[Federal Register: August 19, 1999 (Volume 64, Number 160)]
[Proposed Rules]
[Page 45355-45365]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr19au99-35]

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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Parts 606 and 630

[Docket No. 98N-0607]

General Requirements for Blood, Blood Components, and Blood
Derivatives; Notification of Deferred Donors

AGENCY: Food and Drug Administration, HHS.

ACTION: Proposed rule.

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SUMMARY: The Food and Drug Administration (FDA) is proposing to require
blood and plasma establishments to notify donors of their deferral due
to test results for communicable disease agents or failure to satisfy
suitability criteria with the intent of reducing the risk of
transmission of communicable disease through the use of blood, blood
components, and blood derivatives. Under the proposed rule, blood and
plasma establishments would notify the donors that they have been
deferred and the reason for the deferral; provide information
concerning appropriate medical followup and counseling; describe the
types of donations the donors should not make in the future; and
discuss the possibility that the donor may be found suitable in the
future, where appropriate. FDA is issuing this rule as part of the
agency's ``Blood Initiative'' in which FDA is reviewing and, when
appropriate, revising its regulations, policies, guidance, and
procedures related to blood and blood products, including blood
derivatives.

DATES: Submit written comments by November 17, 1999. Submit written
comments on the information collection provisions by September 20,
1999.

ADDRESSES: Submit written comments to the Dockets Management Branch
(HFA-305), Food and Drug Administration, 5630 Fishers Lane, rm. 1061,
Rockville, MD 20852. Comments should be identified with the docket
number found in brackets in the heading of this document. Submit
written comments on the information collection provisions to the Office
of Information and Regulatory Affairs (OMB), New Executive Office
Bldg., 725 17th St. NW., Washington, DC 20503, Attention: Wendy Taylor,
Desk Officer for FDA.

FOR FURTHER INFORMATION CONTACT: Paula S. McKeever, 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:

I. Introduction

    For a variety of reasons discussed as follows, FDA has decided to
comprehensively review and, as necessary, revise its regulations,
policies, guidance, and procedures related to the licensing and
regulation of blood products. In the Federal Register of June 3, 1994
(59 FR 28821 and 59 FR 28822, respectively), FDA issued two documents
entitled ``Review of General Biologics and Licensing Regulations''
(Docket No. 94N-0066) and ``Review of Regulations for Blood
Establishments and Blood Products'' (Docket No. 94N-0080). The
documents announced the agency's intent to review biologics regulations
(parts 600, 601, 606, 607, 610, 640 and 660 (21 CFR 600, 601, 606, 607,
610, 640 and 660)), and requested written comments from the public.
Interested persons were given until August 17, 1994, to respond to the
documents. In response to requests for additional time, FDA twice
extended the comment period, as announced in the Federal Register of
August 17, 1994

[[Page 45356]]

(59 FR 42193), and November 14, 1994 (59 FR 56448). In addition, FDA
responded to requests for a public meeting to allow for the
presentation of comments regarding the agency's intent to review the
biologics regulations. On January 26, 1995, FDA held a public meeting
to provide an opportunity for all interested individuals to present
their comments and to assist the agency in determining whether the
regulations should be revised, rescinded, or continued without change.
Since the time of the regulation review, FDA has implemented a number
of changes to its regulations and policies applicable to the general
biologics and licensing regulations, some of which have applied to
blood products as well as other biological products. (See, e.g., the
final rules issued May 14, 1996 (61 FR 24313); August 1, 1996 (61 FR
40153); November 6, 1996 (61 FR 57328); July 24, 1997 (62 FR 39890);
and October 15, 1997 (62 FR 53536)).
    Because of the importance of a safe national blood supply, the U.
S. House of Representatives Committee on Government Reform and
Oversight, Subcommittee on Human Resources and Intergovernmental
Relations (the Subcommittee) and other groups such as the General
Accounting Office (GAO), and the Institute of Medicine (IOM) have
reviewed the agency's policies, practices, and regulations. Reports
issued following the respective reviews made a number of
recommendations as to how FDA might improve the biologics regulations,
particularly as they apply to the continued safety of blood products.
The relevant reports are: (1) ``Protecting the Nation's Blood Supply
From Infectious Agents: The Need for New Standards to Meet New
Threats,'' by the Subcommittee (August 2, 1996); (2) ``Blood Supply:
FDA Oversight and Remaining Issues of Safety,'' by GAO (February 25,
1997); (3) ``Blood Supply: Transfusion-Associated Risk,'' by GAO
(February 25, 1997); and (4) ``HIV and the Blood Supply: An Analysis of
Crisis Decisionmaking,'' by IOM (July 13, 1995). These reports are on
file with the Dockets Management Branch (address above) under the
docket number given in the heading of this document.
    FDA has reviewed these reports and agrees with the majority of the
recommendations contained within them. However, rather than to only
respond specifically to the recommendations from the Subcommittee, GAO,
IOM, and the public, FDA has convened a number of internal task forces
to review a variety of issues related to the regulation of blood and
blood products, including how to most appropriately update the existing
regulations applicable to blood and blood products. In the future, FDA
intends to issue a number of blood-related rulemakings that various FDA
task groups are currently preparing. FDA is not describing the specific
recommendations it has received and the numerous objectives of the
Blood Initiative in this document. Future rulemaking and other notices
will describe and discuss specific recommendations and regulatory
objectives.

II. Background on Notification of Deferred Donors

    This rule is proposed in order to reduce the risk of infection due
to communicable disease agents to blood product recipients and to
individuals handling blood or blood products. The safety of the blood
supply is enhanced when donors who may present significant risks of
transmitting infectious disease, because of testing results indicating
evidence of infection due to communicable disease agents or failure to
satisfy suitability criteria associated with the prevention of certain
communicable disease agents, are excluded from donating blood and blood
components. FDA has issued regulations at parts 610 and 640 on donor
testing and suitability in order to help assure the safety of blood
products. The Public Health Service (PHS) and FDA, as part of PHS, also
have periodically issued guidance on donor testing, suitability,
deferral, and notification when new scientific developments warranted.
This rule is also being proposed so that donors may be informed of
their deferral and seek medical counseling or treatment, if
appropriate. Additionally, such notification is expected to improve
blood safety by preventing re-donation by individuals at risk for
transmitting infectious disease. Also, precautions taken to minimize
the risk of transmission by informed donors may reduce the spread of
communicable diseases in the population.
    FDA has taken a number of actions to provide for the notification
of certain deferred donors. Described in the following paragraphs are
some of the more significant actions and their impact on donor
notification.
    In 1983, PHS issued guidelines recommending that individuals at
increased risk for Acquired Immune Deficiency Syndrome (AIDS) refrain
from donating (Ref. 1).
    In 1985, PHS issued guidelines concurrent with the approval of
human immunodeficiency virus (HIV) antibody tests that donors testing
repeatedly reactive in screening tests for human immunodeficiency
virus, type 1 (HIV-1) be notified. In addition, PHS recommended that
the donor be notified if other tests such as the Western blot were
positive (Ref. 2).
    In 1987, PHS recommended that a person be considered to have
serologic evidence of HIV infection only after an enzyme immunoassay
screening test was repeatedly reactive and another test such as Western
blot had been performed to validate the results (Ref. 3). These
recommendations have been updated periodically (Refs. 4 and 5) and
extended to include notification of donors testing positive for
antibody to human immunodeficiency virus, type 2 (HIV-2) (Ref. 6).
    In its 1990 recommendations, FDA recommended to blood
establishments that supplemental testing be performed prior to donor
notification in its Memorandum to Blood Establishments: Recommendations
for the Prevention of Human Immunodeficiency Virus (HIV) Transmission
by Blood and Blood Products.
    In 1988, PHS recommended notification of donors who were confirmed
positive for human T-lymphotropic virus, type I (HTLV-I) of their test
results and that they had been deferred as a donor in Licensure of
Screening Tests for Antibody to T-Lymphotropic Virus, Type I (Ref. 7).
    In 1991, the Department of Health and Human Services (DHHS), in a
PHS Inter-Agency Guideline, recommended notifying donors of the results
of tests for hepatitis B surface antigen (HBsAg), antibody to hepatitis
C virus (anti-HCV), alanine aminotransferase (ALT) and antibody to
hepatitis B core (anti-HBc) in the Public Health Service Interagency
Guideline for Screening Donors of Blood, Plasma, Organs, Tissue and
Semen for Evidence of Hepatitis B and Hepatitis C (Ref. 8).
    In the 1995 Guideline for Quality Assurance in Blood Establishments
(60 FR 36290, July 14, 1995), FDA further identified donor notification
and counseling as two of the five key elements of donor deferral.
    The blood industry has adopted these recommendations as well as
developed their own guidance on donor notification. Industry practice
includes notifying donors who are permanently deferred due to positive
test results for viral markers of their deferred status and providing
recommendations for followup testing, counseling, and appropriate
medical referral. In the past, however, FDA has not issued regulations
on when a deferred donor should be notified. To further enhance the
safety of the blood supply, FDA

[[Page 45357]]

believes that donors should be notified when they are deferred due to
test results or donor suitability criteria. Accordingly, FDA is
proposing to require notification of donors who are deferred for
evidence of infection due to communicable disease agents as required
under proposed Sec. 610.41 and for failure to satisfy suitability
criteria associated with the prevention of communicable diseases. The
proposed rule would help assure consistency in the blood industry's
notification practices, and would provide FDA with clear enforcement
authority if compliance problems occur.
    GAO, at the request of Congressman John Dingell, Ranking Minority
Member, Committee on Commerce, House of Representatives, recently
reviewed the FDA's ``layers of safety'' intended to help ensure the
safety of blood products in order ``to identify issues that might
threaten the nation's blood supply.'' In its report of February 1997
entitled ``Blood Supply: Transfusion Associated Risks,'' GAO concluded
that ``the blood supply is safer today than at any time in recent
history.'' Nevertheless, in an accompanying report (``Blood Supply: FDA
Oversight and Remaining Issues of Safety''), GAO made several
recommendations on improving the safety of our nation's blood supply.
GAO recommended that ``(FDA) require blood facilities to notify all
donors who are permanently deferred that they have been deferred and
the medical reason they are deferred.'' Citing public health concerns,
GAO further recommended that:
     * * * (N)otification be based on positive confirmatory tests
for viral markers (for the viruses that have licensed confirmatory
tests) and all other medical reasons that result in permanent
deferral (for example, the intake of pituitary growth hormone).
Notification should include the reason for the permanent deferral,
possibilities for re-entry as a donor, and counseling or referral to
the donor's physician (including, when pertinent, actions to be
taken to minimize transmission of viruses to others).
In its response, DHHS generally agreed with the GAO recommendations.
FDA believes the proposed donor notification rule would enhance blood
safety by promoting self-exclusion of donors who may present
significant risks to the blood supply. FDA believes that donors who are
informed of and understand the significance of their deferred status
are less likely to attempt to donate again, thus helping to assure a
safer blood supply. Donor notification also would enhance the public
health by informing donors, as appropriate, of the need to seek
treatment and additional medical counseling. Such measures could
benefit the health of the donor and also provide information needed to
prevent further spread of infection.

III. The Impact of Other Proposed Rules

    FDA intends to issue other proposed rules in conjunction with the
proposed donor notification rule. FDA is proposing to revise the donor
testing and deferral regulations in part 610, which apply to blood and
blood components. The related proposed testing and deferral document is
found elsewhere in this issue of the Federal Register. FDA also intends
to issue in the near future a proposed rule to revise donor suitability
requirements.
    The related proposed testing and deferral rule would, among other
things, add requirements to test blood and blood components for
evidence of infection due to hepatitis C virus (HCV), HTLV-I, and HTLV-
II, while retaining testing requirements for hepatitis B virus (HBV),
HIV-1, and HIV-2. FDA intends that the proposed testing rule would
replace the requirements currently found in Secs. 610.40 through
610.45. The testing and deferral requirements for a serologic test for
syphilis (i.e., evidence of infection due to Treponema pallidum) found
in Secs. 640.5 and 640.65 would remain in part 640. The related
proposed testing and deferral rule also would add a requirement in
proposed Sec. 610.41 that, except in certain specified circumstances,
donors testing repeatedly reactive for evidence of infection due to a
communicable disease agent(s) listed in proposed Sec. 610.40(a) be
deferred from future donations of blood or blood components. In
addition, donors testing reactive for a serologic test for syphilis
would also be deferred except as provided in current Sec. 640.65 or
proposed Sec. 610.41. Under the proposed donor notification rule, blood
and plasma establishments would be required to notify donors who have
been deferred under proposed Sec. 610.41.
    As mentioned previously, FDA also intends to propose to revise the
donor suitability requirements for donors of blood and blood
components. FDA intends to identify donor suitability criteria that
would cause a donor to be deferred and thus trigger notification under
the proposed donor notification document. Among those donor suitability
criteria being considered are high risk behavior associated with the
transmission of HIV, HBV, and HCV, such as past or present abuse of
injectable drugs. A new section identifying donor suitability criteria
will be designated in the final rule for donor notification.

 IV. 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 et seq.) and the provisions of the Federal Food,
Drug, and Cosmetic Act (the act) that apply to drugs (21 U.S.C. 201 et
seq.). Under section 361 of the PHS Act, FDA may make and enforce
regulations necessary to prevent the introduction, transmission, and
spread of communicable disease between the States or from foreign
countries into the States (see Sec. I, 1966 Reorg. Plan No. 3 at 42
U.S.C. 202 for delegation of section 361 authority from the Surgeon
General to the Secretary of the Department of Health and Human Services
(Secretary); see 21 CFR 510.(a)(4) for delegation from the Secretary to
the Food and Drug Administration). Intrastate transactions may also be
regulated under section 361 of the PHS Act (see Louisiana v. Mathew,
427 F. Supp. 174, 176 (E.D.La. 1977)).
    Notification of donors that they have been deferred and
consequently should not attempt subsequent donations would help prevent
unsafe units of blood or blood products from entering the blood supply.
The proposed rule targets those donors who may present significant
risks of infectious agents; thus, it works directly to prevent the
introduction and spread of communicable disease. Moreover, the proposed
rule is designed to help ensure that risks of transmitting infectious
disease are excluded from the pool of eligible donors. FDA relies on a
system of overlapping layers of safety to ensure the safety of the
nation's blood products. One of the important layers of safety is the
self-exclusion of donors because of high-risk behaviors associated with
the risk of HIV, or hepatitis B and C, or signs and symptoms of AIDS
and hepatitis. A second crucial layer of safety is the system of donor
deferral registries designed to eliminate unsuitable donors from the
donor population. Notification of donors who are deferred adds to the
protection provided by donor deferral registries by making deferred
donors aware that they should not attempt to donate again.
Consequently, the screening of unsuitable donors provided by the
registries is enhanced by the self-exclusion of donors who have been
made aware of their status and the risks their donation may present to
the blood supply.
    The proposed notification rule also would protect the health of the
deferred donor by assuring that the individual is

[[Page 45358]]

aware he or she may need further medical evaluation including testing,
treatment, and counseling. As FDA has previously made clear ``(i)n an
indirect but no less important manner, the requirements of donor
protection assure * * * that there will be a continuous and healthy
donor population'' (Additional Standards for Human Blood and Blood
Products (41 FR 10762, March 12, 1976)).
    FDA's license revocation regulations provide for the initiation of
revocation proceedings, among other reasons, if 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). Section 351 of
the PHS Act also provides for criminal penalties for violation of the
laws governing biologics. Violations can be punishable by fines or
imprisonment, or both.
    The act also applies to biological products (42 U.S.C. 262(d)), as
amended. Blood and blood components are considered drugs, as that term
is defined in section 201(g)(1) of the act (21 U.S.C. 321(g)(1)) (see
United States v. Calise, 217 F. Supp. 705 (S.D.N.Y. 1962)). Because
blood and blood components are drugs under the act, blood and plasma
establishments must comply with the substantive provisions and related
regulatory scheme of the act. Under section 501(a)(2)(B) of the act,
drugs are deemed ``adulterated'' if the methods used in their
manufacturing, processing, packing, or holding do not conform with
current good manufacturing practices (CGMP's) (21 U.S.C. 351(a)(2)(B)).
Under the proposed donor notification rule, blood and plasma
establishments would be required to develop standard operating
procedures (SOP's) for notifying deferred donors. A blood or plasma
establishment that failed to comply with donor notification procedures
would violate CGMP's and, therefore, would be subject to the act's
enforcement provisions.

V. Description of the Proposed Rule

    FDA is proposing to create a new part 630, General Requirements for
Blood, Blood Components, and Blood Derivatives. This part would include
the following: (1) Consolidation of the criteria to be used when
determining suitability of donors of human blood and blood components;
(2) requirements for donor deferral from future donation when a donor
fails to satisfy the suitability criteria; and (3) requirements for
donor notification and the reason for their deferral due to donor test
results or failure to satisfy suitability criteria. Donor suitability
criteria and donor deferral are not the subject of this proposed rule.
These proposed requirements will be addressed in a rulemaking to be
published in the near future. As necessary, FDA may add other
requirements applicable to blood products in the future. The focus of
this proposed rulemaking would be to require donor notification when
the donor is deferred due to testing results or failure to meet donor
suitability criteria and to provide the reason for the deferral.
    The proposed rule would require blood and plasma establishments to
notify donors who are deferred in accordance with proposed Sec. 610.41
or for failure to satisfy donor suitability criteria that they have
been deferred as donors and the reason for their deferral. Deferred
donors would be informed, as appropriate, that they should not donate
blood or blood components in the future. Donors would also be informed
about the need for additional counseling and medical evaluation, as
appropriate. Under the proposed rule, blood and plasma establishments
would be required to develop SOP's for deferring donors and notifying
deferred donors. FDA is not proposing to require blood and plasma
establishments to notify donors who the blood or plasma establishments
may defer voluntarily for a variety of medical reasons beyond the
requirements in proposed Sec. 610.41 and donor suitability criteria
associated with the prevention of communicable diseases. FDA recognizes
that blood and plasma establishments would need to exercise medical
judgment in determining which donors to defer voluntarily and whether
to notify such donors. PHS and FDA may periodically issue
recommendations on testing, deferral, and notification of donors who
may be at risk of infectious disease.
    Donors whose blood or blood components test repeatedly reactive for
evidence of infection due to a communicable disease agent for which
testing would be required by FDA under proposed Sec. 610.40, or as
specified for syphilis in current Secs. 640.5 or 640.65, would be
deferred in accordance with proposed Sec. 610.41. Blood and plasma
establishments would notify such deferred donors under the proposed
notification rule that they have been deferred, and the reason for
their deferral including their screening test results and the results
of any approved supplemental (i.e., additional, more specific) tests
that were performed. FDA currently requires that supplemental testing
for both HIV-1 and HIV-2 antibodies be performed under Sec. 610.46. PHS
and FDA have recommended that HIV notification should occur after the
results of the approved supplemental testing are available. Results of
supplemental tests are useful in providing additional information for
purposes of medical followup and counseling. Therefore, FDA is
proposing that blood establishments attempt to obtain the results of
supplemental testing proposed under Sec. 610.40(c) prior to notifying
donors of their deferral. FDA has included a maximum time period of 8
weeks to notify the donor. If notification occurs prior to receipt of
the supplemental test results, blood establishments would be required
to renotify the donors with the results of the supplemental testing.
    Blood and plasma establishments would be required to notify
deferred donors where appropriate, of the possibility for re-entry as
donors of blood and blood components if they are found to be suitable
using methods or processes approved by FDA in accordance with proposed
Sec. 610.41 or current Sec. 640.65, provided that the donor meets all
other requirements.
    Under Sec. 610.40 of the proposed testing rule, blood and plasma
establishments would be required to test blood and blood components,
including autologous donations, for evidence of infection due to HIV-1,
HIV-2, HBV, HCV, HTLV-I, and HTLV-II using FDA approved tests. Donors
whose donations test repeatedly reactive for evidence of those agents
required under proposed Sec. 610.40(a) or for syphilis under current
Secs. 640.5 and 640.65 would be deferred in accordance with proposed
Sec. 610.41. This proposed donor notification rule would require that
blood and plasma establishments notify the deferred donor of their
deferral and of their test results.
    In the related proposed Sec. 610.41, FDA is proposing several
exceptions to donor deferral that also have an impact on donor
notification. Autologous donors testing repeatedly reactive for
communicable disease agents would not be deferred. Blood establishments
would not be required under this proposed rule to notify autologous
donors who test repeatedly reactive for communicable disease agents
under proposed Sec. 610.40(a). Nevertheless, FDA recommends that blood
establishments notify autologous donors of repeatedly reactive test
results and supplemental test results, when applicable, for the purpose
of medical followup and counseling. FDA specifically is requesting
comments on whether to require notification of autologous donors of
repeatedly reactive and supplemental test results even though such
donors would not be deferred.

[[Page 45359]]

    In the related proposed Sec. 610.41(a), donors who test repeatedly
reactive for HTLV, types I and II, or anti-HBc on only one occasion,
would be permitted to donate again without being deferred from further
donation unless there is further testing using an approved supplemental
(additional, more specific) test. Should licensed supplemental tests
for HTLV, types I and II be approved, donors would be required to be
deferred after only a single repeatedly reactive donation similar to
most other screening tests. It is FDA's expectation that donor re-entry
algorithms would become feasible at that time. However, until such
time, upon testing repeatedly reactive a second time for HTLV, types I
and II or anti-HBc, the donor would be deferred. Blood establishments
would be required to notify donors that they have been deferred from
donations of Whole Blood, and transfusable components (including
Plasma) only after they had tested repeatedly reactive a second time
for HTLV, types I and II or anti-HBc. FDA specifically requests
comments on whether to notify donors who test repeatedly reactive for
HTLV, types I and II or anti-HBc on only one occasion or to wait to
notify donors upon testing repeatedly reactive the second time. Upon
the availability of an approved supplemental (additional, more
specific) test, a repeatedly reactive donor would be deferred after a
single repeatedly reactive donation. At such time, blood establishments
would notify donors of the test results of both the approved screening
and supplemental tests. As appropriate, blood establishments would
notify such deferred donors that they may be eligible for re-entry if
determined to be suitable by a method or process approved by FDA in
accordance with proposed Sec. 610.41.
    In related Sec. 610.41(b), FDA is proposing to except from deferral
donors testing repeatedly reactive for HTLV, types I and II, or anti-
HBc as donors of Source Plasma. However, the agency is requesting
comments in the proposed rule ``Requirements for Testing Human Blood
Donors for Evidence of Infection Due to Communicable Disease Agents''
(hereinafter the ``proposed rule on donor testing'') on permitting such
donors to donate Source Plasma to be used in the manufacture of plasma
derivatives as it relates to the exposure to other possible risks, such
as through the association of HTLV infection with abuse of intravenous
drugs. The agency also includes in the proposed rule on donor testing a
discussion on the risk of transmitting HTLV, types I and II.
    Related proposed Sec. 610.41(c)(1) would permit deferred donors to
donate blood and blood components used in accordance with proposed
Sec. 610.40(f). In related proposed Sec. 610.40(f), the agency would
require that blood and blood components that test repeatedly reactive
when screened for evidence of infection due to communicable disease
agents listed in proposed Sec. 610.40(a) would not be shipped or used
except for autologous use or for purposes or under conditions approved
in writing by FDA. Blood and plasma establishments that collect blood
or blood components under conditions approved under proposed
Sec. 610.40(f)(2)(ii) or current Sec. 640.65 could notify donors
deferred under proposed Sec. 610.41 or current Sec. 640.65 that they
would be eligible to donate blood or blood components, as appropriate,
for use as a component of an in vitro device or for other approved
uses.
    In related Sec. 610.41(c)(2), the agency is proposing to restrict
the use of blood or blood components from donors showing previous
evidence of infection due to hepatitis B virus when tested in
accordance with proposed Sec. 610.40(a) and (c). Such blood and blood
components may be approved for use only 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. Donors with
previous evidence of infection with hepatitis B when tested in
accordance with proposed Sec. 610.40(a) and (c) may serve as donors of
a component of a medical device or as donors of Source Plasma for use
as a source of antibody to hepatitis B surface antigen for the
preparation of Hepatitis B Immune Globulin (Human). In the proposed
rule on donor testing, the agency has requested comments on the use of
vaccinated donors for HBV as an alternative to using donors previously
showing evidence of infection due to hepatitis B virus in the
preparation of Hepatitis B Immune Globulin (Human) provided their
current donations test nonreactive when tested in accordance with
proposed Sec. 610.40(a) and the donor is otherwise determined to be
suitable. Blood and plasma establishments that are approved to collect
Source Plasma from such donors under proposed Sec. 610.40(f) could
notify deferred donors that they may donate for such purposes.
    In related proposed Sec. 610.41, the agency is proposing to defer
donors who test reactive for a serologic test for syphilis except as
provided under current Sec. 640.65. In related proposed Sec. 610.41(d),
the agency would exempt from deferral donors who test reactive on a
serologic test for syphilis provided the donor is found negative by an
approved specific treponemal test (confirmatory test for syphilis).
Blood and plasma establishments would notify all other donors who test
reactive for evidence of syphilis that they have been deferred and of
the results of tests including the result of the approved specific
treponemal tests. However, as FDA has noted in the preamble to the
related proposed rule on donor testing, there is ongoing debate in the
scientific community as to the continuing need for a testing
requirement for the serological test for syphilis. Therefore, the
proposal to defer donors who test reactive for syphilis is subject to
change pending the outcome of the request for comments on the value of
donor testing for syphilis in the proposed rule on donor testing.
    The proposed rule also would require blood and plasma
establishments to notify donors who have been deferred because of donor
suitability criteria. FDA intends to create in future rulemaking a new
section identifying certain donor suitability criteria which are
intended to reduce the risk of communicable disease agents that would
result in deferral of the donor and require donor notification. Among
those donor suitability criteria being considered are high risk
behavior associated with the transmission of HIV, HBV, and HCV, such as
past or present abuse of injectable drugs. Blood and plasma
establishments would notify deferred donors of their deferral and
advise them to seek further testing or medical counseling, as
appropriate.
    Under the proposed rule, blood and plasma establishments would be
required to provide information to deferred donors concerning
appropriate medical followup and counseling. FDA currently recommends
that this information include disease associations and possible modes
of transmission as well as actions to be taken to minimize the risk of
transmission. FDA believes that such information also would include
referral to their own physician, or, where appropriate, the location of
public health clinics as well as alternative testing and counseling
centers. Blood and plasma establishments should consult current PHS
Guidelines and FDA recommendations for more detailed recommendations on
the content of donor notification.

A. Timeframe for Notification.

    Under Sec. 630.6(c) of the proposed rule, blood and plasma
establishments would be required to notify donors within 8 weeks after
determining that the donor should be deferred. In many instances

[[Page 45360]]

arising under the proposed rule, blood and plasma establishments would
be able to fulfill the notification requirements onsite. For example, a
donor who is deferred because of donor suitability criteria can be
notified at the time of the donor interview or at the first return
visit after the information is available, if within 8 weeks. Blood and
plasma establishments would be required to have SOP's addressing donor
deferral and notification and keep documentation on all deferrals as
well as any resulting notification. Some blood and plasma
establishments may notify deferred donors by registered mail, return
receipt; or may choose to request that the donor return for direct
donor notification, so long as notification of deferral occurred within
the 8-week period. FDA requests comments on (1) methods of notification
that would help assure adequate donor confidentiality and (2) the
current application and sufficiency of Federal, State, and local laws
that protect the privacy of the individual being notified. FDA believes
that at least three attempts should be made within an 8-week period. In
all cases, blood and plasma establishments should document their
attempts to notify donors and maintain a record of these attempts or of
the basis for discontinuing the effort to notify deferred donors.

B. Other Requirements.

    Donor notification should be conducted by trained personnel in
accordance with the requirements in Sec. 606.20. Blood and plasma
establishments would be required to revise their SOP's to include
procedures for notification of deferred donors. For the purposes of
notification under the proposed rule, blood and plasma establishments
would be required to maintain records of the donor's permanent address.
Donors should provide proof of a permanent, fixed address. Individuals
who do not have evidence of a current address or who merely provide an
address of a known or obviously transient nature should not be accepted
as donors.

VI. Analysis of Impacts and Initial Regulatory Flexibility Analysis

    FDA has examined the impacts of the proposed rule under Executive
Order 12866, under the Regulatory Flexibility Act (5 U.S.C. 601-612),
and under the Unfunded Mandates Reform Act (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 Regulatory
Flexibility Act requires agencies to analyze whether a rule may have a
significant impact on a substantial number of small entities and, if it
does, to analyze regulatory options that would minimize the impact.
Section 202(a) of the Unfunded Mandates Reform Act requires that
agencies prepare a written statement of anticipated costs and benefits
before proposing any rule that may result in an expenditure by State,
local, and tribal governments, in the aggregate, or by the private
sector, of $100 million in any one year (adjusted annually for
inflation).
    OMB has determined that the proposed rule is is a significant
regulatory action as defined by the Executive Order and so is subject
to review. Because the rule does not impose any mandates on State,
local, or tribal governments, or the private sector, that will result
in any 1 year of $100 million or more, FDA is not required to perform a
cost-benefit analysis according to the Unfunded Mandate Reform Act.
    The Regulatory Flexibility Act requires agencies to prepare a
Regulatory Flexibility Analysis for each rule unless the agency
certifies that the rule will not have a significant economic impact on
a substantial number of small entities. As explained in the following
sections of this document, the proposed rule is not expected to have a
significant economic impact on a substantial number of small business
entities because donor deferral and notification are considered usual
and customary business for the affected entities.

A. Objectives and Basis of the Proposed Action

    As discussed previously, FDA is considering the proposed action for
the purpose of reducing the risk of infection due to communicable
disease agents to blood recipients and to individuals handling blood or
blood products. The safety of the nation's blood supply is enhanced
when donors whose test results indicate evidence of infection due to
communicable disease agents or fail to satisfy suitability criteria
associated with the prevention of certain communicable disease agents
are excluded from donating blood and blood components. Once donors are
deferred from donation, such donors would be informed of their deferral
and the reason, and advised to seek medical counseling or treatment, as
appropriate. Public health would be protected not only by deferring the
donor from future donations and preventing the transmission of
communicable disease agents through transfusion, but also by counseling
the donor in precautions to minimize the risk of transmitting the
disease to others in daily life.
    This action is taken under the authority of sections 351 and 361 of
the PHS Act and section 501 of the act to prevent the introduction,
transmission, and spread of communicable disease, and to ensure that
methods used in manufacturing conform with CGMP's. Failure to comply
with donor notification procedures would violate CGMP's and, therefore,
would be subject to the act's enforcement provisions. FDA has reviewed
related Federal rules and has not identified any rules that duplicate,
overlap, or conflict with the proposed rule.

B. Nature of the Impact

    The proposed rule requires that blood establishments notify
deferred donors of their deferral based on either suitability criteria
included in the donor screening interview or because of the results of
testing for evidence of infection due to disease agents including HIV,
HTLV, hepatitis B, or hepatitis C. Under the proposed rule, the donor
must be notified that he or she has been deferred, and the reason for
deferral. The deferred donor must also be notified of the types of
blood or blood components that should not be donated in the future. The
notification must also include the results of tests for evidence of
infection due to communicable disease including supplemental test
results, information concerning appropriate medical followup and
counseling, and when applicable, the possibility that the donor may be
found suitable for future donations. The donor notification process
must include three attempts of notification, completed within 8 weeks
of the determination of the donor deferral. In order to implement this
notification process, the proposed rule also requires that blood
establishments obtain a permanent address for each prospective donor.
The establishment must also maintain records of its attempts to notify
a deferred donor within the prescribed timeframe.

C. Type and Number of Entities Affected

    The proposed deferred donor notification requirements will affect
all blood and plasma establishments that collect blood and blood
components from allogeneic donors. FDA's Office of Blood Research and
Review (OBRR) has record of 2,801 registered blood and plasma
establishments, including 487

[[Page 45361]]

plasma centers and 2,314 blood centers. The American Association of
Blood Banks (AABB) estimates that approximately 14 million blood
donations are collected annually. Allogeneic blood donations have
recently accounted for an estimated 87.2 percent of that total (Ref.
9). In 1997, GAO estimated that approximately 12 million donations of
source plasma were collected by plasma centers (Ref. 10).

D. Estimated Impact of Proposed Requirements for Deferred Donor
Notification

    The proposed rule is expected to have a minor net impact on blood
establishments because the blood industry has already generally
implemented deferred donor notification; virtually all establishments
include this process within current operational guidelines. FDA expects
that the primary impacts of the proposed rule will include a one-time
review effort at each facility and a more extensive notification
process at those facilities that currently perform deferred donor
notification over a longer timeframe or with fewer followup attempts
than specified in the rule.
    The one-time effort to review and modify current SOP's is expected
to vary among establishments depending on the extensiveness of a
facility's current protocols for deferred donor notification. For
establishments that already keep required donor information and perform
the level of notification effort specified by the rule, FDA estimates
that it would take approximately 4 hours of staff time to reconcile the
proposed regulations against the facility's current standards. This
process could be performed by a technical specialist who acts as a
regulatory reviewer or manager of quality assurance. Based on the total
average hourly compensation of $25.67 for professional specialty and
technical occupations in the health services industry, as reported by
the Bureau of Labor Statistics for March 1997, the cost would be
approximately $103 per facility. For establishments that already
perform donor deferral notification but information provided to
deferred donors or other aspects of the notification process are not
the same as specified in the proposed rule, FDA assumes that
approximately 24 hours of staff time would be required to align current
SOP's and donor recordkeeping with the provisions of the rule. The cost
in this case would be approximately $616 per facility. FDA does not
have the data to estimate the percentage of facilities that will
require a minimal effort versus a more involved review of SOP's;
however, it is expected that many facilities have SOP's and
recordkeeping standards that are consistent with the rule. Assuming a
minimal review is needed at two-thirds of the currently operating
establishments, and a more extensive review is conducted by the others,
the total one-time cost for the blood and plasma industries is
estimated to be $762,158.
    The yearly increase in cost is based on the ongoing notification of
deferred donors. FDA assumes that all donors deferred based on the
screening interview can be notified onsite at the time of deferral, and
provided with the proposed information. FDA assumes that this will
introduce no new costs for the blood and plasma establishments. The
cost of notifying donors deferred on the basis of blood test findings
is based on a proportional extrapolation of the number of donors who
would test repeatedly reactive for evidence of infection in tests for
HIV, HTLV, HBV, or HCV, and have positive findings in supplemental
testing. Assuming a prevalence rate of 121.9 per 100,000 for viral
markers for HIV, HTLV, HBV, or HCV among prospective donors (Ref. 11),
that approximately 80 percent of donations are made by repeat donors
\1\, that repeat donors average two donated units per year \2\, and
that first time donors contribute one unit, an estimated 8,887 deferred
blood donors and 8,861 plasma donors (including first time and repeat
donors) would be identified each year.
---------------------------------------------------------------------------

    \1\ This percentage is based on American Red Cross estimates
based on donations between January 1996 and June 1997.
    \2\ The estimate of an average of two donations per year for
repeat blood donors is based on the Center for Disease Control's
(CDC's) analysis of blood donations prepared for HCV lookback.
---------------------------------------------------------------------------

    FDA assumes that all facilities currently make at least one
notification attempt for all deferred donors. However, the percentage
of facilities that currently make up to three documented attempts
within an 8-week period is not known. FDA has therefore estimated the
economic impact for two scenarios in which the cost of compliance is
based on the assumption that two additional notification attempts are
needed, and these notifications are made via registered mail with a
return receipt requested, at a cost of $12.54 \3\ per notified donor.
Under the first scenario, FDA assumes half of deferred donors are
currently notified through a process like the one specified in the
proposed rule. In this case, the cost of compliance, based on the cost
of up to two additional notifications to the remaining half of the
estimated deferred donors totals $55,719 for the blood industry, and an
estimated $55,557 for the plasma industry. Under the second scenario,
FDA considers that only one-quarter of deferred donors are currently
receiving up to three notification attempts. Under this scenario, the
cost of up to two additional notifications to the remaining three-
quarters of the estimated deferred donors totals $83,578 for the blood
industry, and an estimated $83,335 for the plasma industry. Thus, the
ongoing notification costs for the blood and plasma industries combined
are estimated to range from $111,276 to $166,913 per year.
---------------------------------------------------------------------------

    \3\ This estimate is based on two mailings, at a cost of $6.27
each. This cost includes $.32 first class postage plus $4.85 fee for
registered mail without insurance, plus $1.10 fee for return receipt
requested at the time of mailing showing whom, signature, date and
addressee's address (if different) source: USPS 1997 Postal Rates @
``www.usps.gov/consumer''.
---------------------------------------------------------------------------

E. Expected Benefits of the Proposed Rule

    As described in the preamble to this rule, notification of donors
that they have been deferred and consequently should not attempt
subsequent donations will help prevent unsafe units of blood or blood
products from entering the blood supply. Notification of donors who are
deferred and can self-defer in the future thus adds to the protection
provided by donor deferral registries. In FDA's proposed rule on donor
testing found elsewhere in this issue of the Federal Register, the
agency provides an extensive discussion of the benefits of reducing
public exposure to the risks of these infectious diseases. FDA refers
the reader to this discussion of the significant public health benefits
of minimizing patients' risk of being unwittingly exposed to infection
with HIV, HTLV, hepatitis B, and hepatitis C.

F. Small Entity Impact

    The proposed rule is not expected to have a significant impact on a
substantial number of small entities, however, the impact on blood and
plasma establishments that qualify as small entities is uncertain. FDA
has therefore prepared an initial regulatory flexibility analysis. The
blood and plasma establishments affected by the proposed rule are
included under the major standard industrial code (SIC) group 80 for
providers of health services. According to section 601 of the
Regulatory Flexibility Act of 1980, the term ``small entity''
encompasses the terms ``small business,'' ``small organization,'' and
``small governmental jurisdiction.'' According to the Small Business
Administration (SBA), a small business within the blood industry is an

[[Page 45362]]

enterprise with less than $5 million in annual receipts. A small
organization is a not-for-profit enterprise which is independently
owned and operated and is not dominant in its field. A ``small
governmental jurisdiction'' generally means governments of cities,
counties, towns, townships, villages, school districts, or special
districts, with a population of less than 50,000.
    As noted in the foregoing analysis, the proposed rule is expected
to have some cost impact on both plasma and blood collection centers.
FDA has registered a total of 487 plasma collection facilities. Of that
total, the General Accounting Office (GAO) (Ref. 12) has identified
approximately 370 for-profit plasma collection centers that primarily
collect paid plasma donations. The remaining 100 or so plasma
collection facilities function within blood collection centers with
volunteer donors, that are either operated by the American Red Cross,
or are independently operated. The vast majority of collected source
plasma is processed by four companies: Alpha Therapeutic Corp., Baxter
Healthcare Corp., Bayer Corp., and Centeon LLC.
    FDA estimates that approximately 90 percent of these 370 paid
plasma collection centers are owned by companies that operate a number
of centers and have annual receipts in excess of $5 million per year.
The remaining 10 percent, or about 37 paid plasma collection centers,
may qualify as small business establishments. Of the 100 or so
volunteer plasma collection facilities within blood collection centers,
the independently operated, not-for-profit blood collection centers
would likely qualify as small entities. The potential impact on plasma
collection facilities will be a function of the number of donors and
the viral marker rates among donors at their facility. The net impact
on these facilities, however, is expected to be minor. For example,
under cost scenario 1, if the additional yearly cost of $55,557 were
evenly distributed across all 487 registered facilities, this would
translate to an added cost of $114 per facility per year. Under
scenario 2, the added cost per facility would be approximately $171 per
year.
    The impact on blood collection facilities that qualify as small
entities is also uncertain, although it is not expected to be
significant. The blood collection facilities that are independent and
not-for-profit organizations may qualify as small entities regardless
of the size of their operations. The analysis that follows, however,
considers the smaller blood collection facilities, because they are
expected to experience the greater cost impact. According to the 1996
directory of the AABB, 34 regional and community blood centers have
annual revenues of less than $5 million; and each collect no more than
30,000 donations per year. Because of the pre-existing practice of
deferred donor notification at these facilities, and the relatively
small number of donors that FDA estimates will be deferred based on
blood test findings, the impact on these small facilities is expected
to be minor. Based on FDA's calculations, facilities with 30,000
donations or less per year would identify about 22 deferred donors per
year through blood testing. At a cost of $6.27 per notification via
registered mail with a return receipt, if all facilities currently need
to make two additional notification attempts under this rule, there
would be an average small facility notification cost of $278 (22 x
$12.54) per year. Because the estimated one-time cost for the review
and revision of current deferral notification SOP's equaled $271 (2/3 x
$103 + 1/3 x $616), or about $39 when annualized over a 10-year payment
period at a 7-percent interest rate, the average annualized cost impact
for the smaller collection centers would be about $317 ($278 + $39), or
roughly $0.01 per donation, assuming approximately 30,000 donations per
year. It should be noted that blood collection centers that collect
both blood and source plasma will not experience a ``double'' impact,
because the same donor pool and donations are used for production of
the center's blood and plasma products.
    The types of professional staff and skills required to perform the
required tasks were described in section VI.D of this document. FDA is
confident that the tasks specified in the proposed rule can be readily
performed by the type of staff already employed at affected blood and
plasma establishments.
    To alleviate the impact on small entities while continuing to
protect public health, the agency is proposing to recommend, but not
require, that autologous donors be notified, if they test repeatedly
reactive for evidence of infection; FDA also does not require that
these donors be deferred. To minimize facility notification efforts
while achieving the public health objectives, FDA proposes that
notification should not occur until after the results of the approved
supplemental testing are available. The proposed regulations are thus
expected to help enhance both public health and public confidence in
the safety of the blood and plasma supply, while imposing minimum
burden on manufacturers.
    As an alternative to this proposal, FDA has considered not
requiring donor notification of deferral from future donation due to
communicable disease testing or failure to satisfy suitability criteria
associated with the prevention of communicable disease because it is
viewed by many as medical practice. However, the agency has rejected
this alternative for the following reason. After a lengthy period of
time during which the agency published recommendations to
establishments on notifying donors of deferral, inconsistency
pertaining to information and counseling provided to the deferred donor
has been demonstrated among the establishments. Notification of donor
deferral has become a public health issue because donors who are not
fully informed of their deferral status due to communicable disease
testing or failure to meet suitability criteria associated with the
prevention of communicable disease may not take precautions to minimize
the transmission of communicable disease to others and may not
recognize the importance of not attempting to donate blood or blood
components in the future.

VII. The Paperwork Reduction Act of 1995

    This proposed rule contains information collection provisions that
are subject to review by the Office of Management and Budget (OMB)
under the Paperwork Reduction Act of 1995 (the PRA) (44 U.S.C. 3501-
3520). The title, description, and respondent description of the
information collection provisions are shown in this section of this
document with an estimate of the annual burden. Included in this
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: (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: General Requirements for Blood, Blood Components, and Blood
Derivatives; Notification of Deferred Donors.

[[Page 45363]]

    Description: FDA is proposing requirements for the donor
notification process which are intended to prevent further donations
from donors who have been deferred for positive test results for
evidence of communicable disease agent(s) or for failing to meet the
donor suitability criteria intended to reduce the risk of communicable
disease agents prior to collection. When a donor is deferred for
failing to meet suitability criteria associated with communicable
disease agents prior to collection, he or she would be advised not to
donate now or in the future and would be provided with information
regarding the need for medical followup and counseling. When test
results for communicable disease agents are finished, establishment
personnel would be required to make at least three attempts to notify
donors with positive supplemental (additional, more specific) test
results that they are deferred and should have medical followup and
counseling. The revisions would require blood and plasma establishments
to develop SOP's for deferring donors and for notifying deferred donors
and to maintain their permanent address, outline the information that
is to be provided to a deferred donor, and to notify deferred donors of
positive test results for evidence of infection by communicable disease
agent(s) within 8 weeks of the donation initiating deferral, or at
their first return visit, whichever is earlier. FDA is proposing these
new requirements to help ensure the nation's blood supply is safe by
excluding donors who may present significant risks from donating in the
future as well as enhancing the public health by assuring that those
donors who have been deferred are advised to seek treatment and
counseling.
    Description of Respondents: Manufacturers of blood, blood
components, and blood derivatives.
    There are an estimated 2,800 FDA registered blood and Source Plasma
collection facilities in the United States that collect approximately
27,000,000 units of Whole Blood and Source Plasma annually. There are
approximately 8 million donors of Whole Blood and 1.5 million donors of
plasma for a total of 9.5 million donors per year. From such
information as is available to FDA, the agency estimates that
approximately 1.2 percent of persons who come to donate annually are
deferred prior to donating because of disqualifying answers to the
medical history and behavior questionnaire. In addition to the 9.5
million donors per year there would be approximately 115,385 potential
donors deferred from donating. It is the customary and usual practice
of virtually all registered establishments to explain to a donor why he
or she is deferred and excluded from donating. Based on such
information as is available to FDA, the agency estimates that currently
two-thirds of registered establishments voluntarily provide additional
information and counseling to a deferred donor. Consequently, only one-
third or 933 collection facilities would have additional burden related
to this proposed rule. Some industry contacts estimated that it takes
on average approximately 5 minutes to provide the deferred donor with
the appropriate medical health information. FDA estimates that
currently 95 percent of the industry that collects 98 percent of the
blood and blood components have voluntarily established SOP's for
notifying donors who have repeatedly reactive test results that also
are positive by supplemental tests for HIV, HBV, or HCV (the number of
donors who test and confirm positive for HTLV is so small that this was
not included in the estimate). FDA estimates based on 9.5 million
donors annually and the viral marker incidence rates for HIV, HBV, and
HCV, that 49,591 donors would be deferred annually due to test results.
Consequently, 5 percent (140) of the industry collecting 2 percent
(992) of the deferred donors would experience new burden related to
this proposed rule. FDA estimates on the average it may take 15 minutes
to allow for up to three attempts to contact a donor and request that
they return for counseling which may take another 15 minutes for a
total of 0.5 hours.

                                  Table 1.--Estimated Annual Reporting Burden<SUP>1</SUP>
----------------------------------------------------------------------------------------------------------------
                                                      Annual
         21 CFR Section               No. of       Frequency per   Total Annual      Hours per      Total Hours
                                    Respondents      Response        Responses       Response
----------------------------------------------------------------------------------------------------------------
 630.6(a) and (b)<SUP>2</SUP>                    933              41          38,462                .08        3,077
 630.6(a), (b), and (c)<SUP>3</SUP>              140               7             992               0.5           496
TOTAL                                                                                               4,069
----------------------------------------------------------------------------------------------------------------
\1\ There are no capital costs or operating and maintenance costs associated with this collection of
  information.
\2\ Potential donors deferred prior to donation. The number of potential donors deferred annually prior to
  donation based on failure to meet suitability criteria associated with communicable disease agents is 115,385.
  Providing information on medical followup and counseling to these deferred donors is estimated to be new
  burden for approximately one-third of the registered blood and plasma collection facilities.
\3\ Donors deferred post donation due to test results. Providing information on medical followup and counseling
  to donors deferred due to test results may be new burden for approximately 5 percent of the industry
  collecting from 2 percent of such deferred donors. One hundred and forty represents 5 percent of the 2,800
  registered establishments and 992 represents 2 percent of the estimated 49,591 donors deferred annually due to
  test results.

                                Table 2.-- Estimated Annual Recordkeeping Burden<SUP>1</SUP>
----------------------------------------------------------------------------------------------------------------
                                                         Annual         Total
           21 CFR Section                No. of       Frequency per     Annual       Hours per      Total Hours
                                      Recordkeepers   Recordkeeping    Records     Recordkeeper
----------------------------------------------------------------------------------------------------------------
 606.100(b)(20)                        2,800               1              2,800         2           5,600
 606.160(b)(1)(ix)<SUP>2</SUP>                    2,800              59            164,976         3           8,400
 606.160(b)(1)(x)<SUP>3</SUP>                     2,800           9,643          27,000,000        0               0
 TOTAL                                                                                             14,000
----------------------------------------------------------------------------------------------------------------
\1\ There are no capital costs or operating and maintenance costs associated with this collection of
  information.
\2\ FDA estimates that annually 115,385 potential donors are deferred prior to donation and 49,591 donors are
  deferred due to test results. Recording the notification of each deferred donor is estimated to require
  between 2 and 5 minutes (3 minutes on average).
\3\ Recording the donor's permanent address is customary and usual practice in the industry and is not new or
  additional burden.

[[Page 45364]]

    In compliance with section 3507(d) of the Paperwork Reduction Act
of 1995 (44 U.S.C. 3507(d)), the agency has submitted a copy of this
proposed rule to OMB for review of the information collection
provisions. Interested persons are requested to submit written comments
regarding information collection by September 20, 1999, to the Office
of Information and Regulatory Affairs, OMB (address above), Attention:
Desk Officer for FDA.

VIII. Environmental Impact

    The agency has determined under 21 CFR 25.31(j) that this action is
of a type that not individually or cumulatively have a significant
effect on the human environment. Therefore, neither an environmental
assessment nor an environmental impact statement is required.

IX. Request for Comments and Effective Date

    Interested persons may, on or before November 17, 1999, submit to
the Docket Management Branch (address above) written comments regarding
this proposed rule. Two copies of any comments are to be submitted,
except that individuals may submit one 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 office above
between 9 a.m. and 4 p.m., Monday through Friday. FDA is proposing that
any final rule that may issue based upon this proposed rule become
effective 180 days after its date of publication in the Federal
Register.

X. References

    The following references have been placed on display in the Dockets
Management Branch (address above) and may be seen by interested persons
between 9 a.m. and 4 p.m., Monday through Friday.
    1. Morbidity and Mortality Weekly Report, vol. 32, pp. 101-103,
March 4, 1983.
    2. Morbidity and Mortality Weekly Report, vol. 34, pp. 1-5,
January 11, 1985.
    3. Morbidity and Mortality Weekly Report, vol. 36, pp. 509-515,
August 14, 1987.
    4. Morbidity and Mortality Weekly Report, vol. 36, pp. 833-840,
January 8, 1988.
    5. Morbidity and Mortality Weekly Report, vol. 38 (No. S-7),
July 21, 1989.
    6. Morbidity and Mortality Weekly Report, vol. 41 (No. RR-2),
pp. 1-9, February 28, 1992.
    7. Morbidity and Mortality Weekly Report, vol. 37, pp. 736-747,
December 9, 1988.
    8. Morbidity and Mortality Weekly Report, vol. 40 (No. RR-4),
pp. 1-17, April 19, 1991.
    9. Wallace, E. L., W. H. Churchill, D. M. Surgenor, J. An, G. Cho,
S. McGurk, and L. Murphy, ``Collection and Transfusion of Blood and
Blood Components in the United States, 1992,'' Transfusion, 1995; vol.
35, No. 10, pp. 802-812.
    10. General Accounting Office, ``Blood Safety: Enhancing Safeguards
Would Strengthen the Nation's Blood Supply,'' GAO-HEHS-97-143, June
1997.
    11. Glynn, S. A., G. B. Schreiber, M. P. Busch, S. H. Kleinman, A.
E. Williams, C. C. Nass, H. E. Ownby, and J. W. Smith, for the
Retrovirus Epidemiology Donor Study, ``Demographic Characteristics,
Unreported Risk Behaviors, and the Prevalence and Incidence of Viral
Infections: A Comparison of Apheresis and Whole-Blood Donors,''
Transfusion, April 1998, vol. 38, pp. 350-358.
    12. General Accounting Office, ``Blood Plasma Safety: Plasma
Product Risks Are Low if Good Manufacturing Practices Are Followed,''
GAO-HEHS-98-205, September 1998.

Lists of Subjects

21 CFR Part 606

    Blood, Labeling, Laboratories, Reporting and recordkeeping
requirements.

 21 CFR Part 630

    Biologics, Blood, Reporting and recordkeeping requirements.
    Therefore, under the Federal Food, Drug, and Cosmetic Act, the
Public Health Service Act, and under 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 606.100 is amended by adding paragraph (b)(20) to read
as follows:

Sec. 606.100   Standard operating procedures.

* * * * *
    (b) * * *
    (20) Procedures for donor deferral as prescribed in Sec. 610.41 of
this chapter and donor notification, including procedures for the
appropriate followup if the initial attempt at notification fails, as
prescribed in Sec. 630.6 of this chapter.
* * * * *
    3. Section 606.160 is amended by adding paragraphs (b)(1)(ix) and
(b)(1)(x) to read as follows:

Sec. 606.160   Records.

* * * * *
    (b) * * *
    (1) * * *
    (ix) Notification of deferred donors, including appropriate
followup if the initial attempt at notification fails.
    (x) To facilitate the notification of deferred donor, the donor's
permanent address.
* * * * *
    4. Part 630 is added to read as follows:

PART 630--GENERAL REQUIREMENTS FOR BLOOD, BLOOD COMPONENTS, AND
BLOOD DERIVATIVES

Sec.
630.6  Donor notification.
    Authority: 21 U.S.C. 321, 331, 351, 352, 355, 360, 371; 42
U.S.C. 216, 262, 263.

Sec. 630.6   Donor notification.

    (a) An establishment that collects blood or blood components shall
notify donors who have been deferred based on results of tests for
evidence of infection with a communicable disease agent as required by
Sec. 610.41 of this chapter or based on deferral for suitability
criteria. Blood establishments shall attempt to obtain the results of
supplemental testing required under Sec. 610.40(c) of this chapter
prior to notifying donors of their deferral. If notification occurs
prior to receipt of such results, blood establishments shall renotify
donors of the results of the supplemental testing. Blood establishments
shall notify donors as described in paragraph (b) of this section.
    (b) The notification shall provide the following information to a
donor who has been deferred from donating as described in paragraph (a)
of this section:
    (1) That the donor has been deferred and the reason for deferral;
    (2) The types of donations of blood or blood components which the
donor should not donate in the future;
    (3) Where applicable, the results of tests for evidence of
infection due to communicable disease agent(s), that were a basis for
deferral under Sec. 610.41 of this chapter, including results of
supplemental (i.e. additional, more specific) tests as required in
Sec. 610.40(c) of this chapter;
    (4) Information concerning appropriate medical followup and
counseling; and
    (5) Where applicable, the possibility that the donor may be found
suitable for future donations.
    (c) The notification process shall include a minimum of three
attempts to

[[Page 45365]]

notify the donor and be completed within 8 weeks after the
determination that the donor should be deferred or at the first return
visit of the deferred donor after the determination is made, whichever
is earlier.

    Dated: April 20, 1999.
Jane E. Henney,
Commissioner of Food and Drugs.
Donna E. Shalala,
Secretary of Health and Human Services.
[FR Doc. 99-21295 Filed 8-18-99; 8:45 am]
BILLING CODE 4160-01-F