Revised Recommendations for Testing Whole Blood (8/5/93)
 
Date:  August 5, 1993 
From:  Acting Director, Office of Blood Research and Review, 
Center for Biologics Evaluation and Research 
Subject:  Revised Recommendations for Testing Whole Blood, 
Blood Components, Source Plasma and Source Leukocytes 
for Antibody to Hepatitis C Virus Encoded Antigen 
(Anti-HCV) 
To:  All Registered Blood Establishments 
This memorandum transmits Revised Recommendations for Testing for
 
Antibody to Hepatitis C Virus Encoded Antigen (Anti-HCV) in Blood
 
Establishments, August, 1993.  These revised recommendations
 
modify those issued on April 23, 1992, in regard to testing for
 
anti-HCV.  A donor who currently tests, or who in the past had
 
tested, repeatedly reactive for anti-HCV with a solid phase
 
enzyme linked immunoassay (ELISA), licensed by the Food and Drug
 
Administration (FDA), may now be considered for re-entry provided
 
that certain criteria, described in this document, are fulfilled. 

On April 23, 1992 FDA recommended (1) that units of Whole Blood
 
and blood components intended for transfusion, and Source Plasma
 
and Source Leukocytes intended for further manufacture, be
 
screened by an FDA licensed test for anti-HCV and (2) that no
 
products repeatedly reactive for anti-HCV be used.  In memoranda
 
issued by FDA concerning testing for anti-HCV dated November 29,
 
1990 and April 23, 1992, no donor re-entry protocol for donors
 
who were repeatedly reactive for anti-HCV by ELISA was
 
recommended because of the lack of an available licensed
 
additional (supplemental), more specific test. 

In public meetings on March 12, 1992 and March 26, 1993, FDA's
 
Blood Products Advisory Committee (BPAC) recommended the use of a
 
re-entry algorithm for donors who test repeatedly reactive for
 
anti-HCV in ELISA tests, should suitable supplemental tests for
 
anti-HCV become available for donor re-evaluation. 

According to the attached recommendations, donors testing (or
 
who, in the past, tested) repeatedly reactive in a licensed
 
screening test for anti-HCV may be re-evaluated after a minimum
 
period of six months.  During the time period prior to
 
reevaluation, the donor should not donate blood or blood
 
products. 

However, additional testing may be done for the purposes of
 
counseling.  Upon retest after 6 months or more, to qualify for
 
re-entry, the donor should test nonreactive in both a licensed
 
multi-antigen* screening test and a licensed multi-antigen*
 
supplemental test for antibodies to HCV. [* Footnote: "Multi antigen" refers to kit component antigens that, in addition to
 
c100-3, includes antigens other than those contained in c100-3.]
 
Donors should be indefinitely deferred from donating Whole Blood
 
and blood components intended for transfusion and for further
 
manufacture, and Source Plasma and Source Leukocytes intended for
 
further manufacture whenever they test repeatedly reactive in a
 
licensed multi-antigen ELISA and reactive (indeterminate or
 
positive) for anti-HCV in a multi-antigen supplemental assay.
 
Blood establishments should also defer donors if they test
 
repeatedly reactive in a licensed multi-antigen ELISA assay on
 
more than one occasion.  No re-entry procedure should be used for
 
these donors.
 
The attached document replaces sections I.A. and I.B. (page 3 to
 
page 4, line 7) of the FDA's prior memorandum in regard to anti-

HCV testing dated April 23, 1992.  Pages 1, 2 and 3 of the April
 
23, 1992, memorandum should now be replaced by pages 1, 2, 3, 3a,
 
3b and 3c of the attached document.  Guidance on all matters not
 
directly related to donor suitability and re-entry in regard to
 
anti-HCV testing (such as "lookback", use of autologous units,
 
donor deferral due to contact with individuals having viral
 
hepatitis, the labeling, quarantine, storage and shipment of
 
units of blood and blood components, etc.) remain unchanged from
 
the April 23, 1992, memorandum, and those sections of that
 
memorandum should be retained.  Labeling, informed consent forms,
 
standard operating procedures, deferral registries, and record
 
keeping procedures should already have been revised as necessary
 
to reflect the blood establishment's implementation of anti-HCV
 
testing.
 
Questions concerning testing for antibodies to HCV and donor re
entry may be directed in writing to the Division of Transfusion
 
Transmitted Diseases, Laboratory of Hepatitis, HFM-325,
 
HHS/PHS/Food and Drug Administration, Center for Biologics
 
Evaluation and Research, Suite 200N, 1401 Rockville Pike,
 
Rockville, MD 20852-1448, FAX: (301) 227-0209.  Questions
 
concerning labeling may be directed in writing to the Division of
 
Blood Establishment and Product Application, HFM-380 (Suite 200N,
 
1401 Rockville, MD 20852-1448), FAX: (301) 295-8973. 

Jay S. Epstein, M.D.
 
__________________________ 
Revised Recommendations for Testing
 
for

 Antibody to Hepatitis C Virus Encoded Antigen (Anti-HCV)
 
in
 
Blood Establishments
 
August, 1993
  U.S. Department of Health and Human Services
 
Public Health Service
 
Food and Drug Administration
 
Center for Biologics Evaluation and Research
 
1401 Rockville Pike, Rockville, MD  20852-1448
 
TABLE OF CONTENTS
 
I.	  Performance of Anti-HCV Testing and Donor Suitability
 
(including re-entry)
 
II.	  Labeling of Whole Blood and Components
 
Intended for Transfusion
 
III.	  Labeling of Whole Blood and Blood Components
 
Intended for Further Manufacturing or Research
 
IV.	  Quarantine and Disposition of Repeatedly
 
Reactive Donations
 
V.	  Lookback 

________________________________ 
REVISED RECOMMENDATIONS FOR TESTING FOR ANTIBODY
 
TO HEPATITIS C VIRUS ENCODED ANTIGEN
 
(ANTI-HCV) IN BLOOD ESTABLISHMENTS
 
August, 1993
 
I.	  PERFORMANCE OF ANTI-HCV TESTING AND DONOR SUITABILITY
 
A.	  Anti-HCV testing, using a multi-antigen*, enzyme-

linked immunoassay (ELISA) test, should be performed
 
and test results interpreted according to the
 
manufacturer's instructions in the package insert. 

Instructions for currently licensed kits may be
 
summarized as follows:
 
[Footnote: * "Multi-antigen" refers to kit component
 
antigens that, in addition to c100-3, includes
 
antigens other than those contained in c100-3.]
 
1.	  A single ELISA test for anti-HCV should be
 
performed on a donor sample for each unit of
 
whole blood or blood component intended for
 
transfusion and on each unit of plasma or
 
source leukocytes for further manufacture. 

This ELISA test will hereafter be referred to
 
as the "initial test."
  2.	  If the initial test result is nonreactive, the
 
donor sample is considered to be negative for
 
anti-HCV.
 
3.	  If the initial test result is reactive, the
 
donor sample is considered to be initially
 
reactive. 

A sample from the same collection should be
 
retested in duplicate, within a single run,
 
using the same procedure and same
 
manufacturer's ELISA test as that used for the
 
initial test.
 
a.	  If both duplicate ELISA repeat test
 
results are nonreactive, the sample is
 
considered to be negative for anti-HCV.
 
b.	  If either one or both of the ELISA
 
duplicate repeat test results are
 
reactive, the sample is considered to be
 
repeatedly reactive for anti-HCV in the
 
screening test, and the products should
 
not be used for transfusion or routinely
 
for further manufacture.  Possible
 
exceptions to permit use of anti-HCV
 
reactive products in special
 
circumstances are described in Section
 
I.C. and Section III.B. regarding anti-

HCV testing.  No further screening tests
 
for anti-HCV should be performed on
 
samples from this unit in an effort to
 
qualify it as suitable for release. 

c.	  Additional testing may be done for the
 
purpose of counseling the donor (see
 
B.4., below) and in the context of the
 
re-entry algorithm described below.  FDA
 
recommends that blood establishments use
 
only licensed supplemental tests for
 
either donor notification or
 
consideration of possible re-entry.
 
B.	  Donors who are repeatedly reactive for anti-HCV,
 
using multi-antigen ELISA screening tests, should be 

indefinitely deferred.  Units collected from deferred
 
donors should be discarded and not released. 

However, at the discretion of the blood
 
establishment, a donor testing repeatedly reactive in
 
a screening test may be further evaluated for
 
possible re-entry as a qualified donor as follows:
 
1.	  A minimum time period of six months should
 
elapse between the index donation (i.e., the
  one that tested repeatedly reactive in a
 
screening ELISA test) and the follow-up sample
 
to evaluate any donor for possible re-entry. 

The follow-up sample should be tested for anti-

HCV in a licensed multi-antigen screening ELISA
 
test as described in I.A. 

a.	  If the ELISA test result is repeatedly
 
reactive, the donor is indefinitely
 
deferred.
 
b.	  If the ELISA test is non reactive, the
 
sample should be tested in a licensed
 
supplemental test as described below in
 
I.B.2.
 
2.	  Anti-HCV testing using a currently licensed
 
multi-antigen supplemental test should be
 
performed on a follow-up sample obtained after
 
a minimum time period of six months from the
 
index donation.  The test results should be
 
interpreted according to the manufacturer's
 
instructions in the package insert.
 
a.	  If the supplemental test result is
 
indeterminate or positive, the test
 
result is considered to be supplemental
 
test reactive, and the donor is
 
indefinitely deferred.
 
b.	  If the supplemental test result is
 
nonreactive, the donor may be re-entered
 
as a qualified donor.
 
c.	  If the follow-up sample is obtained from
 
a donation of a unit, then the ELISA
 
(described in B.1.) and the supplemental
 
test (described in B.2) should be
 
performed on (a) sample(s) from the same
 
collection as the unit.  If both tests
 
are negative, then the current unit may
 
be used.
 
3.	  Donors who were indefinitely deferred because
 
of a unit testing repeatedly reactive for anti-

HCV in
 
a licensed screening ELISA test, and for which
 
a multi-antigen supplemental test was not
 
performed or for which negative results were
 
obtained in a multi-antigen supplemental test,
 
may be re-evaluated as described in B.1., and
 
B.2., above.
  4.	  Any person testing, or who has tested, either
 
repeatedly reactive in a licensed multi-antigen
 
ELISA assay on more than one occasion, or
 
reactive (indeterminate or positive) in a
 
multi-antigen supplemental assay (including
 
unlicensed assays), is indefinitely deferred
 
from donating.  Such persons should not be re
entered+.  [Footnote:  + To avoid unnecessary
 
re-bleeding of the donor, it may be convenient
 
for blood establishments to perform a licensed
 
supplemental test for anti-HCV on a frozen
 
sample from the index donation.]  Donors who
 
were indefinitely deferred based on a
 
repeatedly reactive ELISA screening test for
 
anti-HCV using a single antigen (c100-3) based
 
assay may be considered for re-entry even if
 
such reactivity occurred on more that one
 
determination.  The index donation in I.B.1.
 
should be taken as the most recent reactive
 
donation.
 
5.	  If any additional optional testing is, or has
 
been, performed using licensed multi-antigen
 
ELISA assays or multi-antigen supplemental
 
assays (including unlicensed assays), either on
 
the index donation or subsequently on the
 
donor, all test results obtained should be non
 
reactive and/or negative, if donor re-entry is
 
to be attempted.
 
6.	  General guidance in regard to the testing,
 
counseling, and evaluation of donors tested for
 
hepatitis viruses is described in the Public
 
Health Service Interagency Guidelines for
 
Screening Donors of Blood, Plasma, Organs,
 
Tissues, and Semen for Evidence of Hepatitis B
 
and Hepatitis C, MMWR 1991; 40 (RR-4): 1-17.
 
7.	  These recommendations are subject to future
 
revision as improvements and advances in
 
technology became available.