69378 Federal Register / Vol. 65, No. 222 / Thursday, November 16, 2000 / Proposed Rules

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.

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 bloodrelated 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.

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

§§ 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 nonviralinactivated 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 longterm 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

69380 Federal Register / Vol. 65, No. 222 / Thursday, November 16, 2000 / Proposed Rules

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 (AntiHCV).’’ Consistent with the

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

§ 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

(§ 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.

69382 Federal Register / Vol. 65, No. 222 / Thursday, November 16, 2000 / Proposed Rules

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

§§ 610.46 and 610.47, the HIV

‘‘lookback’’ regulations. The proposed

revisions to §§ 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 § 610.45, ‘‘Human

Immunodeficiency Virus (HIV)

requirements,’’ because its requirements

would be included in the revision of

proposed § 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

§ 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 § 610.40(g),

include the proposed requirements to

initiate HCV ‘‘lookback’’ and

requirements to initiate HIV ‘‘lookback’’

(currently in § 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 § 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 § 610.45(d).)

B. Proposed Revisions to

§ 606.100(b)(19)

FDA is proposing to amend

§ 606.100(b)(19), which currently

prescribes requirements for SOP’s, in

accordance with §§ 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 § 606.100(b)(19) to include

requirements for blood establishments

to have SOP’s, in accordance with

proposed §§ 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 § 606.160

FDA is proposing to amend § 606.160.

Section 606.160(b)(1)(viii) currently

prescribes requirements for maintaining

records of quarantine, notification,

testing, and disposition performed

under §§ 610.46 and 610.47, whenever a

donor subsequently tests repeatedly

reactive for evidence of HIV infection.

FDA is proposing to revise

§ 606.160(b)(1)(viii), to include

requirements for maintaining records of

quarantine, notification, testing, and

disposition performed under proposed

§§ 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 § 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 § 610.45

As previously discussed, in the

Federal Register of August 19, 1999 (64

FR 45340), FDA issued a proposed rule

to revise § 610.40, and to delete

§ 610.45, ‘‘Human Immunodeficiency

Virus (HIV) requirements,’’ because,

except as discussed below, the

requirements of § 610.45 would be

included in proposed § 610.40.

Section 610.45(d) currently requires

blood establishments to comply with

§§ 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 § 610.45. This proposed

rule would include the requirements of

current § 610.45(d) into proposed

§ 610.40(g). Proposed § 610.40(g) would

require blood establishments to comply

with §§ 610.46 and 610.47, and with

proposed §§ 610.48 and 610.49, thereby

requiring compliance with the HIV and

Federal Register / Vol. 65, No. 222 / Thursday, November 16, 2000 / Proposed Rules 69383

HCV ‘‘lookback’’ regulations,

respectively.

E. Proposed Revisions to Headings of

§§ 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 § 610.46 to read

‘‘Human Immunodeficiency Virus (HIV)

‘Lookback;’ quarantine, consignee

notification and further testing’’ to

distinguish it from the new § 610.48,

‘‘Hepatitis C Virus (HCV) ‘‘‘lookback;’’’

quarantine, consignee notification and

further testing.’’ Likewise, FDA is

proposing to amend the heading of

§ 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 § 610.49, ‘‘Hepatitis C

Virus (HCV) ‘‘Lookback;’’ notification of

transfusion recipients.’’ As previously

noted, FDA is proposing to amend

§ 610.46 for consistency with proposed

§ 610.48 of this proposed rule, and to

amend § 610.47 for consistency with

§ 610.49 of this proposed rule. The

corresponding revisions to § 610.46 and

to § 610.47 are noted in the discussion

of proposed § 610.48 and proposed

§ 610.49.

F. Proposed § 610.48(a), Quarantine and

Consignee Notification

Proposed § 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 § 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 § 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

§ 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 §§ 10.48(a), (e), and (f) and the

conforming amendment to 610.46(a).

FDA is also proposing that the

‘‘lookback’’ measures specified in

§ 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 § 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

§ 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 § 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 § 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

§ 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 § 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 § 610.46(a). FDA is

proposing to amend § 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

§ 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

69384 Federal Register / Vol. 65, No. 222 / Thursday, November 16, 2000 / Proposed Rules

prior collection that has not expired

because records are held for 6 months

after the latest expiration date of the

individual product.

G. Proposed § 610.48(b), Further Testing

and Consignee Notification of Results

Proposed § 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 § 610.48(a), and

notification of consignees of the results

of the further testing. Proposed

§ 610.48(b) would require blood

establishments to perform further

testing, in accordance with proposed

§ 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 § 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 § 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 § 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

§ 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 § 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

§ 610.48(h) or (i)) would require use of

a currently licensed test, as specified.

The purpose of § 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

§ 610.48(c)(4) and (c)(5); or (2) has a

record of further testing (as specified in

§ 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 indate 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 § 610.48(g)(2)), and to

notify consignees to quarantine such

prior collections, as specified under

proposed § 610.48(e)(2); to perform

further testing, as specified in proposed

§ 610.48(h)(1), on donors identified in

accordance with proposed § 610.48(c)(4)

and (c)(5); or optionally to perform

further testing in accordance with

§ 610.48(h)(2) on donors identified in

accordance with § 610.48(c)(2) and

(c)(3); and to notify consignees of the

test result, in accordance with proposed

§ 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 § 610.49(b).

Under proposed § 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

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

§ 610.48(c)(1)); or (c)(2) tested

indeterminate on a supplemental test for

HCV (as specified in § 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 § 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

§ 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 § 610.48(g)(2). For donors

identified in accordance with

§ 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 § 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 § 610.48(h)(1).

I. Proposed § 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 § 610.48(d), which

parallels the requirements of § 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 § 610.48(c), which is

based on the multiantigen screening

test, proposed § 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 § 610.48(d), blood

establishments would identify

previously distributed blood and blood

components in any of the following four

instances: (1) As proposed in

§ 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

§ 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 § 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 § 610.48(d)(4), where the

donor tested repeatedly reactive for

69386 Federal Register / Vol. 65, No. 222 / Thursday, November 16, 2000 / Proposed Rules

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 § 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 § 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 § 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

§ 610.48(g)(3).

J. Proposed § 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 § 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

§ 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

§ 610.48(j)(2)), or to destroy or relabel

them (under proposed § 610.48(k)).

Proposed § 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 § 610.48(e)(1) would require

blood establishments to quarantine indate prior collections of blood and

blood components collected from

donors identified in the review of

records, under proposed § 610.48(c),

while further testing is performed, as

required in proposed § 610.48(h)(1) or as

optional testing is performed in

accordance with § 610.48(h)(2).

As previously mentioned, some

exceptions to quarantine are specified in

proposed § 610.48(g)(2). Prior

collections that meet the criteria under

proposed § 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

§ 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 § 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

§ 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 § 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 § 610.48(f), which

parallels the requirements of § 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 § 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

§ 610.48(j)(3)), or to destroy or relabel

them (under proposed § 610.48(k)).

Proposed § 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 § 610.48(f)(1) would require

blood establishments to quarantine indate prior collections of blood and

blood components from donors

identified in the review of historical

testing records, under proposed

§ 610.48(d), while further testing is

performed, as required in proposed

§ 610.48(i)(1) or as optional testing is

performed in accordance with

§ 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

§ 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

§ 610.48(g)(3). Prior collections that

Federal Register / Vol. 65, No. 222 / Thursday, November 16, 2000 / Proposed Rules 69387

meet the criteria under proposed

§ 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 § 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

§ 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 § 610.48(f)

and the appropriateness of the 1-year

timeframe to complete all quarantine

and notification.

Proposed § 610.48(f)(3) would require

consignees notified in accordance with

proposed § 610.48(f)(2) to quarantine all

prior collections of blood and blood

components subject to quarantine under

proposed § 610.48(f)(1), except as

provided in proposed § 610.48(g)(3).

L. Proposed § 610.48(g), Exemption

From Quarantine

Proposed § 610.48(g) specifies which

prior collections are not suspected as

being window period donations and,

therefore, are not subject to quarantine

under proposed § 610.48(a), (e), and (f).

Proposed § 610.48(g)(1) would exempt

from quarantine certain prior collections

otherwise subject to quarantine under

proposed § 610.48(a) when a donor tests

repeatedly reactive on a multiantigen

screening test for evidence of HCV

infection. Proposed § 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 § 610.48(a).

Under proposed § 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 § 610.40(a).

An explanation of ‘‘window period’’

donations and a corresponding example

are provided previously in the

description of proposed § 610.48(c).

In addition, proposed

§ 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 § 610.48(j).

As specified in proposed § 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 § 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 § 610.48(g)(2) provides for

exceptions from quarantine performed

in accordance with proposed § 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

§ 610.48(g)(1), proposed § 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

§ 610.48(g)(2), prior collections of blood

and blood components would not be

subject to quarantine under proposed

§ 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 § 610.48(g)(3) provides for

exceptions from quarantine (performed

in accordance with proposed

§ 610.48(f)) following the review of

records based on screening performed

using a single antigen screening test.

Similar to the provisions of proposed

§ 610.48(g)(1) and (g)(2), proposed

§ 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 § 610.48(g)(3), prior

collections of blood and blood

components would not be subject to

quarantine under proposed § 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 § 610.48(g)(3)(i)); or (2)

records show that the repeatedly

reactive screening test result was

obtained using an HCV EIA 1.0

69388 Federal Register / Vol. 65, No. 222 / Thursday, November 16, 2000 / Proposed Rules

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 § 610.48(g)(3)(ii)); or (3) the

donor identified in accordance with

proposed § 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

§ 610.48(g)(3)(iii)); or (4) the donor

identified in accordance with proposed

§ 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

§ 610.48(g)(3)(iv)).

FDA is also proposing a conforming

amendment to § 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 § 610.48(h), Further Testing

Following Review of Historical Testing

Records and Consignee Notification

Based on Screening Performed Using a

Multiantigen Screening Test

Proposed § 610.48(h) is intended to

require that prior collections identified

in accordance with § 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 § 610.48(j)), or

destroyed or relabeled (under

§ 610.48(k)), and if notification of

transfusion recipients is necessary

(under § 610.49(a)). In addition, blood

establishments would have the option to

perform further testing for prior

collections identified in accordance

with § 610.48(c)(2) and (c)(3). Proposed

§ 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

§ 610.48(c)(4) and (c)(5), as being at

increased risk of transmitting HCV.

Proposed § 610.48(h)(1) would require

that further testing be performed as

follows: (1) As proposed in

§ 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

§ 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

§ 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 § 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 § 610.48(h)(2), blood

establishments would have the option to

perform further testing on prior

collections identified in accordance

with § 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

§ 610.48(h)(2), blood establishments that

have performed the review of records

and identified prior collections in

accordance with proposed § 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 § 610.48(h)(2)(i), if the

donor was identified in accordance with

proposed § 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 § 610.48(h)(2)(ii), if

the donor was identified in accordance

with proposed § 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 § 610.48(g) for more

information regarding use of ‘‘an

appropriately chosen supplemental

test’’); or (3) as proposed in

§ 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 § 610.48(h)(2)(iv), if the

donor was identified in accordance with

proposed § 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

§ 610.48(j), to release from quarantine,

or under proposed § 610.48(k), to

destroy or appropriately label prior

collections, or under proposed

§ 610.49(a), to notify any transfusion

recipients.

Under proposed § 610.48(h)(3), blood

establishments would be required to

notify consignees of the results of the

additional testing, performed in

accordance with proposed § 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

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

§ 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 § 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 § 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 § 610.48(i),

which parallels the requirements of

proposed § 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 § 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

§ 610.48(j)), or destroyed or relabeled

(under § 610.48(k)), and if notification of

transfusion recipients is necessary

(under § 610.49(a)). In addition, blood

establishments would have the option to

perform further testing for prior

collections identified in accordance

with § 610.48(d)(1), (d)(2), and (d)(3).

Proposed § 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

§ 610.48(d)(4), as being at increased risk

of transmitting HCV.

Proposed § 610.48(i)(1) would require

that further testing for donors identified

in accordance with proposed

§ 610.48(d)(4) be performed as follows:

(1) As proposed in § 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 § 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 § 610.48(i)(2), blood

establishments would have the option to

perform further testing on prior

collections identified in accordance

with § 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

§ 610.48(i), blood establishments that

have performed the review of historical

testing records and identified prior

collections in accordance with proposed

§ 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

§ 610.48(i)(2)(i), if the donor was

identified in accordance with proposed

§ 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 § 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 § 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

69390 Federal Register / Vol. 65, No. 222 / Thursday, November 16, 2000 / Proposed Rules

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 § 610.48(i)(3), blood

establishments would be required to

notify consignees of the results of the

additional testing, performed in

accordance with proposed § 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 § 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 § 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 § 610.48(j), Release From

Quarantine

The purpose of proposed § 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 § 610.48(j)(1), those

prior collections subject to quarantine

under proposed § 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 § 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 § 610.48(j)(2), prior

collections subject to quarantine under

proposed § 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

§ 610.48(g)(2), would be released from

quarantine if certain conditions are met

as follows: (1) As proposed in

§ 610.48(j)(2)(i)(A), if the donor’s testing

records meet the conditions specified in

proposed § 610.48(c)(4) (repeatedly

reactive HCV EIA 2.0 screening test

without additional test results) and

further testing was performed in

accordance with § 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

§ 610.48(j)(2)(i)(B), if the donor’s testing

records meet the conditions specified in

proposed § 610.48(c)(4) and the blood

establishment performed further testing

in accordance with proposed

§ 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 § 610.48(j)(2)(ii), if the donor’s testing

records meet the conditions specified in

proposed § 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

§ 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

§ 610.48(j)(2)(iii), if the donor’s testing

records meet the conditions specified in

proposed § 610.48(c)(2) (repeatedly

reactive multiantigen screening test and

indeterminate supplemental test) and

the blood establishment performed

further testing in accordance with

proposed § 610.48(h)(2), and one of

three conditions specified in proposed

§ 610.48(j)(2)(iii)(A), (j)(2)(iii)(B) or

(j)(2)(iii)(C) applies. (Proposed

§ 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

§ 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

§ 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 § 610.48(h)(2)(ii) of this

section using a HCV RIBA 3.0 and the

result is negative. Proposed

§ 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

§ 610.48(h)(2)(iii) of this section using a

licensed supplemental test for HCV and

the result is negative) or; (5) under

proposed § 610.48(j)(2)(iv), if the

donor’s testing records meet the

conditions specified in proposed

§ 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

§ 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 § 610.48(j)(3), prior

collections subject to quarantine under

proposed § 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

§ 610.48(g)(3), would be released from

quarantine if certain conditions are met

as follows: (1) Under proposed

§ 610.48(j)(3)(i), if the donor’s testing

records meet the conditions specified in

proposed § 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

§ 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

§ 610.48(j)(3)(ii), if the donor’s testing

records meet the conditions specified in

proposed § 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

§ 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

§ 610.48(j)(3)(iii), if the donor’s testing

records meet the conditions specified in

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proposed § 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

§ 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 § 610.48(j)(3)(iv),

if the donor’s testing records meet the

conditions specified in proposed

§ 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

§ 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 § 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 § 610.48(k), Destruction or

Labeling of Prior Collections Held in

Quarantine

The purpose of proposed § 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 § 610.48(g) and do not meet

the conditions for release from

quarantine in accordance with proposed

§ 610.48(j). Proposed § 610.48(k) would

require that blood establishments and

consignees take appropriate action for

prior collections subject to quarantine

under proposed § 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 § 610.48(g),

or (2) the prior collection was subject to

release from quarantine under proposed

§ 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

§§ 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 antiHCV. 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 § 610.46, the HIV

‘‘lookback’’ requirements, for

consistency and to clarify the actions to

be taken for prior collections subject to

quarantine under § 610.46(a). FDA is

proposing to redesignate § 610.46(e) as

§ 610.46(f) and to add new § 610.46(e)

Destruction or labeling of prior

collections held in quarantine,

consistent with this proposal.

Q. Proposed § 610.48(l)

Proposed § 610.48(l) specifies that

actions taken under proposed § 610.48

do not constitute a recall. This

regulation is consistent with current

§ 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 § 7.41)

is unnecessary; and (4) the products

being quarantined may not be in

violation of applicable laws (see § 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 § 610.49(a), Hepatitis C

Virus (HCV) ‘‘Lookback;’’ Notification of

Transfusion Recipients

The purpose of proposed § 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 § 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

§ 610.48(a)) and further testing

(performed as specified in proposed

§ 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

§ 610.48(c) or (d)), and further testing (as

shown in historical records or as

performed under proposed § 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 § 610.49(a), would require

transfusion services to take appropriate

actions, in accordance with § 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 § 610.48(a)

and the result of the licensed,

supplemental test performed in

accordance with proposed § 610.48(b) is

positive; or (2) the donor was identified

in accordance with proposed

§ 610.48(c)(1), and the result of the

supplemental test identified in the

review of records is positive; or (3) the

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donor was identified in accordance with

proposed § 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 § 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 § 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

§ 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

§ 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

§ 610.48(h)(1)(iii); or (6) the donor was

identified in accordance with proposed

§ 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 § 610.48(g)(3)) or release from

quarantine (under proposed

§ 610.48(j)(3)) have been met, or the

donor was further tested in accordance

with § 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

§ 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

§ 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

§ 610.48(g)(3)), or release from

quarantine (under proposed

§ 610.48(j)(3)) have been met, or the

donor was further tested in accordance

with proposed § 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 § 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

§ 610.48(i)(2)(iii) is positive; or (10) the

donor was identified in the review of

historical testing records in accordance

with proposed § 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

§ 610.48(i)(1) is positive; or (11) the

donor was identified in the review of

historical testing records, in accordance

with § 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 § 610.48(i)(1)(ii).

FDA is proposing conforming

amendments to HIV ‘‘lookback’’

requirements of § 610.47(a) for

consistency with the HCV ‘‘lookback’’

requirements of proposed § 610.49(a).

FDA is proposing to amend § 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 § 610.46(b)

are positive.

S. Proposed § 610.49(b), Notification of

Recipients of Prior Transfusion

Proposed § 610.49(b) describes the

requirements for the process of

notification of transfusion recipients.

Under proposed § 610.49(b), consistent

with requirements for notification in the

HIV ‘‘lookback’’ regulations in § 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

§ 610.49(b) and under the proposed

conforming amendment to § 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 § 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 § 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

§ 610.48(c)(2) through (c)(5), and

proposed § 610.48(d)(1) through (d)(4)

generally will be further tested by the

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blood establishment in accordance with

§ 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 § 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 § 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 § 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 § 610.46(a) for HIV

‘‘lookback’’ (for HCV ‘‘lookback’’ in

proposed § 610.48(a)). In addition, FDA

is proposing to require HCV ‘‘lookback’’

based on the review of available

historical testing records (proposed

§ 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 § 610.47(b) for

consistency with the HCV ‘‘lookback’’

requirements of proposed § 610.49(b).

FDA is proposing to amend § 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 § 610.49(c), Notification of

Legal Representative or Relative

Proposed § 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 § 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 § 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

§ 606.160. Proposed § 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 § 610.47(c) for

consistency with the HCV ‘‘lookback’’

requirements of proposed § 610.49(c).

FDA is proposing to amend § 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 § 610.49(d), Reference

Tables

Proposed § 610.49(d) includes four

tables intended to assist in identifying

the applicable paragraphs of proposed

§§ 610.48 and 610.49 and the

corresponding ’’lookback’’ actions. In

particular, the requirements of proposed

§§ 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

§ 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 § 610.48(a).

Table 1 of proposed § 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 § 610.48(b),

and prior collections could be released

from quarantine if the conditions of

proposed § 610.48(j)(1) were met.

Tables 2, 3, and 4 of proposed

§ 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

§ 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 § 610.48(c) as

testing repeatedly reactive using an HCV

EIA 2.0 screening test. Table 4 of

proposed § 610.49 identifies applicable

sections based on the review of

historical testing records for donors

identified in accordance with proposed

§ 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,

69394 Federal Register / Vol. 65, No. 222 / Thursday, November 16, 2000 / Proposed Rules

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 (number) One-Time Cost Yearly Cost

Blood Establishments (2,800)

Hepatitis C Virus (HCV) ‘‘Lookback’’ Standard Operating Procedures (SOP’s) $2,875,040

Prospective review $4,558,442

Federal Register / Vol. 65, No. 222 / Thursday, November 16, 2000 / Proposed Rules 69395

TABLE 1.—SUMMARY OF ESTIMATED ONE-TIME YEARLY COSTS FOR BLOOD ESTABLISHMENT AND BLOOD PRODUCT

CONSIGNEES—Continued

Affected Entities (number) One-Time Cost Yearly Cost

Historical review $33,239,402

Subtotal $36,114,442 $4,558,442

Consignees (6,200)

HCV ‘‘Lookback’’ SOP’s $2,546,464

Prospective review $2,114,632

Historical Review $50,106,540

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 CLIAcertified 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 pre1988 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

69396 Federal Register / Vol. 65, No. 222 / Thursday, November 16, 2000 / Proposed Rules

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 onetime review cost of $33,239,402. Again,

this estimate does not account for pre1988 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 onetime 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.

Federal Register / Vol. 65, No. 222 / Thursday, November 16, 2000 / Proposed Rules 69397

TABLE 2.—ESTIMATED COST PER RECIPIENT NOTIFICATION

Cost of ‘‘Lookback’’ and

Notification1 Cost Per Recipient Transfused Cost Per Recipient Notified

Prospective $6,673,0742 $658 $1,541

Historial $83,345,942 $642 $1,440

1Excludes cost of developing SOP’s.

2Annual 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 HCVassociated 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 welldefined, 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 casecontrol 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 costeffectiveness 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 costeffectiveness 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

69398 Federal Register / Vol. 65, No. 222 / Thursday, November 16, 2000 / Proposed Rules

1The 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.

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 interferon2b 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 costeffectiveness 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-ofmagnitude 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 unit1, 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.

Federal Register / Vol. 65, No. 222 / Thursday, November 16, 2000 / Proposed Rules 69399

Autologous blood collection presents

less risk of infectious disease, but it is

not generally considered to be costeffective, 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

69400 Federal Register / Vol. 65, No. 222 / Thursday, November 16, 2000 / Proposed Rules

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 onetime 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;

Federal Register / Vol. 65, No. 222 / Thursday, November 16, 2000 / Proposed Rules 69401

the system may also own non-healthrelated 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 ina-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)

Bed Size Category Non-Federal Hospitals Estimated Percent

Inpatient Surgeries

Estimated Share of

Recipients

Estimated 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

Bed Size Category

Cost per Hospital for

Retrospective

Notification

Gross Annual Revenue

per Hospital

Notification Cost as

Percent of Gross

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 onethousandth 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.

69402 Federal Register / Vol. 65, No. 222 / Thursday, November 16, 2000 / Proposed Rules

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 HCVinfected 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’’ (§§ 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 § 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

§§ 610.46 and 610.47, the HIV

‘‘lookback’’ regulations (61 FR 47413,

September 9, 1996). The proposed

revisions to §§ 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-forProfit) 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 §§ 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

§§ 610.48(a)(1)(ii), 610.48(b), 610.49(b),

610.49(c) and 606.160(b)(1)(viii) for

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

§ 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

§ 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

§§ 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 § 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 §§ 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 § 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 § 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 §§ 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 § 606.100(b)(19) and

consignees approximately 16 hours to

establish written procedures in

accordance with proposed § 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

§ 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

§ 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 §§ 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 BURDEN1

21 CFR Section No. of Respondents Annual Frequency

per Response

Total Annual

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)(ii) 2,800 4.6 12,816 .17 2,179

610.48(b) 2,800 4.6 12,816 .17 2,179

610.49(b)and (c) 6,200 2 10,894 .50 5,447

Total 11,018

1There are no capital costs or operating and maintenance costs associated with this collection of information.

69404 Federal Register / Vol. 65, No. 222 / Thursday, November 16, 2000 / Proposed Rules

TABLE 6.—ESTIMATED ONE-TIME REPORTING BURDEN1

21 CFR Section No. of Respondents Annual Frequency

per Response

Total Annual

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)(i) and (h)(3)(ii) 2,800 41 115,228 .1 11,523

610.48(i)(3)(i) and (i)(3)(ii) 2,800 67 188,448 .1 18,845

610.49(b) and (c) 6,200 42 258,125 .5 129,063

Total 189,799

1There are no capital costs or operating and maintenance costs associated with this collection of information.

TABLE 7.—ESTIMATED ANNUAL RECORDKEEPING BURDEN1

21 CFR Section No. of

Recordkeepers

Annual Frequency of

Recordkeeping

Total Annual

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)(viii) 6,200 4 25,632 .17 4,357

610.49(b) and (c) 6,200 2 12,816 .17 2,179

Total 11,523

1There are no capital costs or operating and maintenance costs associated with this collection of information.

TABLE 8.—ESTIMATED ONE-TIME RECORDKEEPING BURDEN1

21 CFR Section No. of

Recordkeepers

Frequency of

Recordkeeping Total Records Hours per Record Total Hours

606.100(b)(19) 2,800 1 2,800 40 112,000

606.100(b)(19) 6,200 1 6,200 16 99,200

606.160(b)(1)(viii) 2,800 108 303,676 0.08 24,294

606.160(b)(1)(viii) 6,200 49 303,676 0.08 24,294

610.49(b) and (c) 6,200 42 258,125 0.08 20,650

Total 280,438

1There 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,

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

§ 606.100 Standard operating procedures.

* * * * *

(b) * * *

(19) Procedures in accordance with

§§ 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 § 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

§§ 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:

§ 606.160 Records.

* * * * *

(b) * * *

(1) * * *

(viii) Records of quarantine, consignee

notification, further testing, transfusion

recipient notification, and disposition

performed under §§ 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:

§ 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 §§ 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:

§ 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 § 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

69406 Federal Register / Vol. 65, No. 222 / Thursday, November 16, 2000 / Proposed Rules

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 § 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 § 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

§§ 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 antiHIV. 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 § 7.3 of this chapter.

7. Section 610.47 is revised to read as

follows:

§ 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 § 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

§ 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 § 606.160 of this

chapter. Reasons for notifying the

recipient’s relative or legal

representative on his or her behalf shall

be documented under § 606.160 of this

chapter.

8. Section 610.48 is added to subpart

E to read as follows:

§ 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

§ 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 indate blood and blood components

collected from that donor at any time

prior to the repeatedly reactive test,

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

§ 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

§ 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

69408 Federal Register / Vol. 65, No. 222 / Thursday, November 16, 2000 / Proposed Rules

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 § 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 § 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

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

69410 Federal Register / Vol. 65, No. 222 / Thursday, November 16, 2000 / Proposed Rules

(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

§§ 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 antiHCV. 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

§ 7.3 of this chapter.

9. Section 610.49 is added to subpart

E to read as follows:

§ 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 § 610.48(b) and in

accordance with the testing

requirements specified in § 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 § 610.48(c)(1);

(3) The result of the supplemental test

identified in the review of historical

testing records in accordance with

§ 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

§ 610.48(g)(2) have been met; or

(iii) The donor was further tested in

accordance with § 610.48(h)(2)(i),

(h)(2)(ii), or (h)(2)(iii) and any of the

conditions for release from quarantine

specified in § 610.48(j)(2)(iii) have been

met; or

(iv) The donor was further tested in

accordance with § 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 § 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 § 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

Federal Register / Vol. 65, No. 222 / Thursday, November 16, 2000 / Proposed Rules 69411

review of historical testing records, in

accordance with § 610.48(c)(4) and

(c)(5), and no fresh or frozen sample is

available for further testing, as specified

in § 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

§ 610.48(d)(1), unless:

(i) Any of the conditions for

exemption from quarantine specified in

§ 610.48(g)(3) have been met; or

(ii) The donor was further tested in

accordance with § 610.48(i)(2)(i) and

any of the conditions for release from

quarantine specified in § 610.48(j)(3)

have been met; or

(iii) The donor was further tested in

accordance with § 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

§ 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 § 610.48(d)(2),

unless:

(i) Any of the conditions for

exemption from quarantine specified in

§ 610.48(g)(3) have been met; or

(ii) The donor was further tested in

accordance with § 610.48(i)(2)(ii) and

any of the conditions for release from

quarantine specified in § 610.48(j)(3)

have been met; or

(iii) The donor was further tested in

accordance with § 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 § 610.48(i)(2)(iii) is

positive for a donor identified in the

review of historical testing records, in

accordance with § 610.48(d)(3); or

(10) The result of the licensed,

supplemental test for HCV performed in

accordance with § 610.48(i)(1) is

positive for a donor identified in the

review of historical testing records, in

accordance with § 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 § 610.48(d)(4), and no

fresh or frozen sample is available for

further testing, as specified in

§ 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

§ 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 § 606.160 of this

chapter. Reasons for notifying the

recipient’s relative or legal

representative on his or her behalf shall

be documented under § 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 §§ 610.48 and

610.49. Based on the initial screening

test select the appropriate table from the

following:

69412 Federal Register / Vol. 65, No. 222 / Thursday, November 16, 2000 / Proposed Rules

TABLE 1.—OUTLINE OF PROVISIONS OF § 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.

TABLE 2.—OUTLINE OF

PROVISIONS OF § 610.48 FOR

HEPATITIS C VIRUS (HCV) ‘‘LOOKBACK’’ BASED ON

REVIEW OF

HISTORICA

IDENTIFICATION OF

DONORS

TESTING

REPEATEDLY

REACTIVE

USING AN HCV EIA1 3.0 SCREENING

TES

Results of Further Testing: RIBA 2.02 Positive or

RIBA 3.03 Positive

RIBA 2.0 Negative RIBA 2.0 Indeterminate RIBA 3.0 Negative RIBA 3.0 Indeterminate 

Actions To Be Taken: Applicable SectionsIdentify prior collections 610.48(c)(1) 610.48(c)(3) 610.48(c)(2) 610.48(c)(2) Quarantine prior in-date collectionsNotify 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) 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) Perform further testing Perform optional further testing 610.48(h)(2)(iv)4 610.48(h)(2)(iii)4Notify consignees of test results 610.48(h)(3)(ii) 610.48(h)(3)(i)

610.48(h)(3)(ii)

610.48(h)(3)(i)610.48(h)(3)(ii)

610.48(h)(3)(ii) 

Release prior collections from

quarantine

610.48(j)(2)(iv)5 610.48(j)(2)(iii)(C)5 

Destroy or label prior collections 610.48(k) 610.48(k) 610.48(k) 610.48(k) Notify transfusion recipients 610.49(a)(2) 610.49(a)(3) 

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.

TABLE 3.—OUTLINE OF

PROVISIONS OF § 610.48 FOR

HEPATITIS C VIRUS (HCV) ‘‘LOOKBACK’’ BASED ON

REVIEW OF

HISTORICA

IDENTIFICATION OF

DONORS

TESTING

REPEATEDLY

REACTIVE

USING AN HCV EIA1 2.0 SCREENING

TES

Results of Further Testing: RIBA 2.02 Positive

or RIBA 3.0 3

Positive

RIBA 2.0 Negative RIBA 2.0 Indeterminate RIBA 3.0 Negative RIBA 3.0

Indeterminate

No 

Actions to be Taken: Applicable SectionsIdentify prior collections 610.48(c)(1) 610.48(c)(2) 610.48(c)(2) Quarantine prior in-date collectionsNotify 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)

6

Consignees perform quarantine of prior

collections

Exemptions from quarantine 610.48(g)(2)(i) 610.48(g)(2)(ii)(A) 610.48(g)(2)(i) 610.48(g)(2)(ii)(A) 610.48(g)(2)(i) Perform further testing 610.48(h)(1)(i)(A)9 Perform optional further testing 610.48(h) (2)(i)4

610.48(h)(2)(ii)5

610.48(h) (2)(i)6

Notify consignees of test results 610.48(h)(3)(ii) 610.48(h)(3)(i)

610.48(h) (3)(ii)

610.48(h)(3)(i)610.48(h) (3)(ii)

610.48(h) (3)(ii) 610.48(h)(3)(i)

610.48(h)(3)(ii)

Release prior collections from quarantine 610.48(j)(2)(iii)(A)7

610.48(j)(2)(iii)(B)8

610.48(j) (2)(iii)(A)8 610.48(j)(2)(i)(A)12 

Destroy or label prior collections 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)14 

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.9Perform a licensed supplemental test for HCV.10Perform 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.

TABLE 4.—OUTLINE OF

PROVISIONS OF § 610.48 FOR

HEPATITIS C VIRUS (HCV) ‘‘LOOKBACK’’ BASED ON

REVIEW OF

HISTORICA

IDENTIFICATION OF

DONORS

TESTING

REPEATEDLY

REACTIVE

USING AN HCV EIA 1 1.0 SCREENING

TES

RESULTS OF FURTHER

TESTING:

EIA 2.02 Repeatedly

Reactive

EIA 3.03 Repeatedly

Reactive

EIA 2.0 Negative

or EIA 3.0

Negative

RIBA 2.0 Positive

or RIBA 3.0

Positive

RIBA 2.0

Indeterminate

RIBA 3.0

Indeterminate

RIBA 2.0

Negative or RIBA

3.0 Negative

S/CO4 < 2.

ACTIONS TO BE TAKEN: Applicable SectionsIdentify 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) Quarantine prior in-date collectionsNotify consignees to quarantine 610.48(f)(1), (f)(2),

(f)(3)

610.48(f)(1), (f)(2),

(f)(3)

610.48(f)(1),

(f)(2), (f)(3)

610.48(f)(1), (f)(2),

(f)(3)

610.48(f)(1),

(f)(2), (f)(3)

610.48(f)(1),

(f)(2), (f)(3)

Consignees perform quarantine of

prior collections

Exemptions from quarantine 610.48(g)(3)(iii)5 610.48(g)(3)(iii)5 610.48(g)(3)(i) 610.48(g)(3)(iv)7 610.48(g)(3)(ii)Perform further testing Perform optional further testing 610.48(i)(2)(i)6 610.48(i)(2)(i)6 610.48(i)(2)(ii)8 610.48(i) (2)(iiNotify consignees of test results 610.48(i)(3)(i)

610.48(i)(3)(ii)

610.48(i)(3)(i)610.48(i)(3)(ii)

610.48(i)(3)(ii) 610.48(i)(3)(i)

610.48(i)(3)(ii)

610.48(i)(3)(ii) 610.48(i)(3)(i)

610.48(i)(3)(ii)

Release prior collections from

quarantine

610.48(j)(3)(ii)5 610.48(j)(3)(ii)5 610.48(j)(3)(iii)9 610.48(j)(3)(iv

Destroy or label prior collections 610.48(k) 610.48(k) 610.48(k) 610.48(k) 610.48(k) 610.48(k) Notify transfusion recipients 610.49(a)(6) 610.49(a)(6) 610.49(a)(7) 610.49(a)(8) 610.49(a)(9)12 

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 t

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.

69416 Federal Register / Vol. 65, No. 222 / Thursday, November 16, 2000 / Proposed Rules

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

DEPARTMENT OF HEALTH AND

HUMAN SERVICES

Health Care Financing Administration

42 CFR Part 482

[HCFA–3014–P]

RIN 0938–AJ29

Medicare and Medicaid Programs;

Hospital Conditions of Participation:

Laboratory Services

AGENCY: Health Care Financing

Administration (HCFA), HHS.

ACTION: Proposed rule.

SUMMARY: This proposed rule would

require hospitals that transfuse blood

and blood products to prepare and

follow written procedures for

appropriate action when it is

determined that blood and blood

products the hospitals received and

transfused are at increased risk for

transmitting hepatitis C virus (HCV);

quarantine prior collections from a

donor who is at increased risk for

transmitting HCV infection; notify

transfusion recipients, as appropriate, of

the need for HCV testing and

counseling; and extend the records

retention period to 10 years.

These changes are based on

recommendations by the Secretary’s

Advisory Committee on Blood Safety

and Availability. The intent is to aid in

the prevention of HCV infection and to

create opportunities for disease

prevention many years after recipient

exposure to a donor.

DATES: We will consider written

comments if we receive them at the

appropriate address, as provided below,

no later than 5 p.m. on or before January

16, 2001.

ADDRESSES: Mail written comments (one

original and three copies) to the

following address: Health Care

Financing Administration, U.S.

Department of Health and Human

Services, P.O. Box 8010, Attention:

HCFA–3014–P, 7500 Security

Boulevard, Baltimore, Maryland 21244–

8010.

If you prefer, you may deliver your

written comments (one original and

three copies) to one of the following

addresses:

Room 443–G, Hubert H. Humphrey

Building, 200 Independence

Avenue, SW., Washington, DC

20201, or,

Room C5–09–26, 7500 Security

Boulevard, Baltimore, Maryland

21244–1850.

Because of staffing and resource

limitations, we cannot accept audio,

visual, or facsimile (FAX) copies of

comments. In commenting, please refer

to file code HCFA–3014–P. Comments

received timely will be available for

public inspection as they are received,

generally beginning approximately 3

weeks after publication of a document,

in room 443–G of the Department’s

offices at 200 Independence Avenue,

SW., Washington, DC, on Monday

through Friday of each week from 8:30

a.m. to 5 p.m. (phone: (202) 690–7890).

FOR FURTHER INFORMATION CONTACT:

Mary Collins, (410) 786–3189.

SUPPLEMENTARY INFORMATION:

I. Background

In accordance with section 1861(e) of

the Social Security Act (the Act),

hospitals must meet certain conditions

in order to participate in the Medicare

program. These conditions are intended

to protect patient health and safety and

ensure that high-quality care is

provided. Hospitals receiving payment

under Medicaid must meet the Medicare

conditions of participation.

Regulations containing the Medicare

conditions of participation for hospitals

are located in the Code of Federal

Regulations at 42 CFR part 482. The

condition of participation for hospital

laboratory services at § 482.27 (c)

currently specifies the steps hospitals

must take when they become aware they

have administered potentially human

immunodeficiency virus (HIV)

infectious blood or blood products to a

patient. The more detailed requirements

for laboratories appear in 42 CFR part

493, which sets forth requirements for

all laboratories participating in the

Medicare, Medicaid, and Clinical

Laboratory Improvement Amendments

(CLIA) programs.

The Health Care Financing

Administration (HCFA) and the Food

and Drug Administration (FDA) are

responsible for ensuring the safety of

blood and blood products.

Blood banks (referred to as blood

establishments in FDA regulations ) are

subject to the FDA regulations for

current good manufacturing practices

and additional standards for the

manufacture of blood and blood

components under 21 CFR parts 211,

600, 601, 606, 610, and 640.

Laboratories that provide transfusion

services are subject to CLIA

requirements for quality control and

health and safety standards (42 CFR part

493, subpart K). Laboratories in

hospitals are also subject to the hospital

conditions of participation for adequacy

of laboratory services (42 CFR 482.27).

HCFA coordinates inspections of

hospital-based blood banks with the

FDA to minimize duplication of effort

and reduce the burden on affected

facilities.

Hepatitis C virus (HCV) was first

discovered and established as a

causative agent of transfusion-associated

hepatitis in the late 1980s. In October

1989, FDA’s Blood Products Advisory

Committee (BPAC) first discussed steps

to identify and quarantine potentially

HCV infectious blood and blood

products remaining in storage and

notify recipients of the blood. (These

steps are known as ‘‘lookback.’’) 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.

In 1996, the Tenth Report of the U.S.

House of Representatives Committee on

Government Reform and Oversight (H.

Rpt. No. 104–746) focused attention on

the significant public health problem

that HCV infections pose for the nation.

HCV infection is the most common

blood-borne infection in the United

States. The Centers for Disease Control

and Prevention (CDC) estimate that

during the 1980s, as many as 180,000

new HCV infections occurred each year.

Since 1989, the annual number of new

infections has declined by 80 percent.

Currently approximately 4 million

individuals in the United States are

believed to be chronically infected with

HCV.

In 1996, however, data from the Third

National Health and Nutritional

Examination Survey conducted from

1988 to 1994 indicated that chronically

infected persons may not be aware of

their infection. Despite progression of

the 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 liver failure and cirrhosis in

the United States. HCV is also thought

to play a significant role in the

development of liver cancer. Between

8,000 and 12,000 deaths annually result

from HCV-related chronic liver disease.

HCV can be transmitted in a number

of ways, including sharing of drug use

equipment among injection drug users,

blood transfusion and solid organ