[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
