```

[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]

-----------------------------------------------------------------------

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.

-----------------------------------------------------------------------

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
```