the 21st Century. Good afternoon. I'd like to welcome

everyone to this meeting of the General and Plastic Surgical Devices Advisory Panel. I'm Celia Witten, Division Director of the Division of General and Restorative Devices at the FDA. NEAL R. GROSS
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Over the next few days, we will be asking you to provide us with your expert recommendations on three pre-market applications for saline filled breast implants. You are also charged with the very

important task of providing us with recommendations regarding the kind of information that is important to provide in patient labeling so that women can be

adequately informed. I'm going to provide some brief background information for today's meeting. I will summarize the

regulatory history of saline filled breast implants and the events that bring us here today. the types of information provided I will summarize the sponsors to

assist them in planning to collect the preclinical and clinical data needed to support a pre-market approval application. This information is described in the draft breast implant guidance document. This document was

originally provided in 1994 and most recently updated in 1999. The recent updated version incorporated the

clinical study design elements that were highlighted in NEAL R. GROSS
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the points to consider letter issued to industry in June of 1996, which I will also summarize briefly. I will speak also about what we have

learned from the literature since the time that these products were classified. As has already been noted here today,

saline breast implants have been on the market since before 1976. FDA classified these products as Class Because these products were products, they were

III products in 1988. grandfathered as

pre-amendments

allowed to remain as marketed products until such time as FDA issued a rule calling for safety and

effectiveness information.

New products could enter

the market via the 510(k) pathway during this time. Products could also be made available during

investigational study. When FDA issued a rule calling for safety and effectiveness information in a pre-market approval application, changed. market termed PMA, this regulatory status

FDA issued the call for submission of preapplications for the saline filled breast

prosthesis on August 19th, 1999. NEAL R. GROSS
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The sponsors had 90

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days from the time of that call to submit a PMA and have it filed. All products need to have an approval of the pre-market application within 180 days of that call that was issued on August 19th in order to remain on the market. Thus, the review process for these pre-

amendments products, which are already on the market at the time that safety and effectiveness data is called for, is different with respect to timing from the

review of PMAs for novel products that are not yet on the market. For pre-amendments products, there is

limited time for interaction with sponsors during the review process prior to the panel meeting because of the 180-day time frame until products are either

approved or off the market. In addition to working interactively with sponsors prior to the call for PMAs, we continue to work with sponsors during the review process. FDA has provided guidance both in written form and in discussions with sponsors to assist

sponsors to develop the data needed to support a preNEAL R. GROSS
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market application.

The guidance document for these

products that is available provides manufacturers with information regarding data to submit in several

important areas. In particular, the chemistry section

describes -- suggests how to describe and characterize the device, and of the the toxicology types section of includes a

description

biocompatibility

information that is necessary. Mechanical testing as described in the

type of clinical data need is also covered. As I mentioned before, the current

guidance document is a revision of an older version. The clinical portion has been incorporated -- has been updated to incorporate other information the FDA

provided to sponsors.

In particular, I want to note in

1996 the letter that FDA issued to sponsors and to industry that outlined essential elements of a clinical study of these products. key points. The FDA suggested a sample size adequate to determine the adverse event rate with reasonable NEAL R. GROSS
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It is worth highlighting some

precision and suggested 500 women be followed to the end of the study. The suggested worst case precision

within which to be able to describe the incidence of adverse events, such as deflation, was plus or minus four percent. Separate cohorts were augmentation because and of reconstruction potentially

suggested

the

different performance in those groups. A two year minimum follow-up pre-market

was suggested in that letter.

It was also suggested

that sponsors plan ten years' total follow-up, some of the follow-up to be performed post market. The letter

suggested follow-up intervals, and in addition to the primary study endpoints, quality of life, and

connective tissue disease screening were suggested. Since 1988, when these products were

originally classified, there have been a substantial number of public contributions to the scientific

literature that have added to our knowledge of these products. actual Although there are a number of possible and of complications described in the

types

literature, I would like to touch briefly on two types NEAL R. GROSS
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of complications, in particular:

connective tissue

disease and local complications and re-operations. I would like to discuss what we have

learned since 1988 these two subjects.

There have been

a number of epidemiologic studies investigating the potential contribution of these products to the

development of connective tissue disease.

It appears

from the literature that there is no or at most a small increased risk of connective tissue disease from these products. There are some limitations to the studies performed, however, and these include the heterogeneity of the products in most of the studies and the fact that some of these studies looked at classical

connective tissue disease, but were not designed to assess a typical connective tissue disease. We have also learned from the literature that the risk of local complications and re-operations for these products as a whole is not insignificant. Local complications can include deflation, contracture, infections, breast pain, and hematoma. These complication rates are reported in NEAL R. GROSS
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the

literature

very

widely.

The

FDA

and

DHHS

commissioned a report by the Institute of Medicine on the safety of silicone breast implants based on

information in published literature.

The Institute of

Medicine review included saline breast implants which have silicone elastomer shells. The Institute of

Medicine report concluded that local and perioperative complications are the primary safety issue with

silicone breast implants.

This group in their report

also noted a deficiency in the literature with respect to product specific information. Over the next day and a half, you will be reviewing the product specific information that

sponsors have provided in their PMAs.

You will be

asked to evaluate the information in each pre-market approval application and advise us as to whether there is sufficient a information in each application of safety to and

provide

reasonable

assurance

effectiveness. You will be asked to make your

recommendations based on data contained within the PMAs and based on your scientific knowledge. NEAL R. GROSS
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You will be

provided a list of questions for each PMA to consider as you review the data. Each application will be

considered separately on its own merits. We have heard this morning a number of comments from the public, and one of the themes that emerged is the important question about adequate

informed consent from patients and how to make sure that patient consent is truly informed. On Friday, we will seek your guidance on the important task of assessing what information we can provide to women to best assist them to make informed decision regarding breast implant surgery. The FDA very much appreciates your giving of your time and expertise to accomplish this important task. And now I'm going to turn it back over to you,

Dr. Whalen. CHAIRMAN WHALEN: Thank you, Dr. Witten.

Does the panel have any questions for Dr. Witten? (No response.) CHAIRMAN WHALEN: DR. WITTEN: Thank you very much.

Thank you.

NEAL R. GROSS
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CHAIRMAN WHALEN:

Next, Dr. Wendie Berg

will discuss considerations of imaging patients with breast implants. Dr. Berg. DR. BERG: Thank you, Mr. Chairman,

members of the panel. If I can have the lights down a little bit, as a radiologist. (Laughter.) DR. please? I'm considerations diagnosis in going largely women with to be presenting on breast imaging cancer Rupture, BERG: Can I have the next slide,

focusing breast

implants.

particularly with saline implants, is really a clinical diagnosis. Periprosthetic fluid is a common finding on imaging, but we dismissed this. It's not thought to

represent leakage on the whole, and again, I'm going to focus my comments on detection of breast cancer. Could I have the next slide, please? We can argue about the specific number of NEAL R. GROSS
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women

who

have

undergone

breast

implantation,

but

approximately two million women in the United States are affected by it, and again, most of my comments are going to be directed to women with augmentation rather than reconstruction since we do not generally image the breast after mastectomy. If one considers the rate of breast cancer to be approximately one in nine over a course of a lifetime, we can estimate that roughly 200,000 women with breast implants will develop breast cancer. Next slide, please. Mammography remains the standard for early detection of breast cancer. The goal, of course, is to

detect breast cancer before it becomes palpable at an earlier, literature more that curable 90 to stage. 95 We know cure from rates the are

percent

achievable when breast cancer is detected at Stage 0 or Stage 1, and this is nonpalpable disease, largely found by mammographic screening. Survival rates and disease free survival, in particular, drops to 60 to 70 percent when lymph nodes are involved by the tumor. NEAL R. GROSS
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That number further

drops to approximately 40 percent when the lymph nodes are involved and the primary tumor is palpable at

presentation. Next slide, please. There have been several studies looking at the risk of breast cancer in women with implants, and they have rather conclusively demonstrated to date that there is no increased risk of breast cancer as a result of the presence of the implant, and in fact, in several smaller studies rate there of has been actually a slightly to that

decreased expected.

breast

cancer

compared

May I have the next slide, please? Some general considerations first, and

then I'll get into specific data that is available. The American College of Radiology

Standards require the performance of routine views, as well as implant displaced views in order to adequately evaluate the breast tissue in patients with implants. As a result, dose we to can the expect breast at least double the

radiation

tissue

per

mammogram

obtained in such patients. NEAL R. GROSS
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Further, the presence of implants in and of themselves is an indication for diagnostic

mammography, which would allow the mammograms to be reviewed by the radiologist when the patient is there in the suite. the The reason for this is that many times is unable to obtain an optimal

technologist

mammogram at the first pass, and additional views would be needed to adequately compress or evaluate the breast tissue. As a result, we again anticipate at least more than double the cost of annual surveillance

mammography. Next slide, please. These are rather difficult to project, but just to illustrate, this is a mammography with routine views first in a patient with silicone implants, and the next slide, please. The corresponding images are

obtained when the implant is pushed back out of the field of view, allowing better compression of the

implant -- of the parenchyma itself. Next slide, please. Even with such techniques, there is a

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reduction in the visualized breast tissue in patients who have breast implants. It's difficult to answer

absolutely how much that reduction would be in any given patient. There is some data from a series where

patients' mammograms were measured both prior to and after implantation, and overall it was found that 30 percent reduction in the visualized breast parenchyma in the absence of any contracture. If contracture is present, it's more

difficult to compress the breast.

As a result, greater

reduction, on the order of 50 percent, was observed in the amount of visualized parenchyma. Even with implant

displacement techniques, the amount of breast tissue that we see is still decreased compared to a patient without implants, and in fact, on average that was 25 percent still obscured with implant displacement;

greater, on the order of 35 percent, if the implants are subglandular compare to subpectoral locations. Next slide, please. To illustrate, this is a woman who had silicone implant placed behind the muscle and there's very little breast tissue visible on the routine views. NEAL R. GROSS
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Next slide please. And this is difficult to project, but on the implant displaced views, a subtle cluster of

calcifications was noted, and it's actually right here in the middle of a spot magnification view. This

patient had a very small focus of ductile carcinoma in situ that was detected despite the presence of the implants. Next slide, please. However, displace the implant. it's not always so easy to

This woman has a saline implant,

and you can see that it's still quite dense, although you can see a little bit of the internal structure and the folds of the edge of the implant. And despite every attempt at implant

displacement, this is the best mammogram that could be obtained. She had very little breast tissue. Next slide, please. She underwent an ultrasound. I don't know

if we can have the lights down any further -- underwent an ultrasound that showed the implant itself, and there was a very subtle mass anterior to the implant that was NEAL R. GROSS
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an

early

infiltrating

ductile

carcinoma,

completely

invisible on mammography as a result of the implant. Next slide, please. In general, as I've mentioned, the implant can hide the breast tissue directly and, as a result, can hide lesions as well in the breast tissue.

Adequate compression is sometimes difficult to achieve due to contracture, pain, and the mass effect of the implant itself. It can displace the tissue and cause

overlap in the normal parenchyma. It can be difficult to visualize lesions in both projections. You might see that lesion

inferiorally in the breast, and yet it's hidden by the implant in the craniocaudal projection, despite implant displacement techniques, and this can confound

interpretation as well as limit the biopsy options and make it more difficult to biopsy any lesions that are seen. And finally, in the woman who had

undergone removal of an implant, there can be extensive scarring, not always, but there can be. confound interpretation. There can be That can residual

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calcifications, particularly if the capsule is left behind after removal of the implant, and both of these can mimic cancer. Next slide, please. To illustrate, again, this is a patient who has a silicone implant behind the breast tissue, and this was the best mammogram that could be obtained. Very poor compression was achieved in the tissue

itself, and you can see there's a rather large density. This is approximately four centimeter invasive ductile carcinoma was visible, but if there were any other lesions in this breast, it would be very difficult to assess that. Next slide, please. And, again, this doesn't project well in this lighting, but this was a patient who was found to have a subtle cluster of calcifications in the inferior breast. Next slide, please. But bilaterally, and she we had were ruptured unable saline to implants the

localize

calcifications in the other plane because they really NEAL R. GROSS
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proved to be on the inferior breast directly underneath the implant. We were able to biopsy these with

stereotactic technique and found fibrocystic change in this case. Next slide, please. After implant removal we can see a variety of changes that are very suspicious. This particular

patient had explantation of an intact saline implant, but remained with a spiculated density at the chest wall which, if you didn't know the history, would be considered highly suspicious. She then underwent ultrasound -next

slide, please -- and was found to have a seroma. Next slide, please. Another patient who had undergone

explantation, again, had a spiculated density of the chest wall, and there were actually calcifications

evident within this, a lot of deformity in the breast tissue, difficult to get an adequate mammogram,

especially in the inferior breast. This proved to be an infective collection. We're having fund. I think you need a few more

NEAL R. GROSS
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microphones. Next slide, please. I mentioned that the capsule itself can cause some problems with interpretation, and the main reason for that is the presence of calcifications in the capsule itself, a rather common finding. Judy

Distouet and colleagues found about a quarter of the patients capsule. have some degree it's of calcification easy to in the

Usually

relatively

identify

because it's relatively coarse and typically benign, but when it's first starting it can, again, mimic early cancer. Next slide, please. Just capsules. extensive. well. Next slide, please. And the calcification in that capsule can be visible, easily or not. form distinguished If it's from ligament this You an can illustration see it of these can calcified get quite

really

This patient had severe contracture, as

calcification capsule itself

left

behind,

can

the

pocket

for

collecting

NEAL R. GROSS
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fluid, and as I mentioned that one case, infection. Next slide, please. I think the overwhelming question which I was asked to address is really will the diagnosis of breast cancer be delayed in women with implants as a result of suboptimal mammography. Unfortunately I'm There are only

not sure I can answer this question.

several small, retrospective studies that have been performed which are really inadequate to answer this question at this time. Next slide, please. I'm going to present a literature review, but there is, again, minimal data and keep in mind most serious saline. Next slide. I think there is some evidence to suggest, however, that the results may be generalizable between silicone and saline implants. in 1989, A study again from report results from silicone implants, not

Washington

University

using

the

American

College of Radiology and Mammography Phantom, which includes a variety of artifacts, including dense

NEAL R. GROSS
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specks, which mimic calcifications, and densities which mimic early cancerous manifests as masses, was used with a variety of types of implants positioned on top of the Phantom and a normal mammography exposure

performed. In their study, they found the shell alone minimally altered the ability to detect the various artifacts, but the shell filled with either silicone or saline completely obscured all artifacts. Next slide, please. What kind of performance are we expecting from mammography? not sure we have Well, this is a good question. the absolute answer, but in I'm the

American Health Care Policy Research Manual from 1994, we do have benchmarks that were established by a

variety of experts in the field suggesting that with routine screening, we should be able to achieve

detecting of the majority of cancers at Stage 0 or Stage 1, over 50 percent, and that node positivity should be under 25 percent of the patients diagnosed, and overall sensitivity of mammography on the order of 85 percent should be achievable. NEAL R. GROSS
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I think that last number may be a little optimistic. performance. percent There have been multiple studies showing In practice it's closer to 78 to 80 of breast cancer, allowing for a

detection

variety of factors, including errors in interpretation. Next slide, please. These are the references on which I have drawn, the literature that does exist on implants and breast cancer detection. Next slide, please. There's a lot of information here, but

just to summarize, you can see across these studies very small numbers of patients, and I think these are patients silicone who had augmented and were breasts not with usually annual

implants

undergoing

mammographic screening.

So this is simply at the time

of detection looking at results. They had ten patients, six patients, seven who had implant displacement views, as well as routine views, a total of 41 patients in the study of

Silverstein, but all small numbers of patients in these studies. NEAL R. GROSS
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Overall, the degree to which cancers were visible mammographically ranged from 55 percent up to a high of 86 percent. Overall palpability of the lesions The

detected was quite high across all these series.

lowest was the first study here with Leibman and Kruse, where six out of ten cancers were palpable at

presentation, but the vast majority of the cancers in these reflect patients. Nodal positivity was also higher than that benchmark of 25 percent across most of these series. One study in particular I want to call your attention to was that of Laurie Fajardo and colleagues done at Arizona. At the time 18 patients all had implant studies the were lack palpable, of routine and again, this in may these

screening

displaced mammography views, as well as routine views, and in that series the sensitivity was only 67 percent, and in fact, 39 percent had positive lymph nodes at presentation. Next slide, please. So to summarize, the majority of patients in these studies that have been done to date had only NEAL R. GROSS
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routine

mammographic

views

without

implant

displacement, and we've already shown, I think, that it's mandatory that the implant displacement views be obtained in order to adequately evaluate the

parenchyma. More cancers were palpable at diagnosis

than in general. We expect that number to be about 40 percent palpable at presentation. In these series it

was from 80 to 90 percent in the majority of the studies. The stage distribution of cancers,

however, in the papers that had control groups was not found to be significantly different in women with

implants, nor was the survival found to be different. Okay. Next slide, please.

Overall, where it could be assessed, 66 percent of cancers were visible on mammography with implants, and when implant displacement views were

included, again, very small numbers, but 72 percent of those cancers were then visible on mammography. That's lower than the expected

sensitivity, as I mentioned. NEAL R. GROSS
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Next. I think of greatest concern though, it's difficult to make recommendations because the

performance of mammographic screening in women with saline implants or any other implants, for that matter, has really not been adequately evaluated, particularly with high quality mammography and implant displacement views. We can suspect from the data that does exist that there's at least a ten to 20 percent

decrease in mammographic sensitivity, and that alone, even that relatively conservative number, has the

potential for delayed diagnosis of cancer in 20 to 40,000 women. Are mammography? there other alternatives to

Very briefly, yes, there are, but they Ultrasound is

all have their limitations as well. being used more and more widely.

It has a clear role

in evaluating palpable abnormalities in all patients, including those with implants. We also use it when

there's a mammographic density that we're concerned about. NEAL R. GROSS
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It's easy to guide biopsy lesions as we see under ultrasound, is less but the problem to the is screening early situ,

ultrasound carcinomas,

sensitive ductile

very in

particularly

carcinoma

than is mammography. Further, demanding. it's technically extremely

It requires a lot of expertise on the part

of the person doing the ultrasound, usually requires a physician to perform the task, and at least in the United States the costs of screening ultrasound are on the order of $300 per patient compared to approximately $75 for mammography. Further, lesions behind the implant will not be well seen even on ultrasound. Next. Just another slide that illustrates a

cancer adjacent to the implant on ultrasound. Next slide, please. It has been suggested that MRI may be

appropriate in these patients.

In fact, one recent

reference suggested it's the modality of choice for detection of primary breast cancer in the augmented NEAL R. GROSS
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breast. Well, it's clearly a very sensitive test. The implant it does does not obscure detection of of lesions.

However, contrast.

require

injection

intravenous

It's extremely expensive.

A billed cost is

about $1,000 for a contrast enhanced MRI. It's seen only on MRI. difficult to guide biopsy lesions

It's technically very demanding and

not widely available. Next slide, please. Just to illustrate though, it is very nice to demonstrate cancers on MRI. We have here an implant

at the lower right-hand corner of the slide, and you can see the area of enhancement just above it is a spiculated mass with associated rim enhancing lesion, and these were two adjacent cancers that were

nonpalpable in a woman with implants. Next slide, please. MRI done improperly, however, still

doesn't help obviously and it can be very demanding. This is a woman that we saw in our practice with a saline implant, some periprosthetic fluid inferiorally; NEAL R. GROSS
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several cysts in the breast, but no contrast had been administered and, therefore, no lesions were detected of significance, and she had a breast cancer that went undetected for another year. Next slide, please. One other potential method for screening would be nuclear medicine techniques, such as Sestamibi or Miraluma, as it's more commonly known. again, the sensitivity is not very good. However, It's an

expensive test, again, and in particular, I call your attention to the statistic that nonpalpable lesions under a centimeter, only 48 percent of these were

detected. And so I don't think there are very many good alternatives to mammography, in summary, but I think we also have at least reason to consider that there may be some limitations of mammography in

patients with implants. Thank you for your attention. CHAIRMAN WHALEN: questions for Dr. Berg? DR. ROBINSON: I have a question. Do any of the panel have

NEAL R. GROSS
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CHAIRMAN WHALEN: DR. ROBINSON:

Yes. How do

Just a question.

you think MRI will evolve as an imaging technique in the evaluation of women with implants or one where you really cannot get good imaging by your other -DR. BERG: I think more and more we're

finding from data from international studies and grant sponsored research trials now that it is an extremely effective method at finding early cancer. I think the

problem is going to be who's going to foot the bill. It's an extremely expensive test. It's

very demanding, and if insurance companies will foot that bill, great, we can do the test. But I think that

as a society, we really can't afford to screen women with breast MRI at this point. double edged sword. DR. ROBINSON: What numbers would be So we've got that

involved if you weren't screening them per se, but just doing women where you could not get good imaging by another technique? DR. BERG: Well, again, I think you're

looking at at least probably 30 percent of women with NEAL R. GROSS
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implants

where

you've

got

significant

limitations.

You've got women with dense breasts, women who are at high risk. We're probably looking overall at the

population of maybe, again, probably 30 percent of the overall population who has mammography routinely where MRI would stand to benefit them. It is routinely done in women who are at high risk at some centers already, and it's being more and more widely used. DR. impression was. The last question. I'm sorry. For ROBINSON: Yeah, that's what my

lesions behind implant, is spherical CT or helical, anything in that area going to have any implication? DR. BERG: The reason I did not I thought about including CT. is that it's got very high

radiation dose to the patient, on the order of two to three rads as opposed to mammography is on the order of .2. You don't want to irradiate the breast with

tenfold as much radiation.

You're going to be causing

a significant number of cancers. So it also is not -- it's clearly not as NEAL R. GROSS
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sensitive a test for certainly not in situ disease and may pick up invasive cancers with the injection of contrast, but, again, I don't think anybody wants to advocate CT for that purpose. Any other questions? DR. BURKHARDT: I have a question. Most

of the studies that you quoted here are of necessity a few years old. DR. BERG: Right. In the last five years or

DR. BURKHARDT:

so, there's been a tremendous shift in the placement of these implants in the plastic surgery community.

They're almost all put behind the muscle now -DR. BERG: DR. cases. DR. BERG: That's right. Do the ACR standards still Right. -in nonreconstructive

BURKHARDT:

DR. BURKHARDT:

require double the radiation dose? DR. BERG: very explicit. I Yes, they do. in the I think it's recent ACR

looked

most

standards that I have, which is 1998, and it does NEAL R. GROSS
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require the implant displacement views be obtained as part of routine practice, and I think you'd be very hard-pressed to defend if you missed a cancer as a result. It's very difficult. Even with

subpectoral implants it's very difficult to adequately compress the entire tissue, depending how much tissue the patient has. DR. BURKHARDT: Do you have any sense of

what percentage of women in the eligible and in the recommended cancer screening group actually have

mammograms according to the ACR standards? DR. BERG: about discussing that. Good question. I was thinking

I don't really have good data

on that, but I can tell you that many women with implants hesitate to have mammography even once they become of that age because it's a painful exam, and it's more involved. DR. BURKHARDT: implants? DR. BERG: Well, without implants, we know How about women without

it's about 60 to 70 percent who do under -- have had a NEAL R. GROSS
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mammogram within the last two to three years. DR. BURKHARDT: DR. BERG: Thank you.

Un-huh. Ms. Brinkman. For routine screening

CHAIRMAN WHALEN: MS. BRINKMAN:

mammography, does insurance pay for the extra views then for the displacement of the implant? DR. BERG: As a rule, insurance does pay

the additional cost, although oftentimes a woman will still have a deductible and still bear a greater cost as a result of having to have a diagnostic mammogram on a yearly basis for what amounts to screening. CHAIRMAN WHALEN: Thank you, Dr. Berg.

We are now going to proceed to the review of the first PMA, and that is going to be the one of Mentor Corporation. So I would ask those who are going

to be making that presentation to come forward. I would like to remind all of the public observers at this meeting that while this portion of the meeting is open to your public observation, you as public attendees may not participate unless there were to be a specific request of the panel. NEAL R. GROSS
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We now turn it over to Mentor Corporation who, if necessary, can take upwards of a full hour for their presentation. I'm being outvoted by the mutiny here. I

was going to hold off on the break until afterwards, but it seems that all of the panel has bladders the size of walnuts -(Laughter.) CHAIRMAN WHALEN: -- we will take about a

seven minute break and then resume. (Whereupon, the foregoing matter went off the record at 2:43 p.m. and went back on the record at 3:04 p.m.) CHAIRMAN WHALEN: And, again, we are now So we turn the

going with the sponsor's presentation. table over to Mentor Corporation. MR. GETTE:

Thank you, Mr. Chairman and

distinguished members of the advisory panel. I am Anthony Gette, President and CEO of Mentor Corporation. For more than 30 years, Mentor has been dedicated to the research, development, and marketing NEAL R. GROSS
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of innovative and effective medical devices that meet the needs of patients and physicians. We sell products These and here;

in more than 60 countries around the world. products include devices which used we in will plastic present

reconstructive

surgery

products to treat urological disorders, such as for prostate cancer, bladder cancer, erectile dysfunction, and pelvic flora disorders; and a variety of consumable products, primarily for the management of urinary

incontinence. All of our products are designed to

improve the quality of life for patients who use them. Today we focus with you on our saline filled breast implant products. The heart of our presentation is

data that we believe confirms that our implants are both safety and effective and warrant your

recommendation of approval of our PMA to the FDA. For breast implants, our goal is to

provide a safe and effective option so that women can choose whether to restore the breast following cancer, trauma, or correct a deformity, and also to choose a more satisfying breast appearance through augmentation. NEAL R. GROSS
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Saline breast implants have been available for more than 25 years. There is a large body of Reports from such have as the

information based on such a long history. prestigious Institute scientific of Medicine organizations, and others,

provided

invaluable information with respect to the long term safety of breast implants. For a number of years we have worked

closely with the FDA to develop the preclinical and clinical information contained in our PMA submission. We will present some of the results of this

comprehensive effort this afternoon. We clearly risks of believe that our PMA the the application localized first time

demonstrates implant

safety,

defines for

surgery,

and

quantifies the effectiveness and benefits of saline filled breast implants. Our commitment is that the implants we

manufacture are safe, effective, and are appropriately supported by scientific studies. We are proud of our

pivotal trial, the saline prospective study, or SPS, and believe it will significantly advance the clinical NEAL R. GROSS
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knowledge about breast implants. Our job does not end there. We are

committed to continuing research and to the development of ever better products. Our presentation today has four parts.

Mr. Bobby Purkait, Mentor's Senior Vice President for Science and Technology, will describe our preclinical testing program. Ms. Clinical clinical Pamela Powell, Manager will of Mentor's the our

Programs trials we

Department, have

describe including

sponsored,

pivotal trial, the saline prospective study. Dr. Bruce Cunningham of the University of Minnesota will describe the results with regard to

clinical safety. Dr. College of Rebecca Anderson will of the Medical the

Wisconsin

then

describe

effectiveness and benefits of Mentor's saline filled breast implants. At the conclusion, Mr. Purkait will

summarize our presentation and lead our response to your questions. He will also introduce our question NEAL R. GROSS
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and answer response team at that time. It is now my pleasure to introduce Mr. Bobby Purkait. He is a polymer science engineer, and

for the past 15 years has led Mentor's research and development coordinator efforts. of Mentor's He has been the and primary clinical

preclinical

submissions on the saline filled breast implant. Mr. Purkait. MR. PURKAIT: Thank you, Mr. Gette.

Good afternoon, Mr. Chairman and members of the panel. I'll be presenting an overview of our

preclinical data today. In that overview I'll be describing the devices which are seeking approval today. I'll be also

describing the separate issues that we have considered in our evaluation, various and in that evaluation as we have

conducted

testings,

such

biological, I'll be

chemical and mechanical and manufacturing.

describing some of those testings and the findings from those test results, and finally I'll summarize. These pictures represent the Mentor's There are

family of saline filled mammary prosthesis. NEAL R. GROSS
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www.nealrgross.com

two saline filled mammary prosthesis.

The one on the

left-hand side is a fixed polymer prosthesis, which has been filled at the time of implantation. The rightIt's

hand side is an adjustable volume prosthesis. filled intraoperatively or postoperatively.

These two devices come either in smooth or textured surface and also can be found in round or contoured shapes, and the sizes vary from 125 to 700 cc's. All the variations of these sizes and shapes are

denoted by styles number, which has been given in our PMA. These schematic diagrams furthermore

illustrate the design and the materials that we have used in our devices. These two devices, one on the

left-hand side, has elastomer silicone shell, and the right-hand side the adjustable one also has silicone elastomer shell. These silicone materials are being used

commonly in many other medical devices, and a large body of data exists both in Mentor data bank, as well as in the open literature. The left-hand side, the fixed volume one, NEAL R. GROSS
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has a valve called diaphragm valve on the anterior surface of the device, and the right-hand side, the adjustable volume prosthesis called Spectrum has a kink valve which is used to fill intraoperatively or

postoperatively. All variations of these devices have same materials, have been manufactured under similar

conditions, tested and released under same requirement and specification. In our preclinical safety issues we have considered safety assessment by two different ways. First, we concentrated on the toxicological safety

assessment by chemical characterizing our device and materials, and also conducting some various biological battery of testings. To assess the performance and durability of these devices, we have done mechanical testing and also developed information from manufacturing process and quality of the products information. In the toxicological safety assessment, we have used the biomaterial toxicity risk assessment

paradigm.

From that paradigm we have done a chemical NEAL R. GROSS

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COURT REPORTERS AND TRANSCRIBERS 1323 RHODE ISLAND AVE., N.W. WASHINGTON, D.C. 20005-3701

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characterization of the device material and also we have characterized the toxicity of those materials. We

also have developed information regarding exposure to the constituent materials in the course of the device. Now I want to share with you some of the chemical testing that we have conducted. This

particular slide shows a battery of testings, and these testing demonstrate in case of biodegradation we found a device the or material, of stable harsh and nonbiodegradable, of enzyme,

under

exposures

conditions

peroxides or lipids. When we look into the surface, we found the surface composition is made solely from

polydimethosol siloxin (phonetic), and those surfaces were examined by various different instrumentation

techniques, such as IRS, SIMs, SEM, to say some of those instrumentation techniques. When you look into the state of the cure of our shell, we found it is fully polymerized, and the cure is 100 percent cured there. PCBs are not

detectable in our devices.

When we looked into the

metals and extractables, we found all levels are below NEAL R. GROSS
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the toxicological concerned. This shows the total battery of our

chemical calculation of a device and our materials. Similarly battery of we have safety done a significant and this The

biological site, we

testings,

particular

present

those

testings.

results from those, we have not found any reproduction or developmental toxicity problem, no pyrogenicity with our materials or our devices, no genotoxicity. The biostability of our device was found to be excellent. and No when chronic we toxicity into and the

carcinogenicity,

look

immunological response, no adverse reaction from those either. This represents the total battery of testings

for our device and materials. As we move on and characterize these

materials under mechanical testings, these are the test batteries materials. We recognize that this device would be that we have conducted on a device and

used in clinical settings, and in that use there will be -- it will be subjected to mechanical load and NEAL R. GROSS
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stresses in order to establish an evaluative behavior of a device and materials under various mechanical

conditions.

We subjected the device to the various

mechanical testings. Now I will share some of the test results with you now. As you look into the basic mechanical

properties of our material and device, we conduct ASTM testing, such as tensile, ultimate elongation,

tear/break force, et cetera, and we found our device and materials exceed ASTM specification. When you look into the joint testings, we also found it meets the specification as defined by ASTM. Active material, what we use in our device, has However, when it has

excellent abrasion properties.

been upgraded (unintelligible), we found no silicone materials were found on the surface. When looking at the expanded devices, some of the devices were implanted up to six years, but when we test those, we found the mechanical properties have not significantly changed. Fold flaw was determined by the explanted devices. When we examined those devices, we found the NEAL R. GROSS
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fold failure was primarily due to the concentrative force that was onto the fold. The fatigue testing has been applied to our devices. Through this testing we have established

the F and N curve (phonetic), and that has demonstrated a large safety factor against rupture. I'll share with you an example of our test mechanism laboratory. and test This set-up where we used shows in a the

particular

device

procedures or the set-up, what we use to understand the mechanism of rupture failure. in the bottom of this cage. the case. There's a device sitting This is

There's the foam.

The whole thing has been emersed into 37

degree saline solution, and we have applied the load conditions of 30 to 85 pounds and cycled those many, many times. Here is an example for ten million cycles, no failure. We looked into the static impact testing. Our devices can withstand a significant amount of

energy on our device exceeding in excess of three times that one might experience in a car accident for 35 NEAL R. GROSS
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miles an hour collision. I'll show you an example of those test mechanisms again. Here the prosthesis is sitting in

the bottom under the saline solution at 37 degrees, and the weight has been dropped from 9.2 feet, with a load factor of 35 pounds and then 45 pounds. Impact energy

generated on this device, about 444 to 570 and no rupture was noted. However, this device also cycled even

before this for ten million cycles, indicating a great assistance to rupture of these devices. This particular impact test has been shown previously. Again 35 pounds, 45 pounds load were

impacted on these devices and no failure was achieved or seen. Static rupture is also an important When we can

phenomenon for our device to understand.

place our devices to a load of 162 to 344 pounds of weight, we can practically get this device into a

pancake shape without noting any particular rupture or crack on the particular device. Looking at the valve competence test, we NEAL R. GROSS
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found this internal pressure of this valve exceeds in excess of the in vivo use. Looking into the radiolucency testing, we found the radiolucency is significantly higher in

comparison to the silicone gel. As we complete this battery of mechanical testing, we conclude that our devices and materials survive mechanical stress that exceeds the clinical use conditions. We looked into our manufacturing process extensively. We have a rigorous manufacturing process The process validation system

and a quality system.

has been done extensively to understand our processes table, and we produce consistent quality product. have a significant amount of in process and We

other

testing throughout the operation. any product without having any

We do not release finished device

specification being met. We believe that our manufacturing provides a good, consistent, reliable product, and the

conclusion from our operation of the evaluations of the results are devices are produced using a validated

NEAL R. GROSS
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process and equipment under GMP, which meet quality standards. We have a well documented quality system

that insures that we have a safe, reliable, and quality products. I'd testings by like way. to summarize We have has our preclinical an extensive to

this

done been

preclinical

testings

which

documented

understand the behavior of our materials the state of the art methods. We have characterized

and device by

the

potential

extractables, identified and quantified those which are found device to be below the and A no toxicological devices total are of concern. stable Our and

materials

nonbiodegradable. testing devices documented and

battery

biological issues, and

toxicity survived

testing

materials

mechanical

stress

testing that exceeds clinical use conditions. Now I would like to invite Ms. Pamela

Powell to describe our clinical studies. primarily talking about the design and

She will be the design

parameter of our studies. Ms. Powell. NEAL R. GROSS
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MS. POWELL: Mr. the clinical

Thank you, Mr. Purkait. panelists, Mentor I will present in

Chairman, that

studies

has

undertaken

support of the saline PMA and focus primarily on the three year saline prospective study. Mentor indications reconstruction of is seeking approval for the

cosmetic following

augmentation, mastectomy or

breast trauma,

asymmetry, ptosis, aplasia, hypoplasia, replacement or revision of unsatisfactory implants, and combined

breast and chest wall deformities. Mentor clinical studies, The has two funded or conducted and five three include

prospective

retrospective.

prospective

studies

Mentor's three year saline study of 1,680 patients and the large, simple trial, a one year study of 2,400 -excuse me -- 2,347 patients. The Mentor's study three of 822 retrospective patients studies ten include years of

with

follow-up, the SEER study with 1,159 patients with ten years of follow-up, and the Cunningham study with a minimum of ten years of follow-up on 450 patients. NEAL R. GROSS
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These Bruce Cunningham. With

results

will

be

presented

by

Dr.

the

data

of

the

prospective

study

unavailable until its completion in 1998, FDA wanted safety data on a large population in a short period of time. The large, simple trial was designed to meet

those needs and consists of one year of follow-up on 2,347 augmentation, with the reconstruction, safety and to revision assess

patients,

objectives

infection, deflation, and capsular contracture. The patients were seen at baseline four to six weeks, six months and one year. The saline prospective study or pivotal

clinical trial is a comprehensive study designed to look at both safety and effectiveness. safety objective was to assess The primary short term

complications, such as infection, seroma, deflation, capsular contracture, and nipple and breast

sensitivity. The secondary objective was the detection of calcification surrounding the implant. The primary effectiveness objective was

NEAL R. GROSS
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change in breast size.

The secondary objectives were

patient satisfaction and quality of life. Dr. these results. At the baseline visit, study parameters, benefits and risks of the implants and procedure itself were discussed with patients. A history and physical Rebecca Anderson will be presenting

and rheumatology assessment was done by the plastic surgeon, and the patient completed the quality of life questionnaires. Complication reactions occurring or information reported at or adverse or

scheduled

unscheduled visits were also reported to Mentor. The saline prospective study was conduct at 153 centers throughout the United States, providing a broad geographic and demographic diversity of

clinical sites. enrolled in

Sixteen hundred and 80 patients were study; 1,264, or 75 percent,

the

augmentation and 416, or 25 percent, reconstruction, with over 80 percent of the patients returning for their two year visit. The augmentation patients were between the NEAL R. GROSS
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ages of 20 and 40, with about one half married and 30 percent single. The educational level of the patient

population was representative of women throughout the United States. The majority of the reconstruction

patients were between the ages of 30 and 60, 63 percent marries and 15 percent single. Most had some college.

Based on the demographic data and other characteristics presented here, we believe that the saline prospective trial population was a

representative cross-section of women who were seeking breast implants for augmentation, reconstruction, and revision. Now I am pleased to turn the presentation over to Dr. Bruce Cunningham, the Medical Director of the three year saline study, professor and chair of plastic surgery at the University of Minnesota. Dr.

Cunningham is also former chair of Silicone Implant Research for the Plastic Surgery Educational Foundation for the American Society of Plastic Surgeons. Dr. Cunningham. DR. CUNNINGHAM: Thank you, Ms. Powell.

NEAL R. GROSS
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Mr. Chairman, panelists, my name is Dr. Bruce Cunningham. University of I'm a professor of surgery at the and also conduct a busy

Minnesota

clinical practice. the study that have the

I'm the paid Medical Director for is presenting to do today, and in for be

Mentor been

addition, Mentor

contracted

research will

and

McGhan

Corporation,

which

presented by McGhan. I want to address some of the issues of clinical safety. The goals of my presentation are to

characterize and quantify the clinical risks defined by the large, prospective study and other clinical data to demonstrate patient clinical the method and extent of physician to place the and the

information risks in

and

education, with

perspective

medical

literature for similar devices and indications, and then to summarize. There are four types of major safety

concerns which have been raised with respect to saline filled breast implants. important, addressed is by systemic the The first of these, and most disease, of and this has and been other

Institute

Medicine

NEAL R. GROSS
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scientific panel reports. Local complications are a special area,

highlighted by the Institute of Medicine, and will be addressed by the large simple trial and the saline prospective study. Durability or the survivability of the

devices in vivo will be addressed by the Cunningham ten year, multi-center, retrospective outcome study, as

well as the prospective study. And then cancer detection and treatment

issues are very important, and Dr. Lenore Iverson, our breast radiologist, can address those during the

question and answer session. The recent reports of the multi-specialty review panels have drawn some major conclusions. Three

scientific review panels, two in America and one in the United Kingdom, have concluded that there's no evidence for systemic disease associated with these devices. We

believe this is not an issue of major concern at this time. These panels have also concluded that

breast feeding is safe and beneficial for the child, NEAL R. GROSS
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and that there are no second generation effects on children of women with breast implants. The large, simple trial goals have been addressed. The data provided the FDA with assurance

that during the short term, while the long term three year data is being collected, that there were no major serious risks and complications of the procedure. I want to move now to the saline

prospective study, the goals of which were recounted, and this is the signal study that's being presented by the Mentor Corporation today. There were a number of statistical methods which were applied to this data set. survival examine analyses the which to are Most of them are methods of to

statistical

time

occurrence

various

complications.

We felt that the best way to represent

this was with the Kaplan-Meier analysis, which is used to provide the estimate of cumulative incidence for each complication by indication. In some incidences we performed other

analyses, such as a Cox proportional hazards model to examine for risk factors of individual complications NEAL R. GROSS
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and a logistic regression analysis to examine the risk factors for breast and nipple sensitivity. The prospective study includes two

distinct clinical populations with different objectives and different complication rates. them separately. First, the augmentation patients. The So we will present

devices that were placed are shown here.

The majority

of them are the textured SILTEX devices or the textured adjustable volume SPECTRUM device. of them are smooth devices. The quarters in location of placement position, is three is The remaining third

the

submuscular

which

beneficial for mammography, and also gives a better shape and feel to the device. Only 28 percent were

placed in the subglandular position. I want to spend a moment on this slide

because it will serve as a template for the data slide which follow. This is the standard Kaplan-Meier To make it

analysis, and in this case for infection.

easier to depict, the curve always shows one minus the survival curve, and the scale is pretty consistent at NEAL R. GROSS
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40. The graph typically shows the incidence, cumulative incidence at 36 months, banded by the 95 percent confidence interval, and in the upper righthand corner in this book, we will cite the relevant statistics from the medical literature. So in this case, the cumulative incidence in the augmentation patients who are receiving

elective, noncomplicated surgery is 1.7 percent for infection, which is a cumulative over three years, and in a situation where the curve is flat or the graph is flat, this does not mean that this is the incidence which is continuing to occur each year, but a flat graph rather means that there are no new occurrences of the complication. Every time we generated a number or a

complication from the data, we wanted to make sure that it was reflected in the patient and physician

information.

Here's the citation of the data reflected

in the product information data sheet which is given to physicians, and here it is in the product information sheet which was given to patients, citing the data NEAL R. GROSS
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right out of the study. I won't continue to show these, but for every data point we've reflected it in the product information. Here's the Kaplan-Meier analysis for a

significant concern, which is Baker II and IV capsular contracture. A Baker I classification contracture is So we wouldn't report

essentially a normal breast. that.

The Baker II classification is a firmness which

is basically detectable by the patient, and it's only when you get into the III and IV level complications, grades of capsular contracture that the presence of the implant might be detected by someone else. This is the Level III, Baker III

classification, 6.9 percent, and the Baker IV at .6. We feel that the Baker III is not a significant

clinical problem and rarely results in reoperation, but we wanted to check that out. So our statistics show that of patients in this classification of three and four capsular

contracture, only 23.5 chose to have surgical release of this scar tissue contracture. NEAL R. GROSS
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We also had a group of patients who had capsular contractures which are classified as unknown. In order to show the most adverse possible analysis, we included these patients as though they all had Baker III and IV grade classification, and that results in a classification percent. Let's augmentation look at The deflation incidence, among this for augmentation patients of nine

group.

cumulative

incidence at three years of deflation of the implants is 3.3 percent. We did, however, want to know whether

this is a trend that continues or what the long term deflation rate is, and to address that, the Cunningham study was commissioned. This is a multi-center, retrospective

cohort outcome study.

The study design was consistent

with the recommendations made by the FDA epidemiology panel. The study included 450 patients and 882

devices, with a minimum of ten year follow-up.

NinetySo

four percent of these patients were augmentation.

it seems appropriate to include this at this point in the presentation. NEAL R. GROSS
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Well, I'm going to deal with the Mentor devices in a moment. The deflation rate for devices

made by the current manufacturers, which are McGhan and Mentor, was 5.8 percent. This is 5.8 percent

cumulative incidence at three years.

It does not mean It's a

that it is an annual incidence of 5.8 percent. cumulative incidence. With percent of the respect devices to in the the Mentor study

devices, were

86

Mentor

devices, and we could isolate them as we look back at the data. The incidence of deflation per device for Mentor percent or Heyer-Schulte Model 16 at devices ten was 3.7 For

cumulative

incidence

years.

comparison, the saline prospective study, when looked at on a per device incidence, is 1.9 percent. Other significant findings from this long term, ten year retrospective study include an overall patient complication rate of 27.6 percent and an

overall patient reoperation rate of 25.8 percent. However, despite these two complications

and the number of reoperations, 93 percent of patients NEAL R. GROSS
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were satisfied or very satisfied with their implants. The Kaplan-Meier analysis for augmentation patients undergoing reoperation is shown here. incidence is 13.2 percent. The

We wanted to look behind

this number a bit and see what were the causes for this, and here are the causes for reoperation. These are a good assortment of causes and indications which we would expect to see in a group of patients having elective surgery, and I'll address this other classification in a moment. There were a number of patients in this augmentation group who had their devices removed, 8.1 percent, in fact. this occurring. And again, we wanted to know why was

Was there a clinical reason for it?

And when we look at that, we find that there are the usual but things in and that terms this we of are citing as

complications, patient request

also

this

number, for most

alone,

indicates

patients that they're choosing to change the volume of their implant, and in fact, the critical finding is that 72 of the 88 patient implants that were removed were replaced again at the same surgery, indicating NEAL R. GROSS
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that this was an elective procedure, perhaps a size change that the patient chose. Other complications are shown. One of the

goals of the study was to reflect the incidence of calcifications in this patient, which is extremely low, less than one percent. Cancer detection is a significant issue, as Dr. Berg pointed out. The clinical issues are: do

breast implants interfere with mammography? detection delayed?

Is cancer

And is clinical outcome compromised

by the presence of the devices? The data to be presented can be drawn from the SPS study results. However, it's important to

realize that this was not a study design goal, and this data is anecdotal. The population based research conclusions we feel are very important and will be drawn from papers that were included in the PMA submission.

First, let's look at the data from the study. There were two breast cancers detected by mammography among this augmentation cohort. The first

patient had treatment which was effective for a small NEAL R. GROSS
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lesion with a very favorable outcome. The second patient unfortunately had a

very aggressive cancer.

This was detected in the first

six months following implantation with her device, and unfortunately the patient expired five years later. She expired outside of the terms of the study time frame, but we felt it was important to present her data nonetheless. There are two major studies that I would like to address. Alberta, Canada. design which we First is the Birdsell study from This is a population based study feel is much more significant and

powerful study design than the case study reports which have been cited. The study group was 41 women with cosmetic breast implants who had developed breast cancer. The

control group was 13,000 women with breast cancer, but who did not have breast implants. In terms of the findings, the women with implants were diagnosed at a younger age than controls. The study population tumors were smaller. Lymph node

and distant metastases occurred equally frequently in NEAL R. GROSS
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the

two

groups,

and

the

distribution

of

tumor

histological types was not significantly different. Of greatest importance, however, is the

fact that the five and ten year Kaplan-Meier survival rates did not differ between the implanted and the control groups. Another significant study was reported by Dr. Deapen in 1997. study County. using the This is another population based registry from Los Angeles

cancer

It looked at women who were implanted between The study group consisted of 31 breast

1953 and 1980.

cancer patients in 3,182 women with breast implants. The control group was the Los Angeles

County cancer surveillance program, and the patients were demographically matched as closely as possible to the women without implants. The median follow-up was 14.4 years. The

findings showed that the stage at diagnosis did not differ between the implanted and the control groups. In fact, there was a lower than expected incidence of breast cancer with 31 observed cases against an

expected rate of 49.2. NEAL R. GROSS
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This data has been further elaborated on by a recent study that Dr. Deapen published this month. In that study, he points out that cancer detection was not delayed in the group of implanted patients and treatment was not compromised. Let's cohort. population. look now at the reconstruction are a special

Reconstruction

patients

They have more extensive initial surgery.

In that case breast tissue and skin is removed, and flaps or skin grafts may be required just to close the wound. Additional procedures and interventions

are frequent, and the general health of the patient may be severely affected by adjunctive treatment, such as chemotherapy or bone marrow transplantation. A plastic special clinical problem exists for for

surgeons

treating

patients

breast

reconstruction. achieve than a

Symmetry is much more difficult to simple to enlargement be compared of to the the breast. chief

Complications

have

alternative to implants, and not to the augmentation group that we've just discussed. NEAL R. GROSS
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The

major

alternative

to

breast

implant

reconstruction are major flaps and major surgery, and when flaps fail, they have a significant morbidity and impact on the patient's life. The reconstruction patients were implanted by and large, a significant majority, with textured, contoured, textured devices, the SILTEX. The SPECTRUM

device was used in 44 percent of patients, and this is a unique device which is specifically applied and of great use to plastic surgeons in reconstruction because it can serve as a soft tissue expander and as a

permanent implant, allowing many patients to have the reconstruction in one stage. Most of the devices were placed in a

submuscular position.

Some were subglandular, perhaps

in patients who were having lumpectomy and radiation. The Kaplan-Meier analysis for infection

shows an incidence of 9.1 percent cumulative at 36 months, which is three times the amount in augmentation patients. This is in a group of complication prone

individuals who are receiving adjunctive treatments and much more significant surgery. NEAL R. GROSS
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The contracture is

Baker

Grade

III

and

IV 24.1

capsular percent

significantly

higher,

capsular Grade III and 6.7 percent capsular Grade IV. Again, the question arises: how significant is this

and what kind of impact does it make on the patient's life? And of note, only 27.8 percent of patients chose to have the capsule released with surgery. Deflation is a significant problem in this group of patients, again, almost three times as

frequent as in the augmentation group. is a group of patients who are

However, this subsequent radiation,

having

treatment,

biopsies,

needle

aspirations,

chemotherapy to treat their primary underlying disease, and this can easily account for this increased

complication of deflation among this group. We looked at the reoperation rate, which is higher than the ten year retrospective study and is at 40.2 percent. We want to look behind the number.

What are the causes for this, and it's important to note that many of the causes for this operation in this group have to do with the underlying tumor problem, NEAL R. GROSS
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lymphadenopathy, breast cancer or mass, necrosis, which is probably related to the flaps at the time of the mastectomy, or delayed wound healing, again, related to healing at the time of the mastectomy. There undergoing are a lot as of a patients part of who are their

operations

reconstruction, either a staged reconstruction or a nipple/areolar complex or some other part of the breast mound is being built or for asymmetry many of these patients were recorded, although they had surgery on the contralateral breast, such as a reduction or a mastopexy. So there are a number of good clinical reasons not related to the implant for these subsequent operations. The Kaplan-Meier analysis of explantation shows that 26.8 percent of patients have their implants removed, but a lot of them were elective and were being done to release scar capsular contracture or infection or, again, to deal with the problems related to their breast cancer. Of this group, 60 of the 97 percent of NEAL R. GROSS
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implants were replaced at the same time that they were removed, indicating that this was not a group of

patients, by and large, who gave up or abandoned their reconstruction, but rather were a group of patients who were electively trying to fine tune or complete their reconstruction. The revision after explantation, which is the revision group that the sponsor is seeking approval for, the data is shown here. It's a difficult group to

categorize because it includes both augmentation and reconstruction patients, and the variance,

statistically significant variance, from the previous initial operation is shown with the augmentation cohort and the reconstruction cohort and the difference in the variant. This is a summary slide of the short term risks and complications similar to what was presented in the large simple trial for augmentation and

reconstruction. basis.

This is presented on a per patient

The revision was always presented on a per So we can only give you a qualitative

implant basis.

assessment with respect to incidence. NEAL R. GROSS
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Additional statistical analyses were done, and this is one of the major benefits of the study because it will provide significantly important

clinical information for plastic surgeons and for the patients. Cox proportional hazard models were used on

factors contributing to deflation to understand them, and logistic regression analysis was done to determine factors affecting breast and nipple sensitivity. Here are all of the risks factors that were identified and reported in this large group of patients, and the ones which had clinical statistical significance are noted on the right. closer look. In the group of patients who had -- this is an analysis with respect to deflation, and when the augmentation is used as the reference, immediate Let's take a

reconstruction patients had a significantly higher rate of deflation which, again, would go with the fact that they are having and subsequent things to interventions, treat their biopsies, underlying

aspirations

problem, and the delayed reconstruction patients who have by and large completed that process have a lower NEAL R. GROSS
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rate of deflation. The unilateral versus bilateral simply

reflects the statistical chance of having two implants versus one, and this is a clinical interest. The

average incision size is the reference, and incision size below reference of three sonometers results in a two times risk factor for deflation of the device, indicating that surgical choices and surgical technique have a definite impact on the outcome of the durability of the device. Of great significance is the effect of

Betadine, a common antibiotic irrigant which is used by many plastic surgeons, despite the face that the

product labeling specifically interdicts such use, to attempt to prevent an infection. Patients who have

their devices bathed or irrigated with Betadine had a 3.5 times risk factor for deflation of the device. This is clearly information that needs to be in the hand of every plastic surgeon so that this practice is abandoned. We wanted to look at breast and nipple sensitivity. Above the yellow line show patients who NEAL R. GROSS
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had increased sensitivity.

Below the line are patients We

who had less sensation carried out to 36 months.

wanted to know if there were any factors that impacted clinically on this incidence of change in sensation. When we look at the inframammory incision as the reference site and compare it to periareolar or transaxillary incision sites, there are statistically significant findings. Periareolar patients had a

significantly greater risk of diminished or changed sensation than the inframammary site patients, and this would follow from an intervention that occurs close to the insertion of the nerves in the end sensory organs. The significantly transaxillary risk of patients change in had a

lower

sensation,

obviously being operated on from a more remote site. This is good information that will allow plastic

surgeons and their patients to make better informed choices. So what does this all mean? impact of this amount of data? First, complications have the been clinical risks and defined local and What's the

effectively

NEAL R. GROSS
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quantified by the data presented today. patients are fully and informed that's about on

Physicians and the the risks study and data

complications, directly. The

based

risks

are

consistent

with

those

reported in the medical literature for similar devices and indications. Augmentation patients have a lower

risk consistent with their elective surgery. Reconstruction patients have a higher

risk, but they also have greater potential emotional and physical benefits from the implants. Revision patients experience similar or

somewhat higher complication risks than that of their primary indication, and population based studies have shown that breast implants do not delay detection or compromise women. It's now a pleasure to turn the podium over to Dr. Rebecca Anderson. clinical Surgery psychologist at the in the She's a full-time Ph.D. Department of of Plastic in treatment of breast cancer in implanted

Medical

College

Wisconsin

Milwaukee.

She actively counsels patients undergoing NEAL R. GROSS

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COURT REPORTERS AND TRANSCRIBERS 1323 RHODE ISLAND AVE., N.W. WASHINGTON, D.C. 20005-3701

www.nealrgross.com

plastic surgery, and many of those are patients having implants. She also occupies a unique role within

plastic surgery as being one of the key players in the outcomes movement within plastic surgery, which is

funded by the Educational Foundation. Dr. Anderson. DR. ANDERSON: Thank you, Dr. Cunningham.

Members of the panel, guests, I'm Rebecca Anderson, and I'm here today as a paid consultant for Mentor Corporation. in the company. As a psychologist in an academic plastic and reconstructive surgery practice in a university setting, I have the opportunity to speak with thousands of women who have undergone or who plan to undergo breast surgery. I see both augmentation and I have no other financial interest

reconstruction patients in my clinical practice. Women report seeking implants to restore the breast following cancer, trauma, or deformity, or to achieving a satisfying breast appearance through augmentation. NEAL R. GROSS
(202) 234-4433 COURT REPORTERS AND TRANSCRIBERS 1323 RHODE ISLAND AVE., N.W. WASHINGTON, D.C. 20005-3701 www.nealrgross.com

When I see breast reconstruction patients, I generally see them at least once prior to their surgery in an effort to discuss their adjustment to the diagnosis of cancer. I often see these patients during

their hospitalization and again for follow-up as long as the situation dictates. When I see augmentation patients, I

generally see them prior to their surgery to discuss body image issues and expectations of the surgery. I

also try to see these patients at least once following their surgery to discuss their level of satisfaction. Today I will discuss motivations and

expectations of women seeking implants.

I will review

the results of the primary and secondary objectives of the saline prospective study, and I will present a summary of the clinical findings. The effectiveness objectives of the saline prospective study included a primary objective, which was to evaluate a change in breast size. objective was to evaluate patient The secondary and

satisfaction

quality of life outcomes. As Dr. Cunningham mentioned, the breast

NEAL R. GROSS
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augmentation and reconstruction patient are really two distinct patient populations, and for that reason I will also discuss the results separately for these two population groups. Women report seeking augmentation

mammoplasty to improve body image and self-confidence; to enlarge the size of the breast; to make the breast more proportionate with the rest of the body; to regain size and shape following pregnancy and lactation; or to correct severe asymmetry. In the saline prospective study, in an

effort to address the effectiveness in the augmentation mammoplasty patients, the following assessments were provided. change in Breast size was assessed by looking at a bra and cup the size, use of a a change breast in chest

circumference,

dimensional

analysis measurement. Quality of life outcomes were assessed by use of the breast evaluation questionnaire, which was specifically designed and validated for use in this study. Additionally, the multi-dimensional body self-

relations questionnaire and the Tennessee self-concept NEAL R. GROSS
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scale were used. With respect to breast size, a bra cup size change was demonstrated in the augmentation

patients with 96 percent of the patients experiencing at least a one cup size bra cup increase. Breast size was also demonstrated when we looked at chest circumference. to the postoperative From the preoperative there in was a

assessment, increase

statistically

significant

chest

circumference of 7.2 centimeters for the augmentation patients. Based upon these size measurements, it is clear that breast size was increased by use of the implants in the augmentation patients. Quality of life issues were assessed in the augmentation patients. was The breast for of evaluation this study, of

questionnaire, assessed

which

developed a

satisfaction

with

number

aspects

breast size, shape, firmness, and general appearance. The breast evaluation questionnaire utilized a five point scale. their Patients were asked to respond rating from very dissatisfied to very

satisfaction

NEAL R. GROSS
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satisfied. And as you can see, preoperatively the

majority of the patients reported being somewhat or very dissatisfied with the general appearance of their breast. However, postoperatively the majority of the

patients reported being somewhat or very satisfied with the general appearance of their breast. The BEQ looked at size, shape, and

firmness of the breast and patient satisfaction with these attributes across three settings: intimate,

social, and professional. respect reported to low breast size, of

And as you can see, with preoperatively satisfaction, patients whereas

levels

postoperatively there was a statistically significant improvement in satisfaction with breast size, with well over 80 percent of the patients reported being

satisfied or very satisfied with breast size. The same was true with patient

satisfaction regarding breast shape.

Preoperatively,

low levels of satisfaction were reported, and again, postoperatively at the 36 month follow-up there was a statistically significant improvement with, again, over NEAL R. GROSS
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80 percent of the patients reported being satisfied or very satisfied with breast shape. The trend also continued when we looked at breast firmness with the patients improvement reporting in a

statistically satisfaction percent of

significant with the breast patients

their over 80

firmness. were

Again,

satisfied

or

very

satisfied. This significant. is not only statistically

It's clinically relevant to the patient

with respect to their satisfaction of attributes of their breast. The questionnaire patients. assessment. multidimensional also used body the self-relations augmentation

was

with

The MBSRQ is a frequently used body image When taking the MBSRQ, the patient is

asked to record their agreement with statements on a five point Likert (phonetic) scale. And as you can see, from the preoperative to the 36 month follow-up there was a statistically significant appearance increase on the in satisfaction of the MBSRQ with which general assess

scale

NEAL R. GROSS
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satisfaction with general appearance. We looked at a statement on the MBSRQ, "I like the way I look without my clothes," and again, you can see that there was a statistically significant

improvement in agreement with that statement from the preop. into the 12 month follow-up, and that

improvement was maintained through 36 months. With respect to the statement, "I like the way my clothes fit me," there was also a statistically significant improvement in agreement with that

statement from the preop. to the 12 month follow-up, and again, that was maintained at 36 months. Based upon the results of the MBSTQ, we see that there is a clinically significant increase in satisfaction with body image, which is statistically significant and clinically relevant to the patient. In summary, regarding effectiveness for

the augmentation patients, we see that there was an increase in breast size. This was demonstrated by an

increase in bra cup size and an increase in breast circumference. Patient satisfaction and quality of life NEAL R. GROSS
(202) 234-4433 COURT REPORTERS AND TRANSCRIBERS 1323 RHODE ISLAND AVE., N.W. WASHINGTON, D.C. 20005-3701 www.nealrgross.com

outcomes were also demonstrated. breast attributes increased,

Satisfaction with and comfort and

satisfaction with appearance also increased among these patients. The breast reconstruction patient faces a number of emotional and physical challenges. in eight to ten women faces a lifetime Today one risk of

developing breast cancer. Once diagnosed with breast cancer, the

patient will have a number of decisions to make, and her life will be changed. may For women who the face only

mastectomy,

implants

provide

reconstruction option. Women report the following motivations and expectations of reconstruction: to feel whole again

after breast removal; to avoid the need of an external prosthesis; to improve body image and self-confidence; to put the cancer behind them; to wear more clothing styles; to regain a sense of femininity; and to correct deformity. In the saline prospective study, breast

size and quality of life measures were also assessed NEAL R. GROSS
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with regard to effectiveness. chance in chest

Regarding breast size, a was used as a

circumference

measurement, as was the breast dimensional analysis measurement. Regarding was to look at the secondary of life objective, outcomes, which the

quality

multidimensional body self-relations questionnaire, the Tennessee self-concept scale, the functional living

index of cancer, and the Beck depression inventory were used. An increased in chest size was

demonstrated in the delayed reconstruction patients. There breast was size a statistically from the significant to increase the 36 in

preoperative

month

follow-up of 3.8 centimeters.

This is indicative of

restoration of the breast mound in these patients. There was no need to assess change in

breast size among the immediate reconstruction patients because the breast mound was created at the time of the mastectomy. The functional living index of cancer is a widely used assessment which evaluates patient

NEAL R. GROSS
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adjustment following the diagnosis of cancer. scores reflect improved physical and

Higher

psychological

adjustment, and as you can see on the functional living index of cancer, the immediate both and delayed a

reconstruction

patients

experienced

statistically significant improvement in physical and psychological functioning. The Beck depression inventory is a widely used outcome measure for assessing symptoms associated with depression. associated with Lower scores reflect lower symptoms depression. experienced symptoms a The a immediate

reconstruction significant depression. associated

patients in

statistically with

decrease There with

associated in the

was

decrease among was not

symptoms delayed

depression It

reconstruction significant.

patients.

statistically

However, it does represent a trend in the

desired direction. The Beck depression inventory evaluates

various levels of clinical depression.

For example, a

score of ten or greater represents a low level of clinical depression, with scores from ten to 16

NEAL R. GROSS
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indicating mild depression. moderate to severe depression.

Higher scores indicate

We looked at 196 patients for whom we had data, both preoperatively and at 36 month follow-up on the Beck depression inventory, and as you can see, at the preoperative of ten or assessment, greater on 43 patients Beck reported depression

scores

the

inventory, whereas at the postop 36 month follow-up, only 26 patients reported scores of ten or higher on the Beck depression inventory, which is indicative of a statistically significant decrease in symptoms

associated with depression in this population. In effectiveness increase in summary, for breast the with respect to the an

reconstruction was

patients,

size

demonstrated.

Chest

circumference increased in the delayed reconstruction patients, which was indicative of restoration of the breast mound on these patients. Patient satisfaction and quality of life outcomes were also demonstrated. Physical and

psychological adjustment in cancer patients increased, and symptoms associated with depression decreased. NEAL R. GROSS
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So what does this all mean? saline filled mammary prostheses are

The Mentor and

effective

beneficial.

In the augmentation patients, an increase In the reconstruction

in breast size was demonstrated.

patients, the breast mound was restored. The saline prospective study and the

professional literature demonstrate that the risk and benefits are well defined and documented, and these results are consistent with the quality of life

benefits reported in the professional literature. Despite possible complications, patients

report high levels of satisfaction and improved quality of life. And finally, many women facing

reconstruction or desiring augmentation have a wealth of information available to them as they make their decisions, and they continue to choose implants. Mr. remarks. MR. PURKAIT: Thank you, Dr. Anderson. Purkait will return for concluding

Thank you, Dr. Cunningham, and thank you, Ms. Pamela Powell. NEAL R. GROSS
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I'd today.

like

to

summarize

our

presentation

First, we have shared with you the preclinical We have submitted our scientific study data

findings.

in our PMA to show the safety and effectiveness of our product. In the toxicological safety assessment, we have shown that our materials and devices are

extractables below the toxicological concern. In assessment, we our have durability shown that and our performance devices can

withstand excessive forces equal to the interval used. As you look through our clinical findings, we have established risk and complications, and we have shown that the long term durability of our implant through the retrospective study to be over ten years. In our studies we also have well

characterized risks.

We have shown that our product

improved the quality of patients and this information and education materials will be provided to both

patients and physicians for their decision. Thus, we believe that we provide a safe and effective option for women who want to restore the NEAL R. GROSS
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breast following cancer, trauma, or deformity, or to achieve a satisfying breast appearance through

augmentation. Finally, we recognize that there are no objective measures or standards by which the relative risks and benefits of these devices can be weighed against each other. On the patient and individual can

make the decision and will be the judge, and this decision is different from each person. Mentor provides the necessary information to the patient and their physician so that a patient can make a truly informed decision. We thank you for your attention. CHAIRMAN WHALEN: Thank you fry much.

For those members of the panel who now may have any questions of the sponsor. DR. BLUMENSTEIN: Dr. Blumenstein. you compute the

When

Kaplan-Meier estimates of risk, how did you handle the explantation event for the computation of the KaplanMeier curve for something like infection or

contractures, and so forth?

Were these for patients

who had an explantation censored in those curves? NEAL R. GROSS
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MR. PURKAIT:

You know, I have not had a

chance to share with you our Q&A team, but in order to address that, I'd like to invite our biostatistician, Dr. Gene Poggio to explain our Kaplan-Meier analysis on those. If I could just request one thing and show you our Q&A team so that all the questions that will be coming to us, we'll be able to tell you exactly who's answering what. We have Dr. Wally Grant in our hand to address or answer questions about material testings. We addressing questions. We talking about have the Ms. Pamela Powell protocol who will be or have Dr. Gene the Poggio who will be

primarily

biostatistics

related

clinical

designs

implementations. We have Dr. Noel Rose at hand to answer any questions on the immunology. Mr. Clark Scherff from the manufacturing. And Phil Yang for the preclinical data. We also have Dr. Mark Allen for any

NEAL R. GROSS
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particular testings, long term testings. Radiology, Dr. Leonard Everson. And assessment. Thanks for your attention, and we'll be addressing your question now. DR. POGGIO: name is Gene Poggio. Mr. Chairman, Panelists, my For the Dr. Roger Wixtrom on the safety

I'm a biostatistician.

last 15 years, I've directed the biostatistics group at Apt Associates. Apt Associates has contracts with Mentor Corporation to do analysis, data management reporting of clinical studies. with Mentor, Apt and has I no other financial have no

connection

personally

financial connection with Mentor. To address your question, as laid out in the original analysis plan for the study, we did censor patients, with one exception which I'll mention in a moment. We censored patients at the time of

explantation.

We thought it was very important to do

so because -- for two reasons. The patients who are not reimplanted, we NEAL R. GROSS
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felt that we've used a conservative strategy because to keep patients in the denominator for incidence

estimates when they no longer have an implant we would think would bias the estimates. And then for patients getting new

implants, complications that might occur.

It could be

a different device, a different manufacturer's device, and we wouldn't be able to attribute it to a given device. So we thought the cleanest approach was to censor them at the moment immediately after the

explantation, if you will. The one exception I mentioned is we did do some analysis to look at the issue of revision

patients, and for those that was, if you will, the baseline for revision patients. But aside from the

exception or aside from revision patients, they were censored at the moment immediately after the

explantation. DR. BLUMENSTEIN: One more question. Did

you do analyses in an attempt to try to characterize the patients who did not have follow-up at various time NEAL R. GROSS
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points following the original, following baseline? DR. POGGIO: quite high response rate. I mean we basically have a I believe it's off the top We could

of my head about 80 percent at two years. pull those numbers up if you want. We didn't specifically compare

the

ones

who did drop out to the ones who did not. CHAIRMAN WHALEN: Dr. Bandeen-Roche. Yes. I have a related

DR. BANDEEN-ROCHE: question to Dr. Blumenstein's. This involves the

It may also go to you. quality of life and

effectiveness analyses. understanding statistics is that

At the three year visit, my those analyses, who any summary lost to

excluded

individuals

were

follow-up up to that point, and that that loss to follow-up included a relatively substantial number of explantations; is that correct? DR. POGGIO: It is true in the analyses

when we looked at simply the 36 month value, they would have been excluded, but we did have summary measures looking at the average change across all visits. There is generally a very consistent

NEAL R. GROSS
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pattern of one level at baseline and a very different level, especially for the primary efficacy measures or primary effectiveness measures, the one level at

baseline and a quite different level consistently for all the visits after it. DR. BANDEEN-ROCHE: But to summarize, the

people at that different level would comprise people who had not had explanations, correct? DR. POGGIO: for all analyses after Yes, for all analyses. explantation, patients Yes, were

excluded from those analyses aside from the revision patients that I mentioned for separate analyses. DR. BANDEEN-ROCHE: CHAIRMAN WHALEN: DR. LI: this question. My question is when you were doing your either retrospective study or your prospective study, how you counted deflations. Perhaps you can correct me Thank you.

Dr. Li.

Yes, I'm not sure who can take

if I'm wrong, but am I reading patients were scored as having deflation as a reason for explantation when that was the primary identified cause for the revision, but NEAL R. GROSS
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if you went in to revise somebody for contracture and found the device deflated, it was not counted as a deflation; is that correct? DR. CUNNINGHAM: The saline devices,

unlike the gel devices, are readily apparent when they deflate. The saline comes out. Either in the study

that I did, the retrospective study, the majority of patients noticed a significant loss in volume over a period of days or perhaps one week. Some of them noted

it over a longer period of time, but mostly it's a short term, dramatic event. So I think that going to some other

intervention and then finding an incidental deflation is not anything that was reported in our study, and I'm not aware of it being reported in the saline

prospective study. The reason for reoperation would be to

correct, replace a deflated implant. something that would be discovered

It wouldn't be incidentally at

another operation. DR. LI: Just a Thank you. follow-up question, if I could.

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There was a difference in deflation rates between those patients where the surgery was done for augmentation versus reconstruction. You outlined perhaps several

maybe interventionally related reasons why there was that difference in deflation rate. However, can you discount the fact that in the reconstruction group there was four time as many SPECTRUM devices as there were SILTEX, and

coincidentally the incidence of deflation was on that order? So I guess my question is: how sure are

you that it's completely interventional and not device related? MR. PURKAIT: Perhaps if you could just

repeat that question for me so I can truly understand. Are you asking that -DR. LI: Let me simplify it for you. -- if the SILTEX has higher Is

MR. PURKAIT:

deflation rate than the non-SILTEX or the smooth? that the question? DR. LI: that one. Go ahead. NEAL R. GROSS
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I'll take that.

I'll start with

DR. question?

CHANG:

Could

I

rephrase

that

Would you be asking the same question I was Was there stratification in terms of for either augmentation or

going to ask? deflation

rate

reconstruction?

Could you tell if it was a valve leak

or puncture or failure of the shell? Was that stratified as an explanation of deflation? MR. PURKAIT: Yes, we have that

information we will share with you. will show you that information. DR. POGGIO:

Dr. Gene Poggio

I think the Cox proportional

hazards model we used perhaps might be the best answer that we have to the question you're raising. at deflation rate. this, but in We looked

Probably most of the panelists know anyone doesn't, just the Cox

case

proportional hazard model is the most standard way to look at time to occurrence of an event, in this case a complication where you have varying lengths of followup and you want to look at various risk factors, either to adjust for confounding factors or to evaluate the various risk factors. NEAL R. GROSS
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So the factors we have on the left are the various factors we took into account in the model. You'll notice or indication specifically reconstruction immediate and versus delayed

augmentation

reconstruction, augmentation, and so forth. And so the only factors that were found to be significant are the four shown there, indication whether it was unilateral or bilateral, incision size, and Betadine use, and so you'll see that we also have valve type and surface type and implant shape there, and none of those were significant in that model, and it's adjusting for the other variables in the model. DR. LI: I don't see in there a split

though between SPECTRUM and not SPECTRUM, for instance. DR. POGGIO: by device Well, this is characterized and the the SPECTRUM type of is a

characteristics, principally by

characterized texture.

surface

You're correct, but it's characterized by a

textured surface and a specific valve. So if SPECTRUM was different, you would expect to see the difference in the valve type or the surface type, and/or the surface type. NEAL R. GROSS
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DR. CUNNINGHAM:

There are only two value

types, the diaphragm valve and the kink valve, and the kink valve only exists in the SPECTRUM device. valve is a marker in effect for the So the with

product

respect to this analysis. DR. LI: Right, but then the whole

argument would hold only if the valve was the source of the leak? DR. that more fully. would like. CUNNINGHAM: Perhaps I can address

Two, two, 16 would be the slide I

Go ahead. This is a breakdown of the occurrence of

deflation that the manufacturer can actually analyze. There were 74 devices that deflated, and 37 of them were returned to Mentor, and here are the breakdown after physical examination of the devices based on what the final concluding reason was for failure. There were three valve leaks or tears.

There were 18 or there are, rather, eight iatrogenic failures which in most cases were needle biopsy or nicking with a suture or hitting with a scalpel. There were 18 shell tears, which are very NEAL R. GROSS
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difficult

to

evaluate.

It

almost

certainly

is

a

surgical event related to surgical technique, perhaps as it was being removed or explanted. And then there were six in which no

abnormalities were found.

So to answer Dr. Chang's

question, the valve does not seem to be, at least in the group of devices that could be examined, the major cause for deflation. CHAIRMAN WHALEN: question, Dr. Li? DR. LI: for a second. I'm not sure. Let me work on it Does that answer your

I'll come back. Dr. Burkhardt. I have two questions. The

CHAIRMAN WHALEN: DR. BURKHARDT: first is for Dr. Cunningham.

A reoperation rate of 25 percent -- and I tried to follow this when you were presenting it -- is that 25 percent of patients or 25 percent of implants? DR. CUNNINGHAM: analysis. DR. BURKHARDT: So 25 percent of patients On the That is a per patient

who had implants had to go back for surgery. NEAL R. GROSS
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face of it, that would seem to be extraordinarily high, and I couldn't quite understand the breakdown. said 72 of 88 were removed and replaced. You

Were the 88

all -- did that represent all of the patients who were reoperated? DR. CUNNINGHAM: That represented the

patients who were explanted.

So what I was using was

the -- if we could go back to that slide. DR. BURKHARDT: I'm just concerned. One

out of four patients is an awful lot to go back for a second surgery. DR. different CUNNINGHAM: that we So showed. there One are was two the

analyses

reoperation rate, which you're referring to.

The other

was the explantation rate, and the patients that were replaced, that statistic was on patients who had an explantation and a replacement at the same time. So in effect, one of the main causes for reoperation in this group was an elective desire to change the size almost of the device quarters because of them, a large the

proportion,

three

had

device replaced at the same time that they had the NEAL R. GROSS
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previous one removed. Sometimes that may have been removing the device to treat for an infection or capsular

contracture and then replacing it with a new device, but many of them in the augmentations were to perhaps change the size of the device. DR. BURKHARDT: For those patients who had

an elective change of the device for size purposes only, can you tell us how many wanted to go larger and how many wanted to go smaller? DR. CUNNINGHAM: that data for you. DR. impression? DR. CUNNINGHAM: DR. BURKHARDT: DR. CUNNINGHAM: I do not. Thank you. One of our statisticians We would have to find

I don't have any -BURKHARDT: Do you have any

says that the majority of them were to increase size. DR. BURKHARDT: Is this an appropriate

time to ask about the information that's provided with the implant or do you want to wait until Wednesday? CHAIRMAN WHALEN: You mean in terms of

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labeling?

This is an appropriate time to ask any

questions of the sponsor that you feel is appropriately answered by the sponsor. DR. BURKHARDT: Mr. Purkait, I have a

question about the brochure that is provided with the implants by Mentor. When you go to implant shape, you

have a rather carefully constructed sentence that says, "Round implants are thought to give a fuller shape to the breast, while contoured implants are designed to offer a more anatomical shape." And I'm sure that's correct, and then when I look at the pictures that you have, if they weren't labeled, I couldn't tell the difference between the round and the anatomical shaped implant. Do you have

any basis for believing that the use of one implant variety over the other implant variety makes a

difference that can be detected by a blinded observer? MR. Cunningham. PURKAIT: Could you I would like to see Dr. your

please

address

from

experience on the anatomical versus the level implant with the difference in cosmetic application? DR. CUNNINGHAM: I don't believe that we

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broke down or at least I have not seen a breakdown of the data that Dr. Anderson presented, namely the chest circumference measurements by shape, and if we do have it, perhaps we can get it put up. But my personal clinical feeling is that contour devices particularly in reconstructed patients do not confer a significant difference in total outcome of shape than do round devices. DR. BURKHARDT: patients? DR. CUNNINGHAM: Again, my personal How about in augmentation

clinical belief is that when these devices are placed in the submammary position in a thinner woman with a lot of extra skin, it's possible that the shape of the device could be conferred to the overlying breast

parenchyma and the skin envelope. However, the majority of these devices are placed underneath the muscle, and my personal feeling and clinical observation is that underneath the muscle they all become essentially round, and any shape that might be conferred by the implant design is overridden by the forces of the muscle. NEAL R. GROSS
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DR. BURKHARDT:

Thank you. Dr. Li? I

CHAIRMAN WHALEN: DR. LI:

Yeah, I thought about it.

think I need a simpler answer to this. Could you just simply tell me out of those devices that were deflated how many of them were

SPECTRUM?

That's the answer I'm looking -- that's the

question I would like to have answered. MR. PURKAIT: data. Sure. I think we have the

Can I just come back to you while I was just

getting those information? DR. question. LI: Sure, and I have a separate

Dr. Cunningham alluded to it and some of

your literature alluded to the fact that depending on the shape of the device and where you place it or maybe even the size of the incision, that that affects the outcome of the device. So my question is that seems to imply that seems to imply that there's some kind of extra stress or extra loading to or the extra device some that kind of kinematic is not

application

somehow

advantageous to the device if you don't put it in in NEAL R. GROSS
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the appropriate fashion. My question is: do you have any

biomechanical data that would suggest, for instance, if you make the incision two centimeters smaller what that increase in stress actually is, or if you use the wrong profile and put it in the wrong place and the stress is too high, do you have any biomechanical information, again, that tells you exactly what that increase in stress is, or is it stress or is it sheer or is it something else? MR. PURKAIT: We have some information

that shows that when you do apply load, regardless of what incision site and where you're placing, if you take an implant and if you apply certain types of load, we have measurement that shows that what type of

internal pressure you can generate. Now, do we have information between the subglandular or some muscular? At this point in time I

couldn't tell you, but we have a general information if we have a certain amount of load or if certain types of women sleeping on the chest, what sort of stress would be -- internal stress would be developed? NEAL R. GROSS
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We have that information. DR. LI: I've read that information. I

guess what I'm looking for is the link between the laboratory data for those calculations of pressure

under those different conditions to your instruction to the surgeon that says, "Put it in this way or the stresses will be too high." So my question is versus your laboratory data under different conditions where you that generate to your

different

internal

pressures,

compare

instruction to surgeons that say don't do this or the stress will be too high. What's the comparison,

numerical comparison, between those laboratory stress data and then the stresses you think are being

generated in the patient at least to the level where you're concerned enough that you're instructing the surgeon to watch out for it? DR. BOYKIN: I'd like to follow that

before you answer with a similar question because your mechanical data indicates when you have looked at the environment of the implant that a, as you define it, stiffer tissue surrounding the implant significantly NEAL R. GROSS
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lowers the pressure per square inch.

I believe it goes

below two pounds per square inch in this model. It makes me wonder if that could be

translated into some instructions for the surgeon who's trying to optimize the length of the implant. I think

that's what he's getting at because you have data about this pressure on the implant in the environment that it's in. How does that translate to what we can do to

improve the lifetime of it while it's there? The other question I'd like to pose is was there any investigation of the possible presence of clinical capsular contracture before implant deflation. I didn't see that listed as a cause, but did you go back to find or out it was there be a capsule before but it did

inflated,

might

subjective

data,

anybody try to look at that possible correlation? DR. CUNNINGHAM: Could I have Slide 109

while I answer the first question? The first question really has -if I

understand it correctly, you're asking is there a good, effective way to model in the preclinical testing the kinds of forces and effects that would result not from NEAL R. GROSS
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the daily use and activity of the device when it's in the woman's body, but rather that mimics the condition of actually placing the device. DR. LI: question, yes. DR. CUNNINGHAM: Right. Perhaps one of Yes, that would be the global

the materials people can answer that, but let me say that from a clinical point of view, the devices are placed in deflated so that they are, you know, in a very small volume when they're placed through the

incision. So that it would be hard to model that accurately, except for tear or sheer characteristics, which of course have been recorded. Surgeons techniques. vary so widely in their

Some surgeons fill the implant partially

so that they can then aspirate the air bubble and then put it in partially inflated. completely empty. Other surgeons put it in

Some surgeons place it in through a There are

remote incision site, such as the axilla.

some surgeons who wad it up and place it through a long tube through the umbilicus. NEAL R. GROSS
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You

know,

certainly

these

different

techniques would have different stresses and different strains applied to the device. very hard to model. With respect to the question of the I think it would be

associations of risks with the deflation event, this is the series of potential things that we felt could

affect the -- these are the factors that we looked at that could affect deflation, and capsular contracture is not one of them. And these are the things that were found to be statistically significant. DR. BOYKIN: Well, I understand that, but

I guess what I'm asking is that obviously when it's deflated, it's deflated, but could you -- did anyone ask the patient or the physician if there was any indication that a contracture may have been present or developing at that time? I mean that's just kind of a retrospective analysis. DR. CUNNINGHAM: I think from my personal

clinical observation of how these devices function, NEAL R. GROSS
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it's clear that we had a higher deflation rate in reconstructive patients. Reconstructive patients also

had a significantly higher Baker Grade III, Baker IV capsular contracture rate. In many cases personally I

believe that this is reported as a capsular contracture rate when, in fact, what is actually going on is that there is tissue inadequacy. that's been removed. So if I understand your question, it's There has been tissue

dealing with does a tight, confining space in somehow or in some way predispose an implant to fail, and I think the data would indirectly bear that out because the higher degree of capsular contracture reported in the reconstructions parallels a greater deflation rate, and you could understand that that is a more adverse environment. The implant is going to be more likely to

be folded on itself, and so it's not as -- it's a more adverse environment than underneath an unoperated

pectoralis muscle. DR. BOYKIN: Right. This is really

conjecture, but the reason I was curious about the data, the PSI and the firm environment is because what NEAL R. GROSS
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you might be describing is a situation in, which the submuscular pocket which by virtue of the nature of the tissue is a stiffer environment, is probably causing this lower load on the surface of the implant. If it

is significantly lower, does this correlate with the decreased contracture rate? Does this correlate with

an increased lifetime, life span of the implant? And if this information is variable, it could be correlated to some pressure reading through a remote valve that we could do clinically and perhaps look at some U curve with the bottom being the optimum side. When we get past that point we need to make some

changes. So I'm just talking about the information you've got and how we can use that clinically. MR. PURKAIT: your data. Dr. Li, we're still getting

We'll come back to you. CHAIRMAN WHALEN: While we're still

getting that, Dr. Morykwas. DR. MORYKWAS: Yeah, I just had a couple

of things, and one is actually related. MR. PURKAIT: Dr. Li, sorry. I'd like to

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answer if I could, please, and show these data.

The

deflation of SPECTRUM versus SILTEX versus the smooth and the SPECTRUM versus the smooth. Gene. DR. answer. There POGGIO: I have a very specific

I hope this -- you asked how many SPECTRUM. were 21 SPECTRUM had deflation out of 472

devices. DR. LI: So that's 21 out of the 74 that

Dr. Cunningham alluded to? DR. POGGIO: out of 472. DR. LI: So then would that translate, Dr. Oh, that was 37 that 37 of which they It is devices. So 21 devices

Cunningham, to 21 out of your 74? he had. He had 74 deflations,

analyzed. MR. PURKAIT: That's right. The 57, I

suppose, are total deflations.

That's what we've seen.

We received the 37 to examine that was what the cause for the deflation. DR. LI: Right, but is the 21 out of the

74 total or is the 21 out of the 37 that you analyzed? NEAL R. GROSS
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MR. PURKAIT:

I believe it's the total, 24

out of the total 37 or 57, 57 or 74. DR. LI: Seventy-four. Right. So most of them then were

MR. PURKAIT: DR. LI:

Okay.

the prefilled, not SPECTRUM devices; is that right? MR. PURKAIT: I couldn't tell you exactly.

Most like from the data, it looks like that, yes. DR. CUNNINGHAM: And there are no

prefilled devices. surgery. DR. LI: DR. couple of

They're all filled at the time of

So sorry.

Thank you. I guess related I had to a

MORYKWAS: and

Well, one

questions,

is

the

implantation. augmentation

Since a lot of surgeons now do for -not a lot, but some do the

perienvolicol (phonetic) insertion. presented incision data that to shows be that the are

Since you have length you of the to

appears

related,

going

discourage surgeons from using the perienvolicol or would that be something you would consider? DR. CUNNINGHAM: Well, I personally -- and

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I'll let someone else speak to the product labeling as it exists -- but I personally feel that that is a very strenuous and risky thing to do to an implant, and I would not feel comfortable doing that in a patient of mine. risks I don't think that the benefits outweigh the of the device deflating, and I would feel

strongly that it should certainly be an interdicted use of the device. MR. PURKAIT: Yeah, to answer your

question, this information as we have found in our study we have submitted to the agency. As these things

are approved and discussion occurs, we will put in the patient information as well as the physician

information, yes. DR. MORYKWAS: then I had a question about You also had

your infections and how that was related. a delayed wound healing. Now, were they later the infections that the

you

reported, had

infections?

Did

incision

healed and the breast had just swelled or developed a draining tract or was it also just a nonhealing

incision that pus was coming out of at the time of NEAL R. GROSS
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surgery? DR. CUNNINGHAM: events healing reported and at the same at There could be several time, same such as delayed but the

infection

the

time,

infections were all reported either with a positive culture or with a positive clinical assessment. There are times where the implant is in place. A patient might have some symptoms of redness

or malaise, and there are times when you can treat that effectively by intravenous or oral antibiotics. So

those are situations where you would not be able to get an actual tissue culture positive, but it's certainly your clinical impression that that's what it is. If you're able to treat it successfully, the patient is not encumbered with an operation, and it would be dangerous to try to needle aspirate it simply to get a culture. it's clinically So there are certainly cases where strong indication, but not culture

document. DR. MORYKWAS: also indications where the Sure, and then there are patient might have been

double reported as nonhealing or delayed healing plus NEAL R. GROSS
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infection. And then the last thing is you had a very small number of patients that were other. the combined smooth and textured implants? DR. CUNNINGHAM: pie chart of types of devices? DR. MORYKWAS: Yes. In one it was .2 You're talking about the Are those

percent, and in another pie chart it was a one percent and it just said "other." DR. POGGIO: were different devices Just in rare instances there in the two breasts, and it

reflects the mixture of one device in one breast and one in another. CHAIRMAN WHALEN: MS. DUBLER: Ms. Dubler.

I'd like to pursue a little

further the relationship between your findings and your communication with physicians and with patients. The

findings on the Betadine washing are quite startling, and when did you make those findings, and what's

happened to that information since it developed in your database? MR. PURKAIT: The Betadine findings

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approximately we came to know about this about a year, a year and a half ago. As soon as we came to know

about this, we immediately contacted the agency with that information to correct the patient information, as well as the physician information. So that was being done even long before the clinical study results came to us. MS. findings in a and DUBLER: similar your And do you in state your your

fashion

patient

information communications? MR.

physician

information

PURKAIT:

I

believe

definitely

I

recall that we do that in a physician's information on this. I would have to check and get back to you about

the patient and so on. DR. CUNNINGHAM: There would probably not It's I

be a reason to inform the patient about this.

something that occurs while the patient is asleep.

suppose in a best case circumstance the patient might ask the doctor, "Do you do this?" but it may be more information than they can clinically use. They're bombarded NEAL R. GROSS
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with

a

lot

of

information as they try to make this decision. MS. DUBLER: I agree, but there are some

very interesting examples of instances in which giving patients information brought change in practice and giving physicians information didn't. background of my question. DR. CUNNINGHAM: Certainly the reference So that's the

to the hand washing and patients being aware of that and encouraging their physicians to do that is very good, and hopefully this is something that will come up on Wednesday when we discuss or on Friday, rather, when we discuss this more fully. CHAIRMAN WHALEN: DR. ROBINSON: Dr. Robinson. Mr.

A couple of question.

Purkait, in your fatigue impact studies, just to give me a better perspective, what does that -- I know it may be impossible to translate into real time, and that's unfortunate, but can you give me an estimate of what you think that translates to in real time? that falling off a ten foot wall? inflation? your device? NEAL R. GROSS
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Is

Is that an air bag

What do those maximum values tell you about

MR. PURKAIT:

Yeah, sure.

I'd like to

share with you some test data and show that to give you a better understanding what it really means, and I'll take about two minutes of your time. I'd like to

invite Mr. Phil Yang and Dr. Mark Allen to show you some of the data and the test. MR. President of YANG: I'm Phil Yang. I'm Vice for

Technical

Studies

and

Submissions

Mentor Corporation. The fatigue data is really comparing to fatigue activities that you normally see in someone's body. We've modeled this as someone walking. A breast

implant would go up and down.

So we're comparing it to

those types of small, relatively small effects that continually happen to a person in a cyclic manner. those are what we're comparing to. In order to understand how we do the So

testing very quickly and what it means in terms of numbers, I'd like Dr. Mark Allen to come and explain it. DR. ALLEN: I'm Dr. Mark Allen, Mentor

Corporation, Science and Technology Laboratory Manager. NEAL R. GROSS
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I

would

like

to

provide

a

very

brief

overview of the fatigue testing that Mentor conducts for an estimation of the in vivo lifetime prediction or, more appropriately, an assessment of long term

durability of the implant. To do this, as indicated on the slide, the in vivo fatigue testing methodology, both consideration of the fixture of and the and in experimentation, vivo environment, on the include the an

assessment magnitude physical routine.

stress and the

distribution

implant,

activity

associated

with

typical

daily

This then can be used to develop safety factor and lifetime prediction for an endurance limit, safety factor calculation, Basquin relation or the

Gerber relation. This slide indicates that the device, when implanted, chest the posterior region is is adjacent to to the

wall,

and

accordingly

subject

minimal

stress, whereas the annular and anterior region of the device is probably that which is exposed to load

distribution. NEAL R. GROSS
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When

considering

the

activity

of

an

individual and the loads that might be imposed upon the device, one can consider the at rest condition or the emotion condition. one assigns the If this is done at rest, typically mass of the device as the stress In and

induced on the mammary and the regions indicated. motion, one would consider jogging perhaps

equations can be shown which will allow derivation of a magnitude of load of approximately two times the mass of the device. With these considerations then, in vitro testing can be conducted, and this illustrates the

schematic of the test fixture. this earlier.

I believe Bobby showed

This design includes a hemispherical ram which is used to load the device. The device is held The steel

or supported within a steel spring cage.

spring cage actually allows for the anterior region of the device to protrude between the springs so that during this test under compression loading, both the annular region and the anterior region are subjected to loading for us, which is consistent with the in vivo NEAL R. GROSS
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environment. The testing that's typically conducted for this kind of experiment, some of the conditions are listed here, and as I mentioned previously, a typical load that might be experienced by a device in vivo is on the order of three pounds. here for two from different 40 to to 80 types The loads that are used of experiments which is range

anywhere excessive

pounds, in

extremely that's

relative

the

vivo

condition

typically encountered. The failure analysis is then used to

construct the S-N curve.

On the other hand, endurance

analysis is used to determine the load in which failure will not occur. A typical S-N curve is shown here. This

is derived from the data which results in failure, not endurance. However, if one were to construct a

horizontal line along a stress amplitude consistent with that measured for the endurance limit, that would define an elbow region of the curve. DR. interject one? NEAL R. GROSS
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LI:

Excuse

me.

Could

I

just

DR. ALLEN: DR. LI: failure point is? implant has failed? DR. ALLEN:

Yes.

Could you define for us what the At what point do you decide the

Catastrophic rupture defines

the failure for the data which is presented here, and with that catastrophic failure, the failure mode is measured and recorded, including the location,

dimensions, and thickness of the shell at the site of failure. DR. LI: DR. catastrophic Thank you. So that are all of these are

ALLEN:

failures

incurred.

They're

induced intentionally to develop the S-N curve data. From these types of experiments then, one can derive a safety factor. is One the of the most limit

straightforward

approaches

endurance

safety factor which uses, again, that stress amplitude that I mentioned, which does not result in a failure of the device, a catastrophic device from this cycling. That occurs at ten to the seventh cycles or ten million cycles. NEAL R. GROSS
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And then that can be compared to the in vivo stress amplitude, which I identified previously, approximately three pounds for a 325 cc mammary. This

allows for the construction of a safety factor, and that yields in this case for a 325 value of about eight. Unfortunately, safety factor of the this only assesses failure. the An

device

without

alternative approach to develop a safety factor relies upon an equation based upon the Basquin relation, and this allows incorporation of a time even, as indicated below, the time event which would be consistent with activity, daily routines such as jogging and walking. An this case five hours of activity a day were considered with one cycle per second for events, and typically this would calculate to be about seven million cycles per year. If one assigns a ten year life then and incorporates this value into the Basquin equation, a stress amplitude results which is about 28 psi. This

then can be used with the in vivo stress amplitude and yields a safety factor of about 8.6, which is very NEAL R. GROSS
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consistent with the endurance limit safety factor and would offer then a reasonable lifetime, if you will, or long term durability of the implant under these

conditions. One additional relationship that can be

used relies upon the Gerber equation, and that allows also for the incorporation of ultimate tensile strength of the shell to be included in the calculation, and as you can see, a similar safety factor is developed from that. DR. ROBINSON: way? Could I try it a different

The real time part is missing. What would be your conjecture if a woman

was

sitting

in

the

passenger

side

and

an

air

bag

inflated? DR. ALLEN: I'm not the person If I recall correctly -- maybe that should be answering this

question -- but the impact testing resulted in a value which is approximately three times that of a car

collision. DR. ROBINSON: MR. YANG: Okay.

The air bag situation we model

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as impact testing, not as fatigue testing. DR. ROBINSON: Cunningham. CHAIRMAN WHALEN: DR. ROBINSON: Please. I have one more for Dr.

Dr. Cunningham, towards the

end of your presentation you had a group of patients that were explanted and then reimplanted. there was 60 of them if I remember correctly. a little bit off on that. I think I may be

I may have missed it.

Is it too early to comment on those 60 that have been reimplanted? DR. CUNNINGHAM: revision group? DR. ROBINSON: I believe so. It was You're referring to the

towards the end of your presentation, yeah. DR. revision group. MR. PURKAIT: Before we start the revision CUNNINGHAM: We can discuss the

group, one question to answer Ms. Dubler about that, no, we have not had that incorporated in the patient level. We would be doing that, the information about

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And to answer your, Doctor -- I can see your -DR. ROBINSON: MR. PURKAIT: Robinson. -Robinson, about the

safety margin, the question that you have on fatigue, I'd just like to conclude that by saying the model that you have shown here is fatigue testing only to show the safety margin in terms of the load factor that it can take over a time period. The question that you have is data impact. We have tested against a model called 35 miles per hour collision. If somebody had the amount of impact

energy, it would be on the chest, whether it would withstand the breast or not, and we found that our product, it takes about three times more than impact energy to cause rupture. So I just want to clarify that. DR. ROBINSON: for. Thanks. MR. PURKAIT: Thank you. That's what I was looking

To answer the question on the other areas, I'd like to call Dr. Gene Poggio to show some of the NEAL R. GROSS
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information, and then I'll have Dr. Cunningham explain the clinical data on that. DR. POGGIO: This actually connects with

what I mentioned at the beginning when I said there was one exception to when we discontinued the patient to explanation. We did for all of the analyses except for

these analyses where we actually used that as the data, if you will, as a baseline for the next set of

patients. So I'll run through this focusing on the saline perspective defined part, by the but FDA revision as patients that are are

basically

patients

replacing their original implant regardless of whether your original implant was for augmentation or

reconstruction. And in the saline prospective study -- and I must apologize here. of devices. The 196 is actually the number

It's 124 patients, and the 215 in the

large, simple trial is, indeed, the number of patients. Next slide. This slide showed the complication rates in the LST for revision patients with 95 percent

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confidence intervals, in the "large simple trial," I should say, and this is on a per patient basis at 12 months. And the next slide. And now we're looking on a per device

basis at 36 months, and we did actually so that we have the estimated rates for the major complications here with 95 percent confidence intervals, and we tested whether there was a significant difference between -and I'm sorry. This is for prior, where the previous The next slide is the

implant was for augmentation. reconstruction. We statistically estimated compared significant and the

whether difference rates

there

was

a

between the

these

rates

per

original

augmentation, and there was no significant difference with the exception of explantation, which was somewhat higher. Next. And then for reconstruction, again, the

same five major complications with estimated rates, complication rates, and 95 percent confidence

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intervals, and again tested for significant difference between this, and and in we this have case two the original

reconstruction,

significant

differences, one up and one down. And then we also have information on

effectiveness, and I think I'd rather turn that over to Dr. -MR. PURKAIT: -show the complication

rate and then Dr. Anderson will show the effectiveness. MR. POGGIO: Okay. It was of interest to me

DR. CUNNINGHAM:

to try to determine or theorize why these rates of clinically significant changes in these patient cohorts over their primary indication for implantation, and to come up with a clinical story that explains it. The explantation group, which is higher

after the revision, the causes for explantation, the second explantation, are capsular contracture,

deflation, and infection, and I think what we're seeing here is a group of patients who had an intervention to try to solve a problem. They had a capsular

contracture.

They had some other problem and had an NEAL R. GROSS

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implant placed in an attempt to solve that problem. And I think this increased explantation

rate shows that the problem was attempted to be solved, but was not, in effect, solved. clinical situation, as we were So a patient who in a discussing earlier,

might have the signs and symptoms of a cellulitis, you try to deal with it with intravenous or oral

antibiotics.

It does not resolve.

You offer the

patient the choice. The choices are: we remove your device,

let you have no device for a period of time while you heal, and then replace the device. that we offer patients. Another option that we offer patients is we can go in, we can take out the infected device, we can clean the space, we can put you on oral antibiotics or IV antibiotics, and we can try and save you a third operation or another operation and put the implant back in at this time. And I think what we're seeing here is that there are times where we try to do that and were not successful. NEAL R. GROSS
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That's one option

With patients, I think

respect the

to

the

reconstruction of capsular

decreased

number

contracture Baker Grade III or IV that we see after reimplantation indicates the opposite story, but this is a group of patients where we were able to

successfully treat a problem, namely, that of capsular contracture, by operating on the patient, taking out the scar capsule contracture, dividing through the scar capsule, whatever, and that this decreased number

indicates we've been successful. With respect to deflation, it's a more

difficult question to answer for me clinically as to why this group has a slightly greater risk of deflation than when they originally had their device placed, and I feel that I have to come back to the sense that it's a more adverse environment. Perhaps if the surgery was done for a

capsular contracture and the contracture continued to exist for some reason, we know that that might be associated with a greater incidence of rupture. Now, patients who the bigger question undergone is: a how do

have

already

frustrating

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experience?

They've had high hopes of success.

The

operation has been done, and it hasn't worked out. They've had to have another implant placed. significant question is: do they respond to it? So a very How

how do they take this? What's their

satisfaction

level? And I would like to ask Dr. Anderson to spend a second or two talking about that. DR. ANDERSON: We had used the breast

evaluation questionnaire to assess patient satisfaction in the saline perspective study. at patient satisfaction patients on in So we decided to look revision group of

this

augmentation

the

three

aspects,

size,

shape, and firmness. And as you can see, despite the fact that they experienced revision procedures, they still

reported very high levels of satisfaction at the 36 months follow-up with respect to size, shape, and

firmness. CHAIRMAN WHALEN: Dr. Bandeen-Roche. I believe --

DR. BANDEEN-ROCHE: CHAIRMAN WHALEN:

Excuse me one second.

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On that same issue? PARTICIPANT: No. We're going to someone

CHAIRMAN WHALEN: else and then I'll get to you. DR. BANDEEN-ROCHE: series is for Dr. Anderson:

I believe my question

concerns about the quality

of life data, and certainly include the lack of a control group. And so first of all, just correct me if I'm wrong, but my understanding is you really don't have any true quality of life data for the augmentation patients. It's body appearance and self-esteem data

rather than quality of life, is it not? DR. ANDERSON: I suppose you could

characterize it as body image. DR. BANDEEN-ROCHE: slight increase of Okay. I'll In terms of the just voice my

self-esteem,

concerns, and I just want you to respond.

If women

went into the surgery at a particularly low point of their self-esteem, which is certainly reasonable,

slight increase would be consistent with regression to the mean, wouldn't it? NEAL R. GROSS
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DR. but, yes, I

ANDERSON: the

I'm

not

a

statistician, talking

understand

concept

you're

about, and that's probably true. Are you referring to the Tennessee selfconcept scale? DR. BANDEEN-ROCHE: DR. ANDERSON: Yes, I am. With respect to that

Okay.

scale, we've acknowledged that that scale is maybe not the best assessment to have been utilized, and that's one of the reasons even I didn't we present it in my

presentation, significance.

though

did

achieve

clinical

We didn't know if the results were -- I

mean statistical significance -- we didn't know if the result were clinically meaningful. DR. BANDEEN-ROCHE: My next Okay. Thank you. goes to the

question

reconstruction patients.

So you noted increases in I'm just going to state

quality of life on the FLIC. something, and just correct me.

My impression is that those increases are not distinguishable from increases that could have

happened anyway just because they've recovered from NEAL R. GROSS
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their cancer. DR. ANDERSON: It's very possibly true

that they would have over a period of three years adjusted to their cancer and shown an improvement. In

my clinical experience, however, I do see that there is a tremendous amount of satisfaction with restoration of the breast in these patients. DR. BANDEEN-ROCHE: CHAIRMAN WHALEN: MS. BRINKMAN: Thank you.

Ms Brinkman. Yeah. Along that same

vein, I'm interested in your Beck depression inventory because in reconstruction patients, you say, you know, that their scores have decreased, but, I mean, is that a decrease, and how do you know the difference whether it's a decrease due to the fact that they've finished cancer therapy treatment or whether it's actually the fact that they've had an implant? How do you separate that? DR. relatively nice ANDERSON: to see Well, that you know, it a was real

they

weren't

depressed group of patients to start with, which is consistent with one of my studies, which looked at NEAL R. GROSS
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psychological patients, and

adjustment I suppose

in that

breast it is

reconstruction theoretically

possible that levels of depression would have decreased over time in these patients. Again, I relate to my clinical experience. These patients are overwhelmingly satisfied and pleased to wake up from surgery with a breast mound. CHAIRMAN WHALEN: DR. BURKHARDT: door to Dr. Burkhardt. I wasn't going to open the

Betadine, Dr. Cunningham, but it's already

been opened, and I think I have to walk through it. My recollection is that Mentor initially sent out a flyer to users of breast implants saying that Betadine was a problem with the integrity of the implant, and that was from a study in which Betadine had been placed within the device, and the problem at that time was a valve failure. And then there was some furor about it within the plastic surgery community, and as I recall, Mentor did another study or perhaps a parallel study with the implant immersed in Betadine solution and

found no problems with that in vitro. NEAL R. GROSS
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Now, is my memory of that correct? MR. PURKAIT: Some of them, correct, and

some of them -- if I may have your indulgence, I'd like to kind of go and kind of give this. When we looked into the Betadine, this was brought to our attention by many different surgeons. They are the one who called us and said, "Look. Maybe

you should take a look at it because some of the implants are showing failure because of some reason we do not know." Well, when we started looking into their information and the data, we realized that there was a large amount of Betadine was used with our implants in all conditions, whether it has been soaked or put

inside the cavity or put inside the implant. We initiated our internal investigation

and studies to understand was there any relationship between the Betadine and the implant failure. We have

done several experiments three different times, one with the solution inside, one with the soaking, and also to match up the acidity of this particular one to make sure that the acidity doesn't have anything to do NEAL R. GROSS
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with it. So the series of experiments have

indicated that, one, either the implant does fail even with the contact, and when we learned that -DR. BURKHARDT: I'm sorry. I didn't

understand when you said that. fail? MR. PURKAIT: failed.

That the implant does

Failed, yes.

The implant

When I said "failed," it means the pads tends

to come out of the shell or the shell itself, the surface of the shell looks like getting weaker, and you can easily probably break through that. kind of observations we have seen. And when we saw that, we realized that any way we want to do it -- in other words, if we can go back and probably do some more experiments to tease out exactly what conditions and what time, we kind of felt that this is our responsibility to contact the agency with that information, and we did so, and at that point in time, the put agency that with and ourselves decided the with that we Those are the

should

immediately information

with that

patient even the

information,

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slightest contact will provide or will probably fail or show the loss of integrity of the implant in the

future. So that's where it is. DR. BURKHARDT: the failures that you For Dr. Cunningham, were with the Betadine

observed

irrigation, were they valve failures or were they the usual fold flaw failure, or do you know? MR. PURKAIT: We have the failure, the We only saw

deflation, as we have shown you before. two fold flaw failure.

We did see some failure because That's the largest number. difficult sometimes to

of the tear of the shell. Now, it's

very

exactly identify the tear was already there or it was the loss of the shell thickness for some reason. couldn't really identify that very well. DR. BURKHARDT: Thank you very much. Dr. Morykwas. I just wanted to ask a So we

CHAIRMAN WHALEN: DR. MORYKWAS:

follow-up question of Dr. Cunningham on the infection that I brought up before, and just to simplify things, I'll say an early infection is one that is apparent NEAL R. GROSS
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before

the

incision

is

totally

healed,

and

a

late

infection is one after the incision is healed. Do you have the percentage of early versus late, and was it at all correlated to the surface type of the implant, the smooth versus textured? And I guess as a follow-up, did you use any of the partially textured implants? MR. PURKAIT: The last question first.

Partially textured implant was not used to understand that phenomenon, but as far as the breakdown of those, we'll talk to Dr. Gene Poggio to see if he can tease out the information for you. DR. MORYKWAS: DR. POGGIO: question pretty and readily. Okay. I can answer part of your Looking overall, and I across it

augmentation

reconstruction,

have

separately for those if you'd like, in the first year -- this is using the Kaplan-Meier estimates and looking at changes from year to year. So how much happened in

the first year and then how much increased; did it increase between the end of the first year and the end of the second year? NEAL R. GROSS
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So infection overall, 2.8 percent in the first year, 0.5 percent in the second year, and 0.16 percent in the third year. first year. DR. CUNNINGHAM: But in terms of teasing So it's almost all in the

out, I mean you're asking for a time frame of one or two weeks, and the first interval follow-up were data reported presumably as be four to six weeks, and these but would they

detected

earlier

than

that,

would be, you know reported as they accumulated. I think in clinical practice they occur most frequently within the first two weeks, and it's a little bit different than a wound infection without a device because most plastic surgeons, as Dr. Burkhardt has teased out, try to use antibiotics, Betadine,

whatever they can, to make this complication go as close to zero as possible. So there are times where the -plus

giving prophylactic antibiotics -- so there are times where the time course is shifted or delayed out into the future than in a wound where there is, you know, no prophylactic antibiotic, not as much irrigation, but NEAL R. GROSS
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clinically my impression is that they almost all are most apparent within the first two to three weeks, and it's very rare that you see a late complication

associated with, say, some dental procedure or some other seeding. Here's the time to occurrence. Four to Six

six weeks is 53 percent, which is the majority. months is 24 percent. reconstruction infection by

Twelve months is 17 percent for and then in terms of the the

patients, device, the

textured

device,

both

SILTEX and the SPECTRUM, are more likely -- it looks like about 85 to 90 percent -- are more likely to have an infection. CHAIRMAN WHALEN: DR. CHANG: Dr. Change. going to quote Dr.

I'm

Burkhardt again because it is my concern that on the face of it, although in the ten year retrospective study patient satisfaction rate was high, 93 percent, could you help me out? infection, And I presume you're looking at capsular contracture and

significant

deflation rate. words, how

Could you help me out and in your own you explain to a consumer, to a

would

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patient that despite one in four complication rate at ten years, that this is, indeed, a safe product? Overall complication rate is 27 percent. DR. CUNNINGHAM: I can speak to, you know,

what I see clinically, and perhaps Dr. Anderson can speak to that as well. First of all, no plastic surgeon wants a surprised or unhappy patient, particularly when we're doing elective surgery, aesthetic surgery. So I think

one of the ways to explain the fact that despite a one in four risk for complication or reoperation patients are generally satisfied goes to the degree to which they are informed. If I as a plastic surgeon whitewash the possible complications and have the kind of risk of complications that we've demonstrated today, I'm going to have a lot of very unhappy, surprised patients

saying, "How could this happen to me?" Whereas if I go as far as I can to stress what the risks are, make clear what things could go wrong, and make clear that the patient understands that and we're not pretending that it's not going to happen NEAL R. GROSS
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to them, we're saying it could happen to you; I think that sets an expectation set that makes anything that does occur more that's acceptable going to to a patient their and not

something result.

diminish

overall

But I think when we ask the patients to rate themselves on a strongly satisfied dissatisfied, -I can't

dissatisfied,

satisfied,

very

remember what the fifth one was -- the vast majority of them also when we asked them would you do it again, the 90 percent range was, yes, they would. So I think part of it is they're well

informed, and so they tolerate the complications. CHAIRMAN WHALEN: MS. DUBLER: Ms. Dubler.

I'd like to pursue that just

a little bit because I have an epistemological problem. In the context of research where IRBs have to weigh the risk and benefit, there's an articulate, although not the majority of scholars who argue that the informed consent process can cure the defects in the risk-

benefit ratio; that it doesn't really matter what the risk-benefit ratio is. If you can tell the patient and

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the patient can make an informed choice, it solves your problem. But in the context of the FDA's finding that something is safe and effective, I'm not sure that an informed consent response solves the underlying

problem.

So we have a 27.6 overall complication rate. I don't know. I think women want it. I

think they're satisfied.

Your data seems to show that, Now, maybe it's a

but I don't know how we can find it safe. that's a question for the company.

Maybe

question for the FDA, but that's a problem for me. DR. CUNNINGHAM: (Applause.) DR. CUNNINGHAM: You know, I think we Well, I think --

wouldn't want to try to make the assessment for the patient. We are constantly asking them what their That's the basis of the data that Dr. It's the basis of the data that I

assessment is.

Anderson presented. presented. I benefit sets. the think

there

are

two

different

risk-

There's obviously a different set for patient versus the one for the

augmentation

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reconstruction patient. I think another thing that we haven't

really talked about extensively here is that we're not just counting pieces of chalk marking on a blackboard. The complications that we talk about, some of them are significant and impact definitely on a patient's life, and some of them are things that they can control and determine themselves. For instance, the patient who wants to

change their size is recorded as a reoperation, but it's not an obligatory reoperation. It's something

that they choose to do to improve their result. So it's not exactly the same model as some of the others that you might be looking at because the patient is in so much control of the process relative to, you know, you need a heart valve, you need a pacemaker, this you need. It's a different situation.

A lot of these operations are things that patients choose to do. CHAIRMAN WHALEN: DR. BURKHARDT: Dr. Burkhardt. Yes. Dr. Cunningham, I Seventy-two of

forget exactly what the figures were. NEAL R. GROSS
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88 implants that were removed were replaced at the same time, and the problem was apparently size. So rather

than being a concern about the integrity of the device or anything, it does raise some question about how the size is picked in the first place. How did you do that in your study? DR. CUNNINGHAM: determination to the I think we left the size individual practice.

surgeon's

There's no way that the company could help the surgeon decide what size the patient would need for the patient to be happy, and I think certainly I have seen in my own clinical practice where a patient might come in with one set of expectations before they have any

surgery, and then as time goes on, their expectations and their desires change after the operation. So there are times when patients come in and demonstrate or discuss a certain look or

appearance, and then after the surgery they say, you know, that's "I would of like what to we enhance see that the further," implants and are

part

when

changed, particularly for a larger size. DR. BURKHARDT: I guess my point would be

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that as I understand it, then that doesn't reflect deficiency of any sort on the implant, only in the decision making process as to the size originally. DR. CUNNINGHAM: I think what you're

reflecting is a communication issue or a change in communication or change in desire on the part of the patient, not an implant related problem. DR. BURKHARDT: MS. DUBLER: please? CHAIRMAN WHALEN: MS. DUBLER: Yes. Thank you.

Could I follow up with that,

I just want to follow up this

discussion because I think it's very interesting, and that is the Betadine discussion and perhaps the

reoperation to put in a larger prosthesis reflects on the quality of the practice of the surgeons more than it does on the device itself. So, again, it's hard for me to separate out how much of this reoperation and overall

complication rate is related to the device and how much of it is related to surgical patterns of practice, and how we allocate or understand that I think makes a NEAL R. GROSS
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difference in this context. DR. CUNNINGHAM: statement than a question. MS. DUBLER: Okay. I just have one question. I take that as more of a

MS. BRINKMAN:

You're talking about your ten year study, your followup. You're using the SEER data for that? MR. patients primary. MS. BRINKMAN: little over 200? And that sample size is a PURKAIT: That's what the cancer

That's about it, of saline? No. No, the ten year data The SEER data at the

MR. PURKAIT:

DR. CUNNINGHAM:

that I presented is not the SEER data. was another part of the way of

looking

reconstructed patients and what their failure rate was, their deflation rate. MS. BRINKMAN: But in the SEER data, the

saline implant population number was about a couple hundred for the reconstruction? DR. CUNNINGHAM: That data set, I think,

was complicated by the fact that it was a retrospective NEAL R. GROSS
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study.

A lot of charts were looked at, and there were

definite incidences, and perhaps Dr. Poggio or one of the others can pull that out, where devices were

recorded as implants, but clearly as you look back over the medical record, they were not ever meant to be permanent devices. not implants. So I think the large number of those that were soft tissue expanders and not implants kind of clouds that whole data set for us and it makes us very hard for us to interpret what is the actual failure rate in the SEER data for reconstruction patients. CHAIRMAN WHALEN: Are there other members They were soft tissue expanders,

of the panel who have questions for the sponsor? PARTICIPANT: One quick one. Well, I'm asking only move the rest of the

CHAIRMAN WHALEN: because I've been asked to

questions to a later point in time, but if indeed, we're done, we're done. But if there are others, we

are going to move on now to the FDA presentation, and there will be time later for more sponsor questions, which I would project, looking at the schedule, should NEAL R. GROSS
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be some time before 2:00 a.m. (Laughter.) CHAIRMAN WHALEN: So we will move on to

the FDA presentation, and I thank the sponsor for their presentation. For all my fellow panel members, as the FDA is coming up for their presentation, please be aware it is past 5:00 p.m. We now are on overtime,

which means that Jim Dillard will thank us twice on Friday instead of once for our work. PARTICIPANT: -- other questions later on? Not at the table, sir,

CHAIRMAN WHALEN:

because the FDA will be coming up, but please if you could stay in this vicinity, that would be good because there will be questions, and also you have a summation period later on. (Pause in proceedings.) DR. BERKOWITZ: I'll present the FDA

presentation of the Mentor saline filled and SPECTRUM saline filled breast implants. I'm David Berkowitz, the lead reviewer,

and I will give an overview of the status of the NEAL R. GROSS
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preclinical testing, and then I'll finish with a one slide summary of the medical device reports for the Mentor prostheses. And then we'll hear from Sahar Dawisha, who is the clinical reviewer and will review the

clinical results. And then we'll hear from Phyllis

Silverman, who is the statistical reviewer. To describe the device first, the saline filled device is available in six styles. are determined by two things. The styles

One is the shape, like

the round, the profile or the contour, and the other is the nature of the surface. The surface is either

smooth or textured, and SILTEX is the Mentor name for textured. So SILTEX implies textured, and the surfaces

are either smooth, SILTEX or SILTEX PT, which is a partially textured device. The saline filled device has a diaphragm, an anterior diaphragm valve, and of course, it's filled with physiological saline, and both devices, obviously the shells are made from silicone elastomers. The SPECTRUM device differs from the

NEAL R. GROSS
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saline filled device in that it can be postoperatively adjusted. The volume can be postoperatively adjusted,

and when the desired volume is reached, the little valve for postoperative filling can be removed under local anesthesia. The SPECTRUM device has a posterior kink plug value, and like the saline filled, obviously the filler is also saline. The indications for use are augmentation, reconstruction, asymmetry, ptosis, aplasia, hypoplasia of the breast, replacement, and combined breast and chest wall deformities. Mentor has done extensive chemical

analyses on the device.

They've looked at the levels

of the volatiles, extractables, and metals, and these are important because, one, they characterize the

materials present in the device and, secondly, they determine what is there and how quickly those things can diffuse out of the device to cause either local or systemic toxicity. These are some of the toxicology testing. The pharmacokinetics testing came from the literature, NEAL R. GROSS
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but also relied upon the chemical determinations sine by knowing how much is present and how much could leak out, we know what the dangers are. So, in fact, it turns out in terms of

systemic toxicity, even if all of the low molecular weight components present in the device leaked out

immediately, it would still be a wide margin of safety between the levels, say, the blood levels obtained and the toxic levels. The middle group of things that were

determined are all the, I think, quite commonly done biocompatibility things that are tested on most

devices, and I just want to mention at the end that the immunotoxicity is important for these devices, and it was quite extensive. That is, in addition to doing simply the hematology and counting cells, they enumerated, you know, the B and the T cells and the T cell subsets. They enumerated the killer cells, for example, and they also estimated the effects of implanted shell material on killer cell activity and on things like the mixed leukocyte response. NEAL R. GROSS
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So various aspects of the immunology were broadly tested. The remaining, these toxicological things have to do with mutagenesis and in bacterial testing and in mammalian cells, and finally culminating in a two year rat carcinogenicity study which demonstrated no carcinogenicity. The toxicology and company teratology also did and a reproductive that was also

study,

negative, which would have been expected. The mechanical testing, on the other hand, is not complete. Mentor has done some mechanical

testing on each of these topics, and we have also received reviewed. some recent data which have not yet been

But with all the testing we now have, we

think that the data are not yet sufficient to make a recommendation for all the implant styles proposed in the PMA. So we are still going back and forth with Mentor on the mechanical testing. Finally now, to change topics, I'd like to put up a slide summarizing the medical device reporting NEAL R. GROSS
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for

Mentor,

and

this

slide

summarizes

the

medical

device reports that FDA has received for the Mentor saline filled breast implants during the last three year period. The reports -first I column, the that slide is -the the Maude first

oops,

missed

column, the Maude reports, the Maude system received reports directly from patients, health care providers, practitioners, and from manufacturers. The second column lists the five most

frequently reported adverse events that are reported in summary form by Mentor on a quarterly basis. So these

are the sums of the reports for the last -- for over the three years shown above. So that's all I'll say about this, and I think now I'll ask Dr. Dawisha to come and begin the clinical report. DR. DAWISHA: Good afternoon. I am Sahar

Dawisha, a Medical Officer in the Division of General and Restorative Devices, and I will be presenting FDA's clinical perspective of the information provided in the Mentor Corporation's saline filled breast implant PMA. NEAL R. GROSS
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The clinical studies reported in the PMA are summarized on this slide and consist of a

retrospective assessment of implant removal from the SEER data base, a one year large, simple trial, or LST; the saline prospective study, or SPS; and the Mentor retrospective study. The SEER and LST were conducted in

response to suggestions from FDA in 1994 on the type of information needed for PMA approval submission. The

SPS is a prospective clinical study which was approved by FDA in 1995 after all augmentation and some

reconstruction patients had already been enrolled. Because the saline prospective study

contains the main safety and effectiveness information, I will focus on this study summarizing the SEER and LST only briefly. I will not be discussing the Mentor

retrospective study because the patient population in this study is highly selected and because data

ascertainment

bias

severely

limits

the

conclusions

drawn from this study. The analysis of sponsor funded in a a retrospective breast cancer

implant

removal

NEAL R. GROSS
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population cohort from the surveillance epidemiology and end results or SEER program of the National Cancer Institute because they were having difficulty enrolling reconstruction patients in their clinical studies.

Women with a diagnosis of breast cancer in the years of 1983, '85, '87, and '89 with any type of breast

implant, including silicone gel filled, saline filled, and tissue expanders, were asked to respond to a

questionnaire regarding implant removal. The results of this study are shown here. The nonresponse rate was 20 percent overall. 1,375 total implants removed -- I'm sorry. 1,375 total implants, 32 percent were removed. Of were removed. There was information provided based on the 252 saline implants, 43 percent Of the Of the

the reason for removal, and excluding the 28 saline implants removed as part of planned reconstruction -these are the tissue expanders that Dr. Cunningham was referring to -- the reasons for saline implant removal are shown. Capsular contracture constituted the

NEAL R. GROSS
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single

most

common

reason

for

implant

removal,

35

percent of implant removal. The large, simple trial was designed as a prospective followed study for of the a large number endpoints of of patients capsular and

only

safety

contracture,

infection,

rupture,

deflation,

explantation for a total of one year. of 3,000, and 5,000 patients was

The sample size proposed by the

sponsor to estimate complication rates with a precision of one to two percent. The LST results at one year are shown here on a by patient basis. The analysis method used here

is the Kaplan-Meier survival analysis, which shows a risk of a first occurrence of a complication, along with a 95 percent confidence interval, which is shown in parentheses. Not that for the total group, which is in this column, the confidence interval are all within one to two percent as proposed by the sponsor. the intervals for the reconstruction and However, revision

patients are much larger, and in some cases there was insufficient information to estimate the proportion. NEAL R. GROSS
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There enroll with the

were

a

total as

of

2,373

patients and the 47

majority at one

augmentation, was

follow-up percent.

rate

year

approximately

Of capsular generally

the

four

complications Grade

studied or IV

here, was the

contracture, the

Baker

III

complication

encountered

with

greatest overall frequency. Furthermore, you can see that for the two complications information, contracture in which Grade which would III or there be IV, was and sufficient capsular patients

explant the

revision

generally have rates between those of augmentation and reconstruction. With the exception of this study and the implants in the SPS in which there was replacement and follow-up information, the sponsor has not collected safety and effectiveness information on revision

patients. You'll be asking the panel questions to discuss the revision indication. Before I discuss the SPS in detail, I

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would like to show you the implant style studied in Mentor Corporation's clinical studies, as well as those not studied for which the sponsor is seeking approval. Note that the sponsor is no longer

manufacturing implants with an oval shape or with a leaf valve. have a The implants with a contour profile shape contouring the major than those that is are the

greater and

contoured,

difference

here

partially textured devices.

These implants appear to

be unique from all others in that they are textured only on the posterior surface. pronounced. The posterior The texturing is more textured layer is an

additional vulcanized layer, and this layer is made from a different, softer silicone. The sponsor has been asked to clarify how this new texturing differs from the type of texturing in their clinical studies and to explain whether and how the clinical performance can be inferred from this new texturing method. The saline prospective study was initiated in 1993 and approved in 1995 after augmentation and summary construction patient enrollment. NEAL R. GROSS
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The study is

a

prospective,

open

label,

multi-center

study

with

three years of total follow-up for patients seeking primary augmentation and primary reconstruction. Safety was based on local complications, and effectiveness patient was based on and breast quality dimension of life

changes, measures.

satisfaction,

The

sponsor

collected

lactation

and

reproduction history at baseline and connective tissue disease, or CTD, symptomatology and breast conditions at baseline and at follow-up. A sample size of 1,200 to 1,500 patients with at least 20 percent of these as reconstruction was proposed to estimate the 95 percent confidence interval precision for complications. The patient disposition at three years is shown here. Of the 1,265 76 augmentation patients their

enrolled,

approximately

percent

completed

three year visit.

For reconstruction, the completion

rate was 66 percent at three years. Of the patients who were withdrawn, the majority for augmentation were lost to follow-up. NEAL R. GROSS
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For

the

majority

of

reconstruction

patients

who

were

withdrawn, the majority were explanted.

The 15 patient

deaths reported in this study were not implant related. For the 49 augmentation and 75 reconstruction patients who underwent explantation, subsequent complications

are not included in the Kaplan-Meier complication rates to follow. The rates of first three year and cumulative 95 Kaplan-Meier confidence

occurred

percent

intervals for selected complications are shown here on a per patient basis for the patients in the saline prospective study. You can see that the largest 95

confidence intervals are plus or minus three points for augmentation and plus or minus five points for

reconstruction. Note that the capsular contracture shown here includes both Baker Grade III or IV and Baker Grade unknown or unreported, and that the category of any complication here includes reoperation. The cumulative risk of a first occurrence of a complication is 43 and 73 percent, respectively, for augmentation and reconstruction. NEAL R. GROSS
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Although only the

three year rate is shown here, the cumulative rate of first occurrence of any complication increases over time and has not leveled off by three years of followup. The cumulative risk of at least one

reoperation for any reason over the three year period is 13 percent for and augmentation these and 40 as percent well, for are

reconstruction,

rates,

increasing over time. In reconstruction augmentation. The cumulative rates of first occurrence of leakage/deflation, implant removal, breast pain, general, are the complication greater rates than for for

three

times

wrinkling, and nipple changes, which includes both loss of nipple sensation and intense nipple sensitivity, are shown here as well. The most common types of reoperation

procedures performed through three years is shown here based on the number of procedures. sum to 100 because I have Percentages do not infrequently

omitted

performed procedures from this table. NEAL R. GROSS
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There procedures

were

358 in

and the

353

reoperation and three

performed patients,

augmentation through

reconstruction years.

respectively,

For the category of removal with replacement, I

combined the following categories reported in the PMA: implant size exchange, secondary augmentation,

replacement, and revision. Scar/wound adjustment and wound revision management. includes Capsule skin related

procedures include capsulotomy and capsulectomy. The most commonly performed procedure for augmentation patients was removal with replacement, 32 percent of the procedures performed in these patients. And for reconstruction, it was a capsule procedure, 28 percent of the procedures. Not shown here are the nine implant

removals without replacement and augmentation and 40 in reconstruction patients. The information shown on this slide was provided subsequent to the PMA submission at the

agency's request, and it shows the reasons for implant removal through three years on a by implant basis. NEAL R. GROSS
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If

an

implant

was

reported

to

have

been

removed

for

multiple reasons, the hierarchy for categorization into this table is shown in the footnote below the table. Cosmesis includes asymmetry, ptosis,

wrinkling, and scarring. 116 reconstruction

Of the 136 augmentation and removed over the three

implants

years of follow-up, other than a patient request for a size or shape change, the single most common reason for augmentation implant removal was due to

leakage/deflation. Twenty-three percent of all removed

augmentation implants were due to leakage/deflation. Infection and capsular contracture constituted the most common reasons for reconstruction implant removal, each at 26 percent of all reconstruction implant removal. For both augmentation and reconstruction, if you were to take the complications and sum those, you would see to that a the majority of implants than were to

removed

due

complication

rather

due

patient request for a size or shape change. In an effort to characterize the

complication rate in revision patients, the sponsor was NEAL R. GROSS
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asked

to

provide

the

cumulative

Kaplan-Meier

first

occurrence complication rate on a by implant basis for those implants which were removed and replaced during the study and for which there was follow-up

information. This table summarizes this information

through three years of follow-up. size and follow-up is lower than

Because the sample for the primary

implantation in the SPS, the confidence interval for this table are much wider than reported for the primary implantation group. Note that the capsular contracture here, as well as in the other table I showed you, includes both Baker Grade III/IV and Baker grade unknown or unreported, and the any complication category here

includes reoperation. The complication for risk of a first is occurrence similar for of any

this

group

these

implants compared to primary implantation.

However,

for the major complications of reoperation, implant removal, capsular contracture, and leakage deflation, the rates are higher than for primary implantation and NEAL R. GROSS
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lower than for primary reconstruction, which is similar to the revision complication rate reported in the LST. For most other complication the rates are similar or lower than for primary implantation. You'll

be asked to address a revision indication in the panel questions. The analysis for sponsor performed at Cox implant regression variables

several

patient

which they showed you and for the complications of infection, capsular contracture, deflation,

reoperation, and removal, and selected associations are shown on this slide. There were no associations with infection. Implants with leaf valves had two times higher capsular contracture than those with diaphragm valves. Recall

that the sponsor is no longer manufacturing implants with leaf valves. Surgical pocket irrigation with Betadine was associated with a three and a half times greater risk of deflation than without,a nd implants with

SPECTRUM valves were associated with a twofold higher risk of both implant removal and reoperation than those NEAL R. GROSS
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without. With respect to other safety issues, the sponsor collected breast cancer and connective tissue disease information at baseline and at follow-up. note, there were two augmentation patients Of who

developed breast cancer during the course of the study, one patient two years and the other patient five months after implantation. At any follow-up visit complaints

of fatigue, generalized achiness and/or joint pain were reported infrequently in patients without such a report at baseline. There unconfirmed reported cases the were of six confirmed tissue study. and 31

connective of the

diseases The six

over

course

confirmed cases are shown here with the indications shown as well. There were two patients with

osteoarthritis and one with an undetermined arthritis and one with ankylosis spondylitis in the

reconstruction group. In one patient the augmentation systemic patients, there was and

with

lupus

erythematosus

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rheumatoid arthritis reported during the course of the study. Without a control group of sufficient

numbers of similar types of patients followed for the same duration, conclusion regarding the association of the CTDs shown here with these implants cannot be made. With augmentation patients respect and an to effectiveness, the

patients

delayed in

reconstruction breast size. and

experienced patients

increase

Augmentation

were

generally

satisfied,

they experienced small, but statistically significant improvements in one of the ten subscales of the

multidimensional body self-relations questionnaire, or MBSRQ, and small but statistically significant

improvements in the Tennessee self-concepts scale. Reconstruction patients experienced

statistical improvements in the functional living index of cancer scale, or FLIC, and immediate in mastectomy the Beck

patients

experienced

improvements

depression inventory. There were no statistical improvements in the MBSRQ or in the Tennessee self-concept scale for NEAL R. GROSS
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reconstruction patients. Recall that the SPS was initiated in 1993 prior to FDA approval in 1995. approval, the sponsor was Shortly after FDA that continued The

informed

follow-up beyond three years would be advisable.

sponsor contacted patients who were still participating in the SPS at that time to solicit continued follow-up in the form of a yearly postcard assessing for

deflation. Of the 1,045 augmentation patients in the SPS at that time, 519 or 50 percent agreed to the four to ten year follow-up. Of these 519, 362 patients

returned postcards, a 70 percent response rate, and in these 362, there were 36 deflations reported or a rate of ten percent. Of the 375 reconstruction patients in the SPS at this time, 186, or 45 percent, agreed to the four to ten year follow-up. their postcards, an 86 Of the 186, 144 returned response rate, and

percent

deflation was reported in 17, or 12 percent, of these patients. You'll be asked in the panel questions to NEAL R. GROSS
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address the duration and type of follow-up information needed to fully characterize the long term safety of these implants. In summary, the cumulative risk of a first occurrence -- of a first complication is 43 percent for augmentation and 73 percent for reconstruction; is

increasing with time; and has not leveled off by three years. Cumulative complication rates of

reoperation and removal have not leveled off as well at three years. Although cumulative local complication

rates are increasing, the types of local complications are well characterized, and the rates are precisely defined. are In augmentation patients, most reoperations removal. most For implants both are augmentation removed due and to a

implant

reconstruction,

complication rather than due to a patient request for a size or shape change. Breast size benefits were realized for

augmentations and quality of life changes were evident, but small. For reconstruction patients, quality of NEAL R. GROSS
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life measures generally improved. You will be asked to discuss these safety and effectiveness issues in the panel questions to

follow. Thank you. I'd Silverman, perspective. MS. SILVERMAN: I should say good evening. Good afternoon, or perhaps I'm Phyllis Silverman, the who like will to be now introduce the Ms. Phyllis

discussing

statistical

statistical reviewer for the Mentor PMA. The statistical sections of this PMA are well written, comprehensive, and address nearly all of the requests put forth in the draft guidance for breast implants. The sponsor's PMA contains safety and

effectiveness data from five studies. Since the saline prospective study is the only one that utilizes the device in question, includes all of the endpoints of interest, and fulfills the recommended follow-up, I consider it to be the primary study, with the others lending various degrees of

support. NEAL R. GROSS
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Because of the approximate 50 percent loss to follow-up with the large, simple trial, the ability to draw meaningful conclusions from this trial is

limited.

Therefore, my comments will focus on the

saline prospective study. Because there was no control group and

therefore no claims of superiority or equivalence, the safety and effectiveness results for this device must be evaluated by rates, way of descriptive survival be statistics. curves, from and a

Complication effectiveness

implant must

parameters

evaluated

clinical perspective. As a statistician, my role is not to judge the acceptability of these rates, but to evaluate the validity of the data presentation as well as point out any weaknesses in the study design and analysis. will start with some comments on sample size. Because there were no null and alternative hypotheses statistical for the a primary endpoints, the hence making of the I

power

non-issue,

adequacy

sample size was determined by the desired precision around the estimates of complication and reoperation NEAL R. GROSS
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rates.

The larger the sample size, the smaller the

width of the 95 percent confidence intervals which are used to represent the precision. We wanted to insure that the width of the confidence intervals would be no more than about plus or minus four and a half percent when rates were high, for example, a 40 or 50 percent complication rate, and only about one to two percent when rates were low. The sponsor's enrollment of 1,265

augmentation patients and 425 reconstruction patients resulted in a three year accountability sufficient to meet this precision. was adequate. This brings me to the Kaplan-Meier curve. The sponsor used Kaplan-Meier curves to estimate the occurrence of complications and adverse events. This Therefore, I feel the sample size

technique allows women who were not followed for the entire three years to contribute information to the, quote, survival curve for the time that they were in the study. They either experienced the event in

question or they are, quote, censored at their last follow-up, which means they are dropped from the

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denominator at that point. I feel that this is the best technique that the sponsor could have used for this type of data. There are, however, three weaknesses with this The not or

methodology as applied to these particular data. information incidence, collected and thus, reflects new prevalence of and

cases

infection

contracture, for example, could not be distinguished from continuing cases. Therefore, survival curves are based on

the time to the first occurrence of each complication and multiple occurrences could not be analyzed. Secondly, because a patient explanted or revised will be censored from the table and not be in the pool to experience other complications, there is the issue of competing risks which can add an

uncalculated bias to these rates. And, thirdly, with the exception of

deflation, explant, and reoperation, the exact time of onset of a complication could not be known, but would generally have been noted at the next scheduled followup. NEAL R. GROSS
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This interval censoring as it is called can add an additional unknown bias to the data.

Therefore, the curves are not as exact as if one were measuring an endpoint like mortality in days. A summary of the Kaplan-Meier rates for the primary safety endpoints is reiterated on the next slide. It can be seen in the from the table that group the are

complication

rates

reconstruction

about three times what they are in the augmentation group. Because of considerable difference between the

augmentation and reconstruction cohorts, these rates must be considered separately by indication and

evaluated from a risk-benefit perspective. Is a three year explant rate of almost 27 percent or a re-op. rate of 40 percent acceptable for re-com. patients? As you can see from the slide, the

95 percent confidence intervals were plus or minus two percent or less for the augmentation patients and plus or minus three to five percent for the reconstruction patients. This is consistent with the guidelines. Now, I would like to discuss some possible biases with the data. There are several sources of

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possible bias with this data.

With three year follow-

up missing for approximately 25 percent of the cohort, there could be a non-respondent bias in that women who were having problems were more likely to return for follow-up implants. than those who were happy with their

This would result in an overestimation of rate, or there with could be the opposite were not

complication scenario.

Patients

complications

returning for follow-up because they were seeking help elsewhere. This would result in an under estimation of

complication rates. A analysis is key that assumption the for the Kaplan-Meier is

censoring

distribution

independent of the survival distribution.

What this

means in English is that whether or not a patient returns for follow-up should be unrelated to their

level of satisfaction with their implants. Since we do not know to what degree this is true or the reasons for patients not returning, we cannot ascertain this bias. We can only acknowledge

that there probably is some, and the complication rates must be evaluated with this in mind. NEAL R. GROSS
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Because

many

of

the

complications

are

self-reported, there is likely also to be some recall bias, especially with the reporting of connective This

tissue disease and the rheumatology screening. bias could go either way.

That is, it could inflate or

decrease the rates, depending on how a patient's memory compares to reality. This is a weakness of a study design where follow-ups are infrequent and medical conditions are not always confirmed by a physician. The last bias I wish to discuss is

investigator or site bias.

With a study design of 153

sites, it is virtually impossible to justify pooling on a statistical basis, and the sponsor did not attempt it. Although there is always the possibility for difference in follow-up or results among sites, I feel that any site or investigator bias would probably be minimal, especially compared to some of the other variables that emerged as related to outcome. For example, surgical approach, valve

type, and implant shape are significantly associated NEAL R. GROSS
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with contracture, and valve type is also associated with explant and reoperation. Incision size and use of Betadine

irrigation was significantly associated with deflation. The sponsor presented such as an extensive type, analysis implant of co-

variables,

valve

shape,

laterality, incision size and surface type by use of Cox regression. Surface associated with type was the not very significantly thing it was

contracture,

meant to reduce. Of the three biases discussed, my belief is that the nonrespondent bias is of most concern, and that the other two are probably minimal. me to effectiveness. The analysis of sponsor presented by way a very of thorough This brings

effectiveness

descriptive

statistics resulting from numerous surveys administered and objective breast measurements. In addition, before and after comparisons of some effectiveness endpoints showed statistically significant changes. However, I question the

NEAL R. GROSS
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interpretation of the phrase "statistically significant increase in breast size." It does not appear to mean

anything from a clinical perspective. The data must be looked at in the broader sense. The data indicate to me that even though there

were some dissatisfied patients, breast implants are overall effective from both a physical and emotional perspective. Conclusion. In summary, I found the data

analysis presented in this PMA to be comprehensive. The sponsor's analysis laid out was in consistent the with the The

methodologies

guidance.

complication rates must not be taken as exact, but rather as estimates subject to the biases discussed earlier. I would like to close just by presenting a few more statistics. complications per Because there could be multiple patient, and even correlations

between adverse events, for example, contracture and pain, I would like to leave you with the complication free rates at one, two, and three years. These rates

are not subject to the problem of competing risk and NEAL R. GROSS
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would

be

of

particular

interest

to

a

prospective

patient in making an informed decision. Although some complications are more

serious than others, the data show the complications are, indeed, frequent. Approximately 57 percent of

augmentation patients are complication free at three years, as opposed to only 27 percent of reconstruction patients. If breast implants are deemed acceptable for

market, women must be presented with these figures so they can make an informed decision from their own

personal risk-benefit perspective. Thank you for your attention. CHAIRMAN WHALEN: and the entire team. Well, our next order of business would be to have the FDA entertain questions from the panel. We Thank you, Ms. Silverman

have a sort of unscheduled break that we must take because apparently part of this room is not reserved for this block of time. little bit closer, too. So if we would please take a 15 minute break while they resize this room and hopefully that NEAL R. GROSS
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So we're all going to get a

will be sufficient time for them to do what they have to do. (Whereupon, at 5:53 p.m., a recess was

taken, to reconvene at 6:15 p.m., in the same place.)

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E-V-E-N-I-N-G

S-E-S-S-I-O-N (6:15 p.m.)

CHAIRMAN WHALEN:

I would like to ask that

at the real conclusion of the FDA presentation that Dr. Berkowitz review for us the FDA questions that are going to be posed to the panel as the next step. DR. BERKOWITZ: Question one, while the

sponsor provided no long term clinical data on their implant, fatigue testing and fold flaw testing provides some information in the long term rupture leakage of the implants. Please comment on the sponsor's

methodology and results for each of these tests. CHAIRMAN WHALEN: Dr. Berkowitz, if you

could just read all of the questions, we're not going to go into the deliberation upon each one just yet. DR. BERKOWITZ: All right. Question two,

given the data for augmentation patients in the SPS and other data provided by the sponsor, is there reasonable insurance as defined in 21 CFR 860.7 that the product is both safe and effective for augmentation patients? Question reconstruction three in says the given SPS the and data the for

patients

other

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information

provided

by

the

sponsor,

is

there

reasonable assurance as defined in 21 CFR 860.7 that the product is both safe and effective for

reconstruction patients. Question four, with the exception of the LST one year follow-up and the implants in SPS in which there was continued follow-up after explantation, the sponsor has not collected safety and effectiveness Yet

information for the cohort of revision patients.

the sponsor proposes revision as an indication for use. Given that this cohort typically represents at least 30 percent of the patients presenting whether for breast is

implantation,

please

discuss

there

sufficient safety and effectiveness data to include revision should as an indication the and whether the sponsor for

evaluate

safety

and

effectiveness

revision patients as a condition of approval. Please also comment on the information

that would be useful to collect in a post approval study. Question five, given that the sponsor's

data show increasing cumulative rates per year for the NEAL R. GROSS
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majority of complications for both reconstruction and augmentation patients, please comment on whether there is adequate follow-up data to characterize the

frequency and types of long term adverse events. Please address the following pertaining to long term adverse events: follow-up; (b) the type (a) the minimum duration of of visit, i.e., active or

passive, and (c) which types of complications should be assessed. Question six, the sponsor's SPS study was not designed to provide information in the following long term issues of pertinence to women with implants: one, the interference on the ability of screening

mammography to detect tumors in breasts with implants; two, the interference with lactation; and, three, the effects on offspring from women with implants. Please discuss whether the sponsor should evaluate these issues as a condition of approval. so, please discuss the appropriate methods If for

addressing these issues. And the last question is: given the

heterogeneity of surgical practices and post operative NEAL R. GROSS
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management of mammary implantation, please comment on the important issues which should be included in

physician training. CHAIRMAN WHALEN: Thank you.

We now, therefore, proceed to the panel discussion and review of FDA's seven questions, and we will start in that off by having as three lead of the panel make

members

specific

areas

reviewers

comments in their areas of expertise.

Those three will

be Dr. Li in mechanical testing, Dr. Burkhardt on the clinical study, and Dr. Blumenstein on statistical

considerations. First, for mechanical testing, Dr. Li. DR. LI: Thank you.

Let me first say as an overall comment that it appears that mechanical failure of this device in the form of leakage or rupture is one of the primary reasons for revision and reoperation, and this is

purely a mechanical failure in my view of either some combination of material, design and environment, and it's unfortunate that that's actually the one area that was the most incomplete in your PMA. NEAL R. GROSS
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The FDA has done a nice job summarizing their comments regarding your testing in the deficiency letter I believe you have received, and in general I agree with virtually all of your comments, but let me highlight a couple of them, I think, that are more important perhaps than the others. One is, I think, you need to provide data for all models that you intend to market and not just the ones that you have selected. sets of testing. The other is that most of the data, as I understand it, was done with the material of This goes for all the

construction that you refer to as PTC, RTC, silicone. Yet the final products are made with Sytech (phonetic) silicone, and although you make some comparisons of basic material property similarities, I believe this argument is insufficient to merely make a material swap in those raw material properties alone. For instance, one of your own data points suggests that, in fact, Sytech and PTC are not

equivalent in terms of if you look at one of your numerous tables that showed the elongation and break NEAL R. GROSS
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strength of Sytech versus PTC on dry heat.

The Sytech

silicone actually has improved properties of elongation and break strength. However, if you do that same

comparison and the components are gamma sterilized, the order is reversed, and in fact, the Sytech is less strong and has less elongation. So certainly I think your claim that the materials are equivalent is not supported. That raises an odd issue. It appears

through the literature that you have one particular Model 1600 which apparently from my reading may or may not be gamma sterilized, which is a little confusing to me. I'm not sure when you choose to gamma sterilize it

and when you choose not to gamma sterilize it, and this might be important because basically all of the gamma sterilized material properties are significantly less than those that were heat sterilized. So my questions would be: this? why do you do

How do you decide when they're gamma sterilized And more importantly, does the

and when they're not?

physician at the end of the line know when he buys a 1600 component if it's gamma sterilized or not and that NEAL R. GROSS
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there's, in fact, a material property difference? In a more general sense, the thing that I was most taken back is these implants have been around for decades and the leakage and deflation has always been a key complaint or indication for revision, but none of the testing actually directly addressed this particular test, mode as of you failure other it, than is a and your fatigue

which

describe high

catastrophic high cycle,

failure

under

extremely

loads

which is some indication of leakage, but certainly not any mirror of what happens clinically apparently in these leakage phenomena. So on the fatigue testing, there is a high variation in your results. If I can just quote a

couple of your numbers in general, for your Model 2600 of the 175 milliliters volume and an 80 pound load, your cycles to failure varied from 3,000-something to over 32,000-something, a factor of ten from the best to the worst. If you take that same model and do the 325 milliliter sample at 75 pounds, again you get about a factor of ten difference, from 16,000 for the worst to NEAL R. GROSS
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126,000 for the best. And lastly, if you take the Model 2400 at the same volume and load, it actually fails at 850 cycles rather than the thousands mentioned previously. So although your average graph looks very good, if you factor in the actual cycle fatigue for each individual product, there's at least a factor of ten from best to worst for every component, and then the gamma

sterilized version, the 1600 which would be expected to have the worst values, is not done. You do do a lifetime survivorship in a couple of different ways. I don't dispute the

methodology.

However, everybody should be reminded

that that safety factor is for that particular test. So if the end use was, in fact, that kind of cyclic high speed loading in your test rig, then that safety factor would, in fact, be appropriate. But I think it's undoubtedly true that

that particular mode of failure is not what happened clinically. a safety So I think it's not supported at all that is, in fact, carried over to the

factor

clinic. NEAL R. GROSS
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A technical detail, I think, that carries through all of this is the variation of properties and final results as a function of the percent of fill. I

couldn't see actually on your reports that I saw how you exactly filled each one. same volume? Were they filled to the I

Were they filled to the same pressure?

wasn't that exactly sure how that was done. And also in subsequent device tests, there might be cases where the worst case scenario is a device that's under inflated, and in another test

scenario, the worst case scenario might be where it's slightly over inflated, and I see no addressing of the issue of inflation percentage at all, and this actually might be one of the surgically related phenomena that Dr. Cunningham alluded to. A bothersome thing on the load thing is this. It seems to be a belief by yourself and Dr.

Cunningham that how the surgeon puts it in, in fact, makes a difference on the outcome. In fact, there's

even a general agreement that somehow that provides higher isn't; stresses. maybe it's Maybe there's folds; it maybe isn't. there But

puncture;

maybe

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absolutely addressed

none in any

of of

those your

particular testing

factors

are so

components,

basically remains anecdotal even after 30-plus years of use. The other tests are -- I guess I don't know what to do with them. You do a static and dynamic

rupture test, which is either dropping of weights on something or just squeezing it until it breaks, and those are interesting kind of device tests, but I'm not actually sure how clinically relevant either one of those particular tests are unless you're going to tell me car accidents are actually one of the reasons that some of those devices fail. The abrasion test is even more peculiar. I'm not actually sure what the clinical consequence of where is. Are you projecting that the clinical

consequence of where is that the device thins and, therefore, is more likely to rupture or are you worried about where and the fact that it creates some kind of particulate debris that goes on to cause some kind of systemic effect? But in either case neither one of those NEAL R. GROSS
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particular issues is addressed, and you also use a Tabor abrasion test for which panel they stick a flat piece of membrane on a device and then rub against it a very roughened surface. In the crudest sense,

sometimes it's a piece of sandpaper, and again, it's a relatively crude test. They're only testing a portion

of the device, and again, I don't really know what to do with the device, nor am I sure that particular method of where it is, again, clinically relevant. The tear test let's me get into the area of retrieval analysis. Depending on what numbers we

see, the number of devices that were deflated varies somewhere from maybe three percent to, you know, some relatively much higher number at the end. So even if

it's a five percent deflation rate and you've implanted 500,000 of these, there's 25,000 retrieved deflated devices somewhere, and I only see a report that you provide that looks at ten of these devices that were retrieved for either deflation and/or wear, which is a little confusing because you didn't tell me which of the ten were retrieved for deflation and which were wear, and I didn't know if the ones that you called NEAL R. GROSS
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wear were also deflated. So be that as it may, you did look at where -- tried to assess where the flaws were that caused the leakage, and the short answer is they appear to be everywhere. They may or may not be around folds.

Some of your retrieved implants had folds, permanent folds. Others did not. In most cases the cracks that you

associated with leakage were nowhere near the folds. There were a couple that were on the folds, but I don't know if this is just a statistical chance that that's where the crack and the fold happened to meet, but certainly you can have folds without leaks, and

certainly you could have cracks in areas without folds. So your tear testing was a cruder sense. The cracks that you identified in retrieval run the size of hundreds of microns, very small, sometimes even microscopic sizes, but your tear test is relatively gross when we take a big piece of material and you just try to pull it apart. So I'm not quite sure of the relevance of this more macroscopic tear test to the crack initiation NEAL R. GROSS
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or propagation that you've identified as failure modes in the retrieved implants. So, again, you've done a lot of tear

testing, but I actually have no idea how to relate that to the clinical situation, and you also tore it only in one direction, and multi-directional tears and then assessments of you might have survived the tear test, but I didn't see you look at the samples as closely as you looked at the retrieved devices to see if, in fact, you created creases or cracks that may not have failed as a tear, but may have caused pinholes or whatever bit enough to cause a leakage. I'm almost done. Bear with me.

The next to the last item is this issue of fold flaw. I think it's certainly a reasonable

hypothesis that somehow that these permanent folds that end up in this device are somehow related to the

failure, but it's an interesting thing. If you take a brand new implant and try to fold it and you just fold it in half and let it go, the fold doesn't stay there. It goes away, but just

because it's a piece of nice, resilient rubber, but in NEAL R. GROSS
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these retrieved devices, that fold line is often rigid and hard, which indicates either a chemical and/or That's

structural change in material along that fold.

why that fold is permanent as opposed to if you take a brand new implant, fold it up, do some kind of fatigue test. The chemistry and the structure of the two

folds, I believe, are completely different. So I'm not quite sure that the fold flaw tests, as difficult as they are to run, again, have a clinical relevance. And then an item that I didn't put much weight to until today's discussion is what for lack of a better term let me call reverse diffusion. It seems

as if somehow the inside of these bags get infected somehow and microorganisms find their way inside, and perhaps a mechanism for that is there's got to be a way for the bacteria to get into the device. One of the earlier speakers even suggested that the valve, in fact, might be two way in the sense that you can let liquid in as well as liquid out, but, again, I see none of your testing that addresses that. So in summary, I would say that the

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testing

you

have

done

actually

has

been

rather

extensive as far as the number of samples and effort that you've put in, but unfortunately hasn't really helped me answer the question at all, is that will this implant leak; how often will it leak; where will it leak; and there's this big mystery in my mind of the mechanism of why than the they implants do in fail the more in

reconstruction augmentation.

original

There's got to be a biomechanical reason. This is a mechanical failure, and you ought to be able to define how that happens and develop a test to

address that issue. So in the end of it all, I believe that the FDA is correct and I in saying should the that be the tests are and to

incomplete additionally

they think

completed, rate due

reoperation

inflation -- I find if I carry it over to the devices I normally work with are alarmingly high. To have a device fail in the two to three year period mechanically is extremely surprising, and it's also amazing to me that it seems to be tolerated NEAL R. GROSS
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as just something that you just have to live with in these implants, and I don't really see how the design and the materials change or the testing really

addresses that issue. Let me stop there. CHAIRMAN WHALEN: I should point Thank you, Dr. Li. out to all the panel

members, lead reviewers and the rest of the panel, that this is the appropriate juncture when, if there are any further questions for the sponsor or any specific

questions to the FDA presenters that these questions be raised. That being said, there were probably too numerous to count questions, but some of them were rhetorical. Some of them were comments, and some of

them were questions that perhaps an answer is needed, and so with that preface specifically for you, Dr. Li, among those questions you raise or any others that you have, would you like to direct any question

specifically to sponsor or FDA at this juncture? DR. LI: Let's see. Well, I guess I would

like to -- well, I'm not exactly sure because the NEAL R. GROSS
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question is kind of broad ended.

I'm struggling with

asking kind of a non -- all of my specific questions might be kind of trivial, and the big question I'm not sure we can get into. CHAIRMAN WHALEN: Well, there also will be

a closing summation, about ten minutes for each, the sponsor and the FDA, that we'll get to eventually where anything that has been raised during this discussion can be addressed, although no new data will be raised. DR. LI: then. MR. PURKAIT: (Inaudible.) Well, the point I was Let me ask one general question

CHAIRMAN WHALEN:

making is if I were to say to you right now could you answer each of his questions, we'd all have to get cots because it might take the night. DR. LI: question then. Do Well, let me ask you one general you believe that with all the

testing that you have provided that you can a priori determine what the leakage will be? Because you

clearly have some idea of things that you think are important, for instance, surgical placement, just to NEAL R. GROSS
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bring up another issue, where the size of the incision that you at least feel anecdotally are related to the performance of the device. Yet I was frustrated by that because you don't have a hard number, biomechanical data that says, you know, when you make the incision this small, the force goes up 30 percent and the stress goes up this high and this leads to this and this leads to that. I really kind of -I don't see that

particular sequential kind of argument that we normally apply device to a device have failure been in and every other medical to this

that

being

applied

particular device. So what makes you -- what gives you the confidence or the belief that if you change, for

instance, as an example, from PTC to Sytech or from something to partially textured, which you have not clinically proven; what leads you factually to believe, other than your personal belief, but in terms of data that would you believe that the leakage rate is going to be the same, smaller or bigger than your previous device? NEAL R. GROSS
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MR. PURKAIT: see. areas

I think -- let me go try to

You have about -- I don't know -- 15 different that you have questioned, which is quite

interesting because you get me going for the next two hours I probably can do that, but let me see if I could summarize and try to answer those, the simple question first and then go to the complex one. You asked a question about the differences between the sterilization of dry heat versus gamma. Right now we all do dry sterilization. about gamma is out right now. Now, the question was: why did you do the So one issue

gamma nd dry heat and how would one -DR. LI: answer the question. MR. PURKAIT: simple. DR. LI: It's in the application though, Okay. Good. So that was If it's out, you don't have to

as I understand it, right? MR. PURKAIT: The second question you had

about the PTC active versus -DR. LI: Just to clarify that, I raised

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the

issue

of and

that

particular up many

one

because in

it

was PMA

highlighted application. --

takes

pages

your

So you're now withdrawing that particular

MR. PURKAIT: manufacturer operation

No withdrawing. always have

You see any an optional

sterilization procedure because you cannot rely upon one particular type of sterilization. We do qualify

both dry heat and gamma sterilization, and as we have established the process, validation of the dry heat, we have converted all of the sterilization to dry heat. In case that there be a need in the future we probably will do gamma sterilization, but this is not a withdrawal of the gamma sterilization. DR. LI: Well if you're going to do it at

all, then I think you need to answer the questions. MR. PURKAIT: The gamma sterilization and

the dry heat sterilization, we have compared the data, and that has been submitted in the PMA, and if you look carefully in the PMA, you will see that the gamma sterilization does reduce to some extent the mechanical properties in comparison to dry heat. NEAL R. GROSS
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However, the range of the properties, what we see by the gamma, is far superior to the expected results that we believe we are going by, such as the ASTM standards. elongation, For example, if you have a 350 percent what we kind of maintain. Our

that's

product shows consistently over 350 percent elongation. You might question, well, what does this 350 percent elongation mean, you know. Remember in a

body when you put this thing in a cavity, we have a liquid elastomer which goes up to 700 percent

elasticity.

Now, here we are testing for 350 percent.

In a body probably under all loads we know that we can measure, this probably wouldn't extend more than 20 percent to 30 percent. So, you know, to look into the proper

perspective, the elastomer elasticity in this case is much superior or much more higher than is reported in the body. DR. LI: is my general Well, let me stop you here. I guess, with the This

problem,

testing.

First of all, the ASTM methods for those of you who aren't into ASTM methods are proposed standard ways of NEAL R. GROSS
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doing tests, and there's not an ASTM method yet that I've read that doesn't have a disclaimer in there that if you meet these standards, it has nothing to do with projected clinical performance. So if you followed the ASTM standard,

you're basically telling me you're following a standard test, but as the ASTM itself says, it's not performance related. And this is the general problem or concern I've got with all of your testing. MR. PURKAIT: DR. LI: I understand that.

It performs to some standard, but

I can't make the connection to the clinical case where maybe 19 percent are failing by leakage. suggest that. MR. PURKAIT: is not our Bible; that I agree with you. we follow ASTM, The ASTM therefore, Your tests

everything is good.

The ASTM is a standard that's

accepted across the country, across all product lines, all devices that exist. So we do follow their

standard. At the same time, we supplement many other NEAL R. GROSS
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tests to show that not only do we meet ASTM.

We also So

have other tests to show that we go beyond that.

ASTM is not the only study that we do to say that our product -DR. LI: I understand that, but at the end

of the day, you still have a 19-plus percent, up to a 19 or more percent leakage rate. MR. PURKAIT: Now you talk to my heart.

If you look at the in vitro versus in vivo situation, unfortunately we are at a loss to exactly simulate what happened in the body process in vitro. For example, you have seen in our data today that if somebody used Betadine, if somebody used different incision size, if somebody used a bilateral, if somebody used a different valve type, there are some clinical indications that will occur. A clinical

problem will occur that it cannot replicate every time in vitro. I'm not saying that we're not going to try for that. However, at this point in time we took into

consideration the best we can, and we continue to study that all the time. NEAL R. GROSS
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DR. LI: your best. What

I'm not saying that you didn't do I'm saying is that there's a

disconnect for me between the data you generated and the prediction of in vivo performance. I mean I'm not

disputing the hard work that you put into it or you sincerity in doing -MR. PURKAIT: on that. Well, I'm not going to argue

I'm trying to make the point that some of the

test conditions, what we have used, does have some real meaning behind it. That includes one of the areas you also have addressed the fact that our fold flaw or the leakage things -- let me address the leakage one. To understand the deflation or leakage in a body, we considered that there are three ways,

primarily three ways that it can fail:

rupture of the

shell, the valve failure, or maybe fold flaw, or maybe other reasons in the clinical. The testings, such rupture as in the the shell, static we try five the

fatigue,

rupture,

static impact, and so forth.

For the valve competence, We have

we have three different tests for valves. NEAL R. GROSS
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www.nealrgross.com

valve burst test.

We have valve special test.

We have

valve -- the flow properties test. For the fold flaw, we believe that the fold flaw test is very unpredictable because you cannot predict where and when, how the fold will be formed. That has a lot to do with how it has been implanted and how these devices have been put there. And the other question I think previously asked about, the special inferences in different

locations, initially all of these implants are folded and put inside the cavity and then has been placed and then been inflated. So the pressure generated there, whether you put it in submuscular or subglandular, is really determined by what location you're putting and,

regardless whatever the pressure is, we always test for the worst case condition. extreme conditions. We always test for the

So, therefore, we believe that

even if it is within the range, it will maintain the properties. DR. LI: Maybe one last -- I'll try to

make it a last response. NEAL R. GROSS
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If I were to take your data at completely face value, I think I would walk away with the I

impression that this device is near bulletproof.

mean you have to go in your testimony to rather extreme conditions to get rupture, fatigue. the fold flaw. Now, if I look at all of your tests, it actually looks extremely good, except for the -MR. PURKAIT: DR. LI: It is good. Nothing happens in

But you get 19 percent failure

rate, and over 40 percent of them are revised. MR. those -DR. number. MR. PURKAIT: If you break it down into LI: Which is an enormously high PURKAIT: But over 40 percent of

cosmetic versus non-cosmetic -DR. LI: Okay. So 20 percent. Take half.

MR. PURKAIT: DR. LI: years. right?

Okay.

It's still a high number in three

So that's the disconnect that I'm going after,

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I mean your data looks excellent, right? I mean if I just looked at your data in and of itself, I would say from a materials and design standpoint it looks excellent. data, you know, Okay? I'd In the absence of any clinical probably have a completely

different view, right? clinical --

But the problem is I do have a

CHAIRMAN WHALEN: for a moment -DR. LI: Yeah.

Just to focus upon this

CHAIRMAN WHALEN:

-- in the interest of

the flow of things, I don't think we're talking about mechanical testing per se anymore. We are talking

about a highly clinically significant issue. DR. LI: Well, I think they have to be

linked to be meaningful. CHAIRMAN WHALEN: to proceed to other Indeed, and we're going issues. I guess

clinical

refocusing, is there something specific that you would like to inquire about in terms of other mechanical testing that could have or should have been done? DR. LI: Well, I guess, for instance, why

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haven't you looked at the effect of percent fill on the results as an example? MR. PURKAIT: DR. LI: pick a test. whatever. MR. about -DR. LI: And then do an under fill -- do a PURKAIT: Let's say you mention How do you mean?

In other words, doing a fold --

Pick a dynamic test, fatigue, fold,

20 percent under filled, 20 percent over filled, and then -MR. PURKAIT: Well, we don't suggest

anybody to under fill.

In our label copy, we clearly

say, please, please, please don't. DR. LI: never happens? MR. PURKAIT: that's what is supposed I don't know, but we say not to happen. We can't That's So are you going to say that

control this.

We test in the nominal volume.

the way they come in there. You mentioned something. Just to clarify,

the 2600 model, 2400 model, they were failed about NEAL R. GROSS
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3,332 cycles, 16,118, those failures if you're looking back in the data was intentionally done to understand at what pressure and at what load that we can make a failure so that we can make a model. Those does not

show a premature failure of those materials or those devices. DR. LI: That wasn't clear in the

application then in that case. DR. CUNNINGHAM: If I could address your

under fill issue from a clinical point of view, there is a body of information within plastic surgery medical literature which I think would have almost all plastic surgeons feel very strongly that they should not under fill these devices because of the predilection for

possible folds, fold flaws. So I think most plastic surgeons know that there is a small range of fill which these devices are meant to perform within, and in fact, the way you determine what size implant you want to use is fairly precise because there are sizers which are connected with a tube and have the same footprint and dimensions as the implant which you place in, fill with saline NEAL R. GROSS
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until you reach the look or appearance that you think is appropriate for that patient and conforms with the discussions that you've had with that patient, and that gives you the amount of saline and allows you to choose which device to use. So that surgeons are able to choose within that narrow fill range exactly which device is

appropriate for the patient.

So I think in clinical

practice the real world is in this case perhaps more precise than the kind of range of testing that you might think we would have to do. DR. LI: Well, in their own literature, in

their PMA document, they said that -- I don't remember the exact phrase -- but that 20 percent over fill would be something that they would consider as an upper end of what might happen clinically. So at 20 percent over fill, why weren't things tested at 20 percent over fill if that's what they stated as an over fill potential level? MR. PURKAIT: I'm not sure I recall that,

but maybe you are referring to the SPECTRUM product where you can go for adjustment purposes as we allow in NEAL R. GROSS
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our particular product. DR. LI: Right. Yeah, that is okay for the

MR. PURKAIT:

SPECTRUM, not for the regular fixed volume one. DR. LI: I hate to harp Well, the other medical -- again, upon other medical devices, but

typically in these there's a zone where you want the surgeon to be or the physician to be in the

implantation of this device, but for reasons either by skill or by necessity, the person's anatomy or

something beyond the physician's control, they can't always hit that exact target, and they might have to do something, make a decision to go out of that extreme. It happens. Right? It happens. You know

you don't want it to happen. doesn't happen, but it happens.

Most of the time it Right?

And you're faced with a case here where you have a very high number of failures and an

alarmingly little analysis of those retrieved devices, right? And with the absence of that information of how

the device actually deflates, I don't really know how you can discount any possible mechanism. NEAL R. GROSS
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CHAIRMAN WHALEN: Li? DR. LI:

Any other questions, Dr.

I think I'm done. Will I have an opportunity to

DR. ALLEN: respond? CHAIRMAN

WHALEN:

Actually

at

the

summation period if you wish, yes, but no. And I'll get to your question in a moment. We're going to do the lead reviewers first and then we're going to go to general questions from the panel, but we're going to -- okay. the clinical study. DR. question one? CHAIRMAN WHALEN: question one yet. (Laughter.) DR. BURKHARDT: this? How do you want me to do Actually we've not done BURKHARDT: That was all just on Dr. Burkhardt is here for

Do you want me just to address question one? CHAIRMAN WHALEN: No, no, no. study review, This is not with

just

a

general

clinical

reference to any of the particular seven questions. NEAL R. GROSS
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DR. BURKHARDT:

Oh. An overview. Okay. My thoughts on the

CHAIRMAN WHALEN: DR. BURKHARDT:

clinical trial are, first, that -- my thoughts on this whole thing, I think is what you're driving at. CHAIRMAN WHALEN: DR. BURKHARDT: Yes, sir. The question of systemic

illness and second generation problems, the reports are experiential. We don't have any scientific data on

that, and what we have doesn't support it, and I think they have to be disregarded. What we have to worry about is local

complications, and I'm not enough of an engineer to understand what happened, why this incidence was as high as it was, but my understanding is that if you eliminate needle punctures, which are there, and valve failures, that the major problem here is fold flaw failure, and my understanding of that -- you correct me if I'm incorrect -- is that that occurs because of abrasion, internal abrasion at the end of a fold. In other words, it's not material fatigue. Am I correct about that? Because that's what I've been

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told. MR. PURKAIT: To some extent fold flaw,

that what we know of, we can speak for, could occur, could fail in at least three or four different ways. One of the mechanisms may be abrasion. The other would

be, as I mentioned, a localized stress concentration. It's a creep factor. If you have a two fold (phonetic) and some weight has been there for a long time, the material crimps, and that might give a pinhole, and it will fail. And the other probably would be a multiple fold that causes abrasion with different surfaces, and that might be a problem there. DR. BURKHARDT: Thank you.

But the underlying problem is that they're going to fold. If you take an oval, three dimensional

or round three dimensional thing with an oval crosssection and you stand it on its end, which is what we see in these patients when they stand up, for instance, they're going to get folds in them. The material is

not perfectly elastic, and there's no way that I know NEAL R. GROSS
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of that you can get around that. DR. LI: But, Dr. Burkhardt, perhaps to

clear it up, there's some pictures that were difficult to see in black and white, but the FDA gave me the color versions. These are ten retrieved devices that They did a very nice job

Mentor supplied a photograph. on these particular set of ten.

But if you look through these photographs of ten, the cracks which may have been the leak are delineated in black, and on Figure 6 there, you

actually see running across the horizon a white line that's a fold flaw, and you notice the two cracks that probably caused the leak are nowhere near it. And if you look at the ten all the way through, more often than not the cracks and the pin holes that they identified were nowhere near the fold. Now, in two cases, I think they were, but in the other eight they were not. So my point is this

generation of these small cracks is not mimicked in any of their testing that I've seen. DR. BURKHARDT: that are removed, right? Well, these are implants

And --

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DR. LI: DR.

For leakage. Yeah, for leakage, and

BURKHARDT:

what you're saying is that there's no permanent fold there that you can see now. DR. LI: Well, on Figure 6 there's kind of I

a ghostly white line that runs across the horizon. think it's Figure 6, the page I handed you. of them

Now, some

you'll see like a white line that goes across That white line is the permanent

a gray background.

fold, and the black lines that they've delineated are where the cracks and pin holes are, and you'll see that oftentimes, most times that white line -- and sometimes it runs in all different directions -- is nowhere near the black lines that they identify as the source of the crack or the leak. So in other words, this fold flaw thing still, after 30 years, may or may not be the reason these things leak based on the data that they've

supplied. DR. BURKHARDT: lines on here, but these Well, I see some big black were not cracks in the

implant.

Am I correct? NEAL R. GROSS

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DR. LI: all --

Yes.

Yes, the short ones are

DR. BURKHARDT:

Well, now let's find out

about that before we decide that. DR. CUNNINGHAM: picture -DR. BURKHARDT: lines in these pictures. DR. LI: short ones are cracks. You've got big, long black I'm not sure exactly what

Were those the cracks? The

The long ones are wear.

If you see a really long black

line -- and correct me if I'm wrong -- but if I know your nomenclature, there is some implants that have very long black lines in them. Other ones are Those are wear lines. short black lines.

very

The short black lines are cracks and holes. DR. BURKHARDT: don't understand the point. DR. LI: Well, the point is it is not so Okay, and so I guess I

simple as you would like to make it, that if there's a fold it's bad, and if there's no fold, it's good, right? Because some of those have fold -DR. BURKHARDT: Why not?

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DR. LI: there.

Because you've got the data right

If folds and leaks were directly associated,

the black line, the small black marks to indicate holes should be right on all of those ghostly white lines that are folds, and they are not. DR. BURKHARDT: I think I'm not

sophisticated enough to follow that line of reasoning. If the black lines are wear lines, which I would

interpret as being the convex lines of the wear -DR. LI: So, for instance, we're looking This line here, this off

at Figure 6 in your report.

white, that's a fold line as I understand it, and these two lines are where the cracks are. If the fold line was a source of cracks, these crack lines should be right on that line, and they are not. DR. BURKHARDT: The black lines are

described as wear lines, not cracks. DR. LI: to the wear lines." lines, right. DR. BURKHARDT: There's a red line for a "Location of cracks in relation Right. There's cracks and wear

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crack and black lines for the wear lines. DR. unless -CHAIRMAN please. DR. LI: I guess the problem on this one WHALEN: In the microphone, LI: The problem is on this one

is unless Mentor can say that the wear lines are not leak lines, I assume that when you had a wear line it may or may not be the source of a leak; is that

correct? So some of those wear lines may leak and some of those wear lines may not; is that correct? MR. PURKAIT: DR. LI: MR. That's correct.

Okay. But I'm not sure which

PURKAIT:

picture and what you are talking there because it's hard for me to really -DR. LI: I understand. I'm just trying to

fill in for Dr. Burkhardt how I was looking at those photos. DR. BURKHARDT: Okay. Where were we?

Nobody under fills these implants with any knowledge. NEAL R. GROSS
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You can't really legislate physician behavior, but -DR. LI: But you could design for it. Well, maybe you can design Maybe these could be

DR. BURKHARDT:

for it, and again, I don't know.

improved, and that's your jurisdiction more than mine. The leakage rate that is generally

reported from fold flaw failure is in the five to ten percent range, and I don't remember the slides that you showed that brought it up to 19 or why it got to be so high. Questions were raised about the texture to implant. I think it would be worthwhile for everybody

to know why these implants were textured and what gave rise to the origin of the textured implant because it didn't have anything to do with easy insertion through a small incision. A number of years ago a polyurethane

covered implant came out from another company that was called the MIM (phonetic). plastic surgery and short It was widely accepted in term had a very small Long Most

incidence of hardness or capsular contracture. term there's some question about what happened. NEAL R. GROSS
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www.nealrgross.com

of us think they all got hard. At that time the companies that were

producing the silicone implants, the silicone shell implants could not use a polyurethane covered implant because it was patented. So they had to try to do

something to compete economically with the success of the polyurethane covered implant, and the response was to texturize the surface of the silicone implant. Most of us who are in the field thought that that wouldn't accomplish anything at all, but

there have been a number of outcome studies now that show that for some reason that we do not understand that it was helpful. Another reason for the folding that I

think everybody needs to understand is that if you put this sort of flat device which is oval in cross-section in a pocket that then begins to contract and so that the device is now compressed into more of a sphere, it's going to fold, and I don't know any way that the manufacturer or anybody else can really prevent that. In regard to reverse diffusion, that was brought up today. There was no evidence that I could NEAL R. GROSS
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detect that I was aware of that it was a significant problem problem. If there is diffusion of that sort, it would be through the valve, but there's no reason to believe that's significant. Local complications. big problem, with and everybody Contracture is the understand a membrane what that and no evidence presented that it was a

should There's

happens

contracture.

forms around the implant and for some reason that we do not completely understand, the membrane contracts. It often happens unilaterally. It is not

a systemic response, and the most prevalent theory at the present time is that it is a low grade bacterial infection from the breast ducts, which may explain why we get better results in the retromuscular position, and it also explains the use of Betadine, which I think is one of the things that has surprised a lot of people here, because that wasn't brought up. And Betadine is

used in an attempt to sterilize the pocket. There are questions that have been brought up about the shelf life of saline. NEAL R. GROSS
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Saline per se, so

far as I understand it, has an indefinite shelf life. All it is is salt water, and I think that the

expiration date that has been presented here, it really refers to the container more than to the saline itself. Fungal growth in saline, I think most of us have seen that. The situation has changed a lot We used to

since those cases were initially presented. use an open tray to fill the implants.

In other words,

we would pour saline to an open tray on the Mayo stand, take the saline out with a syringe, and use it to fill the implant. care. I think what has happened is that there's airborne fungi, and they would get into the open tray and then be put into the implant. There's no reason to That was pretty much the standard of

believe that that contamination comes from the patient herself, and the method of filling now that so far as I know everyone uses is a closed method of filling from an IV bag with a three-way valve, a three-way stop cock to the syringe. that it once was. Rippling is going to occur, specially in NEAL R. GROSS
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So I don't think that that's the issue

the thin breast.

It's going to be seen.

There's no

way to get around that at the present time because the implants are going to ripple. The information we have in our literature suggests that sensory changes in the nipple and the areolar area are related not so much to the location of the incision as to the position that the implant is placed, whether it's behind the muscle or in front of the muscle, and I realize that that doesn't correspond with what was just presented here, but I think we need to be aware of that. Mammography may be made more difficult

without any question whether the implant is behind the muscle or whether it's behind the breast, but all of the studies we have fail to show any difference in the tumor stage when detected or in the long term survival. So so far as an outcome is concerned, it doesn't seem to be a major issue. That's mine. CHAIRMAN Burkhardt. Actually unless there's specific questions NEAL R. GROSS
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WHALEN:

Thank

you,

Dr.

that

we'll

raise

from

time

to

time,

you

needn't

necessarily reside at that table.

We'll just ask you

to come up to the podium if we do have a question to ask you. Thank you. For statistics, Dr. Blumenstein. DR. BLUMENSTEIN: Well, when I thought

about this, I found myself thinking of how I would respond if the information given to me were given to me as an article to be reviewed for publication in a peer review journal, and so a lot of what I'm going to say here has to do with holding the information to that standard, but there's also the standard of trying to be informative to the potential recipient of an implant. The theme of what I'm going to say has to do with the presentation of the data; do not take into account the censoring and, therefore, the conditional probabilistic aspect of what's going on in the

presentation of the data. clearer as we go along. The Cox

I'll make that a little bit

regression

analysis,

Cox

proportional hazard regression analysis looks like it's NEAL R. GROSS
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somewhat useful.

However, I would point out that that

would be very difficult for the consumer or physicians to understand. Also, for someone who wants to talk to me later, I would have some ideas about how time dependent covariance might be brought into that analysis in order to improve some of the precision of the analysis. However, I want to go on and talk about the data itself, that doing Cox proportional hazard regression on data that's kind of smelly might not be the best thing in the world. I want to talk about several methodologic issues that are more technical in nature, and the first thing I want to say is, of course, and as has been pointed out before, these studies are not randomized clinical trials. not to propose They don't come even close to that, that anybody could do a randomized

clinical trial, but just in terms of weighting the evidence we don't have that kind of evidence here. don't even have control groups, and so these We data

should be very carefully interpreted. Some of the plots that were presented and NEAL R. GROSS
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some of the language that was used tried to represent the individual risks as cumulative incidents. absolutely wrong. That's

They are not cumulative instances.

One minus a Kaplan-Meier curve is not a cumulative incidence curve. That is a cumulative conditional

probability curve.

I have some references if someone We must have these things

wants to look at them.

labeled correctly to the patient. I would suggest that you do look at real cumulative presenting incidence the risk methodology data and as a means of

those

same

references

would address that. The issue of interval censoring has been brought up before. I'm not sure what to do about that. I suspect it's a

That's a difficult problem here.

matter of simply pointing it out in the publication as a source of bias, as has been previously discussed. One of the very difficult issues that's here is that the confidence intervals that are

presented are confidence intervals that represent the experience of a group of patients and do not represent the uncertainty of the estimates that pertain to an NEAL R. GROSS
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individual patient's risk. exists everywhere wherever

This is a problem that risks are trying to be

presented. an answer

It's a difficult problem, and I don't have for it other than in certain specific

situations. Now, there's a number of data issues, and all of them are related to what I call informative censoring, and I think it's absolutely wrong that the data have been presented here without any analyses to show the characteristic, to try to characterize the patients who are not followed for specific time points. There is information that the types of

patients who are dropped out over time could be biasing the data significantly. You could be comparing

demographics.

You could be comparing whatever reasons You could be comparing

for dropout you might have.

baseline assessments in terms of some of the measures of quality of life or some of the mechanical

measurements and so forth. So essentially what I'm saying is you can compare the baseline data between patients who are

included in an analysis for a subsequent point in time NEAL R. GROSS
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to the patients who are not included. minimalist approach to trying to

It's just a very get a handle on

whether the data from patients who are not included in subsequent time points are different from the data that are there. This kind of informative censoring applies to the efficacy data, the quality of life data, and the risk data. study. Dr. Bandeen-Roche pointed out that It applies to everything in this kind of

especially in the quality of life data the patients who were explanted are not represented in the subsequent, the late time point analyses of these data. This is an

extreme limitation and misrepresents the data unless you point it out and very carefully document that

that's exactly what you're doing. It's wrong to represent that as being an unconditional quality of life assessment. The follow-up for the data here are just too short, and I will, I'm sure, talk about that later. In short, my take on all of this is that I cannot accept the accuracy of any of the data here because of NEAL R. GROSS
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the limitations that I'm pointing out.

It may be that

we do have some rough idea, some very crude idea of the relative size of these risks and ranking of the risks, but I cannot feel good about any of the data presented with respect to accuracy and giving that information to an individual patient and having that patient

understand what the real risks are. CHAIRMAN WHALEN: Thank you.

With apologies for twice having put you off, Ms. Domecus, if you have a question. MS. DOMECUS: I just want to go back to

Dr. Li's criticisms regarding the mechanical testing study design. As I understand it, it seemed like he

thought there was a disconnect between the laboratory testing study design and how that could mimic what was seen clinically, and I was just wondering if you had any suggestions on how those tests could be designed at this point or maybe later, but I think that might be helpful to the manufacturer since, as you suggest,

they've done an awful lot of testing, put a lot of effort in, and if it doesn't kind of hit the mark for you, if you had some suggestions, I thought that would NEAL R. GROSS
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be helpful. DR. LI: Well, I suppose I do, but it We'd have to sit down

probably would take a long time.

for a long time and work that out, but I think one suggestion that I could definitely make though is to continue the type of retrieval analysis that they've begun to do because I think that is going to be the proof in the pudding. In other words, in other devices that I work on, the whole purpose of our laboratory is to try to develop an in vitro test that where at the end of it it looks like the failed device, and the closer you can get to that, the better off you are in developing an apparatus or a test that would say, "Look. If I

improve the properties this way, I can measure it and it will be better or worse clinically than what I've got." So in the absence of knowing the exact mechanism for the failure, I'm not exactly sure what test to suggest. CHAIRMAN WHALEN: Did you also have a

question from earlier of the sponsor that -NEAL R. GROSS
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MS. DOMECUS:

It got answered. Thank you.

CHAIRMAN WHALEN:

Do any of the other panel members have any questions first of the sponsor before we go on to attempt to answer the FDA questions? DR. BURKHARDT: for the sponsor. When I have one more question these failures occur, Mr.

Purkait, don't they usually occur at the end of a fold? MR. PURKAIT: Sometimes they do. Sometimes?

DR. BURKHARDT: MR. PURKAIT:

Yes. But not consistently?

DR. BURKHARDT: MR. PURKAIT:

Not consistently. Thank you. Dr. Chang. Also, was there any

DR. BURKHARDT:

CHAIRMAN WHALEN: DR. CHANG:

relationship between thickness of the implant and sell failure? Was that ever measured or considered? There's a variability in the thickness of the models or range of thickness? MR. thickness for PURKAIT: the smooth Yeah, and the we have range which of is

SILTEX,

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textured.

We

have

information

that

shows

that

regardless, within the same model type, whether it's the smooth or SILTEX, within the same specification any of those tests show the same results. does not cause problem. DR. BOYKIN: while you're there? A comment in the summary, and I don't Could I ask one more question So thickness

think we've really talked about this, is that within one device there could be a variation of almost the entire thickness at the thinnest point of the shell, like from 17/1000 to 34 or 35/1000 of an inch; is that correct? MR. PURKAIT: DR. BOYKIN: That's correct. Now, this reflects the

inherent difficulty in fabrication of the device, that you can't control the tolerance of the limits any

closer than that? MR. exactly true. PURKAIT: To some extent that's

The way the shell works is that these

are all done by the dipping process, and if you take a particular viscous material and if you dip the mandrel, NEAL R. GROSS
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and if you turn it over, normally those things tend to drip down there. So you get a variable thickness from That's why you see the 14,000

the top to the bottom.

to 38,000 is the difference. But I just wanted to point out that most of our test data though we target for the area of the thinnest possible shell. CHAIRMAN WHALEN: DR. MORYKWAS: Dr. Morykwas. I just had a thing where

you commented on the white line on the implant is interesting, and if you could, with the repeated

folding have you analyzed any of those where the white line is for the induction of crystallization or crazing or anything in the polymer material itself that might change some accountable properties? MR. PURKAIT: those. thing I We did previously some of One that

We have looked into some of the explants. just want to bring to the attention

explant is very difficult because by the time we get the explant, this particular explant has been altered a few times because they go through sterilization; they go through the wash process; they go through various NEAL R. GROSS
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different handling procedures. Therefore, by the time we really actually do that, we probably have not seen everything that's coming out of the body. Nevertheless, we do try to

characterize as best as we can. To answer your questions, we did not see per se any creasing effect or super crystallization on those areas because of the stress there. CHAIRMAN WHALEN: Are there any Thank you. questions of any of the

panel members for any of the three FDA presenters? (No response.) CHAIRMAN WHALEN: Seeing none, we will

being to attempt to answer FDA's questions. Dr. Berkowitz, would it be possible to reproject those questions sequentially as we try to deal with them? And for -PARTICIPANT: (Inaudible.) You will have a comment

CHAIRMAN WHALEN: period, sir, shortly.

On many of these questions I will poll the NEAL R. GROSS
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entire panel.

On come I will be somewhat more focused,

and the first question which we see projected is one of these more focused ones that Dr. Li is our subject matter expert on, and we'll begin with him. DR. LI: Well, in general, I think the

fatigue testing and fold flaw testing are incomplete in that they either did not test all the models and/or did not test the final materials that ended up in the commercial device, the last issue being the reference to switch to the Sytech silicone from the original PTC, which is the bulk of their data. incomplete. The testing I do fatigue not testing and the any fold long flaw term So it is at best

believe

provide

information to us to the rupture and leakage of the implants. I think looking at their data, I would have

no way to predict when they switch, for instance, from the PTC to the Sytech whether or not the rupture So I and

leakage rate will be the same, better or worse. guess my comment on the sponsor's methodology

results is that the methodology, although it represents some construct testing -- oh, actually one important NEAL R. GROSS
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thing.

Correct me if I'm wrong, but most of your

fatigue and rupture data did not have the valve in the implant; is that correct? PARTICIPANT: DR. LI: Fine. So in general I think the methodology, We did have the valve. Okay.

They did have the valve.

although presents some device testing, I don't think any of it is reflective of what we could expect to happen in the patient. So I think what they've got

unfortunately is a little incomplete, and I don't know what to do with the information as far as projecting what the long term rupture and leakage of the implants will be. CHAIRMAN WHALEN: So in regard to our

first question on this testing, are there other members of the panel that would like to address that? Just to remind everyone on the panel and in the audience, the way this will proceed is that when the panel has attempted to answer the question, I will then attempt to summarize, although there was only one responder in this case, to Dr. Witten on behalf of the NEAL R. GROSS
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FDA what the panel's answer is, and then if Dr. Witten finds that a satisfactory answer, we'll proceed to the next question. Dr. Witten, in regard to question number one, it is the panel's opinion that at best we are given incomplete testing, and that specifically in

regard to fatigue and fold flaw testing, that while the methodology and the results were exposed to us, that there seems to be little or no correlation with the long term clinical actualities that are witnessed. Is that sufficient for your answer? DR. WITTEN: Yes. Thank you. Thank you.

CHAIRMAN WHALEN:

If we can go to question number two on the projection screen, this is one of the questions that I will ask that everyone comment upon the question, and this has to do with the issue for patients who are receiving the implants for augmentation. Given what has been presented to us by the sponsor, do we find in accord with the federal

regulations that the product is both safe and effective for augmentation patients? NEAL R. GROSS
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I will begin going around with Dr. Chang. DR. CHANG: Certainly the analysis

presented by Dr. Anderson gives credence to the fact that with respect to change in size and for some of the parameters of quality of life that the device is

effective for augmentation patients. I want to qualify my comments about safe, safe with qualifications, in that several of the

complications listed, and in fact, the high number of complications listed is not in the purview of the

manufacturer; that it is dependent on the practice of the physician. So it's a very qualified safe product.

And the remaining question in my mind is that 5.8 percent deflation/leakage rate. So augmentation; parameter that for are for safe, effectiveness, a qualified in the yes, yes, in given of

actually

control

physician, not the manufacturer. CHAIRMAN WHALEN: Dr. Morykwas. DR. WITTEN: Excuse me. Yes? Can I clarify Thank you.

before you go around the room?

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The way that 21 CFR 860.7, we're asking you actually about reasonable assurance of safety and effectiveness. effective. So it's not an absolute safe and

The definition is reasonable assurance of

safety and effectiveness. CHAIRMAN WHALEN: DR. MORYKWAS: Thank you. I would just like to also

agree that I think the product has been shown to be effective, and I will just somewhat parrot some of the conclusions of Dr. Chang, that several of, I think, the safety issues aren't really the responsibility of the device itself. who It are is more the it. physician So or the are

physicians

implanting

there

concerns there. And some of that, I guess, is out of our purview. I don't think we can legislate how the

surgeon will do that. But still with -- well, again, I'll get back to Dr. Li also -his comments that it is

relatively safe, yes, but still there is a high degree of deflation that doesn't seem to gibe with in vitro data. NEAL R. GROSS
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CHAIRMAN WHALEN: Ms. Dubler. MS. DUBLER: which is largely rates

Thank you.

I do think the effectiveness, by the response themselves, and is

measured of the

satisfaction

patients

impressive and provides reasonable assurance that it is effective. I'm troubled by the combination of factors that are either under the control of the manufacturer or part of the practice patterns of surgeons or, in the third place, part of the body's reaction to these

devices, and it's hard for me to sort them out. I'm legislative not sure I agree that we can't

how surgeons go.

I don't think we can

legislate it, but I think the notion of best practice is a very powerful one, and I think that if there are better ways to use these devices, that has to be very, very clear in how they're marketed and who uses them and under what conditions. But I am concerned about the 5.8 deflation rate and by the reported 43 percent complication rate and 73 percent complication rate in reconstructive

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patients.

I think that's very, very high, and the

combination of all of that makes we reluctant to say that we can provide reasonable assurance that, in fact, they're safe. CHAIRMAN WHALEN: DR. ROBINSON: Dr. Robinson?

I believe that the product

is effective, with the word "reasonably," "reasonably safe," I'm worried that no matter what type of ex vivo testing we suggest, there won't be a link between that testing and prediction of what happens clinically. So

we may be getting into a situation where we're looking at more and more ex vivo testing and still coming back and asking the question what does it mean clinically. But the use of the word "reasonably" is fine with me. It's reasonably safe. Thank you.

CHAIRMAN WHALEN: Ms. Brinkman. MS. BRINKMAN:

Well,

in

regard

to

effectiveness, obvious it's perceptual. that deflation can't be considered

It's true then effectiveness

because I would think if I had an implant and it deflated I would not think it was very effective. NEAL R. GROSS
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But anyhow, as far as safety goes, I think it's appalling that for there an elective is 43 procedure for

augmentation

that

percent,

first I

complication rate of 43 percent, and it continues. mean, it never levels off. It continues to grow.

And so I guess I feel negatively about the safety of the product, even though I know that there are many women who want them, and I think the

manufacturer does what they can. CHAIRMAN WHALEN: MS. DOMECUS: clearly been shown. adverse I Ms. Domecus.

I think effectiveness has guess when I they look at the look

individual

event

rates

all

reasonable, but the 43 percent number does seem high, especially for a cosmetic indication, and in my

experience I don't know that I've ever seen a medically indicated product have that high of a complication rate and have it be a favorable risk-benefit ratio. would be concerning to me. CHAIRMAN WHALEN: DR. LI: I Dr. Li. with everyone on the So that

agree

effectiveness of the implant. NEAL R. GROSS
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I think the reasonably safe part, I think, would come down to whether or not you believe 5.8 material or design failure of the device is a

reasonable level. short length of

I think for my own purposes, for the time these devices were followed,

that's an alarmingly high what I'll characterize as the design and material failure, and although the surgeon may have a large input on this, and I never intend to legislative surgical behavior and skill, I think part of what we are able to do is either to design or test for the variations that one would expect a physician to apply in the implantation of this device, and I don't believe that particular range of possible surgical

procedures has been explored. So I would say although I would say it's effective, I would have to come that it was

unreasonable for safeness. CHAIRMAN WHALEN: Dr. Blumenstein. DR. BLUMENSTEIN: that there's some efficacy I agree that it appears here in terms of the Thank you.

intended purpose of augmentation. NEAL R. GROSS
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I think the safety

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issue is largely dependent on how well the risks could be communicated to the potential recipient of one of these implants. And I think accuracy has part of that, and so forth. I think the best overall representation to

the potential recipient is the time to first bad thing, which has been already characterized here as being the best measure. CHAIRMAN WHALEN: DR. BOYKIN: Dr. Boykin.

I would agree that we have

evidence that the device is effective, and I would like to underscore the comments concerning the environment that this whole process is taking place in. This procedure, dynamic and operation it is that is an invasive with an surgical

associated occurs

inherently static,

process

around

this

inanimate object, and this is also affected by the patient's own chemistry in terms of how they heal, the drugs they're taking, whether or not they smoke

cigarettes, where they live, and how they live their lives. These are generally considered the

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surgeon's

complications,

if

you

will,

and

not

necessarily the device's. We've seen a disparity between the

mechanical testing and the clinical evidence of failure which to me just basically means we need to go back and redesign some tests. Overall, however, I believe what we can say about the safety is that we understand probably better than ever before what these factors are, what the patient will be faced with, but that to a fairly great degree, I believe that a lot of these

complications are away from the domain of the device itself, and I think that it is reasonably safe. CHAIRMAN WHALEN: Thank you.

Dr. Bandeen-Roche. DR. BANDEEN-ROCHE: Let me just first say

this is an appropriate time for me to read into the record that I'm not a regular member of this panel, that I was asked to serve on this panel because I'm very highly qualified to evaluate the strength of

epidemiologic evidence and had a substantial experience with self-reported health function and quality of life NEAL R. GROSS
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data, but not because I have particular specialty in plastic surgery or implants. That having been said, in terms of safety, my reading of the epidemiologic evidence in its total is that the devices are reasonably safe, if safety is defined as a very hazardous event, such as death,

systemic diseases, that sort of thing. In terms of effectiveness, I believe that the device has been shown to satisfy rather narrow definition of effectiveness, that is, increasing of bust size, some evidence of increase in body image. I

did not find any strong evidence for increases in selfesteem. Quality of life was not really assessed, and I agree with Ms. Brinkman in that in my mind efficacy also has to do with complications, you know, reoperations, cosmetic complications that occur at a high enough rate that I don't feel that I can give a blanket reasonable of a assurance desired in terms and, of high

probability

outcome

therefore,

effectiveness. CHAIRMAN WHALEN: Dr. Burkhardt.

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DR. BURKHARDT:

I believe the safety in It always comes with

surgery is always qualified.

qualifications, and this particular operation is no exception. My comments about physician behavior and the probability of being able to change that through the mechanism of this particular agency are perhaps colored by my knowledge of how training works and the fact, and probably most people are unaware of this. Once you are licensed in a state as a

physician, you are legally entitled to do any operation that you can do, provided you do it in your own

environment, in your office or whatever.

There are no

restrictions legally regarding what any physician may do with any particular patient, and we're in a

situation now where we're seeing more and more of this with people who are not plastic surgeons or who define themselves as plastic surgeons but don't meet the usual qualifications are doing this kind of surgery. And all I'm saying is that that's going to be very difficult to control through this agency or by any action of this committee. NEAL R. GROSS
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I believe that the -CHAIRMAN Burkhardt. WHALEN: Excuse me, Dr.

Dr. Witten was just addressing this. DR. WITTEN: Yeah, I think we want to

focus on for this product. DR. BURKHARDT: I understand that. I

understand that, but that was brought up, and I felt that I should respond to it. I think that so far as I can see these have been proven to be effective, and I think they're reasonably safe. CHAIRMAN WHALEN: Dr. Witten, in Thank you. regards to patients

receiving this device for augmentation purposes, in attempting to answer whether or not we the panel deem it to be reasonably safe and effective, I believe there is near unanimous opinion that it is effective within the important constraints of defining effectiveness as we have viewed it today, but there is less than

consensus on the issue of safety inasmuch as nearly everyone on the panel is significantly troubled by the complication rates that have been reported by the

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sponsor, but there are various interpretations upon the significance of those complication rates inasmuch as they relate to the definition of safety. Does that answer your question? DR. WITTEN: Yes. Thank you. We go on to the third with the same issues of

CHAIRMAN WHALEN: question which has to do

reasonable safety and effectiveness, but this time as regards those patients who receive this implant for reconstructive purposes, and we'll skip over and begin with Dr. Morykwas. DR. MORYKWAS: Well, again, I think that

we can or at least in my opinion the device has proved to be effective, the and then coming rate to the issue of

safety,

complication

does

increase

significantly for this patient population, but some of that is to be expected just due to the nature of the patient and their systemic conditions which has caused them to need to be reconstructed. But I would believe that this device would be reasonably safe even with the higher complication rate. NEAL R. GROSS
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CHAIRMAN WHALEN: And I would

Thank you. interject before Ms.

just

Dubler gives us her answer everything that was said the last time was insightful and important, and I'm not reflecting upon anything anybody said, but if you just simply agree with what you said the last time, it's perfectly acceptable to say, "I feel the same as I did last time." Sorry. MS. DUBLER: Actually I think there's

another factor when reconstruction is at play, and for me, as I think the choice for a woman is different under those circumstances, I would wonder what her

options would be. options for the

In other words, if all of the prosthetic devices have the same

complication rate, I might still say that for a woman facing reconstruction that that might be safe enough under those circumstances. Aside before. CHAIRMAN WHALEN: Dr. Robinson. NEAL R. GROSS
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form

that,

I

ditto

what

I

said

Thank you.

DR. ROBINSON:

Ditto what I said before. I may have started a

CHAIRMAN WHALEN: trend. Ms. Brinkman. MS. BRINKMAN: ditto. I devastating think this

Unfortunately I cannot do a

becomes

even

a

much we

more just

issue

for

me.

Unfortunately

haven't studied a large enough number of patients for me to agree that it's safe and effective. CHAIRMAN WHALEN: Ms. Domecus. MS. DOMECUS: Again, going back to the Thank you.

risk-benefit ratio, I would feel comfortable saying that for this indication that safety and effectiveness have reasonably been shown. Even though the risks are

higher, I think there's a unique benefit here, and the risk-benefit ratio, I think, is favorable for this

patient population. CHAIRMAN WHALEN: Dr. Li. DR. LI: Same answer as before. NEAL R. GROSS
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Thank you.

CHAIRMAN WHALEN: Dr. Blumenstein. DR. BLUMENSTEIN: one qualification on the

Thank you.

I would like to put just answer here. It really

applies to what I said before as well as this, and that is that I want to make sure that the characterization of effectiveness provides adequate data on quality of life benefits appropriately analyzed, and so forth. CHAIRMAN WHALEN: Dr. Boykin. DR. BOYKIN: No change. Thank you. My comments on safety Thank you.

CHAIRMAN WHALEN:

DR. BANDEEN-ROCHE: and complications are unchanged. With think it's regard a this to more case. the

quality

of

life,

I of

even in

narrow No

definition that

effectiveness

evidence

the

implant affected quality of life and not just recovery from surgery, other than anecdotal evidence. Thank you. CHAIRMAN WHALEN: DR. BURKHARDT: Dr. Burkhardt. Effective and reasonably

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safe. CHAIRMAN WHALEN: Dr. Chang. DR. CHANG: Effective and reasonably safe. Thank you. regards to patients as who Thank you.

CHAIRMAN WHALEN: Dr. receive this Witten, in

device and

for

reconstruction generally

regards same

reasonably

safe

effective,

the

opinion that was voiced to you in the prior question is reflected with perhaps two important exceptions, and that is that the effectiveness as regards the frame of reference of indications is different in this

particular subset of patients by virtue of what options the patients may have, and that the single subject matter expert with the best expertise as regards

quality of life type of data feels that that has not been sufficiently answered by the sponsor's

presentation. Does that answer your question? DR. WITTEN: Yes. Thank you. Thank you. With

CHAIRMAN WHALEN:

We proceed to question number four. NEAL R. GROSS
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the exception of the one year follow-up data in the implants sponsor and has the not FBS study, FDA asserts and that the

collected

safety

effectiveness

information for the cohort of revision patients, and yet the sponsor is proposing revision as an indication for use. Since this is about 30 percent of patients who present for this operation, we are asked to discuss whether sufficient safety and effectiveness data, to include revision, as in a mentioned stated indication and whether the sponsor should evaluate the safety and effectiveness for revision patients as a condition of approval. Please also comment on the information that

would be useful to collect in a post approval study. Ms. Dubler. MS. DUBLER: I find this a very hard

question because it builds on the uncertainties of the two that preceded it. Given my lack of comfort with

the first three questions, I would request that the sponsor fashion, investigate although revision beyond in my a more detailed to make

it's

capacity

specific suggestions. NEAL R. GROSS
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But

I

think

before

they

could

include

revision, they would need to collect more data and be very certain what their measures were. CHAIRMAN WHALEN: Dr. Robinson. DR. ROBINSON: Since I believe it's a Thank you.

reasonably effective device, I think revision should continue as an indication and perhaps some discussion could be on a post approval continuing to collect data in this particular group of patients. CHAIRMAN WHALEN: Ms. Brinkman. MS. BRINKMAN: safety and follow-up data. CHAIRMAN WHALEN: MS. DOMECUS: Ms. Domecus. Again, is revision here I believe there's a lack of Thank you.

meaning revision for any reason, not just for cosmetic reasons? CHAIRMAN WHALEN: Well, inasmuch as we're

really sort of focusing it upon a labeling application here and since the word revision is there and not necessarily with qualification. NEAL R. GROSS
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MS. DOMECUS:

I would think we wouldn't

want to preclude patients from undergoing a revision procedure if they wanted to, especially if they're

doing it for a complication.

So even if there isn't as

much data as we'd like to see in it, I think that it should be part of the approval, where many issues can be done post approval. CHAIRMAN WHALEN: Witten order. if a If little we Maybe I would ask Dr. here would be in the

clarification mention

don't

revision

in

indications, that would not in and of itself preclude a patient receiving this device for revision. it would more focus what the standard However, set of

indications for using this device would be. correct in saying that? DR. WITTEN: That's correct. Dr. Li. with that

Am I

CHAIRMAN WHALEN: DR. LI: Yeah,

clarification

I'll say there's not enough information to accept it for safety as revision. The thing that sets me off a

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the deflation rate is so much higher, and now we have a revision series in which we have no information hardly at all. It's unclear how you would predict what that would be. follow-up. CHAIRMAN WHALEN: Dr. Blumenstein. DR. BLUMENSTEIN: Well, I feel like that Thank you. So I think I would definitely ask for a

the patients who are undergoing revision will be a lot more informed than the patients who are undergoing

their first implantation.

And so with that condition,

I feel that there's a little bit less of a concern about informing patients, although other things can happen besides what happened the first time. So I feel that more data need to be

collected, but I would go along with the indication. CHAIRMAN WHALEN: Dr. Boykin. DR. BOYKIN: I believe clinically speaking Thank you.

this indication really falls in between the two areas that we've looked at. It should, I believe, at least

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from my experience, be considered a continuum of the spectrum. While there is relative paucity of data, I believe that this could be continued as a post approval study and that the complications that have been

investigated should continue to be documented. CHAIRMAN WHALEN: Thank you.

Dr. Bandeen-Roche. DR. BANDEEN-ROCHE: While I agree that the

data collection needs to continue hopefully along many of the same parameters that have already been

collected, it is very conceivable to me that medical and biological to and approve mechanical this for analogy revision would if be

sufficient

we're

approving it for the other things, and I would defer to the other subject area experts on that. CHAIRMAN WHALEN: DR. BURKHARDT: Dr. Burkhardt. That's such a fuzzy

question I still can't understand it.

I cannot imagine

a situation in which you would have a patient who has had a safety and effective implantation primarily,

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the first time, but not for the second time." And I can't imagine that an implant that would be judged safe and effective for an initial

procedure would not be judged safe and effective for a revision procedure, and I believe it should be included as safe and effective. CHAIRMAN WHALEN: Dr. Chang. DR. CHANG: I'll be consistent and leave Thank you.

it on as an indication and ask for post marketing study, follow-up. CHAIRMAN WHALEN: Dr. Morykwas. DR. MORYKWAS: I'll also agree that it Thank you.

should be approved with post market approval because you also could run into the situation where a woman with bilateral implants has a unilateral explantation and then couldn't be revised, and that's a peculiar conundrum that would be in there. So I would recommend a yes. CHAIRMAN WHALEN: Thank you.

Dr. Witten, there is not a unanimity of NEAL R. GROSS
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opinion on this particular subject.

However, it is, I

think, the clear preponderance of the panel's opinion that there should be a directive for further data to be collected upon this issue of patients who receive this device for revision. On whether or not this should be a part of the labeling, there is pretty much a division 50-50 of opinion on this particular topic. DR. WITTEN: Thank you. Thank you. number five, this is

CHAIRMAN WHALEN: Going to

question

sort of a side point of what we were talking about a little bit earlier in terms of the complications, but it focuses upon long term adverse events, and I would ask that those in responding address the three lettered subpoints of question number five, and we, I believe, start with Dr. Robinson. DR. ROBINSON: The increasing rates per

year for a device, I mean, devices over time have increasing rates of complications, I think, for most. So I'm not too surprised there are increasing rates. The minimal duration of follow-up to look NEAL R. GROSS
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at

them,

I

think

I

would

have

to

defer

to

the

statisticians.

I'm not sure I have even a gut feeling

for what that should be in terms of a number. The type of visit, I'd have to ask for some clarification. Active versus passive, what

exactly is meant by that? Pardon? DR. from us or -DR. ROBINSON: DR. WITTEN: Yeah, please. Yeah, meaning does the WITTEN: Do you want clarification

patient come in for, you know, to be seen. postcard follow-up?

Is it a

Is it a visit with the physician? So active would be they're

DR. ROBINSON: physically present. DR. WITTEN: mechanism? You know,

Yeah. there's

In other words, what a range of ways of

getting information from follow-up. DR. ROBINSON: If you're going to continue

to do long term follow-up, you should od it in a serious manner, and it should be active. And which types of complication should be NEAL R. GROSS
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addressed? complications

They like

should

be

serious tissue

complications, diseases, and

connective

things like that that I think have been laid to rest by multiple studies should not be included on these

serious complications. CHAIRMAN WHALEN: Ms. Brinkman. MS. BRINKMAN: Well, I believe that the Thank you.

FDA in '95 asked for a minimum of ten years for patient follow-up, at least for deflation, and so certainly a minimum of ten years, although I am not a statistician. So that's my only off the top of my head, non-expert opinion. Certainly an active visit would be

preferred, but I'm not sure I believe that's realistic, and so in light of not being able to get that, then some sort of at least survey or by mail thing or the best that someone can get. Obviously capsular contraction, what types of complications, breast

infection,

deflation,

nipple sensation, leakage, rupture, reoperation, the whole list of complications that we've discussed to NEAL R. GROSS
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this point. CHAIRMAN WHALEN: Ms. Domecus. MS. DOMECUS: Again, I'm not sure if this Thank you.

question refers to preapproval or just any data that's there. CHAIRMAN WHALEN: Actually you can phrase

your answer in whichever way you desire. MS. DOMECUS: From a preapproval

standpoint I think the sponsor has more than met the typical standards for what would be required prior to FDA approval. So that any of this data I think should

be a post approval setting. The ten year stipulation that's already So I

present, I think, is very stringent already. think that should not be extended. Active or passive? I think

either

is

probably a fine way to collect the data.

In terms of

wish complications, I think all complications should be followed for the duration of the study. CHAIRMAN WHALEN: Dr. Li. NEAL R. GROSS
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Thank you.

DR. LI:

I guess I would leave, again, the

minimal follow-up to the statisticians, although the, again, short term performance of these things as far as deflation goes, to me I still consider to be quite high, but I certainly would like to follow that up for a little longer, at least the ten year suggested FDA. I'd like the follow-up to be active. I

think if we could include perhaps so that it would be a little easier to ascertain after the fact if there is a deflation or some mechanical failure that there would be some easy way to ascertain the model, the

sterilization method, or the details of that particular device, and then we could answer the question is there a material and design correlation or is there not with this, and try to answer that question once and for all. And maybe this is outside the purview of a survey, but I certainly would encourage either the

companies or some academic institution to embark on what other implant devices do and have retrieval

collections and analysis because I think in the absence of that we're never going to get to the actual factual answer that will make us all happy. NEAL R. GROSS
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CHAIRMAN WHALEN:

The drum roll for the

first of our statisticians, Dr. Blumenstein. (Laughter.) DR. here. BLUMENSTEIN: So I've been set up

I have to say the number of years, huh? I think a long term follow-up,

No way. active

follow-up would be very useful here for the reasons just cited, and in particular to address this issue of informative censoring, you need to know why patients are not coming back for their follow-up visits and whether that has something related to do with failures or particular types of failures. So I think that an active long term

follow-up study until that Kaplan-Meier curve starts to flatten out a little bit. CHAIRMAN WHALEN: Dr. Boykin. DR. BOYKIN: I believe the ten year period Thank you.

is a reasonable minimum requirement, and that if at all possible, if at all reasonably possible, the patient should be enrolled in an active follow-up phase and that the complications that we have looked at, capsular NEAL R. GROSS
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contracture,

infections,

asymmetry,

breast

feeding

complications, nipple sensation, recent review of the mammography I think would also be important and maybe review of the trauma and illnesses that have occurred while the patients had the implants as well. CHAIRMAN WHALEN: Thank you.

Another statistical opinion, Dr. BandeenRoche. DR. BANDEEN-ROCHE: Well, I would like to

punt a little bit and say that in my opinion statistics can't answer the question about duration if this is If it were then

more than establishing the precision.

we could determine number of events and do a power calculation, but it's a matter of establishing the

natural history of the device.

So that's medicine and

lots of things other than the statistics. That having been said, I agree with Dr. Blumenstein's recommendation. CHAIRMAN WHALEN: Dr. Burkhardt. DR. BURKHARDT: I think that the present Thank you.

study has an adequate follow-up and adequate follow-up NEAL R. GROSS
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for pre-market approval. be nice to get a ten

I would agree that it might year active follow-up, but

pragmatically it's not going to happen, and you will be very lucky if you get a ten year passive follow-up on a significant percentage of these patients. This is a highly mobile population, and unless you have data like they do in Canada where you can trace these people by their Social Security numbers or whatever, you're not going to get them back for follow-up for ten years. CHAIRMAN WHALEN: DR. CHANG: I Dr. Chang. would agree with Dr.

Burkhardt's comments that it would be important to get data regarding deflation rates, but it is not practical to expect an active follow-up, and we should not not get the data and record it because of someone having a passive -- passively giving us this information. CHAIRMAN WHALEN: Dr. Morykwas. DR. MORYKWAS: I'll just also agree that I Thank you.

think in the real world a ten year active follow-up is not possible and even passive follow-up in the last NEAL R. GROSS
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five years from years six to ten is doubtful, but I would agree with the other -with (c) for all

complications. CHAIRMAN WHALEN: Ms. Dubler. MS. DUBLER: for ten years. Ideally an active follow-up Thank you.

If that isn't possible, a passive

follow-up for ten years, and in any event, I think we should track as many complications as we can in that period of time, and with a special focus on the leakage and deflation. CHAIRMAN WHALEN: Dr. Witten, the Thank you. panel in attempting to

answer these questions feels that with the consensus, the ideal follow-up should be active and ten yearsplus, which is really in line with what FDA has already required and/or suggested, but an asterisk perhaps on that should be that some seasoned cynicism or realism, depending upon how you want to put it, thinks that that may or may not be achievable. And that finally, in terms of

complications, clearly all of those complications that NEAL R. GROSS
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we

have

rather

extensively

discussed

already

today

should be tracked inasmuch as they have not plateaued over the period of observation, and any and all other serious complications should be as well. Does that answer the question? DR. WITTEN: Thank you. Thank you.

CHAIRMAN WHALEN:

Going to question number six, in regard to design of the study of the sponsor in providing

information on certain long term issues, we are asked to comment, and I would specifically point out that this is as a condition of approval, although if there is some further editorialization that any of the panel wish to make about post approval, then please do so. And those three issues, as you see posted and before you, have to do with interference of the ability of screening mammography to detect tumors when implants are present, interference with lactation and effects of offspring from women with implants. And I believe, Ms. Brinkman, you're up. MS. BRINKMAN: going to take good I think these issues are and information.

education

NEAL R. GROSS
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Certainly that physicians, radiology techs, mammography techs, and patients need to know the importance of good clinical breast exams, that when compression techniques are available, MRIs aren't practical; that according to Dr. Berg, that we're going to see double in radiation costs and doubles in radiation doses; that people need to know where the placement of the implants are and how that affects the mammogram; that implants viewing can may hide be

breast

tissue;

that

certainly

the

limited by contractures and difficult to visualize. And I think all of those issues need to be made available in provider patient information and

education. CHAIRMAN though, should there WHALEN: be anything Just in follow-up as a

specifically

condition of approval or prior to approval in any of those things that you feel needs to be done? MS. included labeling. CHAIRMAN WHALEN: MS. BRINKMAN: Okay. Thank you. in our BRINKMAN: information Other and than those in are the

education

Are we going to address

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lactation or are we going to just do these one at a time? CHAIRMAN WHALEN: address all three. MS. BRINKMAN: Okay. The same for All three. Yes, please

lactation, that the ability to nurse a child may be certainly affected by having an implant, and the

effects on offspring from women with implants, I don't know that there's any data out there that says that it affects babies born of mothers that had implants. CHAIRMAN WHALEN: Ms. Domecus. MS. DOMECUS: I'm not sure that I'm Thank you.

qualified to design the studies to address these, but I did have a couple of comments. I think question number one about this

interference with mammography, I think that it was Dr. Berg presented data on that. probably been sufficiently So I think that that's addressed, and that the

sponsor shouldn't have to do that post approval. The IOM report addresses interference with lactation and addresses that positively. NEAL R. GROSS
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So that seems

like

an

issue

that

doesn't

need

to

be

further

addressed. The only comment that I'd make on that though is that one of the presenters in the open public section this morning talked about how it could actually reduce the amount of milk even if it didn't put

contamination into the milk, and that's something that maybe a nursing mother, if she didn't ever use a breast pump, would not be aware of. The baby could not be

gaining weight, and you could have some, you know, failure to thrive issues. So maybe I think it's an informed consent issue that nursing mothers need to realize their milk volume may be less if, in fact, the presenter earlier this morning was factual in his statements. And as far as effects on offspring from women with implants, the IOM suggests that that is something that should be further studied. CHAIRMAN WHALEN: Dr. Li. DR. LI: colleagues on this. NEAL R. GROSS
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Thank you.

I'll defer to my more learned

CHAIRMAN WHALEN: Dr. Blumenstein. DR. BLUMENSTEIN:

Thank you.

I've been waiting for a

place to say this all day, and I've finally figured it out. I think that these are very important issues and

are very difficult issues to address in any kind of study or surveillance system. Just as an idea, maybe insurance providers or managed care might have data that would be

obtainable that would address these issues, and I would encourage the FDA and the sponsor to investigate those as possible sources of data addressing these issues. CHAIRMAN WHALEN: Dr. Boykin. DR. BOYKIN: I agree that it would be Thank you.

important to continue to collect information. the IOM studies, study, rather, has given

I think us some

comfort at least in terms of the problems related to mammography and the interference with lactation. And process could I be think that by an the informed consent and

developed

manufacturer

perhaps reviewed by the FDA as a way to take care of NEAL R. GROSS
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this. CHAIRMAN WHALEN: Thank you.

Dr. Bandeen-Roche. DR. BANDEEN-ROCHE: the current study is well I don't believe that designed to rigorously

investigate any of these issues.

I certainly support You know about

collecting data in long term follow-up.

events that occur, but I would not say that further rigorous investigation is a condition for approval. CHAIRMAN WHALEN: DR. BURKHARDT: Dr. Burkhardt. I believe that we have all

the information we need for pre-market approval. CHAIRMAN WHALEN: Dr. Chang. DR. CHANG: study is required I don't believe any further these questions before Thank you.

regarding

approval. CHAIRMAN WHALEN: Dr. Morykwas. DR. MORYKWAS: I also don't believe any Thank you.

other information is required. CHAIRMAN WHALEN: Ms. Dubler.

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MS. DUBLER:

I don't think the information

is required before approval, were all other problems solved, but I think these three areas should be flagged to women as areas of some complexity and uncertainty, and that long term follow-up studies should be

encouraged. CHAIRMAN WHALEN: Dr. Robinson. DR. ROBINSON: As I understand the Thank you.

question, the sponsor to evaluate these issues as a condition of approval, so the answer to two and three would be, no, we have adequate data on that. should not be a condition of approval. One, no, it should not be a condition of approval, but somewhere the panel will have to address the fact that some patients in rare instances will need additional imaging studies, and we should address that if for nothing more to give patients leverage on their payers to support those studies. CHAIRMAN WHALEN: Dr. Witten, in Thank you. regards to the three That

questions, the panel does not collectively feel that NEAL R. GROSS
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any of these issues would need to be evaluated by the sponsor prior to consideration of approval of their application, but nevertheless, I believe there is a preponderance of concern about several of the issues, and specifically mostly centered upon that of the

possible interference with mammography, and that this should be something that would need to be studied in the future. Does that answer the question? DR. WITTEN: Yes, thank you. Thank you. number seven, and

CHAIRMAN WHALEN: And finally,

question

this, I believe, is the other one that we can be a little bit less formal about going around the table, has to do with heterogeneity of surgical practice and recommendations for what issues should be included in physician training vis-a-vis this particular device and its implantation. Does anyone wish to comment upon that? Ms. Dubler. MS. DUBLER: I'm impressed by some of the

discussion of the importance of surgical technique in NEAL R. GROSS
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these sorts of surgeries, and I'm also impressed by the fact that this is a growing field, and cosmetic surgery is now described as one of those fields outside of the restrictions of managed care, and therefore, lots of people are finding it attractive, and that makes me very anxious about some of the people who will be engaged in these surgeries. And, therefore, I would expand this topic not only to address surgical training, but to also address potential patients and tell them to be aware of the fact that surgical training varies in these areas, and it's one of the discussions they ought to have with a prospective provider. CHAIRMAN WHALEN: MS. DOMECUS: Ms. Domecus.

I guess as a follow-on to

that, I think that physician training should not just involve the surgical techniques and information about the device, but apparently information about the

informed consent process. This morning session, that was the most alarming part of all that to me, was how many of these patients didn't feel like they got adequate information NEAL R. GROSS
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or any information on the risks and benefits to make an informed decision, and so I think that the sponsor could go a long way in helping its physician customers understand what an adequate informed consent process looks like. CHAIRMAN WHALEN: Dr. Witten, in an

attempt to answer this question and perhaps even taking the purview of the chair and editorializing a little bit myself as a Program Director in general surgery, I think there is concern about what practitioners do, and there is concern about both physician training and how much the public who is interacting with these

physicians knows about such issues, but I would add myself that I don't know that there's anything that we can impose upon this or any other sponsor which is going to be a requirement vis-a-vis that particular aspect of the training. Does that answer the question? DR. WITTEN: Well, I do have one follow-on

question, and just to see if anyone has anything to add, which is have we learned anything from the study and the information the sponsors provided that leads us NEAL R. GROSS
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or leads you all to recommending anything specific in the label regarding surgical practices and post

operative management with this particular product based on the information that was provided from the studies. CHAIRMAN WHALEN: DR. BURKHARDT: Dr. Burkhardt? The information provided

in the studies shows that you can't push one of these things through a small hole without maybe injuring it, and I would think that it would be reasonable to

suggest to the FDA that they advise against insertion through a long, small tube by way of the umbilicus. DR. WITTEN: DR. CHANG: Thank you. And I think that this issue of

Betadine perhaps changing the integrity of the device, and particularly the length of incision, may be added in the labeling. DR. issue? CHAIRMAN WHALEN: DR. BURKHARDT: Dr. Burkhardt. The two major problems we There is BURKHARDT: Could I speak to that

have are deflation and capsular contraction.

new evidence that is presented here that the Betadine NEAL R. GROSS
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may make deflation more common.

There is evidence in

the literature that it may make capsular contraction less common. And I would suggest to you that this

should not be an issue of device approval, but should be left up to the judgment of the operating surgeon. CHAIRMAN WHALEN: I guess the only

response I would have to that is ultimately it's going to be anyway, isn't it? Ultimately it is going to be

up to the surgeon, and the surgeon is going to do whatever he darn well pleases no matter who tells him anything. Some of you probably think since we

answered all seven questions that we're now going to vote. You're wrong. (Laughter.) CHAIRMAN WHALEN: We will now proceed with

the second open public hearing session of this meeting. All those and only those who have signed up for this -there are four people -- who will address the panel should speak clearly is into the microphone this as means the of

transcriptionist

dependent

upon

NEAL R. GROSS
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providing an accurate record of this meeting. The instructions from this morning still apply, and to briefly encapsulate those, we would ask that you disclose if anyone is paying for your trip or accommodations; if you have any financial ties to

industry or health professional societies.

We would

also ask that you disclose whether you are a witness or party to any lawsuits related to breast implants or whether you derive any of your income from medical procedures involving breast implants or symptoms

attributed to breast implants. Each there's a loud speaker outcry, in was this session, going unless to be

originally

allotted ten minutes, and in view of the hour, the chair is going to ask that you confine that to five minutes, and we only have time for the four scheduled speakers. The first one is Lale Goddard. MS. GODDARD: (Inaudible.) If you feel that it's so

CHAIRMAN WHALEN:

critically important, then please proceed. I'm sorry. Just for the timer's sake

NEAL R. GROSS
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then, ten minutes on this please. MS. GODDARD: My name is Lale Goddard. I don't need

Now can you hear me better? to holler, right? Okay.

My name is Lale Goddard.

Thank you

very much for the opportunity to appear before you today. I paid my own travel and accommodations. I do not have financial ties with industry or health professional societies. I am the plaintiff to a

pending lawsuit related to breast implants. no income from surgical procedures. I'm literature here that today because

I derive

scientific wear debris

states

particulate

generated from implanted medical devices may not be biocompatible. medical devices, Long such term as implantation implants of various joint

breast

and

implants, can generate particulate wear debris. White blood cells, called macrophages, can be stimulated or activated when they ingest silicone elastomer particles. Activated macrophages can

synthesize and release various inflammatory mediators, NEAL R. GROSS
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such as the pro inflammatory cytokines called tumor necrosis factor alpha. Tumor production of necrosis factor alpha induces the

another Tumor

inflammatory necrosis

cytokine

called and

interleukin-1.

factor

alpha

interleukin-1 are both potent and biologically active protein molecules. They act as signals between cells

to regulate the immune response to injury or infection. Biological properties of interleukin-1

suggest that its effects often mimic host response to infection, challenge. Once interleukin-1 can released induce into systemic the circulation, such as inflammation, injury or immunological

systems,

fever, muscle aches, arthralgia, headache, lassitude, sleepiness, changes in metabolism, and hematological dysfunction. Tumor interleukin-1 can necrosis be toxic factor in vivo. alpha and

Inflammatory

cytokines produce at the site of chronic granulomatous for a body reaction can move through the blood stream and activate cells at a distant site. NEAL R. GROSS
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There is growing

evidence involved

that in

the the

tumor onset

necrosis of

factor

alpha

is

inflammatory

arthritis,

whereas the cartilage and bone destructive process is mainly interleukin-1 driven. Interleukin-1 is responsible in the

production of cyclooxygenase, an enzyme that helps make prostaglandins, the substance largely responsible for the pain and inflammation the of arthritis. cytokines When into

scientists

injected

inflammatory

rabbits, the animals developed signs of inflammatory arthritis and join erosion. Tumor necrosis factor alpha and beta are potent stimulators of bone resorption in vivo. Orthopedic surgeons have known implant about the manufacturers adverse and

cellular

responses to particulate wear debris for decades, and they call it a chronic granulomatous foreign body

reaction or particle disease. Scientific literature states that silicone elastomer particles can cause erosive or destructive arthritis that mimic rheumatoid arthritis. Long term

benefits of silicone elastomer use in joint implants NEAL R. GROSS
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probably far outweigh the risks of complications and adverse reactions for most orthopedic patients. The cosmetic and psychological benefits of long term breast implants made with silicone elastomer shell in healthy women may not outweigh the possible risks and complications. for biological The FDA recognized standards of medical devices and

evaluations

guidance documents do not require the manufacturers to do testing for cellular responses to silicone elastomer particles. The particle testing could be done in less than three weeks, according to an article published in the May 1996 issue of Orthopedic Hand Surgery. The

title of the article is "In Vivo Inflammatory Response to Silicone Elastomer Particulate Debris," published by Dr. Sanjiu H. Naidu and his colleagues. The article abstract states the following: "Silastic silicone elastomer particles, polymers, urate

polymethylmethacrylate

monosodium

particles smaller than 10 microns were injected into a rat subcutaneous air pouch lined with synovial

membranelike cells.

Inflammatory exudate from the air NEAL R. GROSS

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pouch was retrieved at 6 hour, 24 hours, 48 hours, and 72 hours after injection. tumor necrosis factor, and White blood cell count, prostaglandin E
2

were

measured in the exudate.

White blood cell and tumor

necrosis factor levels in the exudate were the highest for the silicone group in 24 hours. Prostaglandin E
2

was significantly higher in the silicone group at 24 hours. We concluded specific that and acute that inflammation is

particle-type

silicone

elastomer

particles are acutely inflammatory." In 1998, American Society for Testing and Materials One is developed two particle for testing standards. to

titled

"Testing

Biological

Responses

Particles in Vitro," and the other is titled "Standard Practice for Testing the Biological Responses to

Particles in Vivo." Both standards state the following: "it

is well recognized that the biological responses to particles materials. could be different from those to solid

The interaction of the particles with cells

in the tissue, notably macrophages and other phagocytic cells, is the key to final biological responses." NEAL R. GROSS
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The standards describe techniques used to detect soluble cell products, such as tumor necrosis factor alpha, interleukin-1, interleukin-1 receptor

antagonist, and interleukin-6 due to interaction of phagocytic cells, such as tissue macrophages and

synovial lining cells with particles. For consumer safety sake, please consider making the following recommendations to the FDA. One, Society for the FDA and to recognize the American titled

Testing

Materials

standards

"Testing for Biological Response to Particles in Vitro" and the "Standard Practice for Testing the Biological Responses to Particles in Vivo." Two, the FDA to updated and include the two particle testing standards in the guidance

document. Three, inflatable breast the FDA to not approve silicone

implant

manufacturers'

pre-market

approval application or product development protocol until the manufacturers comply with the revised

guidance document. Four, the FDA to analyze the explanted

NEAL R. GROSS
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elastomer shells to determine the amount of material lost. Five, if the FDA approves breast implant manufacturers' PMAs and PDPs without the testing for cellular responses to silicone elastomer particles,

then the FDA should inform the public that the particle testing was not required for the PMA and PDP approvals. Please do not vote for the approval of breast implant manufacturers' PMAs and PDPs without the requirement for testing for cellular responses to

silicone elastomer particles.

Particles to be tested

should be smaller than 13 microns or small enough to be ingested by macrophages or other phagocytic cells. Manufacturers patients about the should inform doctors to and

cellular

responses

silicone

elastomer shell particles and cytokine production. Thank statement is you very much, at and my my Web written page,

also

available

jps.net/joseeefus/. Have a good evening. CHAIRMAN WHALEN: Thank you.

Next we will hear from Ms. Rosmary Locke NEAL R. GROSS
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on

behalf

of

the

Department

of

Defense

Military

Hospital Beneficiaries. MS. LOCKE: It's been Thank you. a long day, but I really do

appreciate the opportunity to speak to you after one of the manufacturers presented and the FDA made the

comments. My name is Rosmary Locke, and I have no personal financial involvement with manufacturers or health care providers. I'm not involved in a legal

issue, and I'm not being reimbursed. However, national breast in I am a volunteer and for it's Y-ME my

cancer the

organization, they did

understanding

past

receive

small

donations from one manufacturer.

The bulk of our --

that's all public record in our annual reports -- the bulk of our money comes from individual donors and some pharmaceuticals who support our work. I am a breast cancer survivor of 15 years with implants. I'm a military spouse and a health care I'm also a past

advocate for military beneficiaries.

president of the National Military Family Association. NEAL R. GROSS
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Eight years ago I was a member of your advisory implants. panel when it reviewed the PMA on gel

Though I believed that gel implants were

safe, I concurred with the other panelists that the scientific information was lacking for gel approval. Since then a large body of science has emerged showing that breast implants do not cause

systemic disease. IOM review of

The National Academy of Science's the science, its conclusions and

recommendations now provide us with knowledge based on sound science. Saline implants are a very important

option for women who face breast cancer. treatment decisions options made must be considered that

At diagnosis, and difficult can be

with

the

hope

disease

controlled and a more normal life resumed. That is why it's so important to have a full array of treatment options. It gives the cancer

patient some sense of control and restoring her health and quality of life. While saline breast implants generally do not produce the desired aesthetic results of gel in NEAL R. GROSS
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reconstruction, saline offers mastectomy patients the only unrestricted option left since the FDA's

restrictions in 1992. Saline is the only implant option for

breast cancer patients or long term survivors treated in military hospitals, is a and access for many to gel in for the

reconstruction

problem

women

civilian sector. And I know because time is limited you're probably not going to ask any questions on why that is, but it is a significant problem for military

beneficiaries. I urge this panel to stick to the science, consider the exhaustive and definitive review of the IOM of all of the existing research. The IOM found

that there's no evidence that silicone breast implants cause disease or cancer. Yet the FDA restrictions on

gel remain, denying access or causing delays for some women seeking them for reconstruction. Look at the fear and the litigation that happened after the 1992 PMA on gel. should not act in a vacuum. NEAL R. GROSS
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FDA cannot and

Now, there have been many other reviews that were spoken of today, and each found similar

findings to that of the IOM. increase in primary or

The research shows no breast cancer.

recurrent

Indeed, though we've heard from a number of women who have a wide range of medical conditions they attribute to breast implants. Their health needs cannot be

ignored. The FDA, however, cannot make regulatory decisions based on personal anecdotes. to the science. Of course, a woman considering It must stick

reconstruction should seek in depth information about her cancer and her reconstruction. Cancer Institute, FDA, IOM, Now, the National and many medical

institutions have excellent information in print and Web pages, and many women find it helpful to talk to other cancer patients. Consumers device is risk free. And there are risks need to know that no medical

No medical device lasts forever. associated with all surgical

procedures.

That makes informed consent central to the NEAL R. GROSS

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www.nealrgross.com

process.

It's

absolutely

essential

for

doctors

to

advise their patients on the risks and benefits of any medical procedure. Though quite sobering, we welcome the

information coming from the manufacturers on the nature and frequency of complications and reoperations. We also appreciate the opportunity by the FDA to make comments on informed consent and labeling, and we ask to be able to make a statement on that. In summary, I ask that breast cancer

treatment decisions should be made on how best to treat cancer, not on disfiguring surgery, and breast implants offer an important option to women with breast cancer. I recommendations urge on this sound panel science to and base studies its with

reasonable endpoints, a process FDA uses in evaluating all other effective medical devices and therapies. Thank you. I did cut my time. it with the red light going. CHAIRMAN WHALEN: Thank you. It may not seem like

We next will hear from Dr. Diana Zuckerman NEAL R. GROSS
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from the National Center for Policy Research for Women and Families. DR. ZUCKERMAN: Oh, towards me? Is this a good height?

Is that better? That's

I'll be brief if you stay awake. the deal. (Laughter.) CHAIRMAN WHALEN: motivator. Please continue. DR. ZUCKERMAN: Thank you.

Hunger is a wonderful

I just want to briefly say that I come to be here -- oh, I should start with my conflicts of interest. I'm donating my time, and my transportation

here all the way from Bethesda, and my answers to the other conflict of interest questions are no. My background is in epidemiology and

psychology, and I've also talked to hundreds of women with breast implants of the last ten years, and so my goal today is to put those two things together. I know that we as scientists are not

supposed to focus on anecdotes, but sometimes when we listen to patients, it tells us something important, NEAL R. GROSS
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and when we tie that in with what the research does or doesn't tell us, I think it can be very important and give us some insights into where we go next. I'm very concerned about the loss of

patients to follow-up in the studies that you've heard about, and I'm particularly concerned about it because I've talked to a lot of implant patients who have told us, told me personally of experiences where they try to tell their doctor that they have problems. And it isn't getting registered in the

studies that they are supposed to be in, or they get so turned off by doctors who do not seem to believe that their health problems can possibly be related to their implants that they stop seeing those doctors and go find other doctors. And so I think it is not a minor issue that there is this loss of patients to follow-up, and several of you have raised that question, and then I feel it's sort of gotten lost. It's the long day and

it's the end of the day, and so I want to bring you back to that issue, that perhaps part of the reason why the women who had problems sound one way and the

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research seems so entirely different is because some of those women at least are getting lost. And there are, and of course, very we don't know and how I many think

that's

important,

that's a big issue, certainly for me, and I hope it will be for you. I also want to talk a little bit about the quality of the data, and that ties in again. I mean

obviously a study of depression that has no comparison sample or control of the group, whole I mean it to reduces me to the have

credibility

package

something like that be supposed to be evidence that these women are getting better because, of course,

women who have just had surgery for breast cancer are going to be depressed. I used to do research on depression. promise you that's true. They are going to I

feel

better, and without a comparison sample, you don't know anything about how effective this particular treatment is for those women. I also have some concerns about whether all of the right questions were asked in these studies. NEAL R. GROSS
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Pain is a big issue for a long of the women I talk to. I'm not at all convinced that the research that was presented today really deals with pain in a meaningful way. Obviously if women say they're really

satisfied with their implants, you have to assume that pain is not a big problem, but let's remember that the follow-up was quite short for these studies. years is not a very long time. When I've talked to women, most of these women have been very happy with their implants for the first few years. It's only after three or four or five Three

or six or more likely seven or eight years that they start having serious problems. And let me also mention that part of that is that when they do have problems initially their doctors say, "Don't worry. It's going to get better,"

and so they have this hope, and they may feel quite satisfied because they think that the problems that they have of pain or numbness in the nipple area or whatever it might be, that those problems are going to go away and they're going to feel better soon. NEAL R. GROSS
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If you follow them for a longer period of time, they might feel quite differently about how

satisfied they are and how they feel about it. Let me briefly say I'm on the Scientific Advisory implants. Committee for the NCI study of breast

I was very surprised that that study wasn't I Know that the data are not --

mentioned here today.

nobody knows better than me the data are not public yet. I would have thought FDA would have asked for those data. presented those I would have thought they would have data to you. Although it's not

published yet, some of those data are already analyzed, and one of the people at FDA is a co-author of those studies. Those are studies of cancer, breast cancer and other cancers, and a study of connective tissue disease. data. Those are relevant data. Those are important

It's a very large study, the largest study

that's ever been done, and I don't understand why you didn't get it, and I hope that FDA will ask for it and

look at those data before any kind of final decision is NEAL R. GROSS
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made. I'm almost done here. There's one thing I just have to address, and that's the issue of connective tissue disease.

When I was asked to speak today and all the other public comment people were told stick with saline

implants, and I'm happy to do that, but the studies on connective tissue disease do not do that. I may be one of the few people in America who's studies implants. actually on read all of these epidemiological and breast I've

connective

tissue

disease

Here they are.

I've read all of the.

done a review of them. And let me tell you that of the 17 studies that are most often quoted in the Institute of Medicine report, as well as other reports that have been done, only one, one study looked at saline breast implanted women and analyzed them separately. studies did. Most of the studies had no women with None of the other

saline implants or very small numbers that were not analyzed separately. If you want to assume that the

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data on silicone gel implants are relevant to saline, that's a decision to make, but it's kind of an unusual decision to make. Usually you would study, you know,

one product at a time and base your decision on that one product. Finally, I just want to say that there is a lack of long term data. I think that's serious, and

I commend your concern about that and your asking for more data. As someone who's done survey research, I don't think there's any way in the world you're going to get questionnaire data ten years out. You may say

it's impossible to get, you know, actively women coming back in, but you're sure never going to get

questionnaire data like that. If you think that long term data are

important -- I personally think they're very important -- I don't know how you're going to create an incentive for the manufacturer to do that if you approve these devices. If they haven't done it up till now when they

had all these years to do their studies, what's going to give them the incentive to do it in the future? NEAL R. GROSS
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And my understanding is that FDA does not have post market surveillance resources or perhaps

authority for medical devices.

So if you think that

the data that's been presented are not sufficient to prove safety, and I know that some of you have said that here today, then you have to think very carefully about how you're going to make sure that happens when I think there is actually no other way to make sure it happens. And my last comment is just to say that breast cancer patients are a special case, and Dr. -not doctor -- Ms. Dubler and I commend your concern about them, and I share it. I've worked with a lot of breast cancer activists, and I actually met with them very recently to talk about this issue, and there's a wide range of feelings among the breast cancer community about breast implants. Most groups have been neutral on the issue.

They all do want good data. We do women no favor, whether they're

breast cancer patients or any other patients, we do them no favor by leaving something on the market that NEAL R. GROSS
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is not proven safe for them. Thank you. CHAIRMAN WHALEN: Thank you.

Finally we have -- Dr. Zuckerman, if you'd stay at the podium, there's a question. DR. ZUCKERMAN: Sure. This NCI study, I did

DR. BLUMENSTEIN:

not know about it, and I think that it has a possible impact on what other kinds of data we require of the manufacturers, and I would like to know some more

details about it. CHAIRMAN WHALEN: Well, before you go into

any details about that, Dr. Witten, would you like to comment upon the whole process we're about in terms of what PMAs are and what we can review? DR. WITTEN: Yeah. I just want to

reiterate what I had mentioned this morning, which is we want you to base your safety and effectiveness

assessments on the information contained in the PMAs, and in addition, your scientific knowledge, including, you know, what you know from publicly available

scientific literature. NEAL R. GROSS
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CHAIRMAN WHALEN: mandatorily directed to do. DR. WITTEN: to do. DR. ZUCKERMAN:

Which is what we are

Which is what we're directed

No, and I understand that,

but I have heard people say, "We don't have to worry about cancer or connective tissue disease because the studies show there are no problems," and I am not at liberty to say what's in those studies even though I have seen them. I am not allowed to talk about them.

I'm only saying I think that that would be something that FDA would want you all to look at and would want to look at. CHAIRMAN WHALEN: Thank you.

Finally, we have Ms. Jill McClure from the National Alliance of Breast Cancer Organizations. MS. McCLURE: your time. My name is Jill McClure. I'm a health Good evening. Thank you for

educator and a breast cancer information specialist. It's my pleasure to represent the consumer and

professional constituencies of the National Alliance of NEAL R. GROSS
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Breast Cancer Organizations and to offer a point of view to the members of the panel. My travel expenses have been paid for by internal NABCO funds earmarked for advocacy activities. Neither NABCO nor I have any financial ties to implant manufacturers or marketers. funding from any current NABCO does not receive any implant manufacturers.

Neither NABCO nor I are part to any implant related lawsuits. The reason I phrased it current implant manufacturers, implant I know, for and example, they're Bristol was who an has

manufacturer,

somebody

supported a publication of ours this year. to be absolutely clear on that.

So I want

I would like to emphasize that my remarks will be confined to use of these devices for

reconstruction for women who have had breast cancer or breast disease due or to who an have had a risk prophylactic for breast

mastectomy cancer.

established

NABCO cannot and does not comment on the cosmetic use of breast implants of any type. NEAL R. GROSS
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NABCO is a not for profit, information and education resource on breast cancer. network of over 400 member It is also a and a

organizations

nationally recognized voice for the needs and concerns of women with breast cancer, women at increased risk for the disease, and their friends and family. NABCO's frequently called to professional upon serve by as staff members and are

providers patient

health and

professionals

advocates

advisors in medical and policy deliberations and in clinical decision making. We developments also frequently into translate scientific and

and

advances

understandable

compelling language for print and broadcast media. We're and comfortable because taking on these mission roles and

responsibilities

NABCO's

program areas offer us constant exposure to a large and varied constituency. I work in NABCO's Information Services

Department where our Web site and toll free number are NABCO's front line for serving the public and where we handle hundreds of weekly contacts with many segments NEAL R. GROSS
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of patient and survivor communities. Callers express their breast cancer and

educational needs, and as we fulfill those needs with materials, resources, and referrals, we've often heard misinformation, confusion, and concern, but also some reassurance and relief surrounding the emotionally

volatile subject of breast implants. Without question, saline implants are not ideal since they can leak, be subject to capsulary contracture, maintenance, and and are are less sturdy, less require higher

often

aesthetically

acceptable than their silicone filled counterparts. We at NABCO hope and expect that the FDA will address the availability of silicone filled breast implants, again, for breast cancer patients and

survivors at some point later this year, but until these devices are open for discussion, we wish to make several points about saline breast filled implants. Safe, well tested, saline filled breast

implants must continue to be available in as many types and forms as feasible so that options and choices for women with breast cancer are maximized. The

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alternatives of autologous tissue reconstruction and external prosthesis are not appropriate for every

woman, and as individuals differ and vary, so much their options. Like saline breast any medical device be or procedure, and

implants

should

considered

selected by a woman and her medical team after careful discussion and consideration with a full information exchange that includes the risks and benefits. Saline filled implants have been available and, as such, and have not been subject to the more

stringent

highly

regulated

informed

consent

provisions and requirements of clinical trials. However, there still remains confusion

about implants, and for this reason NABCO calls upon the device manufacturers and the medical specialists and providers who use these implants to make special additional efforts. Women who are considering saline implants should receive and an exceptionally thorough, review

comprehensive,

understandable

information

about the devices from their physicians, be given time NEAL R. GROSS
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to ask questions and have those questions answered. Information conveyed should not only

include what to expect when the saline implants are first received, but how the devices will behave over time both under normal circumstances and under unusual circumstances. NABCO encourages giving women contact

information for organizations that can offer accurate and balanced information about implants and breast

health in general.

Understanding and working with her

implant is a woman's lifelong commitment and part of the decision to choose an implant. It should be made clear that replacement of a saline implant is not only possible, but likely, and the woman for shares keeping the up responsibility with with her

physician

developments

about

implant improvements, advances, safety, and this idea of maintenance. Women with saline implants need to know the special considerations and requirements for breast examinations for early detection of breast cancer.

MQSA regulations have specified certain procedures for NEAL R. GROSS
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imaging women with implants, and these must be taken into account at the time a woman has an implant in place or -- I'm sorry -- and the type of implant the woman has in place. Breast self-examination techniques should be reviewed with the woman after the implant has The

resolved to its ultimate size and resting place.

breast cancer survivor should be particularly vigilant about breast examinations and the possibility of

recurrence. Finally, NABCO urges the FDA to move

forward with communication of scientific findings about breast implants, and that all types of these devices be discussed using factual scientific and evidence based information consideration experiences. Women who have survived breast cancer are particularly able to weigh the risks and benefits, rather to than relying on or giving

emotional,

personal,

and

anecdotal

understand that no medical intervention is risk free. Having become informed patients by selecting the

treatments that would extend their lives, patients and NEAL R. GROSS
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survivors need and deserve similar choices even if they seem difficult or challenging, including breast

implants and any other regulated aspect of recovery that may improve the quality of their lives. As their advocates, we have confidence

that these women will make wise choices that are right for each one of them based on full disclosure. Thank you for your time. CHAIRMAN WHALEN: Thank you.

I'd like to thank all of those for taking time out of their schedules to testify at this panel meeting. Is there any further comment from anyone in the FDA? DR. WITTEN: No, thank you. Thank you, Dr. Witten. any further comment from

CHAIRMAN WHALEN: Will there be

Mentor Corporation? Seeing that there will be, I'd like to remind you beforehand that this will be for ten

minutes.

I would ask that the timer be run to that

accord, and also remind you that this is not to present NEAL R. GROSS
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new data, but just to comment upon anything that has already taken place. MR. PURKAIT: Thank you, Mr. Chairman.

Thank you, members of the panel, for your time and the thoughtfulness and seriousness that you have shown to consider our PMA today. There are some issues that I saw or we saw here you panel members are struggling about the data, specifically on the complication rates. I'll take only

a few seconds or minutes jut to show that some of this data that we presented did not show the complication rates increasing over time. I'd please. This is from the augmentation patients. I like to call these slides here,

wouldn't take much time to explain each of those data. I just want to draw your attention to the fact that the year one, year two, year three, you can see the year one they are higher, as it goes down in year two and year three. All categories go down except the

reoperation, what we have explained before. Slide number two please. NEAL R. GROSS
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Similarly necrosis breast pin,

on and

the the

hematoma, others, what which

seroma, we we have have

calculated

through

the

Kaplan-Meier,

submitted also, that shows that the year one, year two, year three decreasing, not increasing. Similarly, on the reconstruction patient, please. On the reconstruction patients, I'd like to

also point out that infection goes high at the year first and goes decreasing rate over two and three. Similarly on the deflation, deflation probably is in the higher scale, which we have explained the reason behind it. Reoperation rate and explantation goes high

in case of the reconstruction. Similarly, in the other areas of

complication, the hematoma, necrosis, seroma, all of them shows higher rate at the year one, year two, and year threes on the decreasing. This one, the extrusions and the rest of the other complications, this is an example to show that what you're struggling before about the safety issues related to the fact that this goes over -increase over time. I like to present this to keep the NEAL R. GROSS
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record straight that this doesn't really. The second thing that I'd like to mention is that in case of the division patients I request strongly to the panel members to consider this

carefully because the division patient groups are in between, and I do not like to see that division patient groups have a cloud over their head that they can get an implant one time, but the next time they can't because there is some problem with the devices. Also I'd like to mention that out SPS

study is quite full of data, we believe rich, and has a lot of new information that we recently uncovered and discovered, and we are understanding, and we believe that as those data are being disseminated and been shared with both physician and FDA, it will be provided in the patient as well as the physician-patient

information in such a way that we'll be able to provide a better information than before, previously, to the whole community. With those notes, again, I thank you very much for your consideration, and I believe that this will give you a pretty good idea about our PMA's data NEAL R. GROSS
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and will help you to understand this data and vote on it. Thanks. CHAIRMAN WHALEN: Dr. Krause will Thank you. now read the voting

instructions for the panel. DR. KRAUSE: I'd now Thank you, Dr. Whalen. like to read the voting

instructions for the panel. The medical device amendments to the

Federal Food, Drug, and Cosmetic Act as amended by the Safe Medical Devices Act of 1990 allows the Food and Drug Administration to obtain a recommendation from an expert advisory panel on designated medical device premarket approval applications that are filed with the agency. The PMA must stand on its own merits, and your recommendation must be supported by safety and effectiveness data in the application or by applicable publicly available information. Safety is defined in the act as reasonable assurance based on valid scientific evidence that the NEAL R. GROSS
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probable

benefits

to

health

under

conditions

on

intended use outweigh any probable risks. Effectiveness assurance that in a is defined as reasonable of the

significant

portion

population the use of the device for its intended uses and conditions of use, when labeled, will provide

clinically significant results. Your recommendation options for the vote are as follows. First option: conditions attached. Second conditions. option: approvable with approval if there are no

The panel may recommend that the PMA be

found approvable subject to specified conditions, such as physician or patient education, labeling changes or a future analysis of existing data. Prior to voting

all of the conditions should be discussed by the panel. Third option: not approvable. The panel

may recommend that the PMA is not approvable if the data do not provide a reasonable assurance that the device is safe or if a reasonable assurance has not been given that the device is effective under the

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conditions of use prescribed, recommended, or suggested in the proposed labeling. Following the voting, the chair will ask each panel member to present a brief statement

outlining the reasons for their vote. CHAIRMAN WHALEN: Thank you, Dr. Krause.

Does one of the panel members wish to make a motion? DR. BURKHARDT: Yes, Mr. Chairman. I move

that the panel recommends approvable with conditions for this PMA, and that those conditions should include post approval studies specifically consisting of some of the mechanical in vitro engineering concerns that have been expressed by Dr. Li. In addition, I would attach labeling

revision concerns, specifically including a revision of the comments regarding the shaped implant and labeling to discourage periumbilical insertion. CHAIRMAN WHALEN: As to the motion that

there be a recommendation that this be approvable with conditions -and we will discuss those conditions

shortly -- but as to that motion, is there a second to NEAL R. GROSS
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the motion? DR. LI: CHAIRMAN Second. WHALEN: We will now consider

each of the conditions which have been stipulated by the motion, and if you could once again please read for us, Dr. Burkhardt, or refresh for us what the first stipulation would be. DR. BURKHARDT: that additional with mechanical the FDA The first stipulation was testing to be performed some of in the

cooperation

address

concerns that have been raised. CHAIRMAN WHALEN: Is stipulation? there any Thank you. discussion of that

Dr. Li. DR. LI: Do you want specific suggestions?

Is that where we are? CHAIRMAN WHALEN: that being a condition or not. DR. LI: Yes. Or amplifying or -Well, just in support of

CHAIRMAN WHALEN: DR. LI: that.

I'm obviously fully in support of

Is that all you want now or do you want the NEAL R. GROSS

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actual conditions for approval? CHAIRMAN WHALEN: ventriloquist. I'm not trying to be a

You can either talk about it as much as

you wish or just say you approve it and leave it there. DR. LI: Oh. Well, I would approve it

with -- surprisingly, I would actually approve it with conditions perhaps. I think minimally you need to

complete the testing of all the models that you intend to sell, and I think it's important that you test them with the materials that you intend to sell in the sterilization conditions in which you sterilize them at. So if you're going to consider gamma

sterilization as a potential fall-back manufacturing process, I think it is imperative that you test it in those conditions. Further, we didn't mention it before, but gamma sterilization raises the whole issue of shelf aging and things like that, which are probably much less important for dry heat. I think there needs to be either a

modification or perhaps even just a further description NEAL R. GROSS
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of your fatigue test results.

In other words, to help

me close that gap between your fatigue test and what happens clinically, perhaps a description of what and where and how your devices fail and fatigue. For instance, if you're generating giant holes in your fatigue test when it blows out that look nothing like your retrievables, then that test is far less meaningful than it is of if you're as actually found in

generating

similar

types

behavior

retrieved devices. I would encourage further analysis of

retrievables, and then the closer you can mimic your laboratory test to what you actually find, the more comfortable, much more comfortable I would be, but I think it behooves you to find some cases or some tests where your implants actually do, in fact, leak and fail because they, in fact, do that clinically, and they do so even more under the reconstructive environment. So I think it would behoove you if you wanted people to make your tests more believable that you actually run tests that actually fail in a

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happens clinically rather than some of the more extreme tests that you've provided so far. CHAIRMAN WHALEN: Thank you, Dr. Li.

As to the first condition -DR. DUBLER: Excuse me. Okay.

CHAIRMAN WHALEN: DR. DUBLER:

I just don't understand if we

stipulate that number and specificity of conditions which are such at odds with the data that's been

presented.

Can that still be considered under the FDA

rules for conditions of approval or does that have to go into the explanation for why the data have not been adequate and don't show safety? CHAIRMAN WHALEN: Anyone, including of

course FDA, correct me if I'm wrong, but what we're discussing and what we will shortly vote upon is that there be a condition that there be in vitro engineering testing. Dr. Li has amplified for us some potential examples of what form that testing may take, but at the point in time when we come to vote upon that being a condition, we are being rather generic in what we are NEAL R. GROSS
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voting upon with only the specificity of the field of testing that would need to be done. Dr. Blumenstein. DR. There were BLUMENSTEIN: I have here, a but question. I have

conditions

specified

additional conditions, but I have additional conditions that I would like to add. CHAIRMAN WHALEN: And we will, indeed, get

-- we're going to discuss each of the ones that have been stipulated as conditions, enlist further

conditions, then vote upon each of those conditions, then vote upon the motion of approvable with those conditions that we have then approved. Dr. Morykwas. DR. MORYKWAS: Well, I'd like to add to

that that a potential testing condition could be done. Instead of just 37 degrees saline, do it in serum or some other biological fluid in case you do get lipid incorporation. which may You get minor swelling of the device alter some of the mechanical

potentially

effects and just try and mimic the in vivo environment a little more in your testing. NEAL R. GROSS
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CHAIRMAN WHALEN:

And we can do that.

The

only response I would say to that is, as I just alluded to, we're going to be voting upon that there be further in vitro testing. that we If get it's very the pleasure in of this that

committee

specific

what

testing is, then by all means we'll do that. But rather generic as in first stipulated, that there we're be being further

specifying

testing. As regards the first potential condition of in vitro engineering we testing, go to is there any further other

discussion conditions?

before

discuss

MS. clarify.

DOMECUS:

Yeah,

I

just

wanted

to

I heard Dr. Li said it's pre-approval and Dr. So I'm not sure what

Burkhardt say it's post approval. the condition is. CHAIRMAN WHALEN:

Dr. Burkhardt, since you

had proposed that condition, did you propose it as post approval or pre-approval? DR. approval. NEAL R. GROSS
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BURKHARDT:

I

proposed

it

as

post

CHAIRMAN WHALEN:

Dr. Li, do you agree

with its being post approval or do you feel that this needs to be done before we can approve, which I would -- which I believe means we would not be then saying it's approvable with conditions if we're saying it's pre-approval. DR. LI: Oh, I misunderstood. I thought

approvable with conditions means we would approve it so long as they met the conditions. MS. DOMECUS: DR. LI: Right. if they don't meet the

And

conditions, then it's not approved. interpreting. Is that --

That's how I was

CHAIRMAN WHALEN: DR. WITTEN:

Dr. Witten?

Well, I think that's up to

you to clarify in your recommendations because you can make the approval. You can make your recommendation

about approval with conditions, that it's approval that some things be done before we go ahead and approve it or you can recommend that something be approved and recommend some post approval additional testing. DR. BURKHARDT: The intent of the motion

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was

to

approve

now

and

proceed

with

post

approval

studies. CHAIRMAN WHALEN: With that actually

having been what was proposed, do you wish to speak against that, Dr. Li, or are you agreeable to that? DR. LI: my second. CHAIRMAN WHALEN: DR. LI: Sorry. Into the microphone. I misunderstood you to If it's post approval, I withdraw

mean pre-approval in the sense that you would approve it before we would move on. So all of my conditions

are that I would vote for approval so long as the conditions of testing are met, but not otherwise. CHAIRMAN WHALEN: DR. LI: those tests. But would you --

So I would not approve it without

Is that what you mean? CHAIRMAN WHALEN: As Dr. Burkhardt has

phrased it, we would recommend that the FDA find this approvable and then subsequently do these studies. DR. LI: question? Can I ask, I guess, a procedural

If we go that route and say it's approved

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that may be, and at the end of it, whatever time period, they go, "Oh, my gosh, this isn't what we should be doing," what is our course of action? DR. WITTEN: Well, usually if you're

recommending something post approval, it's to answer some focused questions. So I guess we'd have to see

what that data showed, but in general it would be to answer a focused question. DR. LI: In that case I would disagree

then with Dr. Burkhardt's motion. CHAIRMAN WHALEN: your second? DR. LI: And I withdraw my second. Well, you withdraw the Very well. And withdraw

CHAIRMAN WHALEN:

second of the motion as approvable with conditions? DR. LI: No, his that it's approvable -Yeah, we don't have to

CHAIRMAN WHALEN:

move and second each individual condition. DR. LI: Okay, fine. So the motion is still discussing this first

CHAIRMAN WHALEN: on the floor, and we're

condition. NEAL R. GROSS
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MS. semantics issue.

DOMECUS:

I

think

there

may

be

a

Post approval means post FDA approval It doesn't mean post panel

of the PMA application. approval today. CHAIRMAN approve anything.

WHALEN:

Correct.

We

don't

We only recommend. Right, but I mean if you say

MS. DOMECUS:

approvable with conditions, those conditions can be met after today's panel approval, but before FDA approval of the PMA. DR. BURKHARDT: May I comment? Dr. Burkhardt. What I'm saying is I don't

CHAIRMAN WHALEN: DR. BURKHARDT:

think we ought to take these things off the market pending these things, pending the new studies. I think

we should leave them on the market at the present time and go ahead and proceed with the studies and

reconsider if the studies do not turn out satisfactory. MS. DOMECUS: But approval with conditions Would

wouldn't take them off the market, would they? it? DR. WITTEN: Well, I'm not sure.

You all

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make a recommendation of approval with conditions, but then our action would be either to have them -- would be -- our action isn't approval with conditions. Our

action is either approving it, possibly with some post approval conditions, or not approving it. So I guess,

you know, it's sort of a difference between what you recommend and, you know, what we end up doing. But we would either approve it with post approval conditions or we wouldn't approve it or we would try to do everything, you know, that you

recommended within the allowed time.

So, you know,

that would be another option depending on how involved, you know, some of these things were. CHAIRMAN WHALEN: MS. BRINKMAN: don't understand. Ms. Brinkman. I have a question that I

So how do you provide accountability

then if you say we'll approve this with post approval conditions and the conditions are not met? what does the FDA do? I don't understand. How then is the So then

manufacturer accountable and what happens? DR. WITTEN: Well, we work very hard with

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the sponsors, with them on their post approval studies. So I'd say, you know, there's accountability both on our end and on the sponsor's. And I'll say that also I don't want to suggest to the panel what you do, but you may look at some of those specifics in the mechanical testing, and maybe differentiate those that really are pre-approval versus post approval. I mean perhaps, you know, retrieval

versus, you know, approving the ones that are tested or in other words, it may not be an all or nothing thing, some of what you're recommending. it and say, "What do of you what think needs So you might look at is to really be a post pre-

approval

condition

done

approval?" I mean you might want to -- I don't want to tell the panel what to do, but you might want to look at the specifics of the suggestions. CHAIRMAN WHALEN: Dr. Li. DR. BLUMENSTEIN: I was just wondering if Dr. Blumenstein and then

we could make it unspecified as to whether it's preNEAL R. GROSS
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approval or post approval and let that be the FDA's discretion. DR. LI: I guess I don't mean to over

complicate this, but I guess I was thinking the last panel I was on was a completely different device

family, that there was a lot of additional testing we required of the sponsor, but the sponsor was not taken off the market during that time. In other words, the FDA and the sponsor agreed on a set of tests and a time frame for which those tests should be completed, and during that time frame the company or the sponsor will still able to sell their device. So I'm not saying you should stop selling their device until all of these tests are met was my intention. DR. BURKHARDT: Would you like to

reinstate your second? CHAIRMAN WHALEN: Well, since we're

dealing with an FDA issue, Dr. Witten. DR. WITTEN: Yeah, I think we'd prefer to

hear, you know, your recommendations about what needs NEAL R. GROSS
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to

be

done

for

approval

of

these

products

versus

getting into a regular -- you know, have the panel get into a regulatory discussion about what the different terminology means. I will just say in this case, as I

mentioned in my background, we have a 180 day total time frame for review from the date on which the call for PMAs was issued, which was in August. So that by

the end of that time, we will need to take a final action. Having said that, I might say that, you know, you could perhaps want to tell us approval with conditions that some issues be addressed if you don't want to get specific and into some of the regulatory issues versus how we would handle some types of

recommendations versus others. Because I think what we really want to know from you is what you think needs to be addressed by this application, you know, rather than your

regulatory assessment. CHAIRMAN WHALEN: line with what Dr. So if I may then, in raised, we are now

Blumenstein

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discussing the motion of approvable with conditions, the first condition of which we are now specifically discussion testing. Does anyone wish to speak further about that condition? (No response.) CHAIRMAN WHALEN: Seeing no one, Dr. is that there be in vitro engineering

Burkhardt, your second condition was, please? DR. BURKHARDT: The second condition was

that the comment regarding the shaped implant in the promotional material or the informational material, There is a

which technically is labeling, be revised.

strong implication that these implants will offer a more anatomical shape. Those are the words used, and

there has been no evidence presented to support that. CHAIRMAN WHALEN: Does anyone wish to

speak to that condition? (No response.) CHAIRMAN WHALEN: Dr. Burkhardt, were

there other conditions that you had raised? DR. BURKHARDT: The third condition was

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that

the

company

labeling,

the

sponsor

labeling

discourage periumbilical insertion. CHAIRMAN WHALEN: Does anyone wish to

speak further to that condition? Ms. Dubler. MS. DUBLER: we get that particular for I'm just distressed that if that there might be be other

instructions

surgeons

that

would

equally

important, and if we stipulate one particular one and don't do a total review of the other possible negative practices, that we will look like we have just merely identified one and approved all the others. So uncomfortable. DR. BURKHARDT: I am reluctant to put that strategically makes me a bit

constraints on the surgeon as a rule, but here we have clear evidence that the deflation rate of these

implants is increased by compression and by insertion through a small incision, to and I think this from is a

reasonable manufacturer.

restriction

recommend

the

If the surgeon wants to do it that way, NEAL R. GROSS
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they're going to do it anyway. CHAIRMAN WHALEN: particular condition? (No response.) CHAIRMAN WHALEN: Dr. Burkhardt, were Further comment on that

there any further conditions that you had? DR. BURKHARDT: No. Thank you. Dr. Morykwas, did you

CHAIRMAN WHALEN: Now, I'm sorry. have anything further? DR. MORYKWAS:

No. Are there any of the

CHAIRMAN WHALEN: panel members -- Dr. Chang. DR. CHANG: In

the

data,

one

of

the

factors that also increased rate of rupture and failure of the implant was an incision smaller than three

centimeters. So I would offer a friendly amendment that if you stipulate a recommendation that the incision of insertion be greater than three centimeters, would that not take care of the practice of putting this through endoscopically or through a long tube? NEAL R. GROSS
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CHAIRMAN WHALEN: DR. BURKHARDT:

Dr. Burkhardt? It would, but it would

also preclude axillary and periareolar insertion, which are very commonly used, and I don't think we should do that. CHAIRMAN WHALEN: Any further discussion

as to that particular condition? (No response.) CHAIRMAN conditions suggest? Dr. Blumenstein. DR. BLUMENSTEIN: I think we discussed that any WHALEN: members Are of there any other to

the

panel

wish

collecting revision data before the indication of the revision data would be approved, although now that I'm reading this, I don't think that was -- I think just collect additional revision data. CHAIRMAN WHALEN: DR. BLUMENSTEIN: a time? CHAIRMAN WHALEN: conditions? NEAL R. GROSS
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Dr. Burkhardt? Do we want to go one at

In terms of additional

DR. BLUMENSTEIN: CHAIRMAN WHALEN:

Yes. If anyone wishes to

address collection of revision data as an additional condition. DR. BURKHARDT: you mean. DR. BLUMENSTEIN: We talked about how the I don't understand what

sample size for data on revision was small and that additional revision data would be helpful. DR. amendment. CHAIRMAN WHALEN: Anyone else wish to BURKHARDT: I would accept that

address that condition, imposition of the necessity of the collection for revision or, quote, indication data? (No response.) CHAIRMAN WHALEN: further, Dr. Blumenstein? DR. estimates BLUMENSTEIN: be done Yes. using That true the risk Do you have something

either

cumulative

incidence methodology or that the risk estimates be appropriately labeled as to their conditional nature, as conditional probability estimates. NEAL R. GROSS
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DR. BURKHARDT: CHAIRMAN

I would accept that. Does anyone wish to

WHALEN:

discuss that condition further? (No response.) CHAIRMAN WHALEN: conditions? DR. showing a BLUMENSTEIN: of Redo the the analyses for to Are there any further

demonstration censoring of

potential data related

informative

missing

dropouts affecting biasing the results. CHAIRMAN WHALEN: I'm sorry. Can you

elucidate that a little further for me again? DR. BLUMENSTEIN: That analyses be done in

which the characteristics of the patients dropping out be documented. CHAIRMAN discuss that? DR. you'd do that. DR. BLUMENSTEIN: You can take the BURKHARDT: I don't understand how WHALEN: Does anyone wish to

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who do not have follow-up data.

This is a very simple

example, and then you can do that for almost all of the baseline characteristics that one has. DR. BURKHARDT: I don't understand data on how I understand that for age. you're who going don't to collect for

complication follow-up.

people

return

DR. BLUMENSTEIN: complication data. have an assessment

No, we're not collecting

We're collecting for patients who at 12 months for a particular

complication, and for the patients who do not have an assessment at 12 months for a particular complication. then you can compare their characteristics at baseline. DR. BURKHARDT: I will accept that,

assuming that the other statisticians understand it. (Laughter.) DR. BLUMENSTEIN: is nodding yes. (Laughter.) CHAIRMAN WHALEN: The question has been the other statistician

raised on this last point that you raise do you wish this for the labeling. NEAL R. GROSS
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DR. BLUMENSTEIN: CHAIRMAN WHALEN: DR. BLUMENSTEIN:

Yes. Okay. In other words, that the

labeling data be published in a way that would be consistent with publication in a peer reviewed journal. That's certainly what I'm getting to. CHAIRMAN conditions? (No response.) CHAIRMAN WHALEN: You still have the WHALEN: Okay. Any further

floor, Dr. Blumenstein. DR.

Is that all of yours? I think I know what

BLUMENSTEIN:

she's going to say. (Laughter.) DR. BLUMENSTEIN: I think that we also

mentioned about long term follow-up data with specific attention to those patients, again, who are part of an informative -potentially part of an informative

censoring pattern. CHAIRMAN WHALEN: Any discussion of that?

Dr. Blumenstein, would you like to take the next one? Why don't you complete whatever you need NEAL R. GROSS
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to do? DR. BLUMENSTEIN: Well, I was going to --

this was a point that Karen raised earlier about the analyses of particularly the quality of life data being labeled in such a way that it's clear that patients who have had a revision prior to the time point in which the analysis is being done are not included in that analysis. CHAIRMAN WHALEN: of that? (No response.) DR. BLUMENSTEIN: CHAIRMAN WHALEN: DR. I'm done. Karen. I don't know how Any further discussion

BANDEEN-ROCHE:

appropriate this is, but I wonder whether we could state as a formal condition that the sponsor and FDA work on a specific protocol to guarantee reasonable assurance informed. And I do this meaning this in more than sort of the generic you write out a label and people have the opportunity to see the label. NEAL R. GROSS
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that

patients

are

accurately

and

fully

You know, it's

not enough to leave a procure on a table.

It's not

reasonable to track people down and interview them in their homes, but there's got to be something in between that meets a standard of reasonable assurance of

accurate and complete information. CHAIRMAN that condition? (No response.) CHAIRMAN conditions? (No response.) CHAIRMAN WHALEN: Seeing none, we are here WHALEN: Are there any other WHALEN: Any discussion as to

listed with ten potential conditions, and we will vote on each of the ten individually before we then vote on the motion. I will try to key word these conditions so

that we can each vote on them. I would remind that there are two nonvoting members of the panel. Ms. Brinkman? MS. BRINKMAN: discussion. I got a bit lost on the So please don't vote.

Did you ask for long term study to be

included in the -NEAL R. GROSS
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CHAIRMAN WHALEN: MS. BRINKMAN: DR. BURKHARDT:

That was number eight.

Thank you. Mr. Chairman, in regard to

the ten conditions, would it be reasonable to ask first if anyone objects to any one of those conditions and then maybe vote on the whole bunch at one? DR. WITTEN: That's up to you. There are vigorous nods

CHAIRMAN WHALEN: from the FDA contingent. (Laughter.) CHAIRMAN WHALEN: excellent suggestion. Among these ten

So thank you for that

conditions,

is

there

anyone who is going to be voting negatively against on any of them? (No response.) CHAIRMAN WHALEN: Seeing none, just to

make it formal, as regards these ten conditions, all those who are voting members who are in favor, please signify approval by raising your hand. (Show of hands.) CHAIRMAN WHALEN: And all ten conditions

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are, indeed, unanimously approved. Thank you. We now go to the motion, which is that we recommend to FDA that the PMA be approvable with the ten conditions we have just approved. Would all those

who are in favor of that motion signify by raising their hand? (Show of hands.) CHAIRMAN opposed? (Show of hands.) CHAIRMAN WHALEN: For the record then, WHALEN: All those that are

since it is not a unanimous vote, opposed to that motion is Ms. Dubler, and therefore, approving that motion are Dr. Li, Dr. Blumenstein, Dr. Boykin, Dr. Bandeen-Roche, Dr. Burkhardt, Dr. Chang, Dr. -DR. MORYKWAS: Morykwas. It's been a long day. and the two non-

CHAIRMAN WHALEN: -and Dr.

Robinson,

voting members have not voted. DR. WITTEN: Dr. Whalen, you know you're

going to have to go around and ask everybody -NEAL R. GROSS
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CHAIRMAN WHALEN:

I know, but I had to

first read that in for the record. DR. WITTEN: CHAIRMAN Okay. Well, I've just been

WHALEN:

requested something to do that I can't do, and that is to read each of those conditions again into the record because all I did was write down key words. So if

that's an obstruction, I'm sorry, but I can't fulfill it. DR. WITTEN: you read the key words? CHAIRMAN WHALEN: to read the key words. DR. WITTEN: Read the key words. We can The key -- I'll be happy Just read the key words. Can

get the rest from the transcript. CHAIRMAN WHALEN: those ten conditions are: In vitro engineering testing; That the shape of the implant in the The key words of each of

present labeling be revised from its present labeling as "more anatomic"; That the sponsor labeling discourage the NEAL R. GROSS
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use of the umbilical distant incision; That data; That there be risk estimates; That the present data be reanalyzed as to the characteristics of those patients dropping out as it pertains to labeling; That there be accumulation of long term follow-up data; That there be labeling which concerns there be accumulation of revision

itself upon those findings regarding quality of life data that has been accumulated; And together to that the to sponsor maximize and the the FDA work of an

attempt

benefit

accurate and fully informed consent process. DR. conditions. CHAIRMAN WHALEN: That's because when I There were nine WITTEN: Well, now, that's nine

went to page 2 I dropped off seven. conditions. DR. WITTEN: Okay.

CHAIRMAN WHALEN:

Now, we're not done.

As

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is our directive, we must go around the table and ask that each of the members comment upon why they voted as they did, and we will start with Dr. Li. DR. LI: It seems quite redundant somehow,

but one more time, the instruction? CHAIRMAN WHALEN: The instruction is that

you indicate to us why you voted as you did, and that is to vote for approval, approvable with the conditions as stipulated. DR. LI: Okay. I think we have the usual

case of a device which has been around a long time and has been quite effective to a large number of patient populations and has been, at least for the majority of cases, been beneficial. I think the approval should be with

conditions, however, because I think unfortunately the mechanical in vitro characterization and testing lags quite a bit behind the clinical experience, and that the testing is incomplete versus the current product line, both in terms of materials and manufacturing

methods, and there is a rather large -- actually it's a disconnect between the data generated and the ability NEAL R. GROSS
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to use that data to predict or assure a certain level of clinical performance. But I believe that gap could be at least closed or made much smaller with more complete testing and perhaps modifications of their current testing. CHAIRMAN WHALEN: Dr. Blumenstein. DR. BLUMENSTEIN: I voted yes because i Thank you.

feel like that there is efficacy here, and that with the conditions, there will be a movement towards a nearly adequate characterization of risk that the

potential patient would be able to understand. CHAIRMAN WHALEN: Dr. Boykin. DR. BOYKIN: I agree that we have a Thank you.

significant level of comfort about the efficacy of the product and its reasonable safety, and that the

conditions of approval, I think, reasonably reflect the deficiencies which I think can be worked through quite easily. CHAIRMAN WHALEN: Thank you.

Dr. Bandeen-Roche. NEAL R. GROSS
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DR.

BANDEEN-ROCHE:

I

found

the

whole

issue of safety and effectiveness and risk and benefit very complicated per my previous comments. approvable with conditions because I I voted for to the

came

conclusion that at this point the best resolution is not for me to decide on risk and benefit. But to leave the device on the market and leave the adjudication of risk and benefit up to the individual patient, the condition being that the

patient be very, very fully informed. And I would also state that I believe that FDA has maybe more than the usual responsibility here to very vigilantly keep up with ongoing developments, as indeed we all do as scientists, and to investigate opportunities to target people with particular risk for adverse outcomes. CHAIRMAN WHALEN: Dr. Burkhardt. DR. BURKHARDT: I think the evidence Thank you.

clearly supports maintaining the availability of these devices; that it would be wrong to take them off the market at this time; but there are some additional NEAL R. GROSS
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housekeeping items that need to be attended to and approvable conditions was the best way to handle this. CHAIRMAN WHALEN: Dr. Chang. DR. provided safety. by the CHANG: PMA a I think that clear the information is relative of Thank you.

shows more

there

There's

demonstration

efficacy, and I believe the previous discussions that we have and approval conditions can be met and worked between the FDA and the sponsor. CHAIRMAN WHALEN: Dr. Morykwas. DR. MORYKWAS: Also be that the efficacy Thank you.

has been met and reasonable safety has been approved or has been proven, with the conditions that we have

stipulated. CHAIRMAN WHALEN: The Dubler. MS. DUBLER: It always makes me anxious to anticipation Thank you. is killing us. Ms.

find myself odd person out, but I think, in fact, that the analysis of the data, especially as provided by NEAL R. GROSS
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Drs. Li and Blumenstein, seem to indicate that the tests that had been done that would permit patient to assess risk and benefit, the data are not there. My question earlier went to the issue of whether there was some way to leave these on the market pending the gathering of adequate data, and the answer appeared to be no. I don't know how to make this choice

because if there were other alternatives that women could use, I would be extremely comfortable with my vote. However, I think that given the deflation rate and the leakage rate and the very clear

explanations of why the test did not, in fact, gather the sorts of data that would permit us to understand these variables, I felt I couldn't vote for the

reasonable safety. CHAIRMAN WHALEN: Dr. Robinson. DR. ROBINSON: Continued access to these Thank you.

devices are very important for a lot of patients, and I think the PMA shows me they're effective and they're NEAL R. GROSS
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reasonably

safe,

and

I

supported

the

conditions,

although the first one luke warmly because I strongly believe that expansive ex vivo new testing probably will not provide additional significant information, but I suppose we can try one more time. CHAIRMAN WHALEN: Thank you.

The recommendation of the panel is that the pre-market approval application for saline filled breast prostheses as from Mentor with Corporation the be

recommended conditions.

approvable

stipulated

We

have,

therefore,

completed

the

first

day's activities, and I feel very much like Bill Murray in the movie Groundhog Day when I say, "We will meet here again tomorrow morning at 8:00 a.m." DR. WITTEN: I'd like to thank our hungry

panel for bearing with us and the sponsor and the public today, as well. (Whereupon, at 9:21 p.m., the meeting was adjourned, to reconvene at 8:00 a.m., Thursday, March 2, 2000.)

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