[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``Draft Guidance for Industry: Current Good Manufacturing 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availability of a draft guidance (dated June 1999) entitled ``Draft 
Guidance for Industry: Current Good Manufacturing Practice for Blood 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 The draft guidance is intended to provide 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 The draft guidance, 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DATES: Written comments on the draft guidance may be submitted at any 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

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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
----------------------------------------------------------------------------------------------------------------
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.





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                                Table 2.--Estimated Annual Recordkeeping Burden1
----------------------------------------------------------------------------------------------------------------
 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