[Federal Register Volume 64, Number 119 (Tuesday, June 22, 1999)]
[Notices]
[Pages 33309-33313]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 99-15754]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
[Docket No. 99D-1878]
``Draft Guidance for Industry: Current Good Manufacturing
Practice for Blood and Blood Components: (1) Quarantine and Disposition
of Prior Collections from Donors with Repeatedly Reactive Screening
Tests for Hepatitis C Virus (HCV); (2) Supplemental Testing, and the
Notification of Consignees and Transfusion Recipients of Donor Test
Results for Antibody to HCV (Anti-HCV);'' Availability
AGENCY: Food and Drug Administration, HHS.
ACTION: Notice.
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SUMMARY: The Food and Drug Administration (FDA) is announcing the
availability of a draft guidance (dated June 1999) entitled ``Draft
Guidance for Industry: Current Good Manufacturing Practice for Blood
and Blood Components: (1) Quarantine and Disposition of Prior
Collections from Donors with Repeatedly Reactive Screening Tests for
Hepatitis C Virus (HCV); (2) Supplemental Testing, and the Notification
of Consignees and Transfusion Recipients of Donor Test Results for
Antibody to HCV (Anti-HCV).'' The draft guidance is intended to provide
recommendations for donor screening and supplemental testing for
antibody to HCV, and notification of consignees and quarantine of prior
collections from a donor who later tests repeatedly reactive for
antibody to HCV (including single antigen and multiantigen screening
tests), notification of consignees and recipients of blood and blood
components at increased risk for transmitting HCV. The draft guidance,
when final, is intended to supersede the September 1998 guidance
entitled ``Guidance for Industry: Current Good Manufacturing Practice
for Blood and Blood Components: (1) Quarantine and Disposition of Units
from Prior Collections from Donors with Repeatedly Reactive Screening
Test for Antibody to Hepatitis C Virus (Anti-HCV); (2) Supplemental
Testing, and the Notification of Consignees and Blood Recipients of
Donor Test Results for Anti-HCV.''
DATES: Written comments on the draft guidance may be submitted at any
time, however, comments should be submitted by August 23, 1999, to
ensure their adequate consideration in preparation of the final
document. Submit written comments on the
[[Page 33310]]
information collection provisions by August 23, 1999.
ADDRESSES: Submit written requests for single copies of the draft
guidance entitled ``Draft Guidance for Industry: Current Good
Manufacturing Practice for Blood and Blood Components: (1) Quarantine
and Disposition of Prior Collections from Donors with Repeatedly
Reactive Screening Test for Hepatitis C Virus (HCV); (2) Supplemental
Testing, and the Notification of Consignees and Transfusion Recipients
of Donor Test Results for Antibody to HCV (Anti-HCV)'' to the Office of
Communication, Training, and Manufacturers Assistance (HFM-40), Center
for Biologics Evaluation and Research (CBER), Food and Drug
Administration, 1401 Rockville Pike, Rockville, MD 20852-1448. Send one
self-addressed adhesive label to assist the office in processing your
requests. The document may also be obtained by mail by calling the CBER
Voice Information System at 1-800-835-4709 or 301-827-1800, or by fax
by calling the FAX Information System at 1-888-CBER-FAX or 301-827-
3844. See the SUPPLEMENTARY INFORMATION section for electronic access
to the draft guidance. Submit written comments to the Dockets
Management Branch (HFA-305), Food and Drug Administration, 5630 Fishers
Lane, rm. 1061, Rockville, MD 20852. Requests and comments should be
identified with the docket number found in brackets in the heading of
this document.
FOR FURTHER INFORMATION CONTACT:
Sharon A. Carayiannis, Center for Biologics Evaluation and Research
(HFM-17), Food and Drug Administration, 1401 Rockville Pike, Rockville,
MD 20852-1448, 301-827-6210.
For technical/scientific questions, contact Robin M. Biswas, Center
for Biologics Evaluation and Research (HFM-325), Food and Drug
Administration, 1401 Rockville Pike, Rockville, MD 20852-1448, 301-827-
3011, or FAX 301-496-0338.
SUPPLEMENTARY INFORMATION:
I. Background
FDA is announcing the availability of a draft guidance (dated June
1999) entitled ``Draft Guidance for Industry: Current Good
Manufacturing Practice for Blood and Blood Components: (1) Quarantine
and Disposition of Prior Collections from Donors with Repeatedly
Reactive Screening Test for Hepatitis C Virus (HCV); (2) Supplemental
Testing, and the Notification of Consignees and Transfusion Recipients
of Donor Test Results for Antibody to HCV (Anti-HCV).'' The draft
guidance is intended to provide recommendations for appropriate action
when a repeat donor subsequently tests repeatedly reactive for HCV
using either a single antigen or multiantigen screening test, commonly
referred to as HCV ``lookback.'' The draft guidance provides
recommendations for the following: (1) Quarantine (and disposition of
products) of prior collections from donors who later test repeatedly
reactive for anti-HCV using either a single antigen or multiantigen
screening test, (2) supplemental testing and notification of consignees
and transfusion recipients, (3) procedures and recordkeeping, (4)
review of records of donor testing for ``historical'' repeatedly
reactive donations, and (5) additional testing of donors with no record
of supplemental testing on the ``historical'' repeatedly reactive
screening test or with an indeterminate recombinant immunoblot assay
2.0 test result.
On March 20, 1998 (63 FR 13675), FDA announced the availability of
``Guidance for Industry: Supplemental Testing and the Notification of
Consignees of Test Results for Antibody to Hepatitis C Virus (Anti-
HCV),'' (the March 1998 guidance). The March 1998 guidance superseded
the recommendations related to HCV in FDA's July 19, 1996, guidance
entitled: ``Recommendations for Quarantine and Disposition of Units
from Prior Collections from Donors with Repeatedly Reactive Screening
Tests for Hepatitis B Virus (HBV), Hepatitis C Virus (HCV) and Human T-
Lymphotropic Virus Type I (HTLV-I)'' (the July 1996 guidance). The
March 1998 guidance did not, however, supersede the recommendations
related to HTLV and HBV in the July 1996 guidance. (Note: The scope of
the July 1996 guidance was limited to enzyme immunoassay (EIA) 2.0 and
3.0 screening performed since 1992.)
On June 18, 1998, at a public meeting of its Blood Products
Advisory Committee (BPAC), FDA announced plans to respond to public
comments submitted to the docket for the March 1998 guidance by
issuance of a comprehensive guidance. At the BPAC meeting, FDA
announced it was considering changes to the HCV ``lookback'' policy
based on considerations which had been raised by public comments. FDA
continued to receive extensive public comments to the docket which were
evaluated carefully by CBER. Under the agency's good guidance
practices, FDA issued a notice on September 8, 1998, to withdraw the
March 1998 guidance pending issuance of a second comprehensive
guidance.
In September 1998, FDA finalized a guidance entitled ``Guidance for
Industry: Current Good Manufacturing Practice for Blood and Blood
Components: (1) Quarantine and Disposition of Units from Prior
Collections from Donors with Repeatedly Reactive Screening Test for
Antibody to Hepatitis C Virus (Anti-HCV); (2) Supplemental Testing, and
the Notification of Consignees and Blood Recipients of Donor Test
Results for Anti-HCV'' (the September 1998 guidance). The September
1998 guidance superseded the March 1998 guidance. FDA announced the
availability of this document in the Federal Register of October 21,
1998 (63 FR 56198).
On January 28, 1999, the Public Health Service Advisory Committee
on Blood Safety and Availability (The PHS Advisory Committee) met to
consider whether to expand the targeted HCV ``lookback'' program to
include recipients of blood from donors subsequently identified as
repeatedly reactive by the single antigen EIA 1.0 screening test for
HCV infection that was licensed in 1990. Approximately 80 percent of
the EIA 1.0 repeatedly reactive donations occurred before the first
supplemental test became available. The PHS Advisory Committee
concluded that, for EIA 1.0 repeatedly reactive donations without
supplemental testing, it would be reasonable to limit the ``lookback''
based on the signal to cutoff value of the screening test in cases
where supplemental testing had not been done. The PHS Advisory
Committee concluded that it would be optimal to perform HCV
``lookback'' on a subset of the donors testing repeatedly reactive on
EIA 1.0 screening tests to capture the vast majority of the true
positives and minimize the unnecessary false recipient notifications.
This draft guidance represents the agency's current thinking on the
management of prior collections from donors testing repeatedly reactive
at a later date using a single antigen or multiantigen screening test
for antibody to HCV, including product quarantine, further testing of
the donor, and notification of consignees and transfusion recipients.
It does not create or confer any rights for or on any person and does
not operate to bind FDA or the public. An alternative approach may be
used if such approach satisfies the requirement of the applicable
statute, regulations, or both. As with other guidance documents, FDA
does not
[[Page 33311]]
intend this document to be all-inclusive and cautions that not all
information may be applicable to all situations. The document is
intended to provide information and does not set forth requirements.
II. Comments
The draft guidance is being distributed for comment purposes only
and is not intended for implementation at this time. Interested persons
may submit to the Dockets Management Branch (address above) written
comments regarding this draft guidance document. Two copies of any
comments are to be submitted, except individuals may submit one copy.
Comments should be identified with the docket number found in brackets
in the heading of this document. A copy of the document and received
comments are available for public examination in the Dockets Management
Branch between 9 a.m. and 4 p.m., Monday through Friday.
III. The Paperwork Reduction Act of 1995
Under the Paperwork Reduction Act (the PRA) (44 U.S.C. 3501-3520),
Federal agencies must obtain approval from the Office of Management and
Budget (OMB) for each collection of information they conduct or
sponsor. ``Collection of information'' is defined in 44 U.S.C. 3502(3)
and 5 CFR 1320.3(c) and includes agency requests or requirements that
members of the public submit reports, keep records, or provide
information to a third party. Section 3506(c)(2)(A) of the PRA (44
U.S.C. 3506(c)(2)(A)) requires Federal agencies to provide a 60-day
notice in the Federal Register concerning each proposed collection of
information before submitting the collection to OMB for approval. To
comply with this requirement, FDA is publishing notice of the proposed
collection of information set forth in this document.
With respect to the following collection of information, FDA
invites comments on: (1) Whether the proposed collection of information
is necessary for the proper performance of FDA's functions, including
whether the information will have practical utility; (2) the accuracy
of FDA's estimate of the burden of the proposed collection of
information, including the validity of the methodology and assumptions
used; (3) ways to enhance the quality, utility, and clarity of the
information to be collected; and (4) ways to minimize the burden of the
collection of information on respondents, including through the use of
automated collection techniques, when appropriate, and other forms of
information technology.
Guidance for Industry: Current Good Manufacturing Practice for
Blood and Blood Components: (1) Quarantine and Disposition of Units
from Prior Collections from Donors with Repeatedly Reactive
Screening Tests for Hepatitis C Virus (HCV); (2) Supplemental
Testing, and the Notification of Consignees and Transfusion
Recipients of Donor Test Results for Antibody to HCV (Anti-HCV).
This draft guidance recommends that blood establishments prepare
and follow written procedures when blood establishments have collected
Whole Blood, blood components, Source Plasma, and Source Leukocytes
later determined to be at risk for transmitting HCV infections. This
draft guidance provides recommendations, similar to the requirements
now in effect for HIV ``lookback'' (21 CFR 610.46 and 610.47 reported
and approved under OMB Control No. 0910-0336), to clarify the status of
the donor who later tests repeatedly reactive for HCV, to quarantine
prior collections from such donors, and to notify consignees and
transfusion recipients, as appropriate, based on further testing of the
donor. The draft guidance recommends that when a donor who previously
donated blood is tested in accordance with this draft guidance on a
later donation, and tests repeatedly reactive for antibody to HCV, the
blood establishment should perform an additional test using a licensed
test, and notify consignees who received Whole Blood, blood components,
Source Plasma, and Source Leukocytes from prior collections so that
appropriate action is taken. The draft guidance document recommends
that blood establishments and consignees quarantine previously
collected Whole Blood, blood components, Source Plasma and Source
Leukocytes from such donors, and if appropriate, consignees should
notify transfusion recipients. In addition to these ``lookback''
recommendations, which are similar to the ``lookback'' requirements for
HIV, this draft guidance recommends a retrospective review of testing
records dating back indefinitely to the extent that electronic or other
readily retrievable records are available, to indentify collections
from donors who had tested repeatedly reactive in the past, prior to
the existence of guidance recommending ``lookback'' activities.
However, the recommendations provide for the review of records to be
limited to a lesser period of time, that is, 12 months prior to the
last negative licensed multiantigen screening test, whenever there is a
record of such a prior test. The draft guidance recommends that blood
establishments notify consignees of the risk of HCV transmission that
exists for prior collections based on the retrospective review of
records and the results of the additional testing performed before or
as a result of the retrospective review of records. In addition, the
draft guidance recommends that blood establishments notify consignees
of the risk of HCV transmission that exists for prior collections from
a donor who tested repeatedly reactive on a screening test for HCV and
for whom the blood establishment has no record of further testing and
the repeatedly reactive results cannot be clarified because further
testing is impractical or infeasible. This draft guidance recommends
that blood establishments maintain records of the source and
disposition of all units of blood and blood products for at least 10
years from the date of disposition or 6 months after the latest product
expiration date, whichever is the later date. Under 21 CFR 606.160
(reported and approved under OMB Control No. 0910-0116), such records
are required to be retained for 5 years. FDA is recommending an
extended records retention period because advances in medical diagnosis
and therapy have created opportunities for disease prevention or
treatment many years after recipient exposure to a donor later
determined to be at increased risk for transfusion-transmitted disease.
Additionally, methods of recordkeeping have advanced, improving the
ability of blood establishments to more easily maintain and retrieve
records. Also, this draft guidance recommends that any consignee of a
blood establishment notify the transfusion recipients or their
physicians of blood and blood components at increased risk for
transmitting HCV. The agency is issuing this draft guidance to promote
the continued safety of the blood supply, to help provide users with
critical information about blood and blood components, and to promote
notification to transfusion recipients who have received blood and
blood components at risk for transmitting HCV so that recipients may
receive medical counseling.
Respondents to this information collection are blood establishments
(business and not-for-profit) and consignees of blood establishments,
including hospitals, transfusion services, and physicians. The total
[[Page 33312]]
reporting and recordkeeping burden is estimated to be 723,508 hours.
However, of this total, approximately 715,986 hours would be expended
on a one-time basis for establishing the written procedures and doing
the one-time retrospective review of records. Therefore, 8,242 hours is
estimated as the ongoing annual burden related to this draft guidance.
The total ongoing prospective annual burden for blood establishments is
estimated to be 2,880 hours. The prospective annual burden for
consignees of blood establishments is estimated to be 5,362 hours.
Based on the June 1998 registration records, there are
approximately 2,800 FDA registered blood collection facilities in the
United States that collect approximately 27 million units of whole
blood and source plasma annually of which, based on the Centers for
Disease Control and Prevention (CDC) estimates, there are approximately
9,750,000 donations from repeat donors per year. Based on the
prevalence of HCV among donors from 1996 to 1998, CDC estimates that
7,200 of those repeat donors per year would test repeatedly reactive
for HCV. For each of these donors, the recommendations in this draft
guidance call for blood establishments to notify the consignee
(transfusion service) two times, once for quarantine purposes and again
with additional test results for a total of 14,400 notifications as an
annual ongoing burden. Based on estimates from CDC, FDA expects that
for the one-time review of records, as many as 1,117,000 blood products
would be at increased risk for transmitting HCV. For each of these
products, blood establishments would notify consignees to quarantine
these products, report additional test results to consignees, and
consignees would notify recipients or recipients' attending physicians.
In March 1999, CDC estimated that there could be approximately 566,000
recipients that should be notified after a retrospective review of
donor records between May 1990 and June 1998. FDA estimates that a
total of 2,234,000 notifications, 1,117,000 affected blood products
times 2 notifications, would result from the retrospective review. The
total annual responses for blood establishments is estimated to be the
combined number of notifications, prospective and retrospective, or
2,248,400. FDA estimates the amount of time for each notification of a
consignee by a blood establishment will be approximately 6 minutes (0.1
hours). Consequently, the total estimated reporting burden hours for
blood establishments is 224,840 hours. However, the ongoing annual
burden not associated with the retrospective review would be 1,440
hours, 14,400 prospective notifications times 0.1 hour per
notification.
CDC expects that approximately 2,232 repeat donors who have
repeatedly reactive HCV screening test results will confirm positive
for HCV each year. Based on CDC's research and information, a donor who
confirms positive for HCV will have donated on the average only two
previous times and on the average two components will have been made
from each donation. Based on this information, there could be 8,936
transfusion recipients that should be notified per year. The total
notifications by consignees is estimated to be 574,936 annually,
566,000 recipients notified due to the retrospective review plus 8,936
recipients due to the prospective review. The time estimated for
consignees to make a notification is 30 minutes or 0.5 hours on
average. This time allows for the possibility of a consignee having to
make up to 3 attempts to complete the notification process and creates
a total reporting burden of 287,468 hours. According to the Health Care
Financing Administration, there are approximately 6,200 consignees that
should be responsible for notification.
In Table 2 of this document, the 40 hours per blood establishment
recordkeeper represents the time to develop written procedures for the
HCV ``lookback'' recommendations and to update an estimated 4 HCV
repeat reactive records as an ongoing annual burden. FDA estimates that
it takes approximately 5 minutes to update each record. Therefore, the
total recordkeeping by blood establishments is estimated to be 112,000
hours 2,800 registered blood establishments times 40 hours per
establishment. FDA estimates that each consignee recordkeeper would
need 16 hours to develop written procedures for the HCV ``lookback''
notification process and to update approximately 1 to 2 transfusion
recipient records. FDA estimates that it takes approximately 5 minutes
to update each record. Therefore, the total recordkeeping burden for
consignees is estimated to be 99,200 hours. The combined total
recordkeeping burden for both blood establishments and consignees is
estimated to be 211,200 hours. However, based on the prospective number
of repeat donors per year and the number that confirm positive for HCV,
the ongoing annual recordkeeping burden may only be 2,334 hours. Over
time, we expect the ongoing annual recordkeeping burden to decline as
the prevalence of HCV among donors has declined due to the
implementation of screening tests for anti-HCV, which helps to reduce
the number of persons infected with HCV from the donor pool.
FDA estimates the burden for this collection of information as
follows:
Table 1.--Estimated Annual Reporting Burden1
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Collection Annual Frequency Total Annual
Activity No. of Respondents per Response Responses Hours per Response Total Hours
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Blood 2,800 803 2,248,400 0.1 224,840
Establishme
nts
Consignees 6,200 93 574,936 0.5 287,468
Total 512,308
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\1\ There are no capital costs or operating and maintenance costs associated with this collection of
information.
[[Page 33313]]
Table 2.--Estimated Annual Recordkeeping Burden1
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Collection No. of Annual Frequency Total Annual Hours per
Activity Recordkeepers per Recordkeeper Records Recordkeeper Total Hours
----------------------------------------------------------------------------------------------------------------
Blood 2,800 5 10,000 40 112,000
Establishme
nts
Consignees 6,200 2.5 15,136 16 99,200
Total 211,200
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\1\ There are no capital costs or operating and maintenance costs associated with this collection of
information.
Maintenance costs were not estimated for the additional maintenance
of records beyond the current 5 years to the recommended 10 years
because modern storage technology has markedly reduced the space needed
to store records.
In compliance with section 3507(d) of the PRA (44 U.S.C. 3507(d)),
the agency has submitted the information collection provisions of this
draft guidance to OMB for review. Interested persons may submit
comments regarding this information collection by August 23, 1999, to
the Office of Information and Regulatory Affairs, OMB, New Executive
Office Bldg., 725 17th St. NW., rm. 10235, Washington, DC 20503, Attn:
Wendy Taylor, Desk Officer for FDA.
IV. Electronic Access
Persons with access to the Internet may obtain the document using
the World Wide Web (WWW). For WWW access, connect to CBER at ``http://
www.fda.gov/cber/guidelines.htm''.
Dated: June 16, 1999.
Margaret M. Dotzel,
Acting Associate Commissioner for Policy Coordination.
[FR Doc. 99-15754 Filed 6-21-99; 8:45 am]
BILLING CODE 4160-01-F
