Federal Register, Volume 66 Issue 112 (Monday, June 11, 2001)

[Federal Register Volume 66, Number 112 (Monday, June 11, 2001)]
[Rules and Regulations]
[Pages 31165-31177]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 01-14409]

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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; Donor Notification

AGENCY: Food and Drug Administration, HHS.

ACTION: Final rule.

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SUMMARY: The Food and Drug Administration (FDA) is amending the
biologics regulations to require blood and plasma establishments to
notify donors, including autologous donors, whenever the donor is
deferred or determined not to be suitable for current or future
donations of blood and blood components. A donor is deferred based on
results of tests for communicable disease agents or determined not to
be suitable for donation based on failure to satisfy suitability
criteria. Blood and plasma establishments also are required to notify
the referring physician of an autologous donor when the autologous
donor is deferred based on tests for evidence of infection with a
communicable disease agent(s). A standard operating procedure (SOP) and
recordkeeping also are required. This final rule is intended to help
protect public health and to promote consistency in the industry.
Elsewhere in this issue of the Federal Register, FDA is publishing a
final rule on the requirements for testing human blood donors for
evidence of infection due to communicable disease agents.

DATES: This rule is effective December 10, 2001.

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:

[[Page 31166]]

I. Background

In the Federal Register of August 19, 1999 (64 FR 45355), we (FDA)
proposed to require that blood and plasma establishments notify donors
of their deferral due to results of tests for communicable disease
agents or based on failure to satisfy donor suitability criteria. We
issued the proposed rule with the intent of reducing the risk of
transmission of communicable disease from the use of blood, blood
components, and blood derivatives. Under the proposed rule, blood and
plasma establishments would: (1) Notify the donors that they are
deferred based on results of tests for evidence of infection due to a
communicable disease agent or based on suitability criteria, and the
reason for the deferral; (2) where applicable, provide the results of
tests for evidence of infection due to a communicable disease agent(s)
that was the basis for deferral, including the results of supplemental
(additional, more specific) tests; (3) provide information concerning
appropriate medical followup and counseling; (4) describe the types of
donations the donors should not donate in the future; and (5) discuss
the possibility that the donor may be found suitable in the future,
where appropriate. We proposed that the notification process should
include a minimum of three attempts to notify the donor and be
completed within 8 weeks after the donor was determined to be deferred
or at the first return visit of the donor, whichever is earlier. FDA
provided 90 days for comments on the proposed rule.
In the same issue of the Federal Register of August 19, 1999 (64 FR
45340), we proposed to revise the general biological product standards
by updating the hepatitis B virus (HBV) and human immunodeficiency
virus (HIV) testing requirements by adding testing requirements for
hepatitis C virus (HCV), human T-lymphotropic virus (HTLV), and by
adding requirements for supplemental (i.e., additional, more specific)
testing when a donation is found to be reactive for any of the required
screening tests for evidence of infection due to communicable disease
agents. (No change was proposed to the requirements for serological
tests for syphilis). We also proposed regulations for the deferral of
donors based on the results of the screening test. FDA provided 90 days
for comment.
In the Federal Register of November 9, 1999 (64 FR 61045), we
announced a public workshop to be held on November 22, 1999, and also
extended to December 22, 1999, the comment period on both proposed
rules, i.e., ``Requirements for Testing Human Blood Donors for Evidence
of Infection Due to Communicable Disease Agents,'' and ``General
Requirements for Blood, Blood Components, and Blood Derivatives;
Notification of Deferred Donors.'' The purpose of the public meeting
was to provide a public forum for gathering information and views
regarding the proposed rules.

II. Highlights and Summary of the Final Rule

A. Plain Language

We have written the final rule using plain language consistent with
the Presidential memorandum on plain language in Government writing,
dated June 1, 1998. We have adopted the plain language approach making
the rule more accessible and understandable to the public. As a result,
we have used pronouns in describing who must comply, e.g., ``you'' is
used to refer to an establishment that collects blood or blood
components. We also have used ``must'' instead of ``shall.''

B. Final Rule

With this final rule, we created a new part 630 entitled ``General
Requirements for Blood, Blood Components, and Blood Derivatives''
containing requirements for notification of deferred and unsuitable
donors. Under Sec. 630.6, establishments that collect blood or blood
components must make reasonable attempts to notify all donors,
including autologous donors, that they are deferred from further
donations based on results of tests for evidence of infection due to
communicable disease agents under part 610 or part 640 (21 CFR part 610
or part 640) in new Sec. 610.41 or determined not to be suitable for
donation based on failure to satisfy suitability criteria under
Sec. 640.3 or Sec. 640.63. The establishment must provide the following
information to the donor: (1) That the donor is deferred or determined
not to be suitable for donation and the reason for that decision; (2)
where appropriate, the types of donations of blood and blood components
that 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, including results of
supplemental (i.e., additional, more specific) tests; and (4) where
appropriate, information concerning medical followup and counseling.
The establishment must make reasonable attempts to notify the donor
within 8 weeks of determining that the donor is deferred or determined
not to be suitable for donation. The establishment must document that
the donor has been successfully notified, or if unsuccessful, that the
establishment made reasonable attempts to notify the donor. In addition
to notifying an autologous donor, the establishment must notify the
autologous donor's referring physician agents, with the same
information and within the same time period, when the donor is deferred
based on results of tests for evidence of infection due to communicable
disease. Each establishment must prepare a SOP for donor notification
and autologous donor referring physician notification, including the
appropriate followup if the initial attempt at notification fails.
Recordkeeping also is required.
This final rule on notification of donors is a companion rule to
the final rule entitled ``Requirements for Testing Human Blood Donors
for Evidence of Infection Due to Communicable Disease Agents'' (testing
final rule) found elsewhere in this issue of the Federal Register. The
testing final rule revises the general biological product standards by
updating the HBV and HIV testing requirements, by adding testing
requirements for HCV and HTLV, and by adding requirements for
supplemental (additional, more specific) testing when a donation is
found to be reactive for any of the required screening tests for
evidence of infection due to communicable disease agents. The testing
final rule also requires the deferral of donors based on the results of
screening tests for communicable disease agents, including syphilis.
The requirements in the testing final rule are referenced throughout
this document. Therefore, in order to understand fully the requirements
of both rulemakings, they should be read together.

III. Comments on the Proposed Rule and FDA Responses

We received 14 letters of comment on the proposed rule, submitted
by blood centers, hospitals, transfusion services, consumer advocacy
groups, and professional associations. The comments predominantly
supported the concept of promptly notifying donors that they are
deferred based on results of tests for communicable disease agents or
that they are determined not to be suitable for donation based on
failure to satisfy suitability criteria. Some comments objected to FDA
mandating how and when notification occurs. Others objected to specific
requirements in the proposed rule. A summary of the comments and the
agency's responses follow.

[[Page 31167]]

A . Scope of the Notification Rule

Proposed Sec. 630.6(a) required an establishment that collects
blood or blood components to notify donors who have been deferred based
on results of tests for evidence of infection due to communicable
disease agents or determined not to be suitable for donation based on
failure to satisfy suitability criteria. In proposed Sec. 630.6(b), the
rule required the establishment to inform a donor that the donor is
deferred or determined not to be suitable for donation and the reason
for that decision. The establishment would also provide the following
information: The types of donations of blood or blood components that
the donor should not donate in the future; where applicable, the
results of tests including supplemental (i.e., additional, more
specific) tests; information concerning appropriate medical followup
and counseling; and, where applicable, the possibility that the donor
may be found suitable for future donations.
(Comment 1) Two comments suggested requiring notification of donors
based on other criteria in addition to those deferred for results of
tests for evidence of infection due to communicable disease agents and
determined not to be suitable as a donor based on suitability criteria.
One of the two comments suggested we require notification of donors
deferred voluntarily by blood banks. The other comment argued that
notification should apply to any preliminary test results carried out
prior to blood or blood component collection.
Under the final rule, we are requiring notification of donors
deferred based on results of required tests for evidence of infection
due to communicable disease agents, or determined not to be suitable
for donation due to failure to satisfy suitability requirements in
Secs. 640.3 and 640.63. The notification requirement is imposed in
conjunction with requirements for testing for infection due to markers
of certain communicable disease agents listed in new Sec. 610.40 or for
syphilis in Secs. 640.5(a), 640.14, 640.23(a), 640.33(a), 640.53(a) and
640.65(b)(2), and for deferral of donors who test reactive for those
markers in new Sec. 610.41. The notification must include screening
test results and the results of any approved supplemental (i.e.,
additional, more specific) tests. As we stated in the proposed rule, we
are not requiring blood and plasma establishments to notify donors that
are deferred voluntarily by blood and plasma establishments for a
variety of medical reasons beyond what is required in the regulation.
We believe notification of donors voluntarily deferred by a blood and
plasma establishment should be left to the medical judgment of the
blood or plasma establishment's medical director.
(Comment 2) Six comments argued that the proposed rule is too
detailed on the method and content of notification. These comments
argued that blood and plasma establishments need flexibility in how and
what they tell donors about their deferred status. Further, the
sensitivity of the information, the setting, and the donor's attitude
may not lend themselves to the detailed notification included in the
proposed rule. Several of the comments pointed out that most blood and
plasma establishments follow the American Association of Blood Banks
(AABB) standards and voluntarily notify donors, so FDA does not need to
codify the details of notification.
The final rule provides blood and plasma establishments with the
framework for notification of deferred donors and donors determined not
to be suitable for donation. Donors who are deferred based on test
results or determined not to be suitable for donation based on failure
to satisfy donor suitability criteria must be informed that they are
deferred or determined not to be suitable for donation and the reason
for that decision. The donor must be given, where appropriate, a
description of the types of donations the donor should not make in the
future and information concerning medical followup and counseling.
Where applicable, the donor must be provided the results of screening
and supplemental tests for evidence of infection due to a communicable
disease agent(s). In the final rule, our intent is not to remove from
blood and plasma establishments the medical judgment necessary to
inform donors fully of their potential infectious disease status.
Rather, the final rule sets out the information the agency considers
necessary to be provided to the donor. We recognize that some donors
may need to be informed of the need for medical followup or counseling,
others may not. A variety of factors may influence a blood and plasma
establishment's decision to inform the donor in person, by phone, or by
mail. The final rule is intended to help ensure consistency in the
blood industry's notification practices. We believe uniform
notification practices by blood and plasma establishments will improve
blood safety by preventing donations by individuals at risk for
transmitting communicable diseases.
(Comment 3) Five comments argued that the requirements of the
proposed rule fall outside FDA's jurisdiction. These comments argued
that donor notification and education don't affect the safety, purity,
or potency of the blood supply because the donor is already deferred
from future donations. The comments also argued that the manner of
notification constitutes the practice of medicine best left to the
discretion of the medical staff (or in the case of an autologous donor,
the donor's referring physician) at the blood and plasma establishment,
and should not be imposed on the collection site staff.
As we explained in the preamble of the proposed rule, notification
of a donor is directly related to preventing the introduction and
spread of communicable diseases. Through notification, a donor learns
of the deferral and the need to refrain from future donations, as well
as the medical significance of the deferral. Where appropriate, the
donor is made aware of the need for further medical treatment or
counseling. We do not agree that donor notification constitutes the
practice of medicine. We believe that this information is pertinent to
the donor's health status and that the donor must be made aware of such
information in order to seek medical care as appropriate. Notification
of donors is currently part of the AABB standards, which recommend that
establishments notify donors of ``any medically significant abnormality
detected during the predonation evaluation or as a result of laboratory
testing'' (see section B3.500 of ``AABB Standards for Blood Banks and
Transfusion Services,'' 19th edition, 1999). As many of the comments
pointed out, this activity is currently performed as usual and
customary business practice. The final rule also requires the
establishment to develop SOP's for notifying donors and the referring
physicians of autologous donors. A blood or plasma establishment that
fails to comply with donor notification procedures is in violation of
current good manufacturing practice (CGMP) and, therefore, is subject
to the enforcement provisions of the Federal Food, Drug, and Cosmetic
Act (the act).
(Comment 4) Two comments pointed out that several States have laws
governing notification of donors and FDA's proposed requirements may
conflict with State provisions and cause confusion for blood collection
establishments.

[[Page 31168]]

We are aware of varying State requirements concerning notification
of the State health authorities of a donor's positive test results, not
of a donor's deferral. Such State laws require that the collecting
establishment notify the State of certain communicable disease test
results. The State may then notify the donor, but not always. Our
requirements prescribe that the donor be notified directly of all test
results that were the basis for deferral and be given information
concerning medical followup and counseling. Our requirements are in
addition to, and do not conflict with, State requirements.
(Comment 5) One comment supported providing donors with information
about the possibility of requalification for donating and suggested
expanding the requirement to include information regarding future
donations even where there is no requalification process or method
(algorithm) approved by FDA for such purpose. Two comments argued
against notifying the donor of possible requalification. These comments
argued that such information would make the notification too long and
confusing and that blood and plasma establishments would be required to
change their notification procedures every time requalification
protocols change.
We have removed the requirement that blood and plasma
establishments notify donors of the possibility that the donor may be
found suitable for future donations. We removed this requirement
because requalification of donors is not required and to explain the
possibility of requalification to a donor would be an unnecessary
burden for an establishment that does not have a requalification
program. Under the related donor testing and deferral rule, blood and
plasma establishments may use blood or blood components from a donor
who was previously deferred as a result of testing reactive on a
screening test(s) for specified communicable disease agent(s) if the
blood or blood components currently test negative for those same
disease agent(s) and the donor has been shown to be suitable to donate
blood by an algorithm approved for that purpose by FDA. Blood and
plasma establishments that requalify donors should consult FDA guidance
on what to tell a donor about the possibility for future donation.
Guidance documents may be obtained from the Office of Communication,
Training, and Manufacturers Assistance (HFM-40), Center for Biologics
Evaluation and Research (CBER), Food and Drug Administration, 1401
Rockville Pike, suite 200N, Rockville, MD 20852-1448. Send one self-
addressed adhesive label to assist that office in processing your
requests. The guidance documents may also be obtained by calling the
CBER Voice Information System at 1-800-835-4709 or 301-827-1800, or by
FAX by calling the FAX Information System at 1-888-CBER-FAX or 301-827-
3844. Persons with access to the Internet may connect to CBER at
``http://www.fda.gov/cber/publications.htm.''

B. Notification of Deferred Autologous Donors

We proposed several exceptions to donor deferral in related
rulemaking that would affect donor notification. Autologous donors
testing reactive for communicable disease agents would not be deferred.
Collecting establishments would not be required to notify autologous
donors who test reactive for a communicable disease agent(s).
Nevertheless, we recommended that collecting establishments notify
autologous donors, when applicable, for the purpose of medical followup
and counseling. We also requested comments on whether to require
notification of autologous donors of reactive and supplemental test
results even though such donors would not be deferred.
(Comment 6) Three comments supported permanently deferring
autologous donors from future allogeneic donations and notifying the
autologous donors of their deferral using the same criteria as for
allogeneic donors. These comments argued that autologous donors and
allogeneic donors present the same risks for future allogeneic
donations. The comments also argued that notification of autologous
donors will help reduce the spread of communicable disease, and help
prevent potentially infectious autologous donors from attempting to
become allogeneic donors in the future. One comment pointed out that
notification of autologous donors of the results of infectious disease
testing is widely practiced already and therefore would not be a burden
on blood and plasma establishments.
Under new Sec. 610.40 found elsewhere in this issue of the Federal
Register, autologous donations must be tested for evidence of infection
due to communicable disease agents only if the blood or plasma
establishment ships autologous donations or maintains a program that
allows autologous donations to be used for allogeneic transfusion. In
such case, if an autologous donor tests reactive, he or she must be
deferred from allogeneic donations under new Sec. 610.41. In order to
prevent donation in the future, deferral under new Sec. 610.41 triggers
the notification requirements of the final notification rule.
Notification of autologous donors also must include the test results
that are the basis for deferral, if applicable; types of donations they
should not make in the future; and where applicable, information
concerning medical followup and counseling. Recognizing that autologous
donation is also a medically ordered procedure, blood and plasma
establishments also must notify the deferred autologous donor's
referring physician that the donor has been deferred based on test
results and the reasons for that decision, including test results that
are the basis for deferral and the types of donations the autologous
donor should not donate in the future for allogeneic use.
An allogeneic donor completes a preliminary screening and physical
assessment prior to donation. If the allogeneic donor is determined not
to be suitable for donation during this process, it is usual and
customary business practice that the donor be notified on site that
they are determined not to be suitable for donation and given the
reason for that decision. We anticipate that any additional required
information will be provided at that time. However, usually when an
autologous donor donates, it is by a physician's prescription and the
autologous donor may not always meet, and is not required to meet, all
the preliminary screening and physical assessment criteria. Even when
the autologous donor is determined not to be suitable for allogeneic
use, the donation is collected and labeled under Sec. 606.121 and the
autologous donor must be provided the information required in
Sec. 630.6(b), i.e., the reason for the determination; if applicable,
types of donations they should not make in the future; and where
applicable, information concerning medical followup and counseling.
(Comment 7) Six comments suggested that abnormal test results
should be sent only to an autologous donor's referring physician, not
the donor. The comments argued that an autologous donor is a patient
under physician care undergoing a medical procedure ordered by that
physician. Under these circumstances, the comments argued it would be
appropriate to give the test results to the referring physician,
similar to any other laboratory results, and let that physician
determine the need to notify the donor for medical followup. These
comments argued that notifying the autologous donor directly could
interfere with the doctor-patient relationship and result in
conflicting advice. Several comments state that notifying the donor's

[[Page 31169]]

physician of test results is current industry practice. Two of the
comments argued that there was no safety issue to justify notification
of the autologous donor because reactive units would not enter the
blood supply and few autologous donors return to donate allogeneic
units.
Under the final rule, we are requiring blood and plasma
establishments to notify both the autologous donor and the autologous
donor's referring physician of the donor's deferral whenever the donor
is deferred as required under new Sec. 610.41. We believe that the
referring physician needs to be informed of the reasons for the
autologous donor's deferral due to test results. Such notification
should include the results of any screening or supplemental tests so
that the physician can make informed medical judgments about the donor
as a patient. We also believe that the donor has a need to be informed
of his or her deferral or determination not to be suitable, and the
reasons for the decision, as well as any appropriate medical counseling
or treatment. We believe notifying the deferred autologous donor is
necessary both for the health of the donor and to help prevent deferred
or unsuitable autologous donors from attempting future allogeneic
donations if indicated. Autologous donors may wish to discuss the
underlying reasons for the determination with their physicians.

C. Notification Based on Results of Tests for HTLV, Types I and II, and
Anti-HBc

In the proposed rule, blood and plasma 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 reactive on a second occasion for anti-HTLV,
types I and II, or anti-hepatitis B core (anti-HBc). The agency
requested comments on whether to notify donors who test reactive for
anti-HTLV, types I and II, or anti-HBc on only one occasion or to wait
to notify donors upon testing reactive on the second occasion. Upon the
availability of an approved supplemental (additional, more specific)
test, a reactive donor would be deferred after a single reactive
donation. At such time, blood establishments would notify donors of the
test results of both the approved screening and supplemental tests.
(Comment 8) Four comments were submitted on the notification of
donors testing reactive for anti-HTLV, types I and II, or anti-HBc. Two
comments favored notifying the donor when the donor is deferred, i.e.,
after the reactive screening test on a second occasion. Another comment
suggested notifying the donor after the reactive screening test on the
first occasion, but not to defer until the reactive screening test
occurs on a second occasion. One comment stated that the reliability of
the tests for anti-HTLV, types I and II or anti-HBc is low enough that
donor notification should not be required.
After reviewing the comments and further evaluation, we have
decided to require blood establishments to notify donors who test
reactive for anti-HTLV, types I and II, or anti-HBc on two occasions
and, consequently, are deferred. Because an approved supplemental test
for HTLV, types I and II, or anti-HBc is not currently available to aid
in the notification, we believe it is appropriate that blood and plasma
establishments not be required to notify donors after a reactive
screening test on the first occasion due to the high rate of false
reactivity in low risk blood bank settings. However, under
newSec. 610.40(h)(1), the donation that tests reactive must not be
shipped or used, and the donor remains in the donor pool until the
donor tests reactive on a second occasion. It is our intent that if
licensed supplemental tests for HTLV, types I and II, or anti-HBc are
approved, blood establishments would be required to defer donors after
a reactive donation on the first occasion regardless of the results of
the supplemental (additional, more specific) tests and notify the donor
of both the screening and supplemental test results as prescribed in
Sec. 630.6(b).

D. Notification of Donors Determined Not to Be Suitable for Donation
Based on Failure to Satisfy Suitability Criteria

The proposed rule would require blood and plasma establishments to
notify donors who are determined not to be suitable based on failure to
satisfy donor suitability criteria.
(Comment 9) Five comments called for clarification of what
suitability requirements would trigger notification of a donor
determined not to be suitable for donation.
Currently, the regulations defining donor suitability in
Secs. 640.3 and 640.63 apply to all donations, including autologous
donations. See comment 6 of this document for further discussion of
notification of an autologous donor when determined not to be suitable
for donation.
(Comment 10) Several comments argued that blood and plasma
establishments already voluntarily notify donors based on failure to
satisfy suitability criteria on site so the proposed rule is not
necessary and too burdensome.
We believe that notification of donors based on failure to satisfy
suitability requirements is necessary to help ensure consistency in
industry practice and further improve the safety of the blood supply.
We do not believe the final rule is too burdensome as it codifies what
many blood and plasma establishments already are performing as usual
and customary business practice. As the final rule discusses in section
III.E of this document, notification of donors based on determination
not to be suitable still may occur on site at the time of deferral.
(Comment 11) Two comments stated that criteria used in determining
the donor not to be suitable for donation and notification of the donor
are decided by medical professionals at blood and plasma establishments
and constitute the practice of medicine. Consequently, the comments
believed the proposed rule goes beyond FDA's jurisdiction.
We disagree with the comments. We believe that donor testing,
deferral, and notification are within our jurisdiction because they
relate to the safety of blood products and the control of communicable
disease. We believe the deferral and notification requirements will
help ensure that the Nation's blood supply is safe by excluding donors
who may present significant risks from donation in the future. These
requirements also will enhance the public health by helping to ensure
that those donors who have been deferred or determined not to be
suitable for donation are advised to seek treatment and counseling,
where appropriate.
(Comment 12) One comment argued that requiring blood and plasma
establishments to notify donors based on their failure to satisfy
suitability criteria under the proposed rule may create a patient-
physician relationship between the donor and the blood and plasma
establishment, therefore violating statutes that prohibit the corporate
practice of medicine.
We disagree with the comment. Our intention is not to encourage the
practice of medicine by the blood and plasma establishments, but to
help ensure that blood and plasma establishments help prevent the
potential spread of communicable disease and provide valuable
information that may affect the donor's health so that the donor can
seek medical care as appropriate. We have revised the language in
Sec. 630.6(b) of the final rule to support these intentions.
(Comment 13) Two comments argued that notification of a donor based
on

[[Page 31170]]

failure to meet suitability criteria is done on site at the time of
donation, so blood and plasma establishments should not be required to
make three attempts at notification at some later date.
The final rule is not prescribing the method of notification to be
used. This will allow the blood and plasma establishments to determine
the best method of notification for a particular donor. This
flexibility allows a collecting establishment to notify the donor on
site either at the time of the donor's screening and physical
assessment or at the time of the donor's return visit, by phone, or by
mail.
The final rule requires that the blood or plasma establishment make
reasonable attempts to notify donors. For example, an establishment may
send a notification letter by regular mail to a donor in compliance
with Sec. 630.6. A week later, the letter is returned to the
establishment by the post office marked ``address unknown.'' The
establishment could then proceed with the additional steps until
successful notification occurs, or until it is clear that further
attempts will not be successful. Such steps could include: Checking the
record of the donor's address for transcription error; or searching a
local phone book for a correct address and then, in either case,
resending the letter. Additionally, the establishment could phone the
donor and either notify the donor at that time or ask for a correct
address in order to resend the letter.
The final rule also clarifies that a blood or plasma establishment
must make reasonable attempts to notify the donor within 8 weeks after
determining the donor is deferred or not suitable until the
establishment actually succeeds in notification or until the blood and
plasma establishment makes sufficient reasonable attempts at
notification and it is clear that further attempts will not be
successful. A blood and plasma establishment that successfully notifies
on site at the time of donation would not have to notify further a
donor determined not to be suitable for donation based on failure to
satisfy suitability criteria under Secs. 630.6 and 640.63.
(Comment 14) One comment argued that blood and plasma
establishments should be allowed to notify donors determined not to be
suitable for donation based on failure to satisfy suitability criteria
by providing the donors with generic letters on site.
The final rule does not prohibit this method of notification as
longas a blood or plasma establishment can fully meet the requirements
of Secs. 630.6 and 630.63 by including the necessary information in a
standardized letter. However, blood and plasma establishments may need
to supplement such a letter on a case-by-case basis with information
specific to the donor.
(Comment 15) Two comments pointed out that many donors determined
not to be suitable for donation based on failure to satisfy suitability
criteria do not need further treatment or counseling.
We agree with the comment. In the final rule, we clarify the intent
to require blood and plasma establishments to provide donors, deferred
or determined not to be suitable for donation, with information
concerning medical followup, treatment or counseling only when
applicable to a particular donor. We recognize that for some donors
referral to medical followup or counseling would be unnecessary.
(Comment 16) One comment argued that the proposed rule should not
treat donors deferred based on test results in the same manner as
donors determined not to be suitable for donation based on failure to
satisfy suitability criteria because the former have known health
problems while the latter probably do not.
We disagree with the comment. Both reactive test results for
communicable disease agents and failure to satisfy suitability criteria
raise health concerns for the donor of which the donor should be aware.
However, the information provided in the notification may vary,
depending on the reason for the deferral or determination not to be
suitable for donation based on failure to satisfy suitability criteria.

E. Method of Notification--How to Notify the Donor

The preamble of the proposed rule discussed the possibility that
blood and plasma establishments would be able to fulfill the
notification requirements on site. It explained that some blood and
plasma establishments may notify donors by registered mail, return
receipt; or may choose to request that the donor return for direct
donor notification. In the preamble of the proposed rule, FDA requested
comments on the methods of notification that would help ensure adequate
donor confidentiality and the current application and sufficiency of
Federal, State, and local laws that protect the privacy of the
individual being notified.
(Comment 17) Four comments argued that blood and plasma
establishments should have flexibility in the manner they meet their
notification obligations under Sec. 630.6(b) and in the way they
protect donor confidentiality. No comments were received on the current
application and sufficiency of the Federal, State, and local laws that
protect the privacy of the individual being notified.
Under the final rule, blood and plasma establishments have the
flexibility to choose the manner in which they notify donors. Provided
that their notification obligations are fulfilled within 8 weeks, blood
and plasma establishments may choose to notify a donor: (1) In person
at the time of actual deferral, (2) in person at the donor's first
return visit, (3) by phone, or (4) by mail.
Personnel performing this activity must be adequately trained as
required under Sec. 606.20. One method of notification that helps
ensure donor confidentiality is person-to-person contact.
(Comment 18) Seven comments objected to FDA requiring that
notification be sent by registered mail. These comments argued that
some donors will not open registered mail and others will be
unnecessarily alarmed by receipt of such a letter. The comments stated
that sending notification by certified mail will not guarantee that the
donor receives it and will add significant expense unnecessarily. The
comments suggested that a letter sent by regular mail, documented by
the blood or plasma establishment, should be sufficient.
The preamble of the proposed rule only discussed the possibility of
notification by certified mail. Blood and plasma establishments may
fulfill their notification obligations by regular mail provided they do
so within 8 weeks after determining that the donor is deferred or is
not suitable to donate and they document their notification attempts.
(Comment 19) Two comments asked for FDA to allow notification of a
donor by telephone or by letter providing a telephone number that the
donor can call for information regarding the deferral.
The final rule does not preclude notification by telephone provided
a blood or plasma establishment meets all of its notification
obligations under Sec. 630.6 and documents notification of the donor.
(Comment 20) Five comments objected to FDA requiring blood and
plasma establishments to make three attempts to notify donors deferred
based on results of tests for communicable disease agents or determined
not to be suitable for donation based on failure to satisfy suitability
criteria. These comments argued that the first attempt should be
sufficient because it is made

[[Page 31171]]

shortly after the donation and subsequent attempts are unlikely to
succeed.
We clarify in the final rule that a blood or plasma establishment
must make reasonable attempts to notify the donor. We eliminate the
requirement for three attempts to emphasize that a blood or plasma
establishment should continue attempting to notify a donor until it is
clear that further attempts would not be successful. If the initial
attempt or attempts are unsuccessful, a blood or plasma establishment
may need to try other methods to contact the donor. If a blood or
plasma establishment is successful in notifying a donor then,
obviously, no other attempts are necessary. Blood and plasma
establishments must document their attempts to notify donors and
maintain a record of these attempts, whether successful or not.
(Comment 21) One comment suggested 8 weeks is not enough time for
blood and plasma establishments to complete notification because some
confirmatory test results take longer to be completed. Another comment
argued that 8 weeks is too long a timeframe for notification.
We believe blood and plasma establishments will be able to complete
notification or reasonable attempts to notify the donor within the
prescribed 8-week timeframe. Blood and plasma establishments must
attempt to obtain the results of supplemental tests prior to notifying
donors of their deferral. However, if the results were unavailable
prior to notification, blood and plasma establishments would be
required to renotify the donor with the results of the supplemental
testing. We believe that the results of tests for communicable disease
agents, including approved supplemental tests, should generally be
available within the 8-week notification timeframe.

F. Permanent Address

In proposed Sec. 606.160(b)(1)(x), FDA proposed to require the
blood or plasma establishment to record the donor's permanent address
to facilitate the notification of the donor.
(Comment 22) Five comments objected to FDA requiring proof of a
permanent fixed address. These comments question what proof of a
permanent, fixed address would be acceptable and point out that certain
donors may not be able to provide such proof. The comments argued it is
not logical that voluntary donors would misrepresent their address.
Several of these comments point out that donors may have privacy
concerns for not giving a permanent address.
We clarify in the final rule that blood and plasma establishments
need to obtain and keep a record of an address where the donor
represents he or she can be reached within 8 weeks after donation. A
donor does not need to prove that the provided current address is fixed
or permanent.

IV. Analysis of Impacts

FDA has examined the impacts of the 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 in any one year by State, local, and tribal governments, in
the aggregate, or by the private sector, of $100 million (adjusted
annually for inflation).
The Office of Management and Budget (OMB) has determined that this
rule 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 an expenditure in any one year of $100 million or
more, FDA is not required to perform a cost-benefit analysis according
to the Unfunded Mandates 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 rule is not expected to have a
significant economic impact on a substantial number of small business
entities because donor notification is considered usual and customary
business practice for the affected entities.

A. Objectives and Basis of the Action

As discussed previously, FDA is implementing this action to
helpprotect the public health and promote consistency in the industry.
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 who fail to satisfy suitability criteria are excluded from
donating blood and blood components. Once donors are deferred from
donation or determined not to be suitable for donation, they would be
informed of the deferral or determination and the reason for that
decision; the types of donations they should not donate in the future;
the screening and supplemental test results, if applicable; and
information concerning 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 to
minimize the risk of transmitting the disease agent.
This action is taken under the authority of sections 351 and 361 of
the Public Health Service Act (42 U.S.C. 262 and 264 et seq.) and the
provisions of the act that apply to drugs, specifically section 501 of
the act (21 U.S.C. 351), in order 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,
the blood or plasma establishment 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
rule.

B. Nature of the Impact

The rule requires that blood and plasma establishments notify
donors, including autologous donors, of their deferral because of the
results of testing for evidence of infection due to communicable
disease agents including HIV, HTLV, hepatitis B, hepatitis C, or
syphilis or that they are determined not to be suitable for donation
based on failure to satisfy suitability criteria. Blood establishments
also are required to notify referring physicians of autologous donors
of reactive test results for evidence of infection due to communicable
disease agents. Under the rule, the donor must be notified of the types
of blood or blood components that the donor should not donate in the

[[Page 31172]]

future, where appropriate. The notification must include the results of
tests for evidence of infection due to communicable disease agents
including the results of supplemental tests, if applicable, and where
appropriate, the types of donation of blood or blood components that
the donor should not donate in the future, and information concerning
medical followup and counseling. The establishments must make
reasonable attempts to notify the donor within 8 weeks of the donor
deferral or determination not to be suitable for donation. In order to
implement this notification process, the rule also requires that blood
and plasma establishments obtain and record an address for each
prospective donor. Establishments must also maintain records of
attempts to notify a deferred or unsuitable donor within the prescribed
timeframe. An establishment also must prepare SOP's describing all
steps required in the notification process.

C. Type and Number of Entities Affected

The donor notification requirements will affect all blood and
plasma establishments that collect blood and blood components. FDA's
registration data base for blood and plasma establishments has record
of approximately 1,041 establishments: 60 licensed plasma
establishments with multiple locations and 981 registered blood
establishments. The AABB estimates that approximately 12.6 million
blood donations are collected annually. Allogeneic blood donations have
recently accounted for an estimated 87.2 percent of that total with
autologous donations comprising an additional 8.1 percent and directed
donations averaging 3.2 percent (Ref. 1). In 1997, the General
Accounting Office (GAO) estimated that approximately 12 million
donations of Source Plasma were collected by plasma centers.

D. Estimated Impact of Requirements for Donor Notification

The rule is expected to have a minor net impact on blood and plasma
establishments because it is already usual and customary business
practice in the blood industry to notify donors that are deferred or
determined not to be suitable for donation; virtually all
establishments include this process within current operational
guidelines. FDA expects that the primary impact of the rule will
include a one-time review effort at each facility and a more extensive
notification process at those facilities that currently perform donor
notification over a longer timeframe or with fewer notification
attempts. The agency received one letter of comment on the estimated
one-time burden on the blood and plasma establishments in complying
with the requirements of the rule.
(Comment 23) One comment asserted that the review of the regulation
alone would require at least 4 hours of staff time to comprehensively
understand the directives. Another comment in the letter asserted that
revisions to procedures could not be accomplished in only 4 hours,
noting that notification letters and computer software would have to be
revised, staff would have to be trained, and there may be a need to
purchase new equipment such as printers.
FDA agrees that the estimated time of 4 hours did not adequately
account for time spent for revising the establishment's SOP's in
addition to reviewing the regulations. Therefore, we are revising the
estimated time for review of the regulation and revision of an
establishment's SOP's to 8 hours for those establishments that
currently maintain donor records and have notification procedures in
place similar to those required by this rule. FDA agrees that
establishments that make substantial changes to their notification
processes (such as the information contained in their notification
letters) will require more time. The agency assumes such facilities
will require 24 hours of staff time and FDA uses this assumption in its
cost models. FDA does not believe this donor notification rule requires
a capital investment in new equipment.
The one-time effort to review and modify current SOP's is expected
to vary among the 1,041 establishments, depending on the extensiveness
of a facility's current protocols for 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 8 hours of staff time to reconcile the
regulations against the facility's current standards. 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 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
$205 per establishment. For establishments that already perform donor
notification but provide different information to donors or have
established a different notification process than specified in the
rule, FDA assumes that approximately 24 hours of staff time would be
required to align current SOP's and recordkeeping with the provisions
of the rule. The cost in this case would be approximately $616 per
establishment. 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 1,041
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 $356,022 ((2/3 x 1,041 x
$205)) + (1/3 x 1,041 x $616)).
The yearly increase in cost is based on the ongoing notification of
donors. FDA assumes that all donors determined not to be suitable for
donation based on the screening interview can be notified onsite at the
time of the determination, and provided with the appropriate
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 the following numbers:
(1) 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 (a prevalence rate of 121.9 per 100,000 for viral markers
among prospective donors) (Ref. 2); (2) that approximately 80 percent
of donations are made by repeat donors\1\ (12.6 million x .80 = 10.08
million blood donations and 12 million x .80 = 9.6 million plasma
donations); (3) that repeat donors average two donated units per
year\2\ (10.08 million/2 = 5.04 million blood donors and 9.6 million/2
= 4.8 million plasma donors); and (4) that the first time donors
contribute one unit per year (12.6 million--10.08 million = 2.52
million blood donors and 12 million--9.6 million = 2.4 million plasma
donors). As a result, an estimated 9,264 deferred blood donors and
8,777 deferred plasma donors (including first time and repeat donors)
would be notified each year, or a total of 18,041 annual notifications.
---------------------------------------------------------------------------

\1\ This percentage is based on American National 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 Centers for Disease Control's
analysis of blood donations prepared for HCV lookback.
---------------------------------------------------------------------------

FDA assumes that all facilities currently make at least one
notification attempt for all donors deferred based on

[[Page 31173]]

test results. However, the percentage of facilities that would attempt
notification more than once within an 8-week period is not known. FDA
has therefore estimated the economic impact for a scenario in which the
cost of compliance is based on the assumption that in one-fourth of the
18,041 notifications or 4,510, two additional notification attempts are
needed, a phone call and a letter once the address has been corrected
for a transcription error. This estimate is conservative and likely
overstates the true frequency. The cost for these two notifications are
estimated to be the cost of 0.5 hours of staff time for the phone call
or $12.84, and 0.25 hours per staff time and 33 cents for the mailing
or $6.75, for a total cost of approximately $19.59. The cost of
compliance would be $181,482 [9,264 x $19.59] for the blood industry,
and an estimated $171,941 [8,777 x $19.59] for the plasma industry.
Because autologous donations constitute approximately 8 percent of all
donations and these donations are referred by physicians, the rule
requires establishments to send notifications to both the autologous
donor and the referring physician. FDA estimates that the blood
industry would incur an additional cost of $14,519 [$181,482 x .08],
for a total of $196,001.

E. Expected Benefits of the Rule

As described in the preamble to this rule, notification of donors
thatthey have been deferred or determined not to be suitable and
consequently should not attempt subsequent donations will help prevent
unsafe units of blood or blood components from entering the blood
supply. Notified donors can then self-defer in the future and help
protect the Nation's blood supply. In & FDA's proposed rule on donor
testing (64 FR 45340, August 19, 1999), 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 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 a regulatory flexibility analysis. The blood and
plasma establishments affected by the rule are included under the major
standard industrial classification (SIC) code major group 80 for
providers of health services.\3\ 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 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 the field. A ``small
government jurisdiction'' generally means government of cities,
counties, town, townships, villages, school districts, or special
districts, with a population of less than 50,000.\4\
---------------------------------------------------------------------------

\3\ A description of SIC major group 80 can be found at: http://www.osha.gov/cgi-bin/sic/sicser4?80.
\4\ The SBA criteria for small business, listed by SIC code can
be found at: http://www.sba.gov/regulations/siccodes/siccodes.pdf.
---------------------------------------------------------------------------

As noted in the foregoing analysis, the rule is expected to have
some cost impact on both plasma and blood collection centers. FDA has
record of a total of 60 licensed plasma centers with multiple
locations. FDA estimates that the vast majority of the plasma is
processed by eight companies and that these companies own 90 percent of
the plasma centers. FDA assumes that the other 52 plasma centers not
associated with the eight companies may qualify as small business
establishments. FDA has estimated that only 10 percent of plasma
locations are owned by the 52 small entities. The potential impact on
plasma collection facilities will be a function of the number of donors
and the viral marker rates at their facility. The net impact on these
facilities, however, is expected to be minor. If the estimated
additional yearly cost of $171,941 was spread evenly over all
locations, then the yearly cost to all 52 small entities would be
$17,194 [$171,941 x 0.10], or approximately $331 [$17,941 / 52] per
small entity 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 organization 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 donor notification at these facilities, and
the relatively small number of donors that FDA estimates will be
notified based on blood test findings, the impact on these small
facilities is expected to be minor. Based on FDA's calculations, the 34
facilities with 30,000 donations or fewer per year, would identify an
estimated 37 deferred donors per year through blood testing (30,000/
100,000 x 121.9 = 37). If these facilities currently need to make two
additional notification attempts under this rule, there would be an
average small facility notification cost of $724 (37 x $19.59) per
year. Because the estimated one-time cost for the review and revision
of current deferral notification SOP's averages $342 (2/3 x $205 + 1/3
x $616) per establishment, the average annualized cost impact for the
smaller collection establishments would be about $1,066 ($724 + $342),
or roughly $0.04 per donation, assuming approximately 30,000 donations
per year.
The types of professional staff and skills required to perform the
required tasks are described in section III.E of this document. FDA is
confident that the tasks specified in the rule can be readily performed
by the type of staff already employed at affected blood and plasma
establishments.
To minimize the impact on small entities while continuing to
protect public health, the agency does not require donor notification
until after the results of the approved supplemental testing are
available.
As an alternative to this rule, FDA considered not requiring
donornotification of deferral from future donation due to communicable
disease testing or failure to satisfy suitability criteria 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 issued recommendations to establishments
on notifying donors of deferral, the establishments have provided the
deferred donor with inconsistent information and counseling.
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
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.

[[Page 31174]]

In the proposed version of this rule, the agency considered making
the notification of reactive autologous donors recommended, but not
mandatory, and that these donors not be deferred. In the final rule,
the agency is requiring that reactive autologous donors, and their
referring physicians, be notified and that these donors be deferred.
The agency believes that that notification of autologous donors and
their referring physicians will generate many of the same benefits as
notification of allogeneic donors.

V. The Paperwork Reduction Act of 1995

This final rule contains information collection requirements that
are subject to review by the 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 below with an estimate of the annual reporting and recordkeeping
burden. Included in the estimate is the time for reviewing
instructions, searching existing data sources, gathering and
maintaining the data needed, and completing and reviewing each
collection of information.
Title: General Requirements for Blood, Blood Components, and Blood
Derivatives; Donor Notification.
Description: This final rule amends Secs. 606.100(b)(20) (Standard
Operating Procedures), and 606.160(b)(1)(ix to xi) (Records), and adds
new part 630 (Donor Notification), all of which contain new information
collection.

A. Standard Operating Procedures (Sec. 606.100(b)(20))

Section 606.100(b)(20), requires blood and plasma establishments to
write, maintain, and follow SOP's for donor deferral, donor
notification, including autologous donors, and notification of
referring physicians of autologous donors. This provision also requires
SOP's for appropriate followup if the initial attempt at notification
fails.

B. Records (Sec. 606.160(b)(1)(ix) to (b)(1)(xi))

Under Sec. 606.160(b)(1)(ix) and (b)(1)(xi) establishments must
maintain records of each notification and notification attempts of
allogeneic donors, autologous donors, and the referring physicians of
autologous donors. Section 606.160(b)(1)(x) requires establishments to
record where the donor may be contacted within 8 weeks of donation.

C. Donor Notification (New Part 630)

Section 630.6(a) requires establishments collecting blood or blood
components to make reasonable attempts to notify donors, including
autologous donors, who are deferred based on the results of tests for
evidence of infection due to a communicable disease agent(s) including
syphilis; or determined not to be suitable for donation based on
failure to satisfy suitability criteria. Section 630.6(b) requires that
notification contain the following information: (1) The donor is
deferred or determined not to be suitable for donation, and the reason
for that decision; (2) the types of blood or blood components the donor
should not donate in the future, where appropriate; (3) the
establishment must provide the results of the test for evidence of
infection due to the communicable disease agent(s) including syphilis
that was the basis for the deferral and results of supplemental
(additional, more specific) tests, when applicable; and (4) where
appropriate, the establishment must provide information concerning
medical followup and counseling.
Under Sec. 630.6(d)(1), the establishment must notify the referring
physician of an autologous donor when the autologous donor is deferred
under new Sec. 610.41. This notification must provide the same
information as required for the notification of a donor.
Description of Respondents: Blood and plasma establishments that
collect blood, and blood components, including Source Plasma.
As required by section 3506(c)(2)(B) of the PRA, FDA provided an
opportunity for public comment on the information collection
requirements of the proposed rule (64 FR 45355). In accordance with the
PRA, OMB reserved approval of the information collection burden in the
proposed rule stating that they will make an assessment in light of
public comments received on the proposed rule. Two letters of comment
on the information collection burden were submitted to the docket.
(Comment 24) One comment, in response to our notification estimate
of a half hour, stated that notification and providing the required
information would more likely take at least 1 hour, especially for
individuals apparently infected with HIV, HBV, or HCV. The comment also
stated that providing followup testing (supplemental) is more likely to
take at least half an hour.
FDA agrees with the comment and is revising the estimated hours per
response in table 1 of this document to 1.5 hours for notifying a donor
with reactive screeningtest results.
(Comment 25) One comment suggested that the burden of the
recordkeeping requirements for documenting the attempts to contact the
donor is significantly underestimated.
The comment did not provide information supporting the statement
that the burden is underestimated. Therefore, we continue to estimate
the time for recording the notification of each donor as an average of
3 minutes. (Comment 26) One comment opined that the estimate of 1.2
percent for donors who are deferred from donating due to failure to
satisfy suitability criteria is far below actuality and that the number
of donors deferred as a result of health history questions average 13
percent.
We have revised our estimate to reflect that an average of 13
percent of donors annually are determined not to be suitable for
donation based on failure to satisfy suitability criteria.
According to FDA's registration data base, there are currently
about 1,041 establishments affected by this rule: Approximately 60
licensed plasma establishments with multiple locations that collect
Source Plasma, and approximately 981 registered blood and plasma
establishments that collect blood and blood components. The number
differs from the number of respondents estimated in the proposed rule
(2,800) because we incorrectly included in the estimated number all
registered establishments, including those that do no collect blood and
plasma. Based on estimates provided by AABB and GAO, these
establishments collect annually approximately 12.6 million donations of
blood and blood components from approximately 8 million donors and
approximately 12 million donations of Source Plasma from 1.5 million
donors. As part of the 12.6 million donations of blood and blood
components, AABB also estimates that approximately 643,000 autologous
donations are collected annually. Assuming each autologous donor makes
an average of 2 donations, we estimate that there are approximately
321,500 autologous donors.

D. Annual Reporting Burden (Table 1)

Industry estimates that approximately 13 percent of 9.5 million
donors (1.2 million donors) who come to donate annually are determined
not to be suitable for donation prior to collection because of failure
to satisfy suitability criteria. It is the usual and customary business
practice of virtually all 1,041 collecting establishments to notify on
site and to explain the reason why the

[[Page 31175]]

donor is determined not to be suitable for donating. Based on such
information as is available to FDA, we estimate that two-thirds of
collecting establishments (697) provide on site additional information
and counseling to a donor determined not to be suitable for donation as
usual and customary business practice. Consequently, we estimate that
only one-third or 344 collection establishments would need to provide
additional information and counseling on site to 400,000 total donors.
Industry representatives estimated that it takes on average
approximately 5 minutes to provide appropriate health information to a
donor determined not to be suitable for donation.
GAO estimates that another 4.5 percent of 9.5 million donors
(427,500 donors) are deferred annually based on test results. We
estimate that currently 95 percent of the establishments that collect
98 percent of the blood and blood components notify donors who have
reactive test results for HIV, HBV, HCV, HTLV, and syphilis as usual
and customary business practice. Consequently, 5 percent (52) of the
industry collecting 2 percent (8,550) of the deferred donors would
experience new burden related to this requirement. We have adjusted our
original estimate of 15 minutes to complete the notification process to
1 hour based on comment from industry. Based on the same comment, we
have also adjusted the time estimated for additional counseling of the
donor once notification is received from 15 minutes to 30 minutes. The
total for notification of each donor is 1.5 hours. As part of usual and
customary business practice, collecting establishments notify an
autologous donor's referring physician of reactive test results
obtained during the donation process. However, we estimate that 5
percent of the 981 blood collection establishments (52) do not notify
the referring physicians of the estimated 2 percent of 321,500
autologous donors with reactive test results (6,430). The time for
these establishments to notify the referring physician is estimated at
1 hour.

E. Recordkeeping Burden (Table 2)

We estimate that 1,041 establishments will each expend, as a one-
time burden, an average of 8 hours to reconcile their SOP's with the
requirements (one-time burden of 7 hours to revise and an on-going
burden of 1 hour to maintain). All plasma and blood establishments
record each donor's address as part of their usual and customary
business practice and, therefore, the requirement under
Sec. 606.160(b)(1)(x) does not create new or additional burden. Section
606.160(b)(1)(ix) requires that establishments record the notification
efforts. We estimate that it will take 3 minutes on average to record
the notification status of each of the 1.2 million donors determined
not to be suitable to donate and each of the 427,500 donors deferred
based on reactive test results for evidence of infection due to
communicable disease agents. Section 606.160(b)(1)(xi) requires that
records be kept regarding an establishment's efforts to notify the
referring physician of a deferred autologous donor. Only the 981
registered blood establishments collect autologous donations and
therefore are required to notify referring physicians. We estimate that
4.5 percent of the 321,500 autologous donors (14,468) will be deferred
under new Sec. 610.41, and thus result in the notification of their
referring physicians.

Table 1.--Estimated Annual Reporting Burden \1\
----------------------------------------------------------------------------------------------------------------
21 CFR AnnualFrequency Total Annual
Section No. ofRespondents perResponse Responses Hours perResponse Total Hours
----------------------------------------------------------------------------------------------------------------
630.6(a)\2\ 344 1,163 400,000 0.08 32,000
630.6(a)\3\ 52 164 8,550 1.5 12,825
630.6(d)(1) 52 124 6,430 1 6,430
Total 51,255
----------------------------------------------------------------------------------------------------------------
\1\ There are no capital costs or operating and maintenance costs associated with this collection of
information.
\2\ Notification of donors determined not to be suitable for donation based on failure to satisfy suitability
criteria.
\3\ Notification of donors deferred based on reactive test results for evidence of infection due to communicable
disease agents.

Table 2.--Estimated Annual Recordkeeping Burden \1\
----------------------------------------------------------------------------------------------------------------
21 CFR No. of Annual Frequency Total Annual Hours per
Section Recordkeepers per Recordkeeping Records Recordkeeper Total Hours
----------------------------------------------------------------------------------------------------------------
606.100(b)(2 1,041 1 1,041 1 1,041
0)
(maintenanc
e of SOP's)
606.160(b)(1 1,041 1,563 1,627,500 0.05 81,375
)(ix)
606.160(b)(1 981 15 14,468 0.05 723
)(xi)
Total 83,139
----------------------------------------------------------------------------------------------------------------
\1\ There are no capital costs or operating and maintenance costs associated with this collection of
information.

Table 3.--Estimated One-Time Recordkeeping Burden\1\
----------------------------------------------------------------------------------------------------------------
21 CFR No. of Annual Frequency Total Annual
Section Recordkeepers per Recordkeeping Records Hours per Record Total Hours
----------------------------------------------------------------------------------------------------------------
606.100(b)(2 1,041 1 1,041 7 7,287
0)
----------------------------------------------------------------------------------------------------------------
\1\ There are no capital costs or operating and maintenance costs associated with this collection of
information.

Prior to the effective date of this final rule, FDA will publish a
notice in the Federal Register announcing OMB's decision to approve,
modify, or disapprove the information collection provisions in this
final rule. An agency may not conduct or sponsor, and a person is not
required to respond to, a collection of information unless it displays
a currently valid OMB number.

[[Page 31176]]

VI. Environmental Impact

The agency has determined under 21 CFR 25.30(j) 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.

VII. Federalism

FDA has analyzed this final rule in accordance with the principles
set forth in Executive Order 13132. FDA has determined that the 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 order and, consequently, a federalism
summary impact statement is not required.

VIII. 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. 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 to 812.
2. 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 entitled ``Demographic
Characteristics, Unreported Risk Behaviors, and the Prevalence and
Incidence of Viral Infections: A Comparison of Aphersis and Whole-Blood
Donors,'' Transfusion, April 1998, vol. 38, pp. 350 to 358.

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, parts 606 and 630 are 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 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. 630.6 of this chapter.
* * * * *
3. Section 606.160 is amended by adding paragraphs (b)(1)(ix) to
(b)(1)(xi) to read as follows:

Sec. 606.160 Records.

* * * * *
(b) * * *
(1) * * *
(ix) Records of notification of donors deferred or determined not
to be suitable for donation, including appropriate followup if the
initial attempt at notification fails, performed under Sec. 630.6 of
this chapter.
(x) The donor's address provided at the time of donation where the
donor may be contacted within 8 weeks after donation.
(xi) Records of notification of the referring physician of a
deferred autologous donor, including appropriate followup if the
initial notification attempt fails, performed under Sec. 630.6 of this
chapter.
* * * * *
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, 264.

Sec. 630.6 Donor notification.

(a) Notification of donors. You, an establishment that collects
blood or blood components, 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 communicable
disease agent(s) as required by Sec. 610.41 of this chapter; or who has
been determined not to be suitable as a donor based on suitability
criteria under Sec. 640.3 or Sec. 640.63 of this chapter. You must
attempt to obtain the results of supplemental testing required under
Sec. 610.40(e) of this chapter prior to notifying a donor of the
deferral. If notification occurs prior to receipt of such results, you
must also notify a deferred donor of the results of the supplemental
testing. You must notify a donor as described in paragraph (b) of this
section.
(b) Content of notification. You must provide the following
information to a donor deferred or determined not to be suitable as a
donor as described in paragraph (a) of this section:
(1) That the donor is deferred or determined not to be suitable for
donation and the reason for that decision;
(2) Where appropriate, the types of donation of blood or blood
components that 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(e) of this chapter; and,
(4) Where appropriate, information concerning medical followup and
counseling.
(c) Time period for notification. You must make reasonable attempts
to notify the donor within 8 weeks after determining that the donor is
deferred or determined not to be suitable for donation as described in
paragraph (a) of this section. You must document that you have
successfully notified the donor or when you are unsuccessful that you
have made reasonable attempts to notify the donor.
(d) Autologous donors. (1) You also must provide the following
information to the referring physician of an autologous donor who is
deferred based on the results of tests for evidence of infection with a
communicable disease agent(s) as described in paragraph (a) of this
section:
(i) Information that the autologous donor is deferred based on the
results of tests for evidence of infection due to communicable disease
agent(s), as required under Sec. 610.41 of this chapter, and the reason
for that decision;
(ii) Where appropriate, the types of donation of blood or blood
components

[[Page 31177]]

that the autologous donor should not donate in the future; and
(iii) 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(e) of this
chapter.
(2) You must make reasonable attempts to notify the autologous
donor's referring physician within 8 weeks after determining that the
autologous donor is deferred as described in paragraph (a) of this
section. You must document that you have successfully notified the
autologous donor's referring physician or when you are unsuccessful
that you have made reasonable attempts to notify the physician.

Dated: June 1, 2001.
Bernard A. Schwetz,
Acting Principal Deputy Commissioner.
[FR Doc. 01-14409 Filed 6-8-01; 8:45 am]
BILLING CODE 4160-01-F