[Federal Register: November 8, 2007 (Volume 72, Number 216)]
[Proposed Rules]
[Page 63415-63444]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr08no07-26]
[[Page 63415]]
-----------------------------------------------------------------------
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
[[Page 63416]]
-----------------------------------------------------------------------
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.
-----------------------------------------------------------------------
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: http://frwebgate.access.gpo.gov/cgi-bin/leaving.cgi?from=leavingFR.html&log=linklog&to=http://www.regulations.gov.
Follow the instructions for submitting comments.
Agency Web site: http://frwebgate.access.gpo.gov/cgi-bin/leaving.cgi?from=leavingFR.html&log=linklog&to=http://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 http://frwebgate.access.gpo.gov/cgi-bin/leaving.cgi?from=leavingFR.html&log=linklog&to=http://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 http://frwebgate.access.gpo.gov/cgi-bin/leaving.cgi?from=leavingFR.html&log=linklog&to=http://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,
[[Page 63417]]
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
[[Page 63418]]
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
[[Page 63419]]
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 Whole Blood, Blood
Components, Source Plasma and Source Leukocytes for Antibody to
Hepatitis C Virus Encoded Antigen (Anti-HCV),'' dated April 23, 1992;
``Draft Guidance for Industry: Revised Recommendations for
Donor and Product Management Based on Screening Tests for Syphilis,''
dated June 2003;
``Recommendations for the Deferral of Current and Recent
Inmates of Correctional Institutions as Donors of Whole Blood, Blood
Components, Source Leukocytes, and Source Plasma,'' dated June 8, 1995;
``Guidance for Industry: Revised Preventive Measures to
Reduce the Possible Risk of Transmission of Creutzfeldt-Jakob Disease
(CJD) and Variant Creutzfeldt-Jakob Disease (vCJD) by Blood and Blood
Products,'' dated January 2002;
Draft ``Guidance for Industry: Recommendations for Donor
Questioning Regarding Possible Exposure to Malaria,'' dated June 2000;
``Guidance for Industry: Recommendations for Assessment of
Donor Suitability and Blood and Blood Product Safety in Cases of
Possible Exposure to Anthrax,'' dated October 2001;
``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;
``Guidance for Industry: Recommendations for Deferral of
Donors and Quarantine and Retrieval of Blood and Blood Products in
Recent Recipients of Smallpox Vaccine (Vaccinia Virus) and Certain
Contacts of Smallpox Vaccine Recipients,'' dated December 2002; and
``Guidance for Industry: Revised Recommendations for the
Assessment of Donor Suitability and Blood Product Safety in Cases of
Suspected Severe Acute Respiratory Syndrome (SARS) or Exposure to
SARS,'' dated September 2003.
[[Page 63425]]
These memoranda and guidance documents further discuss the
applicability of these factors in donor screening. All current
memoranda and guidance documents referenced in this rulemaking may be
found at http://frwebgate.access.gpo.gov/cgi-bin/leaving.cgi?from=leavingFR.html&log=linklog&to=http://www.fda.gov/cber/reading.htm.
Social behaviors (Proposed Sec. 630.10(f)(1)).--Under proposed
Sec. 630.10(f)(1), establishments must determine whether a donor has
engaged in social behaviors associated with increased risk of infection
with relevant transfusion-transmitted infections. Some examples of
social behaviors associated with increased risk of exposure to HIV and
viral hepatitis identified in current guidance are men who have had sex
with another man even one time since 1977; exchanging sex for drugs or
money; or intravenous drug use. Participation in social behaviors
associated with relevant transfusion-transmitted infections would cause
the donor to be ineligible to donate and to be deferred. We have issued
guidance on such deferrals and we will continue to do so, pursuant to
our good guidance practices. We include assessment of certain social
behaviors because of the risk that testing alone would not detect
infection due to testing error, the early stage of the donor's
infection (the window period), or the donor's low antibody level or
intermittent viremia.
To assist us in developing such guidance documents, we intend to
hold workshops and public meetings on social behaviors associated with
increased risk of infection with a relevant transfusion-transmitted
infection. The public will have the opportunity to submit comments on
specific issues as they are presented.
Medical treatment and procedures (Proposed Sec. 630.10 (f)(2)).--
We are proposing that you assess donors to determine whether they have
received medical treatment or undergone a medical procedure that would
put the individual at risk for potential exposure to a relevant
transfusion-transmitted infection. Such donors would be ineligible to
donate. Some examples of treatments or procedures that may transmit a
disease or disease agent are receipt of dura mater graft, transfusion
with blood or blood components within the previous 12 months, or the
receipt of human-derived clotting factor within the previous 12 months.
Signs and symptoms of relevant transfusion-transmitted infections
(Proposed Sec. 630.10(f)(3)).--We would require blood establishments
to assess donors for signs or symptoms of relevant transfusion-
transmitted infections; donors exhibiting such signs or symptoms would
be ineligible to donate blood and blood components. This provision is
intended to help ensure that an individual who exhibits one or more of
the signs and symptoms of HIV infection or viral hepatitis, or any
other relevant transfusion-transmitted infection that would be
applicable under proposed Sec. 630.3(g), and who is, therefore, a
potential source of transmitting a relevant transfusion-transmitted
infection, does not donate blood or blood components.
Institutionalization (Proposed Sec. 630.10(f)(4)).--A collecting
establishment would determine whether a donor is currently an inmate of
a correctional institution or has been incarcerated within the last 12
months, and if so, whether the risk of exposure related to that
incarceration is still applicable at the time of donation. Current
guidance recommends that a donor not be eligible to donate if
incarcerated in a correctional institution for more than 3 consecutive
days during the past 12 months.
Intimate contact (Proposed Sec. 630.10(f)(5)). We would require
collecting establishments to determine whether a donor is or was an
intimate contact of a person who is at an increased risk for exposure
to, or is known to be infected with, a relevant transfusion-transmitted
infection that is spread by intimate contact and, is thus, ineligible
to donate. One example is a heterosexual partner of an injection drug
user. Such individuals are at increased risk for contracting relevant
transfusion-transmitted infections due to the exchange of bodily
fluids, including blood or saliva.
Percutaneous exposure (Proposed Sec. 630.10(f)(6)).--We would
require collecting establishments to assess whether a donor had a
nonsterile percutaneous inoculation within the past year. A piercing of
the skin with an instrument used previously on another person with a
relevant transfusion-transmitted infection could expose the donor to
such infections. Under this provision, establishments would defer
donors who, within the last 12 months, experienced any piercing of the
skin by a nonsterile instrument, such as may be used in tattoos, body
or ear piercing, or intentional or accidental needlestick (percutaneous
exposure). FDA understands that certain establishments are licensed by
a State or credentialed by a responsible certifying body to perform
such procedures with sterile needles. FDA does not intend for such a
procedure performed by a state-licensed or responsibly certified
establishment to be a reason to defer the donor.
Proposed Sec. 630.10(g).--There are other factors that make a
donor ineligible because of the risk they present to the health of the
donor before, during, and after the donation process, or because they
could adversely affect the safety, purity, and potency of the blood and
blood component. Proposed paragraph (g) would require the collecting
establishment to determine the donor ineligible to donate if the
following factors existed and the collecting establishment decided that
donation by the donor would present a risk to the health of the donor,
or to the safety, purity, and potency of the blood and blood component.
In addition to the following discussion, we refer you to the following
current Memoranda to Blood Establishments and Guidances, which discuss
factors related to donor risk or product safety. The draft guidance
documents included in the following bulleted list, when finalized, will
represent FDA's current thinking on that topic.
``Deferral of Blood and Plasma Donors Based on
Medications,'' dated July 28, 1993;
``Deferral of Blood Donors Who Have Received the Drug
Accutane,'' dated February 28, 1984;
``Deferral of Donors Who Have Received Human Pituitary-
Derived Growth Hormone,'' dated November 25, 1987;
Draft ``Guidance for Industry: Precautionary Measures to
Reduce the Possible Risk of Transmission of Zoonoses by Blood and Blood
Products from Xenotransplantation Product Recipients and Their Intimate
Contacts,'' dated February 2002.
Medical or dental treatment, or symptoms of a recent or current
illness (Proposed Sec. 630.10(g)(1).--Under proposed paragraph (g)(1),
the collecting establishment must assess the health of the donor based
on medical or dental treatments. The collecting establishment must also
assess the health of the donor for symptoms of recent or current
illnesses. The establishment must determine whether the donor is
ineligible to donate temporarily, indefinitely, or permanently,
depending on the illness or treatment, if that assessment reveals a
factor that may adversely affect the safety, purity, or potency of the
blood or blood component, or that the donation may adversely affect the
health of the donor. For example, if the donor recently was diagnosed
with pneumonia, the interviewer would further assess the donor to
assure that the donor is in good health at the time of donation and
that the donor's health would not be adversely affected by the
donation. If
[[Page 63426]]
the donor had a recent tooth extraction or oral surgery, the collecting
establishment would temporarily defer the donor due to concern for
possible contamination of blood or blood components due to transient
bacteremia caused by the performance of dental procedures.
Medications (Proposed Sec. 630.10(g)(2)).--We would require
collecting establishments to assess the effects of medication taken by
the donor and to defer that donor if the medication could have an
adverse effect on the blood and blood components, the recipient, or on
the developing fetus of a pregnant recipient. The proposed regulation
is consistent with current industry practice to screen prospective
donors to identify such medications, and evaluate the potential for
each medication to have an adverse effect on the safety of the blood
supply. For example, following current industry practice and FDA
recommendations, collecting establishments would defer from donation,
either temporarily or permanently, a donor who had taken certain
medications (e.g., Accutane and Tegison). We further discuss the use of
certain medications that adversely affect platelet function in section
III.O of this document.
Major surgical procedure (Proposed Sec. 630.10(g)(3)).--We would
require establishments to defer donors who have experienced major
surgery within the past 12 months. This deferral is to protect the
donor whose health may be compromised by the donation and to address
the possibility that the donor may have unknowingly received blood or
blood components during surgery.
Travel to endemic areas for transfusion-transmitted infections
(Proposed Sec. 630.10(g)(4)).--It is known that several transfusion-
transmitted infections exist for which the risk is closely associated
with a geographic area, e.g., leishmania. Typically, such infections
would not be ``relevant transfusion-transmitted infections'' requiring
broader screening and testing because they do not have sufficient
incidence or prevalence in the potential donor population. This
provision is designed to identify donors who may be at risk for
additional transfusion-transmitted infections. Because donors harboring
such infections may be asymptomatic, or the signs and symptoms may be
mild enough to go undetected at the time of donation, we would require
the collecting establishment to assess whether the donor has visited or
is a former resident of endemic areas known to harbor the disease agent
or disease, whether the risk of exposure is still applicable at the
time of donation, and, if so, determine the donor ineligible to donate.
Xenotransplantation product recipient and intimate contact
(Proposed Sec. 630.10(g)(5)).--The potential for infectious disease
transmission and public health risks associated with
xenotransplantation products has become an increasing concern. Because
xenotransplantation disrupts the recipient's usual protective physical
and immunologic barriers, receipt of a xenotransplantation product may
facilitate transmission of infectious agents to humans. Additionally,
transmission of such an infectious agent to an intimate contact of a
xenotransplantation product recipient may be possible. Therefore, a
xenotransplantation product recipient and an intimate contact of a
xenotransplantation product recipient would be determined to be
ineligible and deferred from donating.
Exposure to a released disease agent or disease (Proposed Sec.
630.10(g)(6)).--Recent events have made us aware that donors may be
affected by a released disease agent or disease. The release may occur
accidentally, such as in a laboratory accident, or intentionally, such
as in a bioterrorist attack. An example is the exposure in 2001 of
individuals to Bacillus anthracis through the U.S. mail. Proposed Sec.
630.10(g)(4) would require the collecting establishment to assess the
donor for exposure or possible exposure to a released disease agent or
disease with a potential for transmission by transfusion, when the
establishment becomes aware that such a release of a disease agent or
disease may have occurred in the community. The collecting
establishment would find donors ineligible when the disease agent or
disease may affect the health of the donor, or the safety, purity, or
potency of the blood and blood components.
Pregnancy (Proposed Sec. 630.10(g)(7)).--In order to prevent any
adverse effect on the donor or her fetus, collecting establishments
would determine a pregnant woman ineligible to donate. A woman who is
up to 6 weeks postpartum would also be determined ineligible so as not
to jeopardize her health by donating.
Unreliable answers (Proposed Sec. 630.10(g)(8)).--Section Sec.
640.63(d) requires plasma establishments to defer a Source Plasma donor
from donating if, in the opinion of the interviewer, the individual
appears to be under the influence of drugs or alcohol or does not
appear to be providing credible answers to medical history questions.
In proposed Sec. 630.10(g)(8), this requirement would apply to all
donors of blood and blood components as well as Source Plasma. The
establishment would assess the donor for impairment due to the
influence of drugs or alcohol, or for providing unreliable answers to
the medical history interview. One example of an unreliable answer is
when a donor states that he or she is donating for the purpose of
getting tested for a relevant transfusion-transmitted infection. Such
action would indicate that the donor has reason to believe there is a
possibility of infection due to participation in high-risk activities.
c. Physical assessment.
Sections 640.3(b) and 640.63(c) currently require collecting
establishments to determine that a donor is in good health on the day
of donation, indicated in part by a normal temperature, a blood
pressure within normal limits, and a hemoglobin level of no less than
12.5 grams per 100 milliliters (mL) of blood or no less than a
hematocrit value of 38 percent. We are moving these requirements to
proposed Sec. 630.10(h)(1) through (h)(6) as criteria for determining
that a donor is in good health to protect the health of the donor and
to ensure the safety, purity, and potency of the blood and blood
components.
Temperature (Proposed Sec. 630.10(h)(1)).--We would require the
collecting establishment to determine that the donor has a normal body
temperature. An elevated temperature could indicate a possible
infection. We are proposing that the maximum acceptable temperature not
exceed 37.5 [deg]C (99.5 [deg]F) when taken orally, or the equivalent
if the temperature is taken at an alternative body site. These
acceptable values are consistent with good medical judgment and current
industry practice. Collecting establishments determining body
temperatures using a device that measures body temperature other than
orally, such as by a probe placed in the ear, would list in their SOP
the maximum acceptable temperature adjusted according to the method
used.
Blood pressure (Proposed Sec. 630.10(h)(2)).--For the purpose of
this rulemaking, we would require under proposed paragraph (h)(2) that
the collecting establishment determine not to be eligible a donor whose
blood pressure measures above 180 mm of mercury or below 90 mm of
mercury for the systolic value, and above 100 mm of mercury or below 50
mm of mercury for the diastolic value. These limits are currently an
industry standard in use by many blood establishments. We are
soliciting comments with supporting
[[Page 63427]]
scientific data on the need for such limits on systolic and diastolic
values, on the limits we have proposed, and on adverse events
associated with donation that have been attributed to blood pressure.
In particular, we are seeking comments with supporting scientific data
on the necessity, or lack of necessity, of specific upper or lower
blood pressure limits in blood donation, and any adverse events
attributed to blood pressure and associated with donation. If the
record supports the need for different limits on systolic and diastolic
values, for example, a lower systolic limit of 90 mm of mercury and a
lower diastolic limit of 50 mm of mercury, we will make appropriate
changes in the final rule. We are also soliciting comments on whether
an abnormal blood pressure may be an indication that the donor has an
undetected illness, such as cardiovascular or renal disease, may not be
in good physical health and, therefore, may be harmed by the act of
donating.
We are also seeking comments on the accuracy and interpretation of
blood pressure measurements taken in the setting of blood and plasma
donation. Although the occluding cuff technique is simple and easy to
learn, errors can still be made. A single blood pressure measurement
taken at the time of donation may not represent the donor's true
baseline due to variations in the donor's blood pressure throughout the
day or under different situations. There are also many other causes of
error and inaccuracy in the measurement of blood pressure. There is no
uniform standard methodology for day-to-day use by all donor room
personnel (Ref. 2).
Both aneroid and electronic instruments have some advantages of
portability and ease of use, but few of these instruments have had
adequate validation. Still fewer of these instruments are calibrated
regularly and most of the instruments have not been validated over a
wide range of blood pressures and ages (Ref. 3). Therefore, an isolated
measurement of blood pressure may not reliably assess eligibility for
blood donation.
Hemoglobin or hematocrit determination (Proposed Sec.
630.10(h)(3)).--The current regulations in Sec. 640.3(b)(3) require
that an allogeneic donor have a minimum hemoglobin level of 12.5 grams
per deciliter of blood or a hematocrit value of 38 percent to
participate in a collection program; and that an autologous donor have
a minimum hemoglobin level of 11.0 grams per deciliter of blood or a
hematocrit value of 33 percent. In proposed Sec. 630.10(h)(3), we are
proposing to continue requiring these minimal hemoglobin levels or
hematocrit values for allogeneic donors, including Source Plasma
donors, and autologous donors. The collecting establishment would be
permitted to obtain the blood sample by fingerstick or venipuncture or
by another method providing equivalent results. However, the earlobe
would not be an acceptable site for the collection of a blood sample to
measure the hemoglobin level or hematocrit value. We propose this
restriction based on evidence that a blood sample collected from the
earlobe does not accurately reflect the donor's true venous hemoglobin
level or hematocrit value (Ref. 4).
We are specifically soliciting comments and supporting data on the
following:
Changing the minimum acceptable hemoglobin level to 12.0
grams per deciliter of blood or a hematocrit value of 36 percent as
acceptable minimal values for female allogeneic donors;
The possibility of adverse effects caused by the
collection of blood and blood components from allogeneic donors with
such minimum hemoglobin level of 12.5 grams per deciliter of blood or a
hematocrit value of 38 percent for males, and hemoglobin level of 12.0
grams per deciliter of blood or a hematocrit value of 36 percent for
females, which are considered below normal by medical criteria; or if
such decisions should be left to the discretion of the medical director
of the collecting establishment on a case-by-case basis;
Establishing a more stringent inter-donation interval; and
The use of copper sulfate solution based methods as an
appropriate method to determine acceptable hemoglobin levels.
Pulse (Proposed Sec. 630.10(h)(4).--We would require the
collecting establishment to take the donor's pulse rate, which is an
indicator of the donor's cardiovascular health. We would consider as
acceptable a regular pulse rate and any value between 50 and 100 beats
per minute. Any irregular pulse, or any value below 50 beats per minute
or above 100 beats per minute would be cause to determine the donor
ineligible to donate, unless the responsible physician examines the
donor and determines that the health of the donor would not be
adversely affected.
Weight (Proposed Sec. 630.10(h)(5)).--Proposed Sec.
630.10(h)(5). This paragraph would require that a donor weigh a minimum
of 50 kilograms (110 pounds) and not have any unexplained loss of
greater than 10 percent of body weight within the past 6 months. Except
as stated in proposed Sec. 630.15(b)(2) for donors of Source Plasma,
the proposed regulation would not require collecting establishments to
physically weigh individuals at each donation, but Sec.
606.160(b)(1)(i) would require the collecting establishments to retain
documentation of the donor's responses when asked if the donor weighs
more than 110 pounds, and if the donor experienced an unexplained loss
of greater than 10 percent of body weight within the past 6 months,
which may be a sign or symptom of a relevant transfusion-transmitted
infection.
We recognize that some collecting establishments believe it
acceptable and safe to collect a reduced volume of blood and blood
components from a donor weighing less that 110 pounds. We are
requesting comments and supporting scientific data regarding both the
volume of blood that can be safely collected from a donor in relation
to the donor's body mass, and the criteria to define a standard unit of
blood. We are also seeking comments on the feasibility and impact of
determining that a donor has experienced a significant recent and
unexplained loss of weight, and, if so, whether an unexplained loss of
10 percent of the donor's weight is an appropriate marker of possible
underlying illness, and whether loss of weight in the 6 month time
period prior to donation is an appropriate time frame to indicate that
such weight loss is an appropriate marker for such potential illness.
Collecting establishments routinely weigh donors of Source Plasma
so that they may apply the nomograms for volume limits as recommended
in the Memorandum to All Licensed Source Plasma Establishments issued
November 4, 1992, entitled ``Volume Limits for Automated Collection of
Source Plasma.'' Under proposed Sec. 630.15(b)(2), we would require
collecting establishments to weigh a donor of Source Plasma at each
donation. For donors of Source Plasma, records of donor weight should
be examined for unexplained weight loss at the time of the donor's
annual medical examination. (See also section III.I.2.b of this
document.)
Skin examination (Proposed Sec. 630.10(h)(6)).--We would require
that the collecting establishment examine: (1) The phlebotomy site for
evidence of infection, inflammation, lesions, or pitted skin (to
eliminate contaminating the donation and possibly putting the recipient
at risk for sepsis) and (2) the donor's arms and forearms for punctures
and scars indicative of injected drugs of abuse. Use of injected drugs
not prescribed for medical reasons (drug
[[Page 63428]]
abuse), regardless of the site of injection, would place the donor at
increased risk for exposure to a relevant transfusion-transmitted
infection.
3. Additional Requirements for Determining Donor Eligibility
Proof of identity and mailing address (Proposed Sec.
630.10(i)(1)).--Proposed Sec. 630.10(i)(1) would require the
collecting establishment to obtain, before donation, donor
identification, such as a photograph identification and an address as
required under Sec. 606.160(b)(1)(x). Collecting establishments are
required under Sec. 630.6 (proposed redesignation to Sec. 630.40) to
notify donors that they are deferred from further donation based on the
results of tests for evidence of infection with a communicable disease
agent(s). Having a current address will assist the collecting
establishment in the notification process when necessary.
Donor's written statement of understanding (Proposed Sec.
630.10(i)(2)).--In order to ensure that the donor has been informed of
and understands the collection procedure and the educational material,
the collecting establishments would be required to provide a written
statement to the donor, using appropriate language and literacy level
and taking into account any donor disabilities, to read and sign before
phlebotomy is performed. This statement would be written in a clear and
understandable terminology and not include language that would waive
any of the donor's legal rights. The document would provide the
following information as described in proposed Sec. 630.10(i)(2)(i)
through (i)(2)(vii):
The donor reviewed the provided educational material
regarding the relevant transfusion-transmitted infections, including
HIV, HBV, and HCV, and understands that such infections present
potential risks to the safety of the blood supply;
The donor agrees not to donate if the donation could
result in a potential risk to the safety of the blood supply as
described by the educational material;
The donor understands that, a sample of the donor's blood
taken at the time of phlebotomy will be tested for specified relevant
transfusion-transmitted infections;
The donor understands that, if any of the tests for the
relevant transfusion-transmitted infections required under Sec.
610.40(a) are reactive, the blood sample will be tested further as
necessary and appropriate to determine the donor's infection status;
The donor understands that, if a basis for deferral is
discovered, the donor will be deferred from further donation
temporarily, indefinitely, or permanently, and notified of the basis of
the deferral;
The donor understands the hazards and risks of the
procedure; and
The donor has the opportunity to ask questions and refuse
to donate at any time.
The collecting establishment must not proceed with the
phlebotomy until the donor signs the statement.
We also note that some blood components may be stored
indefinitely before they are used. During that time, we may become
aware of new infectious agents, which may be identified only through
the use of investigational tests. An establishment may want to test
stored blood components using the investigational test, but face
obstacles due to the lack of donor consent to the use of an
investigational test. An establishment may seek to address this
problem, in advance, by obtaining adequate informed consent to
investigational tests at the time of donation. We note that consent to
authorize investigational testing subject to investigational new drug
or investigational device exemption requirements must meet the
requirements of 21 CFR part 50.
I. Donor Eligibility Requirements Specific to Whole Blood and Plasma
Collected by Plasmapheresis (Proposed Sec. 630.15)
The donor eligibility requirements under proposed Sec. 630.10
would apply to all donors of Whole Blood and blood components,
including Plasma collected by plasmapheresis. In addition to these
proposed requirements, other requirements specific to Whole Blood or
Plasma collected by plasmapheresis are proposed in Sec. 630.15.
1. Whole Blood
The following two sections are specific to Whole Blood donation.
a. Donation frequency.
With the establishment of double Red Blood Cells unit collection
programs by some establishments, we are proposing to adjust the
donation frequency requirements currently in Sec. 640.3(f). Proposed
Sec. 630.15(a)(1) would continue the requirement in Sec. 640.3(b)
that collecting establishments collect a single unit of Whole Blood
from a donor no more than once in 8 weeks. We also are proposing that
if a donor is participating in a double Red Blood Cells unit collection
program, i.e., where two units of Red Blood Cells are collected by an
automated blood cell separator on the same occasion, then the
collecting establishment would be required to defer the donor for 16
weeks before allowing the donor to participate in a Whole Blood
collection program, in any apheresis program, or in a double Red Blood
Cells unit collection program again. This is currently recommended in
the January 2001 guidance entitled ``Guidance for Industry:
Recommendations for Collecting Red Blood Cells by Automated Apheresis
Methods.'' This proposed requirement protects the donor's health. We
also are proposing that a donor may donate sooner than the proposed
required time period if the collecting establishment's responsible
physician examines the donor and certifies the donor to be in good
health and one of the following three conditions exist:
The donor presents a physician's prescription for a
therapeutic phlebotomy; or
The donation is an autologous donation; or
The donation is dedicated to a specific recipient based on
documented medical need.
The responsible physician would explain to the donor in the written
statement of understanding (proposed Sec. 630.10(i)(2)(vi)) the
hazards or risks from more frequent donations.
b. Therapeutic phlebotomy.
Currently, under Sec. 640.3(d), we require that blood drawn to
promote the health of the donor not be used as a source of Whole Blood
unless the container label conspicuously indicates the donor's disease
that necessitated the phlebotomy. Under the new proposed Sec.
630.15(a)(2), we would continue to require that the container label
state the donor's disease that necessitated the phlebotomy, but would
permit an exception to this provision. In August 2001, we issued
``Guidance for Industry: Variances for Blood Collection from
Individuals with Hereditary Hemochromatosis,'' which provides guidance
for requesting a variance from the labeling requirement for individuals
with hereditary hemochromatosis (HH). This proposed rule would codify
those recommendations, eliminate the need for a variance request, and
permit all collecting establishments to use a donation from an
individual with HH as a source of Whole Blood and not affix a disease
label for HH, if the following conditions are met:
The donor with HH otherwise meets the same eligibility
requirements under proposed Sec. 630.10 as for other allogeneic donors
whose blood would be used for transfusion or further manufacturing use;
and
The collecting establishment does not charge a fee for any
phlebotomies performed on individuals with HH,
[[Page 63429]]
including those who do not meet the eligibility requirements proposed
under Sec. 630.10. As explained in the August 2001 guidance, if a
blood establishment charged a fee for therapeutic phlebotomy, but not
for a collection of blood for transfusion, the HH donor would have an
incentive to deny risk conditions that might preclude cost-free
donation. Accordingly, this provision removes that incentive. Blood and
blood components collected from persons undergoing therapeutic
phlebotomies who are ineligible to donate would be discarded unless
other arrangements are in place to permit the practice, such as license
amendments, requests for variance, or short supply agreements (for
example, if certain rare antibodies are present, or for manufacture
into an in vitro reagent) (Sec. Sec. 601.12, 610.40(h)(2) and Sec.
640.120).
2. Plasma Collected by Plasmapheresis
a. Examination by a responsible physician.
In addition to the eligibility requirements proposed in Sec.
630.10, proposed Sec. 630.15(b)(1) would require the responsible
physician to examine the donor initially and annually for medical
conditions that would place the donor at risk during the process of
plasmapheresis and explain the hazards of the procedure so that the
donor may choose not to donate. The initial examination would occur no
more than 1 week before the first donation. In addition, under proposed
Sec. 630.15(b)(4), if the donor is participating in an immunization
program for the collection of high-titer plasma, then the examination
must occur no more than 1 week before the first immunization injection.
It is not necessary to repeat the physical examination if the immunized
donor's plasma is collected within 3 weeks of the first immunization
injection. These provisions are currently required under Sec.
640.63(b)(1), (b)(2)(i), and (b)(2)(ii).
b. Weight.
In proposed Sec. 630.15(b)(2), we would require that
establishments determine a donor's weight at each donation. This
information allows you to determine the appropriate amount of plasma
that can be safely removed. We note that, although unexplained weight
loss can be a sign or symptom of a relevant transfusion-transmitted
infection, the proposed rule does not require establishments to measure
donor weight at the time of apheresis as an indicator of underlying
disease. FDA is soliciting comments with supporting data on the
usefulness of measuring weight loss at the time of donation by
apheresis as an indicator to identify health problems in the donor.
c. Total protein.
Under existing Sec. 640.63(c), we require collecting
establishments to test the donor's blood sample for total protein on
the day of and before plasmapheresis. We would continue to require
under proposed Sec. 630.15(b)(3) that collecting establishments test
the donor's sample for a total plasma or serum protein and have a value
of no less than 6.0 grams per deciliter or no more than 9.0 grams per
deciliter, the minimum and maximum normal values, for the donor to
donate. If the value is less than 6.0 grams per deciliter or more than
9.0 grams per deciliter, the collecting establishment would be required
to defer the donor until the donor's total protein level is at an
acceptable value.
d. Deferral due to red blood cell loss.
Under proposed Sec. 630.15(b)(5), in order to protect the donor's
health, we would require the collecting establishment to defer a donor
from donating plasma for 8 weeks after one of the following events:
The donor experienced a red blood cell loss of 200 mL or
more of red blood cells during a single automated or manual
plasmapheresis procedure; or
The donor experienced an unexpected red blood cell loss of
any volume in an automated apheresis procedure on two occasions within
the last 8 week period;
The donor experienced a red blood cell loss equivalent to
or greater than 200 mL of red blood cells as a result of failure to
return red blood cells during a manual plasmapheresis procedure; or
The donor donated a unit of Whole Blood.
However, if a donor participates at any time in a double Red Blood
Cells unit collection program, then the collecting establishment would
be required to defer the donor for 16 weeks after the last double red
blood cell donation under proposed Sec. 630.15(a)(1).
Under proposed Sec. 630.15(b)(6), we would allow exceptions to the
deferral for red blood cell loss if all of the following criteria are
met.
The donor is examined at the time of donation and
certified by the responsible physician to be in good health and the
donor's health permits the plasmapheresis; and
The donor possesses an antibody that is transitory, of a
highly unusual or infrequent specificity, or of an unusually high
titer; and
The collecting establishment documents the special
characteristics of the antibody and the need for plasmapheresis under
proposed Sec. 630.20(c)(2).
e. Exception to the donor eligibility requirements for Plasma
collected by plasmapheresis.
Under Sec. 640.63(c)(9), a Source Plasma donor must be free from
any disease transmissible by blood transfusion, other than malaria,
insofar as the disease can be identified by history and examinations.
In ``Memorandum to Registered Blood Establishments--Recommendations for
Deferral of Donors for Malaria Risk'' issued in July 1994, and a draft
guidance issued for public comment in June 2000, entitled ``Guidance
for Industry: Recommendations for Donor Questioning Regarding Possible
Exposure to Malaria,'' we make recommendations for assessing donors for
malaria risk. These apply only to donations containing intact red blood
cells or platelets, where the protozoa are found. Donors of Source
Plasma collected by plasmapheresis are excluded from the malaria risk
assessment since plasma does not contain intact red blood cells, which
harbor the infectious agent. Moreover, Source Plasma undergoes further
manufacturing to remove or inactivate pathogens. We maintain this
exception in proposed Sec. 630.15(b)(7). However, we are interested in
receiving comments with supporting data on the following: (1) Whether
Fresh Frozen Plasma collected by plasmapheresis can be safely
manufactured from donors with risk of malaria and (2) whether this
exception should be expanded to apply to other parasitic diseases.
J. General Exceptions from the Donor Eligibility Requirements (Proposed
Sec. 630.20)
Proposed Sec. 630.20 would permit, under certain circumstances and
under the supervision of the responsible physician, the collection of
blood and blood components from individuals who do not meet one or more
of the eligibility requirements proposed in Sec. Sec. 630.10(d),
630.15, and 610.41. We would require that the responsible physician
examine the donor and certify that the donor's health permits the
collection procedure, and that the collection be performed under the
supervision of the responsible physician, who is aware of the donor's
health status. We would only allow this exception in the following
situations.
The donation is for autologous use as prescribed by the
donor's physician and is not intended for allogeneic transfusion or for
further manufacturing use; or
[[Page 63430]]
The donor is participating in a plasmapheresis program
that collects plasma for further manufacturing use into products for
which there are no alternative sources, and the program has received
prior approval from the Director, Center for Biologics Evaluation and
Research, consistent with Sec. 606.110. For example, the donor may
serve as a source of antibody to hepatitis B surface antigen for the
preparation of Hepatitis B Immune Globulin (Human) or as a component of
a medical device. Other examples are discussed in the ``Guideline for
Collection of Blood or Blood Products from Donors with Positive Tests
for Infectious Disease Markers (High Risk Donors),'' dated September
1989; or
The donation is for the sole use of a specified recipient
based on documented medical need, and the responsible physician
determines that the donation presents no undue medical risk to the
recipient. The donation must test negative in all tests required under
Sec. 610.40, unless an exception in Sec. 610.40(h)(2) applies.
However, for deferrals under Sec. 610.41, we are soliciting comments
on permitting, in the case of documented medical need, the use of
donations testing reactive for antibody to hepatitis B core antigen.
For example, we are considering whether, when the recipient has a rare
red blood cell antibody and the donor is lacking the red blood cell
antigen for the antibody, to permit the use of a donation that is
reactive when tested for hepatitis B core antibody by a screening test.
K. Exceptions from Certain Donor Eligibility Requirements for
Infrequent Plasmapheresis (Proposed Sec. 630.25)
Under proposed Sec. 630.25, we intend to reduce the medical
examination and laboratory testing burden on collecting establishments
when donors are participating in plasma collection programs at
intervals of 4 weeks or more. Consistent with existing guidance in
memoranda issued March 10, 1995, entitled ``Memorandum to Registered
Blood and Source Plasma Establishments, Revision of FDA Memorandum of
August 27, 1982: Requirements for Infrequent Plasmapheresis Donors''
and November 4, 1992, entitled ``Volume Limits for Automated Collection
of Source Plasma,'' we would except the collecting establishment from
the requirements for frequency of examination in proposed Sec.
630.15(b)(1) and (b)(3), and current Sec. 640.65(b)(1) and (b)(2), if
the following occurs:
The donor has not donated Whole Blood in the preceding 8
weeks or plasma by apheresis in the preceding 4 weeks, or participated
in a double Red Blood Cells unit collection program within the
preceding 16 weeks;
The donor has not donated more than 12.0 liters of plasma
in the past year (14.4 liters of plasma for donors weighing more than
175 lbs.);
The donor is determined by the responsible physician to be
in good health under proposed Sec. 630.10(d); and
The donor is not participating in an immunization program
for the production of high-titer plasma.
L. Donation Suitability Requirements (Proposed Sec. 630.30)
The collecting establishment would determine a donation as suitable
when the following occurs:
The donor is not currently deferred from donation;
The results of the medical history and physical
examination indicate that the donor is in good health and donating
would not adversely affect the health of the donor;
The donor is free from risk factors for, or evidence of,
transfusion-transmitted infections;
The donor's tests for relevant transfusion-transmitted
infections are negative or nonreactive;
For platelet components, the test for bacterial contamination is
negative; and
The donor or donation meets other requirements in 21 CFR subchapter
F.
When one or more of the criteria in proposed Sec. 630.30 for
determining a donation as suitable are not met, the collecting
establishment would determine that the donation is not suitable, would
defer the donor until the basis of deferral is resolved, and must
notify the donor of the reason for the deferral under Sec. 630.6
(redesignated as Sec. 630.40 in this proposed rule). Under Sec.
610.40(h), the collecting establishment must not ship or use donations
that test reactive for tests required under Sec. 610.40(a) and (i),
unless one of the limited exceptions apply. Under proposed Sec.
606.160(e)(2), we also would require that the collecting establishment
provide to appropriate personnel of the establishment a list of those
donors who are not eligible to donate under proposed Sec. 630.10(f)(1)
through (f)(6) and (g)(1) through (g)(6).
M. Requalification of Previously Deferred Donors (Proposed Sec.
630.35)
We would permit the requalification of a previously deferred donor
into the donor pool (commonly referred to as donor re-entry) under
proposed Sec. 630.35. If a donor had been deferred from donation
because the donor did not meet the requirements in part 630, then the
otherwise eligible donor may be determined to be eligible to donate if
the basis for the previous deferral is no longer applicable. To
requalify a donor deferred under Sec. 610.41(a), because the donor
tested reactive by a screening test for evidence of infection due to a
relevant transfusion-transmitted infection, the collecting
establishment would determine the donor to be eligible for donation by
a requalification method found acceptable for such purpose by FDA under
Sec. 610.41(b). For example, FDA issued draft guidance on a
requalification method or process for reentry of donors deferred
because of a reactive screening test for HIV or HCV entitled ``Guidance
for Industry: Nucleic Acid Testing (NAT) for Human Immunodeficiency
Virus Type 1 (HIV-1) and Hepatitis C Virus (HCV): Testing, Product
Disposition, and Donor Deferral and Reentry,'' dated July 2005. Donor
screening tests may yield a number of false positive test results. For
a donor deferred under such a test, an establishment could retest the
donor, following the recommendations for donor re-entry in the
guidance, when finalized. If results of the retesting meet the reentry
criteria found acceptable for such purposes by FDA, the donor would be
requalified under Sec. 610.41(b) and no longer would be deferred. Of
course, the donor would be required to meet the eligibility criteria at
each subsequent donation.
N. Requirements for Notifying Deferred Donors (Proposed Newly
Redesignated Sec. 630.40)
On June 11, 2001, we published a final rule entitled ``General
Requirements for Blood, Blood Components, and Blood Derivatives; Donor
Notification'' (June 2001 final rule) in the Federal Register (66 FR
31165), codified at Sec. 630.6. The June 2001 final rule requires
blood and plasma establishments to notify donors, including autologous
donors, whenever the donors are deferred or determined not to be
eligible for current or future donations of blood and blood components.
Blood and plasma establishments also are required to notify the
referring physician for an autologous donor when the autologous donor
is deferred based on the results of tests for evidence of infection due
to communicable disease agent(s). This proposed rule would amend part
630, redesignate current Sec. 630.6 as Sec. 630.40, and revise all
references to Sec. 630.6 accordingly. We also are proposing to revise
all references to donor eligibility by replacing Sec. Sec. 640.3 and
640.63 with Sec. Sec. 630.10 and 630.15. Consistent with proposed
Sec. 630.30(b)(4), proposed
[[Page 63431]]
newly redesignated Sec. 630.40(a) would require a collecting
establishment to notify a donor whose platelet component tests positive
for an endogenous bacteremia.
O. Eligibility Requirements Specific for Platelet Donors (Proposed
Sec. 640.21)
We are proposing to amend Sec. 640.21 by revising the subject
heading and paragraphs (a) through (c), and by adding paragraphs (d)
and (e) for consistency with other parts of this rulemaking.
In addition to meeting the proposed requirements in Sec. Sec.
630.10 and 630.15, under proposed Sec. 640.21(a)(2), the donor's
written statement of understanding in proposed Sec. 630.10(i)(2)(vi)
would require a statement that the long-term effects of frequent
apheresis are unknown.
Proposed Sec. 640.21(b) for plateletpheresis donors, would require
that a donor not serve as a source of platelets for transfusion after
the donor has ingested drugs that adversely affect platelet function.
At a BPAC meeting held in March 2006, we discussed the deferral of
donors who had recently ingested aspirin or nonsteroidal anti-
inflammatory drugs (NSAIDs). BPAC provided advice on deferral periods
for ingestion of these products. Based on the information received at
this meeting, we intend to issue for public comment a draft guidance on
deferrals for ingestion of drugs that adversely affect platelet
function. The draft guidance document, when finalized, will assist
blood collecting establishments in appropriately deferring donors as a
result of ingestion of aspirin, NSAIDs, and other drugs that may
adversely impact platelet function.
We would permit, under proposed Sec. 640.21(c), plateletpheresis
donations at intervals shorter than 8 weeks provided:
The collecting establishment performs a platelet count
before the initial procedure and before each subsequent procedure; and
The pre-donation count is greater than 150,000/microL; and
the donor's post-donation count is no less than 100,000/microL; and
The donor undergoes no more than a total of 24
plateletpheresis collections within 12 months (e.g., either 24 single,
double, or triple platelet component collection procedures);
For single component collection procedures, there are no
more than 2 plateletpheresis procedures within 7 calendar days; and
there is a minimum of 2 calendar days between procedures;
For double or triple component collection procedures,
there is no more than one plateletpheresis procedure within 7 calendar
days.
At the BPAC meeting held in March 2006, we also discussed the
frequency of platelet collection and the impact on the donor's safety.
Blood establishments commented by providing data on the safety of
collecting more than 24 platelet components per year, including 24
triple platelet component collection procedures per year. BPAC advised
that the data supported continuation of up to 24 platelet collections
of triple components per year. The BPAC also recommended that the
donor's post-donation targeted platelet count not fall below 100,000/
microL.
Under proposed Sec. 640.21(d), we would permit a donor to serve as
a dedicated plateletpheresis donor as often as necessary during a 30-
day period if the donor is in good health and the donor's platelet
count is greater than 150,000/microL. The collecting establishment must
follow the requirements in Sec. 610.40(c)(1) for testing and labeling
for dedicated donors.
Under proposed Sec. 640.21(e), if, over an 8-week period, a donor
cumulatively loses 450 mL or more of whole blood or 200 mL or more of
red blood cells, or donates a unit of Whole Blood, the collecting
establishment must defer the donor for 8 weeks; or, if the donor
participates in a double Red Blood Cells unit collection program, the
collecting establishment must defer the donor for 16 weeks. An
exception to this proposed requirement would be permitted when:
The donor waits 2 calendar days for plateletpheresis after
donating Whole Blood or sustaining a blood loss and
The extracorporeal red blood cell volume during the
plateletpheresis procedure is 100 mL or less.
P. Eligibility Requirements Specific for Source Plasma Donors (Proposed
Sec. Sec. 640.65(b) and 640.69)
In addition to proposed technical amendments to Sec.
640.65(b)(1)(i) and (b)(2)(i), proposed Sec. 640.65(b)(2)(i) would add
an upper value of 9.0 grams per deciliter of plasma sample for
acceptable total protein and a comparable level for a serum sample and
would require the responsible physician to review the laboratory data,
the calculated values of each component, and the collection records
within 14 calendar days after the sample is drawn to determine if the
donor should be deferred from further donation. If the review is not
completed within 14 calendar days, we would require the collecting
establishment to defer the donor pending the review. We have reduced
the time period for record review from 21 to 14 calendar days because
results are typically transmitted and recorded electronically,
permitting faster access.
We are proposing to add to Sec. 640.69 paragraphs (e) and (f).
Proposed Sec. 640.69(e) would require collecting establishments to
ensure that Source Plasma donated by paid donors not be used for
further manufacturing into injectable products unless the paid donor
has a record of two suitable donations within the last 6 months at the
plasma establishment where the donations occurred. Proposed paragraph
Sec. 640.69(f) would require collecting establishments to ensure that
Source Plasma donated by paid donors determined to be suitable for
further manufacturing into injectable products be held in quarantine
for a minimum of 60 days to permit the retrieval of a Source Plasma
donation in the event it is later determined to be unsuitable. Any
Source Plasma shipped prior to 60 days after the date of collection
must be labeled to indicate that the Source Plasma is in quarantine.
These proposed requirements would support product safety. In a report
entitled ``Blood Plasma Safety: Plasma Product Risks Are Low if Good
Manufacturing Practices Are Followed'' (September 9, 1998), the GAO
identified certain voluntary industry initiatives as greatly reducing
the chances of reactive units being used in manufacturing pools. These
voluntary initiatives included the use of repeat donors only and a 60-
day inventory hold on all units to allow manufacturers to retrieve
units from donors who subsequently test positive or are otherwise
deferred. We are proposing to require these practices in the proposed
rulemaking. However, we are soliciting comments and supporting data on
whether other requirements would achieve the same goal. We are also
soliciting comments on whether these provisions should also apply to
Source Plasma from paid donors collected for manufacture into non-
injectable products.
Q. Reporting of Donor Reactions (Proposed Sec. 640.73)
Section 640.73 requires establishments collecting Source Plasma to
report to us any donor fatality associated with plasmapheresis. We are
proposing to retain this requirement in proposed Sec. 640.73(a) and to
add Sec. 640.73(b), which would require establishments collecting
Source Plasma to report to us any donor adverse experience as described
in Sec. 600.80(a) related to the administration of an immunizing
agent, such as red blood cells or a vaccine.
[[Page 63432]]
If the adverse experience is serious or life threatening as
described in Sec. 600.80(a), then we would require the establishment
to report to us as soon as possible by telephone or other rapid means
of communication, and submit a written followup report of the
investigation within 7 days of learning of the donor's adverse
experience; if the adverse experience is neither serious nor life
threatening, the establishment would submit the report in an annual
report on the anniversary of FDA's approval of the immunization
program.
Because manufacturers of blood and blood components are currently
exempt from the safety reporting requirements under Sec. 600.80, we do
not receive adequate information to monitor and assess safety-related
information (other than fatalities) concerning donors enrolled in
immunization programs and the collection of Source Plasma by
plasmapheresis. Such information is essential for evaluating our
scientific and regulatory policies and for monitoring industry
practices and their implications on donor and blood safety.
R. Alternative Procedures (Proposed Sec. 640.120)
We are proposing an amendment which would separate and revise Sec.
640.120(a) into proposed paragraphs (a) and (b), and revise and
redesignate current paragraph (b) as paragraph (c).
Under proposed Sec. 640.120(a), a manufacturer could initiate
agency review of a proposed alternative procedure. The manufacturer
would submit the request either as a written request, which would
include a facsimile or e-mail, or as an oral request. This is
consistent with Sec. 640.120. We are adding proposed paragraph (b) to
permit the Director of the Center for Biologics Evaluation and Research
to issue an exception or alternative to the regulations in the event of
a public health emergency. This procedure would be initiated only when
a variance is necessary to assure the availability of blood, blood
components, and blood products, in a specific location and in response
to an unanticipated immediate need for blood, blood components, and
blood products, as in situations involving large numbers of casualties.
Proposed Sec. 640.120(c) states that FDA periodically would list
approved alternative procedures and exceptions on the Center for
Biologics Evaluation and Research home page on the Internet.
S. Reagent Red Blood Cells (Proposed Sec. 660.31)
In Sec. 660.31, we are proposing to remove ``Sec. 640.3'' and
``except in paragraphs (b)(5) and (b)(6), (d), and (e) of Sec.
640.3,'' and add in its place ``Sec. 630.10 and 630.15.'' This
proposed revision would require donor eligibility determination
requirements for donations intended as a source material or component
of a medical device, including Reagent Red Blood Cells. We would
eliminate the current exceptions to be consistent with the
applicability of donor eligibility determination requirements for blood
and blood components collected for use in the manufacture of other in
vitro diagnostic products. We are interested in receiving comments on
limiting donor eligibility determination requirements to donations
collected in the United States for use in the manufacture of Reagent
Red Blood Cells.
T. Quality Systems Regulations (Proposed Sec. 820.1(a)(1))
In part 820, we have issued current good manufacturing practice
(CGMP) requirements applicable to manufacturers of all finished devices
intended for human use. Section 820.1(a)(1) states that manufacturers
of blood and blood components are not subject to part 820, but are
subject to part 606. We are proposing in this rule to clarify the
applicability of the requirements in 21 CFR Chapter I, subchapter F to
donors of human blood or blood components used in the manufacture of a
medical device as well as for transfusion.
U. Technical Amendments
We also propose technical changes to existing regulations, for
consistency with this proposed rulemaking. We propose to remove
Sec. Sec. 640.3, 640.61, 640.62, and 640.63. We propose to revise
Sec. 606.3(a) and (c), and 1270.3(b) for consistency with proposed
Sec. 630.3(a) and (b). We propose to revise Sec. Sec. 606.100(b)(20),
606.110(b), 606.160(b)(1)(ix) and (b)(1)(xi), 640.4, 640.12, 640.22,
640.31, 640.32, 640.51, 640.52, 640.65(b), and 640.72(a)(2), (a)(3),
and (a)(4) by changing headings or references to CFR cites, and
redesignating paragraphs.
IV. Proposed Effective Date
We propose that any final rule that may issue based on this
proposal become effective 180 days after the date of its publication in
the Federal Register.
V. Analysis of Impacts
FDA has examined the impacts of the proposed rule under Executive
Order 12866, the Regulatory Flexibility Act (5 U.S.C. 601-612), and the
Unfunded Mandates Reform Act of 1995 (Public Law 104-4). Executive
Order 12866 directs agencies to assess all costs and benefits of
available regulatory alternatives and, when regulation is necessary, to
select regulatory approaches that maximize net benefits (including
potential economic, environmental, public health and safety, and other
advantages; distributive impacts; and equity). The agency believes that
this proposed rule is not a significant regulatory action as defined by
the Executive order.
The Regulatory Flexibility Act requires agencies to analyze
regulatory options that would minimize any significant impact of a rule
on small entities. Because this proposed rule incorporates industry's
usual and customary business practices, the agency certifies that the
proposed rule will not have a significant economic impact on a
substantial number of small entities.
Section 202(a) of the Unfunded Mandates Reform Act of 1995 requires
that agencies prepare a written statement, which includes an assessment
of anticipated costs and benefits, before proposing ``any rule that
includes any Federal mandate that may result in the expenditure by
State, local, and tribal governments, in the aggregate, or by the
private sector, of $100,000,000 or more (adjusted annually for
inflation) in any one year.'' The current threshold after adjustment
for inflation is $122 million, using the most current (2005) Implicit
Price Deflator for the Gross Domestic Product. FDA does not expect this
proposed rule to result in any 1-year expenditure that would meet or
exceed this amount.
A. Objectives and Basis of the Action
As discussed previously, we are proposing this action to help
protect donor health and to help ensure the safety, purity, and potency
of the national blood supply. The safety, purity, and potency of the
national blood supply is enhanced when blood donors are assessed for
eligibility and blood donations are assessed for suitability. The
health of the donor is protected through certain physical assessments,
such as those regarding blood pressure and hemoglobin levels.
This action is taken under the authority of sections 351 and 361 of
the PHS Act to prevent the introduction, transmission, and spread of
communicable disease. Since blood and blood components are also drugs
and devices, the provisions of the act (21 U.S.C. et seq.) also
generally apply. In particular, section 501 of the act provides
authority to ensure that methods used in manufacturing conform with
CGMP. See section II.A of
[[Page 63433]]
this document for further details. We have reviewed related Federal
rules and have not identified any rules that duplicate, overlap, or
conflict with the rule.
B. Nature of the Impact
The proposed rule requires that for each donation of blood or blood
component, blood establishments maintain minimum standards for donor
eligibility (proposed Sec. Sec. 630.10 and 630.15), and blood and
blood component suitability (proposed Sec. 630.30). A blood
establishment must also establish, maintain, and follow SOPs for the
determination of donor eligibility (proposed Sec. 606.100(b)).
C. Type and Number of Entities Affected
This proposed rule would affect all blood establishments that
collect blood and blood components, including Source Plasma and Source
Leukocytes. Our registration database for blood and plasma
establishments has records of approximately 1,709 establishments: 81
licensed Source Plasma establishments with multiple locations and 1,628
registered blood establishments. The DHHS estimates that approximately
15 million blood donations are collected annually (Ref. 5). According
to a 2002 report by the Government Accountability Office (at that time,
the General Accounting Office), 13 million donations of Source Plasma
are collected annually by plasma centers (Ref. 6).
D. Estimated Impact of Requirements for Assessment of Donor Eligibility
The rule provides for the establishment of minimum criteria for the
assessment of donor eligibility, and the suitability of the donation of
blood and blood components. The rule is expected to have a minor net
impact on blood establishments because it is already usual and
customary business practice in the blood industry to assess donors for
eligibility, and donations for suitability. We believe the primary
impact of the rule will be the one-time review of current SOPs that the
proposed rule would require each blood collecting establishment to
conduct.
The burden imposed by this one-time effort to review and, if
necessary, modify current SOPs will vary among the 1,709
establishments, depending on an establishment's existing procedures.
For establishments that have already established procedures that
conform to the proposed rule, we estimate that it would take
approximately 40 hours of staff time to review the establishment's
current SOPs to confirm that the SOPs comply with the regulation. A
technical specialist who acts as a regulatory reviewer or manager of
quality assurance could perform this process. Based on the total
average hourly compensation (including benefits) of $37.03 for
management, professional and related occupations in private industry
healthcare and social assistance workers, as reported by the Bureau of
Labor Statistics, the cost would be approximately $1,481 ($37.03 per
hour x 40 hours) per establishment (Ref. 7).
For establishments that do not already conform to the proposed
rule, we estimate that approximately 60 hours of staff time would be
required to align current inadequate SOPs with the provisions of the
rule. As we believe most establishments have SOPs that are consistent
with the rule, the extent that staff would need to be notified of these
updated SOPs would not result in extensive formal training. The cost in
this case would be $2,222 ($37.03 x 60) per establishment. Assuming a
minimal review is needed at two-thirds of the 1,709 currently operating
establishments and a more extensive review is conducted by the other
one-third, the total one-time cost for the blood and plasma industries
is estimated to be $2,953,000 ((2/3 x 1,709) x $1,481)) + ((1/3 x
1,709) x $2,222)).
Our cost estimate assumes that the assessment of donors for
eligibility and donations for suitability are already usual and
customary business practices. We believe that most establishments
already conform to this proposed rule and others nearly conform to this
proposed rule and assume a two-thirds one-third division between the
two groups of establishments. Nevertheless, because we lack information
on the characteristics or fraction of establishments not currently in
compliance, we welcome comment on our assumption. Also, while we assume
the costs are limited to a review of SOPs, if these reviews were to
uncover deficiencies requiring complex operational changes, the impact
of this proposed rule could exceed our estimate. We request comment
from blood establishments on our assumption.
E. Expected Benefits of the Rule
This proposed rule would help ensure the continued safety of the
blood supply. As described in the preamble to this rule, the assessment
of eligibility of donors and the suitability of donations will help
prevent unsafe units of blood or blood components from entering the
blood supply. This will protect the health of donors and will preserve
the safety, purity, and potency of blood and blood components. The rule
is intended to increase the safety of all blood and blood components by
providing recipients with increased protection against communicable
disease transmission.
The gravity of the disease risks associated with blood and blood
components is widely recognized. Transfusion transmission of HIV, the
virus that causes AIDS, continues to cause great concern. Human T-
lymphotropic viruses types I and II were identified in the early 1980s.
Infection with these viruses is associated with tropical spastic
paraparesis, adult T-cell leukemia/ lymphoma, and some inflammatory
disorders (Ref. 8). These viruses are known to be transmitted by
transfusion.
HBV is a major cause of acute and chronic hepatitis, cirrhosis, and
hepatocellular carcinoma worldwide. The Centers for Disease Control and
Prevention (CDC) estimates that 1.25 million Americans are chronically
infected with HBV, 15 to 25 percent of whom will die of chronic liver
disease, and that there are an additional 60,000 new infections each
year (Ref. 9). Approximately 5,000 individuals in the United States die
each year from disease caused by HBV (Ref. 10). Prior to the
development of hepatitis screening tests, transfusion-related risks
were significant.
While recipients of blood products prior to 1992 are at risk for
infection with HCV, blood donor screening for HCV has reduced
transfusion-associated transmission to less than one in 1.6 million
transfused units of blood (Ref. 11). Persons currently at increased
risk for HCV infection include parenteral drug users and health care
workers with occupational exposure to blood. CDC estimates
approximately 26,000 new HCV infections occur annually in the United
States and that 4.1 million Americans have been infected with HCV (Ref.
12). Despite advances in treatment with interferon and ribavirin, HCV
infection remains a leading indication for liver transplant and up to
five percent of those infected will die from the consequences of long-
term infection (Ref. 10).
The requirement that, for each donation of blood or blood
component, blood establishments maintain standards for donor
eligibility and blood and blood component donation suitability
significantly reduces the public risk of exposure to the morbidity and
mortality risks associated with diseases such as HIV types 1 and 2,
HBV, HCV, HTLV types I and II, and syphilis. Such standards also reduce
the attendant costs of these diseases.
[[Page 63434]]
F. Small Entity Impact
The Regulatory Flexibility Act requires agencies to assess whether
a rule may have a significant economic impact on a substantial number
of small entities. This rule is not expected to have a significant
impact on a substantial number of such entities.
According to size standards established by the Small Business
Administration (SBA), a small blood or plasma establishment (NAICS code
621991, Blood and Organ Banks) has annual receipts of less than $9
million (Refs. 13 and 14). The number of blood and plasma collecting
establishments that qualify as small entities is uncertain, but is not
expected to be substantial. For such small entities, the cost of
performing a review of SOPs is expected to be no more than $2,222. We
believe a small independent establishment, not associated with a
hospital, might collect as few as 200 units per week. A small
processing fee for blood and blood components can be between $150 and
$300 per unit, depending on the component and the region of the
country. Assuming this small independent establishment collects a
processing fee for two blood components for every unit collected, and
the processing fee is at the lower end of the fee scale for blood
components, the annual revenues for such an establishment would be
$3.12 million (200 x 2 x 52 x $150). Even for the smallest
establishment, the cost of performing a review of SOPs would be less
than one tenth of one percent of revenues. For establishments
associated with hospitals or establishments with multiple locations, we
believe parent company revenues to be much greater than $2.22 million,
putting the impact of this rule at less than one tenth of one percent
of revenues for those firms, as well. We believe blood establishment
employees already have the skills required to perform the tasks
specified in the rule, and that the rule does not require
establishments to seek out employees with new expertise.
Although the proposed rule would impose some costs on small
entities involved in the collection of blood and blood components,
including Source Plasma and Source Leukocytes, we believe that the
proposed rule represents an effective means of protecting donor health
and helping to ensure the safety, purity, and potency of blood and
blood components. We considered, as a less burdensome alternative to
the proposed rule, continuing with the use of trade organization
standards by industry and FDA guidance. We found this approach would be
inadequate to assure uniform or consistent compliance and would
preclude our ability to effectively monitor the safety, purity, and
potency of blood and blood components, including Source Plasma and
Source Leukocytes. This proposed rule would enhance both public health
and public confidence in the safety and quality of blood and blood
components, while imposing only a minimum burden on the affected
industry.
VI. The Paperwork Reduction Act of 1995
This proposed rule contains information collection provisions that
are subject to review by OMB under the Paperwork Reduction Act of 1995
(the PRA) (44 U.S.C. 3501-3520). A description of these provisions is
given in the following paragraphs with an estimate of the annual
reporting and recordkeeping burden. Included in the estimate is the
time for reviewing the instructions, searching existing data sources,
gathering and maintaining the data needed, and completing and reviewing
each collection of information.
FDA invites comments on these topics: (1) Whether the proposed
collection of information is necessary for the proper performance of
FDA's functions, including whether the information will have practical
utility; (2) the accuracy of FDA's estimate of the burden of the
proposed collection of information, including the validity of the
methodology and assumptions used; (3) ways to enhance the quality,
utility, and clarity of the information to be collected; and (4) ways
to minimize the burden of the collection of information on respondents,
including through the use of automated collection techniques, when
appropriate, and other forms of information technology.
Title: Requirements for Human Blood and Blood Components Intended
for Transfusion or for Further Manufacturing Use
Description: FDA proposes to revise and update the regulations
applicable to blood and blood components, including Source Plasma and
Source Leukocytes, and to add donor eligibility requirements for
consistency with current practices in the blood industry. This proposed
rule's information collection provisions are for recordkeeping and
reporting.
Proposed Sec. 606.100(b)--Current Sec. 606.100(b) requires
collecting establishments to establish and maintain written SOPs for
all steps in the collection, processing, compatibility testing,
storage, and distribution of blood and blood components for transfusion
and for further manufacturing use. We are proposing to revise Sec.
606.100(b) by adding that the collecting establishment would not only
establish and maintain the SOPs, but also would follow the SOPs. We are
proposing to require establishments to establish, maintain, and follow
SOPs for investigating product deviations (Sec. 606.171), and for
recordkeeping related to CGMP (part 606) and biological product
standards (part 610), which would include all recordkeeping
requirements not listed in Sec. 606.100(b)(1) through (b)(20).
Proposed Sec. 606.160(e)--We are proposing to revise current Sec.
606.160(e). Paragraph (e) would require collecting establishments to
maintain a list identifying ineligible donors (otherwise known as a
deferral list or donor deferral registry) and to provide this list to
appropriate personnel to prevent the collection of blood and blood
components from such individuals.
Proposed Sec. 630.10(b)--We are proposing to require that
collecting establishments provide to the donor educational material
containing useful and current information concerning the relevant
transfusion-transmitted infections so that the donor may self-defer
from donation if necessary.
Proposed Sec. 630.10(c)--Proposed Sec. 630.10(c) would permit the
collecting establishment to determine a donor's eligibility and collect
a sample for testing one day before collection, when the donor is
donating blood components that cannot be stored more than 24 hours. We
would require the collecting establishment to identify such blood
components in an SOP.
Proposed Sec. 630.10(i)(2)--In proposed Sec. 630.10(i)(2), we
would require the collecting establishment to provide the donor with
information concerning the donation procedure, and to permit the donor
to ask questions and at any time to withdraw consent to donate.
Proposed Sec. 630.15(b)(6)(iii)--We would redesignate current
Sec. 640.63(e)(3) as proposed Sec. 630.15(b)(6)(iii). Consistent with
the current regulation, we would require plasma collecting
establishments to document the special characteristics of the donor's
antibody and the need for plasmapheresis, i.e., there is no alternative
source.
Proposed Sec. 630.20(c)(3)--Under proposed Sec. 630.20(c)(3), we
would require the collecting establishment to document the recipient's
medical need, which necessitates the collection of blood or blood
components from a donor who is determined to be ineligible to donate.
Proposed Sec. 640.72(a)(2)(i), (a)(3), and (a)(4)--We are
proposing to revise
[[Page 63435]]
current Sec. 640.72(a)(2), (a)(3), and (a)(4). Proposed Sec.
640.72(a)(2)(i) would require the collecting establishment to maintain
for each donor records of initial and periodic examinations, tests,
laboratory data, and interviews as required in proposed Sec. Sec.
630.10, 630.15, and current Sec. Sec. 640.65, 640.66, and 640.67.
Proposed Sec. 640.72(a)(3) and (a)(4) would require the collecting
establishment to maintain a record of the donor's written statement of
understanding and documentation of the donor's good health,
respectively.
Proposed Sec. 640.73--Under proposed Sec. 640.73, we would
require establishments collecting Source Plasma to report adverse
reactions experienced by donors. Proposed Sec. 640.73(a) would require
the reporting of fatal donor reactions associated with plasmapheresis,
and proposed Sec. 640.73(b) would require the reporting of adverse
experiences related to the administration of an immunizing agent.
Proposed Sec. 640.73(c) would require the submission to FDA of a
written followup report within 7 days of learning of the fatality or
the serious or life threatening donor adverse experience related to
immunization of the donor.
Description of respondents: Establishments that collect blood and
blood components, including Source Plasma and Source Leukocytes
According to our registration database, there are currently about
1,709 establishments affected by this rule: (1) Approximately 81
licensed plasma establishments with multiple locations that collect
Source Plasma and (2) approximately 1,628 registered blood
establishments that collect blood and blood components. Based on
estimates provided by HHS and GAO, these establishments collect
annually approximately 15 million units of Whole Blood, and
approximately 13 million donations of Source Plasma. FDA estimates the
information collection burden as follows:
Table 1.--Estimated Annual Recordkeeping Burden\1\
----------------------------------------------------------------------------------------------------------------
No. of Annual Frequency Total Annual
21 CFR Section Recordkeepers per Recordkeeping Records Hours per Record Total Hours
----------------------------------------------------------------------------------------------------------------
606.100(b) 1,709 1 1,709 24 41,016
(Maintenance
of SOPs)
----------------------------------------------------------------------------------------------------------------
606.160(e) 1,628 52 84,656 8 677,248
----------------------------------------------------------------------------------------------------------------
630.15(b)(6)(i 81 1 81 0.17 13.8
ii)
----------------------------------------------------------------------------------------------------------------
640.72(a)(2)(i 81 18,518.5 1,500,000 0.08 120,000
), (a)(3),
and (a)(4)
----------------------------------------------------------------------------------------------------------------
Total 838,277.8
----------------------------------------------------------------------------------------------------------------
\1\There are no capital costs or operating and maintenance costs associated with this collection of information.
Table 2.--Estimated One-Time Recordkeeping Burden\1\
----------------------------------------------------------------------------------------------------------------
No. of Annual Frequency Total Annual
21 CFR Section Recordkeepers per Recordkeeping Records Hours per Record Total Hours
----------------------------------------------------------------------------------------------------------------
606.100(b) 1,139 1 1,139 40 45,560
(Creation of
SOPs)
----------------------------------------------------------------------------------------------------------------
606.100(b) 570 1 570 56 31,920
(Creation of
SOPs)
----------------------------------------------------------------------------------------------------------------
630.10(c) 1,628 1 1,628 16 26,048
----------------------------------------------------------------------------------------------------------------
Total 103,528
----------------------------------------------------------------------------------------------------------------
\1\There are no capital costs or operating and maintenance costs associated with this collection of information.
Table 3.--Estimated Annual Reporting Burden\1\
----------------------------------------------------------------------------------------------------------------
Annual Frequency Total Annual Hours per
21 CFR Section No. of Responses per Response Responses Response Total Hours
----------------------------------------------------------------------------------------------------------------
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
----------------------------------------------------------------------------------------------------------------
\1\There are no capital costs or operating and maintenance costs associated with this collection of information.
Recordkeeping
As shown in table 1 of this document, for each of the 1,709
collecting establishments, we estimate that it will take approximately
24 hours annually to maintain the SOPs. As discussed in section V.C of
this document, we estimate in table 2 of this document that two-thirds
of 1,709 collecting establishments (1,139) will each expend, as a one-
time burden, an average of 40 hours to reconcile their SOPs with the
requirements, and the remaining one-third of the collecting
establishments (570) would expend as a one-time burden an average of 56
hours to reconcile their SOPs with the requirements.
Also, as part of a one-time burden in table 2 of this document,
1,628 blood collecting establishments would create a
[[Page 63436]]
new SOP under proposed Sec. 630.10(c), which we estimate will take 16
hours to create.
In table 1 of this document, under proposed Sec. 606.160(e),
Source Plasma collecting establishments are already providing to
personnel a list identifying unsuitable donors as usual and customary
business practice. Under proposed Sec. 606.160(e), we estimate that it
would take each blood-collecting establishment an average of 8 hours
per week to update and provide their list (1,628 x 52 x 8 = 677,248).
This estimated burden of 8 hours per week may appear to be lower or
higher than the burden experienced by individual establishments. Since
there is no available data, the burden is an estimated burden, taking
into account the range of impact on each establishment. Some
establishments may have the ability to generate the lists by computer;
others may rely on manual preparation.
For proposed Sec. 630.15(b)(6)(iii), Source Plasma collecting
establishments would be permitted to collect plasma from a donor who is
deferred due to red blood cell loss if the establishment documents the
special characteristics of the antibody and the need for the
plasmapheresis. Although we do not have data available, we believe that
such a situation would occur infrequently. Consequently, we are
estimating that each Source Plasma collecting establishment would have
one occurrence per year and that it would take approximately 10 minutes
(0.17 hours) to document the health of the donor and the special
characteristics of the antibody and the need for the plasmapheresis.
Under proposed Sec. 630.20(c)(3), donors who do not meet criteria
under Sec. Sec. 630.10, 630.15, or 610.41 would be permitted to donate
under this proposed provision. Such donations, used solely by a
specified recipient based on documented medical need, would occur
rarely. Consequently, the burden to collecting establishments is
negligible.
In proposed Sec. 640.72(a)(2)(i), (a)(3), and (a)(4), we would
require that Source Plasma collecting establishments maintain records
for each donor of all examinations, tests, laboratory data, interviews,
the donor's written statement of understanding and the donor's good
health respectively. In table 1 of this document, we use GAO's estimate
of approximately 1,500,000 donors that annually donate Source Plasma.
We also estimate that the establishment would expend approximately 5
minutes (0.08 hours) for each donor.
Reporting
Proposed Sec. 630.10(b), would require the collecting
establishments to provide the donor with educational material. There is
no calculated burden for this proposed requirement since establishments
collecting blood and blood components perform this activity as a usual
and customary business practice.
The burden for proposed Sec. 630.10(i)(2) in table 3 of this
document is only calculated for Source Plasma collecting establishments
since the blood collecting establishments already provide the donor
with a statement of understanding as a usual and customary business
practice. We estimate that approximately 81 Source Plasma collecting
establishments would take an estimated 10 minutes (0.17) to perform
this activity. Based on the GAO estimate of approximately 1,500,000
donors that annually donate Source Plasma, the total annual burden
would be 255,000 hours (1,500,000 x 0.17).
Proposed Sec. 640.73(a) would require 81 Source Plasma collecting
establishments to report fatalities associated with plasmapheresis. We
estimate that approximately 3 fatalities would be reported annually. A
written followup report would also be required under Sec. 640.73(c).
Approximately 20 hours is estimated for both the initial and followup
report.
Proposed Sec. 640.73(b) would require Source Plasma collecting
establishments to report any serious or life threatening adverse
reaction experienced by a donor after administration with an
immunization agent. Although we do not have access to data regarding
such reports, we estimate that approximately 3 serious or life-
threatening adverse reactions would occur annually, and that the
establishment would expend approximately 1 hour to complete the initial
and followup reports.
In this rulemaking, we are redesignating current Sec. 630.6 as
proposed Sec. 630.40, which requires the collecting establishment to
notify a donor when the donor is deferred from donation. Current Sec.
630.6 is approved under OMB control number 0910-0116. This approval
expires December 31, 2008.
We are not calculating information collection burden for Sec.
640.120, because by permitting industry to use alternatives in
complying with certain regulations for blood and blood components, we
believe that this provision reduces burden on industry.
In compliance with the Paperwork Reduction Act of 1995 (44 U.S.C.
3507(d)), the agency has submitted the information collection
provisions of this proposed rule to OMB for review. Interested persons
are requested to send comments regarding information collection to OMB
(see DATES and ADDRESSES).
VII. Environmental Impact
The agency has determined under 21 CFR 25.30(h) that this action is
of a type that does not individually or cumulatively have a significant
effect on the human environment. Therefore, neither an environmental
assessment nor an environmental impact statement is required.
VIII. Federalism
FDA has analyzed this proposed rule in accordance with the
principles set forth in Executive Order 13132. FDA has determined that
the proposed rule does not contain policies that have substantial
direct effects on the States, on the relationship between the National
Government and the States, or on the distribution of power and
responsibilities among the various levels of government. Accordingly,
the agency has concluded that the rule does not contain policies that
have federalism implications as defined in the Executive order and,
consequently, a federalism summary impact statement is not required.
IX. Request for Comments
Interested persons may submit to the Division of Dockets Management
(see ADDRESSES) written or electronic comments on this proposed rule.
Submit a single copy of electronic comments or two paper copies of any
mailed comments, except that individuals may submit one paper copy.
Comments are to be identified with the docket number found in brackets
in the heading of this document. Received comments may be seen in the
Division of Dockets Management between 9 a.m. and 4 p.m., Monday
through Friday.
X. References
The following references have been placed on display in the
Division of Dockets Management (see ADDRESSES) and may be seen by
interested persons between 9 a.m. and 4 p.m., Monday through Friday.
(FDA has verified the Web site addresses, but FDA is not responsible
for any subsequent changes to the Web site after this document
publishes in the Federal Register.)
1. Yomtovian R., ``Bacterial Contamination of Blood: Lessons
From the Past and Road Map For the Future,'' Transfusion, March
2004; 44:450-460.
2. Boulton F., ``Determination of Blood Pressure of Blood Donors
at Blood Collection Sessions,'' presented at the 26th meeting of the
Select Committee of Experts on Quality
[[Page 63437]]
Assurance in Blood Transfusion Services, February 2003.
3. Perloff D., et al., ``Human Blood Pressure Determination by
Sphygmomanometry,'' Circulation, November 1993; 88(5 Pt 1):2460-70.
4. Wood, E.M., D.M. Kim, J.P. Miller, ``Accuracy of Predonation
Hct Sampling Affects Donor Safety, Eligibility, and Deferral
Rates,'' Transfusion, March 2001; 41:353-359.
5. HHS, ``The 2005 Nationwide Blood Collection and Utilization
Survey Report,'' p.14, 2005, http://frwebgate.access.gpo.gov/cgi-bin/leaving.cgi?from=leavingFR.html&log=linklog&to=http://www.aabb.org/apps/docs/05nbcusrpt.pdf
.
6. U.S. General Accounting Office, ``Blood Supply Generally
Adequate Despite New Donor Restrictions,'' p. 5 note 7, July 2002,
http://frwebgate.access.gpo.gov/cgi-bin/leaving.cgi?from=leavingFR.html&log=linklog&to=http://www.gao.gov/new.items/d02754.pdf.
7. U. S. Bureau of Labor Statistics, ``Employer Costs for
Employee Compensation,'' table 14, September 2006.
8. Lapane, K. L., et al., ``Hepatitis C Infection Risk Analysis:
Who Should Be Screened? Comparison of Multiple Screening Strategies
Based on the National Hepatitis Surveillance Program,'' The American
Journal of Gastroenterology, April 1998; 93:591-596.
9. U.S. Centers for Disease Control and Prevention, ``Viral
Hepatitis B Fact Sheet,'' July 27, 2007, http://frwebgate.access.gpo.gov/cgi-bin/leaving.cgi?from=leavingFR.html&log=linklog&to=http://www.cdc.gov/ncidod/diseases/hepatitis/b/bfact.pdf
.
10. U.S. Centers for Disease Control and Prevention, ``Viral
Hepatitis B Frequently Asked Questions,'' http://frwebgate.access.gpo.gov/cgi-bin/leaving.cgi?from=leavingFR.html&log=linklog&to=http://www.cdc.gov/ncidod/diseases/hepatitis/b/faqb.htm#gen
.
11. Stramer, S.L. ``US NAT yield: Where Are We After 2 Years?''
Transfusion Medicine, August 2002; 12:243-53.
12. U.S. Centers for Disease Control and Prevention, ``Viral
Hepatitis C Fact Sheet,'' May 24, 2005, http://frwebgate.access.gpo.gov/cgi-bin/leaving.cgi?from=leavingFR.html&log=linklog&to=http://www.cdc.gov/ncidod/diseases/hepatitis/c/cfact.pdf
.
13. North American Industry Classification System (NAICS),
available online at http://frwebgate.access.gpo.gov/cgi-bin/leaving.cgi?from=leavingFR.html&log=linklog&to=http://www.naics.com/sba_sizestandards.htm.
14. U.S. Small Business Administration, Office of Size
Standards, ``Table of Small Business Size Standards,'' 2007, http://frwebgate.access.gpo.gov/cgi-bin/leaving.cgi?from=leavingFR.html&log=linklog&to=http://www.sba.gov/size/sizetable2007.pdf
.
List of Subjects
21 CFR Part 606
Blood, Labeling, Laboratories, Reporting and recordkeeping
requirements.
21 CFR Parts 610 and 660
Biologics, Labeling, Reporting and recordkeeping requirements.
21 CFR Part 630
Blood, Reporting and recordkeeping requirements.
21 CFR Part 640
Blood, Labeling, Reporting and recordkeeping requirements.
21 CFR Part 820
Medical devices, Reporting and recordkeeping requirements.
21 CFR Part 1270
Communicable diseases, HIV/AIDS, Reporting and recordkeeping
requirements.
Therefore, under the Federal Food, Drug, and Cosmetic Act, the
Public Health Service Act, and under the authority delegated to the
Commissioner of Food and Drugs, it is proposed that 21 CFR Chapter I be
amended as follows:
PART 606--CURRENT GOOD MANUFACTURING PRACTICE FOR BLOOD AND BLOOD
COMPONENTS
1. The authority citation for 21 CFR part 606 continues to read as
follows:
Authority: 21 U.S.C. 321, 331, 351, 352, 355, 360, 360j, 371,
374; 42 U.S.C. 216, 262, 263a, 264.
2. Section 606.3 is amended by revising paragraphs (a) and (c) to
read as follows:
Sec. 606.3 Definitions.
* * * * *
(a) Blood means a product that is the fluid containing dissolved
and suspended elements, which circulates in the vascular system of a
human.
* * * * *
(c) Blood component means a product containing a part of human
blood separated by physical or mechanical means.
* * * * *
3. Section 606.100 is amended by revising the introductory text in
paragraph (b); by revising paragraph (b)(20); and by adding paragraph
(b)(21) to read as follows:
Sec. 606.100 Standard operating procedures.
* * * * *
(b) Establishments must establish, maintain, and follow written
standard operating procedures for all steps in the collection,
processing, compatibility testing, storage, and distribution of blood
and blood components for allogeneic transfusion, autologous
transfusion, and further manufacturing purposes; for all steps in the
investigation of product deviations related to Sec. 606.171; and for
all steps in recordkeeping related to current good manufacturing
practice and biological product standards. Such procedures must be
available to the personnel for use in the areas where the procedures
are performed. The written standard operating procedures must include,
but are not limited to, descriptions of the following, when applicable:
* * * * *
(20) Procedures for donor deferral as prescribed in Sec. 610.41 of
this chapter; and
(21) Procedures for donor notification and autologous donor
referring physician notification, including procedures for the
appropriate followup if the initial attempt at notification fails, as
prescribed in Sec. 630.40 of this chapter.
* * * * *
Sec. 606.110 [Amended]
4. Section 606.110(b) is amended by removing ``640.63'' and by
adding in its place ``630.10, 630.15''.
5. Section 606.160 is amended by revising paragraphs (b)(1)(ix),
(b)(1)(xi), and (e) to read as follows:
Sec. 606.160 Records.
* * * * *
(b) * * *
(1) * * *
(ix) Records of notification of donors deferred or determined not
to be eligible for donation, including appropriate followup if the
initial attempt at notification fails, performed under Sec. 630.40 of
this chapter.
* * * * *
(xi) Records of notification of the referring physician of a
deferred autologous donor, including appropriate followup if the
initial attempt at notification fails, performed under Sec. 630.40 of
this chapter.
* * * * *
(e)(1) Establishments must maintain a record of all ineligible
donors so that blood and blood components are not collected from such
individuals while they are ineligible or deferred; and
(2) Establishments must provide, to appropriate personnel at all
locations operating under the same license or under common management,
a collective list of ineligible donors with sufficient information to
prevent the collection of blood and blood components from any donors
currently identified at each location as not eligible to donate under
Sec. 630.10(f) and (g)(1) through (g)(6) of this chapter, or deferred
based on test results under Sec. 610.41 of this chapter.
PART 610--GENERAL BIOLOGICAL PRODUCTS STANDARDS
6. The authority citation for 21 CFR part 610 continues to read as
follows:
Authority: 21 U.S.C. 321, 331, 351, 352, 353, 355, 360, 360c,
360d, 360h, 360i, 371, 372, 374, 381; 42 U.S.C. 216, 262, 263, 263a,
264.
Subpart E [Amended]
7. Subpart E is amended by removing ``communicable disease agents''
and by adding in its place ``relevant transfusion-transmitted
infections'' in
[[Page 63438]]
the subpart heading and everywhere it appears throughout the subpart.
8. Section 610.40 is amended by revising paragraph (a) and (e)
introductory text to read as follows:
Sec. 610.40 Test requirements.
(a) Human blood and blood components. Except as specified in
paragraphs (c) and (d) of this section, and except for syphilis, which
must be tested under Sec. 610.40(i), for each donation of blood and
blood components intended for use in preparing a product, including
donations intended as a component of, or used to prepare a medical
device, you, an establishment that collects blood and blood components,
must test:
(1) For evidence of infection due to the following relevant
transfusion-transmitted infections described in Sec. 630.3(g)(1)(i)
through (g)(1)(iv) of this chapter:
(i) Human immunodeficiency virus, types 1 and 2;
(ii) Hepatitis B virus;
(iii) Hepatitis C virus; and
(iv) Human T-lymphotropic virus, types I and II;
(2) In addition, for evidence of infection due to relevant
transfusion-transmitted infections described in Sec. 630.3(g)(1)(vi)
through (g)(1)(viii) and 630.3(g)(2) of this chapter, provided that
testing for the disease agent or disease is available and necessary to
reduce the risk of transmission of the relevant transfusion-transmitted
infection by the blood or blood component.
* * * * *
(e) Further testing. You must further test each donation, including
autologous donations, found to be reactive by a screening test
performed under paragraphs (a) and (b) of this section using one or
more FDA-approved supplemental (additional, more specific) test(s), or
other appropriate, additional tests. You must perform such further
testing as necessary and appropriate to determine the deferred donor's
infection status for the purpose of donor notification required under
Sec. 630.40 of this chapter, except:
* * * * *
PART 630--REQUIREMENTS FOR HUMAN BLOOD AND BLOOD COMPONENTS
INTENDED FOR TRANSFUSION OR FOR FURTHER MANUFACTURING USE
9. The authority citation for part 630 continues to read as
follows:
Authority: 21 U.S.C. 321, 331, 351, 352, 355, 360, 371; 42
U.S.C. 216, 262, 264.
10. Revise the heading for part 630 to read as set forth above.
11. Add a heading for new subpart C to read as follows:
Subpart C--Donor Notification
12. Redesignate Sec. 630.6 as Sec. 630.40, and transfer newly
designated Sec. 630.40 to subpart C.
13. Amend Sec. 630.40 as follows:
a. Revise the section heading.
b. Remove ``suitable'' wherever it appears and add ``eligible'' in
its place; and remove ``suitability'' wherever it appears and add
``eligibility'' in its place.
c. Revise the first sentence in paragraph (a).
The revisions read as follows:
Sec. 630.40 Requirements for notifying deferred donors.
(a) Notification of donors. You must make reasonable attempts to
notify any donor, including an autologous donor, who has been deferred
based on the results of tests for evidence of infection with a relevant
transfusion-transmitted infection(s) as required by Sec. 610.41 of
this chapter; who has been determined not to be eligible as a donor
based on eligibility criteria under Sec. Sec. 630.10 and 630.15 of
this chapter; or whose platelet component has tested positive for an
endogenous bacterial contamination. * * *
* * * * *
14. Add subparts A and B to part 630 to read as follows:
Subpart A--General Provisions
Sec.
630.1 Purpose and scope.
630.3 Definitions.
Subpart B--Donor Eligibility Requirements
Sec.
630.5 Medical supervision.
630.10 General donor eligibility requirements.
630.15 Donor eligibility requirements specific to Whole Blood and to
Plasma collected by plasmapheresis.
630.20 General exceptions from donor eligibility requirements.
630.25 Exceptions from certain donor eligibility requirements for
infrequent plasmapheresis.
630.30 Donation suitability requirements.
630.35 Requalification of previously deferred donors.
Subpart A--General Provisions
Sec. 630.1 Purpose and scope.
(a) Purpose. What is the purpose of subparts A, B, and C of this
part? The purpose of these subparts, together with Sec. Sec. 610.40
and 610.41 of this chapter, is to provide certain minimum criteria for
each donation of blood and blood components, for:
(1) Determining the eligibility of a donor of blood and blood
components;
(2) Determining the suitability of the donation of blood and blood
components; and
(3) Notifying a donor who is deferred from donation.
(b) Scope. Who must comply with subparts A, B, and C of this part?
You, as defined in Sec. 630.3(l), must comply with subparts A, B, and
C of this part.
Sec. 630.3 Definitions.
As used in this part and 21 CFR part 640 of this chapter:
(a) Blood means a product that is the fluid containing dissolved
and suspended elements, which circulates in the vascular system of a
human.
(b) Blood component means a product containing a part of blood
separated by physical or mechanical means.
(c) Donor means a person who:
(1) Donates blood or blood components for transfusion or for
further manufacturing use or
(2) Presents as a potential candidate for such donation.
(d) Eligibility of a donor means the determination that the donor
is qualified to donate blood and blood components.
(e) Intimate contact means an activity that could result in an
exchange of body fluids, including blood or saliva, with another
individual.
(f) Physician substitute means a trained and qualified person(s)
who is:
(1) A graduate of an education program for health care workers that
includes clinical training;
(2) Currently licensed or certified as a health care worker in the
jurisdiction where the collecting establishment is located;
(3) Currently certified in cardiopulmonary resuscitation; and
(4) Trained and authorized to perform specified functions under the
direction of the responsible physician.
(g) Relevant transfusion-transmitted infection means:
(1) Any of the following transfusion-transmitted infections:
(i) Human immunodeficiency virus, types 1 and 2 (HIV);
(ii) Hepatitis B virus (HBV);
(iii) Hepatitis C virus (HCV);
(iv) Human T-lymphotropic virus, types I and II (HTLV);
(v) Treponema pallidum (syphilis);
(vi) Creutzfeldt-Jakob disease (CJD);
(vii) Variant Creutzfeldt-Jakob disease (vCJD); and
(viii) Plasmodium sp. (malaria).
(2) Other transfusion-transmitted infections not listed in
paragraph (g)(1) of this section:
(i) For which appropriate screening measures are developed and/or
an appropriate screening test for donor
[[Page 63439]]
specimens is licensed, approved, or cleared for such use by FDA and is
available; and
(ii) That:
(A) May have sufficient incidence and/or prevalence to affect the
potential donor population or
(B) May have been released accidentally or intentionally in a
manner that could place donors at risk of infection.
(h) Responsible physician means an individual who is:
(1) Licensed to practice medicine in the jurisdiction where the
collecting establishment is located;
(2) Adequately trained and qualified to direct and control
personnel and relevant procedures concerning the determination of donor
eligibility; collection of blood and blood components; the immunization
of a donor; and the return of red blood cells or other blood components
to the donor during collection of blood component(s) by apheresis; and
(3) Designated by the collecting establishment to direct and
control personnel, and to approve relevant procedures specifying
decision-making criteria for determining donor eligibility, the
collection of blood or blood components, the immunization of a donor,
and the return of red blood cells or other blood components to a donor
during collection of blood component(s) by apheresis.
(i) Suitability of the donation means a determination of whether
the donation is acceptable for transfusion or for further manufacturing
use.
(j) Trained personnel means authorized individuals, including
physician substitutes, who are adequately instructed and qualified to
perform specified functions under the direction of the responsible
physician.
(k) Transfusion-transmitted infection means a disease or disease
agent:
(1) That could be fatal or life-threatening, could result in
permanent impairment of a body function or permanent damage to body
structure, or could necessitate medical or surgical intervention to
preclude permanent impairment of body function or permanent damage to a
body structure; and
(2) For which there may be a risk of transmission by the blood and
blood components collected, or by a blood derivative product
manufactured from the collected blood or blood components, because the
disease agent or disease is potentially transmissible by that blood,
blood component, or blood derivative product.
(l) You means an establishment that collects blood and blood
components as described in paragraphs (a) and (b) of this section.
Subpart B--Donor Eligibility Requirements
Sec. 630.5 Medical supervision.
(a) Who must determine the eligibility of a donor? The responsible
physician authorized by you, as described in Sec. 630.3(l), must
determine the eligibility of a donor of blood or blood components in
accordance with this part.
(b) Must the responsible physician be present at the collecting
establishment at all times? Except as provided in paragraphs (c) and
(d) of this section and Sec. 630.15(b)(1) and (b)(4), you must assure
that the responsible physician is in attendance when any of the
following activities are performed at the collecting establishment:
(1) Determining the eligibility of a donor;
(2) Collecting blood or blood components;
(3) Collecting Source Plasma in an approved collection program from
donors who are otherwise determined to be unsuitable;
(4) Returning red blood cells to the donor during plasmapheresis;
or
(5) Immunizing a donor in an approved hyperimmunization program.
(c) What specified functions of the responsible physician in the
collection of Source Plasma may be performed by a physician substitute?
You may authorize a physician substitute to perform any specified
function listed in paragraph (b) of this section in the collection of
Source Plasma except for red blood cell immunizations performed under
paragraph (b)(5) of this section.
(d) What specified functions of the responsible physician in the
collection of blood and blood components may be performed by a
physician substitute or trained personnel? In the absence of the
responsible physician, you may authorize a physician substitute or
trained personnel to determine donor eligibility and collect blood and
blood components.
(e) Must emergency medical services be available? Yes, you must
establish, maintain, and follow standard operating procedures for
providing within 15 minutes emergency medical services for donors when
medically necessary.
Sec. 630.10 General donor eligibility requirements.
(a) What factors determine the eligibility of a donor? You must not
collect blood and blood components before you determine that the donor
is eligible to donate. A donor is not eligible if the donor is not in
good health or if you identify factors that may adversely affect:
(1) The health of the donor or
(2) The safety, purity, or potency of the blood or blood components
collected from the donor.
(b) What educational material must you provide to the donor before
determining eligibility? Before determining eligibility, you must
provide the donor with educational material containing useful and
current information concerning the relevant transfusion-transmitted
infections defined in Sec. 630.3(g). The educational material must
include an explanation of the signs and symptoms of and the readily
identifiable risk factors closely associated with exposure to the
relevant transfusion-transmitted infections. You must present
educational material in an appropriate form, e.g., in oral, written or
multimedia, and in a manner designed to be understood by the donor. The
educational material must state that the donor may not donate blood and
blood components when such signs and symptoms or risk factors are
present.
(c) When must you determine the eligibility of a donor? You must
determine donor eligibility on the day of donation, and before
collection. When a donor is donating blood components that cannot be
stored for more than 24 hours, you may determine the donor's
eligibility and collect a sample for testing required under Sec.
610.40 and Sec. 640.5 of this chapter, 1 day before the donation. You
must have standard operating procedures in place for identifying such
components.
(d) How must you determine the eligibility of a donor? Before
collection, you must determine the donor's eligibility by the following
procedures:
(1) Assessing the donor's deferral status by checking the
collective list of ineligible donors required under Sec. 606.160(e)(2)
of this chapter;
(2) Assuring that the interval since the donor's last donation is
appropriate, taking into account the donor's participation, if any, in
other blood or blood component collection programs;
(3) Assessing the donor's medical history; and
(4) Performing a physical assessment of the donor.
(e) How do you assess the donor's medical history? Before
collection, you must take a medical history designed to determine if
the donor is in good health and if health care practitioners have ever
advised the donor not to donate; to identify risk factors closely
associated with exposure to, or clinical evidence of, infection due to
a relevant transfusion-transmitted infection; and to
[[Page 63440]]
determine if there are other conditions that may adversely affect the
donor or the safety, purity, or potency of the blood or blood
components or any product produced from the blood or blood components.
(f) What factors make the donor ineligible because of an increased
risk for, or evidence of, a relevant transfusion-transmitted infection?
The donor is ineligible to donate when information provided by the
donor or other reliable evidence indicates possible exposure to a
relevant transfusion-transmitted infection. Information that a donor
has participated in any of the following renders the donor ineligible
if that risk of exposure is still applicable at the time of donation:
(1) Social behaviors associated with relevant transfusion-
transmitted infections;
(2) Medical treatments and procedures associated with exposure to
relevant transfusion-transmitted infections;
(3) Signs and symptoms of relevant transfusion-transmitted
infections;
(4) Institutionalization in a correctional institution;
(5) Intimate contact with an individual who is at an increased risk
for exposure to, or is known to be infected with, a relevant
transfusion-transmitted infection that is spread by such type of
intimate contact; and
(6) Nonsterile percutaneous inoculation.
(g) What other factors make the donor ineligible to donate because
of risk to the health of the donor, or to the safety, purity, or
potency of the blood or blood component? You must assess the donor for
each of the following factors to determine whether donating could
adversely affect the health of the donor, or whether the safety,
purity, or potency of the blood or blood component could be affected,
and if so, you must determine the donor to be ineligible:
(1) Medical or dental treatment, or symptoms of a recent or current
illness;
(2) Medication;
(3) Major surgical procedure;
(4) Travel to, or residence in, an area endemic for a transfusion-
transmitted infection;
(5) Xenotransplantation product recipient or intimate contact of a
xenotransplantation product recipient;
(6) Exposure or possible exposure to a released disease agent or
disease relating to a transfusion-transmitted infection, if you know or
suspect that such a release has occurred;
(7) Pregnancy at the time of, or 6 weeks before, donation; and
(8) Unreliable answers to medical history questions due to the
apparent influence of drugs or alcohol, or due to another reason
affecting the reliability of the donor's answers.
(h) How do you perform a physical assessment of the donor? You must
determine that the donor is in good health based on the following, at a
minimum:
(1) Temperature. The donor's oral body temperature must not exceed
37.5 [deg]C (99.5 [deg]F), or the equivalent if measured at another
body site;
(2) Blood pressure. The donor's systolic blood pressure must not
measure above 180 millimeters of mercury or below 90 millimeters of
mercury, and the diastolic blood pressure must not measure above 100
millimeters of mercury or below 50 millimeters of mercury. A donor with
measurements outside these limits may be permitted to donate only when
the responsible physician has examined the donor and determined that
the health of the donor would not be adversely affected by donating.
(3) Hemoglobin or hematocrit determination for allogeneic donation.
(i) You must determine the donor's hemoglobin level or hematocrit value
by using a sample of blood obtained by fingerstick, venipuncture, or by
a method that provides equivalent results. Blood obtained from the
earlobe is not acceptable; and
(ii) An allogeneic donor must have a hemoglobin level no less than
12.5 grams per deciliter of blood, or a hematocrit value no less than
38 percent. An autologous donor must have a hemoglobin level no less
than 11.0 grams per deciliter of blood, or a hematocrit value no less
than 33 percent.
(4) Pulse. The donor's pulse rate must be regular and between 50
and 100 beats per minute. A donor with an irregular pulse rate or
measurements outside these limits may be permitted to donate only when
the responsible physician has examined the donor and determines that
the health of the donor would not be adversely affected.
(5) Weight. The donor must weigh a minimum of 50 kilograms (110
pounds) and must not have had an unexplained loss of greater than 10
percent of body weight within the past 6 months; and
(6) Skin examination. (i) The donor's phlebotomy site must be free
of infection, inflammation, lesions, and pitted skin; and
(ii) The donor's arms and forearms must be free of punctures and
scars indicative of injected drugs of abuse.
(i) What additional requirements must you complete before
determining the eligibility of the donor? Immediately before donation,
you must obtain the following:
(1) Proof of identity and mailing address. You must obtain proof of
identity of the donor and an address where the donor may be contacted
for 8 weeks after donation; and
(2) Donor's written statement of understanding. You must provide a
written statement of understanding to be read and signed by the donor.
You must establish procedures in accordance with Sec. 606.100 of this
chapter to provide assistance to those unable to read the written
statement of understanding. You must design those procedures to assure
that the donor understands fully the material in the donor's written
statement of understanding, and provide for a signature or acceptable
substitute for a signature to indicate that understanding. The written
statement of understanding must not include any exculpatory language
through which the donor is made to waive or appear to waive any of the
donor's legal rights. The statement must clearly state the following:
(i) The donor has reviewed the provided educational material
required by Sec. 630.10(b) regarding relevant transfusion-transmitted
infections, including the fact that relevant transfusion-transmitted
infections present potential risks to the safety, purity, or potency of
the blood supply;
(ii) The donor agrees not to donate if the donation could result in
a potential risk to the safety, purity, or potency of the blood supply
as described in the educational material;
(iii) A sample of the donor's blood will be tested for specified
relevant transfusion-transmitted infections required in Sec. 610.40(a)
of this chapter and for syphilis.
(iv) If any of the tests required in Sec. 610.40(a) of this
chapter are reactive, the sample of blood will be tested further, as
required in Sec. 610.40(e) of this chapter;
(v) If the donation is determined to be not suitable under Sec.
630.30(a) or if the donor is deferred from donation under Sec. 610.41
of this chapter, the donor's record must identify the donor as
ineligible to donate and the donor must be notified under Sec. 630.40
of the basis for the deferral and the period of deferral;
(vi) The hazards and risks of the donation procedure or of
hyperimmunization, if applicable; and
(vii) the donor has the opportunity to ask questions and withdraw
consent at any time.
[[Page 63441]]
Sec. 630.15 Donor eligibility requirements specific to Whole Blood
and to Plasma collected by plasmapheresis.
(a) What additional donor eligibility requirements are specific to
Whole Blood?--(1) Donation frequency. Whole Blood must not be collected
from a donor more than once in 8 weeks if the donor participates in a
single unit collection program; or more than once in 16 weeks if the
donor participates in a double unit collection program, unless the
donor is examined and certified to be in good health by a responsible
physician at the time of donation and one of the following three
conditions exist:
(i) An individual presents a physician's prescription for
therapeutic phlebotomy for medical reasons; or
(ii) The donation is for autologous use; or
(iii) The donation is a dedicated donation based on the intended
recipient's documented medical need.
(2) Therapeutic phlebotomy. When a donor who is determined to be
eligible under Sec. 630.10(d) undergoes a therapeutic phlebotomy to
promote the health of the donor, the container label must conspicuously
state the disease of the donor that necessitated phlebotomy. However,
no disease labeling is required under this section for a donation
collected from a donor who meets all eligibility criteria and undergoes
a therapeutic phlebotomy as ordered by a physician treating the donor
for Hereditary Hemochromatosis, provided that you perform without
charge therapeutic phlebotomies for all individuals with Hereditary
Hemochromatosis.
(b) What additional donor eligibility requirements are specific to
Plasma collected by plasmapheresis?--(1) Physical examination and
informed consent. (i) In addition to the physical assessment required
in Sec. 630.10(d), the responsible physician must examine the donor
for medical conditions that would place the donor at risk during
plasmapheresis. If the donor is determined to be at risk, you must
defer the donor from donating. In a program of repeat plasmapheresis,
i.e., collections occur more than once every 28 days, the donor must be
examined on the day of the first donation or no more than 1 week before
the first donation and at subsequent intervals of no more than 1 year.
(ii) When conducting the physical examination, the responsible
physician must explain the hazards of the procedure to the donor. The
explanation must include the risks of a hemolytic transfusion reaction
if the donor is given the cells of another donor, and the hazards
involved if the donor is hyperimmunized. The explanation must be made
in such a manner that the donor may give informed consent and has a
clear opportunity to refuse the procedure as required under Sec.
630.10(i)(2).
(2) Weight. You must weigh a donor at each donation.
(3) Total protein level. Before each plasmapheresis procedure, a
donor must have a total plasma protein level of no less than 6.0 grams
per deciliter and no more than 9.0 grams per deciliter of plasma sample
or the comparable level for a serum sample.
(4) Examination before immunization. (i) In addition to the
determination of donor eligibility required in Sec. 630.10(d), the
responsible physician must perform the physical examination no more
than 1 week before the first immunization injection for the production
of high-titer plasma. It is not necessary to repeat the physical
examination requirement in paragraph (b)(1) of this section, if the
immunized donor's plasma is collected within 3 weeks of the first
immunization injection; and
(ii) A donor determined to be eligible under Sec. 630.10(d) and
currently participating in a plasmapheresis program, does not need to
be re-examined before immunization for the production of high-titer
antibody plasma.
(5) Deferral due to red blood cell loss. You must defer a donor
from donating plasma for a period of 8 weeks after any of the following
events:
(i) The donor experienced a red blood cell loss of equal to or
greater than 200 milliliters of red blood cells during a single
automated plasmapheresis procedure; or
(ii) The donor experienced an unexpected red blood cell loss of any
volume in an automated apheresis procedure on two occasions within the
last 8-week period; or
(iii) The donor experienced a red blood cell loss equivalent to or
greater than 200 milliliters of red blood cells as a result of failure
to return red blood cells during a manual plasmapheresis procedure; or
(iv) The donor donated a unit of Whole Blood.
(6) Exceptions to deferral due to red blood cell loss. You are not
required to defer a donor from participation in a plasmapheresis
program due to red blood cell loss if the following occurs:
(i) The donor is examined at the time of the current donation and
certified by the responsible physician to be in good health under Sec.
630.10(h) and the donor's health permits the plasmapheresis; and
(ii) The donor possesses an antibody that is transitory, of a
highly unusual or infrequent specificity, or of an unusually high
titer, and
(iii) The special characteristics of the antibody and the need for
plasmapheresis of the donor under Sec. 630.20(c)(2) are documented at
your establishment.
(7) Malaria. Freedom from risk of malaria is not required for a
donor of Source Plasma.
Sec. 630.20 General exceptions from donor eligibility requirements.
You may collect blood and blood components from a donor who is
determined to be not eligible to donate under Sec. Sec. 630.10(d) and
630.15, or deferred under Sec. 610.41 of this chapter only if:
(a) The responsible physician examines the donor and certifies in
writing that the donor's health permits the collection procedure;
(b) The collection is performed under the supervision of the
responsible physician who is aware of the donor's health status; and
(c) At least one of the following is met:
(1) The donation is for autologous use as prescribed by the donor's
physician, and is not for allogeneic transfusion or for further
manufacturing use;
(2) The donor is participating in a plasmapheresis program that
collects plasma for further manufacturing use into products for which
there are no alternative sources, and the collection program has
received prior approval from the Director, Center for Biologics
Evaluation and Research; or
(3) The donation is restricted for use solely by a specific
recipient based on documented medical need and the responsible
physician determines that the donation presents no undue medical risk
to the recipient.
Sec. 630.25 Exceptions from certain donor eligibility requirements
for infrequent plasmapheresis.
You are not required to perform a physical examination of the donor
for medical conditions under Sec. 630.15(b)(1), to perform a test for
total protein under Sec. 630.15(b)(3), to determine the immunoglobulin
composition of the serum or plasma under Sec. 640.65(b)(1)(i) of this
chapter, or to review the laboratory data as required in Sec.
640.65(b)(2)(i) of this chapter, if:
(a) The donor has not donated Whole Blood in the preceding 8 weeks,
Plasma by plasmapheresis in the preceding 4 weeks, or participated in a
double Red Blood Cells unit collection program within the preceding 16
weeks;
[[Page 63442]]
(b) The donor has not donated more than 12.0 liters of plasma (14.4
liters of plasma for donors weighing more than 175 lbs.) in the past
year;
(c) The donor is determined by the responsible physician to be in
good health under Sec. 630.10(d); and
(d) The donor is not participating in an immunization program for
the production of high-titer plasma.
Sec. 630.30 Donation suitability requirements.
(a) When is a donation suitable? A donation is suitable when:
(1) The donor is not currently deferred from donation;
(2) The results in accordance with Sec. Sec. 630.10 through 630.25
indicate that the donor is in good health and that the donation would
not adversely affect the health of the donor;
(3) The donor is free from risk factors for, or evidence of
transfusion-transmitted infections under Sec. 630.10(f) and (g);
(4) The donor's blood is tested in accordance with Sec. 610.40 of
this chapter, and is negative or nonreactive, unless an exception
applies under Sec. 610.40(h) of this chapter;
(5) For platelet components, you have taken adequate steps to
assure that the donation is tested for bacterial contamination and
found negative; and
(6) The donation meets other requirements in this subchapter.
(b) What must you do when the donation is not suitable? (1) When
the donation does not meet the criteria in paragraphs (a)(1) through
(a)(3) and (a)(5) of this section, the donation is not suitable and you
must defer the donor from donation;
(2) When the donation does not meet the criteria in paragraph
(a)(4) of this section, defer the donor from donation in accordance
with Sec. 610.41(a) of this chapter;
(3) Identify a donor not eligible under Sec. 630.10(f)(1) through
(f)(6) and Sec. 630.10(g)(1) through (g)(6) as not eligible to donate
under Sec. 606.160(e) of this chapter; and
(4) Notify a donor found not eligible to donate under Sec. 610.41
of this chapter, and Sec. Sec. 630.10 through 630.25, or 630.30(a)(5)
of the deferral, the deferral period, and the reason for the deferral,
in accordance with the notification requirements in Sec. 630.40.
Sec. 630.35 Requalification of previously deferred donors.
(a) A deferred donor identified under Sec. 630.30(b)(1) may be
determined eligible as a donor of blood and blood components if, at the
time of the current collection, except for the record of previous
deferral, the donor meets the eligibility criteria in this part; and
the criteria, which were the basis for the previous deferral, are
determined to be no longer applicable.
(b) A deferred donor identified under Sec. 630.30(b)(2) may be
determined eligible as a donor of blood and blood components if, at the
time of the current collection except for the record of the previous
deferral, the donor meets the eligibility criteria in this part; and
the criteria which were the basis for the previous deferral are
determined to be no longer applicable under Sec. 610.41(b) of this
chapter.
PART 640--ADDITIONAL STANDARDS FOR HUMAN BLOOD AND BLOOD PRODUCTS
15. The authority citation for 21 CFR part 640 continues to read as
follows:
Authority: 21 U.S.C. 321, 351, 352, 353, 355, 360, 371; 42
U.S.C. 216, 262, 263, 263a, 264.
Sec. 640.3 [Removed]
16. Section 640.3 is removed.
Sec. 640.4 [Amended]
17. Section 640.4 is amended by removing paragraph (a) and by
redesignating paragraphs (b) through (h) as paragraphs (a) through (g).
18. Section 640.12 is revised to read as follows:
Sec. 640.12 Eligibility of donor.
Collecting establishments must determine the eligibility of donors
of the source blood for Red Blood Cells in accordance with Sec. Sec.
630.10 and 630.15 of this chapter.
19. Section 640.21 is revised to read as follows.
Sec. 640.21 Eligibility of donors.
(a)(1) Collecting establishments must determine the eligibility of
Whole Blood donors and plateletpheresis donors in accordance with
Sec. Sec. 630.10 and 630.15 of this chapter, except as expressly
modified in paragraph (e) of this section.
(2) Under Sec. 630.10(i)(2)(vi) of this chapter, the statement of
understanding must include a statement that the long-term effects of
frequent apheresis are unknown.
(b) A donor must not serve as a source of platelets for transfusion
if the donor has recently ingested drugs that adversely affect platelet
function.
(c) A plateletpheresis donor may donate at intervals shorter than 8
weeks provided:
(1) The establishment performs a platelet count before starting the
initial plateletpheresis procedure and before each subsequent
procedure;
(2) The platelet count required in paragraph (c)(1) of this section
is greater than 150,000/microL;
(3) The donor's post-donation platelet count is no less than
100,000 platelets/microL; and
(4) The donor donates the following:
(i) No more than a total of 24 plateletpheresis collections during
a 12-month period;
(ii) For single component collection procedures, no more than 2
plateletpheresis procedures within a 7 calendar day period with a
minimum of 2 calendar days between procedures;
(iii) For a double or triple component collection procedure, no
more than one procedure within a 7 calendar day period.
(d) For a period not to exceed 30 days, a donor may serve as a
dedicated plateletpheresis donor for a single recipient, in accordance
with Sec. 610.40(c)(1) of this chapter, as often as is medically
necessary, provided that the donor is in good health, as determined by
a physician, and the donor's platelet count is greater than 150,000/
microL, measured at the conclusion of the previous donation or before
initiating apheresis for the current donation.
(e) Except as provided in paragraphs (e)(1) and (e)(2) of this
section, a plateletpheresis donor must be deferred for a period of 8
weeks after donating a unit of Whole Blood or after losing a volume of
whole blood equal to or greater than 450 mL, or red blood cells equal
to or greater than 200 mL, cumulatively over an 8 week period; or be
deferred for a period of 16 weeks after donating a double Red Blood
Cells unit collection. In exception, the plateletpheresis donor may
donate if all of the following criteria are met:
(1) The donor waits 2 calendar days after donating Whole Blood or
after experiencing the blood loss; and
(2) The extracorporeal red blood cell volume during the apheresis
procedure is equal to or less than 100 mL.
Sec. 640.22 [Amended]
20. Section 640.22(b) is amended by removing ``640.62'' and by
adding in its place ``630.5''.
21. Section 640.31 is revised to read as follows:
Sec. 640.31 Eligibility of donors.
(a) Whole Blood donors must meet the criteria for donor eligibility
prescribed in Sec. Sec. 630.10 and 630.15 of this chapter.
(b) Collecting establishments must determine the eligibility of
plasmapheresis donors in accordance with Sec. Sec. 630.10 and 630.15
of this chapter.
[[Page 63443]]
Sec. 640.32 [Amended]
22. Section 640.32(b) is amended by removing ``640.62'' and by
adding in its place ``630.5''.
23. Section 640.51 is revised to read as follows:
Sec. 640.51 Eligibility of donors.
(a) Whole blood donors must meet the criteria for eligibility
prescribed in Sec. Sec. 630.10 and 630.15 of this chapter.
(b) Collecting establishments must determine the eligibility of
plasmapheresis donors in accordance with Sec. Sec. 630.10 and 630.15
of this chapter.
Sec. 640.52 [Amended]
24. Section 640.52(b) is amended by removing ``640.62'' and by
adding in its place ``630.5''.
Sec. 640.61 [Removed]
25. Section 640.61 is removed.
Sec. 640.62 [Removed]
26. Section 640.62 is removed.
Sec. 640.63 [Removed]
27. Section 640.63 is removed.
28. Section 640.65 is amended by revising paragraphs (b)(1)(i) and
(b)(2)(i) to read as follows:
Sec. 640.65 Plasmapheresis.
* * * * *
(b) * * *
(1)(i) Except as provided under Sec. 630.25 of this chapter, a
sample of blood must be drawn from each donor on the day of the initial
physical examination or plasmapheresis, whichever comes first, and at
least every 4 months thereafter. A serological test for syphilis, a
total plasma or serum protein determination, and electrophoresis or
quantitative immuno-diffusion test or an equivalent test to determine
immunoglobulin composition of the plasma or serum, must be performed on
the sample.
* * * * *
(2)(i) Except as provided under Sec. 630.25 of this chapter, the
accumulated laboratory data, including tracings of the plasma or serum
protein electrophoresis pattern, if any, the calculated values of each
component, and the collection records must be reviewed by the
responsible physician as required in Sec. 630.5 of this chapter within
14 calendar days after the sample is drawn to determine whether or not
the donor should be deferred from further donation. If a determination
is not made within 14 calendar days, the donor must be deferred pending
such a determination. The responsible physician must sign the review.
If the protein composition is not within normal limits established by
the testing laboratory, or if the total protein is less than 6.0 grams
per deciliter of plasma sample or more than 9.0 grams per deciliter of
plasma sample, or the comparable level for a serum sample, the donor
must be deferred from donation until the protein composition returns to
acceptable levels. Reinstatement of the donor into the plasmapheresis
program when the donor's values have returned to acceptable levels must
first be approved by the responsible physician.
* * * * *
29. Section 640.69 is amended by adding paragraphs (e) and (f) to
read as follows:
Sec. 640.69 General requirements.
* * * * *
(e) Restrictions on distribution. Establishments must ensure that
Source Plasma donated by paid donors not be used for further
manufacturing into injectable products until the donor has a record of
two suitable donations within the last 6 months.
(f) Hold. Source Plasma donated by paid donors determined to be
suitable for further manufacturing into injectable products must be
held in quarantine for a minimum of 60 days before it is released for
further manufacturing.
30. Section 640.72 is amended by revising paragraphs (a)(2),
(a)(3), and (a)(4) to read as follows:
Sec. 640.72 Records.
(a) * * *
(2)(i) For each donor, a separate and complete record of initial
and periodic examinations, tests, laboratory data, and interviews as
required in Sec. Sec. 630.10 and 630.15 of this chapter and Sec. Sec.
640.65, 640.66, and 640.67, except as provided in paragraph (a)(2)(ii)
of this section.
(ii) Negative results for testing for evidence of infection due to
relevant transfusion-transmitted infections required in Sec. 610.40 of
this chapter, and the volume or weight of plasma withdrawn from a donor
need not be recorded on the individual donor record if such information
is maintained on the premises of the plasmapheresis center where the
donor's plasma has been collected.
(3) The original or a clear copy of the donor's written statement
of understanding for participation in the plasmapheresis program or for
immunization.
(4) Documentation by the responsible physician that the donor is in
good health under Sec. Sec. 630.10 and 630.15 of this chapter on the
day of examination; such documentation must address the eligibility of
the donor as a plasmapheresis donor and, when applicable, an immunized
donor.
* * * * *
31. Section 640.73 is revised to read as follows:
Sec. 640.73 Reporting of donor reactions.
(a) If a donor has a fatal reaction which, in any way, may be
associated with plasmapheresis, you must notify the Director of the
Center for Biologics Evaluation and Research by telephone as soon as
possible.
(b) If a donor enrolled in an immunization program for the
collection of Source Plasma under this subpart has an adverse
experience related to your administration of the immunizing agent, you
must report the event to FDA:
(1) By telephone, facsimile, express mail, or electronic mail as
soon as possible, if the adverse experience is a serious or life
threatening adverse experience, as described in Sec. 600.80(a) of this
chapter; or
(2) In an annual report, if the adverse experience is neither
serious nor life threatening. Such a report is due to FDA on the
anniversary of FDA's approval of your immunization program.
(c) You must follow up the initial report required under paragraphs
(a) and (b)(1) of this section by submitting a written report of the
investigation to the Director, Office of Compliance and Biologics
Quality, Center for Biologics Evaluation and Research, within 7 days of
your first learning of the donor's reaction. (See Sec. 600.2 of this
chapter.)
32. Section 640.120 is revised to read as follows:
Sec. 640.120 Alternative procedures.
(a) The Director, Center for Biologics Evaluation and Research, may
approve an exception or alternative to any requirement in subchapters C
and F of chapter I of title 21 of the Code of Federal Regulations
regarding blood, blood components, or blood products. If the Director
issues such approval orally, the Director will follow up that oral
approval by issuing a written approval. If approval is appropriate, the
Director may issue such an approval in response to:
(1) A written request from an establishment. Licensed
establishments must submit such requests in accordance with Sec.
601.12 of this chapter;
(2) An oral request from an establishment, if there are difficult
circumstances and submission of a written request is not feasible.
Establishments must follow up such oral request by submitting written
[[Page 63444]]
requests under paragraph (a)(1) of this section within 5 working days.
(b) In a public health emergency, the Director may issue an
exception or alternative to any requirement in subchapters C and F of
chapter I of title 21 of the Code of Federal Regulations regarding
blood, blood components, or blood products, if a variance under this
section is necessary to assure that blood, blood components, or blood
products will be available in a specified location to respond to an
unanticipated immediate need for blood, blood components, or blood
products.
(c) Periodically, FDA will provide a list of approved alternative
procedures and exceptions at http://frwebgate.access.gpo.gov/cgi-bin/leaving.cgi?from=leavingFR.html&log=linklog&to=http://www.fda.gov/cber.
PART 660--ADDITIONAL STANDARDS FOR DIAGNOSTIC SUBSTANCES FOR
LABORATORY TESTS
33. The authority citation for 21 CFR part 660 continues to read as
follows:
Authority: 21 U.S.C. 321, 331, 351, 352, 353, 355, 360, 360c,
360d, 360h, 360i, 371, 372; 42 U.S.C. 216, 262, 263, 263a, 264.
34. Section 660.31 is revised to read as follows:
Sec. 660.31 Eligibility of donor.
Donors of peripheral blood for Reagent Red Blood Cells must meet
all the criteria for donor eligibility under Sec. Sec. 630.10 and
630.15 of this chapter.
PART 820--QUALITY SYSTEM REGULATION
35. The authority citation for 21 CFR part 820 continues to read as
follows:
Authority: 21 U.S.C. 351, 352, 360, 360c, 360d, 360e, 360h,
360i, 360j, 360l, 371, 374, 381, 383; 42 U.S.C. 216, 262, 263a, 264.
36. Section 820.1(a)(1) is amended by revising the last sentence to
read as follows:
Sec. 820.1 Scope.
(a) Applicability. (1) * * * Manufacturers of blood and blood
components used for transfusion or for further manufacturing are not
subject to this part, but are subject to subchapter F of this chapter.
* * * * *
PART 1270--HUMAN TISSUE INTENDED FOR TRANSPLANTATION
37. The authority citation for 21 CFR part 1270 continues to read
as follows:
Authority: 42 U.S.C. 216, 243, 264, 271.
38. Section 1270.3 is amended by revising paragraph (b) to read as
follows:
Sec. 1270.3 Definitions.
* * * * *
(b) Blood component means a product containing a part of human
blood separated by physical or mechanical means.
* * * * *
Dated: October 25, 2007.
Jeffrey Shuren,
Assistant Commissioner for Policy.
[FR Doc. E7-21565 Filed 11-7-07; 8:45 am]
BILLING CODE 4160-01-S