101 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 toxicity* tumors radiation mutagenesis, term outcome, it.

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document, year

I read somewhere

in the document And so if throw another out it

that

the

20

was an narbitrarytt arbitrary, discussion.

time. I would It's

really 10 just

is to time

completely stimulate period.

arbitrary

CHAIRMAN SALOMON: they 5 year in the went after this is you've point.

The way I understand got a 1 year Now, you've So let's what do for take point, thrown this as do a

point

and a 20 year point.

10 year

Okay. a year, to

what for

you have to do for 5 years, what

you have to

you have for 20?

10 and do you that as a basis

have to do anything for some discussion?

How about

DR. MULLIGAN: nervous. something terms I'm like curious

I think talk

20 makes everyone about 20 versus in

to directly

10 in terms

of what's

the precedent

of toxicities, as opposed DR. is

long-term toxicities up until 10. The obvious cancer. to

coming on in

20 years

CHAMPLIN: induced

long-term And solid after

radiation

may take

even over

20 years you have that

develop

exposure. it may in

And if fact

assume

insertional longtime

some similar a long

you need for

end point

to evaluate

102 1 2 3 4 5 6 7 8 9 10 11 12 more pertinent would perhaps sufficient then not in you the think would Autoimmune number would off the disease, top and I couldn't but give I would 5 years

of my head,

that

be a much smaller to look in

-- probably outcome.

be plenty

at autoimmune situations a none 5

And so a concern, that follow-up.

where integrating years is

mutagenesis plasmid, might be a

situation If

mutagenesis

a concern,

you probably

do need 20. That field and the it word exempt of latent so-called incidence it is even Von of

DR. SAUSVILLE: to this

Economos' Parkinson/s. exposure

encephalitis

I mean, what or a virus is

was,

whether

was an

clearly

epidemiologically

15
,/

relevant

beyond

20 years. Indeed, briefing I wanted document Disease to concur I think

I

16 17 18 19 20 21 22 23 24 1 25 with Mr.

DR. BISHOP: Champlin. scenarios with In your

we outlined of the

for Hodgkin's leukemia afterwards thyroid,

where some until at 15

problems 5 to

may not

appear

about years.

9 years with

and we plateau breast and other until is data if,

Problems will

solid 15

malignancies years pertinent example,'as following to

not

become apparent And this

about that's

therapy. this

conversation out you're

because looking

for

you pointed

at a single

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103 1 2 3 4 5 6 7 8 9 the outline really apply at the would last event to occurring at the time this of therapy that could until lead many

oncogenesis, later.

may not

be apparent

years

The 20 year period meeting and it

was actually

discussed that at. out is this

was recommended frame to look

be an appropriate The other that we've pertains

time thing

I wanted

to point tier policies term

proposed to

in the

1, 2, 3 that

system would It

potential for long

to gene therapy address

follow-up. would

does not at all

the safety

data that phase

12 13

be collected

as part which

of a traditional is critical

1, phase

2, phase 3 trial of each product.

to the development

So, clearly, 16 there, last 18 from safety particul?r a broad this time that

when I used the word exempted was used by this example patient be Committee idea from to the

was a word that with is this not to that

particular exempt would

and the

follow-up specific

follow-up product, policy

but exempted

from a requirement, requirement that that would

requirement

or broad

would be outlined 23 24 25 try to be an

in the guidance umbrella to

document catch all

potential

scenarios. DR. CHAMPLIN: One would hope that the

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1 2 3 4 5 6 7 8

long-term post card

follow-up and nothing

beyond 5 years that's looking

could

be like than late

on a that,

more onerous for major

because

clearly

you're

events.

And the big problem people enormous negligible aspect of being followed of

is one gets in the

increasing long-term for often want very not is

numbers of just the

amount return. the

paperwork

a smaller to make that simple very and labor

So you really follow-up and, hopefully,

straightforward intensive.

DR. BISHOP: rather than post card.

I use the word questionnaire

DR. MULLIGAN: DR. SIEGEL: easy to target
16

So to try

to move ahead -it'll be such

If we want a target, that carry risk

for

those

factors

as insertion what we're

or replication targeting.

or latency class

where we know you're going going for to to

For this

18

have provide want to target

some guidance in the if

as to what we're follow-up

long-term

these

particular

types

we go to long-term the is just reason that we're card and if for it's

follow-up. the long-term

As of yet, follow-up
23 24 25

we've worried. it worry

heard

gene therapy I don't to solve? we don't

and we're know is

And so if that a post cancer

worried, is going so, then

Are we worried

about

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105 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 that. letting with yet. want about 1 or 2 year, we want in which 20 years? Are we worried want -We gave you

everything,

case we would Okay. --

CHAIRMAN SALOMON: I mean, Dick proposed that

and I was just to come up

the discussion a consensus,

go on before

trying

and I'm not ready proposed

to do a consensus if the risk or

But what Dick risk 20

was that that That that

the putative needed a

was mutageneses, year horizon. capture was his

you probably if it was

autoimmunity, year your horizon. question.

you could So that

within

a 5 to 10 with

way of

dealing

DR. MULLIGAN:

I think

it

would be useful according risk, is a

to go back now and look at what is long-term to the vector, I think there type for is instance. So if it's that

a cancer 20 years

a consensus

sensible say for activation order

of thing.

And we could

then arbitrarily insertional

integrating the

vectors,

mutageneses, follow-uplf

"long-term

has to be on the

of,that. If it's a vector we might long-term I that has potential that for

22 23 24 25

autoimmune follow-up

disease, is a 5 year For

decide

long-term

follow-up. think that's a very

an ex vivo rather

reasonable

way to do it

than have one long-term

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106
'1

follow-up. CHAIRMAN SALOMON: that's where the Committee's I agree. I think

2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 think in tier been hearing to have like tier

going. questions 2 in

Now, I mean I had some specific why is the plasmid 2? I mean, it's not replicating, long-term 2 if this vector very looking

at table

low integration it's not latent now. for

potential and we're How did the it

and it's not

requesting

follow-up as a test

end up in tier this system?

sense of

DR. WILSON:

That's,

I think, that

what we've want into include we've was with reiterated to now just the the a

from the Committee transfer situation kind of safety I we had cells. that

you didn't going didn't

any gene follow-up of this

categories that

long-term collection been

data that that

talking

about. that

thought in

conversation exception and

November And you've discussion

of the ex vivo

actually those

now expanded --

include

CHAIRMAN SALOMON: about the discussion 2 -DR. SIEGEL: of what you're telling No, no. us. today,

So the

way I

would

I would put plasmids

That's

the opposite

That may be why you think

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107 tier 2 3 4 5 6 7 8 that are short that that's there's going period clinical your you told you're doing 2. Tier 1 reflects that that that this Committee said that last a 1 is too low. 2 is the low risk products, about. the ones And now be

Tier

us we didn't telling us these follow-up.

need to worry low risk That's

products

we should

clinical

why they're

in tier

some things into cells of time follow-up. sense.

are not replicating are just going to

where we don't

even need to do tier 1 if

We can eliminate

CHAIRMAN SALOMON: getting doing 16 the idea here me. in tier

I think

that exactly words,

you're end up either

and what you'd I mean, in other

is okay with

you put plasmids follow-up in tier

1 and you add some long-term plasmids in tier in tier 1 right 2

1 or you leave that

18

and there's now. r something long-term.

nothing

I know of

DR. MULLIGAN: before If when you're

Well,

I think

we were on to

thinking

of the different 1 and make Jay some long-term

you go back to the tier about a tier what would be

23 24 25

less

nervous for

follow-up

1 thing. you would make

Let's

take a tumor vaccine,
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108 1 2 3 4 5 6 7 8 9 10 advice that 12 about putting if I get the the case there's therefore Therefore, necessary. term think, up* that, there's there's not a risk not this of insertional long-term activation, cancer risk.

certainly

not the 20 year follow-up what is the satisfies, followlike longI

And so we come up with necessary. in having say it

follow-up our interest And so let's you happy? DR.

And that

some reasonable

5 years

or something

SIEGEL:

I'm

happy

with based.

whatever I think

that's

scientifically was maybe

problem

some misunderstandings 2. But as I'm is, an

what we meant by tier together

1 and tier

what the advice tier

of the Committee is probably

we were to eliminate small

1, which

extremely 16 look years that that

number of things put than into tier

in any case,

but then 20

at what we've may be longer withintier we only

2 and say that for some of

needed

those;

2 we can recreate need 5 or 10 years cancer risks or latent that

a tier because

1 of those they're not risks

significant

infectious

disease

but have other that's 23 24 25 actually

could

be addressed

shorter,

where we would

wind up. That's that fine. That

CHAIRMAN SALOMON: works. that I was just

saying

in November is why I stuck

the examples

we were giving,
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109 1
2 3 4

plasmids saying, tell

in tier was that's

1 and was saying what the

all

the things was trying

I was to a in a

Committee

you,

was that a cell would be.

an ex vivo that

gene transfer short

with

plasmid

into

had a very

survival

5
6 .7 8

the patient tier

be an example Not with

of what we thought no follow-up, though.

1 would

Okay. Anyway. DR. SAUSVILLE: plasmids viruses than that. SO' again, plasmid think it should merely saying is something ludicrous. you're is a I where and run they're being But there into very are uses of

9 10 11
12 13 14 15 16 17 18

put It's

artificial different

systemically.

be X or Y I think

needs to be based on the

usage that

contemplating. DR. completely but did term disease, breakdown hearing gene it if it ,MULLIGAN: I mean, I these but hate things, to

change the way I categorized do it by vedtors that relate

you didn't in terms follow-up that

you actually are longautoimmune they we're on what

19
20 21 22 23 24 25

of the issue; issues relate to that

is there to

cancer.

And although I think depends

somewhat in terms that it really

of vectors, It

depends.

is and so forth. Couldn't we come up with
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1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25

that's not

more based on the nature so specifically tied to that

of the safety issue?

risk

and

DR. SIEGEL:

The intent

here is basically-

CHAIRMAN SALOMON: To be honest, what you're trying to do. That it's not based

that's

DR. SIEGEL: vector vector that's whether replicates, and the rest

on the of the

per se, but on specific that what the link the closely Committee can it to

characteristics those said be in latent, the genetic risks. At

least that it

November, whether

vector whether of those

inserts things.

material,

CHAIRMAN SALOMON: think system give that is. you the the answer is that

Right. that

And,

Jay, tier

I

is what this done in table

I mean, what they've tier. It's not

I is

by vector. fell but are of into I

Then they the tiers. think we're of

gave you in table DR. talking vector right? not about that You'd by vector,

2 what vectors MULLIGAN: Yes, that sorts

gene products lead to certain

independent safety

issues, then and

have to figure right? So let's

by gene product

say an autoimmune vectors, then they

issue fall

can be into the

given

by different

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111 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 risk is the little would versus most here, what different saying year. CHAIRMAN SALOMON: I think and there's you bring to will not wise the do; no way to up, Richard. of the solve it the difficulty today, is is that just in the categories, would require but less that risk we may now be than the 20

of a follow-up

And that vector not all the

addition vector latent, risk

class

and what

integrate,

integrate, is

become relevant being knows gene the

become latent, is But in addition

of which gene

product here

delivered. that. product,

I mean I think you put

everyone

I mean, if that

in an anti-A

poctosis than

would delivering,

be completely I don't

different know,

same vector

a cytokine. just is think to that talk that a

i DR. MULLIGAN: productive about

I actually go ahead time

way to the

more

different

periods

constitute cancer.

a long-term I actually about that, think

follow-up, if

autoimmune come to template risk.

we could a better

some consensus

that's

than to add in okay, Let's certainly retrovirus

now what poses a autoimmune take an cancer, what poses And

a~ cancer that'11

insertion. or AAV.

categorize

vectors

CHAIRMAN SALOMON: Growth
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factor,.

right?

(202) 234-4433

1
2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25

I mean if liver, kicks that's just out

I put

in a growth

factor

and put sits

it

in the and

making .something a growth risk, factor right?

up, and it for the

there

next

five

years,

a cancer

DR. MULLIGAN:

I think

it's

the

only

way

to go about most

this

is to -- I think by us, is this I think, blanket a tier

most people giving 20 year

would be of

comfortable there

a sense long-term

whether follow-up the length

or whether of time

there's of that

system in terms follow-up.

of

long-term

CHAIRMAN SALOMON:

I'm okay with there's a

the tier lot of

system. different risk with

I'm things,

just

saying not just

that

integration

is going point. ~ treating is

to be

cancer. DR.

That was my only MULLIGAN: where the If

you're gene

a not

metabolic oncogenic,

disease you know,

product

Goucher's

Disease of

or something. follow-up risk but safe. Yes, that's of or in a for you the

I mean, you wouldn't that, per se.

need 20 years

I mean, in terms on the nature of

of the cancer the vector,

may depending gene product,

per se, would

be considered Right. That's

.CHAIRMAN SALOMON:

actually where would the

a really

good point. wouldn't it

an example

gene product but

be as important be relevant

be relevant,

would

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113 positive 2 3 now trying concerned sponsors 6 way in terms So I think to bring about of the risk what we're implications. saying is that here, again

some consensus,

what we're demand of not the

is that

we make a reasonable for long-term

in gene therapy demands. and the Twenty

follow-up, regard

unreasonable Committee

And I think

in that same page. seems

FDA is on the year

8 consensus cancer cancer 12 13 14 15 16 17 18 19 feel year 21 22 23 24 25 5 years Be, for had would certainly insertional, given several risk, risk

follow-up protocols have to

to

be have

a a --

for

gene

therapy

that take

and we would would have to

those Yes, it's

be decided. by the vector

going

to be influenced being also

itself, we've by

mutagenesis times, being

the example that could

but it

be mediated

the gene product growth product. factor

delivered,

in an example of the poctosis gene

I mentioned

or an anti-A

Then there probably

is autoimmunity, be managed well

and inthatwe into a 5 to 10

follow-up. And then there or less example, intensive cells short that lives would be examples follow-up in which

would be adequate. ex vivo be at it that least was

were modified that could

relative

targeted'

and demonstrated

in the patient

that

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114 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 put a time a limit generating minute there I don't appropriate record given.' perhaps, 'up period. Are we okay there? MS. LAWTON: I don't for think all I just want a 5 year tier to say for follow-up the is And under suitable those for circumstances than that would be,

no longer

a 5 year

follow-

stating of those

appropriate that look still at

1 level. basis

I think that we be

has to be on a case-by-case some of that's that. all. SALOMON: short or too It long? And 5 years

may not

appropriate,

CHAIRMAN being too

may

not

be

MS. LAWTON: Too long. CHAIRMAN SALOMON: Well, I mean, I guess I mean if we can have a you're And if going you

know how to go any further. product, then

you give discussion to.prove can,

us a specific on what basis that less than just

scientifically 5 years is okay.

I'm a scientist, r ago. Suzanne,

show me the data basically. me a desperate look a

you give

'DR. EPSTEIN: limit

I think

it's

kind

of hard to hard to put of

on autoimmunity products

and it's

on which

do and don't That's all.

have a risk I don't

autoimmunity.

object

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115
1

to your

guess.

It's

as good as any guess.

2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 controversies response think conversion environmental delayed. It's vaccine, causative. relationship, studies they're have being relatively outside more than of the top of

CHAIRMAN SALOMON: I think. DR. CHAMPLIN: my head the You know, latent I don't period know off following disease in data

exposure this type

and the development of scenario. Vaccine MY quickly the risk

of autoimmune

I mean, there's autoimmune is diseases that

probably that these would

out there.

occur. occur

impression and that period.

5 years But if it. if

be on the

somebody knows

me, I'd DR.

be happy to hear EPSTEIN: only.able assume very really Well,

you

look it

at was

then you're If you that's not

to say you think some kind of

temporary and those and

hard been

to

answer

done

properly,

attempted But when unknown, exposure just

now. the might cause be of autoimmune some

is

some virus,

and so on, it

can be extremely

not known. In the that, the breast the implant autoimmune I

DR.

O'FALLON:

there

were claims 10 years long after

was 9 or

implants.

lO.years

is barely

enough.

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116 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 that wanted, Jay. is we've that the DR. MULLIGAN: case-by-case IND. is going I think that this care policy issue of

to be taken that this

of by the issue,

FDA and the we can't sort of

So I think it

do on a case -arbitrary doesn't

has to be kind 10 years sort really,

of a crude of thing. how the IND decide it

5 years, effect

And that

in any way, for

FDA wants to specifically

a particular

how long they want to follow-up. would be impossible for

Because otherwise something.

us to come up with

CHAIRMAN SALOMON: I think given you a consensus. It

my feeling hasn't

here really

varied

much from the beginning. I don't know if it it's reflects exactly what you sense

But I think willing very

our best

of what we're in which should that, just for

to publicly little

commit to in a field data. And in fact, I in most

there's point example, of

out that

my comfort yesterday infections in the

is diminished that the

we heard

common cause patients, was basically latent. latency.

adenovirus also

in transplant that we got, is

and that's

paper

reactivation, we look

which means adenovirus at table 2 it's

Yet.when

marked as no

So, I mean, there adenoviral vectors

just

is --

that

may be no

so far

as we know has

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117 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 asking willing inference stringent. was asking based. us now, stringent in just latency, situation. expert we're but that doesn't seem to be the that working about the I'll biological the most stuff,

So I'm just people in the

saying world clear

even with on this details. let

not

even really DR. SIEGEL:

I'm sorry,

you speak

a second. But let what I wanted to commit that I just for I me just say because you seem -- in it's the most you're to be some less that I

and saying to, was there asking

seemed for

something clear

want to be perfectly that was clear

something in fact

and science to less

And that as I than

what you're it, is

recommending

understand what we‘ve

substantially

designed in the

based on what you sense that we of

recommended designed clinical about trials.

last

November

a program follow-up

in which there because of all for telling

would be 20 years these vast us for uncertainties majority significant

what

all

these

--

the

of

, And now you're

numbers we should up* The only small you're

be considering of less

5 and 10 year followstringency is for that even have 5

issue

extremely need that, years

number where we said saying no those

we didn't also

should

of' follow-up.
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118 1
2 3 4 5

And I hear said something differently,

what

you're tell

saying.

If

I've but 1wrong

me I'm wrong, One thing you're

CHAIRMAN SALOMON:

about

is I don't

believe

that

anyone up here has given for how many things and how would many and

you any sort we think

of percentages 20 years would

needs protocols

follow-up need 5 year

specific anything 9
10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25

follow-up,

in between. I think that you what every the Committee gene is a doesn't therapy 20 year

want

to

do is until

tell

single

protocol guaranteed UP=

otherwise

notified

follow-up

or a 50 year

guaranteed

follow-

DR. percentages. that that if there

SIEGEL:

You

haven't

given

us

You've are not

given

us science

based guidance concerns, for long-term And if opinion, And I'm

specific types that

oconlogical of concerns

most of the other don't what we're that's saying require

follow-up that's then just

long a follow-up. that's your

hearing that

and if

something that's

we can implement. to less

a move toward asking wanted

stringent.

'Because youwere us -suggesting less that I

are you not giving you to I just give us

something

stringent

than what I -on the

wanted You

to make 'sure

we were clear

motivations.

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1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25

heard my negative I wasn't sure what

reactions they

to proposals were. And I think because based right. that scientific in

only there there science.

because was a was a

communication suggestion recognizing right, address You that

problem. they

weren't you're

And

that,

I think in this

I know you're we need concerns. in a say to

especially public have to

field,

concerns, address valid

not just public

concerns if you simply

scientifically we're going

way because follow-up

to do long-term concerns

not on the basis concerns, you have

of scientific then on. not a clue

but public

where to start archive

at what you follow-up every organ specimen on basis, stuck to

You know, we should examines

and do full everybody then

and x-rays isn't to go.

and everything a scientific And we're

forever.

If there know where

you don't

implementing go*

something

where

we don't

know where

I'm much happier discussion
as you

where we are now with can be as conservative

the

that

is based on -to be, but it

want it on risk

fundamentally design

needs to be it to be

based

so we know how to conservative.

appropriately

CHAIRMAN essentially that's well

SALOMON: said, Jay.

Well,

I

think

I mean, what the

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120 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 although work latent can't very case. cite we want vectors. point to risk lines estimate is on, Committee malignancy follow-up. Suzanne's we're is trying risks, If you're to say is if then we're you're looking about context year that or worried at 20 about year

worried into 10

autoimmune

risks,

comment taken about risks

and appreciated, so follow-up. with So

talking

Depending other we're flexibility not known.

on other

might follow-up

be defined is and the okay.

projects, just trying

maybe 5 year to give

sponsors

FDA the are

in a field

in which a lot

of the rules

DR. SIEGEL: one we haven't but time. that's

Latency

and latent

infectious time

specifically another

discussed

area where

you have to

DR. MULLIGAN: at this point to

It's talk do the

just

I'm

not any

sure of

if the

about --

Do you want specifically about

I just that

had one echoes

the adeno vector

in a different r And they're

way what Ann said. that in is, various those you know, of the vectors, into be a I

stages would

getting

e'ffectively, There's any

certainly

no question. studies, that but

And the pox -there's clearly

nonpermissive

pox viruses

upon infection'do

not

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121 1 2 3 4 5 6 7 8 9
10

kill, persist,

necessarily, I don't But

the know. certainly give very

cells. I don't

Now how long

they

know the information. would term that's -gene have in the the see

adeno long

potential guttedadeno that

to

form.

So I think

I would

more like

an AAV type

of situation. I think what we really are

DR. NOGUCHI: saying is that science because the public that We only you're

can take us to perhaps that's when the there science latest

a couple science

of weeks ago, is. for And that the reason

concern, right,

is some basis doesn't And it's know very know the

11 12 13 14 15 16 17 18 19 20 21 22 23 24 25

everything. hard for

know what we know.

us as scientists what it's

to know what we don't going to be. And that's

and predict precise point

about

your

guttedadeno. Well, I'm just they saying were kind maybe that of they

DR. MULLIGAN: you actually out lyers in simplify the old things

since

tier It

2 system, just makes it

shouldn't r progress

be exceptions.

simpler.

CHAIRMAN SALOMON: on that. 'Now there are

I think

we made some

a series we kind

of very of addressed.

specific (It's

questions, 11:15. I'm

some of which trying

to figure

out how to do this. but again this is

What I would

suggest,

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1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25

for

discussion, and try that

would

be to

spend

another four

15 or specific

20

minutes questions

and go through haven't

these

been addressed

and then

-- no.

What do you want to do?
DR. WILSON: It

just

seems to me that we really

at

this

point

that

may be mute since our systems,

need to go And so I right with

back nd revamp think you, we've proposal for the

our proposal. if that's all

sake of time, that we're to,

Dr. Siegel, had and

happy with obviously, your

the discussion refine our

we need into

taking

account

comments today. Jay t that's okay?

CHAIRMAN SALOMON: Philippe? All right. We'll

DR. BISHOP:

be back.
I was afraid

CHAIRMAN SALOMON: DR. SIEGEL:

of that. she of into

I

think that

Amy also, involves a lot input

described scientific what's this it's don't we're and I is

a process and collected going to

as well and

clinical and how.

pragmatic

And there's

no question while

be a process. we're but

Nonetheless, it.

being have

designed

also doing to

You know, we while

any choice

be implementing are useful with

designing, think we'll

and so these come back

discussions that for

something discussions

reflects'our

interpretation

of today's

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123 further 2 3 4 5 6 7 8 9 some specific publicly. And I think soon we could the Committee. I've expressed discussion. CHAIRMAN SALOMON: I think that maybe in not the next that's great.

one, but maybe

get some specific I think before at this is that

protocols.presentedto point the concerns nothing to deal that that with.

there's protocol what if

sharpens

the mind than DR. SIEGEL:

a real

Perhaps

we can do is

marked up protocols Not specific real

we want to do it

protocols. playing,

CHAIRMAN SALOMON: We can do role maybe. 13 we could do. CHAIRMAN SALOMON: 16 17 18 19 anyone listened in to well, I'll just tell you later this point the I'd like to DR. SIEGEL: There's

enough of them that

play

--

what I'll I just

play. ask, that is there having some to

So at the the

audience,

sponsors, today feel

conversation

that want

comment is exclude 22 23 24 25 problem,'and anything you

appropriate? from all the

I certainly fun. Okay.

don't They'll

take

we ‘come up with. And the heckwith I just want to you guys. Twenty years. I go on record that the before, is just practical

we've

said this

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124
1

implications

of this

is

that

even if

we go to

let's

2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25

say 10 year follow-up the dramatics of

-- I don't 20 year'

even want to get into follow-up -for an

investigator tenure thing, on that arrangement multinational around off can't that's practical I'm doing but the in

at an institution they're the

whose may not even have proposing this sort of off Or a big

at the time that to demand that person's with

institution or --

in signing well, yes. isn't

NIH grant a biotech

company that

pharma company that 20 years, -I just that to that

would be definitely have to -sign

my dean would

on this imagine going

have no idea how that happening. I just And scares so don't there's me here. things

I just see how a real I mean,

happen. that right really

issue what's other

in saying

these

up here,

part

of me is going

"Oh my, God." what centers an office where of

DR. CHAMPLIN: Realistically are going you're to have to do is to create to have a staff of people trial

going

and as part is

a contract the 20 year

to do a gene therapy funding for that

to provide longto is on

office

to do the thing

term follow-up. be sure that very short that and

And the responsible follow-up so it

is also

beyond the 5 year point doesn't become onerous

anybody.‘

And so it

needs to be are you alive,
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125 have cancer last year, and have you had a major and that's And impulse forums up, long 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 implement implemented here could follow is, there's sort of it. sort of an longer your irresistible and longer followBut as to illness in the

of organizations

to create for

and you get a 50 pager just is going

annual

and that

to be unworkable.

as one can keep it succinct, it's

short

and sweet and really doable.

the very

probably

CHAIRMAN SALOMON: The frightening I mean what institutions The first of course, than smaller or a bias Dick's saying is correct. up that is that

thing We would bigger time of

have this.

make groups question will is

institutions, doing this

have an easier And that comfortable that.

institutions. that I'm very

is not with

a prejudice creating.

But we are going A second these, thing

to create would that

be right these rules

now if will

we get

I'm afraid

much more quickly

than

any sort

of change can't for 20

in the way the NIH funds see how the years, absence NIH is going

my grants. to give

And I just me funding

you know, of that,

based on my follow-up. you're basically knocking

And in the us out of which

gene therapy, I realize.

and I'm helping

in this

Committee,

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126 1 2 3 4 5 6 7 8 9 10
11

DR. CHAMPLIN,: patient long-term a year or something

But if

it it's

could

be

$10 a simple

a very

follow-up. CHAIRMAN SALOMON: Right. But correct that there's me a $5 at

if

I'm

wrong,

but

I

don't

think

mechanism right .50 cents cents a dollar for

now at the NIH for for the the next next

me to ask for

10 years

-- I mean .50 think I

a year

10 years.

I don't

can do that. I mean, I have to account they'd that wait there's either a grant for that a lot every year. So thing I can't that

have to make some congressional could one. at stake DR. SIEGEL: be 10 years It just -it worries us. long, worries which

12 13 14 15 16 17 18 19 20 21 22 23 24 25

me here

here

Well, being the

That's because will dollars that the be

part the done. won't could help term

of my concern more that I think be spent

about

science less

based,

we ask for there's

research or the of

no question, aspects

and other

research with

have been done. of this data Committee that's --

And so we are defining is that minimal to get our

amount of longadequate, philosophy to simplify it again safety as

necessary and certainly it

collection discussed the

in November, data

would be to try and focus

long-term

collection
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127

1
2 3 4 5 6 7

scientifically concern. it around

around those That said, safety, and however, but there

items that first are

are of specific we'll to focus

of all going that can't patients

be other have we're

efficacy already talking data

activity But took

questions also I

people imagine

raised. -what it

to track

to collect to submit we're it

from them,

to put that

data together I don't think

8 9 10 11
12 13 14 15 16 17 18

to an agency to be talking

in a database, about

going

$10 a patient. No, I was being I'm now. not

CHAIRMAN SALOMON: facetious trying I want talking and so was Dick, to say is this to make sure isn't that's I think.

But the point base issue clear. I'm

a science really

science. Yes, everything you said for doing is correct; we

want science as Phil says,

based reasons to the I'm not extent talking

things,

at least

that about

we know. science If now. I'm

19
20 21 22 23 24 25

talking as we're next to year

about

practical

policies.

you go forward in the down isn't funding an An

recommending or two,

you to do, and at anytime finally there

you know, we get this policy, that day if

an implemented efforts

equal

on the part with

of the NIH and other that really this

agencies

to deal

the issue FDA is

creates, annoying.

unfunded'mandate

to the

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128 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22, 23 24 25 this making to the public requirements we should clear conduct allow just that won't unfunded therapy mandate to academic because scientists you close close business and safe, We won't in us down. you down, you in a manner gene

is a tragedy,

DR. SIEGEL: be able to

We won't conduct

you consider

appropriate

right? be able to

CHAIRMAN SALOMON: business us to hold according an IND.

to a manner in which you'll

DR. SIEGEL: require that.

And what you're right?

telling Let's

us is just be

you to do it,

about

CHAIRMAN SALOMON: I understand. DR. SIEGEL: so that that they That's why we're here talking

we don't think

impose on a community are inappropriate. We got it. I'm not

CHAIRMAN SALOMON:

you out to be the bad guy here. DR. SIEGEL: I misspoke, because sometimes people want

we do inappropriately don't input consider from the

impose requirements'that But involved. saying go to the if we certainly

appropriate. communities

,CHAIRMAN SALOMON: I'm appropriately and we don't funding correctly

you do NIH and

Congress that this

and the other is done

agencies and that

and make sure we get the

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129 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 to know ‘if philosophical factoring But I think than in that this will that's support from these agencies, the day you do this we do it medicine. If it does funded, of something then funds else, and and it'll kill it's the

an unfunded gene therapy

mandate until in academic DR. SIEGEL:

be used for important

this

instead

to know. I think that two the event we did come is exactly And the

DR. MULLIGAN: was a science something, that fashion the

based discussion, the next chapter fashion.

up with

I think

now whittling practical the that nature,

in a practical is titrating

now down requirements requirements will allow to a point to

complexity judgment

in everyone's

gene therapy

go ahead. So I really and whether from a was looking science this would of at this way in a very and not

based kill view, think

gene therapy. which that may be there is that or not

my point

different some sort

Jay's,

I actually practical

of negotiation,

negotiation

now has to be done based on this anything out. For instance, all the we'would propose could

to see whether actually

be .carried

you know you'd

really

love or

institutions,
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how many deans

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130 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 because, requirements -very the . in think at this precise like this. CHAIRMAN SALOMON: My point. DR. SIEGEL: we've for for Well, had that's these Yes. important long term haven't many been that today, 20 year therapy talking funding take That's will whatever something heads like of hospitals this. I'm agreeing you would possibly agree to

CHAIRMAN SALOMON: Well, have a lot of difficulty.

So I don't

know that

we're'really

disagreeing. The question here is if as we discussed about of all it

we go beyond follow-ups 'or gene

5 and start for specific

talking

10 and gene I'm of

categories that's

delivery

protocol, that that types

about.

If we do that, to cover

day the absence will essentially

arrangement

many of us out of those all I'm saying.

of gene therapies.

DR. MULLIGAN: now the next thing but

I'm

just

saying

that

I not the

we ought

to address, exactly

meeting, road

we need to address trying to implement

map for

something

fact, in place

some years a variety

and they

amount of data that we've

of reasons,

valid

collected,

have not really one of the

satisfactory.

And so I think

important,

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131
1

and perhaps about focusing focusing collected. the thing there's university that focusing

the

most these,

important is the that not

condition so much it's is

as we talk not just but can be

2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25

and so that as to data

research we actually about

possible, believe

And when you talk makes the runs

that

system where the

commitment

to do this,

in the back of my mind is, concern. but whether to doing if Not whether

you know,

another

or not they'll do it once

commit to do it, they've the best committed of

or not they'll it. You know,

even with that very

intentions

we have

a system isn't

without

much of

an enforcement it's

and that not clear

actually-accomplishable, we're going

how much data

to wind up collecting. DR. MULLIGAN: In fact, I would argue that to have to give because if that,11 they clear to be are cut very

this us

issue a better

enforcement, sense influence of the and

you're that,

going too,

certainly making

administrators there's they're a very going

obligations guideline,

enforcement worried.

DR. SIEGEL: Suffice regulatory secondarily to say from

Well, the is

we're

exploring of with view

that. our

FDA point largely

relationship with

sponsors, little with

investigators

and very

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132 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 understand important Dan's is to institutions. do certain certain We can require things. actions. If they if there the sponsor don't do it, to commit to we can take

Although

they're

out of business in the ability additional to

or dropped strength require factors of

the product, that

are limitations terms We've of our

hammer in actions. cases, like

certain in,certain

sought

civil

money penalties.

We can continue

to seek those. details, in the importance what we can do, But,

But not to go into know there's there's it's largely to talk limitations

although again, starting limitations,

a significant with about

amount we can do.

the sponsor. the the institution, NIH,

And when we're there's more

although with

obviously,

has more may

relationships have some other explored.

institutions that

and to some extent will

abilities

need to be further

CHAIRMAN SALOMON: Amy and then DR.. PATTERSON: issue. I didn't Yes. want to So this leave

Ed. is an

untouched

comments about entity

NIH funding.

And as OBA is not

a funding fairly

of NIH, I'll

make my comments on this

brief. But I think that NIH it's funds important a number for of everyone long-term to

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133 follow-up 2 years. studies Epidemiologic longer than 5 years, 10 years,
20

studies. to initial do long-term application, meritorious be on those be funded. is that I think that this merit the into data and follow-up and it well that

Your proposal needs to be part needs 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 dovetail in this results institutions, university discussion of the founded. long-term to be of your

scientifically would would

And it follow-up

principles

The second point about NIH support that

and the scientific underscores input of

studies

are contemplated input

need to get much broader the design of-these

and expert and the types

studies

collected. a good start

I mean, the Committee's down that in pathway, depth what

discussion

here is we really of how to how again to

but I think

need much broader design will the these data

consideration are the

studies;

end points, because

be reported for rare

particularly events

you may be looking have to be able r with DR.

and you're data critically. in to a

going

to look

at that

SAUSVILLE: that

That I wanted

way

does

a point

make in that long-term of

formulation we've

of how to go after into the

these

factored universities.

participation

And certainly yesterday,

where the party at

was,

as we discussed
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134 1
2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25

some level imagine always

to the that

generation relevant.

of the product, However, some biotech universities at free

one can not

being

that's

the case. not

And, in fact, gone through investigators

companies but gone standing

have actually to individual

hospitals,

etcetera. So by that way of thinking falls solely company about it, then of to to

this

type

of mandate the regard this

on the shoulders that is going

ultimately potentially being injected go into section diverse in

small that

as an additional And, indeed, scientific was put

impediment what

field.

was just would a study be quite

by Amy, the idea that this, obviously those of the if this

merit into

context, from those

interests industrial

could sector.

So, I think relationships guess broader or I share input here the that

there

are a number of complex mixed together. there needs that all be to I be

are being that

concern

because the effects that is not

of a rule to think,

is -these very

a policy

responsive could, I

different problematic.*

possibilities

CHAIRMAN SALOMON: I'd in terms long-term of Amy's follow-up, point, yes,

also point are

out that of for

there

examples

but most of us are applying
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135 ROl grant there's year awards in which, as far as I'm of funding concern, on a 5

no way to ask for grant award. So the point

ten years

still

is that

there

has to be not some of

some sort 6 that special 8 every

of NIH decision gene therapy of study But,

made, and I hope it's protocol has to go to sort

type

section

or some special the kind

application. that

I mean, that's about. I think we don't

of thing

we have to think

DR. O'FALLON: around destroy passion simple And I 16 the table that if

there

was a passion we might

do this,

gene therapy. that enough think all that

Now there

needs to be an equal to keep this gene therapy. on that

of us to work together it doesn't got to destroy

we really

concentrate

simplicity. DR. PATTERSON: ma. one more right and really

18

passion, design

and that the r studies

is

that

we do it

well. we just the follow-up Right? need to is

CHAIRMAN SALOMON: I think the idea as the that designing

keep straight 22 23 24 25 not that don't to as impoitant part think

studies issues;

long-term well.

has to be designed that there'll

I mean, I appropriate

ever be or is it all

seek consensus

on how to design
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136 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 guess that sense thinking and then -that Okay. that have, the we didn't clarify was trying -talking those about studies. CHAIRMAN SALOMON: 1 agree with to clarify. Okay. so, Well, a little albeit passion you could is good. point out to for to that part: And I was trying And that's to trials for the rest of the world. Well, I assume maybe you're studies that go across

DR. SIEGEL:

epidemiological

what I

amazing,

have the break that to avoid only that

we were supposed and take off credit schedule

but I'm going fact that Dr. we're

5 minutes

introduce

Noguchi. I did make a major not goof here.

Okay. No, Dr.

Noguchi,

you're has just

introduced. out to me is address the and I this

So what Gail we have two prior of the else they

pointed to

requests open public in the

Committee would would invite be.a

as part

hearing, that

anyone time so, that

audience also step

could about

forward. what I

talking

timing the way,

here, it

-'- and I Phil, of doing break for just before

makes more What I was hearing with

you the

leave.

was having lunch,

open public and start

come back

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137
-1

you.

Would that

be okay? going to have the open public

2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 told there that get started 11:40 p.m. minutes. are, I wish hearing. going

Then we're We're going to go to Phil

to have a break. of lunch.

And then we're Okay. We'll work

instead

on that. Okay. Just to show you how flexible tell we're this going to my wife we how

someone would Is that

flexible,

I mean. we'll

to have a break open public thing. 15

now, and then hearing

come back and do the into Dr. Noguchi's

and go right

Thank you all.

See you back in about

(Whereupon, until 12:00

the meeting p.m.)

was adjourned

at

CHAIRMAN SALOMON: Find our seats. with Okay. the break this last set the of the things session. that --

We can

One of is just

I was That

from the Committee. weren't being

was some concernthatwe recognizing speakers.

efficient extent,

enough-in that's

And to that

my fault

as Chairman. do well. of

That's

one of the things to everybody to be looking

I'm supposed'to and we'll

So, I apologize an attempt

make more

around. If people can help me by not just sort of

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1 2 3 4 5 6 7 8 9 lb 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25

jumping want helpful to

in and find speak as well. Okay. in

the people some sort of

who are speaking, order, that would

who be

So, this we just like to

last

of the session right? Sally and

begins Okay.

with

--

1 believe So I'd

go in order, to step ask Dr. up

Seaver

of the

Seaver

Associates

address

Committee. DR. SEAVER: opportunity manufacturing would bit to address group Thank you very Committee. very quiet, you first much for And since I decided a little the the I

the

is being

speak out.

And let

me tell

about

my different I'm,

affiliations. a consultant. products. to the I

as you realized, on all them sorts on

work with And I

people with

of biological issues relating products, FDA. of a committee

work

manufacturing working with

and controlofthose responses I'm also to the chair

including

at

the on and

United

States

Pharmacopeia, cell of the therapy whole that

and it's and tissue complex

the committee engineering, actives and products, division, five

gene therapy, also which chair

includes

committee blood

other vaccines

committees and dietary

in biotechnology, botanical dietary

supplements.

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139
1

And finally, organizing manufacturing various

many people quality

know me from aspects fields. are strictly and

2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 '21 22 23 24 25

conferences,

aspects

in the biological I'm giving

Today the opinions my own. other I'm not representing modes,

anyone or any of these

possible

or any client. disclosure,

And I want to comment on the the proposed in a few rule that Dr. Noguchi on the will

be discussing for

minutes

disclosure

xenotransplantation I proposed rules read from

and gene therapy. the the 70 pages FDA or and final as with rules, that most I very sort sections to me to that it would of

much appreciated discussed

the

first for

61 pages the rule

the rational

and the

of the rules. was that what

And the message that the FDA was that

came through for people

asking

disclose were very help

were things often

were not confidential, anyhow. of the And that safety

disclosed

assure ,

the patients Therefore, today long is

of trials. I'd like 67 of

the issue a section

I have that that's

‘to that

address whole

on page and it's the

70 page disclosure, it actually lists

section

601.52(c)(6) you disclosed. what they

where

information paragraph listed on is

And it's

a multi-inch the things

want.

And one of

NEAL R. GROSS _
(202) 234-4433 COURT REPORTERS AND TRANSdklBERS 1323 RHODE ISLAND AVE., N.W. WASHINGTON, D.C. 20005-3701 (2021234-4433

140 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 I've fact wording confidential some examples that iteration manufacture up to basically manufacturing final factors, used to product. cydicines, purify speed ancillary products And let used during me back off ancillary production. a bit and bring are. people And during in the growth

on what they that are

products

components should so they

used

really And

not be present can include

media

formulations, or

antibodies a gene therapy

a cell

fraction bioractor by the

product.' device ancillary which could use,

The actual

and cell

culturing an

has been suggested product. include Agents

FDA as possibly the product,

used to purify

the columns,

the enzymes you might

and as I said,

media components. this if you really -one

SO' in general of this this

is basically product. conflict FDA' said back.

everything

you use to

Now the where the

comes in that

in you

the can

other hold you here highly

information in this

And let me state

me give right

area and let consider this

most companies

information

confidential. So, for been producing that I've instance, if I'm in adenovirus beginning, less replication and the

and my 293 cells

now moved to a "better
NEAL R. GROSS ~,

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141

1
2 3 4 5 6 7 8

competent potentially I've by

producing

cell.

line"

like

PerC6 The fact

cells that

would have to be disclosed. cesiumchloride

moved away from using virus two after final columns all, and

to separate I use be

how many columns

because in the

none of the column resin so that they

should

products product.

are by definition I might use to

an ancillary

What enzymes product

chop up my xenogeneic product, both

or remove DNAs from my might if have it's

9 10 11
12 13 14 15 16 17 18

gene therapy and quite it

and xenogeneic frankly

to be disclosed, simply benzonase,

sometimes

has been disclosed. conferences, get people to usually products and I can tell discuss not in that

But in organizing you detail that our their ability production And even for if the company to

schemes is approved goes process, it one is. it

successful. the time

most of in often clever, in the

discusses very

particular don't you

a purification which product out which it's

they If is.

disclose can figure

you're But

19
20 21 22 23 24 25

general

disclosure

not there. which product these details it is, they media did, have

If they disclose very often formulations, etcetera. really don't disclose exactly And delivered I'm a lot all what including

like they that

purification companies

of information

to the public,

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142
1

including

Genentech. some really product.

If

you watch important

very details,

closely

when

2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25

they exclude tell

they don't

you which

And what I'm concerned that might it links the product etcetera, with

about the

this

rule

is you

exact

media

use,

saline,

etcetera,

and method of is that this is time and

purification. going both

And when I'm concerned of disputes, of the client a lot and

to cause a lot on' the part

of extra the FDA,

potentially

even some appeals. Some of my clients, they don't have a lot I'm that. purify. going to that we

of problem just using

disclosing the standard very

media because they

say fine, like

media or something about like

But they're Other tell highly might clients

sensitive are

the way they no, I'm not

I have

them anything confidential in a response because

about

the media. we've rule. the about.

I consider discussed

because to this it's

what

But I don't

mind on that

purification I've heard

same purification

Joe Blow talk

So, it'sverycompany-to-companydependent on what people not clear consider confidential. the And it's FDA is that asking it will for also for be an

how much detail products, and it's for

ancillary applied

not clear

uniformly

each reviewer
NEAL R. GROSS. /

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143
1

application. So, in conclusion it were -it's I can't if you do give not clear explain it -- and finally, some of to these even if ancillary and how the

2 3 4 5 6 7 8 9

product, therefore patient this

me personally, to my clients,

is necessarily information. between Okay. All

going right.

to be able

to interpret know the

How do they somebody's

difference media?

DMEN F-12,

proprietary

So, in conclusion, urge from the this FDA preferably list of it, things

number one; ancillary

I'd

really products

to delete to

disclose. define

And if exactly Phil,

they

want to include mean by ancillary do that 16 you want this 18 19 disclosed the start 23 24 25 FDA. the expect in your

to please products.

what you you'll

And I hope,

next

section. help the sponsors understand why

Please info

and for

what purpose.

And please

some appeals. I believe IND. ancillary They should products should be with you is or

in the

be discussed before anyone with

They should trials. with. about often is which

be shown to be safe That's What we're the most not what

disagreeing concerned that's

disagreeing of

disclosure people

information highly

consider

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144 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 know, about have kind this has the BIO, the opportunity from It's the Dr. Michael confidential. Thank you. CHAIRMAN SALOMON: Thank you, The next Werner speaker Dr. Seaver. time is

whose requested BIO.

and representing

MR. WERNER: Thank you. 1,m actually easiest Well, -1,11 good not a doctor, take but thank degree. for the rule from I Michael Werner. I'm Bioethics counsel for BIO Biotechnology more institutions, organizations than Industry 950 state in all Organization. you.

an honorary

afternoon.

Thanks

to provide

comments on the proposed disclosure of certain data

FDA concerning

humangenetherapy

anxenotransplantation

experiments.

represents academic related nations.

biotechnology biotechnology 50 states

companies, centers and

and 33 other

The biotechnology historically implications the

industry, public

as many of you discussion Company of this And

supported

of new technologies. need for and the value dialogue.

recognized of public principle

discussion

and public to heart

has been taken

in particular companies.

by gene therapy

and xenotransplantation
NEAL R. GROSS
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(202) 234-4433

145 Biotech' researchhaveparticipated their clinical trials DNA Advisory appropriate, have also their companies doing gene therapy about the NIH

in public at

discussions of for

meetings

Recombinant And 6 when

Committee

many years. doing in public

companies participated

xenotransplantation meetings about

experiments. BIO supports concerns, to its public dialogue, with the the we FDA

8

Although have some very proposal. calls along seems for with to real

however, preamble of material

According the vast

proposal submitted

majority

an IND to be predicated

be made public. on the notion

The proposal that this

information is 16 simply

is already incorrect. Although

in the public

domain,

and that

gene companies

therapy have the made type

and some of is

xenotransplantation 18 information information much broader publicly

available, under

to be disclosed in scope. Release

the FDA proposal

of the vast

majority

of IND data information of to trade This

22 23 24 25

would the

provide public

potentially and could also

misleading lead

disclosure information.

secret could

and confidential cause serious

commercial competitive

harm to the companies

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146
1

trying.to

develop

products to cure

using disease

gene therapy and reduce

and xeno human

2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25

transplantation suffering.

Now, over gene therapy and about matures

the years

companies

engaged have

in

xenotransplantation their and research. companies issues commercial

been as the to

forthcoming industry

However, get

closer

commercializing release

products,

concerning information

public become

of confidential

more salient. Simply information to develop the end, will put, routine significantly can be brought suffer will because be delayed disclosure of this

make it that will either

more difficult to market. potentially or won't be In

products patients products

lifesaving

commercialized. For decades contained existence Congress,and public proposal thinking, policy in an IND FDA has kept confidential. the In information fact, the The the this

of an IND is confidential the courts reasons

information. endorsed But our

have consistently for this approach. and to

represents troubling It's

a dramatic, change important

way of

in FDA policy. to note that BIO has from

proposed-a

plan

regarding

the disclosure

of data

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147 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 President Genesis, yourself. MR. MCKAY: I'm Malcolm McKay, for Vice Cell that would in a thorough of the would analyze necessary, to believe the pubiic secrets. BIO and its scientific, member companies legal We'll are engaged review official gene therapy agencies trials adverse trials. have Under access the to BIO plan data for from oversight clinical of

would according events

to FDA time and serious of

tables

reporting

adverse experts

events. at the agencies action if

A committee the data,

recommend regulatory report. provide

and make a public that with this would

And we continue the agencies and trade

important

data while

protecting

and competitive be filing

FDA proposal. lay

comments that

out our thoughts much.'

in more detail.

Thank you very

CHAIRMAN SALOMON: Thank you very Is there like anyone else in the audience comments to the

much. today public

to add their

docket? Yes, sir. If you can step up and identify

of Quality

and Regulatory company. with

Affairs

a gene therapy Very briefly

regard

the

proposed

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148 system consider three 4 5 6 7 8
9 10

for

long-term

follow-up, plan that and then

we

urge

you with

to the to on

the original different tiers

FDA put forth allow the or not the

sponsor

have

individual merits tier

discussions

with

FDA based that

scientific fell into

as to whether

company follow-

1 and was exempt from long-term 2 or 3. It might be that we might be in tier tier

UPf or tier

2 for 1 for

phase phase

1 and phase 2 and then 3. With regard to

go back into

11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 The flavor submission. INDs, these docket Cell issues with

the

public

disclosure

of

Genesis

supports

FDA's ability

to discuss to the about

in public, our comments.

and we intend

to write

But we are concerned

the issue and the that public, that

of publishing annual form, not reports sharing serve

an entire on the the

IND, the amendments Internet. information We believe with the

will

the public. a very complicated document. subsequent of

An IND is

of the IND often

changes with wouldn't about

And so the public what's clinical us current trial. to it's

know where to a particular IND

look to findcout or a particular that format. the

And we've use integrated

proposed summary familiar

FDA allow It's friendly,

consistently

NEAL R. GROSS
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149 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 staying continued won't all, stuff that with NDA's and it would give the company information an in

opportunity a succinct

to summarize

the pertinent manner.

and easy to follow Thank you.

CHAIRMAN SALOMON: Thank you very I certainly we're going won't to talk

much.

comment on any of the about now, but just follow-up in

terms of your comment on the long-term I think it is the intention

rule, to allow

of the Committee driven for

the FDA based on scientifically to negotiate be. that therapy I don't as data what think the follow-up

data reporting a vector should suggests of gene

anyone on this and our that

Committee

evolves that

understanding

improves, Dr.

shouldn't

be an option.

Noguchi. Thank you very much for for While after all the the I

DR. NOGUCHI: as long public

as you have, comments that to the awaiting to the let

and of course, we've heard.

I

18 19

speak we're

directly still

comments because, an evaluation of

,

20 21 22 23 24 25

comments submitted everyone all here don't

docket,

I would

encourage ,We take There

Florida

happen again.

comments.

We look

at each one carefully. counts. actually,

are no chads and each voice It is my privilege,

to be able

NEAL R. GROSS.-(202) 2344433 COURT REPORTERS AND TRKNSCRIBERS 1323 RHODE ISLAND AVE., N.W. WASHINGTON, D.C. 20005-3701 (202) 234-4433

150 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 regulated fact Dr. little bit to talk effort to you about that the proposed literally both rule. tens if This is an

has involved

not close at FDA

to a 100 different and previously around

individuals

currently

at FDA, including

several

of our guests

the table. And I'd like to go through, aspects in, of it I hope, first, a

of the philosophical some of the details

and then a short

to go through time.

Now just Seaver in

to

speak to the points

complexity,

in are is an

correctly

out many things This several there

involved example agoI or

a gene therapy that

experiment.

of a report I guess last

was in Nature in which

years

year,

was very type X-SCID be that out of type of

encouraging

data presentedthatperhaps that

a certain GammaC-R for might But

of immunodeficiency,disease, or severe treatable peripheral the -.in combined by a

immunodeficiency gene therapy. cells these live

actually to do

blood these that

mononuclear cases, literally and there gene therapy over

were taken are in the

individuals leave unlike

bubbles,

cannot for them, country. or an FDA, and

the hospital the first

is no treatment patient in this

They run column that

an FDA approved

has monclonal

antibodies

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151
1

other another vector, it

regulated

product

into device.

a Petri

dish,

which a viral

is

2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25

FDA regulated obviously another coated product, but that factor,

You take

FDA regulated plate.

biologic, itself This

put is is

on fibronectic

Fibronectin the flash.

a regulated transduced, have stem cell all of which

as can't Fit-3,

is

be done unless Interleukin-3, be used in clinical

you also PEG-MDF, trials

have or will entity. You put those

as a single

altogether level the

and what you come of transduction are

out with, cells And in seen.

with

a fairly

high

which

are now expressing cases of these they've very

gamma-c receptor. results actually they're are left going

several Several

encouraging that

children

the hospital, to school.

been vaccinated,

Desirable background

outcome,

extremely

complicated

on how we get there. Part of the on is that reason and the need for a and of

disclosure xenotransplantation nature Bacon, basically obeying

rule

gene these

therapy are products

as biologics. "Natura

Even as far

ago as Sr. nisi

Francis or by is

enim non imperatur, cannot be ordered

parendo," except at that

"Nature her."

about,

A different

way of looking

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152 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 brilliant who milk funny little that weive we only we'll know what we know as of yesterday probably it be shown that is there and others there that And I'd "In nature are we're there wrong. and tomorrow Or another or FDA

way to put punishments; reviewers consequence, consequences

are no rewards And our every

consequences." say "For

always

intended

are a 100 mostly

unknown unintended

we must address.@@ like to go through the years. for example, was a some of those

seen through Edward , scientist.

Jenner,

He said he saw some -- the maids got smallpox, but they arms. had these I'm

cows never

pox marks on their that that I'll I can vaccinate I'm treat going

And he said

so convinced the disease,

people to do

and prevent the first, his classic then children

experiment. myself.

my children

Which he did.

And fortunately, became a fairly almost an died epidemic from got way.

were protected. type of treatment, ,in the to Italy

And this but it

widespread death

an early of

because because lesion with didn't

there's

syphilis lesion to

transmission And the

was done needle the

lesion.

contaminated Again, we

syphilis

somewhere

along know. the

know what we didn't In 1901 was

start

of

biologic

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153 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20. 21 22 23 24 25 inactivate was the next over 11,000 they died regulation antiserum therapeutic reverse diphtheria where a horse for that diphtheria. diphtheria. was very, More named Jim was used to prepare Now diphtheria very. useful and died by polio, was could from so it a

children

than has ever been effected disease. died because in that Salk the not

was a devastating

12 children from tetanus

of diphtheria, Jim, the and it

but horse, was

poor

contracted transmitted

tetanus through Jonus

meantime

antitoxin. successful himself with inoculated his killed first

men, women and children was commercialized,

vaccine. lots that to

Once it

the very

were prepared about

when you go from liter

a 10 liter every

carbide forgot

a 10,000

fermented, or else

you had to stir of it people version

the virus

you wouldn't And in fact, with the

get inactivation many of the first first polio. commercial ,

by formaldehyde. that

were inoculated

of the vaccine

came down with

This. continues polio,

on.

Once you knew how to syncytial. After stirred, all, virus, we know simple.

RSV, respiratory

one to be attempted. keep everything time that

how to inactivate, The first

was done when the next

NEAL R. GROSS ,(202) 234-4433 COURT REPORTERS AND TRANSCRIBERS 1323 RHODE ISLAND AVE., N.W. WASHINGTON, D.C. 200053701 (202) 234-4433

154 1 2 3 4 5 6 7 8 9 10 '11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 that. biological a little tell year It or two years experimental dose, in this season came around for RSV, men, women and children whereas the controlled we think now that group there

died who were vaccinated, didn't.

That was because that to do with to this

was something no RSV vaccine antibody still

Tl and T2 immunity. day. There but

There is

is a monchrominal we

as a therapeutic,

as preventative,

don't

know how to do this. University of Pennsylvania this last year in

ago now, an 18 year gene therapy, type others

old patient received

died the event

same both

did not have this trial and other here?

of an adverse

trials.

Do we know what -we really

killed don't

the patient at this time.

Human subject

Even a toavirus 2000 was with prevents cases infantile it All products bit, but causes this withdrawn

vaccine, when it but

approved was widely in

in the used. few

diarrhea,

a very

select

intussusception. is merely to will say let that for

mother nature she always

us push her to

comes back and tries want to

us "You know, route." Now, this They short

maybe you don't

go this

particular

is the proposed

rule

to get into rule on

named it

FDA as the proposed

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155 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 in have fact, a therapy out that public disclosure. This is the longer It official title,

Availability, of January sometime comments. respond At last with this

etcetera.

was published

on the 18th so that'llbe be the final

a 90 day comment period, month on April 18th will

And, again, to the docket count

we encourage either

everyone

to please

in writing like

or by email. 40 all written of which and rule.

we had

something

comments will

and close

90 email

comments,

be read,

evaluated to

and used to go with It's this not

reformulate proposed a final. is for

see where Remember,

we need it's

a proposal.

The scope

and the

purpose

gene

and xenotransplantation. FDA for decades specifically

Mr. Werner did point for INDs. which

has had a policy for

We are speaking is a decade old. Part that different

gene therapy,

of the reasoning gene therapy experience with areas

behind

the rule

is,

and xenotransplantation than other areas of They have is may

clinical,research represent potential it's the team, not unique for just to

FDA regulated of clinical are really

products. research unusual; that that that

risks the

that

human subject It

or patient could be the

subject as'in

adverse.

surgical you could

the case of xenotransplantation
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156 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 transfer‘review, in response provide, for public products a therapy are. with Part actually, discussion This rule, to It the started have transmission or inadvertent, to offspringwhetherthey're and things We've It's seen not of this what just the a single to it. of ‘the rule is to nature. complexities product, it of is verdant

multiple of the

aspects reason

a consistent and public bytheway, 1999 in death

amount of information access. was not promulgated of a gene therapy was this the

individual. public National whether the

1994 when there

discussion AIDS Task or not there

and a departmental Force, that asked

committee, the

question between We went but the

was duplication FDA review discussions

of effort process. with this, time

NIH RAC and the a number question of that

through critical

was asked at that and I would

is even

by 1994 there public by the

was a tradition by the and

say global sponsors,

acceptance academic to present

community, the

by the

especially

pharmaceutical would that

industry

a large This

amount of data that did include things

be available we'll get into

publicly. later. issue

The

at

that

time

was

could

be

sole review

responsibility

to the FDA

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157

1
2 3 4 5 6 7 8

and guarantee you've IND is heard

that

access.

And the answer

is no.

As

by our own laws, and it's

even the existence by our own laws

of an not

traditionally unless This, of

acknowledgeable elsewhere. amount awareness you're

been publicly provide will

disclosed a consistent patient all, if

as we said, it

information, and consumer

enhance After and you're events

protection. trial

entering

a gene therapy the types

not up that can goes

9 10 11
12 13 14 15 16 17 18

to date 'on all happen, for whether

of adverse large or small,

they're

and this

the sponsors,

by the way.

Up to date

information

needs to be available It and up to written part public date will

by one means or another. help, we think, consents ensure as they're but accurate being

informed

and updated. of the rule discussions. Now,

And a small

a significant participate in

is allow

FDA to fully

for

gene

therapy full the access

and to

19
20 21 22 23 24

xenotransplantation, discuss have willing issues this things. been to are early Part

we do have that of it well these to is because

sponsors have that been the at

exceedingly ;discuss going stage

versed things

and knowing

be primarily

safety

related

\
25

of the game. is disclosable, and this is an

Now what

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158 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 proposing patient in this confidential competitive disadvantage confidential experience Recombinant disclosable. I think process, incipients, ancillary important disclosable aspect under Trade of it. Patient statute. information definition It's is is that not was information not

any federal secret

We used the narrow court. that

1968 by the district it's not the idea;

a productive as things like of sort

and we will products

concede

that

certain into

types this

very well

would fall

of a category. There's a limited amount of commercial this of on our Health

information with the

and we're National

basing

Institutes

DNA Advisory

Committee, Group

the departmental and its various

Xenotransplantation meetings Secretary's Xenotransplantation. The that it's

Working had, public

meetings. Committee

And now the for

Advisory

key

factor information to a

here, which

commercial can give that will a

means that advantage the What

competitor

innovator. is disclosable or what we are and

to be disclosable. safety will data and related be the preclinical

This will

be product

information. data, animal

Included data that

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159 1
2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25

very

often

can help

define

or help

guide

us away from and adverse

situations risk.

in which there

may be potential

Name and address Clinical protocol past trial for indications

of sponsor. to be studied We have heard and the in the

each planned that

study.

as an example is commercial since trials

even the design It

of a clinical us in a bit

confidential.

puts

of puzzlement many of forward the when in

most of the trials in gene had and therapy extensive in

and certainly are only gone

FDA has that,

modifications FDA will property

implemented consider rather

many cases

some of this than

to be our intellectual

anyone else. There is written of this informed consent for as

provided not view patient in

in 50.27 itself

chapter. informed

Although consent,

FDA does we clearly adequate

regulate

this

as an important safety .

means of assuring

as we go forth.

Identificationofthebiologicalproducts. if we just here. looked I at this that there the we

Dr. Seaver is correct, are a number of

subparts

think

question will

of ancillary

products

is a good one that

need to address. While we would acknowledge that some

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160 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 sense that we have ancillary ancillary products or things that might be considered of columns be considered and in

such ,as a design are being

and types used could

how many columns the nature

as commercial In terms

confidential. cell lines, I've what shown that is not. but what

of the producer from line the

seen just a cell

few examples

YOU, is that is thought That this

or a biological or safer" it's very

material often

to be "better mean that that the area.

does not does

disqualified, to of fact, know any

mean is know what

we need risks In that we have

and have particular the where many

everyone biological exception there different always adverse acceptance trials, is

product

many with

of the RSV vaccine no present tragedies one, with

we saw before gone through products,

biological

but it's knowing the the these events

been on the basis events, the

of understanding, and getting who participate have very

risks public

actually in

by the which with

sometimes them.

adverse

associated .

Biologics there

are different

from drugs be a dose

in the related and the

may or may not

phenomenon. person's

It very well

may be idiosyncratic

response. IND safety reports.

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3 ;

.

And report. of

then Now, the

information if we look

submitted at the the

in

the

annual

actual of gone of NIH

requirements
4 E 6 7 8 9

annual is rather to been

report, sketchy. outline required have

amount We've

information further information guidelines submitting in

required this that which information. One aspect

proposal has

the by been

types the

sponsors

routinely

that

we're

talking

about

here

10 11
12 13 14 15 16 17 18

is the regulatory it's on hold,

status.of

the INDs, inactive

such as whether Some much of

in effect,

or withdrawn. that far too

of this our time

comes down to the' fact is spent

over the phone with

the media trying suchDoes

to save "Well, and-such that reality to really is the

is such-and-such

on holdV1 and "Is hold mean.

on hold.

What does that

mean somebody has done something of the administrative a minute,

bad." that

And the FDA has

mechanism

say wait clinical ,

we want more information

19
20 21 22 23 24 25

hold. We think that in many respects, can help demystify actually, the fact it's

this that a part

kind clinical

of information hold

is not a good or a bad thing,

of the process. Then finally there the is number ten, of which is

a clause

which

allows

Director

CBER on very

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162 1 2 3 4 5 6 7 8 9 10. 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25
.
(202) 234-4433 -

unusual, all.safety

very

rare

occasions

to require

that

even if

information on a safety that in

has been provided basis fact to disallow

and we have an IND to only by

no objections move forward, petition it's

we can

invoke process. issues this

to the Director, determined that

a lengthy

And if to be

we need ethical ask the question but

discussed, done,

we need to it this

can be it be

we think

can be done safety would be the

should that

done at'all, invoke

clause

we would such as

in order

to have a public Committee,

discussion

the RAC, such as at this advisory committees. We're disclosed. several simple making

such as at other

a proposal it of data, reads

on this this is

could

be

The reason reasons, the

that first this

way is for that it's

which put it

to say get all make it concept public if, that trials that wrong. is going you.

in a database basis. That's is small.. and the grow. We we of

and then a useful

on a periodic

in fact, the for

the population of patients will

We anticipate number anticipate could be the r

number gene

therapy will that

some day there As we do

be products, the amount

information can guarantee

to grow,

FDA is not.

That can we

What we are asking,

therefore,

and part

of

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163 1 2 3 4 5 6 7 8 9 10 11

this

is to help at what

assure is trade

that

the

sponsor always

will

be able

to look information confidential redacted including would and

secret,

what patient

is there

and to determine is each IND. there

what commercial and official to an and IND

information version the of

submission The redacted

original patient limited

document secrets

not a

contain certain

information, amount certain of limited again

trade

commercial amount. because we has but to a

confidential

information, The idea,

and this

is

don't

want to get

in a position

where everything request,

12
13 14 15 16 17 18

to go through rather proposal,

a Freedom of Information in a publicly a certain

make it is that

available

format,

after this

amount of time being correct and

used to make,sure is accurate, it

is administratively

would be forwarded

to a public office create the life

docket. has said an IND of the be

Now, our public that docket each with IND number will the same number. this information

dockets

be used to Through of redacted the official patient

19
20 21 22 23 24 25

IND then, submitted

form would document

to the docket,

which

has both confidential and trade secrets

commercial, would is continue a radical

information

to be submitted. change that in a way, of

Now, this but what‘it is also

is a recognition
NEAL R. GROSS

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(202) 234’4633

1
2 3 4 5 6 7 8

experience

of

gene

therapy in to

and xenotransplantation fact public disclosure development; such as an field moves to

have suggested has not -that

to us that

been detrimental very often to

commercial things

in fact event

even those shape

adverse forward. the public

help

how the it

And that confidence

in fact that

currently up to

has lead

recently

we have

enjoyed

in the area We believe

of gene therapy. that for all the reasons from history different, and given the of

9 10 11
12 13 14 15 16 17 18

before, lessons biologics that that they

that from

if the

we can past that

learn,

especially the are of

throughout biologics amount

regulation require

a certain evolving,

openness

science

is always will It

then in fact

what can will be

be imagined done with this

be done.

And we know this humility, our are

hope.

must be done with the hubris end point, that

and by

we mean not

scientific a part of that to be

decisions the

must be the but

they

19
20 21 22 23 24 25

end point, -science,

we have to also today's dogma,

acknowledge is going

today's tomorrow's

dog meat.

As science

changes,

so does our

interpretation

of what is And finally,

important. as we move forward, it always

needs to be done with Thank you

compassion. very much for your kind

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165

attention. CHAIRMAN SALOMON: There&llbe sale in the lobby with that last one. It'll T-shirts help on the

database. Thank
6

you,

Phil.

That

was,

as always,

done extremely

well. I have no official questions is a to guide what provision for

8

happens discussion

now

and

yet

there

here.

And so I very is that

much have no agenda get a chance to

and my objective speak. Abbey.

everyone

MS. MEYERS: Well,
14 15 -16

I just

want to say from one of the most done. It's

the patient important extraordinarily

community that

this

is probably has ever

FDA important.

And I was at the last
18

RAC meeting should

and they be that is, more went of in is

voted

unanimously There's the that RAC. there And the the

that

there

19
20 21 .22 23 24 25

disclosure. through course, the field.

some type of regulation And one of the problems

seems to be a general only thing that to reprint

secrecy get Street. it

people Wall

basically And writers newspapers.

news that's that

released

pick

up and they on the

in the is

And while

one hand

industry

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166 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 an engineered continue especially concern, of the to learned started, years, is in saying clinical thing we need to trials, secret. trial attract more patients want FDAto into these

they still So if you call

keep the whole

up and ask FDA is there for some disease,

a clinical they can't

on gene therapy you if that there's the

even tell

an IND. lessons since that gene more we've therapy than 10 had public then we I

so,
the which that

I think last is if

10 years actually

a little agriculture

biotech,

industry for

been as opened and there discussion wouldn't like be facing the

had been a forum biotech problem foods,

RAC for this big

we are today. engineered closed doors that

mean, people foods. and it

are scared

to death

of biotech

Why? Because it was in secret.

was done behind And we can't

afford

to

happen with

gene therapy. I mean, nobody's tomato, die genetic going to die for lack of to

but you know people from these horrible which is

are going diseases, my area

diseases, field

of

unless death

this

moves forward.

And because University of

of this

young man at the teetering losing things its right,

Pennsylvania, here. That

I thinkthatwe're the handling public these is

on the edge faith in the is

government

and this

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167 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 proposed perception there, opposite that debate well. you wanted all to support things but let they it read the so%ution to put this out on the Internet a trial so that and,

people hopefully,

can see that

100 people

went into alive. is

95 of them are still What frightens about it that

people

the

fact or they

that see and

in The New York Times 100 people

on 60 Minutes

were in the trial

a 100 of them are dead. So, this this that is the solution. solution. might And I urge you take

I agree perfectly; be patentable

out the secrets,

or the trade on and let

us know the trial adverse events

is going have been.

us see what the

CHAIRMAN SALOMON: Alison, to make a -MS. LAWTON: Yes. I actually Abbey. sides Although here, the agree we're Thanks. with

you looked

like

your

last

comment from say

probably generally absolutely,

coming I would for

I think need,

we recognize and for And for

public as

the FDA's need to have public that very reason industry's

debate

need to

have public

'debate. I think rule of the the the big question right proposed way rule to I have is is this do as it it. is And is, my no,

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168
1

that's

not the way to do it. allowed do it that

And I would

like

to see the

2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25

more time best public form.

to have more discussion to provide the in patients the best

around

way to with

and the possible

information

One thing discussing example, aspect required I would this. During heard, therapy concept you're for example, of the we talked advising follow-up about

we talked of

about

earlier trials,

in for

clinical the

the need for needed

scientific just what's And around

what's

versus point

from a public come back to

perception similar

of view. thing

type

of

the last there's not

couple over sure the

of days we've

also

200 INDs on gene if people information that have any that docket of data get this

trials. of just

And I'm to try about,

and get

talking

Abbey,

to go through

room and to look of 200 INDs is

through not

volumes the best

and volumes way to

information

out to the public. So I think from the safety there's the to solution the perspective and

what this.

trials I

care ongoing, don't have

a better here.

way to do We will But what I

definitely really

be commenting encourage

docket.

FDA is that

you allow
.-

the time.

And

NEAL R. GROSS
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(202) 234&33

169 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 is not the of the docket comments. carefully I know that proposed appropriate for all of you will but to be reading to look make sure at the public, the comments to the we have
the

rule, time the

that best

way to do this patient and FDA

industry,

needs. DR. And, NOGUCHI: of course, Thank you for to look those very

we are going step

and see what the next Just one slight is that, look right

is going

to be.

correction. itwill it in

The actuality be electronic. person, but last each six

in fact, at

You may come and submission months, as of

now for

about

the

everything

coming in is both available

in hard

copy as well

as electronically. MS. LAWTON: I'm just trying to get across

amount of information to actually the safety try of

for

somebody to have to go a question trial, for

through around example.

and come up with a gene therapy

r at

DR. NOGUCHI: all examining It's simply

That is a good point. any saying we think database or

This search

capabilities'. that for these

we have determined this is a limit of But

two areas

what is commercial not anything about

confidential retrieving

and what is not. the information.

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170 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 my feeling not proprietary Investigators anyway. safety publicly very adverse think MS. MEYERS: events they are? MS. LAWTON: Adverse information have to report with is events currently are Do you agree, though, that or you

are not proprietary

information,

because they're them through

reported. to the NIH of the will be a

And, obviously, database available. that

the establishment something is very that

And so that that is

definitely

important

aspect The question

should again

be made publicly how do we do that in looking at those putting populations. very it

available. and is it adverse into All

better events

to have expertise and analyzing it

and, again, of patient

context of those

within aspects,

the types I think,

we have to think

carefully

about. MS. MEYERS: Well, that there should I want to just be no delays register in this. you is

These regulations do about-all information Internet. family that, these about

or changed regulations, little adverse questions, events is that young that

whatever

the main thing should

go on the

And the reason agreed they that their

when the Gelsinger son should had died go into in the who

had no idea testing.

animals

preclinical

They had no idea that
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171
1

were in theltest levels chance. after the

before test.

them had abnormal And they need chance. there your

liver

enzyme

2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25

a fighting

Patients

need a fighting sitting put a trial in the

And when you're about mother, getting document under whole whether or your the you should into

and thinking or you're your not

child and if informed

spouse

whole

truth of course,

consent and

because,

IRBs are overworked else,

funded truth.

and everything The it's going patient

we need to know the community needs it.

Otherwise, whole field

to end up on 60 Minutes

and the

is at risk. CHAIRMAN SALOMON: Again, I have no agenda gets that a chance to we could get the for

today

but to make sure that There I don't to are lots think

everybody of issue

comments. into time that today

really and to what should

we're try should

set up with and define, be in

do that of

example, disclosure should find the

a universe or how it

a public families, that those you'd are out and to

be shown to what is it

be on a web, you know,

when you opened the website. kinds of details that have

I think to

be worked in industry appropriately

between

the FDA, between

the sponsors responds

done in a way, Abbey, your concernsthataccurate,

that

interpretable,

accessible

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1

information that's, real

be available from my limited

to

patients. point,

And I think where the

2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25

view at this

concerns

are. You're.not going to a website model. not going I think, that It's to be able to interpret not to allow complex a

family results It's it

member going in not fair.

an animal It's

appropriate. nor is a

to communicate,

going

to contribute,

to what you want; on the table. those

sense of reassurance So I think the details that

everything's

those

are the issues,

are out.

are going

to need to be worked I'd like to share extent

DR. SAUSVILLE: thoughts in both and actually biologics and extend in

those that

them to the so-called

small toxicology toxicology, concerned

molecule studies toxic that the

drugs the nature are actually effects. undiluted of that hinder

of the preclinical if possible, very

to cause,

And I must say I'm anduninterpreted type patient could be very to trials.

andunfilteredinformation problematic otherwise very and actually reasonably

access

constructed

clinical

'DR. SIEGEL: the website would be --

What, of course, what is

would go on is some And I that

proposed the FDA.

redacted think for

versions a similar

of what --

comes to

notwithstanding
-

the fact

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173 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 the patient else. DR. CHAMPLIN: should have so I always access to support that And while both idea is that there we have general undiluted, studies rather for sophisticated reasons animal scientist don't data. summary like sponsors to Our reports send in us

similar unexplained

animal and

come with

explanatory

interpretations. DR. SAUSVILLE: was a desire of either this to Right. for What I just heard

an Internet is,

disclosure and even initial trial, be very for

at one level if you extend

of what actually adverse event events,

the

occurrencelof again, taken

one adverse

in a clinical context, the could

out of a clinical I mean,

problematic. stopping clinical event. So I think I -trials

usual call for

rules

actually

more than

one adverse

this

is

a very

complex

area. very the

I mean' to

be clear,

I mean I'm amenable to

personally of

and professionally dialogue that to

a constructive to be concerned could

how to that

do this. without

One has

access

interpretation

ultimately

be deleterious. and then who

CHAIRMAN SALOMON: Richard

reasonable events.

information

and be aware

of pending

adverse

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174
1

One has to keep in mind a couple The specific often are not reproduced organ

of things. toxicities very in animals dependent And so if doesn't

2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 trade secret interested in given events

in man. It's

on the species liver toxicity

and the metabolism occurred in the

of drugs. dog, that

necessarily

mean that

it's if

going there's

to happen in humans. detailed species. is you're the of course And information

So one can be mislead about toxicology The in the disease happening data other

in other issue

observed state in there's leukemia

versus

expected.

a background patients, for

of adverse example, the how agent standard has to

undergoing raw adverse much is truly and

chemotherapy. event data,

And that it's not

when you get clear exactly

attributable is those this is to be

to an investigational expected And context, to in so the one and

how much of keep

treatment somehow information balance

patients. all in has

whatever with the

provided overall

be given

of that

discussion.

CHAIRMAN SALOMON: Amy. 'DR. SIEGEL: information Other what is Well, the rule suggests that would would be be

and patient

identifiers

be redacted. essentially

than that, submitted

the documents to the

FDA would

NEAL R. GROSS . .
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175 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 a perhaps because providing that's talking I That's submitted Internet. Is there DR. some commercial A limited redaction? amount, yes. also and redacted form for posting on the

NOGUCHI:

the proposal. CHAIRMAN SALOMON: Any and then --

DR. PATTERSON: I wanted to make a comment think it's an and the important context for issue about

an analysis provided about. to

information Ed was just

public

on what

There has also been out for public synergistic or complimentary of adverse The interplay that I think proposal event

comment from

NIH regarding safety proposals explored involve

the reporting to NIH.

and other two be

information is further.

of these needs that to

something But part

of our proposal

would is

FDA cooperation

or collaboration

and input

the establishment that the

of a national session look

data assessment and would at the

board

would meet in close data reported, into the

look at all data the being two

would comment

entered agencies, basis

database out perhaps

between

and would report

on a quarterly in some sort and report

to the RAC and on an annual summary report of the

basis findings

of written

NEAL R. GROSS 4
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176 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 indulge safety to think right that that fact I think that the information across vector in context, class, across do analysis clinical across trials,

indications. on the table to the is not

So, I justwantedto the federal merely putting agencies

put that

are sensitive

up raw information

necessarily

beneficial. MR. GROSSBARD: Elliott Something of unintended that Dr. Siegel Grossbard. saidpromptedme And you're quite

consequences.

on many submissions studies, for

sponsors

in describing in a fair and the over the ignored matter. or

toxicology

instance, spin

indulge control, and I've of gets

amount of what might FDA reviewers years blown

be called

are very sophisticated just in kind

come to see how it off and people handle

appropriate

Reasonable

can disagree. version this could kind lead if of to short about companies activity were to around

In a redacted themselves studies, with this in

an interesting of a labeling whether the for of an

interchange meeting company's presentation ongoing that

FDA, something but a discussion is

perhaps,

'interpretation to the public

appropriate to kind

and lead a scientific

engagement

around

interpretation

could

be a distraction

in many ways.

NEAL R. GROSS -.-.
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177

1
2 3 4 5 6 7 8
9

CHAIRMAN SALOMON: Alison. MS. LAWTON: comment. I think that's Just part to follow-up on that to how is

of what I was trying to work through information

get at as far we do this

as we need more time timing

and how the

of the

made available, Because could with future so the that's

how the information one example available that where

is made available. information that would be

be made publicly a company's

immediately might

perspective

change in the at it. And

10 11
12 13
2

once the FDA's had a chance to look timing could Likewise, be key. with event adverse may have get that out actually events. a very

You know, different followthat

a serious perspective

adverse

14 15 16 17
18

when you first to find

to having the

up information serious adverse

reason

event

occurred. both details examples around of why we need the processes

So, they're to really and how the r following of course. sort out the

19
20 21 22 23 24 25

information

is made publicly I just

available. think a point yes, said. if or a year

CHAIRMAN SALOMON: sort

of where Abbey was going, I support shouldn't that,

is that

'And we also

as I already

However, data is

go so far fully it

as to say that interpreted might take

there

that often

maybe isn't times because

understood,

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178 or two or 20 more not events necessarily public assume to really put it into

context, not

that's

an a priori domain that

argument

to have that we

in the

in some form. patients and in the you and

Because patients‘ 6 process know, 8 I'm

shouldn't can't informed

families of a true at the

go to the investigator consent about

and say "Well, such-and-such

website about I don't

I read it." necessarily That

concerned

see that in

as any sort very the the that

of

a negative

thing. of we're to fight

is,

some sense, between patient and

positive physicians patient's

aspect -family

a

partnership the

asking take for,

a risk. too,

And I think here is

what we have to responsible 16 for and 18

reasonable, not fight later exact

information

transfer, until

but still it's

no information it's happened mechanism.

transfer 25 times,

5 years

and we know the

molecular

DR. SIEGEL: not envisioned of that this that the

Well,

it

should would There

be noted be the are

it's only other

patients

consumer 22 23 24 25 context. investigators,

information. there

are physicians That's

and so forth. important

cBA1RMAN SALOMOR: Thank you, Michael.
NEAL R. GROSS.,.
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Jay.

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179 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 proposing scale other as many process memorized years in DR. O'FALLON: which every the lead to this Phil, I think you said this which I

massive of course,

document

word of,

has been 6 or 7 sponsors

making,

right? not

So certainly correct? incorrect.

have participated,

is that

MS. LAWTON: No, that's DR. O'FALLON: DR. NOGUCHI: rules do, While events they

No.

They have not? No. go This particular a rule, of

through started it

number

interactions. years another. ago,

we can say it certainly

a number of one way or

propel

We have this rule

indicated for

that

we

would

be

some time, interfered

and even on that or gotten So, it's rule. in the -- no. This

events priorities

have

way f other In this

come in there. -this

particular

is a proposed and it's

has no part

of a public

discussion but it

not by any

means meant to be the final, beginning. DR. SIEGEL: It's

is meant to be the

the nature

of the rules

we have by which we can make rules, by law. ensure getting They're that 'input not just a fair rules. public

which are governed And that input and not in order and we're others, to not and

there's from

some people
NEAL R. GROSS

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180
1

whatever, making discussions. out ' which for

that internally It's is

while

it there

was several were

years broad

in

the

2 3 4 5 6 7 8 9 10

general

at this only

really input

point that the proposal is / a limited period of time, specific Janet proposal. Christensen with

more formal

on the

MS. CHRISTENSEN: Targeted Genetics. I think I've give actually that

one of

the

issues I could a lot

that probably

--

read this

so many times I think

you chapter

and verse.

of us have

in preparing

our comments to the docket. One of the concerns, however, is that when for carried

you

start if I find

talking

about

criminal

prosecution

perjury out, 16 going to-eye, 18

the redaction that personally best

is not appropriately very job, scary.

You know, I'm see eyeAnd that's I find very

to do my very

but if

we don't

I may be criminally of that

prosecuted. proposal that

one of the:aspects concerning. r the full

When you do that employment professionals, we have we are in to act for

in there, regulatory

besides lawyers

being and

regulatory 23 24 25 bias staff. protecting
;
(202) 234-4433

which I must say I have some start to bringing be in legal

towards, And

order

prospectively of jail,

our interests

and keeping

me out

NEAL R. GROSS
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181 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 in follo&up encourage look can tremendous review for that okay. I like my freedom. I think that you inadvertently bureaucracy the lay on a

amount of additional that

and legal law. And in --

to ensure reason

we are following that there's

I believe

a figure

as proposed to each

as having I

an impact would

of about that for

$840 a year with intellectual and exchange law this

company. legal not

suggest not only

additional properWf information' perspective, higher.

review, only for

securities from is going the

and that

as well figure

regulatory

to be significantly

SO' that everybody particular -I

would on the

probably Committee

-to

and I would take I think potential a good that to with the to the

at that have

aspect. it

Because has impact very like a

think

significantly the agency.

have a negative I think we've

on working well with

worked

agency f as well maintain.those threat effect. of

as NIH,

but we'd

to continue

relationships. prosecution in there,

But when you put it has

a quelling

Thank you. CHAIRMAN SALOMON: So the question to that is who will do the redaction? I had I

NEAL R. GROSS / -(202) 234-4433 COURT REPORTERS AND TRiNSCRiSERS 1323 RHODE ISLAND AVE., N.W. WASHINGTON, D.C. 20005-3701 (202) 234-4433

182 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 regulations sanctionable; regulations' are available' the FDA,, that companies, saying that, didn't that why is follow guess in one version that I had heard, and this is by

no means quoting I heard the that was that

anyone in the FDA, but in one version reaction would be actually wa.s brilliant could control have it I to done by because what have they any

companies, way the

which

I thought (a)

companies

redacted fights savings positive

and therefore or issues, in

you didn't course which

and of

was a tremendous also thought was

FDA activity' the sparse redaction this

given

amount of funds. is being done not by that the I'm do I

So if and again

is a question

anyone from the FDA told this that. an issue then

me they would and --

of perjury

DR. NOGUCHI: Any laws that that that there those is So it's industry are if is this being against in that put
YOU

are -- or any by FDA are the that to is

forward don't series

follow of steps If you lie and

whole

one of them. the

regulation

sanctionable. that legal that they where

nature

where to be fair are talking as well. about And but that

and sponsors legal it's

counsel, was one of felt that

we have the it --

counsel not

a stipulation, reemphasizing

would

be worth

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183 this 2 3
i ,

is it

not

meant to be a voluntary be nice spent we feel For are to do, a lot that the but of it's out not to all that

kind it

of a thing is and the in fact effort public are this That's

that

would

something determining interest to

we've and

time in lyers unique

4

do that. which

there to

6 7 8

these particular really

sanctions rule. the nature I will

They apply of it. say about -it's

FDA rules.

the

redaction'

part

of

10 11 12 13 14 15 16

this but

it's the

not really device version.

on certainly all

CBERS part, 510Ks have that for FDA

industry This

does have -is one level it's of it being is

redacted

of clearance implemented on other

is approved. PMAs as well. experience.

And I believe So part The redaction DR. SIEGEL:

based

is done by the But as part it's

companies. reasons under of some

of the

for 18 19 20 21 22 23 24 25 this the

the

underlying that of

question' the

anticipated

proposal amount

FDA would

do some checking you or know,

redaction. competitive

That, reasons

companies r for .:might

other

reasons

choose to redact

more materials that the

than we thought it the

were appropriate. potentially rule. On the could

And if undermine

became extensive' whole point of

other

hand,

if

you

acknowledge

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184 1 2 3 4 5 6 '7 8 9 10
11

there's

limitations

on FDA resources, would be that with

so there

have of

been no -- the anticipation redacting that that

the chore

would be by the sponsors would and with would simply be largely appropriate involve

an expectation and with which, spot

sufficient remedies just

checking cases,

in many call and it were

a telephone

a discussion might involve

of what happened. more severe

But in some cases, actions if there

problems. CHAIRMAN SALOMON: Alison. MS. LAWTON: going the Sally Yes. I was actually as well as we heard level just along from of

12 13 14 15 16 17 18 19 20 21 22 23 24 25

to make a comment on the redaction lines that Jay just said, around take around the

as one example that might

different by companies. this not.

redaction think

place around

And I rule not

one of the questions acceptable

proposed And that's

is what's clear

and what's

at the moment. You know, in the proposed with holds if that, rule such there are

definite,ways companies

to on clinical

deal

as putting of redaction

the level So those

is too much 6r inappropriate. of things we still

are the types

have to work out the details. Yes. that I you'd think actually in

CHAIRMAN SALOMON: thinking'about this, the concern

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185 1 2 3 4 5 6 7 8 9

face potentially -- that was good.

criminal I like

investigation drama. I didn't

for perjury mean that

is to

sound a criticism. But I'm not quite large words, for is risk what if over what exists sure that right that's In a very other

now. accused rule trials

I could there adverse

see you being was an existing in didn't,

of perjury that or you in of

disclosed clinical course not too

events and you the rule.

animal then

trials be against far

you would thinking that's

10 11
12 13 14 15 16 17 18 19 20 21 22 23 24 25

But I'm

from where you're So I guess I'm

at today. -in part of this injury

discussion is here

not quite vis-a-vis

sure what the incremental charge. I think previous per is the thing proposed se,

a perjury

MS. CHRISTENSEN: caught I've there. going don't me is not fpund in looking that at

that rules in we're

language, this rules. example, rules a thing you'll I

included trend

And so perhaps to see in proposed usually those there comply find, for

a newer So it's that

more of you -for

there's

example, of don't criminal
'96,

proposed wasn't with this

for in

GMPs issued there that.

in May if you

be potentially think Phil and

up for Jay's

prosecutions. on the mark.

comments.are

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il.86 1 2 3 4 5 6 7 8 9

But looking the specifically

again,

you

know,

we have

to

react in high as well

at the proposal So whether

as published or not it's

Federal

Register.

drama or not,

it

certainly people's that

got my attention' attention. out there I don't just want I don't relationship

as a number of other I just get an wanted idea. to float

And I think so people to have to we we in an

Because is

what

happen f and this have happen that have with have with

me personally,

want that

the synergistic

10 11
12 13 14 15 16 17 18 19 20 21 22 23 24 25

the regulatory NIH/OBA way for is

agency -- the relationship harmed the or teased apart for

unhelpful development

patients,

product

and moving

forward.

That was my point.

CHAIRMAN SALOMON: Abbey. MS. MEYERS: I run with a charity, the IRS. the It's so interesting and I can't because negotiate should crazy, wants to That kind I of

a nonprofit I can't tell for

them what I think nonprofit. IT's industry them.

go into

regulations

you know, to hear that telli can't the. regulators adjust to it. the But understand People are the sitting when way

the regulated how to But IRS. you're happens there regulate

I wish

I had that

relationship;with

looking on

at Main "Ah,

this, Street. the FDA

this out

saying

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187 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 a little because the been in controls machines, of those it. Another clinical documents thing. trials. for all All of my children signed have my food, my drugs, the cosmetics, the x-ray and each one

the mammograms and everything," we go in there and tells

them how to regulate

I had to of them. I looked "Explain

informed they

consent

The drugs

went on had killed and I said happened that to the here."

animals. doctor And after

at the sentence to me. the What

this

I had all

knowledge them on the be everyday. so

I could,

I made the I'm not Doctors doesn't

judgment

to put You

medicine. m_ paternalistic. If the patient

stupid. are learn

can't that

learning

enough from the doctor, and he finds out the I been

he goes home and he gets out the truth truth anyway. 99 percent Internet to Wall than

on the Internet, And if of these

I want to find people's at what

about

products, they've

go on the releasing Street

and I look Street.

I find

out more from Wall Something for it has got to anymore. died and put "They because if died of you

I can from the FDA. Consumers won't So tell them that next out to it

change here.

stand

the animals that cage, truth, says not

footnote they fell

of their them the

drug'."

But tell

because

NEAL R. GROSS ,.
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1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25

don't, public

you increase faith.

your

liability

and you lose

the

DR. SIEGEL:

I just

wanted

to make clear,

and I know you know this, regulations in the

Abbey,

but when we make new

we are compelled sense that We and I

and we are not compelled to with cases industry that consult

we do so reluctantly consult must say publicly in many

publicly. industry, important implications not just that's always with

regulated we hear of the we may consult industry, protection We want to hear from We order to

perspectives and impact have public

from regulated

of the regulations

appreciated. industry -- with

But we don't regulated

why we are here.

We are a consumer industry. want from to

organization. hear from

We're regulating consumers, we want from all best to we hear

academicians, want to hear do what is

scientists. inn

concerned public

parties interest.

in the I don't

know how the IRS operates are able to make rules bit

in that without surprised

regard, public because

but

if

they

consultation, that wouldn't

I would be a little seem appropriate Well,

to me. I think since actually we know that

CHAIRMAN SALOMON: the comment about that in Congress, the IRS isn't which

is fair

is a public

environment,

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189 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 again, it this unreasonable trying there industry, process discussing of -is all which kinds is the the of input public. tax from the regulated in the here

And they're laws as we sit

changing these so,

regulations. I don't to think have that it's quite industry FDA as long that a but an

situation

regulated with the

to work in a partnership the FDA isn't

as we realize specific it doesn't

bound by anything of companies be heard. aspect of

company or a group mean you can't a very positive

demands,

I think things,

that's not a

probably negative.

I think discussion

that

from what I'm intended

hearing to finish,

here, but in a

wasn't that

seems like

the dynamic

Abbey and Alison one for

way have kind discussion. data really should well

of set up is the right And that is

the next kind of

how much and what to the public that

be available exactly

addresses is a

what Abbey wants,

and that

sense of confidence, of partnership

a sense of participation, is going to be put competitive. patients growth really

a sense to be -on there And by care mix

and how much of that is not going private, most

how much information that the would be considered way, I don't

think

whether

you use a real

complicated

factor

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190 1 2 3 to get out that's -gene transcribed the kind -trials. so I think there want to isn't I mean, that going I don't when you to the be a stem

think really fight, cell

you know, I really

well

"Well, factor."

know about

DR. SIEGEL: care, 8 9 10
11

But,

no, the patients of safety data is

may not If to an

but

public

discussion doing

concerns. and be able the safe critical or

you want to start discuss unsafe 'in

aggregate forum it what

a public

way to proceed,

might

be quite

that

you know which growth And so, patient isn't think it's is the sole

factors again,

went into it's of you're look all not

which product. simply that the which

12 13 14 15 16 17 18 19 20 21 22 23 24 25 an issue this, it, that

consumer issue

these

data,

to undermine we need to important

the

saying,

and I do But

carefully

at everything.

to realize

the perspectives. Well, I guess, quite clear Jay, here saying

CHAIRMAN SALOMON: what I was -- what maybe isn't is -I agree -I understand

either what

you were

back to me. My thinking gets is is that forth it if there's really like of we yet

brought

to a committee to get at part that

whether

we have to close there's for

you know, that

some secret us to

factor

need to 'know about

make a decision,

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1

maybe isn't competitor

going

to

be shared I certainly was we've

with agree that

all

the

other that. public about it

2 3 4 5 6 7 8 9 10
li

companies,
MY

with this

thinking and what that sort

disclosure isn't really

policy for

been talking

of a user. with

I thought the whole field What trials

was more for

the daily

experience

of gene therapy there

and xenotransplantation. about, That's that that feeding things

are and what they're DR. SIEGEL:

and who needs them. a wrong into are perception. this rule is on but NIH data public, Committee discuss facilitating why do going die in our in

It's not the also that

important simply Net that facilitating they wish

to note sure

making

available

12 13 14 15 16 17 18 19 20 21 22 23 24 25

patients

can read

or investigators, to share to present this to with in

our ability to be able

facilitating data public that

our ability we would than prefer behind

to share with to be able doors,

rather

closed

our ability these on with

when symposia at the last

are held,

you know, what's

mice die

RAC meeting,

adenoviruses, r of

why did Jessie November r99. that of that

Gelsinger Facilitating

a RAC meeting ability which

to speak to information may well involve and that's This a lot

we have in hand type of detailed reason

information, for this;

an important

underlying simply

is not to be viewed
NEAL R. GROSS

as a way to

(202) 234-4433

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

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1

put

all

this

information people

for

public

consumption

in a

2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25

raw form for it does

to read on the Internet, that and werre be other that. to reiterate

although some address

involve that

doing there without

hearing

comments other

might doing

ways to

concerns

You know, said, defend Although, the said

I want

what

Phil

and I'm here trying any one position

to explain at this

not particularly point in time. of Phil

obviously, rule. very

I was involved But I want to

in development repeat what

proposed that it's

important

to us that

we have as to

much input encourage

from people.

as broad

a spectrum

as possible

We can insert, proceedings will be part into the docket formal

and I suppose so that record

insert

these here But I

what is said considered.

of the

know that are saying

t,here's that people

a lot isn't to put

that's going that they

underlying said, out.

what people and I would that in and

encourage paper get it

To put

in-whatever into

detail

wish to communicate we really

the docket, all

because

do want to as

be able to consider we work on this rule.

of the concerns

and options

CHAIRMAN SALOMON: excellent clarification, Jay,

I

think

that's

an helps

and that

actually

NEAL R. GROSS
(202) 234-4433 COURT REPORTERS AND TRANSC&RS 1323 RHODE ISLAND AVE., N.W. WASHINGTON, D.C. 200053701 (202) 234-4433

me see it

in a broader

light. this to a close now.

I would tend to bring I would also invite audience. If 6 attended not, I want to any other

comments from the panel

or from the

thank

everyone

who

the meeting I'd like

and contributed. to thank Gail Depolito others and Bill of the FDA and I

8 9 10

Freas staff energy certainly

and Rosanna Harvey, for

and the

whom work an incredible making these it. see you in the time, 1:17 things

amount of time happen. And

into

appreciate We'll

next right? the

FDA meeting,

which 14 15 16

will

have a title (Whereupon,

next at

meeting

was

adjourned.)

18

23 24

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194 CERTIFICATE

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is to certify of:

that

the foregoing

transcript

in the matter

BIOLOGICAL RESPONSEMODIFIERS . ADVISORY COMMITTEE FOOD AND DRUG ADMINISTRATION CENTER FOR BIOLOGICS EVALUATION AND RESEARCH FRIDAY, APRIL 6, 2001

Before:

Date:

Place:

HOLIDAY INN 8120 WISCONSIN AVENUE BETHESDA, MARYLAND

represents aforementioned typewriting.

the

full matter,

and complete as reported

proceedings

of the to

and 'reduced

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