[Federal Register Volume 65, Number 222 (Thursday, November 16, 2000)]
[Proposed Rules]
[Pages 69378-69416]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 00-28907]



[[Page 69377]]

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Part II

Department of Health and Human Services
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Food and Drug Administration



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21 CFR Parts 606 and 610



Current Good Manufacturing Practice for Blood and Blood Components; 
Notification of Consignees and Transfusion Recipients Receiving Blood 
and Blood Components at Increased Risk of Transmitting HCV Infection 
(``Lookback''); Proposed Rule



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Health Care Financing Administration



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42 CFR Part 482



Medicare and Medicaid Programs; Hospital Conditions of Participation: 
Laboratory Services; Proposed Rule

  Federal Register / Vol. 65, No. 222 / Thursday, November 16, 2000 / 
Proposed Rules  

[[Page 69378]]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Parts 606 and 610

[Docket No. 99N-2337]
RIN 0910-AB76


Current Good Manufacturing Practice for Blood and Blood 
Components; Notification of Consignees and Transfusion Recipients 
Receiving Blood and Blood Components at Increased Risk of Transmitting 
HCV Infection (``Lookback'')

AGENCY: Food and Drug Administration, HHS.

ACTION: Proposed rule.

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SUMMARY: The Food and Drug Administration (FDA) is proposing to amend 
the biologics regulations to require that blood establishments 
(including plasma establishments) prepare and follow written procedures 
for appropriate action when it is determined that blood and blood 
components at increased risk of transmitting hepatitis C virus (HCV) 
infection have been collected from a donor who tested repeatedly 
reactive for evidence of HCV infection at a later date. This proposed 
rule would require blood establishments to quarantine prior collections 
from such a donor, perform further testing on the donor, and notify 
transfusion recipients, as appropriate, when such a donor is identified 
at the time of a repeat donation or after performing a review of 
historical testing records to identify donations at increased risk of 
transmitting HCV. In addition, FDA is proposing to extend the record 
retention period to 10 years to create opportunities for disease 
prevention many years after recipient exposure to such a donor. This 
action is taken as part of FDA's ``Blood Initiative'' to 
comprehensively review and, as necessary, revise its regulations, 
policies, guidances, and procedures related to the licensing and 
regulation of blood products. This proposed rule is intended to help 
ensure the continued safety of the blood supply and to help ensure that 
information is provided to consignees and to prior recipients of blood 
and blood components from a donor whose subsequent donation tests 
positive for antibody to HCV or otherwise is determined to have been at 
increased risk of transmitting HCV.

DATES: Submit written comments on the proposed rule by February 14, 
2001. Submit written comments on the information collection provisions 
by December 18, 2000. See section VII of this document for the proposed 
effective date of a final rule based on this document.

ADDRESSES: Submit written comments to the Dockets Management Branch 
(HFA-305), Food and Drug Administration, 5630 Fishers Lane, rm. 1061, 
Rockville, MD 20852. Submit written comments on the information 
collection provisions to the Office of Information and Regulatory 
Affairs, OMB, New Executive Office Bldg., 725 17th St. NW., Washington, 
DC 20503, Attn: Wendy Taylor, Desk Officer for FDA.

FOR FURTHER INFORMATION CONTACT: Sharon A. Carayiannis, Center for 
Biologics Evaluation and Research (HFM-17), Food and Drug 
Administration, 1401 Rockville Pike, suite 200N, Rockville, MD 20852-
1448, 301-827-6210.

SUPPLEMENTARY INFORMATION:

I. Background

A. Blood Initiative

    For a variety of reasons FDA has decided to comprehensively review 
and, as necessary, revise its regulations, policies, guidance, and 
procedures related to the licensing and regulation of blood products. 
In the Federal Register of June 3, 1994 (59 FR 28821 and 59 FR 28822, 
respectively), FDA issued two documents entitled ``Review of General 
Biologics and Licensing Regulations'' (Docket No. 94N-0066) and 
``Review of Regulations for Blood Establishments and Blood Products'' 
(Docket No. 94N-0080). These two documents announced the agency's 
intent to review biologics regulations in 21 CFR parts 600, 601, 606, 
607, 610, 640, and 660 (21 CFR 600, 601, 606, 607, 610, 640, and 660) 
and requested written comments from the public. Interested persons were 
given until August 17, 1994, to respond to the documents. In response 
to requests for additional time, FDA twice extended the comment period, 
as announced in the Federal Register of August 17, 1994 (59 FR 42193), 
and November 14, 1995 (59 FR 56448). In addition, FDA responded to 
requests for a public meeting to allow for the presentation of comments 
regarding the agency's intent to review the biologics regulations. On 
January 26, 1995, FDA held a public meeting to provide an opportunity 
for all interested individuals to present their comments and to assist 
the agency in determining whether the regulations should be revised, 
rescinded, or continued without change. Since the time of the 
regulation review, FDA has implemented a number of changes to its 
regulations and policies applicable to the general biologics and 
licensing regulations, some of which applied to blood products as well 
as other biological products. (See, e.g., the final rules issued on May 
14, 1996 (61 FR 24313); August 1, 1996 (61 FR 40153); November 6, 1996 
(61 FR 57328); July 24, 1997 (62 FR 39890); and October 15, 1997 (62 FR 
53536)).
    Because of the importance of a safe national blood supply, the U.S. 
House of Representatives Committee on Government Reform and Oversight, 
Subcommittee on Human Resources and Intergovernmental Relations (the 
Subcommittee) and other groups such as the General Accounting Office 
(GAO), and the Institute of Medicine (IOM) have reviewed the agency's 
policies, practices, and regulations. Reports issued following the 
respective reviews made a number of recommendations as to how FDA might 
improve the biologics regulations, particularly as they apply to the 
continued safety of blood products. The relevant reports are: (1) 
``Protecting the Nation's Blood Supply From Infectious Agents: The Need 
for New Standards to Meet New Threats,'' by the Subcommittee (August 2, 
1996); (2) ``Blood Supply: FDA Oversight and Remaining Issues of 
Safety,'' by GAO (February 25, 1997); (3) ``Blood Supply: Transfusion-
Associated Risks,'' by GAO (February 25, 1997); and (4) ``HIV and the 
Blood Supply: An Analysis of Crisis Decisionmaking,'' by IOM ( July 13, 
1995). These reports are on file with the Dockets Management Branch 
(address above) under the docket number given in the heading of this 
document.
    FDA has reviewed these reports and agrees with the majority of the 
recommendations contained within them. However, rather than only 
responding specifically to the recommendations from the Subcommittee, 
GAO, IOM, and the public, FDA convened a number of internal task forces 
to review a variety of issues related to the regulation of blood and 
blood products, including how to most appropriately update the existing 
regulations applicable to blood and blood products. In the future, FDA 
intends to issue a number of blood-related rulemakings that various FDA 
task groups are currently preparing. FDA is not describing the specific 
recommendations it has received and the numerous objectives of the 
Blood Initiative in this document. Future rulemaking and other notices 
will describe and discuss specific recommendations and regulatory 
objectives.

[[Page 69379]]

B. Existing Donor Screening and Testing Requirements

    FDA has developed five ``layers of safety'' to help ensure a safe 
blood supply: Donor screening, donor deferral registries, testing 
blood, blood quarantining, and monitoring and investigating problems. 
The five layers of safety are designed to overlap so that they will 
prevent the distribution of blood and blood products that are at 
increased risk of transmitting communicable disease agents such as 
human immunodeficiency virus (HIV) and hepatitis B virus (HBV). With 
regard to screening donors and testing blood, FDA has defined an 
extensive system of donor screening and testing procedures, two of the 
five layers of safety, performed by blood establishments. These 
procedures include the initial screening of individuals that volunteer 
to donate blood using a questionnaire, interview, and physical 
examination. This initial screening process is designed to protect the 
donor and to establish whether the donor is in good health, to rule out 
possible exposure to disease, such as through travel to an area endemic 
for malaria, or through close contact with an infected individual, and 
to identify whether the donor has engaged in behavior that would 
indicate increased risk of a communicable disease. Individuals who 
satisfactorily answer the questionnaire, pass the physical examination, 
and then donate blood are further screened by laboratory testing for 
evidence of infection due to communicable disease agents such as HIV 
and HBV. In the Federal Register of August 19, 1999 (64 FR 45340), FDA 
issued a proposed rule entitled ``Requirements for Testing Human Blood 
Donors for Evidence of Infection Due to Communicable Disease Agents'' 
(hereinafter referred to as the testing proposed rule), to update, 
revise, and redesignate the testing requirements of Sec. 610.45. The 
relevance of the testing proposed rule to this proposed rule is 
discussed in section III of this document.
    As a result of the extensive screening and testing procedures and 
the other layers of safety, the risk of transmitting 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 testable marker is not detectable by a 
screening test, but the infectious agent is present in the donor's 
blood (a ``window'' period). For example, if a donor donates blood on a 
number of occasions and each donation tests negative for antibody to 
HIV, but the donor returns and tests repeatedly reactive for antibody 
to HIV at a later date, prior collections from such a donor would be at 
increased risk of transmitting HIV. In addition, a recipient of a 
transfusion of blood or 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.
    Under such circumstances, FDA requires clarification of the donor's 
status and procedures to ``lookback'' at prior collections, as 
specified in Secs. 610.46 and 610.47 (the HIV ``lookback'' 
regulations). (See the final rule issued in the Federal Register of 
September 9, 1996 (61 FR 47413).) The HIV ``lookback'' regulations 
require facilities involved in the collection, processing, and 
administration of blood to quarantine blood and blood components 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 regulations require blood establishments to inform consignees 
(e.g., hospital transfusion services and manufacturers of plasma 
derivatives) of the collection and distribution of such previously 
donated blood and blood components, to perform further testing on the 
donor, and to notify transfusion recipients, as appropriate.

C. History of HCV Testing

    HCV frequently causes a clinically inapparent, but chronic 
infection of the liver. Approximately 4 million individuals in the 
United States are believed to be chronically infected with HCV. Despite 
progression of disease, HCV infection is usually asymptomatic for about 
20 years, but in many cases causes serious liver injury that is thought 
to be the leading cause of late stage cirrhosis and liver failure in 
the United States and to play a significant role in the development of 
liver cancer. Therapy with licensed interferon produces long-term 
benefit in only about 15 percent of cases, but a newly available 
therapeutic modality, combination therapy using interferon plus 
ribavirin, may improve this outcome.
    The greatest risk for transmission of HCV is through direct 
percutaneous exposure to infectious blood, such as through transfusion 
of infectious blood or blood products, sharing of contaminated 
equipment among injection drug users, or transplantation of organs or 
tissues from infectious donors. Hemodialysis patients and health-care 
workers exposed to needle sticks in the occupational setting are also 
at risk for exposure to infectious blood. Direct percutaneous exposures 
to infectious blood, particularly in the setting of drug abuse, account 
for the majority of HCV infections acquired in the United States (Ref. 
1). The incidence of transfusion transmitted HCV infection has 
decreased markedly since the implementation of donor screening for HCV 
and viral inactivation of clotting factors and intravenous immune 
globulins. However, approximately 7 percent of the 3.9 million 
Americans believed to be chronically infected with HCV were infected as 
a result of transfusion of blood components prior to the availability 
of donor screening tests or due to past use of nonviral-inactivated 
plasma derivative products (Ref. 2).
    HCV was established as a causative agent of transfusion associated 
hepatitis only since its discovery in the late 1980's. In October 1989, 
FDA's Blood Products Advisory Committee (BPAC) first discussed 
``lookback'' for HCV, prior to the availability of donor screening 
tests for HCV. BPAC advised that there was insufficient information 
available concerning HCV infection to propose either product quarantine 
or notification of recipients transfused with products prepared from 
prior collections from donors later determined to be at increased risk 
for transmitting HCV. Blood establishments implemented donor screening 
tests after a single antigen, enzyme linked immunosorbent assay (EIA) 
for antibody to HCV (HCV EIA 1.0 screening test) was licensed in May 
1990. FDA issued a memorandum to all registered blood establishments in 
November 1990, entitled ``Testing for Antibody to Hepatitis C Virus 
Encoded Antigen (Anti-HCV),'' recommending use of approved donor 
screening tests for antibody to HCV. A ``lookback'' program was not 
recommended because: (1) Screening tests available at the time could 
not distinguish between ongoing infection and recovery, and thus, the 
meaning of a reactive test result for any one individual was not clear; 
(2) donor screening for antibody to HCV did not include confirmatory 
testing and most notifications would have been based on false-positive 
donor test results; (3) there was limited knowledge of routes of 
transmission for HCV other than parenteral; and (4) no potential long-
term benefits of therapy were known.
    A significantly more sensitive multiantigen screening test (HCV EIA 
2.0 screening test) was licensed in March 1992. In June 1993, FDA 
licensed an HCV 2.0 strip immunoblot assay (HCV RIBA 2.0), a 
supplemental (additional, more specific) test for antibody to HCV. 
Supplemental tests for

[[Page 69380]]

antibody to HCV are used to distinguish false positive from true 
positive repeatedly reactive screening test results. Except for tests 
available for investigational use, supplemental tests for antibody to 
HCV have only been available since the HCV RIBA 2.0 supplemental test 
was licensed in June 1993.
    In an August 1993 memorandum to all registered blood establishments 
entitled ``Revised Recommendations for Testing Whole Blood, Blood 
Components, Source Plasma and Source Leukocytes for Antibody to 
Hepatitis C Virus Encoded Antigen (Anti-HCV),'' FDA did not recommend a 
``lookback'' program pending the outcome of discussions on the issue at 
the December 1993 BPAC meeting. Following the discussions on HCV at the 
meeting in December 1993, BPAC unanimously recommended product 
quarantine of prior collections from a donor who later tests repeatedly 
reactive for antibody to HCV and tests positive or indeterminate on a 
supplemental test, but only marginally endorsed consignee notification 
for the purpose of transfusion recipient notification, and reiterated 
many of the reservations regarding the lack of an established public 
health benefit in performing this activity. FDA issued a memorandum to 
all registered blood establishments in July 1996 entitled 
``Recommendations for the 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 memorandum 
recommended testing, consignee notification, and quarantine of affected 
products but did not provide recommendations for the notification of 
recipients of such donations because the public health benefit of such 
notification was not clear.
    The Public Health Service Advisory Committee on Blood Safety and 
Availability (the PHS Advisory Committee) discussed improvements in the 
treatment and management of HCV infection and improvements in testing 
for antibody to HCV at public meetings held on April 24 and 25, 1997, 
and August 11 and 12, 1997. The PHS Advisory Committee also discussed 
the public health benefits of notification of transfusion recipients 
receiving prior collections from a donor who subsequently tests 
repeatedly reactive for evidence of HCV infection. Following acceptance 
by the Department of Health and Human Services (DHHS) of 
recommendations for HCV ``lookback'' made in August of 1997 by the PHS 
Advisory Committee, FDA issued a notice in the Federal Register of 
March 20, 1998 (63 FR 13675), announcing the availability of a document 
entitled ``Guidance for Industry: Supplemental Testing and the 
Notification of Consignees of Donor Test Results for Antibody to 
Hepatitis C Virus (Anti-HCV)'' (the March 1998 guidance) in which FDA 
recommended that blood establishments implement HCV ``lookback'' 
procedures. In the March 1998 guidance, FDA recommended that donors 
currently testing repeatedly reactive for antibody to HCV in a licensed 
test be further tested for antibody to HCV using a licensed, 
multiantigen supplemental test. Additionally, FDA recommended that 
consignees of certain blood and blood components collected since 
January 1, 1988, which were anti-HCV negative or untested, be notified 
when donors subsequently test repeatedly reactive for anti-HCV in a 
licensed multiantigen screening test and reactive in a licensed or 
investigational supplemental test. This notification would enable 
recipients to be informed that they had been transfused with units that 
may have contained HCV so that they may obtain further medical 
counseling. The March 1998 guidance provided FDA's recommendations for 
donor screening, a review of past testing records, further testing for 
antibody to HCV, notification of consignees, and transfusion recipient 
notification and counseling by physicians regarding transfusion with 
blood or blood components at increased risk of transmitting HCV. The 
March 1998 guidance was intended to supplement the July 1996 
memorandum.
    In response to comments received, the March 1998 guidance was 
withdrawn on September 8, 1998, and FDA issued a revised guidance on 
October 21, 1998 (63 FR 56198, October 23, 1998) 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 Tests for 
Hepatitis C Virus (HCV); (2) Supplemental Testing, and the Notification 
of Consignees and Blood Recipients of Donor Test Results for Antibody 
to HCV (Anti-HCV),'' (the September 1998 guidance). The September 1998 
guidance replaced the March 1998 guidance, and provided recommendations 
to enable quarantine and disposition of blood and blood components from 
prior collections from donors with repeatedly reactive screening test 
results. The September 1998 guidance was provided on the CBER Home Page 
for comment and implementation on September 23, 1999. Additionally, the 
guidance document was mailed to all blood establishments on November 
20, 1998.
    The September guidance addressed several significant comments and 
requests from industry: (1) FDA revised several time periods for 
``lookback'' actions in response to concerns about impact on industry, 
the need for additional time for testing due to availability problems 
with certain test kits, and to allow time for the physician education 
to be completed (ensuring that counseling messages would be available 
for use in notification of recipients); (2) FDA clarified options for 
further testing with an HCV enzyme linked immunosorbent assay 3.0 (HCV 
EIA 3.0 screening test); (3) FDA made revisions to clarify 
recommendations on labeling of products released from quarantine and 
for consistency with existing regulations on product labeling; (4) FDA 
provided flow chart diagrams to assist industry in implementing 
procedures contained in the guidance; and (5) To permit easier, more 
rapid notification of the recipient, FDA recommended the option of 
transfusion services notifying the transfusion recipient directly as an 
alternative to notifying the transfusion recipient's physician of 
record.
    At public meetings on November 24, 1998, and January 28, 1999, the 
PHS Advisory Committee reconsidered the issue of recipient notification 
related to repeatedly reactive results on the single antigen screening 
test. The PHS Advisory Committee recommended that targeted ``lookback'' 
should be initiated based on a repeatedly reactive HCV EIA 1.0 
screening test result on a repeat donor unless a supplemental test was 
performed and the result did not indicate increased risk of HCV 
infection, or, in the absence of a supplemental test result, the signal 
to cut off (S/CO) value of the repeatedly reactive HCV EIA 1.0 
screening test was less than 2.5, or follow-up testing of the donor was 
negative. FDA published a notice in the Federal Register of June 22, 
1999 (64 FR 33309), announcing the availability of a draft guidance 
entitled, ``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).'' Consistent with the

[[Page 69381]]

recommendations of the PHS Advisory Committee, this revised draft 
guidance addressed ``lookback'' actions related to donor screening by 
HCV EIA 1.0 and also recommended that the search of historical testing 
records of prior donations from donors with repeatedly reactive EIA 
1.0, EIA 2.0, or EIA 3.0 screening tests for HCV should extend back 
indefinitely to the extent that electronic or other readily retrievable 
records exist. In addition, FDA revised the flow chart diagrams to 
reflect the changes to the guidance. FDA added specific recommendations 
for prior collections from a repeatedly reactive autologous donor and 
clarified recommendations on implementing ``lookback'' for repeatedly 
reactive plasma donations.
    Based on comments submitted to the docket, FDA will revise the June 
1999 draft guidance and issue a final guidance document for 
implementation. These comments and comments submitted on any additional 
guidance issued by the agency in the future will be considered in the 
preparation of the final rule for HVC ``lookback.''
    In addition to these recommendations, FDA is proposing in 
Sec. 610.40(c) of the testing proposed rule to require ``Each donation 
found to be repeatedly reactive by a screening test shall be further 
tested whenever a supplemental (additional, more specific) test has 
been approved for such use by FDA.''

II. Legal Authority

    FDA is proposing to issue this new rule under the authority of 
sections 351 and 361 of the Public Health Service Act (the PHS Act) (42 
U.S.C. 262 and 264 et seq.) and the provisions of the Federal Food, 
Drug, and Cosmetic Act (the act) which apply to drugs (21 U.S.C. 201 et 
seq.). Under section 361 of the PHS Act, FDA may make and enforce 
regulations necessary to prevent the introduction, transmission, and 
spread of communicable disease between the States or from foreign 
countries into the States. (See Sec. I, 1966 Reorg. Plan No. 3 at 42 
U.S.C. 202 for delegation of section 361 authority from the Surgeon 
General to the Secretary, Health and Human Services; see 21 CFR 
510(a)(4) for delegation from the Secretary to the Food and Drug 
Administration.) Intrastate transactions may also be regulated under 
section 361. (See Louisiana v. Mathew, 427 F.Supp. 174, 176 (E.D.La. 
1977).) A major purpose of the HCV ``lookback'' proposed rule is to 
prevent the introduction, transmission, and spread of HCV.
    All blood and blood components introduced or delivered for 
introduction into interstate commerce also are subject to section 351 
of the PHS Act (42 U.S.C. 262). Section 351(a) requires that 
manufacturers must have a license which has been issued upon a showing 
that the manufacturing establishment meets all applicable standards, 
prescribed in the biologics regulations, designed to insure the 
continued safety, purity, and potency of the blood and that the product 
is safe, pure, and potent.
    FDA's license revocation regulations provide for the initiation of 
revocation proceedings, among other reasons, if the establishment or 
the product fails to conform to the standards in the license 
application or in the regulations designed to ensure the continued 
safety, purity, or potency of the product (Sec. 601.5). Section 351 of 
the PHS Act also provides for criminal penalties for violation of the 
laws governing biologics. Violations can be punishable by fines or 
imprisonment, or both.
    The act also applies to biological products (42 U.S.C. 262(d), as 
amended). Blood and blood components are considered drugs, as that term 
is defined in section 201(g)(1) of the act (21 U.S.C. 321(g)(1)). (See 
United States v. Calise, 217 F.Supp. 705 (S.D.N.Y. 1962)). Because 
blood and blood components are drugs under the act, blood and plasma 
establishments must comply with the substantive provisions and related 
regulatory scheme of the act. Under section 501 of the act (21 U.S.C. 
351), drugs are deemed ``adulterated'' if the methods used in their 
manufacturing, processing, packing or holding do not conform with 
current good manufacturing practices (CGMP's). Under the proposed HCV 
``lookback'' rule, blood and plasma establishments would be required to 
develop standard operating procedures (SOP's) for HCV ``lookback'' 
quarantine of affected blood and blood components and consignee and 
transfusion recipient notification. A blood or plasma establishment 
that failed to comply with HCV ``lookback'' procedures would violate 
CGMP's and, therefore, would be subject to the act's enforcement 
provisions.

III. Highlights of the Proposed Rule

    FDA and the Health Care Financing Administration (HCFA) are 
proposing steps designed to further protect the blood supply and to 
notify recipients of the possibility that they may have received blood 
or blood components contaminated with HCV. FDA's proposed rule, along 
with HCFA's companion proposed rule published elsewhere in this Federal 
Register, would require facilities involved in the collection, 
processing, and administration of blood to quarantine certain blood and 
blood components and to inform the consignee. The consignee, as 
appropriate, would inform the recipient's attending physician or the 
recipient, of the possibility that blood previously used for 
transfusion was obtained from a donor who subsequently tested 
repeatedly reactive for antibody to HCV. FDA believes that this 
proposed rule, in conjunction with HCFA's companion proposed rule will 
provide a more efficient means of notification.
    As previously discussed in section I.C of this document, chronic 
hepatitis due to HCV is a major health problem in the United States 
because the infection is usually clinically silent, and infected people 
usually are unaware of their disease until serious damage has been 
caused to the liver. Although transfusion transmitted HCV infection 
accounts for only a small proportion of those infected with HCV, it is 
possible to identify and quarantine affected blood and blood 
components, perform further testing, and notify some transfusion 
recipients who have received blood from a donor later determined to be 
at increased risk of transmission of HCV. This process is commonly 
referred to as ``lookback.''
    FDA is issuing this proposed rule for HCV ``lookback'' as a 
consequence of numerous public discussions, and extensive discussion 
within DHHS, of the benefits of notifying recipients of blood at 
increased risk of transmitting HCV. In parallel to this proposed rule, 
there will be a major PHS educational campaign on HCV aimed at both the 
medical community and the public. This proposed rule would establish 
requirements, similar to those now in effect for HIV ``lookback,'' to 
identify and quarantine prior collections later suspected as possible 
window period donations because they were collected from a donor who 
returned to donate and tested repeatedly reactive for evidence of HCV 
infection, and to notify transfusion recipients based on further 
testing of such a donor, as appropriate. In addition to HCV 
``lookback'' requirements based on current testing that are similar to 
those for HIV and that are triggered when a donor returns to donate and 
tests repeatedly reactive on a screening test, this proposed rule would 
require a review of historical testing records to identify prior 
collections from donors at increased risk of transmitting HCV.
    The review of historical testing records would extend back 
indefinitely for computerized electronic records, and to January 1, 
1998, for other readily retrievable records.

[[Page 69382]]

    The requirements for ``lookback'' activity based on multiantigen 
screening test results are handled in separate sections from those 
based on single antigen screening test results because the proposed 
requirements differ. For the purpose of this proposed rule, any 
reference to ``blood or blood components'' will include Source 
Leukocytes and Source Plasma unless specifically addressed. The 
proposal would not require quarantine of products that have already 
been pooled for further processing because the process of fractionation 
inactivates or removes the HCV. For the purpose of this proposed rule, 
any reference to blood establishments will include plasma 
establishments.
    FDA is also proposing conforming amendments to certain provisions 
of Secs. 610.46 and 610.47, the HIV ``lookback'' regulations. The 
proposed revisions to Secs. 610.46 and 610.47 are discussed under the 
corresponding sections of this proposal and are intended to clarify and 
provide consistency between the HIV and HCV ``lookback'' requirements.
    The proposed HCV ``lookback'' regulations are particular to the 
testing methodologies currently used. As testing technology continues 
to develop, the ``window'' period might vary with the testing 
methodology and FDA may determine that it is necessary to amend the 
final rule that results from this proposal. In this section III, FDA 
discusses each of the proposed requirements, the redesignation of 
certain regulations and revisions to existing requirements.

A. Related Rulemaking

    As previously stated, in the Federal Register of August 19, 1999 
(64 FR 45340), FDA issued, as part of the Blood Initiative, a proposed 
rule entitled ``Requirements for Testing Human Blood Donors for 
Evidence of Infection Due to Communicable Disease Agents'' (the testing 
proposed rule). In the testing proposed rule, FDA proposed to revise 
the general biological product standards by adding testing requirements 
for HCV, and by adding requirements for performing a licensed, 
supplemental test when a donation is found to be repeatedly reactive 
for any of the required screening tests for evidence of infection due 
to communicable disease agents. The testing proposed rule would delete 
Sec. 610.45, ``Human Immunodeficiency Virus (HIV) requirements,'' 
because its requirements would be included in the revision of proposed 
Sec. 610.40. The use of the term ``repeatedly reactive'' in this 
rulemaking is consistent with the testing proposed rule, which states 
that ``according to the manufacturer's instructions, initially reactive 
samples are to be tested again, generally in duplicate, and a sample 
that is found to be reactive on any single retest (i.e., on one or more 
of the duplicate retests), is considered to be repeatedly reactive.'' 
Refer to the testing proposed rule for additional discussion of 
repeatedly reactive test results in section D., Further Testing. In 
Sec. 610.40(a) and (c) of the testing proposed rule, FDA would revise 
the requirements for performance of donor screening tests and for 
supplemental testing of a donor who tests repeatedly reactive for 
evidence of infection due to a communicable disease agent, including 
HCV. As discussed in section III.D, this rule proposes that 
Sec. 610.40(g), include the proposed requirements to initiate HCV 
``lookback'' and requirements to initiate HIV ``lookback'' (currently 
in Sec. 610.45(d), which would be deleted as part of the testing 
proposed rule). Initiation of the ``lookback'' processes would be based 
on results of HIV and HCV testing proposed in Sec. 610.40(a) and (c) of 
the testing proposed rule. (Refer to section III.D of this document for 
discussion of the proposed changes to Sec. 610.45(d).)

B. Proposed Revisions to Sec. 606.100(b)(19)

    FDA is proposing to amend Sec. 606.100(b)(19), which currently 
prescribes requirements for SOP's, in accordance with Secs. 610.46 and 
610.47, to look at in-date prior collections from a donor who later 
tests repeatedly reactive on a required test for HIV, or is otherwise 
determined to be unsuitable when tested for HIV, and to notify 
transfusion recipients. FDA is proposing to amend Sec. 606.100(b)(19) 
to include requirements for blood establishments to have SOP's, in 
accordance with proposed Secs. 610.48 and 610.49, for HCV ``lookback,'' 
including procedures for quarantine and testing, and notification of 
transfusion recipients. The revised regulations would require SOP's to 
look at prior collections from a donor who has donated blood and later 
tests repeatedly reactive on a required test for HIV or HCV, or when 
the blood establishment has been made aware of other test results 
indicating evidence of HIV or HCV infection, and to notify transfusion 
recipients, if appropriate.

C. Proposed Revisions to Sec. 606.160

    FDA is proposing to amend Sec. 606.160. Section 606.160(b)(1)(viii) 
currently prescribes requirements for maintaining records of 
quarantine, notification, testing, and disposition performed under 
Secs. 610.46 and 610.47, whenever a donor subsequently tests repeatedly 
reactive for evidence of HIV infection. FDA is proposing to revise 
Sec. 606.160(b)(1)(viii), to include requirements for maintaining 
records of quarantine, notification, testing, and disposition performed 
under proposed Secs. 610.48 and 610.49, whenever a donor subsequently 
tests repeatedly reactive for evidence of HCV infection.
    Section 606.160(d) currently prescribes that the retention period 
for required processing records shall be no less than 5 years after 
completion of the record or 6 months after the latest expiration date 
for the individual product, whichever is a later date. FDA is proposing 
to revise Sec. 606.160(d) by increasing the required retention period 
to no less than 10 years after the records of processing have been 
completed, or 6 months after the latest expiration date for the 
individual product, whichever is a later date. FDA is proposing this 
change in the 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 of transfusion transmitted disease. 
Additionally, methods of recordkeeping have advanced, improving the 
ability of blood establishments to more easily maintain and retrieve 
records.

D. Proposed Revisions to Sec. 610.45

    As previously discussed, in the Federal Register of August 19, 1999 
(64 FR 45340), FDA issued a proposed rule to revise Sec. 610.40, and to 
delete Sec. 610.45, ``Human Immunodeficiency Virus (HIV) 
requirements,'' because, except as discussed below, the requirements of 
Sec. 610.45 would be included in proposed Sec. 610.40.
    Section 610.45(d) currently requires blood establishments to comply 
with Secs. 610.46 and 610.47, the HIV ``lookback'' requirements for 
quarantine, consignee notification, further testing and transfusion 
recipient notification, when applicable, whenever a donor's ``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 * * *.'' As previously discussed in section III.A 
of this document, the testing proposed rule would delete Sec. 610.45. 
This proposed rule would include the requirements of current 
Sec. 610.45(d) into proposed Sec. 610.40(g). Proposed Sec. 610.40(g) 
would require blood establishments to comply with Secs. 610.46 and 
610.47, and with proposed Secs. 610.48 and 610.49, thereby requiring 
compliance with the HIV and

[[Page 69383]]

HCV ``lookback'' regulations, respectively.

E. Proposed Revisions to Headings of Secs. 610.46 and 610.47

    As a result of the addition of HCV ``lookback'' requirements, FDA 
is proposing to revise the headings of the sections applicable to the 
``lookback'' requirements for HIV. FDA is proposing to revise the 
heading of Sec. 610.46 to read ``Human Immunodeficiency Virus (HIV) 
`Lookback;' quarantine, consignee notification and further testing'' to 
distinguish it from the new Sec. 610.48, ``Hepatitis C Virus (HCV) 
```lookback;''' quarantine, consignee notification and further 
testing.'' Likewise, FDA is proposing to amend the heading of 
Sec. 610.47, ``Lookback'' Notification requirements for transfusion 
services,'' to read ``Human Immunodeficiency Virus (HIV) ``Lookback;'' 
notification of transfusion recipients'' to distinguish it from the new 
Sec. 610.49, ``Hepatitis C Virus (HCV) ``Lookback;'' notification of 
transfusion recipients.'' As previously noted, FDA is proposing to 
amend Sec. 610.46 for consistency with proposed Sec. 610.48 of this 
proposed rule, and to amend Sec. 610.47 for consistency with 
Sec. 610.49 of this proposed rule. The corresponding revisions to 
Sec. 610.46 and to Sec. 610.47 are noted in the discussion of proposed 
Sec. 610.48 and proposed Sec. 610.49.

F. Proposed Sec. 610.48(a), Quarantine and Consignee Notification

    Proposed Sec. 610.48(a) identifies the circumstances that would 
trigger the ``lookback'' process when a donor returns to donate and 
tests repeatedly reactive on a screening test, and states the 
requirements for quarantine of blood and blood components, notification 
of consignees, and quarantine of blood and blood components by 
consignees. Under proposed Sec. 610.48(a)(1), blood establishments 
would be required to take appropriate action within 3-calendar days 
after the date on which a donor returns to donate blood or blood 
components and tests repeatedly reactive for evidence of HCV infection 
on a required test, performed in accordance with proposed 
Sec. 610.40(a), or the date on which the blood establishment was made 
aware of other test results indicating evidence of HCV infection, 
provided the testing was performed by a laboratory certified under the 
Clinical Laboratory Improvement Amendments of 1988 (CLIA), using a test 
approved by FDA. In the testing proposed rule (64 FR 45340, August 19, 
1999) proposed Sec. 610.40(a) requires tests for specified communicable 
disease agents, including for HCV, and requirements for further testing 
of repeatedly reactive samples. For example, a blood establishment 
completing a screening test on Tuesday afternoon with a repeatedly 
reactive test result would have until the end of the day on Friday to 
complete the requirements for quarantine and consignee notification.
    FDA is specifically requesting comments on the appropriateness of 3 
calendar days proposed for exemptions of the quarantine of prior 
collections and consignee notification under proposed Secs. 10.48(a), 
(e), and (f) and the conforming amendment to 610.46(a). FDA is also 
proposing that the ``lookback'' measures specified in Sec. 610.48(a) be 
initiated by a blood establishment upon receipt of information that a 
person who has been a donor at that establishment has other test 
results indicating evidence of HCV infection and that the test was 
performed by a CLIA-certified laboratory, using a test approved by FDA, 
regardless of the purpose of the testing. FDA recognizes that blood 
establishments do not routinely receive such information, but should a 
blood establishment become aware of such reliable test results, the 
proposal would require appropriate ``lookback'' measures. State laws 
and public health practices vary widely, making it impossible to 
specify all circumstances under which test results may be provided to 
the blood establishment. However, FDA believes that the blood 
establishment has the obligation, upon the receipt of such reliable 
test results, to initiate appropriate action to protect the blood and 
plasma supply. In addition, the reliability of test results may vary, 
depending on the quality of the test method used and on the 
qualifications of the testing facility to perform the test. 
Accordingly, FDA is proposing to require the initiation of ``lookback'' 
procedures when the test results originate from a laboratory certified 
under CLIA and when the laboratory has used FDA-approved tests.
    Proposed Sec. 610.48(a) would require blood establishments and 
their consignees to identify and quarantine all affected blood and 
blood components collected prior to the donor's repeatedly reactive 
screening test for HCV. Under proposed Sec. 606.160(d), blood 
establishments would retain records for ``* * * no less than 10 years * 
* *'' or, for products that remain in inventory, for 6 months after the 
latest expiration date of the product, whichever is the later date, and 
under proposed Sec. 610.48(a) blood establishments would quarantine any 
in-date prior collections that remain in inventory. If the blood 
establishment has information to assure that there are no in-date prior 
collections, there is no need to trace those products.
    Proposed Sec. 610.48(a)(1)(i) would require blood establishments to 
quarantine all in-date prior collections from a donor testing 
repeatedly reactive for evidence of HCV infection. Proposed 
Sec. 610.48(a)(1)(ii) would require blood establishments to notify 
consignees of the repeatedly reactive HCV screening test result so that 
the consignee may quarantine all in-date prior collections of blood and 
blood components. Proposed Sec. 610.48(a)(2) would require consignees 
to quarantine all in-date prior collections of blood and blood 
components that remain in inventory.
    For consistency, FDA is also proposing conforming amendments to the 
corresponding HIV ``lookback'' requirements of Sec. 610.46(a). FDA is 
proposing to amend Sec. 610.46(a) by changing the title of the 
paragraph to ``Quarantine and consignee notification'' and to clarify 
that blood establishments would be required to complete the quarantine 
and consignee notification requirements within 3-calendar days after 
the date on which the donor tests repeatedly reactive for evidence of 
HIV infection. FDA is proposing to replace the phrase ``or otherwise 
determined to be unsuitable when tested in accordance with 
Sec. 610.45'' with ``or when the blood establishment has been made 
aware of other test results indicating evidence of HIV infection, 
provided the testing was performed by a laboratory certified under the 
Clinical Laboratory Improvement Amendments of 1988, using a test 
approved by FDA'' to eliminate any confusion that might be caused by 
different wording. Likewise, for clarity and consistency, FDA is 
proposing to replace ``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, * * *.'' 
with ``For in-date blood and blood components collected from that donor 
at any time prior to the repeatedly reactive test, whenever records are 
available, if intended for transfusion or for further manufacture into 
injectable products, * * *.'' Also, FDA recognizes that it is not 
necessary for ``lookback'' requirements to distinguish collections 
intended for transfusion from those intended for further manufacturing. 
FDA is clarifying that ``lookback'' requirements should be followed for 
any

[[Page 69384]]

prior collection that has not expired because records are held for 6 
months after the latest expiration date of the individual product.

G. Proposed Sec. 610.48(b), Further Testing and Consignee Notification 
of Results

    Proposed Sec. 610.48(b) would require further testing whenever a 
donor returns to donate and tests repeatedly reactive for evidence of 
HCV infection, as described in Sec. 610.48(a), and notification of 
consignees of the results of the further testing. Proposed 
Sec. 610.48(b) would require blood establishments to perform further 
testing, in accordance with proposed Sec. 610.40(c) of the testing 
proposed rule (as previously discussed), after a donor with a record of 
prior collections tests repeatedly reactive for evidence of HCV 
infection when tested in accordance with proposed Sec. 610.40(a) of the 
testing proposed rule. Blood establishments would be required to notify 
consignees of the results of the further testing within 45-calendar 
days after the day on which the donor tests repeatedly reactive on a 
screening test for evidence of HCV infection.
    FDA is proposing a conforming amendment to Sec. 610.46(b) for HIV 
``lookback'' by changing the maximum time provided for a blood 
establishment to notify consignees of the results of the further 
testing from 30 to 45 days. This change is proposed for consistency 
between the HIV and HCV ``lookback'' regulations and in response to 
comments that although further testing for HIV and HCV can be completed 
within 30 days, additional time is needed to notify consignees 
following completion of the further testing.

H. Proposed Sec. 610.48(c), Review of Historical Testing Records and 
Identification of Donors Tested Using a Multiantigen Screening Test 
Prior to the Effective Date of this Regulation

    As discussed in section I.C of this document in this preamble, 
blood establishments routinely have been testing blood donations for 
antibody to HCV since 1990. In the guidance documents issued in March 
1998, September 1998 and June 1999, FDA issued recommendations (draft 
guidance was issued in June 1999) for blood establishments to initiate 
``lookback'' procedures consistent with those now being proposed, 
including when, through a review of historical testing records, 
previous instances are identified when a donor had tested repeatedly 
reactive on a multiantigen screening test for evidence of HCV 
infection. FDA believes that since 1990, many blood establishments have 
routinely initiated ``lookback'' procedures consistent with the 
regulations now being proposed, and with the issuance of the 
recommendations in 1998 and 1999, many additional establishments have 
undertaken the review of historical testing records and have initiated 
appropriate ``lookback'' procedures. However, because HCV is a chronic, 
often asymptomatic disease that may ultimately have serious 
consequences, FDA believes that it is imperative to identify and notify 
recipients who have been transfused with blood or blood components for 
which there is an increased risk of transmission of HCV as determined 
by subsequent donor testing. Such transfusion recipients should be made 
aware that they should seek further testing to see if they are infected 
and, if so, to receive appropriate counseling and medical care.
    The requirements of proposed Sec. 610.48(c) and (d) are based on 
the agency's understanding of current research in hepatitis testing. 
FDA specifically invites comments on these provisions and requests 
individuals to submit data in support of the comments. To the extent 
the data do not support these provisions, FDA would revise the rule 
accordingly. FDA recognizes that the review of historical testing 
records (performed in accordance with proposed Sec. 610.48(c) and (d)) 
will identify tests performed using both licensed and unlicensed tests, 
HCV EIA 1.0, 2.0, and 3.0, as well as, HCV RIBA 2.0 and 3.0 
supplemental tests. For that reason, the proposed requirements for 
testing performed prior to the effective date of any final rule 
resulting from this proposal (that is, test results identified in the 
review of historical testing records) would take into account the use 
of unlicensed tests, under specific circumstances. In addition, testing 
performed following the effective date of any final rule resulting from 
this proposal (such as further testing performed in accordance with 
proposed Sec. 610.48(h) or (i)) would require use of a currently 
licensed test, as specified.
    The purpose of Sec. 610.48(c) is to identify, through a search of 
available historical testing records, those prior collections that 
might have been collected during the window period, that is, a donation 
that may have been made after the donor became infected with HCV but 
before it was possible for a screening test to detect antibody to HCV. 
The identification of prior collections would be based on the 
multiantigen screening test result and would be followed by appropriate 
steps to perform quarantine, further testing and notification of 
consignees and transfusion recipients, as discussed in detail in this 
and other sections of this proposed rule. Blood establishments would be 
required to perform a review of historical testing records to identify, 
within 1 year of the effective date of any final rule resulting from 
this proposal, prior collections at increased risk of transmitting HCV 
infection because they are from a donor who later tested repeatedly 
reactive for evidence of HCV infection on a multiantigen screening test 
and who either: (1) Has no record of further testing for HCV performed 
on the repeatedly reactive sample and no record of a negative licensed, 
multiantigen screening test performed at a later date (as specified in 
Sec. 610.48(c)(4) and (c)(5); or (2) has a record of further testing 
(as specified in Sec. 610.48(c)(1), (c)(2), and (c)(3)) that 
potentially indicates evidence of HCV infection, as discussed in detail 
later in this proposed rule. As discussed in the following paragraph, 
after the review of historical testing records, ``lookback'' actions 
would be triggered for certain prior collections. Blood establishments 
would be required to quarantine any in-date prior collections still in 
inventory where records show that they were collected from donors later 
found to have a repeatedly reactive multiantigen screening test for 
evidence of HCV infection (unless exempt from quarantine under 
Sec. 610.48(g)(2)), and to notify consignees to quarantine such prior 
collections, as specified under proposed Sec. 610.48(e)(2); to perform 
further testing, as specified in proposed Sec. 610.48(h)(1), on donors 
identified in accordance with proposed Sec. 610.48(c)(4) and (c)(5); or 
optionally to perform further testing in accordance with 
Sec. 610.48(h)(2) on donors identified in accordance with 
Sec. 610.48(c)(2) and (c)(3); and to notify consignees of the test 
result, in accordance with proposed Sec. 610.48(h)(3), as described in 
the following paragraph. Transfusion services notified by blood 
establishments of prior receipt of blood or blood components at 
increased risk of transmitting HCV would either notify the transfusion 
recipients directly or notify the recipient's physician of record 
(i.e., physician of record or physician who ordered the blood or blood 
component), as specified in proposed Sec. 610.49(b).
    Under proposed Sec. 610.48(c), the review would include records, if 
available, dating back indefinitely for computerized electronic 
records, and to January 1988 for other readily retrievable records, or 
12 months prior to the donor's most recent negative

[[Page 69385]]

multiantigen screening test for antibody to HCV, whichever is the 
lesser period. This 12-month time period requirement is intended to 
identify any potential ``window period'' donation. Review of historical 
testing records dating back indefinitely would not be necessary for 
prior collections from many donors (i.e., prior collections from donors 
who have a record of a prior negative multiantigen screening test 
result because the prior collections would not be considered to be 
window period donations.) Examples are provided in the following 
paragraph. In addition, many donors who test repeatedly reactive for 
evidence of HCV infection are first-time donors with no previous 
history of donation. Thus, no ``lookback'' action is needed for such a 
first-time donor because ``lookback'' activity targets prior 
collections and no prior collections exist for a first time donor.
    Proposed Sec. 610.48(c) would limit the review of records to the 
identification of prior collections dating back to ``the date 12 months 
prior to the donor's most recent negative multiantigen screening test 
for HCV.'' FDA believes that this 12-month period prior to the last 
negative multiantigen screening test for HCV establishes with high 
confidence that, prior to that date, possible HCV infection would have 
been detected by a screening test; if any ``window period'' donation 
was collected, it would have occurred after that date. For example, it 
would not be necessary to identify collections dating back indefinitely 
for a donor who has donated every 6 months from January 1983 until 
testing repeatedly reactive on a screening test for evidence of HCV 
infection in January 1998, with the last negative multiantigen 
screening test on July 1, 1997. In this example, the last negative 
multiantigen screening test for antibody to HCV is July 1, 1997, and 12 
months prior to that would be July 2, 1996. Under the proposal, the 
blood establishment would use the later date of July 2, 1996 (rather 
than the maximum time period back to January 1983), and the blood 
establishment would identify donations made on or after July 2, 1996, 
to July 1, 1997, as possible ``window period'' donations. In this 
example, donations made prior to July 2, 1996, would not be suspected 
to be ``window period'' donations, capable of transmitting HCV 
infection to a transfusion recipient. Note that a negative test result 
on a single antigen EIA screening test for HCV may not be used as the 
``most recent negative multiantigen screening test'' and is not a basis 
to limit the ``lookback'' activity, as described previously, due to the 
limited sensitivity of the single antigen HCV EIA test.
    FDA is proposing the review of historical testing records to 
identify five specific instances following a repeatedly reactive 
multiantigen screening test that should be used to identify increased 
risk of transmitting HCV from the donor's prior collections. Under 
Sec. 610.48(c), blood establishments would identify prior collections 
from donors who tested repeatedly reactive for evidence of HCV 
infection on a licensed, multiantigen screening test and who: (1) 
Tested positive on a supplemental test for HCV performed on the 
repeatedly reactive sample (as specified in Sec. 610.48(c)(1)); or 
(c)(2) tested indeterminate on a supplemental test for HCV (as 
specified in Sec. 610.48(c)(2)); or (c)(3) testing repeatedly reactive 
on licensed HCV EIA 3.0 screening test and negative on a licensed HCV 
RIBA 2.0 supplemental test but with no records of a negative licensed 
HCV RIBA 3.0 supplemental test performed on the repeatedly reactive 
sample or a later sample from the same donor; or (4) tested repeatedly 
reactive for evidence of HCV infection on an HCV EIA 2.0 screening test 
with no record of a supplemental test for HCV performed on the 
repeatedly reactive sample or on a later sample from the donor and no 
record of a negative licensed HCV EIA 3.0 screening test performed on 
the repeatedly reactive sample or later on the same donor; or (5) 
tested repeatedly reactive for evidence of HCV infection on a licensed, 
HCV EIA 3.0 screening test with no record of a supplemental test for 
HCV performed on the repeatedly reactive sample or on a later sample 
from the same donor. As discussed previously, the requirements of 
proposed Sec. 610.48(c) for review of historical testing records to 
identify prior collections from affected donors are particular to the 
testing methods used and exceptions are specified in Sec. 610.48(g), 
Exemption from Quarantine. Prior collections that would not be 
identified as possible ``window period'' donations and would not 
require further action are exempted from quarantine as described in 
Sec. 610.48(g)(2). For donors identified in accordance with 
Sec. 610.48(c)(4) and (c)(5) for whom no records of further testing 
exist to clarify the status of prior collections determined to be at 
increased risk of transmitting HCV infection, blood establishments 
would be required, as described under proposed Sec. 610.48(e), to 
perform quarantine and consignee notification for any in-date prior 
collections that remain in inventory and to perform further testing, as 
described under proposed Sec. 610.48(h)(1).

I. Proposed Sec. 610.48(d), Review of Records and Identification of 
Donors Testing Repeatedly Reactive on a Single Antigen Screening Test 
Prior to the Effective Date of this Regulation

    The purpose of Sec. 610.48(d), which parallels the requirements of 
Sec. 610.48(c), is to identify, through a review of historical testing 
records, those prior collections that might have been collected during 
the window period of HCV infection, based on a single antigen screening 
test result. Similar to the requirements of Sec. 610.48(c), which is 
based on the multiantigen screening test, proposed Sec. 610.48(d) 
would: (1) Require blood establishments to review available historical 
records of donor testing that occurred prior to the effective date of 
this regulation to identify prior collections that are potential window 
period donations; (2) require the review of available historical 
testing records dating back indefinitely for computerized electronic 
records and to January 1988 for other readily retrievable records; and 
(3) require that blood establishments complete the review or historical 
testing records within 1 year of the effective date of any final rule 
that results from this proposal.
    Under Sec. 610.48(d), blood establishments would identify 
previously distributed blood and blood components in any of the 
following four instances: (1) As proposed in Sec. 610.48(d)(1), where 
the donor tested repeatedly reactive for evidence of HCV infection on 
the single antigen screening test and repeatedly reactive on an HCV EIA 
2.0 or HCV EIA 3.0 screening test for HCV performed on the repeatedly 
reactive sample or a fresh sample from the same donor; (2) as proposed 
in Sec. 610.48(d)(2), where the donor tested repeatedly reactive for 
evidence of HCV infection on the single antigen screening test and 
either positive or indeterminate on an HCV 2.0 or HCV 3.0 strip 
immunoblot assay (HCV RIBA 2.0 or HCV RIBA 3.0 supplemental test, 
respectively) supplemental test for HCV; or (3) as proposed in 
Sec. 610.48(d)(3), where the donor tested repeatedly reactive for 
evidence of HCV infection on an HCV EIA 1.0 screening test, with a 
signal to cut off (S/CO) value less than 2.5 for at least two out of 
the three EIA tests (i.e., the initial EIA screening test and the 
duplicate retests) with no record of a supplemental test or 
multiantigen screening test for HCV performed on the repeatedly 
reactive sample or on a later sample from the same donor ; or (4) as 
proposed in Sec. 610.48(d)(4), where the donor tested repeatedly 
reactive for

[[Page 69386]]

evidence of HCV infection on an HCV EIA 1.0 screening test, with a S/CO 
value equal to or greater than 2.5 for at least two out of the three 
EIA tests or with no determination of S/CO value for all three EIA 
tests, and with no record of a supplemental test or multiantigen 
screening test for HCV performed on the repeatedly reactive sample or 
on a later sample from the same donor. (The S/CO value for each test 
result is calculated as the ratio of the absorbency value obtained for 
the donor sample divided by the absorbency value for the cutoff in that 
assay run.)
    As previously discussed in section I.C of this document, the PHS 
Advisory Committee met on January 28, 1999, to consider options for 
expanding the targeted HCV ``lookback'' program to include recipients 
of blood from donors subsequently identified as repeatedly reactive by 
the single antigen HCV EIA 1.0 screening test. Approximately 80 percent 
of the HCV EIA 1.0 repeatedly reactive donations were identified before 
the first confirmatory test became available. The PHS Advisory 
Committee concluded that it would be reasonable to limit the 
``lookback'' for EIA 1.0 based on the S/CO value of the screening tests 
in cases where supplemental testing had not been done and further 
testing of the original repeatedly reactive sample or a later sample 
from the same donor was impractical. The PHS Advisory Committee 
concluded that it would be appropriate 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. The requirements 
proposed in Sec. 610.48(d) and (i) reflect the PHS Advisory Committee's 
recommendations for use of the S/CO value based on a critical ratio of 
2.5 in evaluating risk of HCV transmission under ``lookback'' 
circumstances identified in the review of historical testing records.
    As discussed previously, the requirements of proposed 
Sec. 610.48(d) for review of historical testing records to identify 
prior collections from affected donors are particular to the testing 
methods used and exceptions are specified in Sec. 610.48(g), Exemption 
from quarantine. Prior collections that would not be identified as 
possible ``window period'' donations and would not require further 
action are exempted from quarantine as described in Sec. 610.48(g)(3).

J. Proposed Sec. 610.48(e), Quarantine and Consignee Notification 
Following the Review of Historical Testing Records Based on Screening 
Performed Using a Multiantigen Screening Test

    The purpose of proposed Sec. 610.48(e) is to require quarantine of 
prior collections that were identified in the review of historical 
testing records, based on a multiantigen screening test in accordance 
with proposed Sec. 610.48(c), until further testing is completed, if 
necessary, and the blood establishment can make a determination to 
release the prior collections from quarantine (under proposed 
Sec. 610.48(j)(2)), or to destroy or relabel them (under proposed 
Sec. 610.48(k)). Proposed Sec. 610.48(e) would require blood 
establishments to quarantine certain prior collections until further 
testing is completed to clarify the status of the prior collections, 
and to notify consignees so that prior collections they hold can be 
quarantined. This requirement is intended to prevent the transfusion of 
a prior collection from a donor identified in the review of records as 
being at increased risk of transmitting HCV infection while further 
testing is performed.
    Proposed Sec. 610.48(e)(1) would require blood establishments to 
quarantine in-date prior collections of blood and blood components 
collected from donors identified in the review of records, under 
proposed Sec. 610.48(c), while further testing is performed, as 
required in proposed Sec. 610.48(h)(1) or as optional testing is 
performed in accordance with Sec. 610.48(h)(2).
    As previously mentioned, some exceptions to quarantine are 
specified in proposed Sec. 610.48(g)(2). Prior collections that meet 
the criteria under proposed Sec. 610.48(g)(2) would not be suspected as 
``window period'' donations and would be exempt from quarantine, as 
discussed in following sections. If no exemption to quarantine applies, 
blood establishments would be required to perform quarantine within 3 
days of the date on which the establishment identifies a donor's 
repeatedly reactive multiantigen screening test. All identification 
performed in accordance with Sec. 610.48(c) and the resulting 
quarantine and notification must be completed within a maximum of 1 
year from the effective date of any final rule resulting from this 
proposal.
    Proposed Sec. 610.48(e)(2) would require blood establishments, 
within 3-calendar days of the date on which the donor's repeatedly 
reactive multiantigen screening test is identified, to notify 
consignees of the donor's test results, including supplemental test 
results, if available, so that consignees may quarantine all in-date 
prior collections of blood and blood components subject to quarantine 
under proposed Sec. 610.48(e)(1). FDA is specifically requesting 
comments on the appropriateness of the 1-year timeframe to complete all 
quarantine and notification.

K. Proposed Sec. 610.48(f), Quarantine and Consignee Notification 
Following the Review of Records Based on Screening Performed Using a 
Single Antigen Screening Test

    The purpose of Sec. 610.48(f), which parallels the requirements of 
Sec. 610.48(e), is to require quarantine of prior collections that were 
identified in the review of historical testing records based on single 
antigen testing, in accordance with proposed Sec. 610.48(d), until 
further testing is completed, if necessary, and a determination can be 
made to release the prior collections from quarantine (under proposed 
Sec. 610.48(j)(3)), or to destroy or relabel them (under proposed 
Sec. 610.48(k)). Proposed Sec. 610.48(f) would require blood 
establishments to quarantine certain prior collections until further 
testing is completed to clarify the status of the prior collections, 
and to notify consignees so that prior collections they hold can be 
quarantined. This requirement is intended to prevent the transfusion of 
a prior collection from a donor identified in the review of records as 
being at increased risk of transmitting HCV infection while further 
testing is performed.
    Proposed Sec. 610.48(f)(1) would require blood establishments to 
quarantine in-date prior collections of blood and blood components from 
donors identified in the review of historical testing records, under 
proposed Sec. 610.48(d), while further testing is performed, as 
required in proposed Sec. 610.48(i)(1) or as optional testing is 
performed in accordance with Sec. 610.48(i)(2).
    Under this proposal, blood establishments would be required to 
perform quarantine within 3 calendar days of the date on which the 
blood establishment identifies a donor's repeatedly reactive single 
antigen screening test. All identification performed in accordance with 
Sec. 610.48(d) and the resulting quarantine and notification must be 
completed within a maximum of 1 year from the effective date of any 
final rule resulting from this proposal. As previously mentioned, some 
exceptions to quarantine are specified in proposed Sec. 610.48(g)(3). 
Prior collections that

[[Page 69387]]

meet the criteria under proposed Sec. 610.48(g)(3) would not be 
suspected as ``window period'' donations and would, therefore, be 
exempt from quarantine, as discussed in following sections.
    Proposed Sec. 610.48(f)(2) would require blood establishments, 
within 3-calendar days of the date on which the donor's repeatedly 
reactive single antigen screening test is identified, to notify 
consignees of the donor's test results, including supplemental test 
results, if available, so that consignees may quarantine all in-date 
prior collections of blood and blood components subject to quarantine 
under proposed Sec. 610.48(f)(1). FDA is specifically requesting 
comments on the appropriateness of 3-calendar days proposed for 
completion of the quarantine of prior collections and consignee 
notification under Sec. 610.48(f) and the appropriateness of the 1-year 
timeframe to complete all quarantine and notification.
    Proposed Sec. 610.48(f)(3) would require consignees notified in 
accordance with proposed Sec. 610.48(f)(2) to quarantine all prior 
collections of blood and blood components subject to quarantine under 
proposed Sec. 610.48(f)(1), except as provided in proposed 
Sec. 610.48(g)(3).

L. Proposed Sec. 610.48(g), Exemption From Quarantine

    Proposed Sec. 610.48(g) specifies which prior collections are not 
suspected as being window period donations and, therefore, are not 
subject to quarantine under proposed Sec. 610.48(a), (e), and (f). 
Proposed Sec. 610.48(g)(1) would exempt from quarantine certain prior 
collections otherwise subject to quarantine under proposed 
Sec. 610.48(a) when a donor tests repeatedly reactive on a multiantigen 
screening test for evidence of HCV infection. Proposed 
Sec. 610.48(g)(1)(i) is intended to identify certain donations that are 
not suspected of being collected during the ``window period'' because 
they were collected prior to the time a possible window period could 
have existed, and would not be subject to quarantine under proposed 
Sec. 610.48(a). Under proposed Sec. 610.48(g)(1)(i), for donations 
collected more than 12 months prior to the donor's most recent negative 
multiantigen screening test, a high confidence level exists that no 
infection could have existed at the time of donation and remain 
undetected by a screening test, and, therefore, blood establishments 
would not be required to quarantine blood or blood components 
``collected more than 12 months prior to the donor's most recent 
negative multiantigen screening test when tested for HCV in accordance 
with Sec. 610.40(a). An explanation of ``window period'' donations and 
a corresponding example are provided previously in the description of 
proposed Sec. 610.48(c).
    In addition, proposed Sec. 610.48(g)(1)(ii) would provide that when 
an appropriate licensed supplemental test for HCV (discussed in this 
section III.L) is found to be negative and is completed within the 3-
day time period provided for completion of quarantine and consignee 
notification, quarantining of prior collections of blood and blood 
components from that donor would not be required. Thus, if the 
supplemental test is found negative within 3-calendar days after the 
date on which the donor tested repeatedly reactive for evidence of HCV 
infection (the time provided for completion of quarantine and consignee 
notification), then the repeatedly reactive screening test result would 
be interpreted as a ``false positive,'' would not indicate HCV 
infection, and prior collections from that donor would not be 
considered to be at increased risk of transmitting HCV. If, however, 
the supplemental testing is completed more than 3 days after the date 
of the repeatedly reactive screening test result (the time provided for 
completion of quarantine and consignee notification), the blood and 
blood components would be quarantined but could then be released from 
quarantine if the supplemental test is negative, as provided in 
proposed Sec. 610.48(j).
    As specified in proposed Sec. 610.48(g), the supplemental test must 
be appropriately chosen, i.e., the appropriately chosen supplemental 
test should contain all the antigens of the screening test that was 
performed. Under proposed Sec. 610.48(g)(1)(ii), if the repeatedly 
reactive screening test was obtained using an HCV EIA 2.0 screening 
test, then an appropriate supplemental test would be either an HCV RIBA 
2.0 or an HCV RIBA 3.0. However, if the repeatedly reactive screening 
test result was obtained using an HCV EIA 3.0 screening test, then the 
appropriate supplemental test would be an HCV RIBA 3.0. The HCV RIBA 
2.0 supplemental test would not be an appropriately chosen supplemental 
test following an HCV EIA 3.0 screening test because the HCV RIBA 2.0 
supplemental test does not include all antigens contained in the HCV 
EIA 3.0 screening test.
    Proposed Sec. 610.48(g)(2) provides for exceptions from quarantine 
performed in accordance with proposed Sec. 610.48(e) following the 
review of historical testing records based on screening performed using 
a multiantigen screening test. Similar to the provisions of proposed 
Sec. 610.48(g)(1), proposed Sec. 610.48(g)(2) is intended to exempt 
from quarantine those prior collections that are not suspected as being 
collected during the ``window period.'' Under proposed 
Sec. 610.48(g)(2), prior collections of blood and blood components 
would not be subject to quarantine under proposed Sec. 610.48(e) if 
they meet any of the following criteria: (1) The prior collection was 
donated more than 12 months prior to the donor's most recent negative 
multiantigen screening test for evidence of HCV infection that preceded 
the repeatedly reactive screening test; or (2) records show that the 
repeatedly reactive screening test result was obtained using an HCV EIA 
2.0 screening test, and either the original sample or a later sample 
from the same donor was tested and found negative using an HCV RIBA 
2.0, or an HCV RIBA 3.0 supplemental test or an HCV EIA 3.0 screening 
test. (As previously discussed, a negative test result on a single 
antigen EIA screening test for HCV may not be used as the ``most recent 
negative multiantigen screening test'' and is not a basis to limit the 
``lookback'' activity, as described previously, due to the limited 
sensitivity of the HCV EIA 1.0 screening test); or (3) records show 
that the repeatedly reactive screening test result was obtained using 
an HCV EIA 3.0 screening test, and either the original sample or a 
later sample from the same donor was tested and found negative using an 
HCV RIBA 3.0 supplemental test.
    Proposed Sec. 610.48(g)(3) provides for exceptions from quarantine 
(performed in accordance with proposed Sec. 610.48(f)) following the 
review of records based on screening performed using a single antigen 
screening test. Similar to the provisions of proposed Sec. 610.48(g)(1) 
and (g)(2), proposed Sec. 610.48(g)(3) is intended to exempt from 
quarantine those prior collections that are not suspected as being 
collected during the ``window period.'' Under proposed 
Sec. 610.48(g)(3), prior collections of blood and blood components 
would not be subject to quarantine under proposed Sec. 610.48(f) if 
they meet any of the following four criteria: (1) Records show that the 
repeatedly reactive screening test result was obtained using an HCV EIA 
1.0 screening test, and either the original sample or a later sample 
from the same donor was tested and found negative using an HCV EIA 2.0 
or an HCV EIA 3.0 screening test (exempted under proposed 
Sec. 610.48(g)(3)(i)); or (2) records show that the repeatedly reactive 
screening test result was obtained using an HCV EIA 1.0

[[Page 69388]]

screening test, and either the original sample or a later sample from 
the same donor was tested and found negative using a HCV RIBA 2.0 or a 
HCV RIBA 3.0 supplemental test (exempted under proposed 
Sec. 610.48(g)(3)(ii)); or (3) the donor identified in accordance with 
proposed Sec. 610.48(d)(1), as testing repeatedly reactive on an HCV 
EIA 2.0 or 3.0 screening test, was further tested using an HCV RIBA 2.0 
or HCV RIBA 3.0 supplemental test, using a fresh sample, or frozen 
sample from the repeatedly reactive donation and the result was 
negative (exempted under Sec. 610.48(g)(3)(iii)); or (4) the donor 
identified in accordance with proposed Sec. 610.48(d)(2), as testing 
indeterminate on an HCV RIBA 2.0 supplemental test, was further tested 
using either an HCV EIA 3.0 or a HCV RIBA 3.0 supplemental test using a 
fresh sample, or frozen sample from the repeatedly reactive donation 
and the result was negative (exempted under proposed 
Sec. 610.48(g)(3)(iv)).
    FDA is also proposing a conforming amendment to Sec. 610.46(c), 
which specifies requirements for exemption from quarantine for HIV 
``lookback,'' for consistency with the HCV ``lookback'' requirements by 
changing ``Whole Blood, blood components, Source Plasma and Source 
Leukocytes'' to ``blood and blood components.''

M. Proposed Sec. 610.48(h), Further Testing Following Review of 
Historical Testing Records and Consignee Notification Based on 
Screening Performed Using a Multiantigen Screening Test

    Proposed Sec. 610.48(h) is intended to require that prior 
collections identified in accordance with Sec. 610.48(c)(4) and (c)(5), 
based on multiantigen screening test results, either be further tested 
and consignees notified so that blood establishments can determine if 
the prior collection should be released from quarantine (under 
Sec. 610.48(j)), or destroyed or relabeled (under Sec. 610.48(k)), and 
if notification of transfusion recipients is necessary (under 
Sec. 610.49(a)). In addition, blood establishments would have the 
option to perform further testing for prior collections identified in 
accordance with Sec. 610.48(c)(2) and (c)(3). Proposed 
Sec. 610.48(h)(1) would require blood establishments, by 1 year from 
the effective date of any final rule resulting from this proposal, to 
perform further testing to clarify the status of prior collections 
collected from a donor identified, in accordance with Sec. 610.48(c)(4) 
and (c)(5), as being at increased risk of transmitting HCV. Proposed 
Sec. 610.48(h)(1) would require that further testing be performed as 
follows: (1) As proposed in Sec. 610.48(h)(1)(i)(A), if the repeatedly 
reactive test result was obtained using a licensed HCV EIA 2.0 
screening test, blood establishments would perform a licensed 
supplemental test for HCV on a frozen sample from the repeatedly 
reactive donation, if it is available. If such a frozen sample is not 
available, blood establishments would obtain a fresh sample from the 
donor and perform a licensed supplemental test for HCV; or 
alternatively, (2) as proposed in Sec. 610.48(h)(1)(i)(B), if the 
repeatedly reactive test result was obtained using a licensed HCV EIA 
2.0 screening test, blood establishments would perform a licensed HCV 
EIA 3.0 screening test on a frozen sample, if it is available. If such 
a frozen sample is not available, blood establishments would obtain a 
fresh sample from the donor and perform a licensed HCV EIA 3.0 
screening test and a licensed supplemental test if the HCV EIA 3.0 
screening test is repeatedly reactive; or (3) as proposed in 
Sec. 610.48(h)(1)(ii), if the repeatedly reactive test result was 
obtained using a licensed HCV EIA 3.0 screening test, blood 
establishments would perform a licensed supplemental test for HCV on a 
frozen sample, if available. If such a frozen sample is not available, 
blood establishments would obtain a fresh sample from the donor and 
perform a licensed supplemental test for HCV; or (4) as proposed in 
Sec. 610.48(h)(1)(iii), blood establishments would make a determination 
that neither a frozen sample from the repeatedly reactive donation nor 
a fresh sample from the donor is available for further testing. For 
example, the blood establishment might make a determination that 
additional testing is not possible because the sample was not stored 
properly, or the donor could not be located or the donor declined 
further testing.
    Under proposed Sec. 610.48(h)(2), blood establishments would have 
the option to perform further testing on prior collections identified 
in accordance with Sec. 610.48(c)(2) and (c)(3). This provision would 
make it possible to clarify the status of the prior collections and, in 
some instances, based on further testing, it might not be necessary to 
destroy the prior collections or notify transfusion recipients. Under 
proposed Sec. 610.48(h)(2), blood establishments that have performed 
the review of records and identified prior collections in accordance 
with proposed Sec. 610.48(c)(2) or (c)(3) of this section may further 
test a frozen sample from the repeatedly reactive donations or a fresh 
sample from the same donor by 1 year from the effective date of any 
final rule resulting from this proposal, as follows: (1) As proposed in 
Sec. 610.48(h)(2)(i), if the donor was identified in accordance with 
proposed Sec. 610.48(c)(2) of this section as testing repeatedly 
reactive using an HCV EIA 2.0 screening test, and indeterminate on a 
HCV RIBA 2.0 supplemental test, blood establishments have the option to 
perform further testing using either an HCV EIA 3.0 screening test or a 
currently available licensed supplemental test for HCV; or (2) as 
proposed in Sec. 610.48(h)(2)(ii), if the donor was identified in 
accordance with proposed Sec. 610.48 (c)(2) of this section as testing 
repeatedly reactive using an HCV EIA 2.0 screening test, indeterminate 
on a HCV RIBA 2.0 supplemental test, and repeatedly reactive on an HCV 
EIA 3.0 screening test, blood establishments have the option to perform 
further testing using an appropriately chosen licensed supplemental 
test for HCV (refer to section L of this document that discusses 
proposed Sec. 610.48(g) for more information regarding use of ``an 
appropriately chosen supplemental test''); or (3) as proposed in 
Sec. 610.48(h)(2)(iii), if the donor was identified in accordance with 
(c)(2) of this section as testing repeatedly reactive using an HCV EIA 
3.0 screening test, and indeterminate on a HCV RIBA 2.0 supplemental 
test, blood establishments have the option to perform further testing 
using an appropriately chosen licensed supplemental test for HCV; or 
(4) as proposed in Sec. 610.48(h)(2)(iv), if the donor was identified 
in accordance with proposed Sec. 610.48 (c)(3) of this section as 
testing repeatedly reactive using an HCV EIA 3.0 screening test, and 
negative on a HCV RIBA 2.0 supplemental test, blood establishments have 
the option to perform further testing using an appropriately chosen 
licensed supplemental test for HCV. Based on the results of the further 
testing, the blood establishment can make a decision regarding the next 
appropriate step under proposed Sec. 610.48(j), to release from 
quarantine, or under proposed Sec. 610.48(k), to destroy or 
appropriately label prior collections, or under proposed 
Sec. 610.49(a), to notify any transfusion recipients.
    Under proposed Sec. 610.48(h)(3), blood establishments would be 
required to notify consignees of the results of the additional testing, 
performed in accordance with proposed Sec. 610.48(h)(1) or (h)(2), upon 
completing the additional testing and prior to 1 year from the 
effective date of any final rule resulting from this proposal. Blood

[[Page 69389]]

establishments would be required to notify the consignee of any risk of 
HCV transmission that exists for such prior collections, based on the 
results of the additional testing. If the prior collection was from a 
donor identified in the review of historical testing records in 
accordance with proposed Sec. 610.48(c)(1) through (c)(5), and no 
additional testing was performed, or if no sample was available for 
further testing, as provided in proposed Sec. 610.48(h)(1)(iii), the 
blood establishment would be required, within 1 year from the effective 
date of a final rule that results from this proposal, to notify 
consignees of any risk of HCV transmission for such prior collections.
    The review of historical testing records identifies those donors 
whose test results indicate some degree of risk of HCV transmission for 
prior collections. If the testing records do not include supplemental 
testing, further testing of the original repeatedly reactive sample or 
a fresh sample from the donor is needed. The purpose of further testing 
is to provide the opportunity for blood establishments to evaluate the 
test results and determine the next appropriate step in the 
``lookback'' process. Blood establishments must consider several 
significant issues when evaluating HCV screening and supplemental 
tests. Prior collections from donors who subsequently test positive or 
indeterminate on a supplemental test for HCV (except donors testing 
indeterminate on a RIBA 3.0 supplemental test as described below), are 
at increased risk of transmitting HCV. Prior collections from such 
donors would be destroyed or relabeled as proposed in Sec. 610.48(k), 
or, if transfused, would trigger notification of recipients because of 
the increased risk of transmission of HCV infection.
    However, in the case of a donor whose screening test was repeatedly 
reactive by HCV EIA 2.0, if an indeterminate RIBA 2.0 supplemental test 
result is followed by a negative result on an HCV EIA 3.0 screening 
test or an HCV RIBA 3.0 supplemental test, prior collections may be 
released from quarantine, as proposed in Sec. 610.48(j), and 
transfusion recipients need not be notified. This release from 
quarantine is based on current research that indicates absence of 
polymerase chain reaction (PCR) reactivity for HCV RNA in HCV RIBA 2.0 
indeterminate/HCV EIA 3.0 negative samples or in HCV RIBA 2.0 
indeterminate/HCV RIBA 3.0 negative samples. Conversely, prior 
collections from donors who subsequently test repeatedly reactive on an 
EIA screening test and indeterminate on an HCV RIBA 3.0 supplemental 
test must also be destroyed or relabeled because they represent an 
increased risk of HCV transmission (under proposed Sec. 610.48(k)). 
However, if these prior collections have been transfused, consignee 
notification for the purpose of recipient notification need not be 
performed (as noted in relevant sections of proposed Sec. 610.49(a)) 
due to infrequent PCR positivity (only 1.6 percent) in HCV EIA 3.0 
repeatedly reactive/HCV RIBA 3.0 indeterminate samples and infrequent 
(0.5 percent to 4 percent) PCR reactivity in HCV RIBA 2.0 
indeterminate/HCV RIBA 3.0 indeterminate samples.

N. Proposed Sec. 610.48(i), Further Testing and Consignee Notification 
Following Review of Records Based on Screening Performed Using a Single 
Antigen Screening Test

    The purpose of proposed Sec. 610.48(i), which parallels the 
requirements of proposed Sec. 610.48(h), is to require that prior 
collections, identified in the review of historical testing records and 
based on single antigen testing in accordance with Sec. 610.48(d)(4), 
be further tested and consignees notified so that blood establishments 
can determine if the prior collections should be released from 
quarantine (under Sec. 610.48(j)), or destroyed or relabeled (under 
Sec. 610.48(k)), and if notification of transfusion recipients is 
necessary (under Sec. 610.49(a)). In addition, blood establishments 
would have the option to perform further testing for prior collections 
identified in accordance with Sec. 610.48(d)(1), (d)(2), and (d)(3). 
Proposed Sec. 610.48(i)(1) would require blood establishments, within 1 
year of the effective date of any final rule resulting from this 
proposal, to perform further testing to clarify the status of prior 
collections collected from a donor identified, in accordance with 
Sec. 610.48(d)(4), as being at increased risk of transmitting HCV.
    Proposed Sec. 610.48(i)(1) would require that further testing for 
donors identified in accordance with proposed Sec. 610.48(d)(4) be 
performed as follows: (1) As proposed in Sec. 610.48(i)(1)(i), blood 
establishments would be required to perform a licensed supplemental 
test for HCV on a frozen sample from the repeatedly reactive donation, 
if available. If such a frozen sample is not available, blood 
establishments would be required to obtain a fresh sample from the 
donor and perform a licensed RIBA 3.0 supplemental test for HCV; or (2) 
as proposed under Sec. 610.48(i)(1)(ii), blood establishments would be 
required to make a determination that neither a frozen sample from the 
repeatedly reactive donation nor a fresh sample from the donor is 
available for further testing. For example, under certain 
circumstances, the blood establishment could make a determination that 
additional testing is not possible because the sample was not stored 
properly, or the donor could not be located or the donor declined 
further testing.
    Under proposed Sec. 610.48(i)(2), blood establishments would have 
the option to perform further testing on prior collections identified 
in accordance with Sec. 610.48(d)(1) and (d)(2). This provision would 
make it possible to clarify the status of the prior collections and, in 
some instances, based on further testing, it might not be necessary to 
destroy the prior collections or notify transfusion recipients. Under 
proposed Sec. 610.48(i), blood establishments that have performed the 
review of historical testing records and identified prior collections 
in accordance with proposed Sec. 610.48 (d)(1) or (d)(2) of this 
section may further test a frozen sample from the repeatedly reactive 
donation or a fresh sample from the same donor by 1 year from the 
effective date of any final rule resulting from this proposal, as 
follows: (1) As proposed under Sec. 610.48(i)(2)(i), if the donor was 
identified in accordance with proposed Sec. 610.48 (d)(1) of this 
section as testing repeatedly reactive on an HCV EIA 1.0 screening test 
and repeatedly reactive on either an HCV EIA 2.0 or HCV EIA 3.0 
screening test, blood establishments have the option to perform further 
testing using an appropriate licensed supplemental test for HCV; or (2) 
as proposed under Sec. 610.48(i)(2)(ii), if the donor was identified in 
accordance with paragraph (d)(2) of this section as testing repeatedly 
reactive on an HCV EIA 1.0 screening test with an indeterminate test 
result obtained using a HCV RIBA 2.0 supplemental test, blood 
establishments have the option to perform further testing using a 
currently available licensed supplemental test for HCV or an HCV EIA 
3.0 screening test. If such optional further testing is performed using 
an HCV EIA 3.0 screening test and the result is repeatedly reactive, 
blood establishments have the additional option to perform further 
testing using an appropriately chosen licensed supplemental test for 
HCV; or (3) as proposed under Sec. 610.48(i)(2)(iii), if the donor was 
identified in accordance with paragraph (d)(3) of this section as 
testing repeatedly reactive on an HCV EIA 1.0 screening test with a S/
CO value less than 2.5 for at least two out of the three EIA tests, and 
with no record of a supplemental test or multiantigen

[[Page 69390]]

screening test for HCV performed on the repeatedly reactive sample or 
on a later sample from the same donor, blood establishments have the 
option to perform further testing using a licensed multiantigen 
screening test for HCV or a licensed supplemental test for HCV.
    Under proposed Sec. 610.48(i)(3), blood establishments would be 
required to notify consignees of the results of the additional testing, 
performed in accordance with proposed Sec. 610.48(i)(1) or (i)(2), upon 
completing the additional testing and prior to 1 year from the 
effective date of any final rule resulting from this proposal. Blood 
establishments would be required to notify the consignee of any risk of 
HCV transmission that exists for such prior collections, based on the 
results of the additional testing. If the prior collection was from a 
donor identified in the review of historical testing records in 
accordance with proposed Sec. 610.48(d)(1) through (d)(4), and no 
additional testing was performed, or if no sample was available for 
further testing, as provided in proposed Sec. 610.48(i)(1)(ii), the 
blood establishment would be required to notify consignees, within 1 
year from the effective date of a final rule that results from this 
proposal, of any risk of HCV transmission for such prior collections.

O. Proposed Sec. 610.48(j), Release From Quarantine

    The purpose of proposed Sec. 610.48(j) is to identify those prior 
collections of blood and blood components intended for transfusion or 
for manufacture into injectable products that have been quarantined and 
further tested that may be released from quarantine, based on the 
results of the additional testing. Under proposed Sec. 610.48(j)(1), 
those prior collections subject to quarantine under proposed 
Sec. 610.48(a) would be released for use only if the donor's current, 
repeatedly reactive sample is further tested using a licensed, 
supplemental test for HCV, as required in proposed Sec. 610.48(b), and 
the result of the supplemental test is negative. Because the negative 
supplemental test result indicates that the repeatedly reactive 
screening test result was a ``false positive,'' prior collections from 
the donor are not suspected as being a possible window period donation, 
are not at increased risk of transmitting HCV and therefore, may be 
released from quarantine.
    Under proposed Sec. 610.48(j)(2), prior collections subject to 
quarantine under proposed Sec. 610.48(e)(1) (as a result of the review 
of historical testing records and based on a multiantigen screening 
test) would be released from quarantine only if such prior collections 
were not suspected as being ``window'' period donations. Such prior 
collections, if not exempt from quarantine under proposed 
Sec. 610.48(g)(2), would be released from quarantine if certain 
conditions are met as follows: (1) As proposed in 
Sec. 610.48(j)(2)(i)(A), if the donor's testing records meet the 
conditions specified in proposed Sec. 610.48(c)(4) (repeatedly reactive 
HCV EIA 2.0 screening test without additional test results) and further 
testing was performed in accordance with Sec. 610.48(h)(1)(i)(A) on a 
frozen sample from the repeatedly reactive donation or a fresh sample 
from the same donor, and the result of the licensed supplemental test 
for HCV is negative; or (2) as proposed in Sec. 610.48(j)(2)(i)(B), if 
the donor's testing records meet the conditions specified in proposed 
Sec. 610.48(c)(4) and the blood establishment performed further testing 
in accordance with proposed Sec. 610.48(h)(1)(i)(B) on a frozen sample 
from the repeatedly reactive donation or a fresh sample from the same 
donor, using either a licensed HCV EIA 3.0 screening test and the 
result is negative, or the result of the licensed HCV EIA 3.0 screening 
test is repeatedly reactive and further testing is performed using a 
licensed supplemental test for HCV and the result is negative; or (3) 
as proposed in Sec. 610.48(j)(2)(ii), if the donor's testing records 
meet the conditions specified in proposed Sec. 610.48(c)(5) (repeatedly 
reactive HCV EIA 3.0 screening test without additional test results) 
and the blood establishment performed further testing in accordance 
with proposed Sec. 610.48(h)(1)(ii) of this section on a frozen sample 
or a fresh sample from the same donor using a licensed, supplemental 
test for HCV and the result is negative; or (4) as proposed in 
Sec. 610.48(j)(2)(iii), if the donor's testing records meet the 
conditions specified in proposed Sec. 610.48(c)(2) (repeatedly reactive 
multiantigen screening test and indeterminate supplemental test) and 
the blood establishment performed further testing in accordance with 
proposed Sec. 610.48(h)(2), and one of three conditions specified in 
proposed Sec. 610.48(j)(2)(iii)(A), (j)(2)(iii)(B) or (j)(2)(iii)(C) 
applies. (Proposed Sec. 610.48(j)(2)(iii)(A) addresses repeatedly 
reactive sample that was tested using an HCV EIA 2.0 screening test, or 
a later sample from the same donor that was further tested in 
accordance with proposed Sec. 610.48(h)(2)(i) of this section using 
either an HCV EIA 3.0 screening test or a licensed supplemental test 
for HCV and the result is negative. Proposed Sec. 610.48(j)(2)(iii)(B) 
addresses the repeatedly reactive sample that was tested using an HCV 
EIA 2.0 screening test or a later sample from the donor that was 
further tested in accordance with proposed Sec. 610.48(h)(2)(ii) of 
this section using a HCV RIBA 3.0 and the result is negative. Proposed 
Sec. 610.48(j)(2)(iii)(C) addresses the repeatedly reactive sample that 
was tested using an HCV EIA 3.0 screening test or a later sample from 
the same donor that was further tested in accordance with proposed 
Sec. 610.48(h)(2)(iii) of this section using a licensed supplemental 
test for HCV and the result is negative) or; (5) under proposed 
Sec. 610.48(j)(2)(iv), if the donor's testing records meet the 
conditions specified in proposed Sec. 610.48(c)(3) (repeatedly reactive 
HCV EIA 3.0 screening test and indeterminate HCV RIBA 2.0 supplemental 
test) and further testing was performed in accordance with proposed 
Sec. 610.48(h)(2)(iv) of this section on a frozen sample or a fresh 
sample from the same donor using a licensed supplemental test for HCV 
and the result is negative.
    Under proposed Sec. 610.48(j)(3), prior collections subject to 
quarantine under proposed Sec. 610.48(f)(1) (as a result of the review 
of historical testing records and based on a single antigen screening 
test) would be released from quarantine only if such prior collections 
were not suspected as being ``window'' period donations. Such prior 
collections, if not exempt from quarantine under proposed 
Sec. 610.48(g)(3), would be released from quarantine if certain 
conditions are met as follows: (1) Under proposed Sec. 610.48(j)(3)(i), 
if the donor's testing records meet the conditions specified in 
proposed Sec. 610.48(d)(4) (repeatedly reactive HCV EIA 1.0 screening 
test with an S/CO value greater than or equal to 2.5) and further 
testing was performed in accordance with proposed Sec. 610.48(i)(1)(i) 
on a fresh sample, or frozen sample from the repeatedly reactive 
donation using a licensed supplemental test for HCV and the result is 
negative; or (2) under proposed Sec. 610.48(j)(3)(ii), if the donor's 
testing records meet the conditions specified in proposed Sec. 610.48 
(d)(1) (repeatedly reactive HCV EIA 1.0 screening test and repeatedly 
reactive HCV EIA 2.0 or 3.0 screening test) and further testing was 
performed in accordance with proposed Sec. 610.48(i)(2)(i) on a fresh 
sample, or frozen sample from the repeatedly reactive donation and the 
result of the appropriate supplemental test for HCV is negative; or (3) 
under proposed Sec. 610.48(j)(3)(iii), if the donor's testing records 
meet the conditions specified in

[[Page 69391]]

proposed Sec. 610.48 (d)(2) and further testing (in the case of a 
repeatedly reactive HCV EIA 1.0 and indeterminate HCV RIBA 2.0 
supplemental test) was performed in accordance with proposed 
Sec. 610.48 (i)(2)(ii) on a fresh sample, or frozen sample from the 
repeatedly reactive donation and the result when further tested using 
either an HCV EIA 3.0 screening test or a licensed supplemental test 
for HCV is negative; or (4) under proposed Sec. 610.48(j)(3)(iv), if 
the donor's testing records meet the conditions specified in proposed 
Sec. 610.48 (d)(3) (repeatedly reactive HCV EIA 1.0 with an S/CO less 
than 2.5) and further testing was performed in accordance with proposed 
Sec. 610.48(i)(2)(iii) on a fresh sample, or frozen sample from the 
repeatedly reactive donation and the result when further tested using a 
licensed multiantigen screening test for HCV or a licensed supplemental 
test for HCV is negative.
    FDA is proposing a conforming amendment to Sec. 610.46(d), which 
specifies requirements for release from quarantine for HIV 
``lookback,'' for consistency with the HCV ``lookback'' requirements by 
changing ``Whole Blood, blood components, Source Plasma and Source 
Leukocytes'' to ``blood and blood components.''

P. Proposed Sec. 610.48(k), Destruction or Labeling of Prior 
Collections Held in Quarantine

    The purpose of proposed Sec. 610.48(k) is to identify prior 
collections that must be destroyed or appropriately labeled, that is, 
those prior collections that are not exempt from quarantine under 
proposed Sec. 610.48(g) and do not meet the conditions for release from 
quarantine in accordance with proposed Sec. 610.48(j). Proposed 
Sec. 610.48(k) would require that blood establishments and consignees 
take appropriate action for prior collections subject to quarantine 
under proposed Sec. 610.48(a), (e), and (f). Blood establishments would 
be required to either destroy the quarantined prior collections or 
appropriately label the collections for in vitro use unless: (1) The 
prior collection was determined to be exempt from quarantine in 
accordance with proposed Sec. 610.48(g), or (2) the prior collection 
was subject to release from quarantine under proposed Sec. 610.48(j). 
FDA recognizes there may be some limited uses for quarantined prior 
collections which are not suitable for release from quarantine for the 
product's original intended use. Such prior collections should not be 
used for transfusion or for further manufacturing into injectable 
products. FDA recommends that these prior collections be destroyed as a 
general practice; however, in limited situations, release for research 
or manufacture into in-vitro diagnostic reagents may be acceptable. If 
released for these uses, prior collections should be relabeled 
consistent with Secs. 606.121 and 640.70. In addition, these prior 
collections must be relabeled as ``Biohazard'' with the cautionary 
statements as follows:
    Collected from a donor who subsequently tested reactive for anti-
HCV. An increased risk of transmission of hepatitis C is present.''; in 
addition, the label must contain one of the following cautionary 
statements, as appropriate: ``Caution: For Further Manufacturing Into 
In-Vitro Diagnostic Reagents For Which There Are No Alternative 
Sources.'' or ``For Laboratory Research Use Only.
    FDA is proposing a conforming amendment to Sec. 610.46, the HIV 
``lookback'' requirements, for consistency and to clarify the actions 
to be taken for prior collections subject to quarantine under 
Sec. 610.46(a). FDA is proposing to redesignate Sec. 610.46(e) as 
Sec. 610.46(f) and to add new Sec. 610.46(e) Destruction or labeling of 
prior collections held in quarantine, consistent with this proposal.

Q. Proposed Sec. 610.48(l)

    Proposed Sec. 610.48(l) specifies that actions taken under proposed 
Sec. 610.48 do not constitute a recall. This regulation is consistent 
with current Sec. 610.46(e) applicable to the HIV ``lookback'' 
requirements (as noted previously, FDA is proposing to redesignate 
paragraph (e) as paragraph (f)). While there are similarities between 
the product recall process and ``lookback,'' there are several 
important differences: (1) The recall procedures described in part 7 
(21 CFR part 7) are intended as a guideline while ``lookback'' would be 
a regulatory requirement; (2) additional steps are required in 
``lookback'' which are not ordinarily performed in a product recall; 
(3) because each ``lookback'' would be initiated due to similar 
circumstances, a health hazard evaluation and recall classification by 
the agency (see Sec. 7.41) is unnecessary; and (4) the products being 
quarantined may not be in violation of applicable laws (see Sec. 7.40). 
FDA recognizes that a ``lookback'' action does not mean that an 
establishment has erred or did not meet its obligations under the 
regulations and the law in assuring the safety of the blood supply. 
Failure to take appropriate action in accordance with the proposed 
``lookback'' regulations, however, would be a violation and FDA would 
take enforcement action, when appropriate, in such situations.

R. Proposed Sec. 610.49(a), Hepatitis C Virus (HCV) ``Lookback;'' 
Notification of Transfusion Recipients

    The purpose of proposed Sec. 610.49 is to identify the 
circumstances under which it is necessary to notify transfusion 
recipients; who is responsible for performing the notification; and the 
timeframes for completing the notification process. The notification 
process is intended to result in the notification of transfusion 
recipients who have received prior collections of blood and blood 
components from a donor later determined to be at increased risk of 
transmitting HCV infection because they are possible ``window period'' 
donations. Refer to the discussion in the description of proposed 
Sec. 610.48(c) for more information on ``window period'' donations. As 
previously discussed, there are two sets of circumstances which trigger 
``lookback'' activity. The notification of transfusion recipients would 
be performed as a result of: (1) The identification of a donor who 
returns to donate again and tests repeatedly reactive for evidence of 
HCV infection on a licensed multiantigen screening test (as specified 
in Sec. 610.48(a)) and further testing (performed as specified in 
proposed Sec. 610.48(b)) indicates an increased risk of transmitting 
HCV; or (2) the identification of a donor, as a result of the review of 
historical testing records (in accordance with proposed Sec. 610.48(c) 
or (d)), and further testing (as shown in historical records or as 
performed under proposed Sec. 610.48(h) or (i)) indicates an increased 
risk of transmitting HCV. Under the proposal, transfusion recipient 
notification need not be performed for prior collections of Source 
Plasma and Source Leukocytes, because they are intended for further 
manufacture and not for transfusion. Proposed Sec. 610.49(a), would 
require transfusion services to take appropriate actions, in accordance 
with Sec. 610.49(b) and (c), when a transfusion recipient has received 
blood or blood components, from a donor later determined to be at 
increased risk of transmitting HCV infection as follows: (1) The donor 
was identified in accordance with proposed Sec. 610.48(a) and the 
result of the licensed, supplemental test performed in accordance with 
proposed Sec. 610.48(b) is positive; or (2) the donor was identified in 
accordance with proposed Sec. 610.48(c)(1), and the result of the 
supplemental test identified in the review of records is positive; or 
(3) the

[[Page 69392]]

donor was identified in accordance with proposed Sec. 610.48(c)(2), and 
the result of the supplemental test identified in the review of records 
is indeterminate, unless either the historical testing records or 
further testing (in accordance with proposed Sec. 610.48(h)) show the 
indeterminate supplemental test result was obtained using a licensed 
supplemental test, and the initial test result was determined to be a 
false positive because any of the conditions for exemption from 
quarantine or release from quarantine have been met ; or (4) the donor 
was identified in accordance with proposed Sec. 610.48(c)(4) or (c)(5) 
as testing repeatedly reactive on a multiantigen screening test with no 
record of further testing and the result of the licensed, supplemental 
test performed, in accordance with proposed Sec. 610.48(h)(1)(i)(A), 
(h)(1)(i)(B), or (h)(1)(ii) is positive; or (5) the donor was 
identified in accordance with proposed Sec. 610.48(c)(4) or (c)(5) as 
having no record of further testing and no fresh or frozen sample is 
available for further testing, as specified in proposed 
Sec. 610.48(h)(1)(iii); or (6) the donor was identified in accordance 
with proposed Sec. 610.48(d)(1) unless the initial test result was 
determined to be a false positive because any of the conditions for 
exemption from quarantine (under proposed Sec. 610.48(g)(3)) or release 
from quarantine (under proposed Sec. 610.48(j)(3)) have been met, or 
the donor was further tested in accordance with Sec. 610.48(i)(2)(i) 
using an appropriately chosen supplemental test for HCV and the result 
is negative or indeterminate; or (7) the donor was identified in 
accordance with proposed Sec. 610.48(d)(2) and the result of the 
supplemental test performed using an HCV RIBA 2.0 or HCV RIBA 3.0 
supplemental test is positive as identified in the review of historical 
testing records; or (8) the donor was identified in accordance with 
proposed Sec. 610.48(d)(2), and the result of the supplemental test 
performed using HCV RIBA 2.0 is indeterminate, unless any of the 
conditions for exemption from quarantine (under proposed 
Sec. 610.48(g)(3)), or release from quarantine (under proposed 
Sec. 610.48(j)(3)) have been met, or the donor was further tested in 
accordance with proposed Sec. 610.48(i)(2)(ii) using a licensed 
supplemental test for HCV and the result is indeterminate; or (9) the 
donor was identified in the review of historical testing records in 
accordance with proposed Sec. 610.48(d)(3) (repeatedly reactive HCV EIA 
1.0 with an S/CO value less than 2.5) and the result of the licensed, 
supplemental test for HCV performed in accordance with proposed 
Sec. 610.48(i)(2)(iii) is positive; or (10) the donor was identified in 
the review of historical testing records in accordance with proposed 
Sec. 610.48(d)(4) (as testing repeatedly reactive on a single antigen 
screening test with a S/CO value equal to or greater than 2.5 for at 
least two of the three EIA tests, or the S/CO value can not be 
calculated, and with no record of further testing) and the result of 
the licensed, supplemental test for HCV performed in accordance with 
Sec. 610.48(i)(1) is positive; or (11) the donor was identified in the 
review of historical testing records, in accordance with 
Sec. 610.48(d)(4), and no record of further testing is available and no 
fresh or frozen sample is available for further testing, as specified 
in Sec. 610.48(i)(1)(ii).
    FDA is proposing conforming amendments to HIV ``lookback'' 
requirements of Sec. 610.47(a) for consistency with the HCV 
``lookback'' requirements of proposed Sec. 610.49(a). FDA is proposing 
to amend Sec. 610.47(a) to clarify that transfusion services shall 
notify recipients of prior collections of blood and blood components 
from a donor later determined to be at increased risk of transmitting 
HIV infection when tested for evidence of HIV infection and the result 
of the additional tests required in Sec. 610.46(b) are positive.

S. Proposed Sec. 610.49(b), Notification of Recipients of Prior 
Transfusion

    Proposed Sec. 610.49(b) describes the requirements for the process 
of notification of transfusion recipients. Under proposed 
Sec. 610.49(b), consistent with requirements for notification in the 
HIV ``lookback'' regulations in Sec. 610.47, the transfusion service 
would either notify the physician of record (i.e., the physician of 
record or physician who ordered the blood) and ask him or her to inform 
the recipient, or would notify the recipient directly. FDA recognizes 
that, under certain circumstances, the physician may have developed an 
ongoing relationship with the patient and may agree to take 
responsibility for notification and counseling. The transfusion service 
is ultimately responsible for ensuring that the notification takes 
place. The transfusion service might seek assistance in the 
notification process. For example, the transfusion service might 
determine that such notification and counseling would be best conducted 
by staff in another department in the hospital, who may be better 
trained and experienced in counseling patients. Under proposed 
Sec. 610.49(b) and under the proposed conforming amendment to 
Sec. 610.47(b), a transfusion service may elect to notify the 
transfusion recipient directly, without the assistance of the patient's 
physician of record. FDA specifically requests comment whether the 
transfusion service should be required to perform concurrent 
notification of the physician of record whenever the transfusion 
service notifies the transfusion recipient directly.
    Proposed Sec. 610.49(b) would require the transfusion service to 
make a minimum of three attempts to notify the transfusion recipient or 
the recipient's physician of record. The time period provided for 
completion of the recipient notification would be based on the date of 
donor testing and the date of receipt of the supplemental test result 
from the blood establishment. Recipient notification based on donor 
testing completed after the effective date of the regulation, as 
specified in the final rule resulting from this proposal, would be 
required to be completed within a maximum of 12 weeks of receipt of the 
results of the donor's supplemental test for HCV from the blood 
establishment. Recipient notification based on donor testing completed 
prior to the effective date of the regulation, as specified in the 
final rule resulting from this proposal (historical records of donor 
testing), would be required to be completed within 1 year of receipt of 
notification of test results from the blood establishment. FDA is 
proposing a longer period of time for completion of transfusion 
recipient notification based on donor testing completed prior to the 
effective date of the regulation because such notification would be 
made as a result of the review of historical testing records performed 
in accordance with proposed Sec. 610.48(c) and (d), and it is possible 
that a transfusion service could have a large number of notifications 
to complete. However, FDA believes that the transfusion recipient 
notification process should begin and be completed as soon as feasible 
because such a notification will not require a year to complete in all 
cases. FDA recognizes that many blood establishments may be performing 
such transfusion recipient notifications consistent with the 
recommendations of the June 1999 draft guidance. Therefore, FDA 
believes that if a blood establishment has a limited number of 
transfusion recipient notifications to perform as a result of this 
regulation, then the notifications could be completed in less than the 
1-year period that would be provided under this proposal. In addition, 
donors identified in accordance with proposed Sec. 610.48(c)(2) through 
(c)(5), and proposed Sec. 610.48(d)(1) through (d)(4) generally will be 
further tested by the

[[Page 69393]]

blood establishment in accordance with Sec. 610.48(h) and (i), 
respectively. In those instances, FDA would require that the 
notification of recipients based on such a licensed supplemental test, 
performed after the effective date of the regulation, be completed 
within 12 weeks of the date of receipt of the supplemental test result 
from the blood establishment.
    Under proposed Sec. 610.49(b), the transfusion service would be 
responsible for the basic explanation to the recipient, referral for 
counseling and further testing, and documentation of the notification 
or attempts to notify the physician of record or the recipient, under 
Sec. 606.160 of this chapter. Under this proposal, each establishment 
should have a well-designed system for notification, and would need to 
develop SOP's that describe each step in the notification system, as 
well as the required documentation. The SOP would address the need for 
documentation of person(s) contacted, by whom, when and whether the 
transfusion recipient was notified directly, or the physician of record 
agreed to notify the recipient, and the outcome of the notification 
efforts, including the reasons for inability to notify.
    FDA is requesting comment on the appropriateness of requiring a 
minimum of three attempts to notify affected transfusion recipients as 
proposed for HIV and HCV ``lookback.'' FDA is proposing to increase the 
record retention requirement to 10 years (proposed Sec. 606.160(d)) and 
to increase the length of time for which HIV and HCV ``lookback'' must 
be initiated, from a maximum of 5 years as currently required in 
Sec. 610.46(a) for HIV ``lookback'' (for HCV ``lookback'' in proposed 
Sec. 610.48(a)). In addition, FDA is proposing to require HCV 
``lookback'' based on the review of available historical testing 
records (proposed Sec. 610.48(c) and (d)) for those prior collections`` 
* * * dating back indefinitely for computerized electronic records and 
to January 1, 1988, for other readily retrievable records.'' FDA 
specifically requests comment on the minimum number of attempts which 
should be required to notify affected transfusion recipients identified 
in the records that are more than 5 years old and who, therefore, might 
be more difficult to locate. FDA also requests the submission of data 
which support a specific number of attempts to notify affected 
transfusion recipients.
    FDA is proposing conforming amendments to HIV ``lookback'' 
requirements of Sec. 610.47(b) for consistency with the HCV 
``lookback'' requirements of proposed Sec. 610.49(b). FDA is proposing 
to amend Sec. 610.47(b) to clarify that transfusion services have the 
option of either notifying the transfusion recipient directly or 
notifying the recipient's physician of record and asking him or her to 
notify the recipient and that notification (based on donor testing 
completed after the effective date of the regulation) must be completed 
within a maximum of 12 weeks.

T. Proposed Sec. 610.49(c), Notification of Legal Representative or 
Relative

    Proposed Sec. 610.49(c) would require the transfusion service or 
physician to notify a legal representative, designated in accordance 
with State law, if the transfusion recipient has been adjudged 
incompetent by a State court. In addition, if the transfusion recipient 
is competent, but State law permits a legal representative or relative 
to receive the information on the recipient's behalf, proposed 
Sec. 610.49(c) would require the transfusion service or physician to 
notify the recipient, or his or her legal representative or relative. 
If the transfusion recipient is a minor at the time of notification, 
the transfusion service would be required to notify the recipient's 
legal representative. Under proposed Sec. 610.49(c), reasons for 
notifying the recipient's relative or legal representative on his or 
her behalf would be documented, as required in the recordkeeping 
provisions of Sec. 606.160. Proposed Sec. 610.49(c) would not require 
notification efforts to continue if the recipient is deceased because, 
as previously discussed, direct percutaneous exposure to infectious 
blood, particularly in the setting of drug abuse, accounts for the 
majority of HCV infections acquired in the United States. Secondary 
transmission of HCV to sexual partners, care providers or others with 
close contact is very unlikely.
    FDA is proposing conforming amendments to HIV ``lookback'' 
requirements of Sec. 610.47(c) for consistency with the HCV 
``lookback'' requirements of proposed Sec. 610.49(c). FDA is proposing 
to amend Sec. 610.47(c) to clarify that transfusion service or 
physician would be required to notify the legal representative if the 
transfusion recipient is a minor at the time of notification and to 
document the result of the notification or the attempts to complete the 
notification.

U. Proposed Sec. 610.49(d), Reference Tables

    Proposed Sec. 610.49(d) includes four tables intended to assist in 
identifying the applicable paragraphs of proposed Secs. 610.48 and 
610.49 and the corresponding ''lookback'' actions. In particular, the 
requirements of proposed Secs. 610.48 and 610.49 that are based on the 
review of historical testing records require that many different 
testing sequences be addressed. These tables are intended to clarify 
the applicable sections and the corresponding steps of the ``lookback'' 
process that must be considered for a particular sequence of tests.
    Table 1 identifies applicable sections for the ``lookback'' process 
based on current donor testing, for donors identified in accordance 
with proposed Sec. 610.48(a). For example, a donor that tests 
repeatedly reactive for HCV upon returning to donate again, would be 
identified by the blood establishment in accordance with proposed 
Sec. 610.48(a). Table 1 of proposed Sec. 610.49 lists the subsequent 
``lookback'' actions that must be taken and the applicable regulations. 
Continuing with this example, in addition to other ``lookback'' 
actions, table 1 shows that such a donor would be further tested in 
accordance with proposed Sec. 610.48(b), and prior collections could be 
released from quarantine if the conditions of proposed 
Sec. 610.48(j)(1) were met.
    Tables 2, 3, and 4 of proposed Sec. 610.49 identify applicable 
sections for the ``lookback'' process based on the review of historical 
testing records. A different table applies based on the specific 
screening test that was performed. Table 2 identifies applicable 
sections based on the review of historical testing records for donors 
identified in accordance with proposed Sec. 610.48(c) as testing 
repeatedly reactive using an HCV EIA 3.0 screening test. Table 3 
identifies applicable sections based on the review of historical 
testing records for donors identified in accordance with proposed 
Sec. 610.48(c) as testing repeatedly reactive using an HCV EIA 2.0 
screening test. Table 4 of proposed Sec. 610.49 identifies applicable 
sections based on the review of historical testing records for donors 
identified in accordance with proposed Sec. 610.48(d) and tested using 
a single antigen screening test, HCV EIA 1.0.

IV. Analysis of Impacts and Initial Regulatory Flexibility Analysis

    FDA has examined the impacts of the proposed rule under Executive 
Order 12866, under the Regulatory Flexibility Act (5 U.S.C. 601-612), 
and under the Unfunded Mandates Reform Act (Public Law 104-4). 
Executive Order 12866 directs agencies to assess all costs and benefits 
of available regulatory alternatives and, when regulation is necessary, 
to select regulatory approaches that maximize net benefits (including 
potential economic,

[[Page 69394]]

environmental, public health and safety, and other advantages; 
distributive impacts; and equity). The Regulatory Flexibility Act 
requires agencies to analyze whether a rule may have a significant 
impact on a substantial number of small entities and, if it does, to 
analyze regulatory options that would minimize the impact. Section 
202(a) of the Unfunded Mandates Reform Act requires that agencies 
prepare a written statement of anticipated costs and benefits before 
proposing any rule that may result in an expenditure by State, local, 
and tribal governments, in the aggregate, or by the private sector, of 
$100 million in any one year (adjusted annually for inflation).
    The agency has determined that the proposed rule may be a 
significant action as defined by the Executive Order. The analysis 
below details FDA's estimate of the potential costs and benefits of the 
rule. As described in the analysis that follows, the rule is likely to 
have a significant economic effect on a substantial number of small 
entities. FDA has therefore prepared an Initial Regulatory Flexibility 
Analysis. The Unfunded Mandates Reform Act does not require FDA to 
prepare a statement of costs and benefits for the proposed rule, 
because the proposed rule is not expected to result in any 1-year 
expenditure that would exceed $100 million adjusted for inflation. The 
current inflation adjusted statutory threshold is about $110 million.

A. Economic Impact

    The purpose of the proposed rule is to help ensure the continued 
safety of the blood supply and to help ensure that information is 
provided to consignees and recipients of blood products in the event of 
a repeat donor's seroconversion to positivity for hepatitis C. The 
proposed action is considered necessary to interdict prior in-date 
collections at increased risk for transmitting HCV and to help assure 
that blood product recipients receive counseling and treatment if 
necessary, as effective therapies become available for hepatitis C. The 
proposed rule will further support public confidence in safety of the 
U.S. blood supply, recognizing priorities for the reduction of 
infectious disease risks to transfusion recipients. The agency further 
notes that the costs and benefits of the FDA and the Health Care 
Finance Administration (HCFA) rule are not additive, as the impacts 
considered in the HCFA rule are also accounted for in the FDA rule.
1. The Number and Type of Entities Affected
    The proposed rule will affect establishments that collect, process, 
and ship blood and blood components, and establishments that transfuse 
those products. The affected entities include commercial plasma 
centers, regional and community blood collection or donation centers, 
hospitals that operate blood collection centers, and facilities that 
transfuse blood products. The HCFA estimates that there are 
approximately 6,200 transfusing facilities. FDA's Office of Blood 
Research and Review (OBRR) has a record of 2,801 registered blood and 
plasma establishments.
    According to a 1992 survey (Ref. 3), U.S. blood establishments 
collect an annual total of 13,794,000 units of blood. Allogeneic 
donations (not directed for a specific recipient) accounted for 87.2 
percent (12,035,000 units). Approximately 79 percent of allogeneic 
donations are provided by repeat donors. (This percentage is based on 
American Red Cross estimates based on donations between January 1996 
and June 1997.) FDA's analysis of the HCV ''lookback'' rule focuses on 
allogeneic donations by repeat donors, and the subset of those donors 
expected to test repeatedly reactive in a screening test for evidence 
of HCV infection. As outlined in preceding sections of this document, 
the proposed rule includes a set of provisions for processes to be 
performed by blood establishments. In general terms, these provisions 
concern donor recordkeeping, record review, identification and 
quarantine of affected units for repeat reactive donors, notification 
of consignees of unpooled products concerning the HCV status of 
affected units, and further testing to confirm HCV positivity. The 
proposed rule also specifies requirements for blood product consignees 
that relate to quarantine of in-date unpooled products based on blood 
establishment notifications, and recipient notification when 
appropriate.
    Plasma centers will be affected by the proposed rule only to the 
extent that these establishments store and distribute unpooled units to 
consignees that also retain unpooled units in their inventories. FDA 
currently has little information about the volume of unpooled units 
retained by plasma centers that would be affected by this proposal. 
Because this information is essential for the estimation of economic 
impact, FDA requests detailed industry comment on current practices for 
recordkeeping and retention of unpooled units of plasma (including 
estimated numbers of unpooled units), both at collection centers and 
the facilities to which these units are subsequently shipped. For the 
purpose of this analysis, FDA has assumed that most units will be 
pooled prior to the initiation of any ``lookback'' activity and, 
therefore, that plasma establishments will be minimally affected by the 
proposed rule. Plasma establishments similarly will not be affected by 
the proposed requirements for review of historical testing records. 
FDA, therefore, assumes that the primary impact on plasma 
establishments will involve the review of the proposed regulation by 
each establishment to determine how current facility SOP's would be 
affected.
    With the exception of hospitals that both collect and transfuse 
blood products, most establishments affected by the rule will either 
act as a blood collection establishment or as a consignee (transfusion 
service), not as both. To distinguish the impact of the requirements 
for blood establishments and for consignees, the rule provisions 
affecting each type of entity will be treated separately in the 
analysis that follows. Table 1 of this document provides a summary of 
the estimated one-time versus the yearly costs for blood establishments 
and blood product consignees. The basis for these estimates are 
explained in sections IV.A.2 and IV.A.3 of this document.

     Table 1.--Summary of Estimated One-Time Yearly Costs for Blood
               Establishment and Blood Product Consignees
------------------------------------------------------------------------
   Affected
   Entities            One-Time Cost                 Yearly Cost
   (number)
------------------------------------------------------------------------
                      Blood Establishments (2,800)
------------------------------------------------------------------------
Hepatitis C         $2,875,040
 Virus (HCV)
 ``Lookback''
 Standard
 Operating
 Procedures
 (SOP's)
------------------------------------------------------------------------
Prospective                                      $4,558,442
 review
------------------------------------------------------------------------

[[Page 69395]]

 
Historical         $33,239,402
 review
------------------------------------------------------------------------
      Subtotal     $36,114,442                   $4,558,442
------------------------------------------------------------------------
                           Consignees (6,200)
------------------------------------------------------------------------
HCV                 $2,546,464
 ``Lookback''
 SOP's
------------------------------------------------------------------------
Prospective                                      $2,114,632
 review
------------------------------------------------------------------------
Historical         $50,106,540
 Review
------------------------------------------------------------------------
      Subtotal     $52,653,004                   $2,114,632
------------------------------------------------------------------------
      Total        $88,767,446                   $6,673,074
------------------------------------------------------------------------

2. Estimated Impact on Blood and Plasma Establishments
    Many of the provisions of the proposed rule will affect blood 
establishments. Each establishment will need to review the provisions 
of the rule in order to reconcile current facility practices for record 
review, sample quarantine, consignee notification and other related 
processes, and donor and blood product recordkeeping, with the 
requirements of the rule. FDA estimates the cost of performing such a 
one-time review and reconciliation of blood establishment SOP's to be 
approximately $1,027 per establishment, assuming that the review will 
require approximately 40 hours per facility and be performed by a staff 
medical technologist (Ref. 4). This yields a total one-time cost of 
$2,875,040.
    The proposed rule requires that blood establishments extend the 
retention period for required processing records for blood donors from 
5 to 10 years after the records of processing have been completed or 6 
months after the latest expiration date for the individual product, 
whichever is a later date. FDA estimates that this provision will cost 
approximately $3,110,240 per year, assuming that routine maintenance of 
donor files for the additional period of time will require 
approximately 40 hours of additional programming support time per 
facility per year, at a cost of $27.77 per hour of programmer time, 
based on 1997 Bureau of Labor Statistics estimates (40 x $27.77 x 
2,800).
    The proposed rule requires that blood and plasma establishments act 
within 3-calendar days of receiving the results of an FDA-licensed HCV 
test performed by a blood establishment or a CLIA-certified laboratory, 
with repeatedly reactive HCV results for a repeat blood donor. The 
establishment would retain the records for all in-date products and 
quarantine any in-date unpooled product that remain in inventory, 
quarantine all in-date unpooled prior collections, and notify 
consignees of the repeatedly reactive test result so that they may also 
quarantine any in-date unpooled prior collections. However, prior 
collections made more than 12 months prior to the last negative 
multiantigen HCV screening test are exempt from the required 
quarantine. Following the repeatedly reactive results of the initial 
screening tests, the blood establishment would be required to notify 
consignees of the result of the more specific supplemental HCV test 
within 45-calendar days after the day on which the donor tests 
repeatedly reactive in a screening test for evidence of HCV infection. 
If the result of further testing with a licensed supplemental test is 
negative, then the initial screening test result can be considered a 
``false positive'' and the in-date prior collections can be released 
from quarantine.
    FDA's estimated cost of these provisions is based on an estimated 
number of consignee notifications multiplied by the unit cost of each 
notification. First, the number of annual affected blood donations was 
calculated as the product of 12 million donations, an 80 percent repeat 
donor rate, and a 0.12 percent HCV positive donor rate. The resulting 
11,520 figure was then adjusted upward to 12,816 to reflect the 
difference found between the number of donors triggering ``lookback'' 
and the component notifications reported as interim results from a 
recent survey conducted by the Centers for Disease Control and 
Prevention (CDC) (Ref. 4). Assuming a cost of $113 per notification 
based on remarks from a representative of the nation's blood banks 
(Ref. 5) yields a consignee notification cost to blood banks of 
$1,448,202 per year (12,816 x $113). Thus, the prospective review in 
the proposed rule results in a yearly total cost of $4,558,442 
($3,110,240 + $1,448,202) for blood establishments. These costs may be 
slightly understated, because the CDC survey-based projections extend 
back only to 1988 records. Nevertheless, because the proposed rule 
requires pre-1988 searches only for ``computerized electronic 
records,'' this underestimate would be small.
    The proposed rule would also require a review of historical testing 
records of donations collected prior to the effective date of the rule. 
Blood establishments will be required to review records from prior 
collections to identify donors that tested repeatedly reactive in a 
screening test for evidence of HCV infection, for whom either: (1) 
There is no record of further testing, (2) the donor tested 
indeterminate on a supplemental test for HCV (with some exceptions), or 
(3) the donor tested positive on a supplemental test. The purpose of 
the record review is to identify prior collections from donors who are 
likely to be infected in order to notify recipients of such donations, 
and quarantine affected products that remain in inventory.
    Following their review of historical testing records, blood 
establishments would be required to do the following tasks. If the 
records show that the repeat donation, testing repeatedly reactive in a 
screening test for evidence of HCV infection, was followed by an 
appropriate licensed supplemental test with confirmed negative results, 
no further action is needed. If the repeat donation, testing repeatedly 
reactive in a screening test for evidence of HCV infection, was 
followed by a supplemental test with confirmed positive results, the 
blood establishment

[[Page 69396]]

would notify consignees of blood products from the donor's prior 
donations and quarantine affected products that remain in inventory. If 
the records show that the donation, testing repeatedly reactive in a 
screening test for evidence of HCV infection, was followed by a 
supplemental test with indeterminate result, or there is no record of 
supplemental testing to determine the donor's HCV status, the blood 
establishment would try to perform supplemental testing to clarify the 
status of prior collections. If a frozen sample from the donation 
testing repeatedly reactive in a screening test for evidence of HCV 
infection is available, that sample would be used in supplemental 
testing; otherwise, the blood establishment would attempt to contact 
the donor to obtain a fresh sample for testing. If further testing with 
fresh or frozen samples is accomplished, the blood establishment would 
be required to notify consignees of the test result. If no frozen 
sample is available and a fresh sample cannot be retrieved from the 
donor, the blood establishment would be required to notify consignees 
of the results of the repeatedly reactive screening test and the 
inability to clarify the donor's HCV status. Within 1 year of the 
effective date of the final rule, blood establishments would be 
required to perform the testing needed to clarify the status of prior 
collections. Blood establishments would be required to notify 
consignees of HCV positive test results within 45 days of completion of 
further testing performed as a result of the review of historical 
testing records. If no further testing could be performed, consignees 
would be notified within 1 year.
    FDA's estimate of the cost of performing the specified review of 
historical testing records is based on the CDC estimate of 294,154 
attempted notifications (188,448 during the period 1990 to mid-1992 and 
105,706 during the period from mid-1992 to 1998) and the estimated cost 
of $113 per notification (Ref. 5). This yields a one-time review cost 
of $33,239,402. Again, this estimate does not account for pre-1988 
computerized electronic records, but the agency believes there are 
relatively few.
    In total, as shown in table 1, FDA's estimates that blood 
collection agencies will incur ``lookback'' related one-time costs of 
about $36.1 million and annual costs of about $4.6 million. As the 
industry has already initiated this program, it is likely that the 
greater part of these costs have already been incurred.
3. Estimated Impact on Blood Product Consignees
    The proposed rule would require that transfusion services (i.e., 
consignees) notify transfusion recipients who received prior 
collections from a donor at increased risk of transmitting HCV. 
Recipient notification is included in both the prospective ``lookback'' 
and the review of historical testing records to identify prior 
collections. The transfusion service may notify the physician of record 
or notify the recipient directly. If the transfusion recipient is a 
minor or adjudged incompetent by a State court, the transfusion service 
or physician would be required to notify the recipient's legal 
representative. The proposed rule is expected to generate one-time 
costs and some additional annual costs for blood product consignees. 
One-time costs include the development of facility SOP's for recipient 
notification. FDA assumes that these tasks will involve the review of 
current SOP's (e.g., for HIV ``lookback'') and the adaptation or 
modification of current procedures to address the provisions of this 
rule and estimates that they will require an average of 16 hours per 
facility for facilities that act as consignees. The review would be 
performed by a staff medical technologist at an estimated cost of 
$25.67 per hour. Thus, FDA estimates the total one-time cost for the 
6,200 transfusing facilities to be $2,546,464.
    For notifications resulting from prospective donor testing and 
required quarantine, the required notification effort would include a 
minimum of three attempts to notify the transfusion recipient and would 
be completed within a maximum of 12 weeks of receipt from the blood 
establishment of the results of the donor's supplemental test for HCV. 
The agency's estimated cost of compliance with provisions concerning 
the prospective review and recipient notification is based on the 
previously described estimate of 11,520 annual affected donations. This 
figure was adjusted to 12,816 to reflect the CDC survey finding that 
the number of components sent to transfusion facilities exceeded the 
number of donors triggering ``lookback'' at blood centers by 11.2 
percent. The cost per attempted notification is estimated at $165 which 
reflects the average cost quoted by a third party contractor for 
matching, notifying, testing, counciling, and documenting ``lookback'' 
efforts for over 100 hospitals (Ref. 6). Although the proposed rule 
does not specifically require hospitals to perform testing and 
counciling services, many do. These assumptions yield an annual cost of 
$2,114,632 (12,816 x $165) for blood consignees to conduct prospective 
``lookback'' activities.
    Notifications resulting from the review of historical testing 
records and the identification of prior collections are to be completed 
by the transfusion service within 1 year of receipt of notification 
from the blood establishment. The recipient notification provided by 
the transfusion service would include a basic explanation to the 
recipient, referral for counseling and further testing and 
documentation of the notification or attempts to notify the physician 
of record or recipient. The estimated one-time cost of recipient 
notification associated with the review of historical testing records 
is $50,106,540. This is based on the CDC estimate of about 303,676 
recipients identified for notification (188,448 from 1990 to mid-1992 
and 115,228 from 1990 to mid-1992), and the average cost of $165 of 
staff time per component for recipient notification. Thus, FDA 
estimates the total one-time cost to blood transfusion facilities to be 
$52,653,004 ($2,546,464 + $50,106,540) for conducting retrospective 
``lookback''.
    The cost of targeted HCV ``lookback'' notification in the United 
States is expected to compare favorably with the experiences reported 
in earlier efforts, e.g., in Canada (Ref. 7), which were likely based 
on less automated approaches to recordkeeping. Table 2 of this document 
shows the cost of the HCV ``lookback'' per recipient notified, using 
CDC data to project various outcomes of the ``lookback'' effort. As 
shown in table 2, the assumption that a total of 258,551 transfusion 
recipients will be identified for notification through the historical 
``lookback'' effort translates to an estimated one-time cost of about 
$642 per recipient identified. CDC further estimates that approximately 
57,885 will still be living and notified through the retrospective 
review. This estimate implies a one-time cost of $1,440 per notified 
living recipient.

[[Page 69397]]



          Table 2.--Estimated Cost Per Recipient Notification
------------------------------------------------------------------------
                        Cost of           Cost Per          Cost Per
                    ``Lookback'' and      Recipient         Recipient
                    Notification\1\      Transfused         Notified
------------------------------------------------------------------------
Prospective        $6,673,074\2\      $658              $1,541
Historial          $83,345,942        $642              $1,440
------------------------------------------------------------------------
\1\ Excludes cost of developing SOP's.
\2\ Annual cost.

B. Benefits of the Proposed Rule

    The proposed rule is intended to help ensure the continued safety 
and adequacy of the national blood supply. Threats to the safety of the 
blood supply and the importance of a timely regulatory response to 
assure public safety have been the focus of numerous review efforts in 
recent years, by the U.S. House of Representatives Committee on 
Government Reform and Oversight, Subcommittee on Human Resources and 
Intergovernment Relations, the General Accounting Office, IOM, and 
private organizations including the American Liver Foundation and the 
DHHS Advisory Committee on Blood Safety and Availability. The proposed 
``lookback'' effort provides benefits both at the individual level of 
blood recipients and at a societal level, in terms of both the safety 
and continued adequacy of the national blood supply. The discussion 
that follows first addresses individual level benefits and then 
considers societal benefits.
1. Individual Benefits of HCV ``lookback''
    Over the past several years, the improved accuracy of HCV testing, 
the increased understanding of hepatitis C outcomes, the value of 
counseling against risk behaviors that worsen outcomes, and the 
advances in treatment of HCV have collectively created a medical and 
ethical imperative to inform identified transfusion recipients of their 
HCV risk. Prior to the widespread use of HCV screening of blood donors, 
transfusion was one of the most common modes of transmission. Although 
patients with chronic hepatitis C may remain asymptomatic for a number 
of years, the consequences of their disease are extremely serious. For 
example, CDC population-based studies indicate that 40 percent of 
chronic liver disease is HCV-related, resulting in an estimated 8,000 
to 10,000 deaths each year (Ref. 8). Current CDC estimates of medical 
and work-loss costs of all HCV-related acute and chronic liver disease 
(including cases resulting from blood transfusion) are in excess of 
$600 million annually, and HCV-associated end-stage liver disease is 
the most frequent indication for liver transplantation among adults. 
The cost of liver transplantation is estimated to be approximately 
$200,000 in the first year and $20,000 per year for subsequent years; 
and the cost of treatment for hepatocellular carcinoma, another 
sequelae of chronic liver disease, is estimated to be $10,000 per year 
(Ref. 9).
    Timely notification of HCV infection benefits the infected blood 
recipient in several important ways. First, although factors predicting 
severity of liver disease due to HCV have not been well-defined, recent 
data indicate that increased alcohol intake is associated with more 
severe liver disease. According to CDC, even moderate amounts of 
alcohol in patients with chronic hepatitis C might enhance liver 
disease. Consequently, an HCV-infected patient identified by the 
proposed ``lookback'' program could minimize liver damage associated 
with alcohol consumption by restricting his or her intake.
    Next, while other percutaneous exposures currently represent the 
most common means of infection, some case-control studies have also 
reported a positive association with sexual contact with a person with 
a history of hepatitis and acquiring hepatitis C. In fact, 15 to 20 
percent of the acute hepatitis C patients reported to CDC's sentinel 
counties surveillance system have a history of sexual exposure in the 
absence of other risk factors. Infected patients identified through the 
proposed ``lookback'' procedures could take steps to protect sexual 
partners from the risk of infection.
    Next, it is important to note that identified infected patients 
would benefit from treatment with available therapies. Studies of 
patient characteristics and responsiveness to therapy indicate that 
best results are achieved if treatment is initiated earlier in the 
disease, when patients are younger and have not yet developed cirrhosis 
(Ref. 10). For example, Bennett et al. estimated the cost effectiveness 
of a single course (6 months) of treatment with alfa interferon and 
found that patients at age 20 experience an average of 3.1 years of 
life gained at $500 per year of life extended (YLE); 30-year-old 
patients have an average gain of 1.9 years of life, at $7,100/YLE; 
patients starting treatment at age 50 have 6 months of life gained at 
$7,100/YLE; and 70-year-old patients gain an average of 22 days at 
$62,000/YLE (Ref. 11).
    Next, care providers for the identified infected patient would be 
aware of the infection and could use additional precautions to avoid 
the risk of exposure to blood or wounds when providing care to the 
patient. Finally, identified infected patients would be informed that 
they must not donate blood.
    Currently, the primary treatment for chronic hepatitis C is alfa 
interferon therapy (Ref. 12). On average, of those patients who undergo 
interferon treatment, a reported 10 to 20 percent show a sustained 
response after 6 months of therapy, and 20 to 30 percent a sustained 
response if therapy is continued for 12 months. Although alfa 
interferon produces a wide array of adverse side effects (Ref. 13), and 
some patients experience a relapse of HCV infection despite therapy, 
the benefits for patients identified for treatment through HCV 
``lookback'' are likely to continue to increase as improved therapies 
are developed. In particular, combination therapy using alfa interferon 
plus ribavirin has been reported to result in an improved outcome (Ref. 
13).
    In addition to the ``lookback'' costs discussed previously, the 
overall cost-effectiveness of the proposed regulation will vary with 
the cost and effectiveness (i.e., cure rate) of therapy for hepatitis 
C, and the cost of treatment for chronic liver disease and its sequelae 
in the absence of, or with failure of treatment for hepatitis C. A 
single course of alfa interferon therapy has been estimated to cost 
$2,300 (Ref. 9), but hepatitis C therapy is a rapidly changing area of 
clinical practice and the cost-effectiveness of treatment can shift 
dramatically with the introduction of new drugs and the age 
distribution and the comorbidities of the population receiving 
treatment. An illustrative example, however, can demonstrate the 
potential benefits of the increased therapies that might result from 
this

[[Page 69398]]

regulation. Although FDA cannot precisely determine the number of HCV 
positive individuals that would respond to the notification and seek 
medical consultation, a projection derived largely from interim 
findings of the CDC survey indicates that retrospective notification 
activities might identify about 3,764 cases of previously unidentified 
chronic HCV. This projection assumes that about 22.4 percent of 258,551 
potential recipients are notified, about 13 percent of those notified 
test positive for HCV, 66.7 percent of the HCV cases are not currently 
known, and 75 percent of the HCV cases are chronic. Kim et al. (Ref. 9) 
found that, on average, patients with chronic HCV gain 0.25 discounted 
(3 percent) quality adjusted life-years (QALY's) from 6 months of 
interferon- 2b treatment. (The authors do not provide estimates for any 
other discount rates.) On this basis, the above assumptions imply that 
retrospective ``lookback'' would gain a total of 941 QALY's, at a cost 
of about $88,573 per QALY.
    There is no generally accepted means of valuing life-years saved, 
although a number of empirical studies indicate a societal willingness-
to-pay of from $1.6 million to $11.6 million to avoid a statistical 
death. Assuming a mid-range estimate of $5 million and annualizing over 
a 35-year period at 3 percent yields an annual value of $233,000. The 
above assumptions imply that providing 6 months of interferon- 2b 
therapy to an additional 3,764 HCV-positive individuals could produce 
societal willingness-to-pay benefits of $219 million. The additional 
discounted (3 percent) incremental cost of providing such therapy was 
estimated by Kim et al. to be about $1,000 per patient, which implies 
an additional treatment cost of only $3,764,000 (3,764 patients x 
$1,000). Thus, by this measure, the individual benefits of 
retrospective HCV ``lookback'' easily exceed their incremental costs.
    The benefits of the prospective ``lookback'' provisions can be 
similarly analyzed. Based on the CDC interim findings, FDA assumed that 
prospective ``lookback'' notifications would be initiated for 10,894 
transfused recipients, of which 48 percent would be successful, 5.4 
percent of those who are notified would test positive for HCV, 66.7 
percent would be previously unknown, and 75 percent chronic. Thus, 123 
patients could potentially gain 0.25 QALY's per year at a cost of 
roughly $217,011 per QALY. According to the monetization values 
described above, these health gains could generate annual benefits of 
$7.2 million, or roughly the level of the prospective ``lookback'' 
costs.
    The agency recognizes the substantial uncertainty that surrounds 
such estimates. For example, medical cost-effectiveness studies 
sometimes assume a maximum societal value of about $50,000 per QALY. 
This modification would imply one-time retrospective ``lookback'' 
benefits of about $47 million and annual prospective ``lookback'' 
benefits of about $1.5 million, which would cover over half of the 
estimated initial costs of compliance. In addition, the figures assume 
that the distribution of recipient ages would reasonably match those of 
the Kim et al. study. Other studies of HCV treatment outcomes may 
project differently. FDA seeks public comment on the above assumptions 
and estimates.
2. Societal Benefits of HCV ``lookback''
    In addition to the direct benefits of medical treatment, the 
proposed ``lookback'' program will help to boost confidence and trust 
in the national blood supply. Thus, HCV ``lookback'' will generate 
societal benefits that are incremental to the health benefits discussed 
above. Recent public reviews of blood supply issues have recognized the 
importance of assuring both safety and the perception of safety. For 
example, reviews suggest that the public trust in the blood supply 
system was severely shaken by the transmission of HIV by blood 
products. This effect was exacerbated by the perceived failure of blood 
collection centers, public health agencies, and health care providers 
to take timely action to prevent or minimize patient risk. The failure 
to institute an HIV ``lookback'' program at an early date resulted in a 
number of cases in which transfusion recipients were unaware of their 
infection, failed to seek treatment and subsequently infected others 
(Refs. 13 and 14).
    Now that information is available to identify and to offer 
counseling and treatment options for those confirmed HCV-positive, FDA 
believes that the public trust demands the timely communication of 
relevant risk information. Although the agency cannot accurately assess 
the dollar value of this public trust or the potential impact of its 
loss, the following discussion, considers the cost of unfavorable 
shifts in public perception to be a potential indicator of the value of 
stabilizing public trust in the U.S. blood system. The purpose of the 
discussion is to provide an order-of-magnitude value assessment to 
which the estimated costs of HCV ``lookback'' can be compared.
    Potential indicator of yearly cost: Changes in the blood donation 
patterns. The impact of the AIDS epidemic on the perceived safety of 
the nation's blood supply is believed to have contributed to the 
reduction in volunteer blood donations and to the dramatic increase in 
autologous and directed blood donation in subsequent years. The IOM 
discussion of bioethical issues in risk communication regarding the 
blood supply describes blood services as special because ``Trust is 
perhaps uniquely important. You know pretty fast if you have lost the 
public trust because people stop showing up to donate'' (Ref. 17). This 
comment suggests two measures of the loss of public trust in the blood 
supply in the wake of the HIV/AIDS transfusions of the 1980's: The 
reduction in the volume of allogeneic blood donations and the 
substantial increase in the volume of autologous blood collections. 
These shifts have associated opportunity costs and inefficiency costs. 
Part of the observed changes in blood donation reflect tighter donor 
screening and more efficient use of the patient's own blood in 
scheduled surgery. But some of the shift is believed to reflect a 
distrust of the blood supply not warranted based on objective measures 
of disease risk. FDA reviewed the extent of the blood donation decline 
that might be attributable to AIDS-related public mistrust and asked 
whether a similar round of impacts might result if risk communication 
about known HCV exposures were perceived as inadequate by the general 
public.
    CDC estimates that the number of donations per donor has dropped 
from five as recently as 1992 to 1993, to two donations per donor in 
the period 1996 to 1998. This trend was already apparent in the survey 
findings of Wallace et al. published in 1995. Their survey compared 
blood collections in 1989 with collections in 1992, and found that 
904,000 fewer allogeneic units and 462,000 more autologous units of 
blood were collected in 1992 compared with 1989. At an estimated 
average price of $103 per unit\1\, the reduction in (allogeneic) 
donations represents an annual loss to the nation's blood supply valued 
at $93.11 million. If the allogeneic donations yielded more than one 
product per unit donation, the loss of potential supply would be 
greater.
---------------------------------------------------------------------------

    \1\ The estimates of $103 per allogeneic unit and $137 per 
autologous unit represent midpoint values in the range of blood 
costs reported by S. L. Lee in ``Patients' Willingness to pay for 
Autologous Blood Donation'' in Risk in Perspective, Harvard Center 
for Risk Analysis, vol. 6, No. 6, June 1988.

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

[[Page 69399]]

    Autologous blood collection presents less risk of infectious 
disease, but it is not generally considered to be cost-effective, since 
much of the collected product is ultimately discarded because the 
patient does not require it. Of the estimated 1,117,000 autologous 
units collected in 1992, a total of 546,000 was reported as discarded. 
At an estimated average cost of $137 per unit, this represents an 
annual loss valued at $74.80 million. These discarded autologous units 
represent a real cost incurred by either the hospital or other blood 
establishment (if unrecoverable), by the third-party payer, or by the 
patient for a product that provided no therapeutic value. The most 
recent data suggest that the volume of unnecessary autologous 
collections is starting to decline, with clinical practice changes and 
regained public trust in the blood supply. Although the shifting 
patterns of blood collections may largely reflect appropriate responses 
to actual blood safety risks, if even a fraction of the shifts result 
from misperceptions, due to perceived failures in government and 
industry risk communication, then avoidable opportunity and 
inefficiency costs will be incurred.
    FDA cannot assume that the failure to require notification of known 
exposures to hepatitis C among transfusion recipients would produce a 
similar second round of blood supply shifts and costs. However, 
hepatitis C has been characterized in the media, which influences 
public perception, as being as lethal as AIDS (Ref. 18) and its 
prevalence is much greater. If timely communication and support for 
patients, after inadvertent exposure to hepatitis C, were to eliminate 
as little as 15 percent of the yearly costs associated with the supply 
shifts described previously, this annual saving of over $25 million 
would exceed the $19 million in total annualized compliance costs 
estimated to be imposed by this regulation (calculated over 10 years at 
7 percent).
3. Alternatives Considered for HCV ``Lookback''
    FDA finds that the targeted ``lookback'' approach proposed is the 
most effective of several alternatives when evaluated in terms of 
ethical, cost, and effectiveness criteria. The following provides a 
discussion of the alternatives that have been considered.
    a. Alternative: Publication of FDA guidance but no regulatory 
requirement for ``lookback''. One alternative to regulation involves 
FDA taking no further action, as the agency has already issued industry 
guidance concerning HCV ``lookback''. The principle advantage of this 
approach would be the elimination of FDA expenses related to issuing 
and later enforcing the rule. However, although the ``lookback'' 
process described in the guidance is much the same as that required 
under the proposed rule, the approach would be less effective in 
achieving the desired benefits. Because FDA would only recommend a 
process and timeframe, but have no basis for enforcing it, some in 
industry may elect a more extended timeframe for performing the 
``lookback'' based on the review of historical testing records in order 
to spread the costs of this effort. Such delay, however, would increase 
each recipient's risk of serious disease complications and speed the 
spread of infection.
    For blood establishments, a potential cost of such delay would be 
the risk of litigation by blood recipients who discover through other 
means that they have contracted hepatitis C through transfusion. The 
risk of litigation, however, appears relatively small. Blood-product 
related injuries have been removed from the scope of strict liability 
law by blood shield laws in 47 of the 51 jurisdictions in this country. 
Although these laws may protect society's interest in assuring an 
adequate blood supply by shielding providers and manufacturers from 
liability claims in instances where due care is taken, they have also 
made it difficult and often impossible for individuals to obtain 
compensation for infections acquired from blood or blood products. A 
review of transfusion associated AIDS litigation for the period 1984 
through 1993 (Ref. 20) reports only a handful of cases based on failure 
of a blood establishment to perform ``lookback'' and none were reported 
won by a plaintiff on this basis. The adoption of an approach involving 
agency informal action based on the expectation of industry self-
regulation to solve problems has been strongly criticized in the IOM 
review as inadequate to protect the public in the context of HIV/AIDS. 
FDA believes this view is similiarly applicable to HCV.
    b. Alternative: Use of general ``lookback.''. An alternative to 
targeted ``lookback'' is an approach referred to as ``general 
lookback.'' This approach would be implemented through the general 
broadcast and other public media and regional medical organizations. 
The program would be aimed at all patients who received blood before 
the onset of screening, with the recommendation that they be tested for 
evidence of infection. Physicians participate in the program by 
recommending that previously transfused patients be tested for HCV. The 
program often includes a letter campaign to all previously transfused 
patients (regardless of the HCV status of the blood donors) from 
hospitals and other blood consignees who performed the transfusion 
service.
    The cost and ultimate effectiveness of general ``lookback'' would 
vary depending on the program structure. All of the general 
``lookback'' approaches involve reduced costs for blood collection 
centers, because the identification of infected donors would no longer 
be required. Nevertheless, if the general ``lookback'' involves a 
consignee letter campaign, the record review needed to identify current 
addresses for all transfusion recipients could be as great or greater 
than that required to identify only those recipients of blood products 
who are at higher risk of HCV.
    A recent Canadian effort involving general letter ``lookback'' is 
estimated to have cost $1,654 per identified and confirmed positive 
recipient ($2,123 including HCV testing) (Ref. 7). Another Canadian 
hospital had completed a general letter ``lookback'' for HCV when the 
Canadian Red Cross Society began targeted ``lookback'' in 1995. By 
April of 1998, at least 13 new seropositive recipients had been 
identified by targeted ``lookback'' who were missed by general 
``lookback.'' As a result, targeted ``lookback'' raised the number of 
HCV-positive recipients tested at that hospital by at least 9 percent 
over general ``lookback.''
    A general approach without letter notification can be less costly. 
A 1990 electronic media program in Cincinnati, for example, was 
estimated to have cost the blood center only $13,370, or $209 per 
identified positive recipient; although the authors note that ``costs 
to the notified recipients may far exceed those of the Center'' (Ref. 
19). Despite the vigorous public information campaign, less than 5 
percent of these recipients sought testing (Ref. 24). The CDC also is 
undertaking a program of general ``lookback'' media activities, but 
evidence of effectiveness is not yet available.
    At this time, FDA believes that although general ``lookback'' may 
be less costly, it is unlikely to communicate the relevant risk message 
to the majority of affected transfusion recipients. The effectiveness 
of a general ``lookback'' program requires that patients: (1) Be 
reached by the program, (2) be aware of the transfusion episode, and 
(3) seek testing even though the average risk per recipient is small. 
Experience suggests that a substantial share of patients and families 
are not

[[Page 69400]]

aware of earlier transfusions. A review of general ``lookback'' efforts 
in Canada, for example, found that 25 to 32 percent of pediatric 
patients and their families were unaware of an earlier transfusion. FDA 
agrees that general ``lookback'' activities can be important, 
particularly by reaching the population at risk due to parenteral drug 
use or other risk behaviors not involving blood transfusion. General 
``lookback'' activities can also reinforce the effectiveness of 
targeted ``lookback.'' The agency believes, however, that by itself, 
general ``lookback'' does not adequately inform all affected recipients 
of blood transfusions.
    c. Proposed: Use of targeted ``lookback.'' The ``lookback'' 
provisions of the proposed rule can be characterized as a ``targeted 
lookback'' program, meaning that the notification of infection risk is 
limited to or targeted at individuals identified as recipients of blood 
from donors subsequently found to be infected with HCV. Targeted 
``lookback'' requires that the transfusion service be aware that the 
donor subsequently tested positive, donor and product disposition 
records be available to link blood components with the identified 
donors, and the physician or transfusion service know the recipient's 
current whereabouts. Blood consignees would locate recipient records 
for all transfused units from an affected donor, and have current 
recipient or physician address information available so that 
notifications can be delivered. Ideally, the recipient will still be 
alive and be able to receive testing and treatment, if appropriate.
    Recent experiences among Canadian facilities implementing HCV 
``lookback'' suggest that the effectiveness of targeted ``lookback'' 
may vary, depending on the extent to which these conditions for success 
hold true within a community. For example, a Canadian Red Cross Center 
in Toronto reported that although able to identify 5,301 affected 
components, trace 3,209 of those to hospitals, obtain responses for 
2,807 (87 percent) of the units, and identify 2,437 as having been 
transfused, the establishment found that 45 percent of the transfused 
patients had already died. Of those remaining, only 184 patients (8 
percent of the transfused) were finally tested as a result of the 
``lookback'' effort, although as many as 68 percent of those tested 
were found to be HCV positive (Ref. 21).
    Despite the difficulties of implementing targeted ``lookback,'' FDA 
concludes that it remains a valuable means of reaching patients at high 
risk for HCV. As noted previously, a comparison of Canadian efforts in 
targeted ``lookback'' versus general ``lookback'' through physician and 
public education found that a large number of targeted patients and 
families were unaware of the transfusion episode. These recipients 
would not have been reached through the general ``lookback'' effort 
(Ref. 7). Similar experiences have occurred with HIV ``lookback'' 
efforts (Ref. 22).

C. Small Business Impact

    Because of the lack of information to characterize the relevant 
volumes of affected blood and plasma products, the impact on those 
establishments and consignees that might qualify as small entities is 
uncertain. The FDA has therefore prepared an Initial Regulatory 
Flexibility Analysis. The blood establishments and blood product 
consignees affected by the proposed rule are included under the major 
SIC (standard industrialization classification) group 80 for providers 
of Health Services. According to Section 601 of the Regulatory 
Flexibility Act of 1980, the term ``small entity'' encompasses the 
terms ``small business,'' ``small organization'' and ``small 
governmental jurisdiction.'' According to the Small Business 
Administration (SBA), a small business within the blood industry is an 
enterprise with less than $5 million in annual receipts. A small 
organization is a not-for-profit enterprise which is independently 
owned and operated and is not dominant in its field. A ``small 
governmental jurisdiction'' generally means governments of cities, 
counties, towns, townships, villages, school districts, or special 
districts, with a population of less than 50,000.
    The FDA registry of blood establishments does not provide an 
indication of the size of the registered entities. Although uncertain, 
it is likely that some smaller facilities may experience significant 
costs as a result of compliance with the proposed rule. According to 
the 1996 directory of the American Association of Blood Banks (AABB), 
only 34 regional and community blood centers have annual revenues of 
less than $5 million and each collect no more than 30,000 donations per 
year. Based on their survey of the blood industry in 1992, Wallace et 
al. (Ref. 3) estimate an annual total of 12,035,000 units of allogeneic 
blood were collected by blood establishments. Each small blood center 
would therefore account for approximately 0.2 percent (30,000/
12,035,000) of all collections. Assuming that the one-time and annual 
costs of HCV ``lookback'' for blood collection facilities (see table 1 
of section IV of this document) will be proportionate to the volume of 
collections, this implies that the small centers would each experience 
a one-time cost of approximately $72,229 ($36,114,442 x 0.002) and 
yearly costs of approximately $9,117 ($4,558,442 x 0.002). Based on an 
estimated average price of $103 per allogeneic unit (see footnote 1) 
this one-time cost would represent approximately 2 percent ($72,229/
($103 x 30,000)) of annual average revenues. The yearly costs of on-
going prospective ``lookback'' would represent approximately 0.3 
percent of average annual revenues ($9,117/($103 x 30,000)).
    Hospitals are expected to be the primary entity affected by the 
proposed requirements for transfusion services, but the extent of the 
small business impact is uncertain. Although the details of transfusion 
activities at hospitals are not available, FDA examined other data to 
develop a preliminary assessment of small business impact. The size of 
U.S. hospitals varies substantially. The 1998 American Hospital 
Association (AHA) survey data indicate a total of 5,134 U.S. registered 
community hospitals grouped into eight bed size categories. The average 
annual revenues for facilities in these bed size categories range from 
approximately $5.5 million to $513 million. However, since many 
hospitals are not-for-profit or are operated by state and local 
governments, the SBA annual receipts criteria for small businesses 
would not apply to these facilities. Of the 5,134 U.S. community 
hospitals included in the AHA report 1,330 are under the control of 
State and local government, 3,045 are nonprofit institutions and the 
remaining 759 are reported to be investor-owned.
    The number of hospitals that would meet at least one of the various 
SBA definitions for small entities is uncertain. According to the AHA 
statistics for 1998, the smallest reported hospital size category 
includes 262 hospitals with 6 to 24 beds, and total gross revenues of 
$1.43 billion, yielding average revenues of $5.46 million. FDA assumes 
that the 11 facilities reported to be investor-owned within this bed 
size category could qualify as small entities. Although it is possible 
that all nonprofit hospitals may qualify as small entities, it appears 
that a number of facilities might be excluded from that definition 
because they are reported to be hospitals in a system. According to the 
AHA survey definition, ``hospitals in a system'' refer to those 
``hospitals belonging to a corporate body that owns and/or manages 
health provider facilities or health-related subsidiaries;

[[Page 69401]]

the system may also own non-health-related facilities'' (Ref. 23). The 
AHA currently has record of 1,592 hospitals that are non-Federal and 
nonprofit (including State and local government controlled) that are 
hospitals in a system. If these facilities were excluded, FDA estimates 
that 2,783 (1,330 State and local + 3,045 nonprofit - 1,592 in-a-
system) non-Federal, nonprofit hospitals may qualify as small entities. 
Thus, a total of 2,794 (2,783 + 11) hospitals might qualify as small 
entities.
    The agency does not know how many of the estimated affected 
transfusion recipients received their transfusion as part of care 
provided at a hospital qualifying as a ``small entity.'' The following 
analysis of potential impact by size of hospital suggests that, 
regardless of hospital size, the cost impact may be limited if the 
number of affected transfusion recipients is proportionate to the 
number of inpatient surgeries performed by hospitals in different size 
categories. Table 3 of this document estimates the percentage of all 
inpatient hospital surgeries, based on the number of inpatient 
surgeries reported to AHA as performed by hospitals in different bed 
size categories. This percentage is used to estimate a share of the 
total 303,676 retrospective recipient notification activities initiated 
by hospitals in each category. The number of transfusion recipients to 
be contacted per hospital within a bed size category is based on the 
total estimated recipients per bed size category divided by the number 
of hospitals reported for each category. These estimates are presented 
in the right-most column of table 3. (Note that estimated values are 
rounded).

  Table 3.--Estimated Number of Affected Blood Recipients Per Hospital, Based on Estimated Number of Facilities
            and Distribution of Important Surgeries By Hospital Size Category (Retrospective Review)
----------------------------------------------------------------------------------------------------------------
                               Non-Federal        Estimated Percent    Estimated Share of   Estimated Recipients
    Bed Size Category           Hospitals        Inpatient Surgeries       Recipients           per Hospital
----------------------------------------------------------------------------------------------------------------
6 to 24                          262                     0.21                627                     2
25 to 49                         906                     2.02              6,121                     7
50 to 99                       1,128                     6.03             18,315                    16
----------------------------------------------------------------------------------------------------------------

    Table 4 presents estimates of the cost per hospital, which are 
derived from estimates of the number of transfusion recipients per 
hospital (as shown in table 3) and the estimated notification cost of 
$165 per recipient. To provide additional perspective on relative 
impact, table 4 includes the notification cost shown as a percentage of 
average annual gross revenues per hospital. The notification cost is 
estimated to be approximately 0.01 percent of the average annual gross 
revenues for every size category.

Table 4.--Estimated Notification Cost as a Percent of Gross Annual Revenue, Based on Estimates of Average Annual
                                                Hospital Revenue
----------------------------------------------------------------------------------------------------------------
                                                  Cost per Hospital                         Notification Cost as
               Bed Size Category                  for Retrospective   Gross Annual Revenue    Percent of Gross
                                                    Notification          per Hospital         Annual Revenue
----------------------------------------------------------------------------------------------------------------
6 to 24                                               $395                    $5.459 million         0.01 percent
25 to 49                                            $1,115                   $12.606 million         0.01 percent
50 to 99                                            $2,679                   $27.711 million         0.01 percent
100 to 199                                          $7,256                   $74.803 million         0.01 percent
----------------------------------------------------------------------------------------------------------------

    A similar analysis of the yearly cost impact of prospective on-
going notification, that would involve an estimated 12,816 affected 
components distributed across all hospitals, produces costs per 
hospital per year ranging from $17 per facility for the smallest 
hospital size category, to approximately $1,936 per facility for 
hospitals in the 500 + bed size category. For all bed size categories, 
the estimated yearly costs represent less than one-thousandth of a 
percent of average annual revenues.
    These findings of the Initial Regulatory Flexibility Analysis 
suggests that the relative cost impact may be fairly consistent across 
hospitals of different sizes, if the number of affected transfusion 
recipients per hospital is proportionate to the number of inpatient 
surgeries performed by hospitals in different size categories. However, 
the distribution of affected transfusion recipients across hospitals of 
different size and types of ownership is currently unknown. Because 
this information is essential for the estimation of the economic impact 
on small entities, FDA requests industry comment on the anticipated 
numbers of affected transfusion recipients, the ability to trace 
transfused products, and the volume of transfused products handled by 
consignees, particularly those that can be classified as small 
entities.
    In general, it is expected that the regulatory costs for blood 
establishments will be a function of the volume of donors, the number 
of donations testing repeatedly reactive in a screening test for 
evidence of HCV infection, the volume of donor blood components that 
must be traced, the quality of facility recordkeeping and the number of 
different consignees to which the collection facility distributes blood 
products. These factors are likely to be larger and generate higher 
potential costs for larger blood establishments. Yet careful screening 
is already in place in most facilities, which will minimize the number 
of affected units over time. It is similarly expected that transfusing 
facilities will already have recordkeeping systems and SOP's in place 
that can be readily adapted to HCV ``lookback.'' Also, recordkeeping 
and procedures to support targeted ``lookback'' for HIV are expected to 
provide a ready capability to trace donations and components affected 
by the proposed rule. FDA anticipates therefore that most of the 
information infrastructure needed for HCV ``lookback'' will already be 
in place for both blood establishments and blood transfusion services. 
For both types of establishments, the cost of compliance will primarily 
involve additional staff time.

[[Page 69402]]

    As described earlier, FDA has considered several alternatives, and 
considers that a targeted ``lookback'' will be the most effective 
approach to contacting affected recipients of HCV-infected blood 
products. However, within that approach the agency allows for 
flexibility in the facility's individual approach to compliance, to 
help minimize the resource impact. For example, the particular design 
and systems for record-keeping and standard operating procedures 
developed in response to the proposed rule are under the control of the 
facility, as is the approach taken to notification. This will enable 
each facility to develop procedures that are most appropriate and cost-
effective given the resources available. In addition, the agency has 
specified a limited time frame for notification, and a maximum required 
number of attempts, in order to provide a clear endpoint to facility 
efforts related to the ``lookback.''
    Although FDA has obtained initial estimates of the number of blood 
centers that would be classified as small entities, the agency 
currently does not have data on the distribution of repeat donors, 
donations testing repeatedly reactive in a screening test for evidence 
of HCV infection, and affected blood components, for those 
establishments that would qualify as small business entities. Because 
this information is essential for the estimation of the economic impact 
on small businesses, FDA requests industry comment on the current 
recordkeeping, the ability to trace products, and the volumes of 
donation units and components handled by these facilities.

V. The Paperwork Reduction Act of 1995

    This proposed rule contains information collection provisions that 
are subject to review by the Office of Management and Budget (OMB) 
under the Paperwork Reduction Act of 1995 (the PRA) (44 U.S.C. 3501-
3520). The title, description, and respondent description of the 
information collection provisions are shown in section V of this 
document with an estimate of the annual reporting and recordkeeping 
burden. Included in this estimate is the time for reviewing the 
procedures, searching existing data sources, gathering and maintaining 
the data needed, and completing and reviewing each 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.
    Title: Reporting and recordkeeping requirements within Current Good 
Manufacturing Practices for Blood and Blood Components: Notification of 
Consignees and Transfusion Recipients Receiving Blood and Blood 
Components at Increased Risk for Transmitting HCV Infection 
(``lookback'').
    Description: This proposed rule would require 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 HCV infections. Under the proposed rule, blood 
establishments would be required to include procedures that are similar 
to procedures now in effect for HIV ``lookback'' (Secs. 610.46 and 
610.47), for clarifying the status of the donor who later tests 
repeatedly reactive in a licensed screening test for HCV, quarantining 
prior collections from such donors, and notifying transfusion 
recipients, as appropriate, based on further testing of the donor. When 
a donor who previously donated blood is tested in accordance with 
Sec. 610.40 on a later donation, and tests repeatedly reactive for 
antibody to HCV, the blood establishment would be required to perform a 
supplemental 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. 
Blood establishments and consignees would be required to quarantine 
previously collected Whole Blood, blood components, Source Plasma and 
Source Leukocytes from such donors (some exemptions apply), and where 
appropriate, consignees would notify transfusion recipients.
    Under the proposed rule, blood establishments additionally would be 
required to perform a one-time retrospective review of historical HCV 
testing records that will identify prior collections from donors at 
increased risk for transmitting HCV. The retrospective review of HCV 
testing records would be limited to a 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. Blood establishments 
would be required to notify consignees of the risk of HCV transmission 
that exists for prior collections based on the retrospective review of 
HCV testing records and the results of the supplemental HCV testing 
performed before or as a result of the retrospective review of testing 
records. Blood establishments would 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 further 
testing is impractical or infeasible (an exception may apply). Under 
this proposal, consignees would notify the transfusion recipients.
    FDA is also proposing conforming amendments to certain provisions 
of Secs. 610.46 and 610.47, the HIV ``lookback'' regulations (61 FR 
47413, September 9, 1996). The proposed revisions to Secs. 610.46 and 
610.47, discussed under the corresponding sections of this proposal, 
are intended to clarify and provide consistency between the HIV and HCV 
``lookback'' requirements but do not include a requirement for the 
retrospective review of historical HIV testing records. The agency is 
issuing this proposed rule to help ensure that the blood supply 
continues to be safe, that information is provided to users of blood 
and blood components, and that transfusion recipients of blood and 
blood components at risk for transmitting HCV will be notified, as 
appropriate.
    Description of Respondents: Blood establishments (Business and Not-
for-Profit) and consignees of blood establishments, including 
hospitals, transfusion services and physicians.
    The total reporting and recordkeeping burden for the first year is 
estimated to be 492,148 hours. However, of this total approximately 
470,237 hours would be expended on a one-time basis for establishing 
the written procedures and doing the one-time retrospective review of 
historical HCV testing records. Therefore, 21,911 hours is estimated as 
the ongoing annual burden related to this proposed regulation. The 
total ongoing annual burden for blood collection facilities under 
Secs. 610.46(a), 610.46(b), 610.47(b) and 606.160(b)(1)(viii) for HIV 
``lookback'' is estimated to be 1,843 hours. The total ongoing annual 
burden for blood collection facilities under Secs. 610.48(a)(1)(ii), 
610.48(b), 610.49(b), 610.49(c) and 606.160(b)(1)(viii) for

[[Page 69403]]

HCV ``lookback'' is estimated to be 20,698 hours.
    Based on information previously discussed in section IV of this 
document, there are approximately 2,800 FDA registered blood 
establishments in the United States that collect approximately 12 
million allogeneic donations annually. The CDC estimates there are 
approximately 9,628,000 donations from repeat donors per year. The 
following reporting and recordkeeping estimates are based on 
information provided by industry, and FDA experience.

1. HIV Reporting Burden

    In table 5, it is estimated that approximately 3,500 repeat donors 
(an annual average of 1.25 repeat donors per establishment) will test 
repeatedly reactive on a screening test for HIV. Under proposed 
Secs. 610.46(a) and (b), this estimate results in 3,500 notifications 
of the HIV screening test results to consignees by blood establishments 
for the purpose of quarantine of affected units, and another 3,500 
notifications to consignees of subsequent test results. FDA estimates 
an average of 10 minutes per notification of consignees.
    In addition, it is estimated that 180 transfusion services not 
subject to HCFA regulations will be required under Sec. 610.47(b) to 
notify physicians, or in some cases recipients, an average of 0.14 
times per year resulting in a total number of 25 notifications. The 
estimate of one-half hour for notifications under Sec. 610.47(b) is 
based on the minimum requirement of three attempts to notify recipients 
by transfusion services. FDA estimates that each repeat donor has 
donated two previous times and two components were made from each 
donation. The estimates for HIV ``lookback'' provided in the tables 
differ from the estimates for HIV ``lookback'' provided in a notice 
published in the Federal Register of November 4, 1999 (64 FR 60212) 
because FDA has new, updated information from industry representatives 
from which to base its estimates.

2. HCV Reporting Burden

    Based on the interim results from a recent CDC survey (ref. 4), CDC 
estimates that 11,520 repeat donors per year would test repeatedly 
reactive for antibody to HCV. Under proposed Secs. 610.48(a)(1)(ii) and 
610.48(b), blood establishments would notify the consignee two times 
for each of the 12,816 components prepared from these donations, once 
for quarantine purposes and again with additional HCV test results for 
a total 25,632 notifications as an annual ongoing burden. Under 
proposed Sec. 610.49(b) and (c), FDA estimates that approximately 6,200 
transfusion services would notify two recipients annually.
A. HCV One-time Reporting Burden
    Based on estimates from CDC, FDA expects that for the one-time 
retrospective review of historical testing records, as many as 303,676 
blood components would be at increased risk for transmitting HCV. For 
each of these products, under Secs. 610.48(e)(2), 610.48(f)(2), 
610.48(h)(3)(i) and (ii), and 610.48(i)(3)(i) and (ii), blood 
establishments would notify consignees to quarantine these products and 
report additional HCV test results to consignees, and, under 
Sec. 610.49(b) and (c), consignees would notify transfusion recipients 
or recipients' physicians of record. CDC estimated that there could be 
approximately 258,125 transfusion recipients that would be notified 
after a one-time retrospective review of historical test results for 
HCV screening. The numbers in the hours per response column are based 
on FDA's knowledge and experience regarding notification.
B. HCV Ongoing Annual Reporting Burden
    Under Sec. 610.49(b) and (c), it is estimated that transfusion 
services may be expected to notify approximately 10,894 transfusion 
recipients per year, as previously discussed. The estimated average 0.5 
hours to complete notification under Secs. 610.47(b), 610.49(b) and (c) 
is based on FDA's knowledge and experience. The estimates of 13 hours, 
5,447 hours, and 129,063 hours, respectively, allow for a consignee to 
make up to three attempts to complete the notification process.

3. HIV and HCV Recordkeeping Burden

    In the recordkeeping charts, the numbers in the hours per record 
column are based on FDA's estimate of the time to complete one record. 
FDA estimates that it will take blood collection facilities 
approximately 40 hours to establish the written procedures proposed 
under Sec. 606.100(b)(19) and consignees approximately 16 hours to 
establish written procedures in accordance with proposed Sec. 610.49(b) 
and (c). In table 7, the estimate of 154 recordkeepers and 175 total 
annual records are based on the estimate that the HIV ``lookback'' 
requirements of Sec. 610.47(b) are already implemented voluntarily by 
more than 95 percent of the facilities, which collect 98 percent of the 
Nation's blood supply. FDA estimates that it takes transfusion services 
approximately 10 minutes to document and maintain the records to relate 
the donor with the unit number of each previous donation. The time 
required for recordkeeping under Sec. 606.160(b)(1)(viii) is estimated 
to be approximately 10 minutes for each HIV or HCV repeatedly reactive 
donation record and approximately 10 minutes per transfusion recipient 
record required under Secs. 610.47(b) and 610.49(b) and (c).
    FDA estimates the burden for this collection of information as 
follows:

                                 Table 5.--Estimated Annual Reporting Burden\1\
----------------------------------------------------------------------------------------------------------------
   21 CFR                          Annual Frequency      Total Annual
   Section    No. of Respondents     per Response          Responses      Hours per Response      Total Hours
----------------------------------------------------------------------------------------------------------------
610.46(a)         2,800                   1.25            3,500                    .17              600
610.46(b)         2,800                   1.25            3,500                    .17              600
610.47(b)           180                   0.14               25                    .50               13
610.48(a)(i)      2,800                   4.6            12,816                    .17            2,179
 (ii)
610.48(b)         2,800                   4.6            12,816                    .17            2,179
610.49(b)and      6,200                   2              10,894                    .50            5,447
 (c)
Total                                                                                           11,018
----------------------------------------------------------------------------------------------------------------
\1\ There are no capital costs or operating and maintenance costs associated with this collection of
  information.


[[Page 69404]]


                                Table 6.--Estimated One-Time Reporting Burden\1\
----------------------------------------------------------------------------------------------------------------
   21 CFR                          Annual Frequency      Total Annual
   Section    No. of Respondents     per Response         Respondents     Hours per Response      Total Hours
----------------------------------------------------------------------------------------------------------------
610.48(e)(2)      2,800                  41             115,228                    .1            11,523
610.48(f)(2)      2,800                  67             188,448                    .1            18,845
610.48(h)(3)      2,800                  41             115,228                    .1            11,523
 (i) and
 (h)(3)(ii)
610.48(i)(3)      2,800                  67             188,448                    .1            18,845
 (i) and
 (i)(3)(ii)
610.49(b)         6,200                  42             258,125                    .5           129,063
 and (c)
Total                                                                                          189,799
----------------------------------------------------------------------------------------------------------------
\1\ There are no capital costs or operating and maintenance costs associated with this collection of
  information.


                               Table 7.--Estimated Annual Recordkeeping Burden\1\
----------------------------------------------------------------------------------------------------------------
   21 CFR           No. of         Annual Frequency      Total Annual
   Section       Recordkeepers     of Recordkeeping         Records        Hours per Record       Total Hours
----------------------------------------------------------------------------------------------------------------
606.160(b)(1
 )(viii)
HIV                 154                   1.14              175                    .17               30
HIV               2,800                   1.25            3,500                    .17              600
HCV               2,800                   9              25,632                    .17            4,357
606.160(b)(1      6,200                   4              25,632                    .17            4,357
 )(viii)
610.49(b)         6,200                   2              12,816                    .17            2,179
 and (c)
Total                                                                                           11,523
----------------------------------------------------------------------------------------------------------------
\1\ There are no capital costs or operating and maintenance costs associated with this collection of
  information.


                              Table 8.--Estimated One-Time Recordkeeping Burden\1\
----------------------------------------------------------------------------------------------------------------
   21 CFR           No. of           Frequency of
   Section       Recordkeepers       Recordkeeping       Total Records     Hours per Record       Total Hours
----------------------------------------------------------------------------------------------------------------
606.100(b)(1      2,800                   1               2,800                  40             112,000
 9)
606.100(b)(1      6,200                   1               6,200                  16              99,200
 9)
606.160(b)(1      2,800                 108             303,676                   0.08           24,294
 )(viii)
606.160(b)(1      6,200                  49             303,676                   0.08           24,294
 )(viii)
610.49(b)         6,200                  42             258,125                   0.08           20,650
 and (c)
Total                                                                                          280,438
----------------------------------------------------------------------------------------------------------------
\1\ There are no capital costs or operating and maintenance costs associated with this collection of
  information.

    There are no capital costs or operating and maintenance costs 
associated with this collection of information.
    In compliance with the Paperwork Reduction Act of 1995 (44 U.S.C. 
3507(d)), the agency has submitted the information collection 
provisions of this proposed rule to OMB for review. Interested persons 
are requested to submit written comments regarding information 
collection by December 18, 2000, to the Office of Information and 
Regulatory Affairs, OMB (address above), Attention: Wendy Taylor, Desk 
Officer for FDA.

VI. Request for Comments

    Interested persons may submit to the Dockets Management Branch 
(address above) written comments regarding this proposed rule by 
February 14, 2001. Two copies of any comments are to be submitted, 
except that individuals may submit one copy. Comments are to be 
identified with the docket number found in brackets in the heading of 
this document. Received comments may be seen in the office above 
between 9 a.m. and 4 p.m., Monday through Friday.

VII. Proposed Effective Date

    The agency is proposing that any final rule that may issue based 
upon this proposed rule become effective 180 days after its date of 
publication in the Federal Register.

VIII. References

    The following references have been placed on display in the Dockets 
Management Branch (address above) and may be seen by interested persons 
between 9 a.m. and 4 p.m., Monday through Friday.

    1. Alter, M., ``Epidemiology of Hepatitis C,'' Hepatology, 
26:62S-65S, 1997.
    2. Alter, M., ``Epidemiology of Hepatitis C,'' Hepatology, 
26:62S-65S, 1997.
    3. Wallace, E. L., W. H. Churchill, D. M. Surgenor, J. An, G. 
Cho, S. McGurk, and L. Murphy, ``Collection and Transfusion of Blood 
and Blood Components in the United States, 1992,'' Transfusion, 35: 
802-812, 1995.
    4. Alter, M., CDC Survey Interim Results.
    5. MacPherson, J., America's Blood Centers, ``Advisory Committee 
on Blood Safety and Availability'' Tenth Meeting, vol. II, p. 7.
    6. Quattrocchi, R., Home Access Health Corp.
    7. Goldman, M., S. Juodvalkis, P. Gill, and G. Spurll, 
``Hepatitis C Lookback,'' Transfusion Medicine Review, vol. 12, No. 
2: 84-93, 1998.
    8. U.S. Department of Health and Human Services, Center for 
Disease Control and Prevention, ``Recommendations for Prevention and 
Control of Hepatitis C Virus (HCV) Infection and HCV-Related Chronic 
Disease,'' Morbidity and Mortality Weekly Report, vol. 47, No. RR-
19, October 16, 1998.
    9. Kim, W. R., J. J. Poterucha, J. E. Hermans, T. M. Therneau, 
E. R. Dickson, R. W. Evans, and J. B. Gross, ``Cost-Effectiveness of 
6 and 12 Months of Interferon-alfa Therapy for Chronic Hepatitis 
C,'' Annals of Internal Medicine, vol. 127, No. 10, November 1997.
    10. Davis, G. L., and J. Y. N. Lau, ``Factors Predictive of a 
Beneficial Response to Therapy of Hepatitis C,'' Hepatology, vol. 
26, No. 3, Suppl.1: 122s-126s.
    11. Bennett, W. G., Y. Inoue, J. R. Beck, J. B Wong, S. G. 
Pauker, and G. L. Davis, ``Estimates of the Cost-Effectiveness of a 
Single Course of Interferon-alfa2b in Patients with Histologically 
Mild Chronic Hepatitis C,'' Annals of Internal Medicine, vol. 127, 
No. 10, November 1997.
    12. National Institutes of Health (NIH) Consensus Development 
Conference Panel Statement: Management of Hepatitis C,

[[Page 69405]]

Hepatology, vol. 26, No. 3, Suppl. 1:2s-10s, 1997.
    13. Dusheiko, G., ``Side Effects of Alpha Interferon in Chronic 
Hepatitis C,'' Hepatology, vol. 26, No. 3, Suppl. 1:112s-119s, 1997.
    14. J. G. McHutchison et al., New England Journal of Medicine, 
339: 1485, 1998.
    15. Leveton, L. B., H. C. Sox, Jr., and M. A. Stoto, editors, 
HIV and the Blood Supply: An Analysis of Crisis Decisionmaking, 
Chapter 7, Institute of Medicine, National Academy Press, 
Washington, DC, 1995.
    16. Ottosen, J. S., The Blood Conspiracy: How to Avoid Getting 
AIDS and Hepatitis in a Transfusion, Aspen Leaf Press, Woodland 
Park, CO, 1993.
    17. Moreno, J. D., ``Attitudes Toward Risk: The Right to Know 
and the Right to Give Informed Consent'' in Blood and Blood 
Products: Safety and Risk, Institute of Medicine, National Academy 
Press, Washington, DC, 1996.
    18. Groopman, J., ``The Shadow Epidemic'' The New Yorker, May 
11, 1998.
    19. Zuck, T. F., G. A. Rose, U. J. Dumaswala, N. J. Geer, 
``Experience with a Transfusion Recipient Education Program about 
Hepatitis C,'' Transfusion, vol. 30, No. 8, 761, 1990.
    20. Kern, J. M., and B. B. Croy, ``A Review of Transfusion-
Associated AIDS Litigation: 1984 Through 1993,'' Transfusion, vol. 
34, No. 6, 1994.
    21. Wall, A., W. Lau, J. Lewis, J. A. Chiavetta, S. Mohammad, 
and R. Herst, ``Hepatitis C Virus (HCV) Targeted Lookback Program,'' 
Transfusion, vol. 37 Suppl. s392, 1997.
    22. Gill, M. J., D. Towns, S. Allaire, and G. Meyers, 
``Transmission of Human Immunodeficiency Virus Through Blood 
Transfusion: The Use of Lookback and Traceback Approaches to 
Optimize Recipient Identification in a Regional Population,'' 
Transfusion, vol. 37, 513-516, 1997.
    23. Healthcare InfoSource, Inc., a subsidiary of the American 
Hospital Association, Hospital Statistics, 1998 ed., Chicago IL.
    24. AuBuchon, J., ``Public Health, Public Trust, and Public 
Decision Making: Making Hepatitis C Virus Lookback Work,'' 
Transfusion, vol. 39, p. 124, 1999.

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 and the 
Public Health Service Act, and under authority delegated to the 
Commissioner of Food and Drugs, it is proposed that 21 CFR parts 606 
and 610 be amended as follows:

PART 606--CURRENT GOOD MANUFACTURING PRACTICE FOR BLOOD AND BLOOD 
COMPONENTS

    1. The authority citation for 21 CFR part 606 continues to read as 
follows:

    Authority: 21 U.S.C. 321, 331, 351, 352, 355, 360, 360j, 371, 
374; 42 U.S.C. 216, 262, 263a, 264.
    2. Section 606.100 is amended by revising paragraph (b)(19) to read 
as follows:


Sec. 606.100  Standard operating procedures.

* * * * *
    (b) * * *
    (19) Procedures in accordance with Secs. 610.46 and 610.48 of this 
chapter to look at prior donations of blood and blood components from a 
donor who has donated blood and subsequently tests repeatedly reactive 
for evidence of human immunodeficiency virus (HIV) infection or 
hepatitis C virus (HCV) infection when tested in accordance with 
Sec. 610.40 of this chapter or when a blood establishment has been made 
aware of other test results indicating evidence of HIV or HCV 
infection. Procedures to quarantine in-date blood and blood components, 
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; procedures to notify 
consignees of blood and blood components from such donors of the 
results of the HIV and HCV testing performed on such donors; procedures 
in accordance with Secs. 610.47 and 610.49 of this chapter to notify 
physician of record so that recipients of transfusion with blood or 
blood components are informed that they may have received blood or 
blood components at increased risk of transmitting HIV and HCV, 
respectively.
* * * * *
    3. Section 606.160 is amended by revising paragraph (b)(1)(viii) 
and the second sentence of paragraph (d) to read as follows:


Sec. 606.160  Records.

* * * * *
    (b) * * *
    (1) * * *
    (viii) Records of quarantine, consignee notification, further 
testing, transfusion recipient notification, and disposition performed 
under Secs. 610.46, 610.47, 610.48, and 610.49 of this chapter.
* * * * *
    (d) * * * The retention period shall be no less than 10 years after 
the records of processing have been completed or 6 months after the 
latest expiration date for the individual product, whichever is the 
later date. * * *
* * * * *

PART 610--GENERAL BIOLOGICAL PRODUCTS STANDARDS

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

    Authority:  21 U.S.C. 321, 351, 352, 353, 355, 360, 371; 42 
U.S.C. 216, 262, 263, 263a, 264.
    5. Section 610.40 is amended by adding paragraph (g) to read as 
follows:


Sec. 610.40  Test for hepatitis B surface antigen.

* * * * *
    (g) For a donor whose test result for HIV or HCV is repeatedly 
reactive when tested in accordance with paragraphs (a), (c), and (d) of 
this section, or when a blood establishment has been made aware of 
other test results indicating evidence of HIV or HCV infection, the 
blood establishment shall comply, as applicable, with Secs. 610.46, 
610.47, 610.48, and 610.49.
    6. Section 610.46 is amended by revising the section heading and 
paragraph (a), the heading for paragraph (b), the first sentence of 
paragraphs (b) and (c), and paragraph (d); by redesignating paragraph 
(e) as paragraph (f); by revising newly redesignated paragraph (f); and 
by adding new paragraph (e) to read as follows:


Sec. 610.46  Human Immunodeficiency Virus (HIV) ``Lookback;'' 
quarantine, consignee notification and further testing.

    (a) Quarantine and consignee notification. (1) All blood and plasma 
establishments shall take appropriate action when a donor of blood or 
blood components tests repeatedly reactive for evidence of HIV 
infection on a screening test in accordance with Sec. 610.40(a), or 
when the blood establishment has been made aware of other test results 
indicating evidence of HIV infection, provided the testing was 
performed by a laboratory certified under the Clinical Laboratory 
Improvement Amendments of 1988, using a test approved by FDA. For blood 
and blood components collected from that donor at any time prior to the 
repeatedly reactive test, whenever records are available, if intended 
for transfusion or for further manufacture into injectable products, 
except those products exempt from quarantine in accordance with 
paragraph (c) of this section, the blood establishment shall, within 3-
calendar days after the date on which the donor tested repeatedly 
reactive for evidence of HIV infection or after the date on which the 
blood establishment was made aware of other test results

[[Page 69406]]

indicating evidence of HIV infections, identify the prior collections 
from that donor and:
    (i) Quarantine all such prior collections of blood and blood 
components; and
    (ii) Notify consignees of the repeatedly reactive HIV screening 
test result so that the consignee may quarantine all such prior 
collections of blood and blood components.
    (2) Consignees notified in accordance with paragraph (a)(1)(ii) of 
this section shall quarantine all such prior collections of blood and 
blood components held at that establishment, except as provided in 
paragraph (c) of this section.
    (b) Further testing and consignee notification of results. Blood 
establishments shall perform further testing on the donor's blood, as 
specified in Sec. 610.40(c), and shall notify the consignee(s) of the 
results of this test within 45-calendar days after the date on which 
the donor tested repeatedly reactive for evidence of HIV infection on a 
screening test. * * *
    (c) Exemption from quarantine. Prior collections otherwise subject 
to quarantine under paragraph (a) of this section need not be held in 
quarantine if a determination has been made that the blood or blood 
component was collected more than 12 months prior to the donor's most 
recent negative screening test when tested for HIV in accordance with 
Sec. 610.40(a). * * *
    (d) Release from quarantine. Prior collections of blood and blood 
components intended for transfusion or further manufacture into 
injectable products which have been quarantined under paragraph (a) of 
this section may be released if the donor's current repeatedly reactive 
sample 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) Destruction or labeling of prior collections held in 
quarantine. Blood establishments and consignees shall destroy or 
appropriately label for in vitro use prior collections of blood and 
blood components otherwise subject to quarantine in accordance with 
paragraphs (a) and (d) of this section, unless such prior collections 
are determined to be exempt from quarantine in accordance with 
paragraph (c) of this section or subject to release from quarantine in 
accordance with paragraph (d) of this section. Quarantined prior 
collections made available for in vitro use shall be appropriately 
relabeled consistent with Secs. 606.121 and 640.70 of this chapter. In 
addition, these units must be relabeled as ``Biohazard'' with the 
cautionary statement as follows:

``Collected from a donor who subsequently tested positive for anti-HIV. 
An increased risk for transmission of human immunodeficiency virus is 
present;'' in addition, the label must contain one of the following 
cautionary statements, as appropriate: ``Caution: For Further 
Manufacturing Into In Vitro Diagnostic Reagents For Which There Are No 
Alternative Sources.'' or ``For Laboratory Research Use Only.''
    (f) Actions under this section. Actions under this section do not 
constitute a recall as defined in Sec. 7.3 of this chapter.
    7. Section 610.47 is revised to read as follows:


Sec. 610.47  Human Immunodeficiency Virus (HIV) ``Lookback;'' 
notification of transfusion recipients.

    (a) Appropriate actions following further testing. 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 prior collections of blood or blood components 
from a donor later determined to be unsuitable when tested for evidence 
of infection due to HIV and the result 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 blood or blood components as 
described in paragraph (a) of this section, the transfusion service 
shall either notify the recipient directly or notify the recipient's 
physician of record (i.e., physician of record or physician who ordered 
the blood or blood component) and ask him or her to inform the 
recipient of the need for HIV testing and counseling. If the physician 
is not available 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, or the recipient's 
physician, and be completed within a maximum of 12 weeks of receipt of 
the result of the licensed, more specific test for HIV from the blood 
establishment. The transfusion service is responsible for notification, 
including basic explanations to the recipient and referral for 
counseling and further testing, and shall document the notification and 
the result of attempts to notify the recipient and the recipient's 
physician of record, if contacted, under Sec. 606.160 of this chapter.
    (c) Notification of legal representative or relative. If the 
transfusion recipient has been adjudged incompetent by a State court, 
the legal representative, designated in accordance with State law, 
shall be notified. 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 the 
physician who agreed to perform the notification on behalf of the 
transfusion service shall notify the recipient or his or her legal 
representative or relative. If the transfusion recipient is a minor at 
the time of notification, the transfusion service or physician, as 
described in this paragraph, shall notify the recipient's legal 
representative or relative. If the transfusion recipient is deceased, 
the transfusion service or physician, as described in this paragraph, 
shall continue the notification process and inform the deceased 
recipient's legal representative or relative. The transfusion service 
is responsible for notification, including basic explanations to the 
recipient's legal representative or relative and referral for 
counseling and further testing of the recipient, and shall document the 
notification and the result of attempts to notify the recipient's legal 
representative or relative and the recipient's physician of record, if 
contacted, under Sec. 606.160 of this chapter. Reasons for notifying 
the recipient's relative or legal representative on his or her behalf 
shall be documented under Sec. 606.160 of this chapter.
    8. Section 610.48 is added to subpart E to read as follows:


Sec. 610.48  Hepatitis C Virus (HCV) ``Lookback;'' quarantine, 
consignee notification and further testing.

    (a) Quarantine and consignee notification. (1) Repeatedly reactive 
screening test. All blood and plasma establishments shall take 
appropriate action when a donor of blood or blood components tests 
repeatedly reactive for evidence of HCV infection on a screening test, 
in accordance with Sec. 610.40(a), or when the blood establishment has 
been made aware of other test results indicating evidence of HCV 
infection, provided the testing was performed by a laboratory certified 
under the Clinical Laboratory Improvement Amendments of 1988, using a 
test approved by FDA. For in-date blood and blood components collected 
from that donor at any time prior to the repeatedly reactive test,

[[Page 69407]]

whenever records are available, if intended for transfusion, or if 
intended for further manufacture into injectable products, except those 
products exempt from quarantine in accordance with paragraph (g)(1) of 
this section, the blood establishment shall, within 3-calendar days 
after the date on which the donor tested repeatedly reactive for 
evidence of HCV infection or after the date on which the blood 
establishment was made aware of other test results indicating evidence 
of HCV infection, identify the prior collections from that donor and:
    (i) Quarantine all such prior collections of blood and blood 
components; and
    (ii) Notify consignees of the repeatedly reactive HCV screening 
test result so that the consignee may quarantine all such prior 
collections of blood and blood components.
    (2) Quarantine by consignee. Consignees notified in accordance with 
paragraph (a)(1)(ii) of this section shall quarantine all such prior 
collections of blood and blood components held at that establishment, 
except as provided in paragraph (g)(1) of this section.
    (b) Further testing and consignee notification of results. In the 
case of a donor with a repeatedly reactive screening test for HCV, 
blood establishments shall perform further testing on the donor's 
blood, as specified in Sec. 610.40(c). Where prior collections from the 
same donor were distributed, blood establishments shall notify the 
consignee(s) of the results of this test within 45-calendar days after 
the date on which the donor tested repeatedly reactive for evidence of 
HCV infection on a screening test.
    (c) Review of historical testing records and identification of 
donors tested using a multiantigen screening test prior to [the 
effective date of the final rule]. Blood establishments shall review 
records of donor testing completed prior to [the effective date of the 
final rule] in order to identify donors who tested repeatedly reactive 
for evidence of HCV infection on a multiantigen screening test for HCV 
and to identify prior collections from such donors. Blood 
establishments shall, by (date 1 year from the effective date of the 
final rule), identify previously distributed blood and blood components 
from such donors, based on available required records maintained in 
accordance with Sec. 606.160 of this chapter, dating back indefinitely 
for computerized electronic records and to January 1, 1988, for other 
readily retrievable records, or to the date 12 months prior to the 
donor's most recent negative multiantigen screening test for antibody 
to HCV, whichever is the lesser period. Blood establishments shall 
identify previously distributed blood and blood components from such 
donors in any of the following instances:
    (1) First instance. Where the donor tested repeatedly reactive for 
evidence of HCV infection on the multiantigen screening test and 
positive on a supplemental test for HCV performed on the repeatedly 
reactive sample;
    (2) Second instance. Where the donor tested repeatedly reactive for 
evidence of HCV infection on the multiantigen screening test and 
indeterminate on a supplemental test for HCV performed on the 
repeatedly reactive sample;
    (3) Third instance. Where the donor tested repeatedly reactive for 
evidence of HCV infection on an HCV EIA 3.0 multiantigen screening test 
and negative on a HCV 2.0 strip immunoblot assay (HCV RIBA 2.0 
supplemental test) with no record of a negative licensed HCV 3.0 strip 
immunoblot assay (RIBA 3.0 supplemental test) performed on the 
repeatedly reactive sample or a later sample from the same donor.
    (4) Fourth instance. Where the donor tested repeatedly reactive for 
evidence of HCV infection on a licensed HCV EIA 2.0 screening test with 
no record of a supplemental test for HCV performed on the repeatedly 
reactive sample or on a later sample from the same donor and no record 
of a negative licensed HCV EIA 3.0 screening test performed on the 
repeatedly reactive sample or a later sample from the same donor; or
    (5) Fifth instance. Where the donor tested repeatedly reactive for 
evidence of HCV infection on a licensed HCV EIA 3.0 screening test with 
no record of a supplemental test for HCV performed on the repeatedly 
reactive sample or on a later sample from the same donor.
    (d) Review of historical testing records and identification of 
donors tested using a single antigen screening test prior to [the 
effective date of the final rule]. Blood establishments shall review 
records of donor testing completed prior to [the effective date of the 
final rule] in order to identify donors who tested repeatedly reactive 
for evidence of HCV infection on a single antigen screening test for 
HCV and to identify prior collections from such donors. Blood 
establishments shall, by (date 1 year from the effective date of the 
final rule), identify previously distributed blood and blood components 
from such donors, based on available required records maintained in 
accordance with Sec. 606.160 of this chapter, dating back indefinitely 
for computerized electronic records and to January 1, 1988, for other 
readily retrievable records, or to the date 12 months prior to the 
donor's most recent negative multiantigen screening test for antibody 
to HCV, whichever is the lesser period, in any of the following 
instances:
    (1) First instance. Where the donor tested repeatedly reactive for 
evidence of HCV infection on the single antigen screening test and 
repeatedly reactive on an HCV EIA 2.0 or HCV EIA 3.0 screening test 
performed on the repeatedly reactive sample or a fresh sample from the 
same donor;
    (2) Second instance. Where the donor tested repeatedly reactive for 
evidence of HCV infection on the single antigen screening test and 
either positive or indeterminate on an HCV 2.0 or HCV 3.0 strip 
immunoblot assay (HCV RIBA 2.0 or HCV RIBA 3.0, respectively) 
supplemental test for HCV performed on the repeatedly reactive sample 
or a fresh sample from the same donor;
    (3) Third instance. Where the donor tested repeatedly reactive for 
evidence of HCV infection on an HCV EIA 1.0 screening test, with a 
signal to cutoff (S/CO) value less than 2.5 for at least two out of the 
three EIA tests (i.e., the initial EIA screening test and the duplicate 
retests), with no record of a supplemental test or multiantigen 
screening test for HCV performed on the repeatedly reactive sample or 
on a later sample from the same donor; or
    (4) Fourth instance. Where the donor tested repeatedly reactive for 
evidence of HCV infection on an HCV EIA 1.0 screening test, with a S/CO 
value equal to or greater than 2.5 for at least two out of the three 
EIA tests (i.e., the initial EIA screening test and the duplicate 
retests) or with no determination of S/CO value for all three EIA 
tests, and with no record of a supplemental test or multiantigen 
screening test for HCV performed on the repeatedly reactive sample or 
on a later sample from the same donor.
    (e) Quarantine and consignee notification following the review of 
historical testing records based on screening performed using a 
multiantigen screening test. Blood establishments shall, by (date 1 
year from the effective date of the final rule), complete all 
quarantine and consignee notification requirements for prior 
collections from donors identified in the review of historical testing 
records in accordance with paragraph (c) of this section as follows:
    (1) Quarantine. Blood establishments shall, within 3-calendar days 
of the date of the identification of the donor's repeatedly reactive 
multiantigen screening test for HCV, quarantine all in-date prior 
collections of blood and blood components collected from such a donor 
at any time prior to the

[[Page 69408]]

repeatedly reactive multiantigen screening test and identified in 
accordance with paragraph (c) of this section, if intended for 
transfusion, or if intended for further manufacture into injectable 
products, except those products exempt from quarantine in accordance 
with paragraph (g)(2) of this section.
    (2) Consignee notification. Blood establishments shall, within 3-
calendar days of the date of identification of the donor's repeatedly 
reactive multiantigen screening test for HCV, notify consignees of the 
donor's test results, including the supplemental test results, if 
available, so that consignees may quarantine all in-date prior 
collections of blood and blood components subject to quarantine under 
paragraph (e)(1) of this section.
    (3) Quarantine by consignees. Consignees notified in accordance 
with paragraph (e)(2) of this section shall quarantine all in-date 
prior collections of blood and blood components subject to quarantine 
under paragraph (e)(1) of this section, except as provided in paragraph 
(g)(2) of this section.
    (f) Quarantine and consignee notification following the review of 
historical testing records based on screening performed using a single 
antigen screening test. (1) Quarantine. Blood establishments shall, by 
(date 1 year from the effective date of the final rule) and within 3-
calendar days of the date of the identification of the donor's 
repeatedly reactive single antigen screening test for HCV, quarantine 
all in-date prior collections of blood and blood components collected 
from such a donor at any time prior to the repeatedly reactive single 
antigen screening test and identified in accordance with paragraph (d) 
of this section, if intended for transfusion, or if intended for 
further manufacture into injectable products, except those products 
exempt from quarantine in accordance with paragraph (g)(3) of this 
section.
    (2) Consignee notification. Blood establishments shall, within 3-
calendar days of the date of identification of the donor's repeatedly 
reactive single antigen screening test for HCV, notify consignees of 
the donor's test results, including the supplemental test results, if 
available, so that consignees may quarantine all in-date prior 
collections of blood and blood components subject to quarantine under 
paragraph (f)(1) of this section.
    (3) Quarantine by consignees. Consignees notified in accordance 
with paragraph (f)(2) of this section shall quarantine all in-date 
prior collections of blood and blood components subject to quarantine 
under paragraph (f)(1) of this section, except as provided in paragraph 
(g)(3) of this section.
    (g) Exemption from quarantine. As used in Sec. 610.48, an 
appropriately chosen licensed supplemental test is one which includes 
all antigens contained in the screening test that was performed.
    (1) Prior collections subject to quarantine under paragraph (a) of 
this section. Prior collections otherwise subject to quarantine under 
paragraph (a) of this section need not be placed in quarantine if a 
determination has been made that:
    (i) The blood or blood component was collected more than 12 months 
prior to the donor's most recent negative multiantigen screening test 
when tested for HCV in accordance with Sec. 610.40(a); or
    (ii) An appropriately chosen licensed supplemental test for HCV, 
performed in accordance with paragraph (b) of this section has been 
completed within 3-calendar days of the date of the donor's repeatedly 
reactive screening test and the result is negative.
    (2) Prior collections subject to quarantine under paragraph (e)(1) 
of this section. Prior collections otherwise subject to quarantine 
under paragraph (e)(1) of this section need not be placed in quarantine 
if a determination has been made that:
    (i) The blood or blood component was collected more than 12 months 
prior to the donor's most recent negative multiantigen screening test 
for HCV that preceded the repeatedly reactive screening test; or
    (ii)(A) The repeatedly reactive screening test result was obtained 
using an HCV EIA 2.0 screening test, and either the original sample or 
a later sample from the same donor was tested and found negative using 
an HCV RIBA 2.0 or HCV RIBA 3.0 supplemental test or an HCV EIA 3.0 
screening test; or
    (B) The repeatedly reactive screening test result was obtained 
using an HCV EIA 3.0 screening test, and either the original sample or 
a later sample from the same donor was tested and found negative using 
an HCV RIBA 3.0 supplemental test;
    (3) Prior collections subject to quarantine under paragraph (f)(1) 
of this section. Prior collections otherwise subject to quarantine 
under paragraph (f)(1) of this section need not be placed in quarantine 
if the donor's testing records show that:
    (i) The repeatedly reactive screening test result was obtained 
using an HCV EIA 1.0 screening test, and either the original sample or 
a later sample from the same donor was further tested and found 
negative using an HCV EIA 2.0 or 3.0; or
    (ii) The repeatedly reactive screening test result was obtained 
using an HCV EIA 1.0 screening test, and either the original sample or 
a later sample from the same donor was tested and found negative using 
an HCV RIBA 2.0 or HCV RIBA 3.0 supplemental test ; or
    (iii)(A) The donor, identified in accordance with paragraph (d)(1) 
of this section, as testing repeatedly reactive on an HCV EIA 2.0, was 
further tested using a HCV RIBA 2.0 or HCV RIBA 3.0 supplemental test, 
on a fresh sample, or frozen sample from the repeatedly reactive 
donation and the result was negative; or
    (B) The donor, identified in accordance with paragraph (d)(1) of 
this section, as testing repeatedly reactive on an HCV EIA 3.0, was 
further tested using an HCV RIBA 3.0 supplemental test, on a fresh 
sample, or frozen sample from the repeatedly reactive donation and the 
result was negative; or
    (iv) The donor identified in accordance with paragraph (d)(2) of 
this section, as testing indeterminate on a HCV RIBA 2.0 supplemental 
test, was further tested using either an HCV EIA 3.0 or a HCV RIBA 3.0 
supplemental test on a fresh sample, or frozen sample from the 
repeatedly reactive donation and the result was negative.
    (h) Further testing following review of historical testing records 
and consignee notification based on screening performed using a 
multiantigen screening test. (1) Further testing. Blood establishments 
that have performed the review of records and identified prior 
collections in accordance with paragraphs (c)(4) and (c)(5) of this 
section shall, by (date 1 year from the effective date of the final 
rule):
    (i)(A) If the repeatedly reactive test result was obtained using a 
HCV EIA 2.0 screening test, perform a licensed supplemental test for 
HCV on a frozen sample from the repeatedly reactive donation, if 
available; or if such a frozen sample is not available, obtain a fresh 
sample from such a donor and perform a licensed supplemental test for 
HCV; or
    (B) If the repeatedly reactive test result was obtained using a HCV 
EIA 2.0 screening test, perform a licensed HCV EIA 3.0 screening test 
on a frozen sample, if available, or on a fresh sample from such a 
donor and perform a licensed supplemental test if the HCV EIA 3.0 
screening test is repeatedly reactive; or
    (ii) If the repeatedly reactive test result was obtained using a 
HCV EIA 3.0 screening test, perform a licensed supplemental test for 
HCV on a frozen

[[Page 69409]]

sample, if available, or on a fresh sample from such a donor; or
    (iii) Make a determination that neither a frozen sample from the 
repeatedly reactive donation nor a fresh sample from the donor is 
available for further testing.
    (2) Options for further testing. Blood establishments that have 
performed the review of records and identified certain prior 
collections in accordance with paragraphs (c)(2) or (c)(3) of this 
section, and as described in paragraphs (h)(2)(i) through (h)(2)(iv) of 
this section may further test a frozen sample from the repeatedly 
reactive donation or a fresh sample from the same donor by (date 1 year 
from the effective date of the final rule), as follows:
    (i) Donors identified in accordance with paragraph (c)(2) of this 
section as testing repeatedly reactive using an HCV EIA 2.0 screening 
test, and indeterminate on an HCV RIBA 2.0 supplemental test, may be 
further tested using either a licensed HCV EIA 3.0 screening test or a 
currently available licensed supplemental test for HCV;
    (ii) Donors identified in accordance with paragraph (c)(2) of this 
section as testing repeatedly reactive using an HCV EIA 2.0 screening 
test, indeterminate on a HCV RIBA 2.0 supplemental test, and repeatedly 
reactive on an HCV EIA 3.0 screening test, performed in accordance with 
paragraph (h)(2)(i) of this section, may be further tested using an 
appropriately chosen licensed supplemental test for HCV;
    (iii) Donors identified in accordance with paragraph (c)(2) of this 
section as testing repeatedly reactive using an HCV EIA 3.0 screening 
test, and indeterminate on a HCV RIBA 2.0 supplemental test, may be 
further tested using an appropriately chosen licensed supplemental test 
for HCV;
    (iv) Donors identified in accordance with paragraph (c)(3) of this 
section as testing repeatedly reactive using an HCV EIA 3.0 screening 
test, and negative on a HCV RIBA 2.0 supplemental test with no record 
of a negative HCV RIBA 3.0 supplemental test, may be further tested 
using an appropriately chosen licensed supplemental test for HCV.
    (3) Consignee notification. Except for blood and blood components 
exempt from quarantine in accordance with paragraph (g)(2) of this 
section, blood establishments shall:
    (i) Within 45 days following completion of additional testing and 
prior to (date 1 year from the effective date of the final rule), 
notify consignees of the results of the additional licensed screening 
test and/or the licensed, supplemental test performed in accordance 
with paragraphs (h)(1) and (h)(2) of this section; or
    (ii) Prior to (date 1 year from the effective date of the final 
rule), notify consignees of the test results for a donor who was 
identified in the review of historical testing records, in accordance 
with paragraphs (c)(1) through (c)(5) of this section.
    (i) Further testing following review of historical testing records 
and consignee notification based on screening performed using a single 
antigen screening test. (1) Further testing. Blood establishments that 
have performed the review of records and identified prior collections 
in accordance with paragraph (d)(4) of this section shall, by (date 1 
year from the effective date of the final rule):
    (i) Perform a licensed, supplemental test for HCV on a frozen 
sample from the repeatedly reactive donation, if available; or if such 
a frozen sample is not available, obtain a fresh sample from such a 
donor and perform a licensed supplemental test for HCV; or
    (ii) Make a determination that neither a frozen sample from the 
repeatedly reactive donation nor a fresh sample from the donor is 
available for further testing.
    (2) Options for further testing. Blood establishments that have 
performed the review of records and identified certain prior 
collections in accordance with paragraphs (d)(1) or (d)(2) of this 
section and described in paragraphs (i)(2)(i) through (i)(2)(iii) of 
this section may further test a frozen sample from the repeatedly 
reactive donation or a fresh sample from the same donor, by (date 1 
year from the effective date of the final rule), as follows:
    (i) Donors identified in accordance with paragraph (d)(1) of this 
section as testing repeatedly reactive on an HCV EIA 1.0 screening test 
and repeatedly reactive on either an HCV EIA 2.0 or HCV EIA 3.0 
screening test may be further tested using an appropriately chosen 
licensed supplemental test for HCV; or
    (ii) Donors identified in accordance with paragraph (d)(2) of this 
section as testing repeatedly reactive on an HCV EIA 1.0 screening test 
with an indeterminate test result obtained using an HCV RIBA 2.0 
supplemental test, may be further tested using a currently available 
licensed supplemental test for HCV or an HCV EIA 3.0. If such optional 
further testing is performed using an HCV EIA 3.0 and the result is 
repeatedly reactive, blood establishments may perform further testing 
using an appropriately chosen licensed supplemental test for HCV.
    (iii) Donors identified in accordance with paragraph (d)(3) of this 
section as testing repeatedly reactive on an HCV EIA 1.0 screening test 
with a S/CO value less than 2.5 for at least two out of the three EIA 
tests, and with no record of a supplemental test or multiantigen 
screening test for HCV performed on the repeatedly reactive sample or 
on a later sample from the same donor, may be further tested using a 
licensed multiantigen screening test for HCV or a licensed supplemental 
test for HCV.
    (3) Consignee notification. Except for blood and blood components 
exempt from quarantine in accordance with paragraph (g)(3) of this 
section, blood establishments shall:
    (i) Within 45 days following completion of additional testing and 
prior to (date 1 year from the effective date of the final rule), 
notify consignees of the results of the additional licensed screening 
test and/or the licensed, supplemental test performed in accordance 
with paragraphs (i)(1) and (i)(2) of this section; or
    (ii) Prior to (date 1 year from the effective date of the final 
rule), notify consignees of the test results for a donor who was 
identified in the review of historical testing records in accordance 
with paragraphs (d)(1) through (d)(4) of this section.
    (j) Release from quarantine. (1) Prior collections subject to 
quarantine under paragraph (a) of this section. Prior collections of 
blood and blood components intended for transfusion or further 
manufacture into injectable products which are subject to quarantined 
under paragraph (a) of this section may be released if the donor's 
current, repeatedly reactive sample is subsequently tested using a 
licensed, supplemental test for HCV as provided in paragraph (b) of 
this section and the result is negative.
    (2) Prior collections subject to quarantine under paragraph (e)(1) 
of this section. Prior collections of blood and blood components, which 
are not exempt from quarantine under paragraph (g)(2) of this section, 
and are otherwise subject to quarantine under paragraph (e)(1) of this 
section may be released from quarantine if:
    (i)(A) The donor's testing records meet the conditions specified in 
paragraph (c)(4) of this section and further testing was performed in 
accordance with paragraph (h)(1)(i)(A) of this section on a frozen 
sample from the repeatedly reactive donation or a fresh sample from the 
same donor using a licensed supplemental test for HCV, and the result 
of the licensed supplemental test for HCV is negative; or

[[Page 69410]]

    (B) The donor's testing records meet the conditions specified in 
paragraph (c)(4) of this section and further testing was performed in 
accordance with paragraph (h)(1)(i)(B) of this section on a frozen 
sample from the repeatedly reactive donation or a fresh sample from the 
same donor using a licensed, HCV EIA 3.0 screening test and the result 
is negative, or using a licensed, supplemental test if the HCV EIA 3.0 
screening test is repeatedly reactive and the result of the licensed, 
supplemental test is negative; or
    (ii) The donor's testing records meet the conditions specified in 
paragraph (c)(5) of this section and further testing was performed in 
accordance with paragraph (h)(1)(ii) of this section on a frozen sample 
or a fresh sample from the same donor using a licensed, supplemental 
test for HCV and the result is negative; or
    (iii) The donor's testing records meet the conditions specified in 
paragraph (c)(2) of this section and further testing was performed, in 
accordance with paragraph (h)(2) of this section, as follows:
    (A) The repeatedly reactive sample (test performed using an HCV EIA 
2.0 screening test), or a later sample from the donor was further 
tested in accordance with paragraph (h)(2)(i) of this section using 
either a licensed HCV EIA 3.0 screening test or a licensed supplemental 
test for HCV and the result is negative; or
    (B) The repeatedly reactive sample (test performed using an HCV EIA 
2.0 screening test) or a later sample from the donor was further tested 
in accordance with paragraph (h)(2)(ii) of this section using an 
licensed supplemental test for HCV and the result is negative; or
    (C) The repeatedly reactive sample (test performed using an HCV EIA 
3.0 screening test) or a later sample from the donor was further tested 
in accordance with paragraph (h)(2)(iii) of this section using a 
licensed supplemental test for HCV and the result is negative; or
    (iv) The donor's testing records meet the conditions specified in 
paragraph (c)(3) of this section and further testing was performed in 
accordance with paragraph (h)(2)(iv) of this section on a frozen sample 
or a fresh sample from the same donor using a licensed supplemental 
test for HCV and the result is negative.
    (3) Prior collections subject to quarantine under paragraph (f)(1) 
of this section. Prior collections of blood and blood components, which 
are not exempt from quarantine under paragraph (g)(3) of this section, 
and are otherwise subject to quarantine under paragraph (f)(1) of this 
section may be released from quarantine if:
    (i) The donor's testing records meet the conditions specified in 
paragraph (d)(4) of this section and further testing was performed in 
accordance with paragraph (i)(1)(i) of this section on a fresh sample, 
or frozen sample from the repeatedly reactive donation using a licensed 
supplemental test for HCV and the result is negative; or
    (ii) The donor's testing records meet the conditions specified in 
paragraph (d)(1) of this section and further testing was performed in 
accordance with paragraph (i)(2)(i) of this section on a fresh sample, 
or frozen sample from the repeatedly reactive donation and the result 
of the an appropriately chosen licensed supplemental test for HCV is 
negative; or
    (iii) The donor's testing records meet the conditions specified in 
paragraph (d)(2) of this section and further testing was performed in 
accordance with paragraph (i)(2)(ii) of this section on a fresh sample, 
or frozen sample from the repeatedly reactive donation and the result 
when further tested using either a licensed HCV EIA 3.0 screening test 
or a licensed supplemental test for HCV is negative;
    (iv) The donor's testing records meet the conditions specified in 
paragraph (d)(3) of this section and further testing was performed in 
accordance with paragraph (i)(2)(iii) of this section on a fresh 
sample, or frozen sample from the repeatedly reactive donation and the 
result when further tested using a licensed multiantigen screening test 
for HCV or a licensed supplemental test for HCV is negative.
    (k) Destruction or labeling of prior collections held in 
quarantine. Blood establishments and consignees shall destroy or 
appropriately label for in vitro use prior collections of blood and 
blood components otherwise subject to quarantine in accordance with 
paragraphs (a), (e), and (f) of this section, unless such prior 
collections are determined to be exempt from quarantine in accordance 
with paragraph (g) of this section or subject to release from 
quarantine in accordance with paragraph (j) of this section. 
Quarantined prior collections made available for in vitro use shall be 
appropriately relabeled consistent with Secs. 606.121 and 640.70 of 
this chapter. In addition, these units must be relabeled as 
``Biohazard'' with the cautionary statement as follows:
    ``Collected from a donor who subsequently tested reactive for anti-
HCV. An increased risk of transmission of hepatitis C virus is 
present.''; in addition, the label must contain one of the following 
cautionary statements as appropriate: ``Caution: For Further 
Manufacturing Into In-Vitro Diagnostic Reagents For Which There Are No 
Alternative Sources'' or ``For Laboratory Research Use Only.''
    (l) Recalls. Actions under this section do not constitute a recall 
as defined in Sec. 7.3 of this chapter.
    9. Section 610.49 is added to subpart E to read as follows:


Sec. 610.49  Hepatitis C Virus (HCV) ``Lookback;'' notification of 
transfusion recipients.

    (a) Appropriate actions following further testing. Transfusion 
services are required to take appropriate action in accordance with 
paragraphs (b) and (c) of this section when a recipient has received 
prior collections of blood or blood components from a donor later 
determined to be at increased risk of transmitting HCV infection when 
tested for evidence of infection due to HCV and:
    (1) The result of the licensed, supplemental test, performed as 
prescribed in Sec. 610.48(b) and in accordance with the testing 
requirements specified in Sec. 610.40(c), is positive;
    (2) The result of the supplemental test identified in the review of 
historical testing records is positive, as specified in 
Sec. 610.48(c)(1);
    (3) The result of the supplemental test identified in the review of 
historical testing records in accordance with Sec. 610.48(c)(2) is 
indeterminate, unless:
    (i) The review of historical testing records shows the supplemental 
test was performed using an HCV RIBA 3.0 supplemental test; or
    (ii) Any of the conditions for exemption from quarantine specified 
in Sec. 610.48(g)(2) have been met; or
    (iii) The donor was further tested in accordance with 
Sec. 610.48(h)(2)(i), (h)(2)(ii), or (h)(2)(iii) and any of the 
conditions for release from quarantine specified in 
Sec. 610.48(j)(2)(iii) have been met; or
    (iv) The donor was further tested in accordance with 
Sec. 610.48(h)(2)(ii) or (h)(2)(iii) using a supplemental test for HCV 
and the result is indeterminate;
    (4) The result of the licensed supplemental test performed in 
accordance with Sec. 610.48(h)(1)(i)(A), (h)(1)(i)(B), or (h)(1)(ii) is 
positive for a donor identified in the review of historical testing 
records in accordance with Sec. 610.48(c)(4) and (c)(5), as testing 
repeatedly reactive on a multiantigen screening test in the past with 
no record of further testing;
    (5) No record of further testing is available for a donor 
identified in the

[[Page 69411]]

review of historical testing records, in accordance with 
Sec. 610.48(c)(4) and (c)(5), and no fresh or frozen sample is 
available for further testing, as specified in Sec. 610.48(h)(1)(iii);
    (6) The result of the additional test using HCV EIA 2.0 or 3.0 
identified in the review of historical testing records is repeatedly 
reactive, as specified in Sec. 610.48(d)(1), unless:
    (i) Any of the conditions for exemption from quarantine specified 
in Sec. 610.48(g)(3) have been met; or
    (ii) The donor was further tested in accordance with 
Sec. 610.48(i)(2)(i) and any of the conditions for release from 
quarantine specified in Sec. 610.48(j)(3) have been met; or
    (iii) The donor was further tested in accordance with 
Sec. 610.48(i)(2)(i) using an appropriately chosen licensed 
supplemental test for HCV and the result is indeterminate; or
    (7) The result of the supplemental test performed using an HCV RIBA 
2.0 or HCV RIBA 3.0 is positive for a donor identified in the review of 
historical testing records in accordance with Sec. 610.48(d)(2);
    (8) The result of the supplemental test performed using an HCV RIBA 
2.0 is indeterminate, for a donor identified in the review of 
historical testing records in accordance with Sec. 610.48(d)(2), 
unless:
    (i) Any of the conditions for exemption from quarantine specified 
in Sec. 610.48(g)(3) have been met; or
    (ii) The donor was further tested in accordance with 
Sec. 610.48(i)(2)(ii) and any of the conditions for release from 
quarantine specified in Sec. 610.48(j)(3) have been met; or
    (iii) The donor was further tested in accordance with 
Sec. 610.48(i)(2)(ii) using a licensed supplemental test for HCV and 
the result is indeterminate; or
    (9) The result of the licensed, supplemental test for HCV or a 
licensed multiantigen screening test performed in accordance with 
Sec. 610.48(i)(2)(iii) is positive for a donor identified in the review 
of historical testing records, in accordance with Sec. 610.48(d)(3); or
    (10) The result of the licensed, supplemental test for HCV 
performed in accordance with Sec. 610.48(i)(1) is positive for a donor 
identified in the review of historical testing records, in accordance 
with Sec. 610.48(d)(4), as testing repeatedly reactive on a single 
antigen screening test with a S/CO value equal to or greater than 2.5 
for at least two of the three EIA tests, or the S/CO value can not be 
calculated, and with no record of further testing; or
    (11) No record of further testing is available for a donor 
identified in the review of historical testing records, in accordance 
with Sec. 610.48(d)(4), and no fresh or frozen sample is available for 
further testing, as specified in Sec. 610.48(i)(1)(ii).
    (b) Notification of recipients of prior transfusion. If the 
transfusion service has administered blood or blood components later 
determined to be at increased risk of transmitting HCV infection, as 
described in paragraph (a) of this section, the transfusion service 
shall either notify the recipient directly or notify the recipient's 
physician of record (i.e., physician of record or physician who ordered 
the blood or blood component) and ask him or her to inform the 
recipient of the need for HCV testing and counseling. If the physician 
is not available or declines to notify the recipient, the transfusion 
service shall notify the recipient and inform the recipient of the need 
for HCV testing and counseling. The notification of transfusion 
recipients based on donor testing completed after (the effective date 
of the final rule) shall include a minimum of three attempts to notify 
the recipient or the recipient's physician of record and be completed 
within a maximum of 12 weeks of receipt of the result of the 
supplemental test for HCV from the blood establishment. The 
notification of transfusion recipients based on donor testing completed 
prior to (the effective date of the final rule) shall include a minimum 
of three attempts to notify the recipient or the recipient's physician 
of record and be completed within 1 year of the date on which the 
transfusion service received notification from the blood establishment. 
The transfusion service is responsible for notification, including 
basic explanations to the recipient and referral for counseling and 
further testing, and shall document the notification and the result of 
attempts to notify the recipient and the recipient's physician of 
record, if contacted, under Sec. 606.160 of this chapter.
    (c) Notification of legal representative or relative. If the 
transfusion recipient has been adjudged incompetent by a State court, 
the legal representative, designated in accordance with State law, 
shall be notified. 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 the 
physician who agreed to perform the notification on behalf of the 
transfusion service shall notify the recipient or his or her legal 
representative or relative. If the transfusion recipient is a minor at 
the time of notification, the transfusion service or physician, as 
described in this paragraph, shall notify the recipient's legal 
representative or relative. If the transfusion recipient is deceased, 
the transfusion service or physician, as described in this paragraph, 
may discontinue the notification process. The transfusion service is 
responsible for notification, including basic explanations to the 
recipient's legal representative or relative and referral for 
counseling and further testing of the recipient, and shall document the 
notification and the result of attempts to notify the recipient's legal 
representative or relative and the recipient's physician of record, if 
contacted, under Sec. 606.160 of this chapter. Reasons for notifying 
the recipient's relative or legal representative on his or her behalf 
shall be documented under Sec. 606.160 of this chapter.
    (d) Reference tables. Tables 1 through 4 of this paragraph show the 
various tests performed for HCV (including both current donor testing 
shown in table 1 of this paragraph and tests identified in the review 
of historical testing records in tables 2 through 4 of this paragraph), 
steps of the ``lookback'' process, and applicable provisions of 
Secs. 610.48 and 610.49. Based on the initial screening test select the 
appropriate table from the following:

[[Page 69412]]



 Table 1.--Outline of Provisions of Sec.  610.48 for Hepatitis C Virus (HCV) ``Lookback'' Based on Current Donor
                                                     Testing
----------------------------------------------------------------------------------------------------------------
                  Actions to be taken                                     Applicable section(s):
----------------------------------------------------------------------------------------------------------------
Identify prior collections                               610.48(a)(1)
Quarantine prior in-date collections                     610.48(a)(1)(i)
Notify consignees to quarantine                          610.48(a)(1)(ii)
Consignees perform quarantine of prior collections       610.48(a)(2)
Exemptions from quarantine                               610.48(g)(1)(i)
                                                         610.48(g)(1)(ii)
Perform further testing                                  610.48(b)
Notify consignees of test results                        610.48(b)
Release prior collections from quarantine                610.48(j)(1)\1\
Destroy or label prior collections                       610.48(k)
Notify transfusion recipients                            610.49(a)(1)\2\
----------------------------------------------------------------------------------------------------------------
\1\ If the licensed supplemental test for HCV is negative.
\2\ If the licensed supplemental test for HCV is positive.


[[Page 69413]]


 Table 2.--Outline of Provisions of Sec.  610.48 for Hepatitis C Virus (HCV) ``Lookback'' Based on Review of Historical Testing Records and Identification of Donors Testing Repeatedly Reactive Using an HCV EIA\1\ 3.0 Screening Test
----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
 
----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
   Results of Further Testing:       RIBA 2.0\2\ Positive or RIBA          RIBA 2.0 Negative            RIBA 2.0 Indeterminate          RIBA 3.0 Negative         RIBA 3.0 Indeterminate               No Supplemental Test Done
                                            3.0\3\ Positive
----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
Actions To Be Taken:                                                                                                        Applicable Sections
----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
Identify prior collections         610.48(c)(1)                     610.48(c)(3)                    610.48(c)(2)                                              610.48(c)(2)                                   610.48(c)(5)
----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
Quarantine prior in-date
 collections
----------------------------------
Notify consignees to quarantine    610.48(e)(1), (e)(2), (e)(3)     610.48(e)(1), (e)(2), (e)(3)    610.48(e)(1), (e)(2), (e)(3)                              610.48(e)(1), (e)(2), (e)(3)           610.48(e)(1), (e)(2), (e)(3)
----------------------------------
Consignees perform quarantine of
 prior collections
----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
Exemptions from quarantine         610.48(g)(2)(i)                  610.48(g)(2)(i)                 610.48(g)(2)(i)                 610.48(g)(2)(ii)(B)       610.48(g)(2)(i)                               610.48(g)(2)(i)
----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
Perform further testing                                                                                                                                                                       610.48(h)(1)(ii)\4\   610.48(h)(1)(iii)\6\
----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
Perform optional further testing                                    610.48(h)(2)(iv)\4\             610.48(h)(2)(iii)\4\
----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
Notify consignees of test results  610.48(h)(3)(ii)                 610.48(h)(3)(i)                 610.48(h)(3)(i)                                           610.48(h)(3)(ii)                610.48(h)(3)(i)       610.48(h)(3)(i)
                                                                    610.48(h)(3)(ii)                610.48(h)(3)(ii)                                                                          610.48(h)(3)(ii)      610.48(h)(3)(ii)
----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
Release  prior  collections  from                                   610.48(j)(2)(iv)\5\             610.48(j)(2)(iii)(C)\5\                                                                   610.48(j)(2)(ii)\5\
  quarantine
----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
Destroy or label prior             610.48(k)                        610.48(k)                       610.48(k)                                                 610.48(k)                       610.48(k)             610.48(k)
 collections
----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
Notify transfusion recipients      610.49(a)(2)                                                     610.49(a)(3)                                                                              610.49(a)(4)\7\       610.49(a)(5)
----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
\1\ ``EIA'' means enzyme linked immunosorbant assay.
\2\ ``RIBA 2.0'' means HCV 2.0 strip immunoblot assay.
\3\ ``RIBA 3.0'' means HCV 3.0 strip immunoblot assay.
\4\ Using a licensed supplemental test for HCV.
\5\ If the licensed supplemental test for HCV is negative.
\6\ No frozen or fresh sample is available for further testing.
\7\ If the licensed supplemental test for HCV is positive.


[[Page 69414]]


 Table 3.--Outline of Provisions of Sec.  610.48 for Hepatitis C Virus (HCV) ``Lookback'' Based on Review of Historical Testing Records and Identification of Donors Testing Repeatedly Reactive
                                                                             Using an HCV EIA\1\ 2.0 Screening Test
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
 
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
        Results of Further Testing:           RIBA 2.0\2\        RIBA 2.0          RIBA 2.0 Indeterminate           RIBA 3.0         RIBA 3.0                No Supplemental Test Done
                                               Positive or       Negative                                           Negative       Indeterminate
                                              RIBA 3.0 \3\
                                                Positive
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
Actions to be Taken:                                                                                         Applicable Sections
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
Identify prior collections                  610.48(c)(1)                                610.48(c)(2)                             610.48(c)(2)                      610.48(c)(4)
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
Quarantine prior in-date collections                                                                            ...............  ...............
-------------------------------------------
Notify consignees to quarantine             610.48(e)(1),                       610.48(e)(1), (e)(2), (e)(3)                     610.48(e)(1),             610.48(e)(1), (e)(2), (e)(3)
                                             (e)(2), (e)(3)                                                                       (e)(2), (e)(3)
-------------------------------------------
Consignees perform quarantine of prior                                                                          ...............  ...............
 collections
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
Exemptions from quarantine                  610.48(g)(2)(i)  610.48(g)(2)(ii           610.48(g)(2)(i)          610.48(g)(2)(ii  610.48(g)(2)(i)                  610.48(g)(2)(i)
                                                              )(A)                                               )(A)
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
Perform further testing                                                                                                                           610.48(h)(1)(i  610.48(h)       610.48(h)
                                                                                                                                                   )(A)\9\         (1)(i)(B) \10   (1)(iii) \11\
                                                                                                                                                                   \
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
Perform optional further testing                                              610.48(h)        610.48(h)
                                                                               (2)(i)\4\        (2)(i)\6\
                                                                              610.48(h)(2)(ii
                                                                               )\5\
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
Notify consignees of test results           610.48(h)(3)(ii                   610.48(h)(3)(i)  610.48(h)(3)(i)                   610.48(h)        610.48(h)(3)(i  610.48(h)(3)(i  610.48(h)(3)(i
                                             )                                610.48(h)        610.48(h)                          (3)(ii)          )               )               )
                                                                               (3)(ii)          (3)(ii)                                           610.48(h)(3)(i  610.48(h)(3)(i  610.48(h)(3)(i
                                                                                                                                                   i)              i)              i)
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
Release prior collections from quarantine                                     610.48(j)(2)(ii  610.48(j)                                          610.48(j)(2)(i  610.48(j)(2)
                                                                               i)(A)\7\         (2)(iii)(A)\8\                                     )(A)\12\        (i)(B)\13\
                                                                              610.48(j)(2)(ii
                                                                               i)(B)\8\
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
Destroy or label prior collections          610.48(k)                         610.48(k)        610.48(k)                         610.48(k)        610.48(k)       610.48(k)       610.48(k)
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
Notify transfusion recipients               610.49(a)(2)                      610.49(a)(3)     610.49(a)(3)                                       610.49(a)(4)\1  610.49(a)(4)\1  610.49(a)(5)
                                                                                                                                                   4\              4\
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
\1\ ``EIA'' means enzyme linked immunosorbant assay.
\2\ ``RIBA 2.0'' means HCV 2.0 strip immunoblot assay.
\3\ ``RIBA 3.0'' means HCV 3.0 strip immunoblot assay.
\4\ Using an HCV EIA 3.0 screening test.
\5\ If the HCV EIA 3.0 screening test is repeatedly reactive, may perform a licensed supplemental test for HCV.
\6\ Using a licensed supplemental test for HCV.
\7\ If the HCV EIA 3.0 screening test is negative.
\8\ If the licensed supplemental test for HCV is negative.
\9\ Perform a licensed supplemental test for HCV.
\10\ Perform an HCV EIA 3.0 screening test and perform a licensed supplemental test for HCV if the HCV EIA 3.0 screening test is repeatedly reactive.
\11\ No frozen or fresh sample is available for further testing.
\12\ If the licensed supplemental test for HCV is negative.
\13\ If the HCV EIA 3.0 screening is negative; or, if it is repeatedly reactive, the licensed supplemental test for HCV is negative.
\14\ If the licensed supplemental test for HCV is positive.


[[Page 69415]]


 Table 4.--Outline of Provisions of Sec.  610.48 for Hepatitis C Virus (HCV) ``Lookback'' Based on Review of Historical Testing Records and Identification of Donors Testing Repeatedly Reactive
                                                                             Using an HCV EIA \1\ 1.0 Screening Test
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
 
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
   RESULTS OF FURTHER TESTING:        EIA 2.0\2\         EIA 3.0\3\        EIA 2.0        RIBA 2.0        RIBA 2.0        RIBA 3.0       RIBA 2.0     S/CO\4\  2.5          S/CO >2.5 or No
                                      Repeatedly         Repeatedly       Negative or    Positive or    Indeterminate   Indeterminat    Negative or                  Determination         of S/
                                       Reactive           Reactive          EIA 3.0       RIBA 3.0                            e          RIBA 3.0                              CO
                                                                           Negative       Positive                                       Negative
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
ACTIONS TO BE TAKEN:                                                                                    Applicable Sections
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
Identify prior collections        610.48(d)(1)       610.48(d)(1)                      610.48(d)(2)   610.48(d)(2)     610.48(d)(2)                  610.48(d)(3)           610.48(d)(4)
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
Quarantine prior in-date          .................  .................  .............  .............  ...............  .............  .............  .............
 collections
---------------------------------
Notify consignees to quarantine   610.48(f)(1),      610.48(f)(1),                     610.48(f)(1),  610.48(f)(1),    610.48(f)(1),  .............  610.48(f)(1),  610.48(f)(1), (f)(2), (f)(3)
                                   (f)(2), (f)(3)     (f)(2), (f)(3)                    (f)(2),        (f)(2), (f)(3)   (f)(2),                       (f)(2),
                                                                                        (f)(3)                          (f)(3)                        (f)(3)
---------------------------------
Consignees perform quarantine of  .................  .................  .............  .............  ...............  .............  .............  .............
 prior collections
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
Exemptions from quarantine        610.48(g)(3)(iii)  610.48(g)(3)(iii)  610.48(g)(3)(                 610.48(g)(3)(iv                 610.48(g)(3)(  .............
                                   \5\                \5\                i)                            )\7\                            ii)
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
Perform further testing                                                                                                                                             610.48(i)(1)(  610.48(i)(1)(
                                                                                                                                                                     i)\13\         ii)\14\
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
Perform optional further testing  610.48(i)(2)(i)\6  610.48(i)(2)(i)\6  .............  .............  610.48(i)(2)(ii  .............  .............  610.48(i)      .............  .............
                                   \                  \                                                )\8\                                           (2)(iii)\10\
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
Notify consignees of test         610.48(i)(3)(i)    610.48(i)(3)(i)    .............  610.48(i)(3)(  610.48(i)(3)(i)  610.48(i)(3)(  .............  610.48(i)(3)(  610.48(i)(3)(  610.48(i)(3)(
 results                          610.48(i)(3)(ii)   610.48(i)(3)(ii)                   ii)           610.48(i)(3)(ii   ii)                           i)             i)             i)
                                                                                                       )                                             610.48(i)(3)(  610.48(i)(3)(  610.48(i)(3)(
                                                                                                                                                      ii)            ii)            ii)
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
Release prior collections from    610.48(j)(3)(ii)\  610.48(j)(3)(ii)\  .............  .............  610.48(j)(3)(ii  .............  .............  610.48(j)(3)(  610.48(j)(3)(
 quarantine                        5\                 5\                                               i)\9\                                          iv)\11\        i)\15\
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
Destroy or label prior            610.48(k)          610.48(k)          .............  610.48(k)      610.48(k)        610.48(k)      .............  610.48(k)      610.48(k)      610.48(k)
 collections
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
Notify transfusion recipients     610.49(a)(6)       610.49(a)(6)       .............  610.49(a)(7)   610.49(a)(8)     .............  .............  610.49(a)(9)\  610.49(a)(10)  610.49(a)(11)
                                                                                                                                                      12\            \16\
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
\1\ ``EIA'' means enzyme linked immunosorbant assay.
\2\ ``RIBA 2.0'' means HCV 2.0 strip immunoblot assay.
\3\ ``RIBA 3.0'' means HCV 3.0 strip immunoblot assay.
\4\ ``S/CO'' means ``Signal to cut off.''
\5\ If further testing using an appropriately chosen supplemental test for HCV was performed and the result was negative.
\6\ May perform further testing using an appropriately chosen licensed supplemental test for HCV.
\7\ If further testing using an HCV EIA 3.0 screening test or an HCV RIBA 3.0 supplemental test was performed and the result was negative.
\8\ May perform further testing using an HCV EIA 3.0 screening test or a licensed supplemental test for HCV. If an HCV EIA 3.0 screening test is performed and is repeatedly reactive, may
  perform further testing using a licensed supplemental test for HCV.
\9\ If further testing using an HCV EIA 3.0 screening test or a licensed supplemental test for HCV was performed and the result was negative.
\10\ May perform further testing using a licensed multiantigen screening test for HCV or a licensed supplemental test for HCV.
\11\ If further testing using a licensed multiantigen screening test for HCV or a licensed supplemental test for HCV was performed and the result was negative.
\12\ If further testing using a licensed multiantigen screening test for HCV or a licensed supplemental test for HCV was performed and the result was positive.
\13\ Using a licensed supplemental test for HCV.
\14\ No frozen or fresh sample is available for further testing.
\15\ If the licensed supplemental test for HCV is negative.
\16\ If the licensed supplemental test for HCV is positive.



[[Page 69416]]

    Dated: December 3, 1999.
Jane E. Henney,
Commissioner of Food and Drugs.

Donna E. Shalala,
Secretary of Health and Human Services.
[FR Doc. 00-28907 Filed 11-15-00; 8:45 am]
BILLING CODE 4160-01-F