[Federal Register Volume 61, Number 175 (Monday, September 9, 1996)]
[Rules and Regulations]
[Pages 47413-47423]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 96-22709]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Parts 606 and 610

[Docket No. 91N-0152]
RIN 0910-AA05


Current Good Manufacturing Practices for Blood and Blood 
Components: Notification of Consignees Receiving Blood and Blood 
Components at Increased Risk for Transmitting HIV Infection

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 that blood establishments (including 
plasma establishments) prepare and follow written procedures for 
appropriate action when it is determined that Whole Blood, blood 
components (including recovered plasma), Source Plasma and Source 
Leukocytes at increased risk for transmitting human immunodeficiency 
virus (HIV) infection have been collected. This final rule requires 
that when a donor who previously donated blood is tested on a later 
donation in accordance with the regulations, and tests repeatedly 
reactive for antibody to HIV, the blood establishment shall perform 
more specific testing using a licensed test, if available, and notify 
consignees who received Whole Blood, blood components, Source Plasma or 
Source Leukocytes from prior collections so that appropriate action is 
taken. Blood establishments and consignees are required to quarantine 
previously collected Whole Blood, blood components, Source Plasma and 
Source Leukocytes from such donors, and if appropriate, notify 
transfusion recipients.
    The Health Care Financing Administration (HCFA) is also issuing a 
final rule, published elsewhere in this Federal Register, which 
requires all transfusion services subject to HCFA's conditions of 
Medicare participation for hospitals to notify transfusion recipients 
who have received Whole Blood or blood components from a donor whose 
subsequent donation test results are positive for antibody to HIV 
(hereinafter referred to as HCFA's final rule). FDA is requiring 
transfusion services that do not participate in Medicare and are, 
therefore, not subject to HCFA's final rule, to take steps to notify 
transfusion recipients.
    FDA is taking this action to help ensure the continued safety of 
the blood supply, and to help ensure that information is provided to 
consignees of Whole Blood, blood components, Source Plasma and Source 
Leukocytes and to recipients of Whole Blood and blood components from a 
donor whose subsequent donation tests positive for antibody to HIV.

DATES: This regulation is effective November 8, 1996. Written comments 
on the information colelction requirements should be submitted by 
February 7, 1997.

ADDRESSES: Submit written comments on the information collection 
requirements to the Dockets Management Branch (HFA-305), Food and Drug 
Administration, 12420 Parklawn Dr., rm. 1-23, Rockville, MD 20857.
FOR FURTHER INFORMATION CONTACT:
Sharon Carayiannis, Center for Biologics Evaluation and Research (HFM-
630), Food and Drug Administration, 1401 Rockville Pike, suite 200N, 
Rockville, MD 20852-1448, 301-594-3074.

SUPPLEMENTARY INFORMATION: 

I. Introduction

    FDA has implemented an extensive system of donor screening and 
testing procedures performed by blood establishments before, during, 
and after donation, to help prevent the transfusion of blood products 
that are at increased risk for transmitting HIV. HIV is the virus that 
causes acquired immune deficiency syndrome (AIDS), a

[[Page 47414]]

communicable disease that can be transmitted through transfusion.
    As a result of the screening and testing procedures, the risk of 
transmitting HIV infection through blood transfusion is very low. 
Despite the best practices of blood establishments, however, a person 
may donate blood early in infection, during the period when the 
antibody to HIV is not detectable by a screening test, but HIV is 
present in the donor's blood (a so-called ``window'' period). If the 
donor attempts to donate blood at a later date, the test for antibody 
to HIV may, at that time, be repeatedly reactive. Therefore, FDA 
believes such circumstances require clarification of the donor's status 
through testing with a more specific antibody test and procedures to 
``lookback'' at prior collections. Previously collected Whole Blood and 
blood components would be at increased risk for transmitting HIV and a 
recipient of a transfusion of Whole Blood and blood components 
collected during the ``window'' period would not know that he or she 
may have become infected with HIV through the transfusion unless 
notified.
    In the Federal Register of June 30, 1993 (58 FR 34962), FDA issued 
a proposed rule to require appropriate action when it is later 
determined that blood and blood components might have been collected 
during the ``window'' period. FDA has reviewed comments submitted on 
the proposed rule and is now issuing this final rule to require 
facilities involved in the collection, processing, and administration 
of blood to quarantine Whole Blood, blood components, Source Plasma and 
Source Leukocytes which were collected from a donor who tested negative 
at the time of previous donations but subsequently tests repeatedly 
reactive for antibody to HIV. The final rule requires blood 
establishments to inform consignees (e.g., hospital transfusion 
services and manufacturers of plasma derivatives) of the collection and 
distribution of such previously donated Whole Blood, blood components, 
Source Plasma and Source Leukocytes.
    In the Federal Register of June 30, 1993 (58 FR 34977), HCFA also 
issued a proposed rule which would require certain transfusion services 
to notify recipients of transfusions determined to be from a donor 
whose subsequent donation tests positive for antibody to HIV 
(hereinafter referred to as HCFA's proposed rule). The final rules 
issued by both FDA and HCFA require transfusion services to perform 
such notifications.
    In a memorandum of understanding (MOU), FDA and HCFA agreed to 
coordinate the inspections of transfusion services in medicare 
participating hospitals to minimize duplication of effort and to reduce 
the burden on affected facilities. Blood establishments, including 
those hospital transfusion services not subject to HCFA's regulations 
on the conditions of Medicare participation for hospitals, such as 
Indian Health Service and Veteran's Administration Hospitals, are 
subject to FDA's final rule. Thus, all transfusion services are subject 
to the requirements for quarantine and transfusion recipient 
notification under either the FDA or HCFA rule.

II. Highlights of the Final Rule

    Under the biologics licensing and quarantine provisions of the 
Public Health Service Act (42 U.S.C. 262-264) and the drug, device, and 
the general administrative provisions of the Federal Food, Drug, and 
Cosmetic Act (the act) (21 U.S.C. 351-353, 355-360, and 371-374), FDA 
has the authority to promulgate regulations designed to protect the 
public from unsafe or ineffective biological products and to issue 
regulations necessary to prevent the transmission of communicable 
diseases into the United States or from one State to another.
    Under these statutory authorities, FDA currently requires that each 
donation be tested and found negative for antibody to HIV under 
Sec. 610.45 (21 CFR 610.45). Existing regulations already restrict the 
use, for transfusion or further manufacture, of a donation testing 
repeatedly reactive for antibody to HIV. Even though current licensed 
screening tests for antibody to HIV are very sensitive, testing may not 
identify all units capable of transmitting HIV infection. For this 
reason, many blood establishments have instituted special procedures 
when blood or plasma has been collected from a donor testing positive 
for antibody to HIV at a later date. These procedures, commonly 
referred to as ``lookback'' procedures, involve determining the 
suitability of prior collections of Whole Blood, blood components, 
Source Plasma and Source Leukocytes from such a donor. These existing 
procedures may also involve notifying consignees that have received 
prior collections from the donor so consignees can quarantine such 
products and, as appropriate, take steps to notify the transfusion 
recipients of such Whole Blood and blood components.
    While many blood establishments have voluntarily developed written 
``lookback'' procedures, these existing procedures vary significantly 
among blood establishments. As proposed in the Federal Register of June 
30, 1993, FDA is amending the biologics regulations to require blood 
establishments to prepare and follow written standard operating 
procedures (SOP's), defining steps to be taken when ``lookback'' 
circumstances arise.
    The final rule requires blood establishments to perform more 
specific testing of the donor's blood using a licensed test, and to 
notify consignees who received Whole Blood, blood components, Source 
Plasma and Source Leukocytes from prior collections so that appropriate 
action is taken. Blood establishments and consignees shall quarantine, 
as described later in this document, previously collected Whole Blood, 
blood components, Source Plasma and Source Leukocytes from such donors 
until the donor's status is clarified through further testing. FDA is 
requiring that other informative test results, if available, be 
considered when determining the status of the donor and the suitability 
of prior collections.
    Upon completion of more specific testing, the final rule also 
requires hospital transfusion services that do not participate in 
Medicare and are, therefore, not subject to HCFA's final rule, to take 
steps to notify transfusion recipients, as appropriate. Such 
transfusion recipients shall receive notification for the purpose of 
testing for evidence of HIV infection, early treatment, if indicated, 
and counseling to take appropriate precautions to prevent the further 
spread of the virus such as to sexual partners.

III. HCFA's Companion Rule

    Under HCFA's proposed rule, transfusion services operated by 
hospitals participating in Medicare and inspected by HCFA that receive 
notification of previously collected Whole Blood and blood components 
at increased risk for transmitting HIV, would be required to quarantine 
such prior collections and notify the transfusion recipient's attending 
physician, the transfusion recipient, or other authorized person, as 
appropriate. HCFA's final rule requires the hospital transfusion 
service to have a written agreement with each blood supplier 
documenting these procedures.
    As referenced in section I. of this document, FDA and HCFA 
coordinate the inspections of transfusion services in medicare 
participating hospitals to minimize duplication of effort and to reduce 
the burden on affected facilities. In the MOU, it was estimated that 
HCFA would be responsible for inspecting and surveying approximately 
3,000 transfusion services. FDA continues to conduct the inspections of

[[Page 47415]]

establishments were activities include more than the performance of 
compatibility testing. (See 49 FR 34448, August 31, 1984, and 21 CFR 
607.65.)

IV. Other Sources of Information

    As FDA recognized in the preamble to the proposed rule, blood 
establishments may receive information from other sources which 
indicate that a donor may be infected with HIV. FDA encourages blood 
establishments to initiate ``lookback'' procedures whenever they have 
information that a donor has become infected with HIV. FDA recognizes 
the existence of diagnostic modalities for HIV infection, other than 
antibody testing, such as virus culture or direct viral assays. FDA 
encourages blood establishments to consider such test results, when 
available and reliable, and to voluntarily initiate the ``lookback'' 
process as described in this final rule. Additionally, the final rule 
requires that such results be considered prior to release of units 
quarantined in a ``lookback'' procedure.
    In particular, FDA recommends that blood establishments voluntarily 
initiate ``lookback'' procedures based on HIV antigen testing, as 
indicated in the August 8, 1995, Memorandum to All Registered Blood 
Establishments, Regarding Recommendations for Donor Screening with a 
Licensed Test for HIV-1 Antigen. In the August 8, 1995, memorandum FDA 
provided recommendations for the implementation of donor screening 
tests for HIV type 1 (HIV-1) antigen(s) within 3 months of the 
commercial availability of the first test for HIV-1 antigen(s). The 
August 8, 1995, memorandum stated that the average infectious 
``window'' period, when HIV antibody is not detectable by the screening 
test, is estimated to be approximately 22 to 25 days for screening with 
combination assays for antibodies to HIV-1 and HIV-2. The memorandum 
further stated that HIV antigen screening could reduce the ``window'' 
period by an estimated 6 days and could be expected to prevent up to 25 
percent of the current ``window'' period donations or about 5 to 10 
cases of transfusion associated HIV per year. Because HIV-1 antigen 
screening will reduce but not eliminate the residual risk for HIV-1 
from transfusion, FDA regards such screening as an interim measure 
pending the availability of improved technology for this purpose. FDA 
encourages continued development of new methods no further reduce the 
risk of HIV transmission due to ``window'' period donations.

V. Responses to Letters of Comment

    FDA provided interested individuals 60 days to submit written 
comments on the proposed rule. FDA received a total of 25 letters of 
comment, which included 10 from blood collection facilities or blood 
banks, 8 from pathologists or pathology associations, 6 from blood 
banking associations, and 1 from a parent of children with hemophilia.
    Twenty-one comments agreed with the concept of ``lookback''. There 
were differences of opinion as to how the ``lookback'' process should 
be conducted and concerns regarding liability of various individuals 
involved in the process. Three comments indicated support for the 
strengthening of the ``lookback'' requirements, while eight comments 
suggested that the proposed rule's cost to industry would pose a 
significant burden with little benefit to public health.
    After review and consideration of all comments, FDA continues to 
believe that the new requirements for the handling of prior collections 
of Whole Blood, blood components, Source Plasma and Source Leukocytes 
later found to be at increased risk for transmitting HIV infection are 
important public health measures. Below, FDA provides responses to the 
comments received.

A. General Comments

1. Terminology Used by FDA and HCFA
    Two comments expressed some confusion over specific terminology and 
the differences in terminology used by FDA and HCFA. One comment 
suggested the use of ``transfusion service'' instead of ``consignee.'' 
One comment suggested the use of a more specific term for 
``recipient.''
    FDA's use of the term consignee includes any facility to which the 
Whole Blood, blood components, Source Plasma and Source Leukocytes have 
been shipped (e.g., a transfusion service, a manufacturer of blood 
products, or another blood banking establishment). As written, when the 
rule uses the term consignee, it refers to more than a transfusion 
service. The FDA and HCFA rules refer to ``transfusion services'' when 
the rules are specific to transfusion services. To interchange these 
terms would cause more confusion and would not achieve the goals 
sought.
    As suggested by one comment, FDA has amended the rule to use the 
terms transfusion recipient or transfused patient in a number of places 
to make it clear that FDA is referring to the recipient of the 
transfusion. Where the term ``recipient'' is used alone, FDA believes 
that the context makes it clear that the term refers to patients and 
not to consignees.
    FDA believes that the terminology used in the rules is appropriate 
and understood by the entities subject to FDA regulation. FDA also 
believes that the terminology used by HCFA is understood by the 
entities regulated by HCFA.
2. Blood Donor Locator Service
    Three comments stated an interest in using the Blood Donor Locator 
Service (BDLS) as a part of the ``lookback'' process. One request was 
to expand this service to locate recipients also.
    The BDLS final rule which was published in the Federal Register of 
December 24, 1991 (56 FR 66561), addressed similar comments calling for 
the expanded use of the service. The statutory authority to conduct the 
BDLS, as defined by section 8008 of the Technical and Miscellaneous 
Revenue Act of 1988 (Pub. L. 100-647), only authorizes the Social 
Security Administration to provide address information for blood donors 
whose test results for antibody to HIV show that they are, or may be, 
infected with HIV. The legislation authorizing the BDLS does not extend 
to transfusion recipients or to any other individual. Participation in 
the BDLS by State agencies and blood donation facilities is voluntary, 
but participants must agree to comply with the provisions of the 
statute and the regulations as defined in the BDLS final rule.
3. Organization of Information in the Final Rule
    One comment suggested that the organization of information in the 
regulations was confusing, and asked for clarification of the intent of 
the regulations.
    The rule is divided into subsections that provide specific 
direction on each aspect of the ``lookback'' process. Each subsection 
of the rule must be reviewed for a complete understanding of all 
aspects of this important information. The following description serves 
as a brief overview of the regulations. Section 606.100 (21 CFR 
606.100) states the requirements for SOP's, and Sec. 606.160 (21 CFR 
606.160) states the requirements for recordkeeping. Section 610.45(d) 
identifies the circumstances under which the ``lookback'' process shall 
be initiated. Section 610.46(a) (21 CFR 610.46(a)) states the 
requirements for the initial steps of the ``lookback'' process. Section 
610.46(a)(1) establishes the circumstances for quarantine and requires 
notification of consignees to

[[Page 47416]]

quarantine such products. Section 610.46(a)(2) discusses quarantine of 
products held by consignees.
    Section 610.46(b) specifies the time limit for completion of the 
licensed, more specific test and the notification of the consignee of 
those test results. Section 610.46(c) addresses products that are 
exempt from quarantine and Sec. 610.46(d) discusses requirements for 
release from quarantine. Section 610.46(e) makes clear that these 
actions are not considered to be product recalls. Section 610.47(a) (21 
CFR 610.47(a)) covers those transfusion services not subject to HCFA's 
regulations. Section 610.47(b) contains requirements for notification 
of recipients and Sec. 610.47(c) addresses the notification of a legal 
representative or relative acting on behalf of the recipient.

B. Comments on Sec. 606.100

    Four comments requested more specific direction regarding the 
content of SOP's.
    It is intention of FDA to allow appropriate flexibility to blood 
establishments in the development of their procedures. For example, as 
mentioned in one comment, a blood establishment could identify by title 
or name the individuals authorized to provide and receive consignee 
notification in the ``lookback'' process. FDA further discusses the 
content of SOP's in the responses to comments on specific subsections 
of the rule.

C. Comments on Sec. 610.45(d)

1. Use of Information from Other Sources to Initiate ``Lookback'' 
Process
    One comment stated that there will be additional circumstances when 
a blood establishment can reliably and consistently receive information 
that should result in the initiation of a ``lookback'' process. The 
sources of this information may include the U.S. military, health 
departments or physicians of former donors now found to be HIV-infected 
or diagnosed as having AIDS.
    FDA agrees that there will be circumstances when the initiation of 
``lookback'' may be based on reliable information provided by the U.S. 
military, health departments, and other sources and recommends 
appropriate action in those instances. However, a blood establishment 
generally has no control over whether they will be appropriately 
contacted by these outside sources. In addition, the laws and 
procedures governing such notifications will vary from State to State. 
Therefore, FDA's final rule does not contain specific additional 
circumstances under which ``lookback'' is required because the ability 
for each establishment to meet the requirements will vary so widely, 
based upon varying State laws, local practices, and confidentiality 
issues.
2. Initiation of ``Lookback'' Process Based on Repeatedly Reactive 
Screening Results
    Three comments objected to the initiation of the ``lookback'' 
process based on the repeatedly reactive antibody screening test 
results before the completion of the licensed, more specific test. One 
comment stated that any ``lookback'' action, beyond the quarantine of 
product, based on the antibody screening test results would be 
inappropriate because those tests have a high rate of false positive 
results and were not intended to be diagnostic without further 
confirmatory testing.
    One comment stated that there is a very high cost associated with 
preventing the transfusion of very few infectious units based on: (1) 
The estimate that of all donations made each year, most blood and blood 
components will be transfused before a donor is permitted to donate 
again 56 days later; (2) the estimate that only one half of donors will 
return to donate again; and (3) the very low number of units expected 
to be infectious despite proper testing.
    One comment in support of the rule stated that the rule did not 
place undue hardship on the blood banking industry. One comment 
objected to the more stringent requirements for notification due to the 
current burden of escalating demands and diminishing resources, 
including increased workload due to more complicated patient illnesses, 
vacant technical positions that cannot be filled due to the declining 
numbers of skilled, qualified medical technologists, and hospital costs 
rising faster than revenues. One comment stated concern that patient 
needs would not be met because the increased regulation would force 
hospital based donor centers to close as a result of economic 
pressures.
    One comment cited a threefold increase in the rate of repeatedly 
reactive screening tests for antibody to HIV with none of those 
confirmed by Western Blot in the past year, which would result in much 
higher expected total annualized costs than projected by FDA. Two 
comments stated that the actual costs would be twice that estimated by 
FDA. Three comments stated that the goals of the proposed rule are 
laudable but also estimated that most HIV infections are spread through 
other modes of transmission and, therefore, our limited health care 
dollars are better spent in other ways.
    FDA is charged with the responsibility of protecting the public 
from unsafe biological products and has the authority to promulgate 
regulations to accomplish its public health mission. Comments on the 
proposed rule indicate that SOP's for the ``lookback'' process are 
already in place in a large percentage of blood establishments. Based 
on comments received, FDA believes that the modification of existing 
SOP's to meet the requirements of this rule would not impose an 
unreasonable burden or expense to the large number of establishments 
with an existing system for handling ``lookback'' circumstances.
    FDA believes the prevention of a small number of transmissions of 
HIV per year that will result from the initiation of the ``lookback'' 
process based on the repeatedly reactive antibody screening test 
results or other informative test results is a clear benefit. FDA 
believes that steps must be taken to avoid transfusion of potentially 
unsuitable Whole Blood and blood components while waiting for the 
completion of further testing, especially since the time limit for such 
testing has been extended to 30 days, as described later in this 
document. FDA recognizes that the requirement for the initiation of 
this process at the time of the repeatedly reactive HIV antibody test 
will result in some additional costs to blood establishments that 
currently do not begin the process at this point. However, FDA believes 
these steps are warranted to increase the safety of the nation's blood 
supply.

D. Comments on Sec. 610.46(a)

1. Notification of Consignees
    One comment stated concern regarding the notification of consignees 
of the results of the licensed, more specific test and the potential 
for confusion if the product in question had already been returned to 
the blood donor center.
    The final rule requires that blood establishments notify consignees 
to quarantine Whole Blood, blood components, Source Plasma and Source 
Leukocytes that are at increased risk for transmitting HIV infection. 
Upon notification by the blood establishment, the consignee is to 
promptly, within 72 hours, quarantine the affected products until 
notified of the negative results of a licensed, more specific test. 
Return of such products to the blood establishment is not a requirement 
of this rule, and, therefore, should not create confusion. However, if 
the

[[Page 47417]]

consignee does return the blood or blood components to the blood 
establishment, no further consignee notification would be required. FDA 
has amended the final rule to clarify the requirement to promptly 
notify consignees, within 72 hours, for the purpose of identifying 
those products that remain in inventory and require quarantine.
2. Products for Further Manufacture
    One comment concerned Sec. 610.46(a)(2), which requires that 
unpooled products held by the consignee shall be quarantined. The 
comment stated that while it appears that the proposed rule is 
structured to exclude large pools of plasma from some requirements, the 
rule might be interpreted to have a different result when the 
collecting facility and the manufacturing facility hold the same 
license. The comment stated further that in this situation, both large 
and small pools would be quarantined since the products were not 
shipped to a consignee to be pooled.
    The comment also asked that small pools of plasma intended for 
further manufacture into noninjectable products also be exempt from 
quarantine because they are sometimes pooled at the collection facility 
and may include plasma considered to be in short supply. The comment 
stated that small pools of plasma intended for the manufacture of 
noninjectable products should be exempt from quarantine because they 
are sufficiently safe as noninjectable products.
    A collection facility would be required to quarantine all in-house 
or ``on-site'' Whole Blood, blood components, Source Plasma and Source 
Leukocytes. A manufacturing facility that shares an establishment 
license with the collecting facility is not required to quarantine 
pooled products. To avoid a shortage of injectable and noninjectable 
products the final rule exempts from quarantine pooled Source Plasma 
and Source Leukocytes intended for further manufacture into injectable 
and noninjectable products, as described in Sec. 610.46(c). FDA 
believes this requirement will better identify those affected products 
to be quarantine while ensuring the availability of blood products for 
further manufacture.
    Additionally, FDA agrees that pools intended for further 
manufacture into noninjectable products are sufficiently safe due to 
their intended use as noninjectable products and are, therefore, exempt 
from quarantine. The rule has been amended to clarify that Pooled 
Source Plasma and Pooled Source Leukocytes are exempt from quarantine. 
Appropriate safeguards must be used to prevent such products intended 
for further manufacture into non-injectable products from being used 
for further manufacture into injectable products.

E. Comments on Sec. 610.46(b)

1. Two Week Limit for Completion of Licensed, More Specific Test
    One comment supported proposed Sec. 610.46(b) which requires the 2-
week time limit for completion of the licensed, more specific test and 
consignee notification, while twenty-three comments expressed 
disagreement with the time limit. The 2-week time limit was cited as 
too short due to shipping of samples, batching of laboratory work, the 
additional number of tests run when the sample is not negative, 
dependence upon reference laboratories for this work, and unforeseen 
circumstances that are beyond the control of the blood establishment. 
The suggestions for a more appropriate timeframe ranged from 3 weeks to 
8 weeks to ``as soon as possible''.
    After consideration of the additional information provided in the 
comment letters, FDA believes that it is appropriate and reasonable to 
change the time limit for completion of the licensed, more specific 
test and consignee notification of the test results. FDA is amending 
Sec. 610.46(b) by allowing a maximum of 30 calendar days for completion 
of the licensed, more specific test for antibody to HIV and consignee 
notification of the test results.
    FDA's concern for the prompt notification of the transfusion 
recipient, without undue burden to industry, dictates that the time 
limit for completion of testing not exceed 30 days. FDA's extension of 
the time limit for the completion of these steps is intended to give 
blood establishments a reasonable time period to comply with the 
regulation. FDA expects that blood establishments will initiate and 
complete such testing expeditiously, but take no longer than 30 
calendar days.
    The written SOP's of the establishment required under 
Sec. 606.100(b)(19) should be adequate to ensure that the required 
testing and consignee notification is routinely completed within 30 
days. In rare circumstances, such as when there are testing problems, 
testing and notification may take longer than 30 days. In such cases 
the establishment should document in its records the reason for the 
failure to meet the requirement. If the establishment frequently fails 
to meet the required time limits, the establishment should review its 
procedures to determine how testing and consignee notification can be 
expedited.
2. Positive Test for Antibody to HIV-2
    Two comments on Sec. 610.46(b) requested clarification on further 
testing and notification of consignee and recipients when donors 
subsequently test positive for antibody to HIV-2.
    In the Memorandum to All Registered Blood Establishments, Revised 
Recommendations for the Prevention of HIV Transmission by Blood and 
Blood Products, dated April 23, 1992, FDA provided guidance 
recommending that all blood establishments collecting Whole Blood, 
blood components, Source Plasma, or Source Leukocytes implement a 
licensed test for detection of antibody to HIV-2 by June 1, 1992. FDA 
modified existing recommendations for prevention of HIV transmission by 
blood and blood products to include HIV-2 testing at that time. The 
revised recommendations for donor testing, deferral, and reentry are 
found in section II. and the recommendations on ``lookback'' are found 
in section IV. of the April 23, 1992, memorandum.
    This final rule is similar to the FDA guidance on supplemental 
tests recommended in the April 23, 1992, Memorandum. FDA has amended 
Sec. 610.46(b) of the final rule to clarify requirements for HIV-2 
testing. Currently, there is no ``licensed, more specific'' test for 
antibody to HIV-2. Thus, the final rule requires the following:
    (1) When a donor's screening test for antibody to HIV is repeatedly 
reactive, a licensed, more specific test for antibody to HIV shall be 
performed.
    (2) When the repeatedly reactive screening test is performed using 
a single virus test for antibody to HIV-2 or combination test for 
antibody to HIV-1/HIV-2, a second screening test for HIV-2, which is 
different from the original HIV-2 test, must also be performed. This 
second, different enzyme immuno-assay (EIA) test must be a licensed 
test and can be either a single virus test or a combination test.
    Whole Blood, blood components, Source Plasma and Source Leukocytes 
from prior collections may be released from quarantine only if the 
donor is tested for antibody to HIV-1 by a licensed, more specific test 
and the result is negative; and if the screening test is repeated using 
a different EIA test for antibody to HIV-2, either single virus or 
combination test, and the result is negative, absent other informative 
test

[[Page 47418]]

results. Release from quarantine is not permitted under any other test 
results. Transfusion recipient notification is required when the 
licensed, more specific test for HIV-1 is positive or when the second, 
different EIA test for antibody to HIV-2 is repeatedly reactive.
    Whole Blood, blood components, Source Plasma and Source Leukocytes 
are exempt from quarantine if the collection occurred more than 12 
months prior to the donor's most recent negative screening test(s). If 
the most recent negative screening test for antibody to HIV was 
performed prior to the implementation of HIV-2 testing in June of 1992, 
then the negative screening test for HIV-1 is sufficient to establish 
the 12-month time period.
    This final rule supersedes the existing recommendations for 
``lookback'' procedures in section IV. of the April 23, 1992, 
Memorandum, Exclusion/Retrieval of Potentially Contaminated Units From 
Prior Collections and Notification of Consignees.

F. Comments on Sec. 610.46 (c) and (d)

1. Release From Quarantine and Western Blot Indeterminate Results
    Two comments indicated confusion regarding the disposition of 
components collected both greater than and less than the 12-month 
period prior to the most recent nonreactive test result. Additionally, 
two comments on the subject of Western blot indeterminate results asked 
for clarification and for exemption from the ``lookback'' process due 
to what the commentor believes is the unlikely occurrence that a unit 
with an indeterminate Western blot test result would be infectious.
    FDA is requiring prompt quarantine for Whole blood, blood 
components, Source Plasma and Source Leukocytes collected from a donor 
at increased risk for transmitting HIV infection. Quarantine is 
required for units from such a donor collected within the 5years prior 
to the repeatedly reactive test for antibody to HIV, if intended for 
transfusion, or collected within 6 months prior to the repeatedly 
reactive test result, if intended for further manufacture. Section 
610.46(c) describes the situation in which Whole Blood, blood 
components, Source Plasma and Source Leukocytes are exempt from 
quarantine because there is serological evidence that the donation(s) 
was not made during the ``window'' period.
    In the preamble to the proposed rule, FDA stated that, based on 
experience, current estimates predict with approximately 95 percent 
confidence that in all cases of HIV infection, the person will test 
positive for antibody to HIV by a licensed test within 6 months from 
the date of infection. As stated in the preamble to the proposed rule, 
to provide an additional margin of safety, FDA has extended the period 
for quarantine to 12 months, to more closely approximate a 99 percent 
confidence interval. Accordingly, FDA's requirement to quarantine all 
Whole Blood, blood components, Source Plasma and Source Leukocytes 
collected within 12 months prior to the most recent negative screening 
test provides an added margin of safety during the months when an 
infected donor may not yet test positive for antibody to HIV. All 
donations made before this 12-month period would be outside the 
``window'' period and would be exempt from quarantine.
    The final rule is amended to clarify the requirements when other 
informative test results are available. Section 610.46(d) of the final 
rule states that a product may be released from quarantine if the 
donor's blood is tested for antibody to HIV by a licensed, more 
specific test and the test result is negative, absent other informative 
test results. FDA believes that release from quarantine is possible 
only if the more specific test is negative and there are no other 
informative test results that show evidence of HIV infection. This 
regulation does not allow the release from quarantine following and 
indeterminate Western blot test result.
    Blood establishments may voluntarily perform other FDA approved 
informative tests for HIV and must consider those test results when 
determining the status of the donor and the suitability of prior 
collections. For example, FDA has recently recommended donor screening 
for HIV-1 antigen(s) using approved tests. Testing for HIV-1 antigen(s) 
using seroconversion samples has shown that donors with recent HIV 
infection test repeatedly reactive for antibody to HIV, yet test as 
negative or indeterminate by a more specific antibody test but positive 
for HIV-1 antigen(s). Prior collections from such a donor would not be 
exempt from quarantine unless collected more than 12 months prior to 
the donor's most recent negative screening test for HIV antibody.
    Disposition of prior collections at increased risk for transmitting 
HIV infection should follow the establishment's SOP for appropriate 
disposal of blood products that are unsuitable for transfusion, in 
accordance with Sec. 606.40. The Memorandum to All Registered Blood 
Establishments from the Director, Center for Biologics Evaluation and 
Research, Control of Unsuitable Blood and Blood Components, dated April 
6, 1988, provides additional guidance for quarantine and disposition of 
products unsuitable for transfusion.
    In situations where an establishment fails to comply within the 30-
day limit for completion of further testing, and subsequently the test 
result is negative, the Whole Blood, blood components, Source Plasma 
and Source Leukocytes may be released from quarantine and consignees 
must be notified promptly upon availability of the test results. 
Destruction of quarantined units is not required merely because further 
testing was completed after the 30-day deadline. No release of 
quarantined Whole Blood, blood components, Source Plasma and Source 
Leukocytes is permitted before the results of the further testing are 
available.
2. Use of Test Results From Other Laboratories
    Two comments asked that blood establishments be allowed to use the 
laboratory test results from other laboratories as evidence of the most 
recent negative screening test for antibody to HIV, thus allowing the 
quarantine and notification to be limited to units collected within 12 
months prior to that negative result. One comment stated that evidence 
of such negative screening results could be provided by independent 
clinical laboratories, State health departments, military laboratories, 
other blood banks, etc.
    FDA agrees that test results from the Clinical Laboratories 
Improvement Amendments of 1988 (42 U.S.C. 263a) certified laboratories 
or licensed blood establishments may be accepted as evidence of the 
most recent negative screening test for antibody to HIV, provided that 
the blood establishment has assurance that the laboratory is certified 
and is using a licensed test kit. The blood establishment should 
receive and retain testing records documenting the test results.

G. Comments on Sec. 610.47(a)

1. Notification of Transfusion Recipient Prior to Completion of 
Licensed, More Specific Test
    Two comments disagreed with the proposed requirement to notify 
recipients of potentially infectious units based upon screening results 
if the licensed, more specific test results are not available within 2 
weeks. One comment stated that upon notification, the transfusion 
recipient would experience unnecessary worry since

[[Page 47419]]

more than 90 percent of repeatedly reactive screening results are not 
confirmed by Western Blot testing.
    As previously discussed in this final rule, the time limit for the 
completion of the licensed, more specific test for HIV and the 
consignee notification of those test results has been extended from 2 
weeks to a maximum of 30-calendar days. This change makes it highly 
unlikely that complete results will not be available prior to the 
deadline for notification. If a situation of noncompliance occurs, 
however, FDA has amended Sec. 610.47(a) so that recipient notification 
prior to completion of the licensed, more specific test for HIV is not 
required. This change is consistent with FDA's proposal to notify 
recipients only if there are positive test results but not when the 
test results are indeterminate.
    FDA agrees that notification of transfusion recipients that the 
transfused blood or blood component was at increased risk for 
transmitting HIV is very likely to cause the recipient, and possibly 
others, extreme anxiety and concern. Based on the rate of repeatedly 
reactive screening tests that are not confirmed by further testing, a 
significant percentage of recipients would be subjected to a tentative 
notification which would prove to be alarming, confusing, and 
unnecessary. Such recipients would be notified when the increased risk 
for transmitting HIV has been confirmed by further testing.
2. Establishments Subject to ``Lookback'' Regulations
    One comment asked for clarification on Sec. 610.47(a) which 
addresses those establishments subject to FDA's rule and those 
hospitals subject to HCFA's rule. Two comments asked if these 
regulations apply to all regulated blood establishments, including 
small, hospital-based transfusion services that also draw blood donors. 
Section 610.47(a) specifically states that transfusion services that 
are not subject to HCFA's regulations on the conditions of Medicare 
participation for hospitals (42 CFR part 482) are subject to this rule. 
FDA inspects establishments where activities include more than the 
performance of compatibility testing, e.g., blood collection, washing 
or freezing of red blood cells, and irradiating of blood components. 
Therefore, small, hospital-based transfusion services that also draw 
blood donors would be subject to this rule and inspection by FDA. 
Certain establishments that do not participate in Medicare, such as 
Indian Health Services and Veteran's Administration hospitals, are also 
subject to FDA regulations.
    HCFA's regulations apply to hospital transfusion services where 
activities do not include more than the performance of compatibility 
testing and that participate in Medicare. Section III. of this document 
describes the division of responsibilities between FDA and HCFA for 
inspections of blood establishments. HCFA's final rule is published 
elsewhere in this issue of the Federal Register. This division of 
responsibilities between FDA and HCFA, consistent with the MOU, 
eliminates duplication of effort and reduces the burden on blood 
establishments and hospitals.

H. Comments on Sec. 610.47(b)

1. Clarification of Responsibility for Transfusion Recipient 
Notification
    Two comments asked for clarification as to which entity is 
responsible for notification of the transfusion recipient or his or her 
physician in situations where the transfusion services are provided to 
hospitals by community blood centers. One comment suggested more 
consistent requirements between FDA and HCFA because it appeared that 
the HCFA proposal makes the hospital responsible for the notification 
of the recipient's physician rather than the transfusion service, as is 
the case in the FDA proposed rule.
    It is not the intention of FDA to designate the individual or the 
department that will contact the recipient but rather to designate that 
the transfusion service that issues the Whole blood or blood component 
for transfusion will be ultimately responsible for ensuring that the 
notification takes place. In a similar manner, HCFA holds the hospital 
responsible for ensuring the notification is completed.
2. Process and Documentation for Transfusion Recipient Notification
    Twenty-five comments expressed concern over the process and 
timeframe for notification of the transfusion recipient. There were 
some questions as to where the ultimate responsibility falls for 
transfusion recipient notification and as to the documentation that is 
required. Three comments asked that attending physicians be required to 
comply with these regulations and asked for guidance in situations 
where the recipient's physician declines to notify the recipient due to 
conditions such as terminal illness, celibacy, or when the harmful 
effects may exceed the benefits of notification. Additionally, two 
comments expressed concern over respect for the doctor-patient 
relationship and the authority to interfere with that relationship.
    As stated previously, FDA intends that each establishment have the 
flexibility to develop SOP's that describe the steps in this process 
and all appropriate documentation. The SOP should address documentation 
of person(s) contacted, by whom, when and whether the physician agreed 
to notify the recipient, and any additional, pertinent information. 
Some institutions may choose to designate a specific department or 
person within the hospital to conduct the notification and counseling 
for the recipient.
    The SOP should be consistent with applicable local and State laws 
and shall specify both a well designed system for accomplishing 
notification and the required documentation of the outcome of these 
efforts.
    FDA believes that because the attending physician has developed as 
relationship with the patient and is most familiar with that patient's 
history, the patient's interests are best served when the attending 
physician takes the responsibility for contact and counseling. In those 
instances when this does not prove to be appropriate or possible, the 
transfusion service is ultimately responsible for ensuring that the 
notification takes place. If the patient is competent, but the 
physician believes the information should not be given to the patient 
and State law permits a legal representative or relative to receive 
information on the patient's behalf, then the transfusion service or 
physician should notify the patient's legal representative or relative. 
Further, FDA believes that transfusion services should, upon learning 
of the death of the transfusion recipient, continue the notification 
process to inform the patient's family. Public health concerns would 
warrant the notification process continue and include the deceased 
patient's legal representative or relative. It would not be appropriate 
for a physician or transfusion service to determine that the patient or 
someone acting on his or her behalf need not be informed. The final 
rule has been amended to clarify the notification requirements in 
Secs. 610.46(c) and 610.47(b).
    FDA has no regulatory authority over physicians in their role as 
attending physicians, and for that reason, the agency is not able to 
require their participation. Upon accepting responsibility for 
recipient notification and counseling, it is reasonable to expect that 
the physician would, in good faith, determine the appropriate

[[Page 47420]]

content and completeness of information provided to the recipient.
    FDA is relying on HCFA's expertise in the area of hospital practice 
in setting time limits for transfusion recipient notification. 
Consistent with HCFA's final rule, published elsewhere in this issue of 
the Federal Register, FDA believes that the hospital's notification 
effort should consist of, at the minimum, three attempts by telephone 
or in writing to reach the recipient, the recipient's legal 
representative or relative. The final rule has been amended to clarify 
that the transfusion service's notification effort should begin 
immediately after receiving results of further testing for HIV and 
should be completed 8 weeks later. The rule has also been amended to 
clarify that the transfusion service should notify the patient, the 
patient's legal representative or relative, as appropriate.

VI. Analysis of Impacts

    FDA has examined the impacts of the final rule under Executive 
Order 12866 and the Regulatory Flexibility Act (Pub. L. 96-354). 
Executive Order 12866 directs agencies to assess all costs and benefits 
of available regulatory alternatives and, when regulation in necessary, 
to select regulatory approaches that maximize net benefits (including 
potential economic, environmental, public health and safety, and other 
advantages; distributive impacts; and equity). The agency believes that 
this final rule is consistent with the regulatory philosophy and 
principles identified in the Executive Order, and has determined that 
this is not a significant regulatory action.
    The purpose of the ``lockback'' requirement is to reduce the risk 
of transfusion transmitted HIV infection through the quarantine of 
blood and blood components that might have been collected during the 
``window'' period, when the antibody to HIV is not yet detectable by a 
screening test. Notification of consignees to quarantine the affected 
products, until a more specific test for antibody to HIV is completed, 
will prevent any further transmission of the virus. Upon completion of 
more specific testing, all recipients of prior collections from a donor 
that subsequently tests positive for antibody to HIV will be notified 
by their attending physician, when possible, or by the transfusion 
service. Such transfusion recipients shall receive notification for the 
purpose of testing for evidence of HIV infection, early treatment, if 
indicated, and counseling to take appropriate precautions to prevent 
the further spread of the virus such as to sexual partners.
    Most blood establishments already participate in a ``lookback'' 
program. Ninety-five percent of blood establishments, collecting 98 
percent of the nation's blood supply, already participate in a 
``lookback'' notification of their customers to quarantine previously 
shipped blood later determined to be at increased risk for transmitting 
HIV. Thus, requirements for written procedures, records of consignee 
notification, and records that relate the prior collections to the 
donor, later found to be repeatedly reactive for antibody to HIV, would 
affect at most about 5 percent of blood establishments; the remaining 
establishments may need to make minor changes to their existing 
procedures. Therefore, FDA believes this final rule should have a 
minimal impact. FDA expects the total annualized cost of the final rule 
to blood establishments to be $3,248,354. FDA anticipates only a small 
number of cases per year that will involve transfusion recipient 
notification. In conclusion, FDA has determined that the final rule is 
not a significant regulatory action as defined in Executive Order 
12866.
    At the time of the proposed rule, the agency certified that the 
proposed requirements would not have a significant impact on a 
substantial number of small entities. However, in response to industry 
comments and in light of amended requirements for analyzing impact on 
small entities (as enacted by Pub. L. 104-121), it was determined that 
a final regulatory flexibility analysis would be useful. Accordingly, 
the agency has assessed this final rule in accordance with the 
Regulatory Flexibility Act, with the following results:
    Need for, and objective of, the rule. As described elsewhere in 
this preamble, FDA is taking this action to help ensure the continued 
safety of the blood supply, and to help ensure that information is 
provided to consignees of Whole Blood, blood components, Source Plasma 
and Source Leukocytes and to recipients of Whole Blood and blood 
components from a donor whose subsequent donation test positive for 
antibody to HIV.
    Types and number of small entities affected. This rule will affect 
all of the 3,015 registered U.S. blood establishments. Of these 
registered establishments, approximately 400 are part of the American 
Red Cross, which supplies approximately 45 percent of blood products 
nationally. An additional 286 are Federal or State facilities. Many, or 
most, of the remaining 2,204 establishments may be small entities as 
defined by the Regulatory Flexibility Act.
    The affect of this rule is greatest for those blood establishments 
that have not already voluntarily implemented ``lookback'' procedures 
similar to those required here. As stated in the proposed rule (58 FR 
34962), FDA estimated that at least 95 percent of establishments, 
supplying 98 percent of the nation's blood, have such voluntary 
procedures and would need to make only minor changes to ensure that 
they are in compliance with this rule. The remaining up to 150 
establishments would require more substantial changes in their 
procedures. FDA considers 150 to be an upper bound, since it is likely 
that liability concerns and advances in automated data technology have 
prompted most establishments that did not previously have ``lookback'' 
procedures to have them in place by now.
    Projected reporting, recordkeeping, and other compliance 
requirements. To comply with this rule, all blood establishments 
subject to this rule, including small entities, must: (1) Review and, 
if necessary, modify their SOP's; (2) maintain the necessary records to 
carry out these procedures; and (3) notify consignees within 72 hours 
of repeatedly reactive test results. Blood establishments that provide 
transfusion services and that are not subject to HCFA regulations must 
also notify physicians of prior donation recipients, or the recipients 
themselves, of the need for HIV testing and counseling. The estimated 
time needed for establishments to comply with the reporting, 
disclosure, and recordkeeping requirements of this rule are described 
in detail in the reporting and recordkeeping tables in section VII. of 
this document.
    FDA estimates that two types of skills will be necessary to meet 
these reporting and recordkeeping requirements. The skills of a medical 
technologist, or a person with equivalent training and experience, will 
be necessary to record donor, quarantine, testing, and disposition 
information, and to notify consignees of test results. Updating SOP's 
and notifying physicians and recipients of test results will require a 
person knowledgeable and experienced in medical laboratory practice.
    Based on the reporting, disclosure, and recordkeeping burden 
described in section VII. of this document, FDA estimates that 
establishments that currently have ``lookback'' procedures will require 
approximately 27 hours per year to bring their procedures into 
compliance with this rule, while establishments without such procedures 
will require approximately 40 hours

[[Page 47421]]

annually to complete the required tasks. Establishments whose 
transfusion services are also covered by this rule will require an 
additional 8 hours per year to comply. Based on an estimated average 
hourly cost of $37.98 to perform the required tasks, FDA predicts that 
the average annual cost of these requirements for establishments that 
currently lack ``lookback'' procedures is $1,520 per facility for most 
establishments and $1,820 for facilities that transfuse as well as 
collect blood. Average annual costs for the great majority of 
establishments that already have ``lookback'' procedures are expected 
to be approximately $1,030 for most establishments and $1,340 for 
covered establishments that also provide transfusions.
    In addition to these reporting and recordkeeping costs, all 
facilities will bear the additional cost of disposing of any affected 
units; conducting licensed, more specific tests for HIV; and replacing 
discarded units.
    With the exception of the initial development of SOP's, all costs 
related to implementing the requirements of this rule are related to 
the number of units of blood collected from repeat donors who test 
positive for HIV, which in turn is related to total blood collections. 
The average number of units of blood drawn per establishment covered by 
this rule is approximately 8,000 units per year. Smaller establishments 
will have lower costs of compliance than the averages described above, 
while larger blood facilities will have higher costs, in proportion to 
the number of units of blood drawn per year.
    Steps to minimize the economic impact on small entities. The 
significant issues raised by public comments on the costs of putting in 
place the required procedures, and the burdens imposed by the 
timeframes in the proposed rule, are described elsewhere in this 
preamble, FDA agrees with the numerous comments suggesting that 2 weeks 
is too short a time period to allow for completion of the licensed, 
more specific test and subsequent notification of consignees, and that 
4 weeks is a more reasonable period. Accordingly, FDA has amended the 
rule to allow 30 calendar days for the completion of these tasks. This 
change should reduce the impact of the rule on small entities and 
reduce the chance that blood transfusion recipients will fail to 
receive notification that they had received blood or blood components 
that are at increased risk of transmitting HIV infection and or fail to 
receive appropriate counseling. In response to another comment, FDA 
amended the proposed rule to specify that certain pooled blood products 
intended for further manufacture into noninjectable products are exempt 
from quarantine. This change should also reduce the burden of the rule 
on some small entities. FDA rejected the option of excluding all small 
entities from the rule, because to do so would exempt a substantial 
proportion of establishments and defeat the objective of ensuring that 
all establishments have appropriate procedures in place to ensure the 
continued safety of the blood supply.
    FDA's selection of the regulatory option described in this rule is 
based on its legal authority under sections 351 and 361 of the Public 
Health Service Act and section 501 of the Federal Food, Drug, and 
Cosmetic Act (21 U.S.C. 351). The need for regulatory action results 
from the fact that a small but significant number of new HIV infections 
each year continue to be transmitted through blood transfusions; the 
fact that a small minority of blood establishments still lack 
appropriate procedures for identification of blood products at 
increased risk for transmitting HIV infection and notification of 
recipients of such products; and the need to ensure that those 
establishments with voluntary ``lookback'' procedures in place have 
procedures that are adequate and vigorously followed. The primary 
policy consideration in the formulation of this rule is to protect the 
public health.

VII. Paperwork Reduction Act of 1995

    This final rule contains information collections which are subject 
to review by the Office of Management and Budget (OMB) under the 
Paperwork Reduction Act of 1995. The title, description, and respondent 
description of the information collection are shown below with an 
estimate of the annual reporting and recordkeeping burden. Included in 
the estimate is the time for reviewing procedures, searching existing 
data sources, gathering and maintaining the data needed, and completing 
and reviewing the collection of information.
    Title: Current Good Manufacturing Practices for Blood and Blood 
Components; Notification of Consignees Receiving Blood and Blood 
Components at Increased Risk for Transmitting HIV Infection.
    Description: The final rule requires that blood establishments 
prepare and follow written procedures when the blood establishments 
have collected Whole Blood, blood components, Source Plasma and Source 
Leukocytes later determined to be at risk for transmitting HIV 
infections. This final rule requires that when a donor who previously 
donated blood is tested in accordance with Sec. 610.45 on a later 
donation, and tests repeatedly reactive for antibody to HIV, the blood 
establishment shall perform more specific testing using a licensed 
test, and notify consignees who received Whole Blood, blood components, 
Source Plasma or Source Leukocytes from prior collections so that 
appropriate action is taken. Blood establishments and consignees are 
required to quarantine previously collected Whole Blood, blood 
components, Source Plasma and Source Leukocytes from such donors, and 
if appropriate, notify transfusion recipients. The agency is issuing 
this final rule to help ensure the continued safety of the blood 
supply, to help ensure that information is provided to users of blood 
and blood components, and to help ensure that transfusion recipients of 
blood and blood components at risk for transmitting HIV will be 
notified as appropriate.
    Description of Respondents: Blood establishments (Business and Not-
for-Profit).
    Individuals and organizations had an opportunity to comment on the 
information collection requirements in the proposed rule. FDA has 
revised these estimates based on current data. These estimates are an 
approximation of the average time expected to be necessary for the 
collection of information. They are based on such information as is 
available to FDA. There are no capital costs, or operating and 
maintenance costs associated with this information collection.
    As required by the Paperwork Reduction Act of 1995, FDA will submit 
a copy of this rule to OMB for review and approval of these information 
requirements. Individuals and organizations may submit comments on the 
information collection requirements by November 8, 1996. FDA 
particularly invites comments on: (1) Whether the proposed collection 
of information is necessary for the proper performance of FDA's 
functions, including whether the information will have practical 
utility; (2) the accuracy of FDA's estimate of the burden of the 
collection of information, including the validity of the methodology 
and assumption used; (3) ways to enhance the quality, utility, and 
clarity of the information to be collected; and (4) ways to minimize 
the burden of the collection of information on respondents, including 
through the use of automated collection techniques, when appropriate, 
and other forms of information technology. Comments

[[Page 47422]]

should be directed to the Dockets Management Branch (address above).
    At the close of the 60-day comment period, FDA will review the 
comments received, make revisions as necessary to the information 
collection requirements, and submit the requirements to OMB for review 
and approval. Additional time will be allotted for public comment to 
OMB on the requirements and OMB review. Prior to the effective date of 
this final rule, FDA will publish a notice in the Federal Register of 
OMB's decision to approve, modify, or disapprove the information 
collection requirements. 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 control number.

                                  Estimated Annual Reporting/Disclosure Burden                                  
----------------------------------------------------------------------------------------------------------------
                                                                Annual                                          
                                                 Number of    frequency      Total       Hours per              
                21 CFR section                  respondents      per         annual      response    Total hours
                                                               response    responses                            
----------------------------------------------------------------------------------------------------------------
610.46(a).....................................        3,015           60      180,900           .17       30,753
610.46(b).....................................        3,015           60      180,900           .17       30,753
610.47(b).....................................          200           16        3,200           .5         1,600
                                               -----------------------------------------------------------------
      Total...................................  ...........  ...........  ...........  ............       63,106
----------------------------------------------------------------------------------------------------------------


                                      Estimated Annual Recordkeeping Burden                                     
----------------------------------------------------------------------------------------------------------------
                                                               Annual        Total                              
              21 CFR section                  Number of     frequency of     annual      Hours per   Total hours
                                            recordkeepers  recordkeeping    records    recordkeeper             
----------------------------------------------------------------------------------------------------------------
606.100(b)(19)............................         3,015              1         3,015           2          6,300
606.160(b)(1)(vii)........................           150            160        24,000          12.8        1,920
606.160(b)(1)(viii).......................         3,015             60       180,900           4.8       14,472
                                           ---------------------------------------------------------------------
      Total...............................  .............  .............  ...........  ............       22,422
----------------------------------------------------------------------------------------------------------------

VIII. Environmental Impact

    The agency has determined under 21 CFR 25.24(c)(10) 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.

List of Subjects

21 CFR Part 606

    Blood, Labeling, Laboratories, Reporting and recordkeeping 
requirements.

21 CFR Part 610

    Biologics, Labeling, 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, 21 CFR parts 606 and 610 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: Secs. 201, 301, 501, 502, 505, 510, 520, 701, 704 of 
the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 321, 331, 351, 
352, 355, 360 360j, 371, 374); secs. 215, 351, 353, 361 of the 
Public Health Service Act (42 U.S.C. 216, 262, 263a, 264).

    2. Section 606.100 is amended by adding new paragraph (b)(19) to 
read as follows:


Sec. 606.100   Standard operating procedures.

* * * * *
    (b) * * *
    (19) Procedures in accordance with Sec. 610.46 of this chapter to 
look at prior donations of Whole Blood, blood components, Source Plasma 
and Source Leukocytes from a donor who has donated blood and 
subsequently tests repeatedly reactive for antibody to human 
immunodeficiency virus (HIV) or otherwise is determined to be 
unsuitable when tested in accordance with Sec. 610.45 of this chapter. 
Procedures to quarantine in-house Whole Blood, blood components, Source 
Plasma and Source Leukocytes intended for further manufacture into 
injectable products that were obtained from such donors; procedures to 
notify consignees regarding the need to quarantine such products; 
procedures to determine the suitability for release of such products 
from quarantine; procedures to notify consignees of Whole Blood, blood 
components, Source Plasma and Source Leukocytes from such donors of the 
results of the antibody testing of such donors; and procedures in 
accordance with Sec. 610.47 of this chapter to notify attending 
physicians so that transfusion recipients are informed that they may 
have received Whole Blood and, blood components at increased risk for 
transmitting human immunodeficiency virus.
* * * * *
    3. Section 606.160 is amended by adding paragraphs (b)(1)(vii) and 
(b)(1)(viii) to read as follows:


Sec. 606.160  Records.

* * * * *
    (b) * * *
    (1) * * *
    (vii) Records to relate the donor with the unit number of each 
previous donation from that donor.
    (viii) Records of quarantine, notification, testing, and 
disposition performed pursuant to Secs. 610.46 and 610.47 of this 
chapter.
* * * * *

PART 610--GENERAL BIOLOGICAL PRODUCTS STANDARDS

    4. The authority citation for 21 CFR part 610 continues to read as 
follows:

    Authority: Secs. 201, 501, 502, 503, 505, 510, 701 of the 
Federal Food, Drug, and Cosmetic Act (21 U.S.C. 321, 351, 352, 353, 
355, 360, 371); secs. 215, 351, 352, 353, 361 of the Public Health 
Service Act (42 U.S.C. 216, 262, 263, 263a, 264).


[[Page 47423]]


    5. Section 610.45 is amended by adding a new paragraph (d) to read 
as follows:


Sec. 610.45   Human immunodeficiency virus (HIV) requirements.

* * * * *
    (d) For a donor whose test results for antibody to HIV are 
repeatedly reactive or otherwise determined to be unsuitable when 
tested in accordance with paragraph (a) of this section, the blood 
establishment shall comply, as applicable, with Secs.  610.46 and 
610.47.
    6. New Secs. 610.46 and 610.47 are added to subpart E to read as 
follows:


Sec. 610.46  ``Lookback'' requirements.

    (a) Quarantine and notification. (1) All blood and plasma 
establishments are required to take appropriate action when a donor of 
Whole Blood, blood components, Source Plasma and Source Leukocytes 
tests repeatedly reactive for antibody to human immunodeficiency virus 
(HIV), or otherwise is determined to be unsuitable when tested in 
accordance with Sec. 610.45. For Whole Blood, blood components, Source 
Plasma and Source Leukocytes collected from that donor within the 5 
years prior to the repeatedly reactive test, if intended for 
transfusion, or collected within the 6 months prior to the repeatedly 
reactive test, if intended for further manufacture into injectable 
products, except those products exempt from quarantine in accordance 
with Sec. 610.46(c), the blood establishment shall promptly, within 72 
hours:
    (i) Quarantine all such Whole Blood, blood components, Source 
Plasma and Source Leukocytes from previous collections held at that 
establishment; and
    (ii) Notify consignees of the repeatedly reactive HIV screening 
test results so that all Whole Blood, blood components, Source Plasma 
and Source Leukocytes from previous collections they hold are 
quarantined.
    (2) Consignees notified in accordance with paragraph (a)(1)(ii) of 
this section shall quarantine Whole Blood, blood components, Source 
Plasma and Source Leukocytes held at that establishment except as 
provided in paragraph (c) of this section.
    (b) Further testing and notification of consignees of results. 
Blood establishments that have collected Whole Blood, blood components, 
Source Plasma or Source Leukocytes from a donor as described in 
paragraph (a) of this section shall perform a licensed, more specific 
test for HIV on the donor's blood, and in the case of distributed 
products, further shall notify the consignee(s) of the results of this 
test, within 30 calendar days after the donor's repeatedly reactive 
test. Pending the availability of a licensed, more specific test for 
HIV-2, a second, different screening test for antibody to HIV-2 shall 
be used along with a licensed, more specific test for HIV-1.
    (c) Exemption from quarantine. Products intended for transfusion 
need not be held in quarantine if a determination has been made that 
the Whole Blood, blood components, Source Plasma or Source Leukocytes 
was collected more than 12 months prior to the donor's most recent 
negative antibody screening test when tested in accordance with 
Sec. 610.45. Pooled Source Plasma and Source Leukocytes are exempt from 
quarantine.
    (d) Release from quarantine. Whole Blood, blood components, Source 
Plasma and Source Leukocytes intended for transfusion or further 
manufacture which have been quarantined under paragraph (a) of this 
section may be released if the donor is subsequently tested for 
antibody to HIV as provided in paragraph (b) of this section and the 
test result is negative, absent other informative test results.
    (e) Actions under this section do not constitute a product recall 
as defined in Sec. 7.3(g) of this chapter.


Sec. 610.47  ``Lookback'' notification requirements for transfusion 
services.

    (a) Transfusion services that are not subject to the Health Care 
Financing Administration's regulations on conditions of Medicare 
participation for hospitals (42 CFR part 482) are required to take 
appropriate action in accordance with paragraphs (b) and (c) of this 
section when a recipient has received Whole Blood or blood components 
from a donor determined to be unsuitable when tested for human 
immunodeficiency virus (HIV) infection in accordance with Sec. 610.45 
and the results of the additional tests as provided for in 
Sec. 610.46(b) are positive.
    (b) Notification of recipients of prior transfusion. If the 
transfusion service has administered Whole Blood or blood components as 
described in paragraph (a) of this section, the transfusion service 
shall notify the recipient's attending physician (physician of record) 
and ask him or her to inform the recipient of the need for HIV testing 
and counseling. If the physician is unavailable or declines to notify 
the recipient, the transfusion service shall notify the recipient and 
inform the recipient of the need for HIV testing and counseling. The 
notification process shall include a minimum of three attempts to 
notify the recipient and be completed within a maximum 8 weeks of 
receipt of the result of the licensed, more specific test for HIV. The 
transfusion service is responsible for notification, including basic 
explanations to the recipient and referral for counseling, and shall 
document the notification or attempts to notify the attending physician 
or the recipient, pursuant to Sec. 606.160 of this chapter.
    (c) Notification to legal representative or relative. If the 
transfusion recipient has been adjudged incompetent by a State court, 
the transfusion service or physician must notify a legal representative 
designated in accordance with State law. If the transfusion recipient 
is competent, but State law permits a legal representative or relative 
to receive the information on the recipient's behalf, the transfusion 
service or physician must notify the recipient or his or her legal 
representative or relative. If the transfusion recipient is deceased, 
the transfusion service or physician must continue the notification 
process and inform the deceased recipient's legal representative or 
relative. Reasons for notifying the recipient's relative or legal 
representative on his or her behalf shall be documented pursuant to 
Sec. 606.160 of this chapter.

    Dated: July 11, 1996.
David A. Kessler,
Commissioner of Food and Drugs.

Donna E. Shalala,
Secretary of Health and Human Services.
[FR Doc. 96-22709 Filed 9-6-96; 8:45 am]
BILLING CODE 4160-01-M