Requirements for Human Blood and Blood Components Intended for Transfusion or for Further Manufacturing Use, 63416-63444 [E7-21565]

Agencies

• Food and Drug Administration
• DEPARTMENT OF HEALTH AND HUMAN SERVICES

[Federal Register Volume 72, Number 216 (Thursday, November 8, 2007)]
[Proposed Rules]
[Pages 63416-63444]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: E7-21565]



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Part IV





Department of Health and Human Services





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Food and Drug Administration



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21 CFR Parts 606, 610, et al.



Requirements for Human Blood and Blood Components Intended for 
Transfusion or for Further Manufacturing Use; Proposed Rule

Federal Register / Vol. 72, No. 216 / Thursday, November 8, 2007 / 
Proposed Rules

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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Parts 606, 610, 630, 640, 660, 820, and 1270

[Docket No. 2006N-0221]


Requirements for Human Blood and Blood Components Intended for 
Transfusion or for Further Manufacturing Use

AGENCY: Food and Drug Administration, HHS.

ACTION: Proposed rule.

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SUMMARY: The Food and Drug Administration (FDA) proposes to revise and 
update the regulations applicable to blood and blood components, 
including Source Plasma and Source Leukocytes, to add donor 
requirements that are consistent with current practices in the blood 
industry, and to more closely align the regulations with current FDA 
recommendations. FDA is taking this action to help ensure the safety of 
the national blood supply and to help protect donor health by requiring 
establishments to evaluate donors for factors that may adversely affect 
the safety, purity, and potency of blood and blood components or the 
health of a donor during the donation process.

DATES: Submit written or electronic comments on the proposed rule by 
February 6, 2008. Submit comments regarding information collection by 
December 10, 2007 to OMB (see ADDRESSES). See section IV of this 
document for the proposed effective date of a final rule based on this 
proposal.

ADDRESSES: You may submit comments, identified by Docket No. 2006N-
0221, by any of the following methods:
Electronic Submissions
    Submit electronic comments in the following ways:
     Federal eRulemaking Portal: https://www.regulations.gov. 
Follow the instructions for submitting comments.
     Agency Web site: https://www.fda.gov/dockets/ecomments. 
Follow the instructions for submitting comments on the agency Web site.
Written Submissions
    Submit written submissions in the following ways:
     FAX: 301-827-6870.
     Mail/Hand delivery/Courier [For paper, disk, or CD-ROM 
submissions]: Division of Dockets Management (HFA-305), Food and Drug 
Administration, 5630 Fishers Lane, rm. 1061, Rockville, MD 20852.
    To ensure more timely processing of comments, FDA is no longer 
accepting comments submitted to the agency by e-mail. FDA encourages 
you to continue to submit electronic comments by using the Federal 
eRulemaking Portal or the agency Web site, as described previously, in 
the ADDRESSES portion of this document under Electronic Submissions.
    Instructions: All submissions received must include the agency name 
and Docket No(s). and Regulatory Information Number (RIN) (if a RIN 
number has been assigned) for this rulemaking. All comments received 
may be posted without change to https://www.fda.gov/ohrms/dockets/
default.htm, including any personal information provided. For 
additional information on submitting comments see the ``Comments'' 
heading of the SUPPLEMENTARY INFORMATION section of this document.
    Docket: For access to the docket to read background documents or 
comments received, go to https://www.fda.gov/ohrms/dockets/default.htm 
and insert the docket number(s), found in brackets in the heading of 
this document, into the ``Search'' box and follow the prompts and/or go 
to the Division of Dockets Management, 5630 Fishers Lane, rm. 1061, 
Rockville, MD 20852.
    Information Collection Provisions: Submit written comments on the 
information collection provisions to the Office of Information and 
Regulatory Affairs, Office of Management and Budget (OMB). To ensure 
that comments on the information collection are received, OMB 
recommends that written comments be faxed to the Office of Information 
and Regulatory Affairs, OMB, Attn: FDA Desk Officer, FAX: 202-395-6974.

FOR FURTHER INFORMATION CONTACT: Brenda R. Friend, Center for Biologics 
Evaluation and Research (HFM-17), Food and Drug Administration, 1401 
Rockville Pike, suite 200N, Rockville, MD 20852-1448, 301-827-6210.

SUPPLEMENTARY INFORMATION:

Table of Contents

I. Introduction
    A. The Blood Initiative
    B. Existing Donor Screening Requirements
    C. Proposed Regulations for Determining Donor Eligibility (Proposed 
Part 630)
II. Legal Authority
III. Summary of the Proposed Rule
    A. General Description
    B. Standard Operating Procedures (SOPs) (Proposed Sec.  606.100(b))
    C. Records (Proposed Sec.  606.160(e))
    D. Testing Requirements (Proposed Sec.  610.40(a) and (e) and Sec.  
630.30(a)(5))
    E. Purpose and Scope (Proposed Sec.  630.1)
    F. Definitions (Proposed Sec.  630.3)
    G. Medical Supervision (Proposed Sec.  630.5)
    H. General Donor Eligibility Requirements (Proposed Sec.  630.10)
    I. Donor Eligibility Requirements Specific to Whole Blood and 
Plasma Collected by Plasmapheresis (Proposed Sec.  630.15)
    J. General Exceptions from the Donor Eligibility Requirements 
(Proposed Sec.  630.20)
    K. Exceptions from Certain Donor Eligibility Requirements for 
Infrequent Plasmapheresis (Proposed Sec.  630.25)
    L. Donation Suitability Requirements (Proposed Sec.  630.30)
    M. Requalification of Previously Deferred Donors (Proposed Sec.  
630.35)
    N. Requirements for Notifying Deferred Donors (Proposed Newly 
Redesignated Sec.  630.40)
    O. Eligibility Requirements Specific for Platelet Donors (Proposed 
Sec.  640.21)
    P. Eligibility Requirements Specific for Source Plasma Donors 
(Proposed Sec. Sec.  640.65(b) and 640.69)
    Q. Reporting of Donor Reactions (Proposed Sec.  640.73)
    R. Alternative Procedures (Proposed Sec.  640.120)
    S. Reagent Red Blood Cells (Proposed Sec.  660.31)
    T. Quality Systems Regulations (Proposed Sec.  820.1(a)(1))
    U. Technical Amendments
IV. Proposed Effective Date
V. Analysis of Impacts
    A. Objectives and Basis of the Action
    B. Nature of the Impact
    C. Type and Number of Entities Affected
    D. Estimated Impact of Requirements for Assessment of Donor 
Eligibility
    E. Expected Benefits of the Rule
    F. Small Entity Impact
VI. The Paperwork Reduction Act of 1995
VII. Environmental Impact
VIII. Federalism
IX. Request for Comments
X. References

I. Introduction

A. The Blood Initiative

    For a variety of reasons we, FDA, decided to review comprehensively 
and, as necessary, revise our regulations to include definitions, 
policies, guidance,

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and procedures related to the licensing and regulation of blood 
products. In the Federal Register of June 3, 1994 (59 FR 28821 and 
28822, respectively), we issued two documents, ``Review of General 
Biologics and Licensing Regulations'' (Docket No. 1994N-0066) and 
``Review of Regulations for Blood Establishments and Blood Products'' 
(Docket No. 1994N-0080). These documents announced our intent to review 
biologics regulations (parts 600, 601, 606, 607, 610, 640, and 660 (21 
CFR parts 600, 601, 606, 607, 610, 640, and 660)), and requested 
written comments from the public. We gave interested persons until 
August 17, 1994, to respond to the documents. In response to requests 
for additional time, we twice extended the comment period, as announced 
in the Federal Register of August 17, 1994 (59 FR 42193), and November 
14, 1994 (59 FR 56448). In addition, we responded to requests for a 
public meeting to allow the public to present comments regarding our 
review of the biologics regulations. At the public meeting on January 
26, 1995, interested individuals presented their comments, which 
assisted us in determining whether certain regulations should be 
revised, rescinded, or continued without change. Since the time of the 
regulation review, we have implemented a number of changes to the 
regulations and policies applicable to the general biologics and 
licensing requirements, some of which applied to blood products as well 
as other biological products.
    The United States House of Representatives Committee on Government 
Reform and Oversight, Subcommittee on Human Resources and 
Intergovernmental Relations (the Subcommittee) and other groups such as 
the Government Accountability Office (previously, the General 
Accounting Office GAO), and the Institute of Medicine (IOM), have 
reviewed our policies, practices, and regulations. Reports issued 
following the respective reviews made a number of recommendations to 
improve the biologics regulations, particularly as they apply to 
assuring the continued safety of blood products. The relevant reports 
are:
     ``Blood Supply Generally Adequate Despite New Donor 
Restrictions'' by GAO (July 22, 2002);
     ``Protecting the Nation's Blood Supply From Infectious 
Agents: The Need for New Standards to Meet New Threats'' by the 
Subcommittee (August 2, 1996);
     ``Blood Supply: FDA Oversight and Remaining Issues of 
Safety'' by GAO (February 25, 1997);
     ``Blood Supply: Transfusion-Associated Risks'' by GAO 
(February 25, 1997); and,
     ``HIV and the Blood Supply: An Analysis of Crisis 
Decisionmaking'' by IOM (July 13, 1995).
    These reports are on file with the Division of Dockets Management 
(see ADDRESSES) under the docket number found in the heading of this 
document.
    We have reviewed these reports and agree with the majority of the 
recommendations contained within them. We are not describing all the 
specific recommendations we received and the numerous objectives of the 
Blood Initiative in this document. However, in response to the GAO 
recommendations, FDA has completed rulemakings, including the 
following: (1) Requirements for Testing Human Blood Donors for Evidence 
of Infection Due to Communicable Disease Agents (66 FR 31146; June 11, 
2001); (2) General Requirements for Blood, Blood Components, and Blood 
Derivatives; Donor Notification (66 FR 31165; June 11, 2001); (3) 
Revisions to the Requirements Applicable to Blood, Blood Components and 
Source Plasma, Confirmation in Part and Technical Amendment (66 FR 
1834; January 10, 2001); (4) Current Good Manufacturing Practice for 
Blood and Blood Components; Notification of Consignees and Transfusion 
Recipients Receiving Blood and Blood Components at Increased Risk of 
Transmitting HCV Infection (``Lookback'') (65 FR 69378; November 16, 
2000); and (5) Biological Products: Reporting of Biological Product 
Deviations in Manufacturing (65 FR 66621; November 7, 2000, and 65 FR 
67477; November 9, 2000 (Correction)). This rulemaking and other 
notices describe and discuss specific recommendations and regulatory 
objectives as they apply to each rulemaking.
    Through the years, we issued a number of guidance documents 
containing recommendations intended to assure a safe, pure, and potent 
blood supply. One objective of this rulemaking is to make more visible 
the connections between the regulations and current recommendations. In 
many cases in this preamble, we will describe the general intended 
meaning of the proposed regulations and will also discuss those 
recommendations, contained in current guidance, which fall under a 
proposed regulation. Although it is neither possible nor desirable to 
codify all the specific details contained in recommendations, we 
believe the proposed rule will more explicitly describe donor 
eligibility standards and will clarify the relationship between the 
regulations and the applicable recommendations.
    The Secretary of the Department of Health and Human Services (HHS) 
seeks to maximize blood safety and blood availability and has 
designated the Assistant Secretary of Health to be responsible for 
these issues. The supply of blood is generally adequate to meet medical 
needs; however, only about 6 percent of the U.S. general public donates 
blood each year. Periodically, local, regional or national shortages 
can occur. Although blood establishments are primarily responsible for 
recruiting and retaining blood donors, HHS plays a key role in 
monitoring the blood supply to identify potential shortages. Also, the 
Secretary of HHS has developed a number of initiatives to encourage 
individuals to donate routinely and during times of shortage or 
national disasters. In times of acute blood shortage, HHS has sponsored 
national appeals for blood donation.
    Under the HHS Blood Action Plan, HHS and the Public Health Service 
agencies of HHS act to increase blood availability by removing 
unnecessary restrictions to blood donation while maintaining the 
highest level of safety for the recipient. HHS brings donor eligibility 
issues for discussion at scientific workshops and at FDA scientific 
advisory committees, including the Blood Products Advisory Committee 
and the Transmissible Spongiform Encephalopathies Advisory Committee, 
where we seek advice and scientific-based recommendations. Additionally 
the HHS Advisory Committee on Blood Safety and Availability provides 
advice on global public health, economic, social, and ethical issues 
related to FDA policies on donor eligibility. These discussions have 
often focused on the impact of donor deferrals on blood availability as 
well as the safety of blood for the recipient. During the development 
of policies on donor eligibility, including donor screening, testing 
and deferral, FDA considers the impact of candidate policies on blood 
availability and tries to balance anticipated donor loss with safety 
gained. One example of this balancing approach may be found in FDA's 
development of a guidance recommending deferral of persons who may have 
been exposed to the Bovine Spongiform Encephalopathy (BSE) agent (the 
agent that causes Mad Cow Disease) and thus create an increased risk of 
transfusion transmission of variant Creutzfeldt-Jakob Disease (vCJD). 
FDA commissioned the studies that produced the first available data 
regarding donor travel patterns and used the data to optimize the 
balance between a

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reduction in the risk of transfusion-transmitted vCJD (estimated at 91 
percent) and donor loss (estimated at 7 percent).
    In developing this proposed rule, FDA has reviewed the proceedings 
of numerous workshops and advisory committee meetings, mindful of the 
goals of the HHS Blood Action plan: increasing blood availability by 
removing unnecessary restrictions to blood donation, while maintaining 
the highest level of safety for the recipient. For example, we have 
tried to achieve those goals by our proposal to change labeling 
requirements for certain donations from patients with hereditary 
hemochromatosis. This provision would remove a barrier to safe blood 
collection from these individuals. FDA welcomes comments on the risks 
and benefits of the donor eligibility criteria proposed in this 
rulemaking with regard to potential donor loss versus gains in blood 
product safety and donor safety.

B. Existing Donor Screening Requirements

    We have developed five ``layers of safety'' to help ensure a safe 
blood supply:
     Donor suitability standards (part 640);
     Donor deferral lists (Sec.  606.160(e));
     Testing blood for communicable disease agents (Sec.  
610.40);
     Quarantining unsuitable blood and blood components (Sec.  
606.40(a)(6)); and
     Monitoring establishments by requiring the investigation 
of problems in manufacturing (21 CFR 211.192), reporting of fatalities 
(Sec.  606.170) and reporting of product deviations (Sec.  606.171).
    The five layers of safety are designed to overlap and help prevent 
the distribution of blood and blood components that are at increased 
risk for transmitting infectious agents such as human immunodeficiency 
virus (HIV), hepatitis B virus (HBV), and hepatitis C virus (HCV).
    In addition to safeguarding against transmission of disease agents 
from donor to recipient, the current donor suitability standards are 
designed to prevent harm to a donor from the donation process, and to 
help ensure the safety, purity, and potency of blood and blood 
components. Usually, collecting establishments review donor deferral 
lists to identify, before donation, individuals not eligible to donate. 
Collecting establishments conduct a prescribed limited physical 
examination and medical history interview for each donor. These steps 
are performed to:
     Establish that the donor is in good health;
     Rule out relevant disease infection; and,
     Identify any risk factors that would increase the 
possibility of transmitting a transfusion-transmitted infection through 
the donation.
    In addition, under Sec.  610.40, a blood sample collected from the 
donor at the time of donation must be tested for evidence of infection 
due to communicable disease agents such as HIV and viral hepatitis. By 
performing these steps, the collecting establishment helps assure the 
safety, purity, and potency of blood and blood components.

C. Proposed Regulations for Determining Donor Eligibility (Proposed 
Part 630)

    Although we currently have donor suitability requirements 
applicable to blood and blood components, including Source Plasma and 
Source Leukocytes, parts 606, 610, 640, and 660, we intend to 
reorganize and revise current regulations, to make more visible the 
connections between the regulations and current FDA recommendations, to 
make them consistent with current practices in the blood industry, and 
to remove unnecessary or outdated requirements. Based on the 
recommendations of the 1997 GAO report, ``Blood Supply: FDA Oversight 
and Remaining Issues of Safety,'' we are issuing in the form of 
regulations provisions of the memoranda and guidance on donor 
eligibility that we believe are essential to help ensure the safety of 
the national blood supply.
    Subsequent to the February 1997 GAO report, we conducted numerous 
workshops to obtain public input. The subjects discussed included for 
example:
     Screening and testing for evidence of infection due to 
communicable diseases;
     Donor history of hepatitis;
     Use of a donor deferral registry;
     Donor blood volume;
     Donor deferral based on cancer; and,
     Streamlining the donor history questionnaire.
    We have consolidated information from memoranda, guidances, other 
workshops, advisory committee meetings, current Sec.  630.6 requiring 
donor notification, and the donor suitability requirements in Sec.  
640.3 and 640.63 in developing the requirements for donors of blood and 
blood components intended for transfusion or for further manufacturing 
use in proposed part 630. For the purpose of this proposed rulemaking, 
when the term ``blood and blood components'' is used, Source Plasma and 
Source Leukocytes are included. We also use the term ``donor 
eligibility'' when referring to criteria to permit donation. This 
proposed rule uses the term ``suitability'' only when discussing the 
acceptability of the donated blood and blood components for transfusion 
or for further manufacturing use. (For further discussion, see section 
III.E of this document.)

II. Legal Authority

    FDA is proposing to issue this new rule under the authority of 
sections 351 and 361 of the Public Health Service Act (PHS Act) (42 
U.S.C. 262 and 264), and the provisions of the Federal Food, Drug, and 
Cosmetic Act (the act) that apply to drugs and devices (21 U.S.C. 201 
et seq.).
    The establishment of these criteria for determining the eligibility 
of a donor of blood and blood components and the suitability of blood 
and blood components for transfusion or for further manufacturing, is 
intended to prevent unsafe units of blood or blood components that may 
transmit a relevant transfusion-transmitted infection from entering the 
blood supply, while safeguarding the health of donors.
    FDA has been delegated authority under section 361 of the PHS Act 
to make and enforce regulations necessary to prevent the introduction, 
transmission, or spread of communicable disease from foreign countries 
into the States or possessions, or from one State or possession into 
any other State or possession. Intrastate transactions affecting 
communicable disease transmission may also be regulated under section 
361 of the PHS Act (see Louisiana v. Mathews, 427 F. Supp. 174, 176 
(E.D. La. 1977)). FDA recently exercised this authority when the agency 
issued three rules requiring tissue establishments to register and list 
the human tissues manufactured; to conduct donor screening and testing; 
and to manufacture tissues in accordance with good tissue practices, 
including manufacturing practices, SOPs, recordkeeping, and other 
practices designed to prevent the transmission of communicable disease 
(66 FR 5447 (January 19, 2001), 69 FR 29786 (May 25, 2004), 69 FR 68612 
(November 24, 2004)).
    It is important to recognize that blood manufacturing presents 
significant risks of communicable disease transmission. As FDA has 
previously noted, section 361 of the PHS Act authority ``is designated 
to eliminate the introduction of communicable disease, such as 
hepatitis, from one state to another. Of

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necessity, therefore, this authority must be exercised upon the disease 
causing substance within the state where it is collected, manufactured, 
or otherwise found. Thus, the Commissioner of Food and Drugs may 
promulgate current good manufacturing practice regulations for 
intrastate blood banking, pursuant to the act, as hepatitis is a 
communicable disease. Without proper controls, it is likely to spread 
on an interstate basis.'' (39 FR 18614, May 28, 1974). These statements 
are equally true today, where the spectrum of disease agents has 
increased to include, for example, HIV-1 and -2, agents that cause 
AIDS, and HCV, an additional cause of hepatitis. We understand 
communicable diseases to include, but not be limited to, those 
transmitted by viruses, bacteria, fungi, parasites, and transmissible 
spongiform encephalopathy agents. Preventing the spread of communicable 
disease is the important purpose underlying the comprehensive 
regulations for blood establishments now in place, which this proposed 
rule would somewhat modify and modernize.
    Under section 361 of the PHS Act, FDA is authorized to enforce the 
regulations it issues to prevent the introduction, transmission, or 
spread of communicable disease interstate through such means as 
inspection, disinfection, sanitation, destruction of animals or 
articles found to be so infected or contaminated as to be sources of 
dangerous infection in human beings, and other measures that may be 
necessary. In addition, under section 368(a) of the PHS Act, any person 
who violates a regulation prescribed under section 361 of the PHS Act 
may be punished by imprisonment for up to 1 year. Individuals may also 
be punished for violating such a regulation by a fine of up to $100,000 
if death has not resulted from the violation or up to $250,000 if death 
has resulted. For organizational defendants, fines range up to $200,000 
and $500,000. Individuals and organizations also face possible 
alternative fines based on the amount of gain or loss (18 U.S.C. 3559 
and 3571(b) through (d)). Federal District Courts also have 
jurisdiction to enjoin individuals and organizations from violating 
regulations implementing section 361 of the PHS Act. (See Califano v. 
Yamasaki, 442 U.S. 682, 704-05 (1979); United States v. Beatrice Foods 
Co., 493 F.2d 1259, 1271-72 (8th Cir. 1974), cert. denied, 420 U.S. 961 
(1975).)
    Blood and blood components introduced or delivered for introduction 
into interstate commerce are subject to section 351 of the PHS Act, 
which requires that such products be licensed (42 U.S.C. 262). Section 
351 of the PHS Act further authorizes FDA, by delegation, to establish 
requirements for such biologics licenses (42 U.S.C. 262(a)(2)(A)). In 
addition to its authority under section 361 of the PHS Act, FDA relies 
on this authority when the proposed regulations would be applied to 
products subject to biologics license. To obtain a license, applicants 
must show that the manufacturing establishment meets all applicable 
standards designed to assure the continued safety, purity, and potency 
of the blood and blood components, and that the product is safe, pure, 
and potent. FDA's license revocation regulations provide for the 
initiation of revocation proceedings if, among other reasons, the 
establishment or the product fails to conform to the standards in the 
license application or in the regulations designed to ensure the 
continued safety, purity, or potency of the product (Sec.  601.5). 
Violations of section 351 are punishable by a 1-year term of 
imprisonment, a fine as described in the preceding paragraph, or both 
(42 U.S.C. 262(f), 18 U.S.C. 3571).
    Blood and blood components are also drugs or devices, as those 
terms are defined in sections 201(g)(1) and (h) of the act (21 U.S.C. 
321(g)(1) and (h); see United States v. Calise, 217 F. Supp. 705, 708-
09 (S.D.N.Y. 1962)); 42 U.S.C. 262(j) (``The Federal Food, Drug, and 
Cosmetic Act applies to a biological product subject to regulation 
under this section, except that a product for which a license has been 
approved * * * shall not be required to have an approved [new drug] 
application''). Since blood and blood components are drugs or devices 
generally subject to the act, in issuing these regulations, FDA relies 
on the act's grant of authority to issue regulations for the efficient 
enforcement of the act (21 U.S.C. 371(a)). The act requires collecting 
establishments to comply with the act's current good manufacturing 
practice provisions and related regulatory scheme. Under section 501 of 
the act (21 U.S.C. 351), drugs, including blood and blood components, 
are deemed ``adulterated'' if the methods used in their manufacturing, 
processing, packing, or holding do not conform with current good 
manufacturing practice (21 U.S.C. 351(a)(2)(B)). Devices are deemed 
``adulterated'' if the methods used in, or the facilities or controls 
used for, their manufacture, packing, storage, or installation are not 
in conformity with good manufacturing practice requirements established 
by FDA in regulations (21 U.S.C. 351(h) and 360j(f)(1)). We propose to 
specify that the provisions of the proposed rule are critical aspects 
of good manufacturing practice. The proposed rule would require 
collecting establishments to assure that donors of blood and blood 
components meet the essential criteria for eligibility, and that blood 
and blood components are suitable for transfusion or further 
manufacturing. Blood and blood components not manufactured in 
accordance with good manufacturing practice, including the provisions 
of the proposed rule, would be considered adulterated under 21 U.S.C. 
351(a)(2)(B) or 21 U.S.C. 351(h) and 360j(f)(1), and collecting 
establishments and blood and blood components would be subject to the 
act's enforcement provisions for violations of the act. These include 
seizure of violative products (section 304 of the act) (21 U.S.C. 
332)), injunction against ongoing and future violations, and criminal 
penalties (section 303 of the act) (21 U.S.C. 333 and 18 U.S.C. 3571)). 
The act punishes both misdemeanor and felony violations of the act. 
Misdemeanor violations are punishable by a term of imprisonment of up 
to 1 year, a fine as described previously, or both. (21 U.S.C. 
333(a)(1), 18 U.S.C. 3571). Individuals convicted of felony violations 
may be sentenced to a term of imprisonment of up to 3 years, a fine of 
up to $250,000, or both. Organizations convicted of felony violations 
may be sentenced to a fine of up to $500,000. Individuals and 
organizations also face possible alternative fines based on the amount 
of gain or loss (18 U.S.C. 3571(b) through (d)).

III. Summary of the Proposed Rule

A. General Description

    The proposed regulations in subparts A, B, and C of part 630 would 
apply to you, establishments that collect and process blood and blood 
components. The proposed rule would add donor requirements for blood 
and blood components, including Source Plasma and Source Leukocytes, to 
make them consistent with current practices in the blood industry. The 
proposed regulations also would assemble into one part certain current 
provisions applicable to determining the eligibility of a donor. These 
general regulations would apply to any blood and blood component 
intended for transfusion or for further manufacturing use, including 
Source Plasma and Source Leukocytes, and those blood and blood 
components used in the manufacture of a medical device. We are 
proposing a new title for part 630 to reflect this application. For 
purposes of this document, whenever

[[Page 63420]]

we discuss blood and blood components, the source is human.

B. Standard Operating Procedures (SOPs) (Proposed Sec.  606.100(b))

    We propose to clarify current Sec.  606.100(b) to state that you 
must not only establish and maintain, but must also follow written 
procedures, in accordance with all applicable regulations for all steps 
in the collection, processing, compatibility testing, storage and 
distribution of blood and blood components intended for transfusion and 
for further manufacturing use. We propose to distinguish the types of 
transfusions as ``allogeneic'' and ``autologous.'' We also propose to 
add, to current Sec.  606.100(b), language making explicit the 
requirement that you establish, maintain, and follow SOPs for 
investigating product deviations (Sec.  606.171), and for recordkeeping 
related to current good manufacturing practice requirements (part 606) 
and biological product standards (part 610).

C. Records (Proposed Sec.  606.160(e))

    Current Sec.  606.160(e) requires collecting establishments to have 
records available to identify unsuitable donors and prevent the 
distribution of blood and blood components collected from such 
individuals. This is sometimes accomplished by establishing a coding 
system, which allows personnel to identify a donor as ineligible 
without revealing the reason for the deferral to those who do not have 
a need to know the information. We propose to continue this requirement 
in Sec.  606.160(e), which would require establishments to maintain a 
record of donors determined to be ineligible to donate in order to 
prevent the collection of blood or blood components from such 
individuals while they are ineligible or deferred. We also are 
proposing in Sec.  606.160(e)(2) that all donor screening locations of 
a collecting establishment operating under a common organization, e.g., 
under the same license number, use a collective master list of donors 
determined at each location to be ineligible to donate. This list is 
also known as a donor deferral registry. Under proposed Sec.  
630.10(d)(1), the collecting establishment would be required to review 
the donor deferral registry before collection to prevent the collection 
of blood and blood components from donors deferred from donation 
temporarily (when the temporary deferral is in effect when the donor 
presents), indefinitely, or permanently.
    Under proposed Sec.  606.160(e)(2), we are proposing to limit entry 
into the shared donor deferral registry to those donors who are 
determined to be ineligible to donate due to a possible exposure to a 
relevant transfusion-transmitted infection (proposed Sec.  630.10(f)), 
or to certain other factors that may adversely affect the health of the 
donor, or the safety, purity, or potency of the blood or blood 
component (proposed Sec.  630.10(g)(1) through (g)(6)). We are 
interested in receiving comments on:
     The information that should be included on a donor 
deferral registry used in common by all donor screening locations of a 
collecting establishment operating under a common organization (e.g., 
under the same license number);
     The adequacy of the criteria listed in proposed Sec.  
630.10(f) and (g)(1) through (g)(6) to prevent the collection of blood 
and blood components that may be harmful to the donor or that may 
result in an unsuitable product due to possible exposure of the donor 
to a transfusion-transmitted infection; and
     The technical feasibility of complying with the proposed 
requirement.
    We are also seeking comments on the feasibility of sharing donor 
deferral lists between licensed establishments for deferrals required 
by the FDA. Such national deferral registries have existed for Source 
Plasma collections for many years.
    Proposed Sec.  606.160(e) would help prevent the collection of 
unsuitable blood and blood components and reduce recipients' exposure 
to blood and blood components with an increased risk of transmitting an 
infectious agent. For example, under proposed Sec.  606.160(e)(2), if a 
collecting establishment collected blood at four locations and three 
mobile sites, donors deferred from further donation at any of the seven 
sites would be listed on a donor deferral registry available at all 
seven sites. The requirement to review the record of ineligible donors 
before collection and to make the record of ineligible donors available 
to collecting establishments operating under a common organization 
would improve blood safety by reducing the likelihood of accidental 
release of potentially infectious units. We discussed the practice of 
reviewing a donor deferral registry before the collection of blood and 
blood components at the Blood Product Advisory Committee meeting of 
October 20, 1994, and recommended the practice in the guidance document 
entitled ``Guideline for Quality Assurance in Blood Establishments'' 
(60 FR 36290, July 14, 1995).
    We are considering whether to include, in the final rule, a 
provision requiring that donor deferral records be used and disclosed 
only for purposes consistent with subchapter F of 21 CFR Chapter I.
     We request comment on this proposal, including the 
following specific issues:
    Whether the current practices and protections adequately protect 
the confidentiality of donor records;
    Whether those current practices and protections will still be 
adequate if FDA requires that establishments make donor deferral 
records available at all collection sites operating under the same 
license or common management; and
    Whether a regulation limiting the use and disclosure of such 
records would actually further the goal of protecting the 
confidentiality of the records.
    In addition, we request comment on the following:
    We believe that few, if any, blood collection establishments are 
HIPAA-covered entities under the HIPAA Privacy Rule. However, to 
evaluate the impact of this rule on any such HIPAA-covered entities, we 
are seeking public comment from any facilities that may be covered by 
the HIPAA Privacy Rule, regarding whether or how HIPAA requirements may 
impact their ability to comply with this proposed rule.

D. Testing Requirements (Proposed Sec.  610.40(a) and (e) and Sec.  
630.30(a)(5))

1. Testing for Relevant Transfusion-transmitted Infections
    Section 610.40(a) requires that a collecting establishment test 
each donation of blood or blood component intended for transfusion or 
for further manufacturing use in preparing a product for evidence of 
infection due to the listed communicable disease agents. We are 
proposing to revise Sec.  610.40(a) by replacing ``communicable disease 
agents'' with ``relevant transfusion-transmitted infections described 
in Sec.  630.3(g).'' This change would require testing and, where 
appropriate, screening, for additional relevant transfusion-transmitted 
infections that present a potential risk to the health of the recipient 
and for which appropriate testing methods are available. Donor 
screening or testing for a relevant transfusion-transmitted infection 
may vary based on the characteristics of the blood product. For 
example, we do not currently require testing of Source Plasma for human 
T-lymphotropic virus (type I or II) because the virus is cell-
associated and readily removed and inactivated during manufacturing. 
Similarly, testing for another relevant transfusion-transmitted 
infection may

[[Page 63421]]

not be required if viral inactivation or removal procedures have been 
validated to ensure inactivation or removal of the infectious agent and 
screening for risk factors is available, unless the risk of harm from 
transmission is too great to rely solely on viral inactivation 
procedures and screening for risk factors.
2. Testing Further With One or More Supplemental (Additional, More 
Specific) Test(s)
    When a donation is found to be reactive by a screening test, Sec.  
610.40(e) currently requires that the establishment further test the 
donation with a supplemental (additional, more specific) test approved 
for such use by FDA. In proposed Sec.  610.40(e), we are proposing to 
require that additional testing may be performed with additional tests 
that are not necessarily ``more specific'' provided that the additional 
test(s) is appropriate to determine the donor's infection status prior 
to notification. At a meeting of the Blood Products Advisory Committee 
(BPAC) on March 18 and 19, 2004, the committee heard presentations on 
alternative algorithms for additional testing for HIV and HCV after an 
initially reactive screening test. The committee recommended that FDA 
reconsider its requirement that supplemental testing be performed using 
more specific tests. At that meeting, industry representatives provided 
information on the need for and the use of alternative testing 
algorithms to confirm the deferred donor's infection status that 
involved the use of more than one enzyme immunoassay (EIA) screening 
test, including the use of multiple EIA screening tests in lieu of a 
supplemental test. A Public Health Service (PHS) working group reviewed 
the data presented at the March 2004 BPAC and all available data and 
concluded that when donor screening tests were reactive for antibody to 
HIV and reactive on an individual HIV-1 nucleic acid test (NAT) test, 
supplemental testing for HIV antibody was not necessary. A similar 
conclusion that supplemental testing for HCV was not necessary was 
reached for donor screening tests that were reactive for antibody to 
HCV and reactive on an individual HCV NAT test. However, the PHS 
working group was unable to recommend the use of multiple EIA screening 
tests in lieu of the HIV-1 or HCV supplemental tests when the 
individual HIV-1 or HCV NAT test was non-reactive.
    The intent of this section is to allow for the use of multiple 
screening tests to ``confirm'' infection or to provide additional 
information on the presence of the analyte when described in guidance, 
as appropriate. It is not FDA's intention to move away from 
confirmatory or supplemental testing where such an approved test 
exists, but rather to recognize that under certain circumstances 
alternative testing schemes may provide confirmatory or supplemental 
testing information. In the case of HIV NAT, FDA has allowed the HIV-1 
Western Blot not to be performed when the HIV EIA is reactive and HIV 
NAT is positive. If the HIV NAT is negative, the Western Blot must 
still be performed. If this rule is finalized, we intend to make 
initial recommendations for additional testing algorithms in draft 
guidance issued for public comment.
3. Testing for Bacterial Contamination for Platelets and Other 
Transfusible Blood Components
    Bacteria remain a significant contaminant in blood and blood 
components (Ref. 1). Bacterial contamination of platelets has been 
discussed at an FDA workshop held on September 24, 1999, at the 
December 2002 BPAC meeting, and at the April 2004 meeting of the Public 
Health Service Advisory Committee on Blood Safety and Availability. 
AABB (formerly known as the American Association of Blood Banks) 
established an accreditation standard, effective March 2004, requiring 
accredited blood banks and transfusion services to have methods to 
limit and detect bacterial contamination in all platelet components. 
Currently, bacterial detection is being performed using a variety of 
methods, including FDA-approved quality control tests. However, we are 
proposing in Sec.  630.30(a)(5) that a platelet component would not be 
suitable until tests for bacterial contamination are found negative. 
(See section III.L of this document.) In some instances, specific 
bacteria identified as contaminants in a blood component could indicate 
an underlying bacteremia or serious illness in the donor. Therefore, we 
are also soliciting comments on: (1) Whether to require, in the context 
of testing of platelet components prior to release, the identification 
of the species of the bacterial contaminant and (2) whether to require 
donor deferral and notification when identification of the contaminant 
indicates possible endogenous bacteremia, and not contamination during 
collection and processing. Additionally, we are also considering 
whether to extend, to other blood components for transfusion, the 
requirement for testing for bacterial contamination, and donor deferral 
and notification based on the results. We also invite comment on this 
issue.

E. Purpose and Scope (Proposed Sec.  630.1)

    The proposed rule would require that a blood establishment make two 
determinations: (1) The donor is eligible to donate and (2) the 
donation is suitable for use in transfusion or further manufacturing 
use. The proposed requirements in part 630 would provide criteria for 
the collecting establishment to use to determine the eligibility of the 
donor to donate. We would require that the collecting establishment 
determine on the day of donation that the donor is in good health and 
is not deferred from donating. Proposed Sec.  630.1 also makes 
reference to previously issued requirements in part 630 that describe 
the process for notifying donors of their deferral due to failure to 
satisfy the eligibility criteria or test results for relevant 
transfusion-transmitted infections required under Sec.  610.40.
    This proposed rule would apply to any establishment or facility 
that collects any blood or blood component from donors:
     For transfusion, including autologous use;
     For further manufacturing use; or
     For use as a component of a medical device.
    Creating this separate part for donor eligibility requirements for 
donors of blood and blood components would allow for a consistent set 
of criteria for all individuals participating in various collection 
programs.

F. Definitions (Proposed Sec.  630.3)

    Section 630.3(a) through (l) of the proposed rule contains proposed 
definitions of terms specifically used in this rulemaking.
    We are proposing in Sec.  630.3(a) and (b) to define blood and 
blood component as used in part 630. We would define blood as a product 
and describe the product as a fluid containing dissolved and suspended 
elements, which circulates in a human's vascular system. Blood 
component also would be defined as a product, and described as 
containing a part of blood separated by physical or mechanical means.
    In proposed Sec.  630.3(e), the definition for intimate contact is 
intended to help you determine whether the donor is at risk for 
contracting a transfusion-transmitted infection from another individual 
who may be infected with a transfusion-transmitted infection.
    We are defining relevant transfusion-transmitted infection in 
proposed Sec.  630.3(g)(1) to identify the currently recognized disease 
agents that are

[[Page 63422]]

associated with transmission from the donor to the recipient by 
transfusion, infusion, or injection of a blood component or blood 
derivative and for which there are appropriate screening and/or testing 
measures available. These are: HIV, types 1 and 2; HBV; HCV; human T-
lymphotropic virus (HTLV), types I and II; Treponema pallidum 
(syphilis); Creuztfeldt-Jakob disease (CJD), variant Creutzfeldt-Jakob 
disease (vCJD); and Plasmodium sp. (malaria).
    In the proposed rule entitled ``Requirements for Testing Human 
Blood Donors for Evidence of Infection Due to Communicable Disease 
Agents'' (64 FR 45340, August 19, 1999), we solicited comments, with 
supporting data, from the public in regard to the value of donor 
testing for syphilis as a marker of increased risk behavior, as a 
surrogate test for other infectious diseases, and in preventing the 
transmission of syphilis through blood transfusion. After reviewing the 
comments and submitted scientific data, we determined that the comments 
did not provide sufficient supporting data to justify eliminating the 
requirements for screening and testing the donor for syphilis. We 
continue to consider this issue, including any further studies that 
address the issues of transfusion-related syphilis infection or testing 
for syphilis as a surrogate marker for other communicable diseases; and 
we again request comments and data concerning whether establishments 
could discontinue syphilis testing without adversely affecting the 
safety of the blood supply. If we receive adequate data, we will 
eliminate or modify this testing requirement in the final rule.
    The second part of the definition in Sec.  630.3(g)(2), proposes 
criteria for identifying additional disease agents that present a risk 
of transmission from the donor to the recipient by transfusion of blood 
or blood components. This risk would include disease and disease agents 
with a known, presumptive, or theoretical risk of infection through 
transfusion, such as West Nile virus. (See ``Guidance for Industry: 
Assessing Donor Suitability and Blood and Blood Product Safety in Cases 
of Known or Suspected West Nile Virus Infection,'' dated June 2005.) To 
be a relevant transfusion-transmitted infection, a disease agent or 
disease must meet all of the following criteria:
     The disease agent or disease must present a significant 
health risk that could be fatal, life-threatening, cause permanent 
impairment of a body function or damage to body structure, or 
necessitate medical intervention to preclude such impairment or damage; 
and
     There must be appropriate screening and/or testing methods 
available; and
     The disease agent or disease must present a risk of 
transmission by the transfusion of the blood or blood component 
collected, or by the use of a blood derivative product manufactured 
from collected blood or blood components, to the potential recipient. 
The disease agent or disease must be potentially transmissible by that 
blood, blood component, or blood derivative product; and either have 
sufficient incidence and/or prevalence to affect the potential donor 
population; or have been accidentally or intentionally released in a 
manner that would place donors at risk of infection, such as a 
bioterrorism attack or laboratory accident that releases an agent, 
e.g., anthrax or smallpox, into the population.
    We are also proposing in Sec.  630.3(k) a definition for 
transfusion-transmitted infection. This definition would include any 
transfusion-transmitted disease not included under proposed Sec.  
630.3(g). The criteria for a transfusion-transmitted infection are as 
follows:
     The transfusion-transmitted infection must present a 
significant health risk that could be fatal, life-threatening, cause 
permanent impairment of a body function or damage to body structure, or 
necessitate medical intervention to preclude such impairment or damage; 
and
     The disease agent or disease may present a risk of 
transmission by the transfusion of the blood or blood component 
collected, or by the use of a blood derivative product manufactured 
from collected blood or blood components, to the potential recipient.
    The definition of a transfusion-transmitted infection differs from 
a relevant transfusion-transmitted infection in that the existence of 
sufficient incidence and/or prevalence to affect the potential donor 
population is not a part of the definition. Available screening and 
testing methods may also be limited. One example of such a transfusion-
transmitted infection is leishmania.
    It is our intention to issue guidance following the good guidance 
practices in 21 CFR 10.115 to advise you when we believe that a new 
disease agent or disease meets the criteria for a relevant transfusion-
transmitted infection, and that we recommend that you take steps to 
screen and/or test donors of all or certain blood components for that 
particular risk of transmission. The criteria expressed in this 
provision would support such a notification only when there is a 
significant concern. Moreover, good guidance practices provide the 
public with an opportunity to comment on guidance before its 
implementation, unless prior public participation is not feasible or 
appropriate, e.g., in a public health emergency. In addition, we intend 
to hold public meetings and/or consult with advisory committees where 
appropriate, to help us determine whether a disease agent or disease 
meets these criteria, and whether FDA should recommend that 
establishments perform donor screening and/or testing for it.
    We believe that the issuance of such guidance will assist 
collecting establishments, especially small establishments that are not 
able to track emerging disease agents and diseases in a timely manner. 
By providing these notifications, we will perform an important 
communications function and assist collecting establishments in meeting 
their regulatory obligations to screen and test donors.
    Donor, as used in the proposed regulation in Sec.  630.3(c), is 
defined to include a person who is a potential candidate as well as a 
person who completes the act of donation.
    We are defining eligibility of a donor in proposed Sec.  630.3(d) 
and suitability of the donation in proposed Sec.  630.3(i) so as to 
distinguish between the acceptability of a donor for donation and the 
acceptability of the donation for transfusion or for further 
manufacturing use.
    We have defined physician substitute in proposed Sec.  630.3(f), 
responsible physician in proposed Sec.  630.3(h), and trained personnel 
in proposed Sec.  630.3(j) according to the education and 
qualifications required to fulfill the position description.
    You, in proposed Sec.  630.3(l), is defined so as to establish who 
must comply with the requirements in proposed part 630.

G. Medical Supervision (Proposed Sec.  630.5)

    In Sec.  630.5, we are proposing to include requirements 
prescribing the level of medical supervision at collecting 
establishments responsible for determining the eligibility of a donor, 
collecting blood and blood components, or performing other procedures 
with significant implications for both the continued health of donors 
and the safety of the blood supply. Proposed Sec.  630.5 would:
     Apply to the collection of blood and blood components;
     Amend, combine, and redesignate certain regulations; and
     Codify certain recommendations currently in guidance 
documents.

[[Page 63423]]

    Except as provided otherwise, proposed Sec.  630.5(a) would require 
you to authorize a responsible physician, who is trained and qualified, 
to determine the eligibility of a donor of blood or blood components in 
accordance with part 630. We would require that each collecting 
establishment have a qualified physician on the premises when 
determining donor eligibility, immunizing donors for the purpose of 
producing high-titer plasma, collecting Whole Blood or blood 
components, and returning red blood cells to the donor.
    Proposed Sec.  630.5(b) would consolidate these requirements, and 
would require collecting establishments to have a responsible physician 
present during the determination of eligibility of a donor, the 
collection of blood and blood components, the collection of Source 
Plasma from ineligible donors in an approved program, the return of red 
blood cells to the donor, and the immunization of donors. The 
responsible physician would:
     Direct and control the physician substitutes and trained 
personnel; and
     Approve procedures concerning the determination of donor 
eligibility, the collection of blood and blood components, the 
immunization of a donor, and the return of red blood cells or other 
blood constituents to the donor during apheresis.
    Proposed Sec.  630.5(c) would permit a collecting establishment to 
authorize a physician substitute to perform the same functions of a 
responsible physician in the collection of Source Plasma, except the 
responsible physician would be required to be present for red blood 
cell immunizations. Many plasma collecting establishments currently 
have FDA approval under alternative procedures regulations in Sec.  
640.120 for the use of a physician substitute program for a variety of 
activities. These include supervising the collection of Source Plasma 
from donors who meet all normal donor suitability requirements, and for 
the scheduling and administration of the injection of a licensed 
vaccine for the production of high titer plasma. However, the 
responsible physician is required to be present during red blood cell 
immunization and high-risk collections. This proposed rule is 
consistent with these alternative procedures and with our 
recommendations issued in the August 15, 1988, memorandum to all plasma 
establishments entitled ``Physician Substitutes.'' We believe that the 
use of a physician substitute is adequate to help ensure the continued 
safety of Source Plasma donors and that the Source Plasma collected 
from these donors is safe, pure, and potent.
    Proposed Sec.  630.5(d) would permit collecting establishments to 
authorize trained personnel, including physician substitutes, to 
determine the donor's eligibility and collect blood and blood 
components in the absence of a responsible physician. Under Sec.  
606.100(b), we would require the collecting establishment to establish, 
maintain, and follow SOPs specifying criteria for determining donor 
eligibility, and for the collection of blood and blood components.
    The collecting establishment would be required in proposed Sec.  
630.5(e) to have SOPs for providing emergency medical services to a 
donor within 15 minutes when necessary. Although we currently require 
the presence of appropriately trained medical personnel, our current 
regulations do not directly address the availability of emergency 
medical services, which a donor may require. We are interested in 
receiving comments on what would be considered as appropriate for 
available emergency medical services.

H. General Donor Eligibility Requirements (Proposed Sec.  630.10)

    We propose in Sec.  630.10 to require certain steps for determining 
the eligibility of a donor to donate blood and blood components. In 
proposed Sec.  630.10(a), a collecting establishment would be required 
to perform these prescribed steps, or assessments, to determine if the 
donation may adversely affect:
     The health of the donor or
     The safety, purity, or potency of blood or blood 
components.
    We are proposing to combine and revise the donor suitability 
requirements in Sec. Sec.  640.3 and 640.63 and to redesignate these 
requirements as Sec.  630.10. Proposed Sec.  630.10 would contain the 
requirements for determining the eligibility of the donor to donate 
blood and blood components, whether intended for transfusion or for 
further manufacturing use.
1. Educational Material
    In Sec.  630.10(b), we propose to require collecting establishments 
to provide to all donors, before donation, information about the 
relationship among behaviors that increase risks of relevant 
transfusion-transmitted infections, signs and symptoms of such 
infections, and the consequent risk to the safety of the blood and 
blood component. This information may be provided in oral, written, or 
multimedia form in a manner designed to be understood by the donor, in 
appropriate language and literacy level and taking into account any 
disabilities. When screening for behavioral risk factors is required 
for a relevant transfusion-transmitted infection (for example, HIV, 
HBV, or HCV), the material would instruct donors to self-defer if they 
determine that they have participated in an increased-risk behavior 
for, or show signs or symptoms of, that relevant transfusion-
transmitted infection. Currently, we recommend that establishments 
provide educational material to inform potential donors of the risks of 
HIV transmission and the need to self-defer. The current 
recommendations for educational material are described in the 
memorandum entitled ``Revised Recommendation for the Prevention of 
Human Immunodeficiency Virus (HIV) Transmission by Blood and Blood 
Products,'' issued April 23, 1992. We intend to issue additional 
guidance on educational material in the future. The proposed rule would 
also require that educational material include behavioral risks and 
signs and symptoms for hepatitis and other relevant transfusion-
transmitted infections determined to present a risk to the blood 
supply. We are soliciting comments on this provision, particularly on 
how comprehensive the educational material should be and the format or 
style in which it is presented.
2. Assessment of the Donor's Eligibility to Donate
    Current Sec.  640.3 requires that the donor be in good health and 
that the collecting establishment determine the donor's suitability for 
donation on the day of collection. The status of the donor's health is 
determined by performing a prescribed physical examination, and the 
donor may not serve as the source of Whole Blood more than once in 8 
weeks.
    Proposed Sec.  630.10(c) would require that the collecting 
establishment perform an assessment of the donor's eligibility on the 
day of donation, and before collection. An exception would be allowed 
for the collection of blood components that cannot be stored for more 
than 24 hours, such as granulocytes for transfusion. For such 
components, the collecting establishment may perform a donor assessment 
and the testing required under Sec.  610.40(a) and (b) 1 day before the 
collection of such products. Establishments would be required to have 
SOPs in place to identify such components.
    In proposed Sec.  630.10(d), determination of a donor's eligibility 
to

[[Page 63424]]

donate would consist of four assessments:
     Assessing the donor's deferral status;
     Assuring that the donation interval is appropriate, taking 
into account whether the donor is participating simultaneously in other 
blood or blood component collection programs;
     Assessing the donor's medical history; and
     Assessing the donor's health by performing a physical 
assessment of the donor.
    Consistent with the good guidance practice regulations, we intend 
to issue guidance on determining the eligibility of a donor of blood 
and blood components. The guidance document would represent our current 
thinking on describing the assessment factors, signs, and symptoms, and 
recommended deferral periods to be included in a medical history 
questionnaire and a physical examination.
    a. Deferral status and donation history.
    After the donor has reviewed the educational material and does not 
self-defer, under proposed Sec.  630.10(d)(1) the collecting 
establishment would check the donor deferral registry to determine 
whether the donor is deferred temporarily, indefinitely or permanently. 
(See section III.C of this document.) If the donor is deferred from 
allogeneic donation indefinitely, or permanently, or the temporary 
deferral period has not expired, the donor is ineligible to donate. 
Donor deferrals are based on the degree of risk to the donor's health, 
or the safety, purity, and potency of the donated blood or blood 
components. Under proposed Sec.  630.10(d)(2), the collecting 
establishment would check the donor's most recent donation to assure 
that the donation interval is appropriate for the type of donation, as 
described in proposed Sec.  630.15(a)(1) (Whole Blood), and Sec.  
640.22(b) (Platelets) and 640.65(b)(4) (Plasmapheresis) (Sec. Sec.  
640.22(b) and 640.65(b)(4)). In the interest of donor protection, we 
are proposing to include in proposed Sec.  630.10(d)(2) the requirement 
that the establishment take into account whether the donor is 
participating in other blood or plasma collection programs, which could 
put the donor at risk by possible over-collection of a blood component. 
This is currently recommended in a blood memorandum dated March 10, 
1995, to registered blood and Source Plasma establishments entitled 
``Revision of FDA Memorandum of August 27, 1982: Requirements for 
Infrequent Plasmapheresis Donors.''
    b. The donor's medical history.
    Proposed Sec.  630.10(e) would require the collecting establishment 
to establish that the donor is in good health. This is usually 
accomplished by administering an appropriate medical history 
questionnaire in oral, written, or multimedia form, and taking into 
account any disabilities using appropriate language and literacy level, 
to the donor on each day of donation. With frequent donation, e.g., 
frequent Source Plasma donations, an appropriate abbreviated 
questionnaire may be used if it adequately captures necessary donor 
medical history. The use of an abbreviated donor history questionnaire 
was discussed at the Blood Products Advisory Committee meeting held on 
December 11, 2003.
    The questionnaire would enable the collecting establishment to do 
the following:
     Determine if the donor is in good health and if healthcare 
practitioners have advised the donor not to donate;
     Identify risk factors for relevant transfusion-transmitted 
infections;
     Determine the possibility of exposure to, or clinical 
evidence of, relevant transfusion-transmitted infections; and
     Determine whether there are other conditions that may 
adversely affect the donor or the safety, purity, or potency of the 
donated blood or blood component, such as by examining the phlebotomy 
site for infection or inflammation which may cause contamination of the 
unit being collected.
    Proposed Sec.  630.10(f) and (g) describe factors that make a donor 
ineligible to donate and that must be addressed in medical history 
questions.
    Proposed Sec.  630.10(f).--Proposed Sec.  630.10(f) would require 
the collecting establishment to assess the donor for certain described 
factors, which may indicate that the donor is at increased risk for, or 
has evidence of, a relevant transfusion-transmitted infection; and to 
determine the donor ineligible to donate when the assessment indicates 
possible exposure to a relevant transfusion-transmitted infection that 
is still applicable at the time of donation. These factors are listed 
in proposed paragraphs (f)(1) through (f)(6). In addition to the 
following discussion of these factors, we refer you to the following 
current Memoranda to Blood Establishments and Blood Guidances, which 
discuss factors related to exposure to a relevant transfusion-
transmitted infection. The draft guidances included in the following 
bulleted list, when finalized, will represent FDA's current thinking on 
those topics.
     ``Recommendations for the Management of Donor and Units 
that are Initially Reactive for Hepatitis B Surface Antigen (HBsAg),'' 
dated December 2, 1987;
     ``FDA Recommendations Concerning Testing for Antibody to 
Hepatitis B Core Antigen (Anti-HBc),'' dated September 10, 1991;
     ``Revised Recommendations for the Prevention of Human 
Immunodeficiency Virus (HIV) Transmission by Blood and Blood 
Products,'' dated April 23, 1992;
     ``Revised Recommendations for Testing Who