Proposed Rule: Administrative Rulings and Decisions: Ozone-Depleting Substances&#8212 Human Blood and Blood Components Intended For Transfusion or Further Manufacturing Use Requirements

Thursday,
November 8, 2007
Part IV
Department of
Health and Human
Services
Food and Drug Administration
21 CFR Parts 606, 610, et al.

Requirements for Human Blood and
Blood Components Intended for
Transfusion or for Further Manufacturing
Use; Proposed Rule
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63416 Federal Register / Vol. 72, No. 216 / Thursday, November 8, 2007 / Proposed Rules
DEPARTMENT OF HEALTH AND To ensure more timely processing of C. Records (Proposed § 606.160(e))
HUMAN SERVICES comments, FDA is no longer accepting D. Testing Requirements (Proposed
comments submitted to the agency by e- § 610.40(a) and (e) and
Food and Drug Administration mail. FDA encourages you to continue § 630.30(a)(5))
to submit electronic comments by using E. Purpose and Scope (Proposed
21 CFR Parts 606, 610, 630, 640, 660, the Federal eRulemaking Portal or the § 630.1)
820, and 1270 agency Web site, as described F. Definitions (Proposed § 630.3)
[Docket No. 2006N–0221] previously, in the ADDRESSES portion of G. Medical Supervision (Proposed
this document under Electronic § 630.5)
Requirements for Human Blood and Submissions. H. General Donor Eligibility
Blood Components Intended for Instructions: All submissions received Requirements (Proposed § 630.10)
Transfusion or for Further must include the agency name and I. Donor Eligibility Requirements
Manufacturing Use Docket No(s). and Regulatory Specific to Whole Blood and
Information Number (RIN) (if a RIN Plasma Collected by Plasmapheresis
AGENCY: Food and Drug Administration, number has been assigned) for this (Proposed § 630.15)
HHS. rulemaking. All comments received may J. General Exceptions from the Donor
ACTION: Proposed rule. be posted without change to http:// Eligibility Requirements (Proposed
www.fda.gov/ohrms/dockets/ § 630.20)
SUMMARY: The Food and Drug default.htm, including any personal K. Exceptions from Certain Donor
Administration (FDA) proposes to revise information provided. For additional Eligibility Requirements for
and update the regulations applicable to information on submitting comments Infrequent Plasmapheresis
blood and blood components, including see the ‘‘Comments’’ heading of the (Proposed § 630.25)
Source Plasma and Source Leukocytes, SUPPLEMENTARY INFORMATION section of L. Donation Suitability Requirements
to add donor requirements that are this document. (Proposed § 630.30)
consistent with current practices in the Docket: For access to the docket to M. Requalification of Previously
blood industry, and to more closely read background documents or Deferred Donors (Proposed
align the regulations with current FDA comments received, go to http:// § 630.35)
recommendations. FDA is taking this www.fda.gov/ohrms/dockets/ N. Requirements for Notifying
action to help ensure the safety of the default.htm and insert the docket Deferred Donors (Proposed Newly
national blood supply and to help number(s), found in brackets in the Redesignated § 630.40)
protect donor health by requiring heading of this document, into the O. Eligibility Requirements Specific
establishments to evaluate donors for ‘‘Search’’ box and follow the prompts for Platelet Donors (Proposed
factors that may adversely affect the and/or go to the Division of Dockets § 640.21)
safety, purity, and potency of blood and Management, 5630 Fishers Lane, rm. P. Eligibility Requirements Specific
blood components or the health of a 1061, Rockville, MD 20852. for Source Plasma Donors
donor during the donation process. Information Collection Provisions: (Proposed §§ 640.65(b) and 640.69)
DATES: Submit written or electronic Submit written comments on the Q. Reporting of Donor Reactions
comments on the proposed rule by information collection provisions to the (Proposed § 640.73)
February 6, 2008. Submit comments Office of Information and Regulatory R. Alternative Procedures (Proposed
regarding information collection by Affairs, Office of Management and § 640.120)
December 10, 2007 to OMB (see Budget (OMB). To ensure that S. Reagent Red Blood Cells (Proposed
ADDRESSES). See section IV of this comments on the information collection § 660.31)
document for the proposed effective are received, OMB recommends that T. Quality Systems Regulations
date of a final rule based on this written comments be faxed to the Office (Proposed § 820.1(a)(1))
proposal. of Information and Regulatory Affairs, U. Technical Amendments
ADDRESSES: You may submit comments, OMB, Attn: FDA Desk Officer, FAX: IV. Proposed Effective Date
identified by Docket No. 2006N–0221, 202–395–6974. V. Analysis of Impacts
by any of the following methods: FOR FURTHER INFORMATION CONTACT: A. Objectives and Basis of the Action
Electronic Submissions Brenda R. Friend, Center for Biologics B. Nature of the Impact
Submit electronic comments in the Evaluation and Research (HFM–17), C. Type and Number of Entities
following ways: Food and Drug Administration, 1401 Affected
• Federal eRulemaking Portal: http:// Rockville Pike, suite 200N, Rockville, D. Estimated Impact of Requirements
www.regulations.gov. Follow the MD 20852–1448, 301–827–6210. for Assessment of Donor Eligibility
instructions for submitting comments. E. Expected Benefits of the Rule
SUPPLEMENTARY INFORMATION:
• Agency Web site: http:// F. Small Entity Impact
www.fda.gov/dockets/ecomments. Table of Contents VI. The Paperwork Reduction Act of
Follow the instructions for submitting I. Introduction 1995
comments on the agency Web site. A. The Blood Initiative VII. Environmental Impact
Written Submissions B. Existing Donor Screening VIII. Federalism
Submit written submissions in the Requirements IX. Request for Comments
following ways: C. Proposed Regulations for X. References
• FAX: 301–827–6870. Determining Donor Eligibility I. Introduction
• Mail/Hand delivery/Courier [For (Proposed Part 630)

paper, disk, or CD–ROM submissions]: II. Legal Authority A. The Blood Initiative
Division of Dockets Management (HFA– III. Summary of the Proposed Rule For a variety of reasons we, FDA,
305), Food and Drug Administration, A. General Description decided to review comprehensively and,
5630 Fishers Lane, rm. 1061, Rockville, B. Standard Operating Procedures as necessary, revise our regulations to
MD 20852. (SOPs) (Proposed § 606.100(b)) include definitions, policies, guidance,
Federal Register / Vol. 72, No. 216 / Thursday, November 8, 2007 / Proposed Rules 63417
and procedures related to the licensing • ‘‘Blood Supply: Transfusion- regulations and the applicable
and regulation of blood products. In the Associated Risks’’ by GAO (February 25, recommendations.
Federal Register of June 3, 1994 (59 FR 1997); and, The Secretary of the Department of
28821 and 28822, respectively), we • ‘‘HIV and the Blood Supply: An Health and Human Services (HHS) seeks
issued two documents, ‘‘Review of Analysis of Crisis Decisionmaking’’ by to maximize blood safety and blood
General Biologics and Licensing IOM (July 13, 1995). availability and has designated the
Regulations’’ (Docket No. 1994N–0066) These reports are on file with the Assistant Secretary of Health to be
and ‘‘Review of Regulations for Blood Division of Dockets Management (see responsible for these issues. The supply
Establishments and Blood Products’’ ADDRESSES) under the docket number of blood is generally adequate to meet
(Docket No. 1994N–0080). These found in the heading of this document. medical needs; however, only about 6
documents announced our intent to We have reviewed these reports and percent of the U.S. general public
review biologics regulations (parts 600, agree with the majority of the donates blood each year. Periodically,
601, 606, 607, 610, 640, and 660 (21 recommendations contained within local, regional or national shortages can
CFR parts 600, 601, 606, 607, 610, 640, them. We are not describing all the occur. Although blood establishments
and 660)), and requested written specific recommendations we received are primarily responsible for recruiting
comments from the public. We gave and the numerous objectives of the and retaining blood donors, HHS plays
interested persons until August 17, Blood Initiative in this document. a key role in monitoring the blood
1994, to respond to the documents. In However, in response to the GAO supply to identify potential shortages.
response to requests for additional time, recommendations, FDA has completed Also, the Secretary of HHS has
we twice extended the comment period, rulemakings, including the following: developed a number of initiatives to
as announced in the Federal Register of (1) Requirements for Testing Human encourage individuals to donate
August 17, 1994 (59 FR 42193), and Blood Donors for Evidence of Infection routinely and during times of shortage
November 14, 1994 (59 FR 56448). In Due to Communicable Disease Agents or national disasters. In times of acute
addition, we responded to requests for (66 FR 31146; June 11, 2001); (2) blood shortage, HHS has sponsored
a public meeting to allow the public to General Requirements for Blood, Blood national appeals for blood donation.
present comments regarding our review Components, and Blood Derivatives; Under the HHS Blood Action Plan,
of the biologics regulations. At the Donor Notification (66 FR 31165; June HHS and the Public Health Service
public meeting on January 26, 1995, 11, 2001); (3) Revisions to the agencies of HHS act to increase blood
interested individuals presented their Requirements Applicable to Blood, availability by removing unnecessary
comments, which assisted us in Blood Components and Source Plasma, restrictions to blood donation while
determining whether certain regulations Confirmation in Part and Technical maintaining the highest level of safety
should be revised, rescinded, or Amendment (66 FR 1834; January 10, for the recipient. HHS brings donor
continued without change. Since the 2001); (4) Current Good Manufacturing eligibility issues for discussion at
time of the regulation review, we have Practice for Blood and Blood scientific workshops and at FDA
implemented a number of changes to Components; Notification of Consignees scientific advisory committees,
the regulations and policies applicable and Transfusion Recipients Receiving including the Blood Products Advisory
to the general biologics and licensing Blood and Blood Components at Committee and the Transmissible
requirements, some of which applied to Increased Risk of Transmitting HCV Spongiform Encephalopathies Advisory
blood products as well as other Infection (‘‘Lookback’’) (65 FR 69378; Committee, where we seek advice and
biological products. November 16, 2000); and (5) Biological scientific-based recommendations.
The United States House of Products: Reporting of Biological Additionally the HHS Advisory
Representatives Committee on Product Deviations in Manufacturing Committee on Blood Safety and
Government Reform and Oversight, (65 FR 66621; November 7, 2000, and 65 Availability provides advice on global
Subcommittee on Human Resources and FR 67477; November 9, 2000 public health, economic, social, and
Intergovernmental Relations (the (Correction)). This rulemaking and other ethical issues related to FDA policies on
Subcommittee) and other groups such as notices describe and discuss specific donor eligibility. These discussions
the Government Accountability Office recommendations and regulatory have often focused on the impact of
(previously, the General Accounting objectives as they apply to each donor deferrals on blood availability as
Office GAO), and the Institute of rulemaking. well as the safety of blood for the
Medicine (IOM), have reviewed our Through the years, we issued a recipient. During the development of
policies, practices, and regulations. number of guidance documents policies on donor eligibility, including
Reports issued following the respective containing recommendations intended donor screening, testing and deferral,
reviews made a number of to assure a safe, pure, and potent blood FDA considers the impact of candidate
recommendations to improve the supply. One objective of this rulemaking policies on blood availability and tries
biologics regulations, particularly as is to make more visible the connections to balance anticipated donor loss with
they apply to assuring the continued between the regulations and current safety gained. One example of this
safety of blood products. The relevant recommendations. In many cases in this balancing approach may be found in
reports are: preamble, we will describe the general FDA’s development of a guidance
• ‘‘Blood Supply Generally Adequate intended meaning of the proposed recommending deferral of persons who
Despite New Donor Restrictions’’ by regulations and will also discuss those may have been exposed to the Bovine
GAO (July 22, 2002); recommendations, contained in current Spongiform Encephalopathy (BSE) agent
• ‘‘Protecting the Nation’s Blood guidance, which fall under a proposed (the agent that causes Mad Cow Disease)
Supply From Infectious Agents: The regulation. Although it is neither and thus create an increased risk of
Need for New Standards to Meet New possible nor desirable to codify all the transfusion transmission of variant
Threats’’ by the Subcommittee (August specific details contained in Creutzfeldt-Jakob Disease (vCJD). FDA
2, 1996); recommendations, we believe the commissioned the studies that produced
• ‘‘Blood Supply: FDA Oversight and proposed rule will more explicitly the first available data regarding donor
Remaining Issues of Safety’’ by GAO describe donor eligibility standards and travel patterns and used the data to
(February 25, 1997); will clarify the relationship between the optimize the balance between a
reduction in the risk of transfusion- • Rule out relevant disease infection; used, Source Plasma and Source
transmitted vCJD (estimated at 91 and, Leukocytes are included. We also use
percent) and donor loss (estimated at 7 • Identify any risk factors that would the term ‘‘donor eligibility’’ when
percent). increase the possibility of transmitting a referring to criteria to permit donation.
In developing this proposed rule, FDA transfusion-transmitted infection This proposed rule uses the term
has reviewed the proceedings of through the donation. ‘‘suitability’’ only when discussing the
numerous workshops and advisory In addition, under § 610.40, a blood acceptability of the donated blood and
committee meetings, mindful of the sample collected from the donor at the blood components for transfusion or for
goals of the HHS Blood Action plan: time of donation must be tested for further manufacturing use. (For further
increasing blood availability by evidence of infection due to discussion, see section III.E of this
removing unnecessary restrictions to communicable disease agents such as document.)
blood donation, while maintaining the HIV and viral hepatitis. By performing
II. Legal Authority
highest level of safety for the recipient. these steps, the collecting establishment
For example, we have tried to achieve helps assure the safety, purity, and FDA is proposing to issue this new
those goals by our proposal to change potency of blood and blood rule under the authority of sections 351
labeling requirements for certain components. and 361 of the Public Health Service Act
donations from patients with hereditary (PHS Act) (42 U.S.C. 262 and 264), and
C. Proposed Regulations for the provisions of the Federal Food,
hemochromatosis. This provision would Determining Donor Eligibility (Proposed
remove a barrier to safe blood collection Drug, and Cosmetic Act (the act) that
Part 630) apply to drugs and devices (21 U.S.C.
from these individuals. FDA welcomes
comments on the risks and benefits of Although we currently have donor 201 et seq.).
the donor eligibility criteria proposed in suitability requirements applicable to The establishment of these criteria for
this rulemaking with regard to potential blood and blood components, including determining the eligibility of a donor of
donor loss versus gains in blood product Source Plasma and Source Leukocytes, blood and blood components and the
safety and donor safety. parts 606, 610, 640, and 660, we intend suitability of blood and blood
to reorganize and revise current components for transfusion or for
B. Existing Donor Screening regulations, to make more visible the further manufacturing, is intended to
Requirements connections between the regulations prevent unsafe units of blood or blood
We have developed five ‘‘layers of and current FDA recommendations, to components that may transmit a
safety’’ to help ensure a safe blood make them consistent with current relevant transfusion-transmitted
supply: practices in the blood industry, and to infection from entering the blood
• Donor suitability standards (part remove unnecessary or outdated supply, while safeguarding the health of
640); requirements. Based on the donors.
• Donor deferral lists (§ 606.160(e)); recommendations of the 1997 GAO FDA has been delegated authority
• Testing blood for communicable report, ‘‘Blood Supply: FDA Oversight under section 361 of the PHS Act to
disease agents (§ 610.40); and Remaining Issues of Safety,’’ we are make and enforce regulations necessary
• Quarantining unsuitable blood and issuing in the form of regulations to prevent the introduction,
blood components (§ 606.40(a)(6)); and provisions of the memoranda and transmission, or spread of
• Monitoring establishments by guidance on donor eligibility that we communicable disease from foreign
requiring the investigation of problems believe are essential to help ensure the countries into the States or possessions,
in manufacturing (21 CFR 211.192), safety of the national blood supply. or from one State or possession into any
reporting of fatalities (§ 606.170) and Subsequent to the February 1997 GAO other State or possession. Intrastate
reporting of product deviations report, we conducted numerous transactions affecting communicable
(§ 606.171). workshops to obtain public input. The disease transmission may also be
The five layers of safety are designed subjects discussed included for regulated under section 361 of the PHS
to overlap and help prevent the example: Act (see Louisiana v. Mathews, 427 F.
distribution of blood and blood • Screening and testing for evidence Supp. 174, 176 (E.D. La. 1977)). FDA
components that are at increased risk for of infection due to communicable recently exercised this authority when
transmitting infectious agents such as diseases; the agency issued three rules requiring
human immunodeficiency virus (HIV), • Donor history of hepatitis; tissue establishments to register and list
hepatitis B virus (HBV), and hepatitis C • Use of a donor deferral registry; the human tissues manufactured; to
virus (HCV). • Donor blood volume; conduct donor screening and testing;
In addition to safeguarding against • Donor deferral based on cancer; and to manufacture tissues in
transmission of disease agents from and, accordance with good tissue practices,
donor to recipient, the current donor • Streamlining the donor history including manufacturing practices,
suitability standards are designed to questionnaire. SOPs, recordkeeping, and other
prevent harm to a donor from the We have consolidated information practices designed to prevent the
donation process, and to help ensure the from memoranda, guidances, other transmission of communicable disease
safety, purity, and potency of blood and workshops, advisory committee (66 FR 5447 (January 19, 2001), 69 FR
blood components. Usually, collecting meetings, current § 630.6 requiring 29786 (May 25, 2004), 69 FR 68612
establishments review donor deferral donor notification, and the donor (November 24, 2004)).
lists to identify, before donation, suitability requirements in § 640.3 and It is important to recognize that blood
individuals not eligible to donate. 640.63 in developing the requirements manufacturing presents significant risks
Collecting establishments conduct a for donors of blood and blood of communicable disease transmission.
prescribed limited physical examination components intended for transfusion or As FDA has previously noted, section
and medical history interview for each for further manufacturing use in 361 of the PHS Act authority ‘‘is
donor. These steps are performed to: proposed part 630. For the purpose of designated to eliminate the introduction
• Establish that the donor is in good this proposed rulemaking, when the of communicable disease, such as
health; term ‘‘blood and blood components’’ is hepatitis, from one state to another. Of
necessity, therefore, this authority must (42 U.S.C. 262). Section 351 of the PHS the provisions of the proposed rule are
be exercised upon the disease causing Act further authorizes FDA, by critical aspects of good manufacturing
substance within the state where it is delegation, to establish requirements for practice. The proposed rule would
collected, manufactured, or otherwise such biologics licenses (42 U.S.C. require collecting establishments to
found. Thus, the Commissioner of Food 262(a)(2)(A)). In addition to its authority assure that donors of blood and blood
and Drugs may promulgate current good under section 361 of the PHS Act, FDA components meet the essential criteria
manufacturing practice regulations for relies on this authority when the for eligibility, and that blood and blood
intrastate blood banking, pursuant to the proposed regulations would be applied components are suitable for transfusion
act, as hepatitis is a communicable to products subject to biologics license. or further manufacturing. Blood and
disease. Without proper controls, it is To obtain a license, applicants must blood components not manufactured in
likely to spread on an interstate basis.’’ show that the manufacturing accordance with good manufacturing
(39 FR 18614, May 28, 1974). These establishment meets all applicable practice, including the provisions of the
statements are equally true today, where standards designed to assure the proposed rule, would be considered
the spectrum of disease agents has continued safety, purity, and potency of adulterated under 21 U.S.C. 351(a)(2)(B)
increased to include, for example, HIV– the blood and blood components, and or 21 U.S.C. 351(h) and 360j(f)(1), and
1 and –2, agents that cause AIDS, and that the product is safe, pure, and collecting establishments and blood and
HCV, an additional cause of hepatitis. potent. FDA’s license revocation blood components would be subject to
We understand communicable diseases regulations provide for the initiation of the act’s enforcement provisions for
to include, but not be limited to, those revocation proceedings if, among other violations of the act. These include
transmitted by viruses, bacteria, fungi, reasons, the establishment or the seizure of violative products (section
parasites, and transmissible spongiform product fails to conform to the 304 of the act) (21 U.S.C. 332)),
encephalopathy agents. Preventing the standards in the license application or injunction against ongoing and future
spread of communicable disease is the in the regulations designed to ensure the violations, and criminal penalties
important purpose underlying the continued safety, purity, or potency of (section 303 of the act) (21 U.S.C. 333
comprehensive regulations for blood the product (§ 601.5). Violations of and 18 U.S.C. 3571)). The act punishes
establishments now in place, which this section 351 are punishable by a 1-year both misdemeanor and felony violations
proposed rule would somewhat modify term of imprisonment, a fine as of the act. Misdemeanor violations are
and modernize. described in the preceding paragraph, or
Under section 361 of the PHS Act, punishable by a term of imprisonment
both (42 U.S.C. 262(f), 18 U.S.C. 3571). of up to 1 year, a fine as described
FDA is authorized to enforce the
regulations it issues to prevent the Blood and blood components are also previously, or both. (21 U.S.C. 333(a)(1),
introduction, transmission, or spread of drugs or devices, as those terms are 18 U.S.C. 3571). Individuals convicted
communicable disease interstate defined in sections 201(g)(1) and (h) of of felony violations may be sentenced to
through such means as inspection, the act (21 U.S.C. 321(g)(1) and (h); see a term of imprisonment of up to 3 years,
disinfection, sanitation, destruction of United States v. Calise, 217 F. Supp. a fine of up to $250,000, or both.
animals or articles found to be so 705, 708–09 (S.D.N.Y. 1962)); 42 U.S.C. Organizations convicted of felony
infected or contaminated as to be 262(j) (‘‘The Federal Food, Drug, and violations may be sentenced to a fine of
sources of dangerous infection in Cosmetic Act applies to a biological up to $500,000. Individuals and
human beings, and other measures that product subject to regulation under this organizations also face possible
may be necessary. In addition, under section, except that a product for which alternative fines based on the amount of
section 368(a) of the PHS Act, any a license has been approved * * * shall gain or loss (18 U.S.C. 3571(b) through
person who violates a regulation not be required to have an approved (d)).
prescribed under section 361 of the PHS [new drug] application’’). Since blood
and blood components are drugs or III. Summary of the Proposed Rule
Act may be punished by imprisonment
for up to 1 year. Individuals may also devices generally subject to the act, in A. General Description
be punished for violating such a issuing these regulations, FDA relies on
regulation by a fine of up to $100,000 the act’s grant of authority to issue The proposed regulations in subparts
if death has not resulted from the regulations for the efficient enforcement A, B, and C of part 630 would apply to
violation or up to $250,000 if death has of the act (21 U.S.C. 371(a)). The act you, establishments that collect and
resulted. For organizational defendants, requires collecting establishments to process blood and blood components.
fines range up to $200,000 and comply with the act’s current good The proposed rule would add donor
$500,000. Individuals and organizations manufacturing practice provisions and requirements for blood and blood
also face possible alternative fines based related regulatory scheme. Under components, including Source Plasma
on the amount of gain or loss (18 U.S.C. section 501 of the act (21 U.S.C. 351), and Source Leukocytes, to make them
3559 and 3571(b) through (d)). Federal drugs, including blood and blood consistent with current practices in the
District Courts also have jurisdiction to components, are deemed ‘‘adulterated’’ blood industry. The proposed
enjoin individuals and organizations if the methods used in their regulations also would assemble into
from violating regulations implementing manufacturing, processing, packing, or one part certain current provisions
section 361 of the PHS Act. (See holding do not conform with current applicable to determining the eligibility
Califano v. Yamasaki, 442 U.S. 682, good manufacturing practice (21 U.S.C. of a donor. These general regulations
704-05 (1979); United States v. Beatrice 351(a)(2)(B)). Devices are deemed would apply to any blood and blood
Foods Co., 493 F.2d 1259, 1271-72 (8th ‘‘adulterated’’ if the methods used in, or component intended for transfusion or
Cir. 1974), cert. denied, 420 U.S. 961 the facilities or controls used for, their for further manufacturing use, including
(1975).) manufacture, packing, storage, or Source Plasma and Source Leukocytes,

Blood and blood components installation are not in conformity with and those blood and blood components
introduced or delivered for introduction good manufacturing practice used in the manufacture of a medical
into interstate commerce are subject to requirements established by FDA in device. We are proposing a new title for
section 351 of the PHS Act, which regulations (21 U.S.C. 351(h) and part 630 to reflect this application. For
requires that such products be licensed 360j(f)(1)). We propose to specify that purposes of this document, whenever
we discuss blood and blood shared donor deferral registry to those requiring that donor deferral records be
components, the source is human. donors who are determined to be used and disclosed only for purposes
ineligible to donate due to a possible consistent with subchapter F of 21 CFR
B. Standard Operating Procedures
exposure to a relevant transfusion- Chapter I.
(SOPs) (Proposed § 606.100(b))
transmitted infection (proposed • We request comment on this
We propose to clarify current § 630.10(f)), or to certain other factors proposal, including the following
§ 606.100(b) to state that you must not that may adversely affect the health of specific issues:
only establish and maintain, but must the donor, or the safety, purity, or Whether the current practices and
also follow written procedures, in potency of the blood or blood protections adequately protect the
accordance with all applicable component (proposed § 630.10(g)(1) confidentiality of donor records;
regulations for all steps in the through (g)(6)). We are interested in Whether those current practices and
collection, processing, compatibility receiving comments on: protections will still be adequate if FDA
testing, storage and distribution of blood • The information that should be requires that establishments make donor
and blood components intended for included on a donor deferral registry deferral records available at all
transfusion and for further used in common by all donor screening collection sites operating under the
manufacturing use. We propose to locations of a collecting establishment same license or common management;
distinguish the types of transfusions as operating under a common organization and
‘‘allogeneic’’ and ‘‘autologous.’’ We also (e.g., under the same license number); Whether a regulation limiting the use
propose to add, to current § 606.100(b), • The adequacy of the criteria listed and disclosure of such records would
language making explicit the in proposed § 630.10(f) and (g)(1) actually further the goal of protecting
requirement that you establish, through (g)(6) to prevent the collection the confidentiality of the records.
maintain, and follow SOPs for of blood and blood components that In addition, we request comment on
investigating product deviations may be harmful to the donor or that may the following:
(§ 606.171), and for recordkeeping result in an unsuitable product due to We believe that few, if any, blood
related to current good manufacturing possible exposure of the donor to a collection establishments are HIPAA-
practice requirements (part 606) and transfusion-transmitted infection; and covered entities under the HIPAA
biological product standards (part 610). • The technical feasibility of Privacy Rule. However, to evaluate the
complying with the proposed impact of this rule on any such HIPAA-
C. Records (Proposed § 606.160(e))
requirement. covered entities, we are seeking public
Current § 606.160(e) requires We are also seeking comments on the comment from any facilities that may be
collecting establishments to have feasibility of sharing donor deferral lists covered by the HIPAA Privacy Rule,
records available to identify unsuitable between licensed establishments for regarding whether or how HIPAA
donors and prevent the distribution of deferrals required by the FDA. Such requirements may impact their ability to
blood and blood components collected national deferral registries have existed comply with this proposed rule.
from such individuals. This is for Source Plasma collections for many
sometimes accomplished by years. D. Testing Requirements (Proposed
establishing a coding system, which Proposed § 606.160(e) would help § 610.40(a) and (e) and § 630.30(a)(5))
allows personnel to identify a donor as prevent the collection of unsuitable
1. Testing for Relevant Transfusion-
ineligible without revealing the reason blood and blood components and
transmitted Infections
for the deferral to those who do not have reduce recipients’ exposure to blood
a need to know the information. We and blood components with an Section 610.40(a) requires that a
propose to continue this requirement in increased risk of transmitting an collecting establishment test each
§ 606.160(e), which would require infectious agent. For example, under donation of blood or blood component
establishments to maintain a record of proposed § 606.160(e)(2), if a collecting intended for transfusion or for further
donors determined to be ineligible to establishment collected blood at four manufacturing use in preparing a
donate in order to prevent the collection locations and three mobile sites, donors product for evidence of infection due to
of blood or blood components from such deferred from further donation at any of the listed communicable disease agents.
individuals while they are ineligible or the seven sites would be listed on a We are proposing to revise § 610.40(a)
deferred. We also are proposing in donor deferral registry available at all by replacing ‘‘communicable disease
§ 606.160(e)(2) that all donor screening seven sites. The requirement to review agents’’ with ‘‘relevant transfusion-
locations of a collecting establishment the record of ineligible donors before transmitted infections described in
operating under a common organization, collection and to make the record of § 630.3(g).’’ This change would require
e.g., under the same license number, use ineligible donors available to collecting testing and, where appropriate,
a collective master list of donors establishments operating under a screening, for additional relevant
determined at each location to be common organization would improve transfusion-transmitted infections that
ineligible to donate. This list is also blood safety by reducing the likelihood present a potential risk to the health of
known as a donor deferral registry. of accidental release of potentially the recipient and for which appropriate
Under proposed § 630.10(d)(1), the infectious units. We discussed the testing methods are available. Donor
collecting establishment would be practice of reviewing a donor deferral screening or testing for a relevant
required to review the donor deferral registry before the collection of blood transfusion-transmitted infection may
registry before collection to prevent the and blood components at the Blood vary based on the characteristics of the
collection of blood and blood Product Advisory Committee meeting of blood product. For example, we do not
components from donors deferred from October 20, 1994, and recommended the currently require testing of Source
donation temporarily (when the practice in the guidance document Plasma for human T-lymphotropic virus
temporary deferral is in effect when the entitled ‘‘Guideline for Quality (type I or II) because the virus is cell-
donor presents), indefinitely, or Assurance in Blood Establishments’’ (60 associated and readily removed and
permanently. FR 36290, July 14, 1995). inactivated during manufacturing.
Under proposed § 606.160(e)(2), we We are considering whether to Similarly, testing for another relevant
are proposing to limit entry into the include, in the final rule, a provision transfusion-transmitted infection may
not be required if viral inactivation or of the analyte when described in notification based on the results. We
removal procedures have been validated guidance, as appropriate. It is not FDA’s also invite comment on this issue.
to ensure inactivation or removal of the intention to move away from
E. Purpose and Scope (Proposed
infectious agent and screening for risk confirmatory or supplemental testing
§ 630.1)
factors is available, unless the risk of where such an approved test exists, but
harm from transmission is too great to rather to recognize that under certain The proposed rule would require that
rely solely on viral inactivation circumstances alternative testing a blood establishment make two
procedures and screening for risk schemes may provide confirmatory or determinations: (1) The donor is eligible
factors. supplemental testing information. In the to donate and (2) the donation is
case of HIV NAT, FDA has allowed the suitable for use in transfusion or further
2. Testing Further With One or More manufacturing use. The proposed
Supplemental (Additional, More HIV–1 Western Blot not to be performed
when the HIV EIA is reactive and HIV requirements in part 630 would provide
Specific) Test(s)
NAT is positive. If the HIV NAT is criteria for the collecting establishment
When a donation is found to be negative, the Western Blot must still be to use to determine the eligibility of the
reactive by a screening test, § 610.40(e) performed. If this rule is finalized, we donor to donate. We would require that
currently requires that the establishment intend to make initial recommendations the collecting establishment determine
further test the donation with a for additional testing algorithms in draft on the day of donation that the donor
supplemental (additional, more specific) guidance issued for public comment. is in good health and is not deferred
test approved for such use by FDA. In from donating. Proposed § 630.1 also
proposed § 610.40(e), we are proposing 3. Testing for Bacterial Contamination makes reference to previously issued
to require that additional testing may be for Platelets and Other Transfusible requirements in part 630 that describe
performed with additional tests that are Blood Components the process for notifying donors of their
not necessarily ‘‘more specific’’ deferral due to failure to satisfy the
provided that the additional test(s) is Bacteria remain a significant
contaminant in blood and blood eligibility criteria or test results for
appropriate to determine the donor’s relevant transfusion-transmitted
infection status prior to notification. At components (Ref. 1). Bacterial
contamination of platelets has been infections required under § 610.40.
a meeting of the Blood Products This proposed rule would apply to
Advisory Committee (BPAC) on March discussed at an FDA workshop held on
September 24, 1999, at the December any establishment or facility that
18 and 19, 2004, the committee heard collects any blood or blood component
presentations on alternative algorithms 2002 BPAC meeting, and at the April
2004 meeting of the Public Health from donors:
for additional testing for HIV and HCV • For transfusion, including
after an initially reactive screening test. Service Advisory Committee on Blood
autologous use;
Safety and Availability. AABB (formerly
The committee recommended that FDA • For further manufacturing use; or
reconsider its requirement that known as the American Association of • For use as a component of a
supplemental testing be performed Blood Banks) established an medical device.
using more specific tests. At that accreditation standard, effective March Creating this separate part for donor
meeting, industry representatives 2004, requiring accredited blood banks eligibility requirements for donors of
provided information on the need for and transfusion services to have blood and blood components would
and the use of alternative testing methods to limit and detect bacterial allow for a consistent set of criteria for
algorithms to confirm the deferred contamination in all platelet all individuals participating in various
donor’s infection status that involved components. Currently, bacterial collection programs.
the use of more than one enzyme detection is being performed using a
immunoassay (EIA) screening test, variety of methods, including FDA- F. Definitions (Proposed § 630.3)
including the use of multiple EIA approved quality control tests. However, Section 630.3(a) through (l) of the
screening tests in lieu of a supplemental we are proposing in § 630.30(a)(5) that proposed rule contains proposed
test. A Public Health Service (PHS) a platelet component would not be definitions of terms specifically used in
working group reviewed the data suitable until tests for bacterial this rulemaking.
presented at the March 2004 BPAC and contamination are found negative. (See We are proposing in § 630.3(a) and (b)
all available data and concluded that section III.L of this document.) In some to define blood and blood component as
when donor screening tests were instances, specific bacteria identified as used in part 630. We would define
reactive for antibody to HIV and reactive contaminants in a blood component blood as a product and describe the
on an individual HIV–1 nucleic acid test could indicate an underlying bacteremia product as a fluid containing dissolved
(NAT) test, supplemental testing for HIV or serious illness in the donor. and suspended elements, which
antibody was not necessary. A similar Therefore, we are also soliciting circulates in a human’s vascular system.
conclusion that supplemental testing for comments on: (1) Whether to require, in Blood component also would be defined
HCV was not necessary was reached for the context of testing of platelet as a product, and described as
donor screening tests that were reactive components prior to release, the containing a part of blood separated by
for antibody to HCV and reactive on an identification of the species of the physical or mechanical means.
individual HCV NAT test. However, the bacterial contaminant and (2) whether In proposed § 630.3(e), the definition
PHS working group was unable to to require donor deferral and for intimate contact is intended to help
recommend the use of multiple EIA notification when identification of the you determine whether the donor is at
screening tests in lieu of the HIV–1 or contaminant indicates possible risk for contracting a transfusion-
HCV supplemental tests when the endogenous bacteremia, and not transmitted infection from another
individual HIV–1 or HCV NAT test was contamination during collection and individual who may be infected with a
non-reactive. processing. Additionally, we are also transfusion-transmitted infection.
The intent of this section is to allow considering whether to extend, to other We are defining relevant transfusion-
for the use of multiple screening tests to blood components for transfusion, the transmitted infection in proposed
‘‘confirm’’ infection or to provide requirement for testing for bacterial § 630.3(g)(1) to identify the currently
additional information on the presence contamination, and donor deferral and recognized disease agents that are
associated with transmission from the • There must be appropriate Moreover, good guidance practices
donor to the recipient by transfusion, screening and/or testing methods provide the public with an opportunity
infusion, or injection of a blood available; and to comment on guidance before its
component or blood derivative and for • The disease agent or disease must implementation, unless prior public
which there are appropriate screening present a risk of transmission by the participation is not feasible or
and/or testing measures available. These transfusion of the blood or blood appropriate, e.g., in a public health
are: HIV, types 1 and 2; HBV; HCV; component collected, or by the use of a emergency. In addition, we intend to
human T-lymphotropic virus (HTLV), blood derivative product manufactured hold public meetings and/or consult
types I and II; Treponema pallidum from collected blood or blood with advisory committees where
(syphilis); Creuztfeldt-Jakob disease components, to the potential recipient. appropriate, to help us determine
(CJD), variant Creutzfeldt-Jakob disease The disease agent or disease must be whether a disease agent or disease meets
(vCJD); and Plasmodium sp. (malaria). potentially transmissible by that blood, these criteria, and whether FDA should
In the proposed rule entitled blood component, or blood derivative recommend that establishments perform
‘‘Requirements for Testing Human product; and either have sufficient donor screening and/or testing for it.
Blood Donors for Evidence of Infection incidence and/or prevalence to affect We believe that the issuance of such
Due to Communicable Disease Agents’’ the potential donor population; or have guidance will assist collecting
(64 FR 45340, August 19, 1999), we been accidentally or intentionally establishments, especially small
solicited comments, with supporting released in a manner that would place establishments that are not able to track
data, from the public in regard to the donors at risk of infection, such as a emerging disease agents and diseases in
value of donor testing for syphilis as a bioterrorism attack or laboratory a timely manner. By providing these
marker of increased risk behavior, as a accident that releases an agent, e.g., notifications, we will perform an
surrogate test for other infectious anthrax or smallpox, into the important communications function and
diseases, and in preventing the population. assist collecting establishments in
transmission of syphilis through blood We are also proposing in § 630.3(k) a meeting their regulatory obligations to
transfusion. After reviewing the definition for transfusion-transmitted screen and test donors.
comments and submitted scientific data, infection. This definition would include
Donor, as used in the proposed
we determined that the comments did any transfusion-transmitted disease not
regulation in § 630.3(c), is defined to
not provide sufficient supporting data to included under proposed § 630.3(g). The
include a person who is a potential
justify eliminating the requirements for criteria for a transfusion-transmitted
candidate as well as a person who
screening and testing the donor for infection are as follows:
• The transfusion-transmitted completes the act of donation.
syphilis. We continue to consider this
infection must present a significant We are defining eligibility of a donor
issue, including any further studies that
health risk that could be fatal, life- in proposed § 630.3(d) and suitability of
address the issues of transfusion-related
threatening, cause permanent the donation in proposed § 630.3(i) so as
syphilis infection or testing for syphilis
impairment of a body function or to distinguish between the acceptability
as a surrogate marker for other
damage to body structure, or necessitate of a donor for donation and the
communicable diseases; and we again
medical intervention to preclude such acceptability of the donation for
request comments and data concerning
whether establishments could impairment or damage; and transfusion or for further manufacturing
discontinue syphilis testing without • The disease agent or disease may use.
adversely affecting the safety of the present a risk of transmission by the We have defined physician substitute
blood supply. If we receive adequate transfusion of the blood or blood in proposed § 630.3(f), responsible
data, we will eliminate or modify this component collected, or by the use of a physician in proposed § 630.3(h), and
testing requirement in the final rule. blood derivative product manufactured trained personnel in proposed § 630.3(j)
The second part of the definition in from collected blood or blood according to the education and
§ 630.3(g)(2), proposes criteria for components, to the potential recipient. qualifications required to fulfill the
identifying additional disease agents The definition of a transfusion- position description.
that present a risk of transmission from transmitted infection differs from a You, in proposed § 630.3(l), is defined
the donor to the recipient by transfusion relevant transfusion-transmitted so as to establish who must comply with
of blood or blood components. This risk infection in that the existence of the requirements in proposed part 630.
would include disease and disease sufficient incidence and/or prevalence G. Medical Supervision (Proposed
agents with a known, presumptive, or to affect the potential donor population § 630.5)
theoretical risk of infection through is not a part of the definition. Available
transfusion, such as West Nile virus. screening and testing methods may also In § 630.5, we are proposing to
(See ‘‘Guidance for Industry: Assessing be limited. One example of such a include requirements prescribing the
Donor Suitability and Blood and Blood transfusion-transmitted infection is level of medical supervision at
Product Safety in Cases of Known or leishmania. collecting establishments responsible
Suspected West Nile Virus Infection,’’ It is our intention to issue guidance for determining the eligibility of a
dated June 2005.) To be a relevant following the good guidance practices in donor, collecting blood and blood
transfusion-transmitted infection, a 21 CFR 10.115 to advise you when we components, or performing other
disease agent or disease must meet all believe that a new disease agent or procedures with significant implications
of the following criteria: disease meets the criteria for a relevant for both the continued health of donors
• The disease agent or disease must transfusion-transmitted infection, and and the safety of the blood supply.
present a significant health risk that that we recommend that you take steps Proposed § 630.5 would:
could be fatal, life-threatening, cause to screen and/or test donors of all or • Apply to the collection of blood and
permanent impairment of a body certain blood components for that blood components;
function or damage to body structure, or particular risk of transmission. The • Amend, combine, and redesignate
necessitate medical intervention to criteria expressed in this provision certain regulations; and
preclude such impairment or damage; would support such a notification only • Codify certain recommendations
and when there is a significant concern. currently in guidance documents.
Except as provided otherwise, the Source Plasma collected from these level and taking into account any
proposed § 630.5(a) would require you donors is safe, pure, and potent. disabilities. When screening for
to authorize a responsible physician, Proposed § 630.5(d) would permit behavioral risk factors is required for a
who is trained and qualified, to collecting establishments to authorize relevant transfusion-transmitted
determine the eligibility of a donor of trained personnel, including physician infection (for example, HIV, HBV, or
blood or blood components in substitutes, to determine the donor’s HCV), the material would instruct
accordance with part 630. We would eligibility and collect blood and blood donors to self-defer if they determine
require that each collecting components in the absence of a that they have participated in an
establishment have a qualified responsible physician. Under increased-risk behavior for, or show
physician on the premises when § 606.100(b), we would require the signs or symptoms of, that relevant
determining donor eligibility, collecting establishment to establish, transfusion-transmitted infection.
immunizing donors for the purpose of maintain, and follow SOPs specifying Currently, we recommend that
producing high-titer plasma, collecting criteria for determining donor establishments provide educational
Whole Blood or blood components, and eligibility, and for the collection of material to inform potential donors of
returning red blood cells to the donor. blood and blood components. the risks of HIV transmission and the
Proposed § 630.5(b) would The collecting establishment would need to self-defer. The current
consolidate these requirements, and be required in proposed § 630.5(e) to recommendations for educational
would require collecting establishments have SOPs for providing emergency material are described in the
to have a responsible physician present medical services to a donor within 15 memorandum entitled ‘‘Revised
during the determination of eligibility of minutes when necessary. Although we Recommendation for the Prevention of
a donor, the collection of blood and currently require the presence of Human Immunodeficiency Virus (HIV)
blood components, the collection of appropriately trained medical Transmission by Blood and Blood
Source Plasma from ineligible donors in personnel, our current regulations do Products,’’ issued April 23, 1992. We
an approved program, the return of red not directly address the availability of intend to issue additional guidance on
blood cells to the donor, and the emergency medical services, which a educational material in the future. The
immunization of donors. The donor may require. We are interested in proposed rule would also require that
responsible physician would: receiving comments on what would be educational material include behavioral
• Direct and control the physician considered as appropriate for available risks and signs and symptoms for
substitutes and trained personnel; and emergency medical services. hepatitis and other relevant transfusion-
• Approve procedures concerning the
H. General Donor Eligibility transmitted infections determined to
determination of donor eligibility, the
Requirements (Proposed § 630.10) present a risk to the blood supply. We
collection of blood and blood
are soliciting comments on this
components, the immunization of a We propose in § 630.10 to require provision, particularly on how
donor, and the return of red blood cells certain steps for determining the comprehensive the educational material
or other blood constituents to the donor eligibility of a donor to donate blood
during apheresis. should be and the format or style in
and blood components. In proposed which it is presented.
Proposed § 630.5(c) would permit a § 630.10(a), a collecting establishment
collecting establishment to authorize a would be required to perform these 2. Assessment of the Donor’s Eligibility
physician substitute to perform the prescribed steps, or assessments, to to Donate
same functions of a responsible determine if the donation may adversely
physician in the collection of Source Current § 640.3 requires that the
affect: donor be in good health and that the
Plasma, except the responsible • The health of the donor or collecting establishment determine the
physician would be required to be • The safety, purity, or potency of
present for red blood cell donor’s suitability for donation on the
blood or blood components.
immunizations. Many plasma collecting We are proposing to combine and day of collection. The status of the
establishments currently have FDA revise the donor suitability donor’s health is determined by
approval under alternative procedures requirements in §§ 640.3 and 640.63 and performing a prescribed physical
regulations in § 640.120 for the use of a to redesignate these requirements as examination, and the donor may not
physician substitute program for a § 630.10. Proposed § 630.10 would serve as the source of Whole Blood more
variety of activities. These include contain the requirements for than once in 8 weeks.
supervising the collection of Source determining the eligibility of the donor Proposed § 630.10(c) would require
Plasma from donors who meet all to donate blood and blood components, that the collecting establishment
normal donor suitability requirements, whether intended for transfusion or for perform an assessment of the donor’s
and for the scheduling and further manufacturing use. eligibility on the day of donation, and
administration of the injection of a before collection. An exception would
licensed vaccine for the production of 1. Educational Material be allowed for the collection of blood
high titer plasma. However, the In § 630.10(b), we propose to require components that cannot be stored for
responsible physician is required to be collecting establishments to provide to more than 24 hours, such as
present during red blood cell all donors, before donation, information granulocytes for transfusion. For such
immunization and high-risk collections. about the relationship among behaviors components, the collecting
This proposed rule is consistent with that increase risks of relevant establishment may perform a donor
these alternative procedures and with transfusion-transmitted infections, signs assessment and the testing required
our recommendations issued in the and symptoms of such infections, and under § 610.40(a) and (b) 1 day before
August 15, 1988, memorandum to all the consequent risk to the safety of the the collection of such products.
plasma establishments entitled blood and blood component. This Establishments would be required to
‘‘Physician Substitutes.’’ We believe that information may be provided in oral, have SOPs in place to identify such
the use of a physician substitute is written, or multimedia form in a manner components.
adequate to help ensure the continued designed to be understood by the donor, In proposed § 630.10(d),
safety of Source Plasma donors and that in appropriate language and literacy determination of a donor’s eligibility to
donate would consist of four Proposed § 630.10(e) would require • ‘‘Recommendations for the
assessments: the collecting establishment to establish Management of Donor and Units that are
• Assessing the donor’s deferral that the donor is in good health. This is Initially Reactive for Hepatitis B Surface
status; usually accomplished by administering Antigen (HBsAg),’’ dated December 2,
• Assuring that the donation interval an appropriate medical history 1987;
is appropriate, taking into account questionnaire in oral, written, or • ‘‘FDA Recommendations
whether the donor is participating multimedia form, and taking into Concerning Testing for Antibody to
simultaneously in other blood or blood account any disabilities using Hepatitis B Core Antigen (Anti-HBc),’’
component collection programs; appropriate language and literacy level, dated September 10, 1991;
• Assessing the donor’s medical to the donor on each day of donation. • ‘‘Revised Recommendations for the
history; and With frequent donation, e.g., frequent Prevention of Human
• Assessing the donor’s health by Source Plasma donations, an Immunodeficiency Virus (HIV)
performing a physical assessment of the appropriate abbreviated questionnaire Transmission by Blood and Blood
donor. may be used if it adequately captures Products,’’ dated April 23, 1992;
Consistent with the good guidance necessary donor medical history. The
practice regulations, we intend to issue • ‘‘Revised Recommendations for
use of an abbreviated donor history Testing Whole Blood, Blood
guidance on determining the eligibility questionnaire was discussed at the
of a donor of blood and blood Components, Source Plasma and Source
Blood Products Advisory Committee Leukocytes for Antibody to Hepatitis C
components. The guidance document meeting held on December 11, 2003.
would represent our current thinking on Virus Encoded Antigen (Anti–HCV),’’
The questionnaire would enable the dated April 23, 1992;
describing the assessment factors, signs, collecting establishment to do the
and symptoms, and recommended • ‘‘Draft Guidance for Industry:
following: Revised Recommendations for Donor
deferral periods to be included in a • Determine if the donor is in good
medical history questionnaire and a and Product Management Based on
health and if healthcare practitioners Screening Tests for Syphilis,’’ dated
physical examination. have advised the donor not to donate;
June 2003;
a. Deferral status and donation • Identify risk factors for relevant
history. transfusion-transmitted infections; • ‘‘Recommendations for the Deferral
After the donor has reviewed the • Determine the possibility of of Current and Recent Inmates of
educational material and does not self- exposure to, or clinical evidence of, Correctional Institutions as Donors of
defer, under proposed § 630.10(d)(1) the relevant transfusion-transmitted Whole Blood, Blood Components,
collecting establishment would check infections; and Source Leukocytes, and Source
the donor deferral registry to determine • Determine whether there are other Plasma,’’ dated June 8, 1995;
whether the donor is deferred conditions that may adversely affect the • ‘‘Guidance for Industry: Revised
temporarily, indefinitely or donor or the safety, purity, or potency Preventive Measures to Reduce the
permanently. (See section III.C of this of the donated blood or blood Possible Risk of Transmission of
document.) If the donor is deferred from component, such as by examining the Creutzfeldt-Jakob Disease (CJD) and
allogeneic donation indefinitely, or phlebotomy site for infection or Variant Creutzfeldt-Jakob Disease (vCJD)
permanently, or the temporary deferral inflammation which may cause by Blood and Blood Products,’’ dated
period has not expired, the donor is contamination of the unit being January 2002;
ineligible to donate. Donor deferrals are collected. • Draft ‘‘Guidance for Industry:
based on the degree of risk to the Proposed § 630.10(f) and (g) describe Recommendations for Donor
donor’s health, or the safety, purity, and factors that make a donor ineligible to Questioning Regarding Possible
potency of the donated blood or blood donate and that must be addressed in Exposure to Malaria,’’ dated June 2000;
components. Under proposed medical history questions. • ‘‘Guidance for Industry:
§ 630.10(d)(2), the collecting Proposed § 630.10(f).—Proposed Recommendations for Assessment of
establishment would check the donor’s § 630.10(f) would require the collecting Donor Suitability and Blood and Blood
most recent donation to assure that the establishment to assess the donor for Product Safety in Cases of Possible
donation interval is appropriate for the certain described factors, which may Exposure to Anthrax,’’ dated October
type of donation, as described in indicate that the donor is at increased 2001;
proposed § 630.15(a)(1) (Whole Blood), risk for, or has evidence of, a relevant • ‘‘Guidance for Industry: Assessing
and § 640.22(b) (Platelets) and transfusion-transmitted infection; and to Donor Suitability and Blood and Blood
640.65(b)(4) (Plasmapheresis) determine the donor ineligible to donate Product Safety in Cases of Known or
(§§ 640.22(b) and 640.65(b)(4)). In the when the assessment indicates possible Suspected West Nile Virus Infection,’’
interest of donor protection, we are exposure to a relevant transfusion- dated June 2005;
proposing to include in proposed transmitted infection that is still • ‘‘Guidance for Industry:
§ 630.10(d)(2) the requirement that the applicable at the time of donation. Recommendations for Deferral of
establishment take into account whether These factors are listed in proposed Donors and Quarantine and Retrieval of
the donor is participating in other blood paragraphs (f)(1) through (f)(6). In Blood and Blood Products in Recent
or plasma collection programs, which addition to the following discussion of Recipients of Smallpox Vaccine
could put the donor at risk by possible these factors, we refer you to the (Vaccinia Virus) and Certain Contacts of
over-collection of a blood component. following current Memoranda to Blood Smallpox Vaccine Recipients,’’ dated
This is currently recommended in a Establishments and Blood Guidances, December 2002; and
blood memorandum dated March 10, which discuss factors related to • ‘‘Guidance for Industry: Revised
1995, to registered blood and Source exposure to a relevant transfusion- Recommendations for the Assessment of
Plasma establishments entitled transmitted infection. The draft Donor Suitability and Blood Product
‘‘Revision of FDA Memorandum of guidances included in the following Safety in Cases of Suspected Severe
August 27, 1982: Requirements for bulleted list, when finalized, will Acute Respiratory Syndrome (SARS) or
Infrequent Plasmapheresis Donors.’’ represent FDA’s current thinking on Exposure to SARS,’’ dated September
b. The donor’s medical history. those topics. 2003.
These memoranda and guidance or symptoms would be ineligible to Proposed § 630.10(g).—There are
documents further discuss the donate blood and blood components. other factors that make a donor
applicability of these factors in donor This provision is intended to help ineligible because of the risk they
screening. All current memoranda and ensure that an individual who exhibits present to the health of the donor
guidance documents referenced in this one or more of the signs and symptoms before, during, and after the donation
rulemaking may be found at http:// of HIV infection or viral hepatitis, or process, or because they could adversely
www.fda.gov/cber/reading.htm. any other relevant transfusion- affect the safety, purity, and potency of
Social behaviors (Proposed transmitted infection that would be the blood and blood component.
§ 630.10(f)(1)).—Under proposed applicable under proposed § 630.3(g), Proposed paragraph (g) would require
§ 630.10(f)(1), establishments must and who is, therefore, a potential source the collecting establishment to
determine whether a donor has engaged of transmitting a relevant transfusion- determine the donor ineligible to donate
in social behaviors associated with transmitted infection, does not donate if the following factors existed and the
increased risk of infection with relevant blood or blood components. collecting establishment decided that
transfusion-transmitted infections. Institutionalization (Proposed donation by the donor would present a
Some examples of social behaviors § 630.10(f)(4)).—A collecting risk to the health of the donor, or to the
associated with increased risk of establishment would determine whether safety, purity, and potency of the blood
exposure to HIV and viral hepatitis a donor is currently an inmate of a and blood component. In addition to the
identified in current guidance are men correctional institution or has been following discussion, we refer you to
who have had sex with another man incarcerated within the last 12 months, the following current Memoranda to
even one time since 1977; exchanging and if so, whether the risk of exposure Blood Establishments and Guidances,
sex for drugs or money; or intravenous related to that incarceration is still which discuss factors related to donor
drug use. Participation in social applicable at the time of donation. risk or product safety. The draft
behaviors associated with relevant Current guidance recommends that a guidance documents included in the
transfusion-transmitted infections donor not be eligible to donate if following bulleted list, when finalized,
would cause the donor to be ineligible incarcerated in a correctional institution will represent FDA’s current thinking
to donate and to be deferred. We have for more than 3 consecutive days during on that topic.
issued guidance on such deferrals and the past 12 months. • ‘‘Deferral of Blood and Plasma
we will continue to do so, pursuant to Intimate contact (Proposed Donors Based on Medications,’’ dated
our good guidance practices. We § 630.10(f)(5)). We would require July 28, 1993;
include assessment of certain social collecting establishments to determine • ‘‘Deferral of Blood Donors Who
behaviors because of the risk that testing whether a donor is or was an intimate Have Received the Drug Accutane,’’
alone would not detect infection due to contact of a person who is at an dated February 28, 1984;
testing error, the early stage of the increased risk for exposure to, or is • ‘‘Deferral of Donors Who Have
donor’s infection (the window period), known to be infected with, a relevant Received Human Pituitary-Derived
or the donor’s low antibody level or transfusion-transmitted infection that is Growth Hormone,’’ dated November 25,
intermittent viremia. spread by intimate contact and, is thus, 1987;
To assist us in developing such ineligible to donate. One example is a • Draft ‘‘Guidance for Industry:
guidance documents, we intend to hold heterosexual partner of an injection Precautionary Measures to Reduce the
workshops and public meetings on drug user. Such individuals are at Possible Risk of Transmission of
social behaviors associated with increased risk for contracting relevant Zoonoses by Blood and Blood Products
increased risk of infection with a transfusion-transmitted infections due from Xenotransplantation Product
relevant transfusion-transmitted to the exchange of bodily fluids, Recipients and Their Intimate
infection. The public will have the including blood or saliva. Contacts,’’ dated February 2002.
opportunity to submit comments on Percutaneous exposure (Proposed Medical or dental treatment, or
specific issues as they are presented. § 630.10(f)(6)).—We would require symptoms of a recent or current illness
Medical treatment and procedures collecting establishments to assess (Proposed § 630.10(g)(1).—Under
(Proposed § 630.10 (f)(2)).—We are whether a donor had a nonsterile proposed paragraph (g)(1), the collecting
proposing that you assess donors to percutaneous inoculation within the establishment must assess the health of
determine whether they have received past year. A piercing of the skin with an the donor based on medical or dental
medical treatment or undergone a instrument used previously on another treatments. The collecting establishment
medical procedure that would put the person with a relevant transfusion- must also assess the health of the donor
individual at risk for potential exposure transmitted infection could expose the for symptoms of recent or current
to a relevant transfusion-transmitted donor to such infections. Under this illnesses. The establishment must
infection. Such donors would be provision, establishments would defer determine whether the donor is
ineligible to donate. Some examples of donors who, within the last 12 months, ineligible to donate temporarily,
treatments or procedures that may experienced any piercing of the skin by indefinitely, or permanently, depending
transmit a disease or disease agent are a nonsterile instrument, such as may be on the illness or treatment, if that
receipt of dura mater graft, transfusion used in tattoos, body or ear piercing, or assessment reveals a factor that may
with blood or blood components within intentional or accidental needlestick adversely affect the safety, purity, or
the previous 12 months, or the receipt (percutaneous exposure). FDA potency of the blood or blood
of human-derived clotting factor within understands that certain establishments component, or that the donation may
the previous 12 months. are licensed by a State or credentialed adversely affect the health of the donor.
Signs and symptoms of relevant by a responsible certifying body to For example, if the donor recently was
transfusion-transmitted infections perform such procedures with sterile diagnosed with pneumonia, the
(Proposed § 630.10(f)(3)).—We would needles. FDA does not intend for such interviewer would further assess the
require blood establishments to assess a procedure performed by a state- donor to assure that the donor is in good
donors for signs or symptoms of licensed or responsibly certified health at the time of donation and that
relevant transfusion-transmitted establishment to be a reason to defer the the donor’s health would not be
infections; donors exhibiting such signs donor. adversely affected by the donation. If
the donor had a recent tooth extraction time of donation, and, if so, determine of blood and blood components as well
or oral surgery, the collecting the donor ineligible to donate. as Source Plasma. The establishment
establishment would temporarily defer Xenotransplantation product would assess the donor for impairment
the donor due to concern for possible recipient and intimate contact due to the influence of drugs or alcohol,
contamination of blood or blood (Proposed § 630.10(g)(5)).—The or for providing unreliable answers to
components due to transient bacteremia potential for infectious disease the medical history interview. One
caused by the performance of dental transmission and public health risks example of an unreliable answer is
procedures. associated with xenotransplantation when a donor states that he or she is
Medications (Proposed products has become an increasing donating for the purpose of getting
§ 630.10(g)(2)).—We would require concern. Because xenotransplantation tested for a relevant transfusion-
collecting establishments to assess the disrupts the recipient’s usual protective transmitted infection. Such action
effects of medication taken by the donor physical and immunologic barriers, would indicate that the donor has
and to defer that donor if the medication receipt of a xenotransplantation product reason to believe there is a possibility of
could have an adverse effect on the may facilitate transmission of infectious infection due to participation in high-
blood and blood components, the agents to humans. Additionally, risk activities.
recipient, or on the developing fetus of transmission of such an infectious agent
a pregnant recipient. The proposed to an intimate contact of a c. Physical assessment.
regulation is consistent with current xenotransplantation product recipient Sections 640.3(b) and 640.63(c)
industry practice to screen prospective may be possible. Therefore, a currently require collecting
donors to identify such medications, xenotransplantation product recipient establishments to determine that a
and evaluate the potential for each and an intimate contact of a donor is in good health on the day of
medication to have an adverse effect on xenotransplantation product recipient donation, indicated in part by a normal
the safety of the blood supply. For would be determined to be ineligible temperature, a blood pressure within
example, following current industry and deferred from donating. normal limits, and a hemoglobin level of
practice and FDA recommendations, Exposure to a released disease agent no less than 12.5 grams per 100
collecting establishments would defer or disease (Proposed § 630.10(g)(6)).— milliliters (mL) of blood or no less than
from donation, either temporarily or Recent events have made us aware that a hematocrit value of 38 percent. We are
permanently, a donor who had taken donors may be affected by a released moving these requirements to proposed
certain medications (e.g., Accutane and disease agent or disease. The release § 630.10(h)(1) through (h)(6) as criteria
Tegison). We further discuss the use of may occur accidentally, such as in a for determining that a donor is in good
certain medications that adversely affect laboratory accident, or intentionally, health to protect the health of the donor
platelet function in section III.O of this such as in a bioterrorist attack. An and to ensure the safety, purity, and
document. example is the exposure in 2001 of potency of the blood and blood
Major surgical procedure (Proposed individuals to Bacillus anthracis components.
§ 630.10(g)(3)).—We would require through the U.S. mail. Proposed Temperature (Proposed
establishments to defer donors who § 630.10(g)(4) would require the § 630.10(h)(1)).—We would require the
have experienced major surgery within collecting establishment to assess the collecting establishment to determine
the past 12 months. This deferral is to donor for exposure or possible exposure that the donor has a normal body
protect the donor whose health may be to a released disease agent or disease temperature. An elevated temperature
compromised by the donation and to with a potential for transmission by could indicate a possible infection. We
address the possibility that the donor transfusion, when the establishment are proposing that the maximum
may have unknowingly received blood becomes aware that such a release of a acceptable temperature not exceed
or blood components during surgery. disease agent or disease may have 37.5 °C (99.5 °F) when taken orally, or
Travel to endemic areas for occurred in the community. The the equivalent if the temperature is
transfusion-transmitted infections collecting establishment would find taken at an alternative body site. These
(Proposed § 630.10(g)(4)).—It is known donors ineligible when the disease agent acceptable values are consistent with
that several transfusion-transmitted or disease may affect the health of the good medical judgment and current
infections exist for which the risk is donor, or the safety, purity, or potency industry practice. Collecting
closely associated with a geographic of the blood and blood components. establishments determining body
area, e.g., leishmania. Typically, such Pregnancy (Proposed temperatures using a device that
infections would not be ‘‘relevant § 630.10(g)(7)).—In order to prevent any measures body temperature other than
transfusion-transmitted infections’’ adverse effect on the donor or her fetus, orally, such as by a probe placed in the
requiring broader screening and testing collecting establishments would ear, would list in their SOP the
because they do not have sufficient determine a pregnant woman ineligible maximum acceptable temperature
incidence or prevalence in the potential to donate. A woman who is up to 6 adjusted according to the method used.
donor population. This provision is weeks postpartum would also be Blood pressure (Proposed
designed to identify donors who may be determined ineligible so as not to § 630.10(h)(2)).—For the purpose of this
at risk for additional transfusion- jeopardize her health by donating. rulemaking, we would require under
transmitted infections. Because donors Unreliable answers (Proposed proposed paragraph (h)(2) that the
harboring such infections may be § 630.10(g)(8)).—Section § 640.63(d) collecting establishment determine not
asymptomatic, or the signs and requires plasma establishments to defer to be eligible a donor whose blood
symptoms may be mild enough to go a Source Plasma donor from donating if, pressure measures above 180 mm of
undetected at the time of donation, we in the opinion of the interviewer, the mercury or below 90 mm of mercury for
would require the collecting individual appears to be under the the systolic value, and above 100 mm of
establishment to assess whether the influence of drugs or alcohol or does not mercury or below 50 mm of mercury for
donor has visited or is a former resident appear to be providing credible answers the diastolic value. These limits are
of endemic areas known to harbor the to medical history questions. In currently an industry standard in use by
disease agent or disease, whether the proposed § 630.10(g)(8), this many blood establishments. We are
risk of exposure is still applicable at the requirement would apply to all donors soliciting comments with supporting
scientific data on the need for such § 630.10(h)(3), we are proposing to stated in proposed § 630.15(b)(2) for
limits on systolic and diastolic values, continue requiring these minimal donors of Source Plasma, the proposed
on the limits we have proposed, and on hemoglobin levels or hematocrit values regulation would not require collecting
adverse events associated with donation for allogeneic donors, including Source establishments to physically weigh
that have been attributed to blood Plasma donors, and autologous donors. individuals at each donation, but
pressure. In particular, we are seeking The collecting establishment would be § 606.160(b)(1)(i) would require the
comments with supporting scientific permitted to obtain the blood sample by collecting establishments to retain
data on the necessity, or lack of fingerstick or venipuncture or by documentation of the donor’s responses
necessity, of specific upper or lower another method providing equivalent when asked if the donor weighs more
blood pressure limits in blood donation, results. However, the earlobe would not than 110 pounds, and if the donor
and any adverse events attributed to be an acceptable site for the collection experienced an unexplained loss of
blood pressure and associated with of a blood sample to measure the greater than 10 percent of body weight
donation. If the record supports the hemoglobin level or hematocrit value. within the past 6 months, which may be
need for different limits on systolic and We propose this restriction based on a sign or symptom of a relevant
diastolic values, for example, a lower evidence that a blood sample collected transfusion-transmitted infection.
systolic limit of 90 mm of mercury and from the earlobe does not accurately We recognize that some collecting
a lower diastolic limit of 50 mm of reflect the donor’s true venous establishments believe it acceptable and
mercury, we will make appropriate hemoglobin level or hematocrit value safe to collect a reduced volume of
changes in the final rule. We are also (Ref. 4). blood and blood components from a
soliciting comments on whether an We are specifically soliciting donor weighing less that 110 pounds.
abnormal blood pressure may be an comments and supporting data on the We are requesting comments and
indication that the donor has an following: supporting scientific data regarding both
undetected illness, such as • Changing the minimum acceptable the volume of blood that can be safely
cardiovascular or renal disease, may not hemoglobin level to 12.0 grams per collected from a donor in relation to the
be in good physical health and, deciliter of blood or a hematocrit value donor’s body mass, and the criteria to
therefore, may be harmed by the act of of 36 percent as acceptable minimal define a standard unit of blood. We are
donating. values for female allogeneic donors; also seeking comments on the feasibility
We are also seeking comments on the • The possibility of adverse effects and impact of determining that a donor
accuracy and interpretation of blood caused by the collection of blood and has experienced a significant recent and
pressure measurements taken in the blood components from allogeneic unexplained loss of weight, and, if so,
setting of blood and plasma donation. donors with such minimum hemoglobin whether an unexplained loss of 10
Although the occluding cuff technique level of 12.5 grams per deciliter of blood percent of the donor’s weight is an
is simple and easy to learn, errors can or a hematocrit value of 38 percent for appropriate marker of possible
still be made. A single blood pressure males, and hemoglobin level of 12.0 underlying illness, and whether loss of
measurement taken at the time of grams per deciliter of blood or a weight in the 6 month time period prior
donation may not represent the donor’s hematocrit value of 36 percent for to donation is an appropriate time frame
true baseline due to variations in the females, which are considered below to indicate that such weight loss is an
donor’s blood pressure throughout the normal by medical criteria; or if such appropriate marker for such potential
day or under different situations. There decisions should be left to the discretion illness.
are also many other causes of error and of the medical director of the collecting Collecting establishments routinely
inaccuracy in the measurement of blood establishment on a case-by-case basis; weigh donors of Source Plasma so that
pressure. There is no uniform standard • Establishing a more stringent inter- they may apply the nomograms for
methodology for day-to-day use by all donation interval; and volume limits as recommended in the
donor room personnel (Ref. 2). • The use of copper sulfate solution Memorandum to All Licensed Source
Both aneroid and electronic based methods as an appropriate Plasma Establishments issued
instruments have some advantages of method to determine acceptable November 4, 1992, entitled ‘‘Volume
portability and ease of use, but few of hemoglobin levels. Limits for Automated Collection of
these instruments have had adequate Pulse (Proposed § 630.10(h)(4).—We Source Plasma.’’ Under proposed
validation. Still fewer of these would require the collecting § 630.15(b)(2), we would require
instruments are calibrated regularly and establishment to take the donor’s pulse collecting establishments to weigh a
most of the instruments have not been rate, which is an indicator of the donor’s donor of Source Plasma at each
validated over a wide range of blood cardiovascular health. We would donation. For donors of Source Plasma,
pressures and ages (Ref. 3). Therefore, consider as acceptable a regular pulse records of donor weight should be
an isolated measurement of blood rate and any value between 50 and 100 examined for unexplained weight loss at
pressure may not reliably assess beats per minute. Any irregular pulse, or the time of the donor’s annual medical
eligibility for blood donation. any value below 50 beats per minute or examination. (See also section III.I.2.b of
Hemoglobin or hematocrit above 100 beats per minute would be this document.)
determination (Proposed cause to determine the donor ineligible Skin examination (Proposed
§ 630.10(h)(3)).—The current regulations to donate, unless the responsible § 630.10(h)(6)).—We would require that
in § 640.3(b)(3) require that an physician examines the donor and the collecting establishment examine:
allogeneic donor have a minimum determines that the health of the donor (1) The phlebotomy site for evidence of
hemoglobin level of 12.5 grams per would not be adversely affected. infection, inflammation, lesions, or
deciliter of blood or a hematocrit value Weight (Proposed § 630.10(h)(5)).— pitted skin (to eliminate contaminating
of 38 percent to participate in a Proposed § 630.10(h)(5). This paragraph the donation and possibly putting the
collection program; and that an would require that a donor weigh a recipient at risk for sepsis) and (2) the
autologous donor have a minimum minimum of 50 kilograms (110 pounds) donor’s arms and forearms for punctures
hemoglobin level of 11.0 grams per and not have any unexplained loss of and scars indicative of injected drugs of
deciliter of blood or a hematocrit value greater than 10 percent of body weight abuse. Use of injected drugs not
of 33 percent. In proposed within the past 6 months. Except as prescribed for medical reasons (drug
abuse), regardless of the site of injection, donor will be deferred from further required to defer the donor for 16 weeks
would place the donor at increased risk donation temporarily, indefinitely, or before allowing the donor to participate
for exposure to a relevant transfusion- permanently, and notified of the basis of in a Whole Blood collection program, in
transmitted infection. the deferral; any apheresis program, or in a double
• The donor understands the hazards Red Blood Cells unit collection program
3. Additional Requirements for
and risks of the procedure; and again. This is currently recommended in
Determining Donor Eligibility • The donor has the opportunity to the January 2001 guidance entitled
Proof of identity and mailing address ask questions and refuse to donate at ‘‘Guidance for Industry:
(Proposed § 630.10(i)(1)).—Proposed any time. Recommendations for Collecting Red
§ 630.10(i)(1) would require the • The collecting establishment must Blood Cells by Automated Apheresis
collecting establishment to obtain, not proceed with the phlebotomy until Methods.’’ This proposed requirement
before donation, donor identification, the donor signs the statement. protects the donor’s health. We also are
such as a photograph identification and •We also note that some blood proposing that a donor may donate
an address as required under components may be stored indefinitely sooner than the proposed required time
§ 606.160(b)(1)(x). Collecting before they are used. During that time, period if the collecting establishment’s
establishments are required under we may become aware of new infectious responsible physician examines the
§ 630.6 (proposed redesignation to agents, which may be identified only donor and certifies the donor to be in
§ 630.40) to notify donors that they are through the use of investigational tests. good health and one of the following
deferred from further donation based on An establishment may want to test three conditions exist:
the results of tests for evidence of stored blood components using the • The donor presents a physician’s
infection with a communicable disease investigational test, but face obstacles prescription for a therapeutic
agent(s). Having a current address will due to the lack of donor consent to the phlebotomy; or
assist the collecting establishment in the use of an investigational test. An • The donation is an autologous
notification process when necessary. establishment may seek to address this donation; or
Donor’s written statement of problem, in advance, by obtaining • The donation is dedicated to a
understanding (Proposed adequate informed consent to specific recipient based on documented
§ 630.10(i)(2)).—In order to ensure that investigational tests at the time of medical need.
the donor has been informed of and donation. We note that consent to The responsible physician would
understands the collection procedure authorize investigational testing subject explain to the donor in the written
and the educational material, the to investigational new drug or statement of understanding (proposed
collecting establishments would be investigational device exemption § 630.10(i)(2)(vi)) the hazards or risks
required to provide a written statement requirements must meet the from more frequent donations.
to the donor, using appropriate language requirements of 21 CFR part 50. b. Therapeutic phlebotomy.
and literacy level and taking into Currently, under § 640.3(d), we
account any donor disabilities, to read I. Donor Eligibility Requirements require that blood drawn to promote the
and sign before phlebotomy is Specific to Whole Blood and Plasma health of the donor not be used as a
performed. This statement would be Collected by Plasmapheresis (Proposed source of Whole Blood unless the
written in a clear and understandable § 630.15) container label conspicuously indicates
terminology and not include language The donor eligibility requirements the donor’s disease that necessitated the
that would waive any of the donor’s under proposed § 630.10 would apply to phlebotomy. Under the new proposed
legal rights. The document would all donors of Whole Blood and blood § 630.15(a)(2), we would continue to
provide the following information as components, including Plasma collected require that the container label state the
described in proposed § 630.10(i)(2)(i) by plasmapheresis. In addition to these donor’s disease that necessitated the
through (i)(2)(vii): proposed requirements, other phlebotomy, but would permit an
• The donor reviewed the provided requirements specific to Whole Blood or exception to this provision. In August
educational material regarding the Plasma collected by plasmapheresis are 2001, we issued ‘‘Guidance for Industry:
relevant transfusion-transmitted proposed in § 630.15. Variances for Blood Collection from
infections, including HIV, HBV, and Individuals with Hereditary
1. Whole Blood Hemochromatosis,’’ which provides
HCV, and understands that such
infections present potential risks to the The following two sections are guidance for requesting a variance from
safety of the blood supply; specific to Whole Blood donation. the labeling requirement for individuals
• The donor agrees not to donate if a. Donation frequency. with hereditary hemochromatosis (HH).
the donation could result in a potential With the establishment of double Red This proposed rule would codify those
risk to the safety of the blood supply as Blood Cells unit collection programs by recommendations, eliminate the need
described by the educational material; some establishments, we are proposing for a variance request, and permit all
• The donor understands that, a to adjust the donation frequency collecting establishments to use a
sample of the donor’s blood taken at the requirements currently in § 640.3(f). donation from an individual with HH as
time of phlebotomy will be tested for Proposed § 630.15(a)(1) would continue a source of Whole Blood and not affix
specified relevant transfusion- the requirement in § 640.3(b) that a disease label for HH, if the following
transmitted infections; collecting establishments collect a conditions are met:
• The donor understands that, if any single unit of Whole Blood from a donor • The donor with HH otherwise
of the tests for the relevant transfusion- no more than once in 8 weeks. We also meets the same eligibility requirements
transmitted infections required under are proposing that if a donor is under proposed § 630.10 as for other
§ 610.40(a) are reactive, the blood participating in a double Red Blood allogeneic donors whose blood would
sample will be tested further as Cells unit collection program, i.e., be used for transfusion or further
necessary and appropriate to determine where two units of Red Blood Cells are manufacturing use; and
the donor’s infection status; collected by an automated blood cell • The collecting establishment does
• The donor understands that, if a separator on the same occasion, then the not charge a fee for any phlebotomies
basis for deferral is discovered, the collecting establishment would be performed on individuals with HH,
including those who do not meet the indicator to identify health problems in plasmapheresis under proposed
eligibility requirements proposed under the donor. § 630.20(c)(2).
§ 630.10. As explained in the August c. Total protein. e. Exception to the donor eligibility
2001 guidance, if a blood establishment Under existing § 640.63(c), we require requirements for Plasma collected by
charged a fee for therapeutic collecting establishments to test the plasmapheresis.
phlebotomy, but not for a collection of donor’s blood sample for total protein Under § 640.63(c)(9), a Source Plasma
blood for transfusion, the HH donor on the day of and before donor must be free from any disease
would have an incentive to deny risk plasmapheresis. We would continue to transmissible by blood transfusion,
conditions that might preclude cost-free require under proposed § 630.15(b)(3) other than malaria, insofar as the
donation. Accordingly, this provision that collecting establishments test the disease can be identified by history and
removes that incentive. Blood and blood donor’s sample for a total plasma or examinations. In ‘‘Memorandum to
components collected from persons serum protein and have a value of no Registered Blood Establishments—
undergoing therapeutic phlebotomies less than 6.0 grams per deciliter or no Recommendations for Deferral of
who are ineligible to donate would be more than 9.0 grams per deciliter, the Donors for Malaria Risk’’ issued in July
discarded unless other arrangements are minimum and maximum normal values, 1994, and a draft guidance issued for
in place to permit the practice, such as for the donor to donate. If the value is public comment in June 2000, entitled
license amendments, requests for less than 6.0 grams per deciliter or more ‘‘Guidance for Industry:
variance, or short supply agreements than 9.0 grams per deciliter, the Recommendations for Donor
(for example, if certain rare antibodies collecting establishment would be Questioning Regarding Possible
are present, or for manufacture into an required to defer the donor until the Exposure to Malaria,’’ we make
in vitro reagent) (§§ 601.12, 610.40(h)(2) donor’s total protein level is at an recommendations for assessing donors
and § 640.120). acceptable value. for malaria risk. These apply only to
2. Plasma Collected by Plasmapheresis d. Deferral due to red blood cell loss. donations containing intact red blood
Under proposed § 630.15(b)(5), in cells or platelets, where the protozoa are
a. Examination by a responsible order to protect the donor’s health, we found. Donors of Source Plasma
physician. would require the collecting collected by plasmapheresis are
In addition to the eligibility establishment to defer a donor from excluded from the malaria risk
requirements proposed in § 630.10, donating plasma for 8 weeks after one assessment since plasma does not
proposed § 630.15(b)(1) would require of the following events: contain intact red blood cells, which
the responsible physician to examine • The donor experienced a red blood harbor the infectious agent. Moreover,
the donor initially and annually for cell loss of 200 mL or more of red blood Source Plasma undergoes further
medical conditions that would place the cells during a single automated or manufacturing to remove or inactivate
donor at risk during the process of manual plasmapheresis procedure; or pathogens. We maintain this exception
plasmapheresis and explain the hazards • The donor experienced an in proposed § 630.15(b)(7). However, we
of the procedure so that the donor may unexpected red blood cell loss of any are interested in receiving comments
choose not to donate. The initial volume in an automated apheresis with supporting data on the following:
examination would occur no more than procedure on two occasions within the (1) Whether Fresh Frozen Plasma
1 week before the first donation. In last 8 week period; collected by plasmapheresis can be
addition, under proposed § 630.15(b)(4), • The donor experienced a red blood safely manufactured from donors with
if the donor is participating in an cell loss equivalent to or greater than risk of malaria and (2) whether this
immunization program for the 200 mL of red blood cells as a result of exception should be expanded to apply
collection of high-titer plasma, then the failure to return red blood cells during to other parasitic diseases.
examination must occur no more than 1 a manual plasmapheresis procedure; or
J. General Exceptions from the Donor
week before the first immunization • The donor donated a unit of Whole
injection. It is not necessary to repeat Eligibility Requirements (Proposed
Blood.
the physical examination if the § 630.20)
However, if a donor participates at
immunized donor’s plasma is collected any time in a double Red Blood Cells Proposed § 630.20 would permit,
within 3 weeks of the first unit collection program, then the under certain circumstances and under
immunization injection. These collecting establishment would be the supervision of the responsible
provisions are currently required under required to defer the donor for 16 weeks physician, the collection of blood and
§ 640.63(b)(1), (b)(2)(i), and (b)(2)(ii). after the last double red blood cell blood components from individuals
b. Weight. donation under proposed § 630.15(a)(1). who do not meet one or more of the
In proposed § 630.15(b)(2), we would Under proposed § 630.15(b)(6), we eligibility requirements proposed in
require that establishments determine a would allow exceptions to the deferral §§ 630.10(d), 630.15, and 610.41. We
donor’s weight at each donation. This for red blood cell loss if all of the would require that the responsible
information allows you to determine the following criteria are met. physician examine the donor and certify
appropriate amount of plasma that can • The donor is examined at the time that the donor’s health permits the
be safely removed. We note that, of donation and certified by the collection procedure, and that the
although unexplained weight loss can responsible physician to be in good collection be performed under the
be a sign or symptom of a relevant health and the donor’s health permits supervision of the responsible
transfusion-transmitted infection, the the plasmapheresis; and physician, who is aware of the donor’s
proposed rule does not require • The donor possesses an antibody health status. We would only allow this
establishments to measure donor weight that is transitory, of a highly unusual or exception in the following situations.
at the time of apheresis as an indicator infrequent specificity, or of an • The donation is for autologous use
of underlying disease. FDA is soliciting unusually high titer; and as prescribed by the donor’s physician
comments with supporting data on the • The collecting establishment and is not intended for allogeneic
usefulness of measuring weight loss at documents the special characteristics of transfusion or for further manufacturing
the time of donation by apheresis as an the antibody and the need for use; or
• The donor is participating in a plasma by apheresis in the preceding 4 then the otherwise eligible donor may
plasmapheresis program that collects weeks, or participated in a double Red be determined to be eligible to donate if
plasma for further manufacturing use Blood Cells unit collection program the basis for the previous deferral is no
into products for which there are no within the preceding 16 weeks; longer applicable. To requalify a donor
alternative sources, and the program has • The donor has not donated more deferred under § 610.41(a), because the
received prior approval from the than 12.0 liters of plasma in the past donor tested reactive by a screening test
Director, Center for Biologics Evaluation year (14.4 liters of plasma for donors for evidence of infection due to a
and Research, consistent with § 606.110. weighing more than 175 lbs.); relevant transfusion-transmitted
For example, the donor may serve as a • The donor is determined by the infection, the collecting establishment
source of antibody to hepatitis B surface responsible physician to be in good would determine the donor to be
antigen for the preparation of Hepatitis health under proposed § 630.10(d); and eligible for donation by a requalification
B Immune Globulin (Human) or as a • The donor is not participating in an method found acceptable for such
component of a medical device. Other immunization program for the purpose by FDA under § 610.41(b). For
examples are discussed in the production of high-titer plasma. example, FDA issued draft guidance on
‘‘Guideline for Collection of Blood or a requalification method or process for
L. Donation Suitability Requirements
Blood Products from Donors with reentry of donors deferred because of a
(Proposed § 630.30)
Positive Tests for Infectious Disease reactive screening test for HIV or HCV
Markers (High Risk Donors),’’ dated The collecting establishment would entitled ‘‘Guidance for Industry: Nucleic
September 1989; or determine a donation as suitable when Acid Testing (NAT) for Human
• The donation is for the sole use of the following occurs: Immunodeficiency Virus Type 1 (HIV–
a specified recipient based on • The donor is not currently deferred 1) and Hepatitis C Virus (HCV): Testing,
documented medical need, and the from donation; Product Disposition, and Donor Deferral
responsible physician determines that • The results of the medical history and Reentry,’’ dated July 2005. Donor
the donation presents no undue medical and physical examination indicate that screening tests may yield a number of
risk to the recipient. The donation must the donor is in good health and false positive test results. For a donor
test negative in all tests required under donating would not adversely affect the deferred under such a test, an
§ 610.40, unless an exception in health of the donor; establishment could retest the donor,
§ 610.40(h)(2) applies. However, for • The donor is free from risk factors following the recommendations for
deferrals under § 610.41, we are for, or evidence of, transfusion- donor re-entry in the guidance, when
soliciting comments on permitting, in transmitted infections; finalized. If results of the retesting meet
the case of documented medical need, • The donor’s tests for relevant the reentry criteria found acceptable for
the use of donations testing reactive for transfusion-transmitted infections are such purposes by FDA, the donor would
antibody to hepatitis B core antigen. For negative or nonreactive; be requalified under § 610.41(b) and no
example, we are considering whether, For platelet components, the test for longer would be deferred. Of course, the
when the recipient has a rare red blood bacterial contamination is negative; and donor would be required to meet the
cell antibody and the donor is lacking The donor or donation meets other eligibility criteria at each subsequent
the red blood cell antigen for the requirements in 21 CFR subchapter F. donation.
antibody, to permit the use of a When one or more of the criteria in
donation that is reactive when tested for proposed § 630.30 for determining a N. Requirements for Notifying Deferred
hepatitis B core antibody by a screening donation as suitable are not met, the Donors (Proposed Newly Redesignated
test. collecting establishment would § 630.40)
determine that the donation is not On June 11, 2001, we published a
K. Exceptions from Certain Donor suitable, would defer the donor until the final rule entitled ‘‘General
Eligibility Requirements for Infrequent basis of deferral is resolved, and must Requirements for Blood, Blood
Plasmapheresis (Proposed § 630.25) notify the donor of the reason for the Components, and Blood Derivatives;
Under proposed § 630.25, we intend deferral under § 630.6 (redesignated as Donor Notification’’ (June 2001 final
to reduce the medical examination and § 630.40 in this proposed rule). Under rule) in the Federal Register (66 FR
laboratory testing burden on collecting § 610.40(h), the collecting establishment 31165), codified at § 630.6. The June
establishments when donors are must not ship or use donations that test 2001 final rule requires blood and
participating in plasma collection reactive for tests required under plasma establishments to notify donors,
programs at intervals of 4 weeks or § 610.40(a) and (i), unless one of the including autologous donors, whenever
more. Consistent with existing guidance limited exceptions apply. Under the donors are deferred or determined
in memoranda issued March 10, 1995, proposed § 606.160(e)(2), we also would not to be eligible for current or future
entitled ‘‘Memorandum to Registered require that the collecting establishment donations of blood and blood
Blood and Source Plasma provide to appropriate personnel of the components. Blood and plasma
Establishments, Revision of FDA establishment a list of those donors who establishments also are required to
Memorandum of August 27, 1982: are not eligible to donate under notify the referring physician for an
Requirements for Infrequent proposed § 630.10(f)(1) through (f)(6) autologous donor when the autologous
Plasmapheresis Donors’’ and November and (g)(1) through (g)(6). donor is deferred based on the results of
4, 1992, entitled ‘‘Volume Limits for tests for evidence of infection due to
Automated Collection of Source M. Requalification of Previously communicable disease agent(s). This
Plasma,’’ we would except the Deferred Donors (Proposed § 630.35) proposed rule would amend part 630,
collecting establishment from the We would permit the requalification redesignate current § 630.6 as § 630.40,
requirements for frequency of of a previously deferred donor into the and revise all references to § 630.6
examination in proposed § 630.15(b)(1) donor pool (commonly referred to as accordingly. We also are proposing to
and (b)(3), and current § 640.65(b)(1) donor re-entry) under proposed revise all references to donor eligibility
and (b)(2), if the following occurs: § 630.35. If a donor had been deferred by replacing §§ 640.3 and 640.63 with
• The donor has not donated Whole from donation because the donor did §§ 630.10 and 630.15. Consistent with
Blood in the preceding 8 weeks or not meet the requirements in part 630, proposed § 630.30(b)(4), proposed
newly redesignated § 630.40(a) would than one plateletpheresis procedure because results are typically transmitted
require a collecting establishment to within 7 calendar days. and recorded electronically, permitting
notify a donor whose platelet At the BPAC meeting held in March faster access.
component tests positive for an 2006, we also discussed the frequency We are proposing to add to § 640.69
endogenous bacteremia. of platelet collection and the impact on paragraphs (e) and (f). Proposed
the donor’s safety. Blood establishments § 640.69(e) would require collecting
O. Eligibility Requirements Specific for commented by providing data on the
Platelet Donors (Proposed § 640.21) establishments to ensure that Source
safety of collecting more than 24 platelet Plasma donated by paid donors not be
We are proposing to amend § 640.21 components per year, including 24 used for further manufacturing into
by revising the subject heading and triple platelet component collection injectable products unless the paid
paragraphs (a) through (c), and by procedures per year. BPAC advised that donor has a record of two suitable
adding paragraphs (d) and (e) for the data supported continuation of up to donations within the last 6 months at
consistency with other parts of this 24 platelet collections of triple the plasma establishment where the
rulemaking. components per year. The BPAC also donations occurred. Proposed paragraph
In addition to meeting the proposed recommended that the donor’s post- § 640.69(f) would require collecting
requirements in §§ 630.10 and 630.15, donation targeted platelet count not fall establishments to ensure that Source
under proposed § 640.21(a)(2), the below 100,000/µL. Plasma donated by paid donors
donor’s written statement of Under proposed § 640.21(d), we
determined to be suitable for further
understanding in proposed would permit a donor to serve as a
manufacturing into injectable products
§ 630.10(i)(2)(vi) would require a dedicated plateletpheresis donor as
be held in quarantine for a minimum of
statement that the long-term effects of often as necessary during a 30-day
60 days to permit the retrieval of a
frequent apheresis are unknown. period if the donor is in good health and
Source Plasma donation in the event it
Proposed § 640.21(b) for the donor’s platelet count is greater than
is later determined to be unsuitable.
plateletpheresis donors, would require 150,000/µL. The collecting
Any Source Plasma shipped prior to 60
that a donor not serve as a source of establishment must follow the
days after the date of collection must be
platelets for transfusion after the donor requirements in § 610.40(c)(1) for testing
labeled to indicate that the Source
has ingested drugs that adversely affect and labeling for dedicated donors.
Under proposed § 640.21(e), if, over Plasma is in quarantine. These proposed
platelet function. At a BPAC meeting
an 8-week period, a donor cumulatively requirements would support product
held in March 2006, we discussed the
loses 450 mL or more of whole blood or safety. In a report entitled ‘‘Blood
deferral of donors who had recently
200 mL or more of red blood cells, or Plasma Safety: Plasma Product Risks
ingested aspirin or nonsteroidal anti-
donates a unit of Whole Blood, the Are Low if Good Manufacturing
inflammatory drugs (NSAIDs). BPAC
collecting establishment must defer the Practices Are Followed’’ (September 9,
provided advice on deferral periods for
donor for 8 weeks; or, if the donor 1998), the GAO identified certain
ingestion of these products. Based on
participates in a double Red Blood Cells voluntary industry initiatives as greatly
the information received at this meeting,
unit collection program, the collecting reducing the chances of reactive units
we intend to issue for public comment
establishment must defer the donor for being used in manufacturing pools.
a draft guidance on deferrals for
16 weeks. An exception to this proposed These voluntary initiatives included the
ingestion of drugs that adversely affect
requirement would be permitted when: use of repeat donors only and a 60-day
platelet function. The draft guidance
• The donor waits 2 calendar days for inventory hold on all units to allow
document, when finalized, will assist
plateletpheresis after donating Whole manufacturers to retrieve units from
blood collecting establishments in
Blood or sustaining a blood loss and donors who subsequently test positive
appropriately deferring donors as a
• The extracorporeal red blood cell or are otherwise deferred. We are
result of ingestion of aspirin, NSAIDs,
volume during the plateletpheresis proposing to require these practices in
and other drugs that may adversely
procedure is 100 mL or less. the proposed rulemaking. However, we
impact platelet function.
We would permit, under proposed are soliciting comments and supporting
P. Eligibility Requirements Specific for data on whether other requirements
§ 640.21(c), plateletpheresis donations Source Plasma Donors (Proposed
at intervals shorter than 8 weeks would achieve the same goal. We are
§§ 640.65(b) and 640.69) also soliciting comments on whether
provided:
• The collecting establishment In addition to proposed technical these provisions should also apply to
performs a platelet count before the amendments to § 640.65(b)(1)(i) and Source Plasma from paid donors
initial procedure and before each (b)(2)(i), proposed § 640.65(b)(2)(i) collected for manufacture into non-
subsequent procedure; and would add an upper value of 9.0 grams injectable products.
• The pre-donation count is greater per deciliter of plasma sample for Q. Reporting of Donor Reactions
than 150,000/µL; and the donor’s post- acceptable total protein and a (Proposed § 640.73)
donation count is no less than 100,000/ comparable level for a serum sample
µL; and and would require the responsible Section 640.73 requires
• The donor undergoes no more than physician to review the laboratory data, establishments collecting Source Plasma
a total of 24 plateletpheresis collections the calculated values of each to report to us any donor fatality
within 12 months (e.g., either 24 single, component, and the collection records associated with plasmapheresis. We are
double, or triple platelet component within 14 calendar days after the sample proposing to retain this requirement in
collection procedures); is drawn to determine if the donor proposed § 640.73(a) and to add
• For single component collection should be deferred from further § 640.73(b), which would require
procedures, there are no more than 2 donation. If the review is not completed establishments collecting Source Plasma
plateletpheresis procedures within 7 within 14 calendar days, we would to report to us any donor adverse
calendar days; and there is a minimum require the collecting establishment to experience as described in § 600.80(a)
of 2 calendar days between procedures; defer the donor pending the review. We related to the administration of an
• For double or triple component have reduced the time period for record immunizing agent, such as red blood
collection procedures, there is no more review from 21 to 14 calendar days cells or a vaccine.
If the adverse experience is serious or of § 640.3,’’ and add in its place directs agencies to assess all costs and
life threatening as described in ‘‘§ 630.10 and 630.15.’’ This proposed benefits of available regulatory
§ 600.80(a), then we would require the revision would require donor eligibility alternatives and, when regulation is
establishment to report to us as soon as determination requirements for necessary, to select regulatory
possible by telephone or other rapid donations intended as a source material approaches that maximize net benefits
means of communication, and submit a or component of a medical device, (including potential economic,
written followup report of the including Reagent Red Blood Cells. We environmental, public health and safety,
investigation within 7 days of learning would eliminate the current exceptions and other advantages; distributive
of the donor’s adverse experience; if the to be consistent with the applicability of impacts; and equity). The agency
adverse experience is neither serious donor eligibility determination believes that this proposed rule is not a
nor life threatening, the establishment requirements for blood and blood significant regulatory action as defined
would submit the report in an annual components collected for use in the by the Executive order.
report on the anniversary of FDA’s manufacture of other in vitro diagnostic The Regulatory Flexibility Act
approval of the immunization program. products. We are interested in receiving requires agencies to analyze regulatory
Because manufacturers of blood and comments on limiting donor eligibility options that would minimize any
blood components are currently exempt determination requirements to significant impact of a rule on small
from the safety reporting requirements donations collected in the United States entities. Because this proposed rule
under § 600.80, we do not receive for use in the manufacture of Reagent incorporates industry’s usual and
adequate information to monitor and Red Blood Cells. customary business practices, the
assess safety-related information (other agency certifies that the proposed rule
than fatalities) concerning donors T. Quality Systems Regulations will not have a significant economic
enrolled in immunization programs and (Proposed § 820.1(a)(1)) impact on a substantial number of small
the collection of Source Plasma by In part 820, we have issued current entities.
plasmapheresis. Such information is good manufacturing practice (CGMP) Section 202(a) of the Unfunded
essential for evaluating our scientific requirements applicable to Mandates Reform Act of 1995 requires
and regulatory policies and for manufacturers of all finished devices that agencies prepare a written
monitoring industry practices and their intended for human use. Section statement, which includes an
implications on donor and blood safety. 820.1(a)(1) states that manufacturers of assessment of anticipated costs and
blood and blood components are not benefits, before proposing ‘‘any rule that
R. Alternative Procedures (Proposed includes any Federal mandate that may
§ 640.120) subject to part 820, but are subject to
part 606. We are proposing in this rule result in the expenditure by State, local,
We are proposing an amendment to clarify the applicability of the and tribal governments, in the aggregate,
which would separate and revise requirements in 21 CFR Chapter I, or by the private sector, of $100,000,000
§ 640.120(a) into proposed paragraphs subchapter F to donors of human blood or more (adjusted annually for inflation)
(a) and (b), and revise and redesignate or blood components used in the in any one year.’’ The current threshold
current paragraph (b) as paragraph (c). manufacture of a medical device as well after adjustment for inflation is $122
Under proposed § 640.120(a), a as for transfusion. million, using the most current (2005)
manufacturer could initiate agency Implicit Price Deflator for the Gross
review of a proposed alternative U. Technical Amendments Domestic Product. FDA does not expect
procedure. The manufacturer would We also propose technical changes to this proposed rule to result in any 1-
submit the request either as a written existing regulations, for consistency year expenditure that would meet or
request, which would include a with this proposed rulemaking. We exceed this amount.
facsimile or e-mail, or as an oral request. propose to remove §§ 640.3, 640.61, A. Objectives and Basis of the Action
This is consistent with § 640.120. We 640.62, and 640.63. We propose to
are adding proposed paragraph (b) to revise § 606.3(a) and (c), and 1270.3(b) As discussed previously, we are
permit the Director of the Center for for consistency with proposed § 630.3(a) proposing this action to help protect
Biologics Evaluation and Research to and (b). We propose to revise donor health and to help ensure the
issue an exception or alternative to the §§ 606.100(b)(20), 606.110(b), safety, purity, and potency of the
regulations in the event of a public 606.160(b)(1)(ix) and (b)(1)(xi), 640.4, national blood supply. The safety,
health emergency. This procedure 640.12, 640.22, 640.31, 640.32, 640.51, purity, and potency of the national
would be initiated only when a variance 640.52, 640.65(b), and 640.72(a)(2), blood supply is enhanced when blood
is necessary to assure the availability of (a)(3), and (a)(4) by changing headings donors are assessed for eligibility and
blood, blood components, and blood or references to CFR cites, and blood donations are assessed for
products, in a specific location and in redesignating paragraphs. suitability. The health of the donor is
response to an unanticipated immediate protected through certain physical
need for blood, blood components, and IV. Proposed Effective Date assessments, such as those regarding
blood products, as in situations We propose that any final rule that blood pressure and hemoglobin levels.
involving large numbers of casualties. may issue based on this proposal This action is taken under the
Proposed § 640.120(c) states that FDA become effective 180 days after the date authority of sections 351 and 361 of the
periodically would list approved of its publication in the Federal PHS Act to prevent the introduction,
alternative procedures and exceptions Register. transmission, and spread of
on the Center for Biologics Evaluation communicable disease. Since blood and
V. Analysis of Impacts blood components are also drugs and
and Research home page on the Internet.

FDA has examined the impacts of the devices, the provisions of the act (21
S. Reagent Red Blood Cells (Proposed proposed rule under Executive Order U.S.C. et seq.) also generally apply. In
§ 660.31) 12866, the Regulatory Flexibility Act (5 particular, section 501 of the act
In § 660.31, we are proposing to U.S.C. 601–612), and the Unfunded provides authority to ensure that
remove ‘‘§ 640.3’’ and ‘‘except in Mandates Reform Act of 1995 (Public methods used in manufacturing
paragraphs (b)(5) and (b)(6), (d), and (e) Law 104–4). Executive Order 12866 conform with CGMP. See section II.A of
this document for further details. We specialist who acts as a regulatory blood components. The rule is intended
have reviewed related Federal rules and reviewer or manager of quality to increase the safety of all blood and
have not identified any rules that assurance could perform this process. blood components by providing
duplicate, overlap, or conflict with the Based on the total average hourly recipients with increased protection
rule. compensation (including benefits) of against communicable disease
$37.03 for management, professional transmission.
B. Nature of the Impact The gravity of the disease risks
and related occupations in private
The proposed rule requires that for industry healthcare and social associated with blood and blood
each donation of blood or blood assistance workers, as reported by the components is widely recognized.
component, blood establishments Bureau of Labor Statistics, the cost Transfusion transmission of HIV, the
maintain minimum standards for donor would be approximately $1,481 ($37.03 virus that causes AIDS, continues to
eligibility (proposed §§ 630.10 and per hour x 40 hours) per establishment cause great concern. Human T-
630.15), and blood and blood (Ref. 7). lymphotropic viruses types I and II were
component suitability (proposed For establishments that do not already identified in the early 1980s. Infection
§ 630.30). A blood establishment must conform to the proposed rule, we with these viruses is associated with
also establish, maintain, and follow estimate that approximately 60 hours of tropical spastic paraparesis, adult T-cell
SOPs for the determination of donor staff time would be required to align leukemia/ lymphoma, and some
eligibility (proposed § 606.100(b)). current inadequate SOPs with the inflammatory disorders (Ref. 8). These
C. Type and Number of Entities Affected provisions of the rule. As we believe viruses are known to be transmitted by
most establishments have SOPs that are transfusion.
This proposed rule would affect all consistent with the rule, the extent that HBV is a major cause of acute and
blood establishments that collect blood staff would need to be notified of these chronic hepatitis, cirrhosis, and
and blood components, including updated SOPs would not result in hepatocellular carcinoma worldwide.
Source Plasma and Source Leukocytes. extensive formal training. The cost in The Centers for Disease Control and
Our registration database for blood and this case would be $2,222 ($37.03 x 60) Prevention (CDC) estimates that 1.25
plasma establishments has records of per establishment. Assuming a minimal million Americans are chronically
approximately 1,709 establishments: 81 review is needed at two-thirds of the infected with HBV, 15 to 25 percent of
licensed Source Plasma establishments 1,709 currently operating whom will die of chronic liver disease,
with multiple locations and 1,628 establishments and a more extensive and that there are an additional 60,000
registered blood establishments. The review is conducted by the other one- new infections each year (Ref. 9).
DHHS estimates that approximately 15 third, the total one-time cost for the Approximately 5,000 individuals in the
million blood donations are collected blood and plasma industries is United States die each year from disease
annually (Ref. 5). According to a 2002 estimated to be $2,953,000 ((2/3 x 1,709) caused by HBV (Ref. 10). Prior to the
report by the Government x $1,481)) + ((1/3 x 1,709) x $2,222)). development of hepatitis screening
Accountability Office (at that time, the Our cost estimate assumes that the tests, transfusion-related risks were
General Accounting Office), 13 million assessment of donors for eligibility and significant.
donations of Source Plasma are donations for suitability are already While recipients of blood products
collected annually by plasma centers usual and customary business practices. prior to 1992 are at risk for infection
(Ref. 6). We believe that most establishments with HCV, blood donor screening for
already conform to this proposed rule HCV has reduced transfusion-associated
D. Estimated Impact of Requirements for transmission to less than one in 1.6
and others nearly conform to this
Assessment of Donor Eligibility million transfused units of blood (Ref.
proposed rule and assume a two-thirds
The rule provides for the one-third division between the two 11). Persons currently at increased risk
establishment of minimum criteria for groups of establishments. Nevertheless, for HCV infection include parenteral
the assessment of donor eligibility, and because we lack information on the drug users and health care workers with
the suitability of the donation of blood characteristics or fraction of occupational exposure to blood. CDC
and blood components. The rule is establishments not currently in estimates approximately 26,000 new
expected to have a minor net impact on compliance, we welcome comment on HCV infections occur annually in the
blood establishments because it is our assumption. Also, while we assume United States and that 4.1 million
already usual and customary business the costs are limited to a review of Americans have been infected with HCV
practice in the blood industry to assess SOPs, if these reviews were to uncover (Ref. 12). Despite advances in treatment
donors for eligibility, and donations for deficiencies requiring complex with interferon and ribavirin, HCV
suitability. We believe the primary operational changes, the impact of this infection remains a leading indication
impact of the rule will be the one-time proposed rule could exceed our for liver transplant and up to five
review of current SOPs that the estimate. We request comment from percent of those infected will die from
proposed rule would require each blood blood establishments on our the consequences of long-term infection
collecting establishment to conduct. assumption. (Ref. 10).
The burden imposed by this one-time The requirement that, for each
effort to review and, if necessary, E. Expected Benefits of the Rule donation of blood or blood component,
modify current SOPs will vary among This proposed rule would help ensure blood establishments maintain
the 1,709 establishments, depending on the continued safety of the blood standards for donor eligibility and blood
an establishment’s existing procedures. supply. As described in the preamble to and blood component donation
For establishments that have already this rule, the assessment of eligibility of suitability significantly reduces the
established procedures that conform to donors and the suitability of donations public risk of exposure to the morbidity
the proposed rule, we estimate that it will help prevent unsafe units of blood and mortality risks associated with
would take approximately 40 hours of or blood components from entering the diseases such as HIV types 1 and 2,
staff time to review the establishment’s blood supply. This will protect the HBV, HCV, HTLV types I and II, and
current SOPs to confirm that the SOPs health of donors and will preserve the syphilis. Such standards also reduce the
comply with the regulation. A technical safety, purity, and potency of blood and attendant costs of these diseases.
F. Small Entity Impact would be inadequate to assure uniform transfusion and for further
The Regulatory Flexibility Act or consistent compliance and would manufacturing use. We are proposing to
requires agencies to assess whether a preclude our ability to effectively revise § 606.100(b) by adding that the
rule may have a significant economic monitor the safety, purity, and potency collecting establishment would not only
impact on a substantial number of small of blood and blood components, establish and maintain the SOPs, but
entities. This rule is not expected to including Source Plasma and Source also would follow the SOPs. We are
have a significant impact on a Leukocytes. This proposed rule would proposing to require establishments to
substantial number of such entities. enhance both public health and public establish, maintain, and follow SOPs for
According to size standards confidence in the safety and quality of investigating product deviations
established by the Small Business blood and blood components, while (§ 606.171), and for recordkeeping
Administration (SBA), a small blood or imposing only a minimum burden on related to CGMP (part 606) and
plasma establishment (NAICS code the affected industry. biological product standards (part 610),
621991, Blood and Organ Banks) has which would include all recordkeeping
VI. The Paperwork Reduction Act of
annual receipts of less than $9 million requirements not listed in
1995
(Refs. 13 and 14). The number of blood § 606.100(b)(1) through (b)(20).
This proposed rule contains Proposed § 606.160(e)—We are
and plasma collecting establishments information collection provisions that proposing to revise current § 606.160(e).
that qualify as small entities is are subject to review by OMB under the Paragraph (e) would require collecting
uncertain, but is not expected to be Paperwork Reduction Act of 1995 (the establishments to maintain a list
substantial. For such small entities, the PRA) (44 U.S.C. 3501–3520). A identifying ineligible donors (otherwise
cost of performing a review of SOPs is description of these provisions is given known as a deferral list or donor
expected to be no more than $2,222. We in the following paragraphs with an deferral registry) and to provide this list
believe a small independent estimate of the annual reporting and to appropriate personnel to prevent the
establishment, not associated with a recordkeeping burden. Included in the collection of blood and blood
hospital, might collect as few as 200 estimate is the time for reviewing the components from such individuals.
units per week. A small processing fee instructions, searching existing data Proposed § 630.10(b)—We are
for blood and blood components can be sources, gathering and maintaining the proposing to require that collecting
between $150 and $300 per unit, data needed, and completing and establishments provide to the donor
depending on the component and the reviewing each collection of educational material containing useful
region of the country. Assuming this information. and current information concerning the
small independent establishment FDA invites comments on these relevant transfusion-transmitted
collects a processing fee for two blood topics: (1) Whether the proposed infections so that the donor may self-
components for every unit collected, collection of information is necessary defer from donation if necessary.
and the processing fee is at the lower for the proper performance of FDA’s Proposed § 630.10(c)—Proposed
end of the fee scale for blood functions, including whether the § 630.10(c) would permit the collecting
components, the annual revenues for information will have practical utility; establishment to determine a donor’s
such an establishment would be $3.12 (2) the accuracy of FDA’s estimate of the eligibility and collect a sample for
million (200 x 2 x 52 x $150). Even for burden of the proposed collection of testing one day before collection, when
the smallest establishment, the cost of information, including the validity of the donor is donating blood components
performing a review of SOPs would be the methodology and assumptions used; that cannot be stored more than 24
less than one tenth of one percent of (3) ways to enhance the quality, utility, hours. We would require the collecting
revenues. For establishments associated and clarity of the information to be establishment to identify such blood
with hospitals or establishments with collected; and (4) ways to minimize the components in an SOP.
multiple locations, we believe parent burden of the collection of information Proposed § 630.10(i)(2)—In proposed
company revenues to be much greater on respondents, including through the § 630.10(i)(2), we would require the
than $2.22 million, putting the impact use of automated collection techniques, collecting establishment to provide the
of this rule at less than one tenth of one when appropriate, and other forms of donor with information concerning the
percent of revenues for those firms, as information technology. donation procedure, and to permit the
well. We believe blood establishment Title: Requirements for Human Blood donor to ask questions and at any time
employees already have the skills and Blood Components Intended for to withdraw consent to donate.
required to perform the tasks specified Transfusion or for Further Proposed § 630.15(b)(6)(iii)—We
in the rule, and that the rule does not Manufacturing Use would redesignate current § 640.63(e)(3)
require establishments to seek out Description: FDA proposes to revise as proposed § 630.15(b)(6)(iii).
employees with new expertise. and update the regulations applicable to Consistent with the current regulation,
Although the proposed rule would blood and blood components, including we would require plasma collecting
impose some costs on small entities Source Plasma and Source Leukocytes, establishments to document the special
involved in the collection of blood and and to add donor eligibility characteristics of the donor’s antibody
blood components, including Source requirements for consistency with and the need for plasmapheresis, i.e.,
Plasma and Source Leukocytes, we current practices in the blood industry. there is no alternative source.
believe that the proposed rule This proposed rule’s information Proposed § 630.20(c)(3)—Under
represents an effective means of collection provisions are for proposed § 630.20(c)(3), we would
protecting donor health and helping to recordkeeping and reporting. require the collecting establishment to
ensure the safety, purity, and potency of Proposed § 606.100(b)—Current document the recipient’s medical need,
blood and blood components. We § 606.100(b) requires collecting which necessitates the collection of
considered, as a less burdensome establishments to establish and blood or blood components from a
alternative to the proposed rule, maintain written SOPs for all steps in donor who is determined to be
continuing with the use of trade the collection, processing, compatibility ineligible to donate.
organization standards by industry and testing, storage, and distribution of Proposed § 640.72(a)(2)(i), (a)(3), and
FDA guidance. We found this approach blood and blood components for (a)(4)—We are proposing to revise
current § 640.72(a)(2), (a)(3), and (a)(4). require the reporting of fatal donor According to our registration
Proposed § 640.72(a)(2)(i) would require reactions associated with database, there are currently about 1,709
the collecting establishment to maintain plasmapheresis, and proposed establishments affected by this rule: (1)
for each donor records of initial and § 640.73(b) would require the reporting Approximately 81 licensed plasma
periodic examinations, tests, laboratory of adverse experiences related to the establishments with multiple locations
data, and interviews as required in administration of an immunizing agent. that collect Source Plasma and (2)
proposed §§ 630.10, 630.15, and current Proposed § 640.73(c) would require the approximately 1,628 registered blood
§§ 640.65, 640.66, and 640.67. Proposed submission to FDA of a written establishments that collect blood and
§ 640.72(a)(3) and (a)(4) would require followup report within 7 days of blood components. Based on estimates
the collecting establishment to maintain learning of the fatality or the serious or provided by HHS and GAO, these
a record of the donor’s written statement life threatening donor adverse establishments collect annually
of understanding and documentation of experience related to immunization of
the donor’s good health, respectively. approximately 15 million units of
Proposed § 640.73—Under proposed the donor. Whole Blood, and approximately 13
§ 640.73, we would require Description of respondents: million donations of Source Plasma.
establishments collecting Source Plasma Establishments that collect blood and FDA estimates the information
to report adverse reactions experienced blood components, including Source collection burden as follows:
by donors. Proposed § 640.73(a) would Plasma and Source Leukocytes
TABLE 1.—ESTIMATED ANNUAL RECORDKEEPING BURDEN1

No. of Annual Frequency Total Annual Hours per
21 CFR Section Total Hours
Recordkeepers per Recordkeeping Records Record
606.100(b) (Maintenance of SOPs) 1,709 1 1,709 24 41,016
606.160(e) 1,628 52 84,656 8 677,248
630.15(b)(6)(iii) 81 1 81 0.17 13.8
640.72(a)(2)(i), (a)(3), and (a)(4) 81 18,518.5 1,500,000 0.08 120,000
Total 838,277.8
1There are no capital costs or operating and maintenance costs associated with this collection of information.
TABLE 2.—ESTIMATED ONE-TIME RECORDKEEPING BURDEN1

Recordkeepers per Recordkeeping Records Record
606.100(b) (Creation of SOPs) 1,139 1 1,139 40 45,560
606.100(b) (Creation of SOPs) 570 1 570 56 31,920
630.10(c) 1,628 1 1,628 16 26,048
Total 103,528
TABLE 3.—ESTIMATED ANNUAL REPORTING BURDEN1

Responses per Response Responses Response
630.10(i)(2) 81 18,518.5 1,500,000 0.17 255,000
640.73(a) and (c) 81 .037 3 20 60
640.73(b) 81 .037 3 1 3
Total 255,063
Recordkeeping estimate in table 2 of this document that establishments (570) would expend as a
As shown in table 1 of this document, two-thirds of 1,709 collecting one-time burden an average of 56 hours
for each of the 1,709 collecting establishments (1,139) will each to reconcile their SOPs with the
establishments, we estimate that it will expend, as a one-time burden, an requirements.
take approximately 24 hours annually to average of 40 hours to reconcile their Also, as part of a one-time burden in
maintain the SOPs. As discussed in SOPs with the requirements, and the table 2 of this document, 1,628 blood
section V.C of this document, we remaining one-third of the collecting collecting establishments would create a
new SOP under proposed § 630.10(c), Proposed § 630.10(b), would require Interested persons are requested to send
which we estimate will take 16 hours to the collecting establishments to provide comments regarding information
create. the donor with educational material. collection to OMB (see DATES and
In table 1 of this document, under There is no calculated burden for this ADDRESSES).
proposed § 606.160(e), Source Plasma proposed requirement since
collecting establishments are already establishments collecting blood and VII. Environmental Impact
providing to personnel a list identifying blood components perform this activity The agency has determined under 21
unsuitable donors as usual and as a usual and customary business CFR 25.30(h) that this action is of a type
customary business practice. Under practice. that does not individually or
proposed § 606.160(e), we estimate that The burden for proposed cumulatively have a significant effect on
it would take each blood-collecting § 630.10(i)(2) in table 3 of this document the human environment. Therefore,
establishment an average of 8 hours per is only calculated for Source Plasma neither an environmental assessment
week to update and provide their list collecting establishments since the nor an environmental impact statement
(1,628 x 52 x 8 = 677,248). This blood collecting establishments already is required.
estimated burden of 8 hours per week provide the donor with a statement of
may appear to be lower or higher than understanding as a usual and customary VIII. Federalism
the burden experienced by individual business practice. We estimate that FDA has analyzed this proposed rule
establishments. Since there is no approximately 81 Source Plasma in accordance with the principles set
available data, the burden is an collecting establishments would take an forth in Executive Order 13132. FDA
estimated burden, taking into account estimated 10 minutes (0.17) to perform has determined that the proposed rule
the range of impact on each this activity. Based on the GAO estimate does not contain policies that have
establishment. Some establishments of approximately 1,500,000 donors that substantial direct effects on the States,
may have the ability to generate the lists annually donate Source Plasma, the on the relationship between the
by computer; others may rely on manual total annual burden would be 255,000 National Government and the States, or
preparation. hours (1,500,000 x 0.17). on the distribution of power and
For proposed § 630.15(b)(6)(iii), Proposed § 640.73(a) would require 81 responsibilities among the various
Source Plasma collecting establishments Source Plasma collecting establishments levels of government. Accordingly, the
would be permitted to collect plasma to report fatalities associated with agency has concluded that the rule does
from a donor who is deferred due to red plasmapheresis. We estimate that not contain policies that have
blood cell loss if the establishment approximately 3 fatalities would be federalism implications as defined in
documents the special characteristics of reported annually. A written followup the Executive order and, consequently,
the antibody and the need for the report would also be required under
a federalism summary impact statement
plasmapheresis. Although we do not § 640.73(c). Approximately 20 hours is
is not required.
have data available, we believe that estimated for both the initial and
such a situation would occur followup report. IX. Request for Comments
infrequently. Consequently, we are Proposed § 640.73(b) would require
Source Plasma collecting establishments Interested persons may submit to the
estimating that each Source Plasma
to report any serious or life threatening Division of Dockets Management (see
collecting establishment would have
ADDRESSES) written or electronic
one occurrence per year and that it adverse reaction experienced by a donor
after administration with an comments on this proposed rule.
would take approximately 10 minutes
immunization agent. Although we do Submit a single copy of electronic
(0.17 hours) to document the health of
not have access to data regarding such comments or two paper copies of any
the donor and the special characteristics
of the antibody and the need for the reports, we estimate that approximately mailed comments, except that
plasmapheresis. 3 serious or life-threatening adverse individuals may submit one paper copy.
Under proposed § 630.20(c)(3), donors reactions would occur annually, and Comments are to be identified with the
who do not meet criteria under that the establishment would expend docket number found in brackets in the
§§ 630.10, 630.15, or 610.41 would be approximately 1 hour to complete the heading of this document. Received
permitted to donate under this proposed initial and followup reports. comments may be seen in the Division
provision. Such donations, used solely In this rulemaking, we are of Dockets Management between 9 a.m.
by a specified recipient based on redesignating current § 630.6 as and 4 p.m., Monday through Friday.
documented medical need, would occur proposed § 630.40, which requires the X. References
rarely. Consequently, the burden to collecting establishment to notify a
collecting establishments is negligible. donor when the donor is deferred from The following references have been
In proposed § 640.72(a)(2)(i), (a)(3), donation. Current § 630.6 is approved placed on display in the Division of
and (a)(4), we would require that Source under OMB control number 0910–0116. Dockets Management (see ADDRESSES)
Plasma collecting establishments This approval expires December 31, and may be seen by interested persons
maintain records for each donor of all 2008. between 9 a.m. and 4 p.m., Monday
examinations, tests, laboratory data, We are not calculating information through Friday. (FDA has verified the
interviews, the donor’s written collection burden for § 640.120, because Web site addresses, but FDA is not
statement of understanding and the by permitting industry to use responsible for any subsequent changes
donor’s good health respectively. In alternatives in complying with certain to the Web site after this document
table 1 of this document, we use GAO’s regulations for blood and blood publishes in the Federal Register.)
estimate of approximately 1,500,000 components, we believe that this 1. Yomtovian R., ‘‘Bacterial Contamination
of Blood: Lessons From the Past and Road

donors that annually donate Source provision reduces burden on industry. Map For the Future,’’ Transfusion, March
Plasma. We also estimate that the In compliance with the Paperwork 2004; 44:450–460.
establishment would expend Reduction Act of 1995 (44 U.S.C. 2. Boulton F., ‘‘Determination of Blood
approximately 5 minutes (0.08 hours) 3507(d)), the agency has submitted the Pressure of Blood Donors at Blood Collection
for each donor. information collection provisions of this Sessions,’’ presented at the 26th meeting of
Reporting proposed rule to OMB for review. the Select Committee of Experts on Quality
Assurance in Blood Transfusion Services, 21 CFR Part 1270 (21) Procedures for donor notification
February 2003. and autologous donor referring
3. Perloff D., et al., ‘‘Human Blood Pressure Communicable diseases, HIV/AIDS,
Reporting and recordkeeping physician notification, including
Determination by Sphygmomanometry,’’ procedures for the appropriate followup
Circulation, November 1993; 88(5 Pt 1):2460– requirements.
70. Therefore, under the Federal Food, if the initial attempt at notification fails,
4. Wood, E.M., D.M. Kim, J.P. Miller, Drug, and Cosmetic Act, the Public as prescribed in § 630.40 of this chapter.
‘‘Accuracy of Predonation Hct Sampling Health Service Act, and under the * * * * *
Affects Donor Safety, Eligibility, and Deferral authority delegated to the Commissioner
Rates,’’ Transfusion, March 2001; 41:353– § 606.110 [Amended]
of Food and Drugs, it is proposed that
359. 21 CFR Chapter I be amended as 4. Section 606.110(b) is amended by
5. HHS, ‘‘The 2005 Nationwide Blood removing ‘‘640.63’’ and by adding in its
follows:
Collection and Utilization Survey Report,’’ place ‘‘630.10, 630.15’’.
p.14, 2005, http://www.aabb.org/apps/docs/
PART 606—CURRENT GOOD 5. Section 606.160 is amended by
05nbcusrpt.pdf.
6. U.S. General Accounting Office, ‘‘Blood MANUFACTURING PRACTICE FOR revising paragraphs (b)(1)(ix), (b)(1)(xi),
Supply Generally Adequate Despite New BLOOD AND BLOOD COMPONENTS and (e) to read as follows:
Donor Restrictions,’’ p. 5 note 7, July 2002, 1. The authority citation for 21 CFR § 606.160 Records.
http://www.gao.gov/new.items/d02754.pdf.
part 606 continues to read as follows: * * * * *
7. U. S. Bureau of Labor Statistics,
‘‘Employer Costs for Employee Authority: 21 U.S.C. 321, 331, 351, 352, (b) * * *
Compensation,’’ table 14, September 2006. 355, 360, 360j, 371, 374; 42 U.S.C. 216, 262, (1) * * *
8. Lapane, K. L., et al., ‘‘Hepatitis C 263a, 264. (ix) Records of notification of donors
Infection Risk Analysis: Who Should Be 2. Section 606.3 is amended by deferred or determined not to be eligible
Screened? Comparison of Multiple Screening revising paragraphs (a) and (c) to read as for donation, including appropriate
Strategies Based on the National Hepatitis follows:
Surveillance Program,’’ The American
followup if the initial attempt at
Journal of Gastroenterology, April 1998; § 606.3 Definitions. notification fails, performed under
93:591–596. * * * * * § 630.40 of this chapter.
9. U.S. Centers for Disease Control and (a) Blood means a product that is the * * * * *
Prevention, ‘‘Viral Hepatitis B Fact Sheet,’’ fluid containing dissolved and (xi) Records of notification of the
July 27, 2007, http://www.cdc.gov/ncidod/ suspended elements, which circulates referring physician of a deferred
diseases/hepatitis/b/bfact.pdf.
in the vascular system of a human. autologous donor, including appropriate
10. U.S. Centers for Disease Control and
Prevention, ‘‘Viral Hepatitis B Frequently * * * * * followup if the initial attempt at
Asked Questions,’’ http://www.cdc.gov/ (c) Blood component means a product notification fails, performed under
ncidod/diseases/hepatitis/b/faqb.htm#gen. containing a part of human blood § 630.40 of this chapter.
11. Stramer, S.L. ‘‘US NAT yield: Where separated by physical or mechanical * * * * *
Are We After 2 Years?’’ Transfusion means. (e)(1) Establishments must maintain a
Medicine, August 2002; 12:243–53. record of all ineligible donors so that
12. U.S. Centers for Disease Control and
* * * * *
3. Section 606.100 is amended by blood and blood components are not
Prevention, ‘‘Viral Hepatitis C Fact Sheet,’’
May 24, 2005, http://www.cdc.gov/ncidod/ revising the introductory text in collected from such individuals while
diseases/hepatitis/c/cfact.pdf. paragraph (b); by revising paragraph they are ineligible or deferred; and
13. North American Industry Classification (b)(20); and by adding paragraph (b)(21) (2) Establishments must provide, to
System (NAICS), available online at http:// to read as follows: appropriate personnel at all locations
www.naics.com/sbalsizestandards.htm. operating under the same license or
14. U.S. Small Business Administration, § 606.100 Standard operating procedures. under common management, a
Office of Size Standards, ‘‘Table of Small * * * * * collective list of ineligible donors with
Business Size Standards,’’ 2007, http:// (b) Establishments must establish, sufficient information to prevent the
www.sba.gov/size/sizetable2007.pdf. maintain, and follow written standard collection of blood and blood
List of Subjects operating procedures for all steps in the components from any donors currently
collection, processing, compatibility identified at each location as not eligible
21 CFR Part 606 testing, storage, and distribution of to donate under § 630.10(f) and (g)(1)
Blood, Labeling, Laboratories, blood and blood components for through (g)(6) of this chapter, or
Reporting and recordkeeping allogeneic transfusion, autologous deferred based on test results under
requirements. transfusion, and further manufacturing § 610.41 of this chapter.
purposes; for all steps in the
21 CFR Parts 610 and 660 investigation of product deviations PART 610—GENERAL BIOLOGICAL
Biologics, Labeling, Reporting and related to § 606.171; and for all steps in PRODUCTS STANDARDS
recordkeeping requirements. recordkeeping related to current good
manufacturing practice and biological 6. The authority citation for 21 CFR
21 CFR Part 630 product standards. Such procedures part 610 continues to read as follows:
Blood, Reporting and recordkeeping must be available to the personnel for Authority: 21 U.S.C. 321, 331, 351, 352,
requirements. use in the areas where the procedures 353, 355, 360, 360c, 360d, 360h, 360i, 371,
are performed. The written standard 372, 374, 381; 42 U.S.C. 216, 262, 263, 263a,
21 CFR Part 640 operating procedures must include, but 264.
Blood, Labeling, Reporting and are not limited to, descriptions of the
Subpart E [Amended]
recordkeeping requirements. following, when applicable:
* * * * * 7. Subpart E is amended by removing
21 CFR Part 820
(20) Procedures for donor deferral as ‘‘communicable disease agents’’ and by
Medical devices, Reporting and prescribed in § 610.41 of this chapter; adding in its place ‘‘relevant
recordkeeping requirements. and transfusion-transmitted infections’’ in
the subpart heading and everywhere it 11. Add a heading for new subpart C (2) Determining the suitability of the
appears throughout the subpart. to read as follows: donation of blood and blood
8. Section 610.40 is amended by components; and
revising paragraph (a) and (e) Subpart C—Donor Notification (3) Notifying a donor who is deferred
introductory text to read as follows: 12. Redesignate § 630.6 as § 630.40, from donation.
and transfer newly designated § 630.40 (b) Scope. Who must comply with
§ 610.40 Test requirements. subparts A, B, and C of this part? You,
(a) Human blood and blood to subpart C.
13. Amend § 630.40 as follows: as defined in § 630.3(l), must comply
components. Except as specified in with subparts A, B, and C of this part.
a. Revise the section heading.
paragraphs (c) and (d) of this section, b. Remove ‘‘suitable’’ wherever it
and except for syphilis, which must be § 630.3 Definitions.
appears and add ‘‘eligible’’ in its place;
tested under § 610.40(i), for each and remove ‘‘suitability’’ wherever it As used in this part and 21 CFR part
donation of blood and blood appears and add ‘‘eligibility’’ in its 640 of this chapter:
components intended for use in place. (a) Blood means a product that is the
preparing a product, including c. Revise the first sentence in fluid containing dissolved and
donations intended as a component of, paragraph (a). suspended elements, which circulates
or used to prepare a medical device, The revisions read as follows: in the vascular system of a human.
you, an establishment that collects (b) Blood component means a product
blood and blood components, must test: § 630.40 Requirements for notifying containing a part of blood separated by
(1) For evidence of infection due to deferred donors. physical or mechanical means.
the following relevant transfusion- (a) Notification of donors. You must (c) Donor means a person who:
transmitted infections described in make reasonable attempts to notify any (1) Donates blood or blood
§ 630.3(g)(1)(i) through (g)(1)(iv) of this donor, including an autologous donor, components for transfusion or for
chapter: who has been deferred based on the further manufacturing use or
(i) Human immunodeficiency virus, results of tests for evidence of infection (2) Presents as a potential candidate
types 1 and 2; with a relevant transfusion-transmitted for such donation.
(ii) Hepatitis B virus; infection(s) as required by § 610.41 of (d) Eligibility of a donor means the
(iii) Hepatitis C virus; and this chapter; who has been determined determination that the donor is
(iv) Human T-lymphotropic virus, not to be eligible as a donor based on qualified to donate blood and blood
types I and II; eligibility criteria under §§ 630.10 and components.
(2) In addition, for evidence of 630.15 of this chapter; or whose platelet (e) Intimate contact means an activity
infection due to relevant transfusion- component has tested positive for an that could result in an exchange of body
transmitted infections described in endogenous bacterial contamination. * * fluids, including blood or saliva, with
§ 630.3(g)(1)(vi) through (g)(1)(viii) and * another individual.
630.3(g)(2) of this chapter, provided that * * * * * (f) Physician substitute means a
testing for the disease agent or disease 14. Add subparts A and B to part 630 trained and qualified person(s) who is:
is available and necessary to reduce the to read as follows: (1) A graduate of an education
risk of transmission of the relevant program for health care workers that
transfusion-transmitted infection by the Subpart A—General Provisions
includes clinical training;
blood or blood component. Sec. (2) Currently licensed or certified as a
630.1 Purpose and scope.
* * * * * 630.3 Definitions.
health care worker in the jurisdiction
(e) Further testing. You must further where the collecting establishment is
test each donation, including autologous Subpart B—Donor Eligibility Requirements located;
donations, found to be reactive by a Sec. (3) Currently certified in
screening test performed under 630.5 Medical supervision. cardiopulmonary resuscitation; and
paragraphs (a) and (b) of this section 630.10 General donor eligibility (4) Trained and authorized to perform
using one or more FDA-approved requirements. specified functions under the direction
630.15 Donor eligibility requirements
supplemental (additional, more specific) specific to Whole Blood and to Plasma
of the responsible physician.
test(s), or other appropriate, additional collected by plasmapheresis. (g) Relevant transfusion-transmitted
tests. You must perform such further 630.20 General exceptions from donor infection means:
testing as necessary and appropriate to eligibility requirements. (1) Any of the following transfusion-
determine the deferred donor’s infection 630.25 Exceptions from certain donor transmitted infections:
status for the purpose of donor eligibility requirements for infrequent (i) Human immunodeficiency virus,
notification required under § 630.40 of plasmapheresis. types 1 and 2 (HIV);
630.30 Donation suitability requirements. (ii) Hepatitis B virus (HBV);
this chapter, except: 630.35 Requalification of previously
* * * * * (iii) Hepatitis C virus (HCV);
deferred donors.
(iv) Human T-lymphotropic virus,
PART 630—REQUIREMENTS FOR Subpart A—General Provisions types I and II (HTLV);
HUMAN BLOOD AND BLOOD (v) Treponema pallidum (syphilis);
COMPONENTS INTENDED FOR § 630.1 Purpose and scope. (vi) Creutzfeldt-Jakob disease (CJD);
TRANSFUSION OR FOR FURTHER (a) Purpose. What is the purpose of (vii) Variant Creutzfeldt-Jakob disease
MANUFACTURING USE subparts A, B, and C of this part? The (vCJD); and
purpose of these subparts, together with (viii) Plasmodium sp. (malaria).
9. The authority citation for part 630 §§ 610.40 and 610.41 of this chapter, is (2) Other transfusion-transmitted
continues to read as follows: to provide certain minimum criteria for infections not listed in paragraph (g)(1)
Authority: 21 U.S.C. 321, 331, 351, 352, each donation of blood and blood of this section:
355, 360, 371; 42 U.S.C. 216, 262, 264. components, for: (i) For which appropriate screening
10. Revise the heading for part 630 to (1) Determining the eligibility of a measures are developed and/or an
read as set forth above. donor of blood and blood components; appropriate screening test for donor
specimens is licensed, approved, or described in paragraphs (a) and (b) of eligible if the donor is not in good
cleared for such use by FDA and is this section. health or if you identify factors that may
available; and adversely affect:
(ii) That: Subpart B—Donor Eligibility (1) The health of the donor or
(A) May have sufficient incidence Requirements (2) The safety, purity, or potency of
and/or prevalence to affect the potential the blood or blood components
§ 630.5 Medical supervision.
donor population or collected from the donor.
(B) May have been released (a) Who must determine the eligibility (b) What educational material must
accidentally or intentionally in a of a donor? The responsible physician you provide to the donor before
manner that could place donors at risk authorized by you, as described in determining eligibility? Before
of infection. § 630.3(l), must determine the eligibility determining eligibility, you must
(h) Responsible physician means an of a donor of blood or blood provide the donor with educational
individual who is: components in accordance with this material containing useful and current
(1) Licensed to practice medicine in part. information concerning the relevant
the jurisdiction where the collecting (b) Must the responsible physician be transfusion-transmitted infections
establishment is located; present at the collecting establishment defined in § 630.3(g). The educational
(2) Adequately trained and qualified at all times? Except as provided in material must include an explanation of
to direct and control personnel and paragraphs (c) and (d) of this section the signs and symptoms of and the
relevant procedures concerning the and § 630.15(b)(1) and (b)(4), you must readily identifiable risk factors closely
determination of donor eligibility; assure that the responsible physician is associated with exposure to the relevant
collection of blood and blood in attendance when any of the following transfusion-transmitted infections. You
components; the immunization of a activities are performed at the collecting must present educational material in an
donor; and the return of red blood cells establishment: appropriate form, e.g., in oral, written or
or other blood components to the donor (1) Determining the eligibility of a multimedia, and in a manner designed
during collection of blood component(s) donor; to be understood by the donor. The
by apheresis; and (2) Collecting blood or blood educational material must state that the
(3) Designated by the collecting components; donor may not donate blood and blood
establishment to direct and control (3) Collecting Source Plasma in an components when such signs and
personnel, and to approve relevant approved collection program from symptoms or risk factors are present.
procedures specifying decision-making donors who are otherwise determined to (c) When must you determine the
criteria for determining donor be unsuitable; eligibility of a donor? You must
eligibility, the collection of blood or (4) Returning red blood cells to the determine donor eligibility on the day of
blood components, the immunization of donor during plasmapheresis; or donation, and before collection. When a
a donor, and the return of red blood (5) Immunizing a donor in an donor is donating blood components
cells or other blood components to a approved hyperimmunization program. that cannot be stored for more than 24
donor during collection of blood (c) What specified functions of the hours, you may determine the donor’s
component(s) by apheresis. responsible physician in the collection eligibility and collect a sample for
(i) Suitability of the donation means a of Source Plasma may be performed by testing required under § 610.40 and
determination of whether the donation a physician substitute? You may § 640.5 of this chapter, 1 day before the
is acceptable for transfusion or for authorize a physician substitute to donation. You must have standard
further manufacturing use. perform any specified function listed in operating procedures in place for
(j) Trained personnel means paragraph (b) of this section in the identifying such components.
authorized individuals, including collection of Source Plasma except for (d) How must you determine the
physician substitutes, who are red blood cell immunizations performed eligibility of a donor? Before collection,
adequately instructed and qualified to under paragraph (b)(5) of this section. you must determine the donor’s
perform specified functions under the (d) What specified functions of the eligibility by the following procedures:
direction of the responsible physician. responsible physician in the collection (1) Assessing the donor’s deferral
(k) Transfusion-transmitted infection of blood and blood components may be status by checking the collective list of
means a disease or disease agent: performed by a physician substitute or ineligible donors required under
(1) That could be fatal or life- trained personnel? In the absence of the § 606.160(e)(2) of this chapter;
threatening, could result in permanent responsible physician, you may (2) Assuring that the interval since the
impairment of a body function or authorize a physician substitute or donor’s last donation is appropriate,
permanent damage to body structure, or trained personnel to determine donor taking into account the donor’s
could necessitate medical or surgical eligibility and collect blood and blood participation, if any, in other blood or
intervention to preclude permanent components. blood component collection programs;
impairment of body function or (e) Must emergency medical services (3) Assessing the donor’s medical
permanent damage to a body structure; be available? Yes, you must establish, history; and
and maintain, and follow standard operating (4) Performing a physical assessment
(2) For which there may be a risk of procedures for providing within 15 of the donor.
transmission by the blood and blood minutes emergency medical services for (e) How do you assess the donor’s
components collected, or by a blood donors when medically necessary. medical history? Before collection, you
derivative product manufactured from must take a medical history designed to
the collected blood or blood § 630.10 General donor eligibility determine if the donor is in good health
components, because the disease agent requirements. and if health care practitioners have
or disease is potentially transmissible by (a) What factors determine the ever advised the donor not to donate; to
that blood, blood component, or blood eligibility of a donor? You must not identify risk factors closely associated
derivative product. collect blood and blood components with exposure to, or clinical evidence
(l) You means an establishment that before you determine that the donor is of, infection due to a relevant
collects blood and blood components as eligible to donate. A donor is not transfusion-transmitted infection; and to
determine if there are other conditions influence of drugs or alcohol, or due to before donation, you must obtain the
that may adversely affect the donor or another reason affecting the reliability of following:
the safety, purity, or potency of the the donor’s answers. (1) Proof of identity and mailing
blood or blood components or any (h) How do you perform a physical address. You must obtain proof of
product produced from the blood or assessment of the donor? You must identity of the donor and an address
blood components. determine that the donor is in good where the donor may be contacted for
(f) What factors make the donor health based on the following, at a 8 weeks after donation; and
ineligible because of an increased risk minimum:
for, or evidence of, a relevant (2) Donor’s written statement of
(1) Temperature. The donor’s oral
transfusion-transmitted infection? The understanding. You must provide a
body temperature must not exceed
donor is ineligible to donate when written statement of understanding to be
37.5 °C (99.5 °F), or the equivalent if
information provided by the donor or read and signed by the donor. You must
measured at another body site;
other reliable evidence indicates establish procedures in accordance with
(2) Blood pressure. The donor’s § 606.100 of this chapter to provide
possible exposure to a relevant systolic blood pressure must not
transfusion-transmitted infection. assistance to those unable to read the
measure above 180 millimeters of written statement of understanding. You
Information that a donor has mercury or below 90 millimeters of
participated in any of the following must design those procedures to assure
mercury, and the diastolic blood that the donor understands fully the
renders the donor ineligible if that risk pressure must not measure above 100
of exposure is still applicable at the time material in the donor’s written
millimeters of mercury or below 50 statement of understanding, and provide
of donation: millimeters of mercury. A donor with
(1) Social behaviors associated with for a signature or acceptable substitute
measurements outside these limits may for a signature to indicate that
relevant transfusion-transmitted be permitted to donate only when the
infections; understanding. The written statement of
responsible physician has examined the understanding must not include any
(2) Medical treatments and
donor and determined that the health of exculpatory language through which the
procedures associated with exposure to
the donor would not be adversely donor is made to waive or appear to
relevant transfusion-transmitted
affected by donating. waive any of the donor’s legal rights.
infections;
(3) Signs and symptoms of relevant (3) Hemoglobin or hematocrit The statement must clearly state the
transfusion-transmitted infections; determination for allogeneic donation. following:
(4) Institutionalization in a (i) You must determine the donor’s
hemoglobin level or hematocrit value by (i) The donor has reviewed the
correctional institution; provided educational material required
(5) Intimate contact with an using a sample of blood obtained by
fingerstick, venipuncture, or by a by § 630.10(b) regarding relevant
individual who is at an increased risk
method that provides equivalent results. transfusion-transmitted infections,
for exposure to, or is known to be
Blood obtained from the earlobe is not including the fact that relevant
infected with, a relevant transfusion-
acceptable; and transfusion-transmitted infections
transmitted infection that is spread by
(ii) An allogeneic donor must have a present potential risks to the safety,
such type of intimate contact; and
(6) Nonsterile percutaneous hemoglobin level no less than 12.5 purity, or potency of the blood supply;
inoculation. grams per deciliter of blood, or a (ii) The donor agrees not to donate if
(g) What other factors make the donor hematocrit value no less than 38 the donation could result in a potential
ineligible to donate because of risk to percent. An autologous donor must have risk to the safety, purity, or potency of
the health of the donor, or to the safety, a hemoglobin level no less than 11.0 the blood supply as described in the
purity, or potency of the blood or blood grams per deciliter of blood, or a educational material;
component? You must assess the donor hematocrit value no less than 33 (iii) A sample of the donor’s blood
for each of the following factors to percent. will be tested for specified relevant
determine whether donating could (4) Pulse. The donor’s pulse rate must transfusion-transmitted infections
adversely affect the health of the donor, be regular and between 50 and 100 beats required in § 610.40(a) of this chapter
or whether the safety, purity, or potency per minute. A donor with an irregular and for syphilis.
of the blood or blood component could pulse rate or measurements outside (iv) If any of the tests required in
be affected, and if so, you must these limits may be permitted to donate § 610.40(a) of this chapter are reactive,
determine the donor to be ineligible: only when the responsible physician
(1) Medical or dental treatment, or the sample of blood will be tested
has examined the donor and determines further, as required in § 610.40(e) of this
symptoms of a recent or current illness; that the health of the donor would not
(2) Medication; chapter;
be adversely affected.
(3) Major surgical procedure; (5) Weight. The donor must weigh a (v) If the donation is determined to be
(4) Travel to, or residence in, an area not suitable under § 630.30(a) or if the
minimum of 50 kilograms (110 pounds)
endemic for a transfusion-transmitted donor is deferred from donation under
and must not have had an unexplained
infection; § 610.41 of this chapter, the donor’s
(5) Xenotransplantation product loss of greater than 10 percent of body
weight within the past 6 months; and record must identify the donor as
recipient or intimate contact of a ineligible to donate and the donor must
xenotransplantation product recipient; (6) Skin examination. (i) The donor’s
phlebotomy site must be free of be notified under § 630.40 of the basis
(6) Exposure or possible exposure to for the deferral and the period of
a released disease agent or disease infection, inflammation, lesions, and
pitted skin; and deferral;
relating to a transfusion-transmitted
infection, if you know or suspect that (ii) The donor’s arms and forearms (vi) The hazards and risks of the
such a release has occurred; must be free of punctures and scars donation procedure or of
(7) Pregnancy at the time of, or 6 indicative of injected drugs of abuse. hyperimmunization, if applicable; and
weeks before, donation; and (i) What additional requirements must (vii) the donor has the opportunity to
(8) Unreliable answers to medical you complete before determining the ask questions and withdraw consent at
history questions due to the apparent eligibility of the donor? Immediately any time.
§ 630.15 Donor eligibility requirements hazards involved if the donor is (ii) The donor possesses an antibody
specific to Whole Blood and to Plasma hyperimmunized. The explanation must that is transitory, of a highly unusual or
collected by plasmapheresis. be made in such a manner that the infrequent specificity, or of an
(a) What additional donor eligibility donor may give informed consent and unusually high titer, and
requirements are specific to Whole has a clear opportunity to refuse the (iii) The special characteristics of the
Blood?—(1) Donation frequency. Whole procedure as required under antibody and the need for
Blood must not be collected from a § 630.10(i)(2). plasmapheresis of the donor under
donor more than once in 8 weeks if the (2) Weight. You must weigh a donor § 630.20(c)(2) are documented at your
donor participates in a single unit at each donation. establishment.
collection program; or more than once (3) Total protein level. Before each (7) Malaria. Freedom from risk of
in 16 weeks if the donor participates in plasmapheresis procedure, a donor must malaria is not required for a donor of
a double unit collection program, unless have a total plasma protein level of no Source Plasma.
the donor is examined and certified to less than 6.0 grams per deciliter and no
be in good health by a responsible § 630.20 General exceptions from donor
more than 9.0 grams per deciliter of eligibility requirements.
physician at the time of donation and plasma sample or the comparable level
one of the following three conditions for a serum sample. You may collect blood and blood
exist: (4) Examination before immunization. components from a donor who is
(i) An individual presents a determined to be not eligible to donate
(i) In addition to the determination of
physician’s prescription for therapeutic under §§ 630.10(d) and 630.15, or
donor eligibility required in § 630.10(d),
phlebotomy for medical reasons; or deferred under § 610.41 of this chapter
the responsible physician must perform
(ii) The donation is for autologous only if:
the physical examination no more than
use; or (a) The responsible physician
(iii) The donation is a dedicated 1 week before the first immunization
injection for the production of high-titer examines the donor and certifies in
donation based on the intended writing that the donor’s health permits
recipient’s documented medical need. plasma. It is not necessary to repeat the
physical examination requirement in the collection procedure;
(2) Therapeutic phlebotomy. When a (b) The collection is performed under
donor who is determined to be eligible paragraph (b)(1) of this section, if the
immunized donor’s plasma is collected the supervision of the responsible
under § 630.10(d) undergoes a physician who is aware of the donor’s
therapeutic phlebotomy to promote the within 3 weeks of the first
immunization injection; and health status; and
health of the donor, the container label (c) At least one of the following is
must conspicuously state the disease of (ii) A donor determined to be eligible
under § 630.10(d) and currently met:
the donor that necessitated phlebotomy. (1) The donation is for autologous use
However, no disease labeling is required participating in a plasmapheresis
program, does not need to be re- as prescribed by the donor’s physician,
under this section for a donation and is not for allogeneic transfusion or
collected from a donor who meets all examined before immunization for the
production of high-titer antibody for further manufacturing use;
eligibility criteria and undergoes a (2) The donor is participating in a
therapeutic phlebotomy as ordered by a plasma.
plasmapheresis program that collects
physician treating the donor for (5) Deferral due to red blood cell loss.
plasma for further manufacturing use
Hereditary Hemochromatosis, provided You must defer a donor from donating
into products for which there are no
that you perform without charge plasma for a period of 8 weeks after any
alternative sources, and the collection
therapeutic phlebotomies for all of the following events:
program has received prior approval
individuals with Hereditary (i) The donor experienced a red blood
from the Director, Center for Biologics
Hemochromatosis. cell loss of equal to or greater than 200
Evaluation and Research; or
(b) What additional donor eligibility milliliters of red blood cells during a
(3) The donation is restricted for use
requirements are specific to Plasma single automated plasmapheresis
solely by a specific recipient based on
collected by plasmapheresis?—(1) procedure; or
documented medical need and the
Physical examination and informed (ii) The donor experienced an
responsible physician determines that
consent. (i) In addition to the physical unexpected red blood cell loss of any
the donation presents no undue medical
assessment required in § 630.10(d), the volume in an automated apheresis
risk to the recipient.
responsible physician must examine the procedure on two occasions within the
donor for medical conditions that would last 8-week period; or § 630.25 Exceptions from certain donor
place the donor at risk during (iii) The donor experienced a red eligibility requirements for infrequent
plasmapheresis. If the donor is blood cell loss equivalent to or greater plasmapheresis.
determined to be at risk, you must defer than 200 milliliters of red blood cells as You are not required to perform a
the donor from donating. In a program a result of failure to return red blood physical examination of the donor for
of repeat plasmapheresis, i.e., cells during a manual plasmapheresis medical conditions under § 630.15(b)(1),
collections occur more than once every procedure; or to perform a test for total protein under
28 days, the donor must be examined on (iv) The donor donated a unit of § 630.15(b)(3), to determine the
the day of the first donation or no more Whole Blood. immunoglobulin composition of the
than 1 week before the first donation (6) Exceptions to deferral due to red serum or plasma under § 640.65(b)(1)(i)
and at subsequent intervals of no more blood cell loss. You are not required to of this chapter, or to review the
than 1 year. defer a donor from participation in a laboratory data as required in
(ii) When conducting the physical plasmapheresis program due to red § 640.65(b)(2)(i) of this chapter, if:
examination, the responsible physician blood cell loss if the following occurs: (a) The donor has not donated Whole
must explain the hazards of the (i) The donor is examined at the time Blood in the preceding 8 weeks, Plasma
procedure to the donor. The explanation of the current donation and certified by by plasmapheresis in the preceding 4
must include the risks of a hemolytic the responsible physician to be in good weeks, or participated in a double Red
transfusion reaction if the donor is given health under § 630.10(h) and the donor’s Blood Cells unit collection program
the cells of another donor, and the health permits the plasmapheresis; and within the preceding 16 weeks;
(b) The donor has not donated more eligibility criteria in this part; and the (2) The platelet count required in
than 12.0 liters of plasma (14.4 liters of criteria, which were the basis for the paragraph (c)(1) of this section is greater
plasma for donors weighing more than previous deferral, are determined to be than 150,000/µL;
175 lbs.) in the past year; no longer applicable. (3) The donor’s post-donation platelet
(c) The donor is determined by the (b) A deferred donor identified under count is no less than 100,000 platelets/
responsible physician to be in good § 630.30(b)(2) may be determined µL; and
health under § 630.10(d); and eligible as a donor of blood and blood (4) The donor donates the following:
(d) The donor is not participating in components if, at the time of the current (i) No more than a total of 24
an immunization program for the collection except for the record of the plateletpheresis collections during a 12-
production of high-titer plasma. previous deferral, the donor meets the month period;
eligibility criteria in this part; and the (ii) For single component collection
§ 630.30 Donation suitability requirements. procedures, no more than 2
criteria which were the basis for the
(a) When is a donation suitable? A previous deferral are determined to be plateletpheresis procedures within a 7
donation is suitable when: no longer applicable under § 610.41(b) calendar day period with a minimum of
(1) The donor is not currently of this chapter. 2 calendar days between procedures;
deferred from donation; (iii) For a double or triple component
(2) The results in accordance with PART 640—ADDITIONAL STANDARDS collection procedure, no more than one
§§ 630.10 through 630.25 indicate that FOR HUMAN BLOOD AND BLOOD procedure within a 7 calendar day
the donor is in good health and that the PRODUCTS period.
donation would not adversely affect the (d) For a period not to exceed 30 days,
health of the donor; 15. The authority citation for 21 CFR
a donor may serve as a dedicated
(3) The donor is free from risk factors part 640 continues to read as follows:
plateletpheresis donor for a single
for, or evidence of transfusion- Authority: 21 U.S.C. 321, 351, 352, 353, recipient, in accordance with
transmitted infections under § 630.10(f) 355, 360, 371; 42 U.S.C. 216, 262, 263, 263a, § 610.40(c)(1) of this chapter, as often as
and (g); 264.
is medically necessary, provided that
(4) The donor’s blood is tested in § 640.3 [Removed] the donor is in good health, as
accordance with § 610.40 of this determined by a physician, and the
16. Section 640.3 is removed.
chapter, and is negative or nonreactive, donor’s platelet count is greater than
unless an exception applies under § 640.4 [Amended] 150,000/µL, measured at the conclusion
§ 610.40(h) of this chapter; 17. Section 640.4 is amended by of the previous donation or before
(5) For platelet components, you have removing paragraph (a) and by initiating apheresis for the current
taken adequate steps to assure that the redesignating paragraphs (b) through (h) donation.
donation is tested for bacterial as paragraphs (a) through (g). (e) Except as provided in paragraphs
contamination and found negative; and 18. Section 640.12 is revised to read (e)(1) and (e)(2) of this section, a
(6) The donation meets other as follows: plateletpheresis donor must be deferred
requirements in this subchapter. for a period of 8 weeks after donating a
(b) What must you do when the § 640.12 Eligibility of donor. unit of Whole Blood or after losing a
donation is not suitable? (1) When the Collecting establishments must volume of whole blood equal to or
donation does not meet the criteria in determine the eligibility of donors of the greater than 450 mL, or red blood cells
paragraphs (a)(1) through (a)(3) and source blood for Red Blood Cells in equal to or greater than 200 mL,
(a)(5) of this section, the donation is not accordance with §§ 630.10 and 630.15 of cumulatively over an 8 week period; or
suitable and you must defer the donor this chapter. be deferred for a period of 16 weeks
from donation; 19. Section 640.21 is revised to read after donating a double Red Blood Cells
(2) When the donation does not meet as follows. unit collection. In exception, the
the criteria in paragraph (a)(4) of this plateletpheresis donor may donate if all
section, defer the donor from donation § 640.21 Eligibility of donors.
of the following criteria are met:
in accordance with § 610.41(a) of this (a)(1) Collecting establishments must (1) The donor waits 2 calendar days
chapter; determine the eligibility of Whole Blood after donating Whole Blood or after
(3) Identify a donor not eligible under donors and plateletpheresis donors in experiencing the blood loss; and
§ 630.10(f)(1) through (f)(6) and accordance with §§ 630.10 and 630.15 of (2) The extracorporeal red blood cell
§ 630.10(g)(1) through (g)(6) as not this chapter, except as expressly volume during the apheresis procedure
eligible to donate under § 606.160(e) of modified in paragraph (e) of this is equal to or less than 100 mL.
this chapter; and section.
(4) Notify a donor found not eligible (2) Under § 630.10(i)(2)(vi) of this § 640.22 [Amended]
to donate under § 610.41 of this chapter, chapter, the statement of understanding 20. Section 640.22(b) is amended by
and §§ 630.10 through 630.25, or must include a statement that the long- removing ‘‘640.62’’ and by adding in its
630.30(a)(5) of the deferral, the deferral term effects of frequent apheresis are place ‘‘630.5’’.
period, and the reason for the deferral, unknown. 21. Section 640.31 is revised to read
in accordance with the notification (b) A donor must not serve as a source as follows:
requirements in § 630.40. of platelets for transfusion if the donor
has recently ingested drugs that § 640.31 Eligibility of donors.
§ 630.35 Requalification of previously adversely affect platelet function. (a) Whole Blood donors must meet the
deferred donors. (c) A plateletpheresis donor may criteria for donor eligibility prescribed
(a) A deferred donor identified under donate at intervals shorter than 8 weeks in §§ 630.10 and 630.15 of this chapter.
§ 630.30(b)(1) may be determined provided: (b) Collecting establishments must
eligible as a donor of blood and blood (1) The establishment performs a determine the eligibility of
components if, at the time of the current platelet count before starting the initial plasmapheresis donors in accordance
collection, except for the record of plateletpheresis procedure and before with §§ 630.10 and 630.15 of this
previous deferral, the donor meets the each subsequent procedure; chapter.
§ 640.32 [Amended] normal limits established by the testing plasmapheresis donor and, when
22. Section 640.32(b) is amended by laboratory, or if the total protein is less applicable, an immunized donor.
removing ‘‘640.62’’ and by adding in its than 6.0 grams per deciliter of plasma * * * * *
place ‘‘630.5’’. sample or more than 9.0 grams per 31. Section 640.73 is revised to read
23. Section 640.51 is revised to read deciliter of plasma sample, or the as follows:
as follows: comparable level for a serum sample,
the donor must be deferred from § 640.73 Reporting of donor reactions.
§ 640.51 Eligibility of donors.
donation until the protein composition (a) If a donor has a fatal reaction
(a) Whole blood donors must meet the returns to acceptable levels. which, in any way, may be associated
criteria for eligibility prescribed in Reinstatement of the donor into the with plasmapheresis, you must notify
§§ 630.10 and 630.15 of this chapter. plasmapheresis program when the the Director of the Center for Biologics
(b) Collecting establishments must donor’s values have returned to Evaluation and Research by telephone
determine the eligibility of acceptable levels must first be approved as soon as possible.
plasmapheresis donors in accordance by the responsible physician. (b) If a donor enrolled in an
with §§ 630.10 and 630.15 of this
* * * * * immunization program for the
chapter.
29. Section 640.69 is amended by collection of Source Plasma under this
§ 640.52 [Amended] adding paragraphs (e) and (f) to read as subpart has an adverse experience
24. Section 640.52(b) is amended by follows: related to your administration of the
removing ‘‘640.62’’ and by adding in its immunizing agent, you must report the
§ 640.69 General requirements. event to FDA:
place ‘‘630.5’’.
* * * * * (1) By telephone, facsimile, express
§ 640.61 [Removed] (e) Restrictions on distribution. mail, or electronic mail as soon as
25. Section 640.61 is removed. Establishments must ensure that Source possible, if the adverse experience is a
Plasma donated by paid donors not be serious or life threatening adverse
§ 640.62 [Removed] used for further manufacturing into experience, as described in § 600.80(a)
26. Section 640.62 is removed. injectable products until the donor has of this chapter; or
a record of two suitable donations (2) In an annual report, if the adverse
§ 640.63 [Removed]
within the last 6 months. experience is neither serious nor life
27. Section 640.63 is removed. (f) Hold. Source Plasma donated by
28. Section 640.65 is amended by threatening. Such a report is due to FDA
paid donors determined to be suitable on the anniversary of FDA’s approval of
revising paragraphs (b)(1)(i) and (b)(2)(i) for further manufacturing into injectable
to read as follows: your immunization program.
products must be held in quarantine for
(c) You must follow up the initial
§ 640.65 Plasmapheresis. a minimum of 60 days before it is
report required under paragraphs (a)
* * * * * released for further manufacturing.
and (b)(1) of this section by submitting
(b) * * * 30. Section 640.72 is amended by
a written report of the investigation to
(1)(i) Except as provided under revising paragraphs (a)(2), (a)(3), and
the Director, Office of Compliance and
§ 630.25 of this chapter, a sample of (a)(4) to read as follows:
Biologics Quality, Center for Biologics
blood must be drawn from each donor § 640.72 Records. Evaluation and Research, within 7 days
on the day of the initial physical (a) * * * of your first learning of the donor’s
examination or plasmapheresis, (2)(i) For each donor, a separate and reaction. (See § 600.2 of this chapter.)
whichever comes first, and at least every complete record of initial and periodic 32. Section 640.120 is revised to read
4 months thereafter. A serological test examinations, tests, laboratory data, and as follows:
for syphilis, a total plasma or serum interviews as required in §§ 630.10 and
protein determination, and § 640.120 Alternative procedures.
630.15 of this chapter and §§ 640.65,
electrophoresis or quantitative immuno- 640.66, and 640.67, except as provided (a) The Director, Center for Biologics
diffusion test or an equivalent test to in paragraph (a)(2)(ii) of this section. Evaluation and Research, may approve
determine immunoglobulin composition (ii) Negative results for testing for an exception or alternative to any
of the plasma or serum, must be evidence of infection due to relevant requirement in subchapters C and F of
performed on the sample. transfusion-transmitted infections chapter I of title 21 of the Code of
* * * * * required in § 610.40 of this chapter, and Federal Regulations regarding blood,
(2)(i) Except as provided under the volume or weight of plasma blood components, or blood products. If
§ 630.25 of this chapter, the withdrawn from a donor need not be the Director issues such approval orally,
accumulated laboratory data, including recorded on the individual donor record the Director will follow up that oral
tracings of the plasma or serum protein if such information is maintained on the approval by issuing a written approval.
electrophoresis pattern, if any, the premises of the plasmapheresis center If approval is appropriate, the Director
calculated values of each component, where the donor’s plasma has been may issue such an approval in response
and the collection records must be collected. to:
reviewed by the responsible physician (3) The original or a clear copy of the (1) A written request from an
as required in § 630.5 of this chapter donor’s written statement of establishment. Licensed establishments
within 14 calendar days after the sample understanding for participation in the must submit such requests in
is drawn to determine whether or not plasmapheresis program or for accordance with § 601.12 of this
the donor should be deferred from immunization. chapter;
further donation. If a determination is (4) Documentation by the responsible (2) An oral request from an
not made within 14 calendar days, the physician that the donor is in good establishment, if there are difficult
donor must be deferred pending such a health under §§ 630.10 and 630.15 of circumstances and submission of a
determination. The responsible this chapter on the day of examination; written request is not feasible.
physician must sign the review. If the such documentation must address the Establishments must follow up such
protein composition is not within eligibility of the donor as a oral request by submitting written
requests under paragraph (a)(1) of this Authority: 21 U.S.C. 321, 331, 351, 352, further manufacturing are not subject to
section within 5 working days. 353, 355, 360, 360c, 360d, 360h, 360i, 371, this part, but are subject to subchapter
372; 42 U.S.C. 216, 262, 263, 263a, 264. F of this chapter.
(b) In a public health emergency, the 34. Section 660.31 is revised to read
Director may issue an exception or * * * * *
as follows:
alternative to any requirement in
§ 660.31 Eligibility of donor. PART 1270—HUMAN TISSUE
subchapters C and F of chapter I of title
Donors of peripheral blood for INTENDED FOR TRANSPLANTATION
21 of the Code of Federal Regulations
regarding blood, blood components, or Reagent Red Blood Cells must meet all 37. The authority citation for 21 CFR
blood products, if a variance under this the criteria for donor eligibility under part 1270 continues to read as follows:
section is necessary to assure that blood, §§ 630.10 and 630.15 of this chapter.
Authority: 42 U.S.C. 216, 243, 264, 271.
blood components, or blood products 38. Section 1270.3 is amended by
PART 820—QUALITY SYSTEM
will be available in a specified location revising paragraph (b) to read as follows:
REGULATION
to respond to an unanticipated
immediate need for blood, blood 35. The authority citation for 21 CFR § 1270.3 Definitions.
components, or blood products. part 820 continues to read as follows: * * * * *
Authority: 21 U.S.C. 351, 352, 360, 360c, (b) Blood component means a product
(c) Periodically, FDA will provide a
360d, 360e, 360h, 360i, 360j, 360l, 371, 374, containing a part of human blood
list of approved alternative procedures
381, 383; 42 U.S.C. 216, 262, 263a, 264. separated by physical or mechanical
and exceptions at www.fda.gov/cber.
36. Section 820.1(a)(1) is amended by means.
PART 660—ADDITIONAL STANDARDS revising the last sentence to read as * * * * *
FOR DIAGNOSTIC SUBSTANCES FOR follows: Dated: October 25, 2007.
LABORATORY TESTS § 820.1 Scope. Jeffrey Shuren,
(a) Applicability. (1) * * * Assistant Commissioner for Policy.
33. The authority citation for 21 CFR [FR Doc. E7–21565 Filed 11–7–07; 8:45 am]
Manufacturers of blood and blood
part 660 continues to read as follows: components used for transfusion or for BILLING CODE 4160–01–S

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21 CFR Parts 606, 610, et al.

• Mail/Hand delivery/Courier [For (Proposed Part 630)

(1975).) manufacture, packing, storage, or Source Plasma and Source Leukocytes,

and Research home page on the Internet.

TABLE 1.—ESTIMATED ANNUAL RECORDKEEPING BURDEN1

606.100(b) (Maintenance of SOPs) 1,709 1 1,709 24 41,016

606.160(e) 1,628 52 84,656 8 677,248

630.15(b)(6)(iii) 81 1 81 0.17 13.8

640.72(a)(2)(i), (a)(3), and (a)(4) 81 18,518.5 1,500,000 0.08 120,000

TABLE 2.—ESTIMATED ONE-TIME RECORDKEEPING BURDEN1

606.100(b) (Creation of SOPs) 1,139 1 1,139 40 45,560

606.100(b) (Creation of SOPs) 570 1 570 56 31,920

630.10(c) 1,628 1 1,628 16 26,048

TABLE 3.—ESTIMATED ANNUAL REPORTING BURDEN1

630.10(i)(2) 81 18,518.5 1,500,000 0.17 255,000

640.73(a) and (c) 81 .037 3 20 60

of Blood: Lessons From the Past and Road

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