[Code of Federal Regulations]
[Title 21, Volume 7]
[Revised as of April 1, 2001]
From the U.S. Government Printing Office via GPO Access
[CITE: 21CFR610.40]
[Page 71-73]
TITLE 21--FOOD AND DRUGS
DEPARTMENT OF HEALTH AND HUMAN SERVICES--(Continued)
PART 610--GENERAL BIOLOGICAL PRODUCTS STANDARDS--Table of Contents
Subpart E--Hepatitis Requirements
Sec. 610.40 Test for hepatitis B surface antigen.
(a) Test sensitivity. Each donation of blood, plasma, or serum to be
used in preparing a biological product shall be tested for the presence
of hepatitis B surface antigen by a method of sufficient sensitivity to
detect all sera labeled A, (A), B, (B), and C in the Reference Hepatitis
B Surface Antigen Panel distributed by the Center for Biologics
Evaluation and Research; except that, in emergency situations, a test
method of sufficient sensitivity to detect all sera labeled A, (A), and
B in the Reference Hepatitis B Surface Antigen Panel may be used and, in
dire emergency situations, blood and blood products may be issued
without any HB8 Ag testing, provided that a test otherwise
required by this paragraph is performed as soon as possible after
issuance of the blood and blood product.
(b) Procedures. Only Antibody to Hepatitis B Surface Antigen
licensed under this subchapter shall be used in performing the test and
the test method(s) used shall be that for which the antibody product is
specifically designed to be effective as recommended by the manufacturer
in the package insert. The sample of blood, plasma, or serum to be
tested shall have been taken from the donor at the time of donation of
that unit. The test need not be performed on the day of the withdrawal
of the sample. If the radioimmunoassay method is used, it must be
performed in one of the following ways:
(1) The complete test is performed at the collection facility.
(2) The test is performed at the collection facility up to the point
of counting the radioactivity of the samples, which counting,
thereafter, is performed at another facility by personnel from the
collection facility or by personnel from the counting facility.
(3) The complete test is performed by the personnel at an
establishment licensed to manufacture blood or blood derivatives under
section 351(a) of the Public Health Service Act (42 U.S.C. 262(a)), or
by a clinical laboratory which meets the standards of the Clinical
Laboratories Improvement Act of
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1967 (CLIA) (42 U.S.C. 263a), provided the establishment or the clinical
laboratory is qualified to perform radioimmunoassay testing for the
presence of hepatitis B surface antigen.
(4) Except as provided in this paragraph (b)(4), a collection
facility shall not ship any blood product as a biological product or
ship such a blood product where it is intended for use in manufacturing
a biological product until the test for hepatitis B surface antigen is
completed and the written test results are received by the collection
facility. Notwithstanding the provisions of Sec. 610.1 of this chapter,
in the case of an emergency, or as otherwise approved in writing by the
Director, Center for Biologics Evaluation and Research, a collection
facility may ship a blood product before the test for hepatitis B
surface antigen is completed. To obtain approval for such shipments, the
collection facility shall submit a description of the control procedures
to be used by both the collection facility and the manufacturing
facility to the Director, Center for Biologics Evaluation and Research
(HFB-1), Food and Drug Administration, 8800 Rockville Pike, Bethesda, MD
20892. The control procedures to be used by the collection facility and
the manufacturing facility shall include, but may not be limited to, a
system of communicating the test results to the manufacturing facility,
use of specific labeling warnings for the product to ensure that persons
handling the shipment know that it may be infectious, procedures for
quarantine of the untested or incompletely tested product both at the
collection facility and at the manufacturing facility, and a procedure
at the manufacturing facility to identify, preclude use of, and dispose
of any blood product that is received and later found to be reactive for
hepatitis B surface antigen.
(c) Materials in storage. All blood, plasma, or serum in storage
which has not been tested for the presence of the hepatitis B surface
antigen shall be tested as required in paragraphs (a) and (b) of this
section before use as a biological product, or before use in the
manufacture of a biological product. All blood, plasma, or serum in
storage which has been tested for the presence of the hepatitis B
surface antigen by a method of second generation sensitivity may be used
as a biological product or in manufacture of a biological product,
provided it is used on or before March 15, 1976.
(d) Restrictions on use. Blood, plasma, or serum that is reactive
when tested for hepatitis B surface antigen or that was collected from a
donor known to be reactive for hepatitis B surface antigen shall not be
used in manufacturing biological products except as provided in
paragraphs (d) (1) and (2) of this section.
(1) Injectable biological products and licensed in vitro diagnostic
biological products. Blood, plasma, or serum that is reactive when
tested for hepatitis B surface antigen or that was collected from a
donor known to be reactive for hepatitis B surface antigen may be used
in manufacturing hepatitis B vaccine and licensed in vitro diagnostic
biological products if all of the following conditions are met:
(i) The final product cannot be prepared from blood, plasma, or
serum that is nonreactive when tested for hepatitis B surface antigen,
due either to the nature or to the scarcity of the final product.
(ii) The label of the source blood, plasma, or serum conspicuously
states either that it is reactive when tested for hepatitis B surface
antigen and it may transmit viral hepatitis; or that the source blood,
plasma, or serum was collected from a donor known to be reactive for
hepatitis B surface antigen and it may transmit viral hepatitis,
although confirmatory hepatitis testing has not been done.
(iii) The package label of the licensed in vitro diagnostic
biological product prepared from such blood, plasma, or serum states
conspicuously that either the product was prepared from source material
that was reactive when tested for hepatitis B surface antigen and it may
transmit viral hepatitis; or that the source material was collected from
a donor known to be reactive for hepatitis B surface antigen and it may
transmit viral hepatitis, although confirmatory hepatitis testing has
not been done.
(iv) The package label of the licensed injectable biological product
prepared
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from such blood, plasma, or serum states that the product has been
inactivated.
(v) The Director, Center for Biologics Evaluation and Research (HFB-
1), Food and Drug Administration, 8800 Rockville Pike, Bethesda MD
20892, is notified in writing at the time of the shipment, or in the
case of repetitive shipments, or April 1 and October 1 of each year, of
each shipment of source blood, plasma, or serum for manufacture into
hepatitis B vaccine or into a licensed in vitro diagnostic biological
product. Such shipments shall not be subject to the requirements of
paragraph (b)(3) of this section. Each notification shall identify the
kind and amount of source material shipped, the name and address of the
consignee, the date of shipment, and the manner in which the source
material is labeled.
(2) Unlicensed in vitro diagnostic biological products. Blood,
plasma, or serum that is reactive when tested for hepatitis B surface
antigen or that was collected from a donor known to be reactive for
hepatitis B surface antigen may be used in manufacturing unlicensed in
vitro diagnostic biological products including clinical chemistry
control reagents if all of the following conditions are met:
(i) The final product cannot be prepared from blood, plasma, or
serum that is nonreactive when tested for hepatitis B surface antigen,
due either to the nature or to the scarcity of the final product.
(ii) The label of the source blood, plasma, or serum states
conspicuously that either it is reactive when tested for hepatitis B
surface antigen and it may transmit viral hepatitis; or that the source
blood, plasma, or serum was collected from a donor known to be reactive
for hepatitis B surface antigen and it may transmit viral hepatitis,
although confirmatory hepatitis testing has not been done.
(iii) The manufacturer of the source blood, plasma, or serum obtains
written assurance from the manufacturer(s) of the final unlicensed
product that package labels of all unlicensed products will
conspicuously state, as required by Sec. 809.10(a)(4) of this chapter,
that the product was prepared from blood, plasma, or serum that was
reactive when tested for hepatitis B surface antigen and it may transmit
viral hepatitis; or that the source material was collected from a donor
known to be reactive for hepatitis B surface antigen and it may transmit
viral hepatitis, although confirmatory hepatitis testing has not been
done.
(iv) At the time of shipment, the Director, Center for Biologics
Evaluation and Research (HFB-1), Food and Drug Administration, 8800
Rockville Pike, Bethesda, MD 20892, is notified in writing of each
shipment of source blood, plasma, or serum signifying the kind and the
amount of source material shipped, the name and address of the
consignee, the date of shipment, and the manner in which such source
material was labeled. Such shipments shall not be subject to the
requirements of paragraph (b)(3) of this section.
(e) Manufacturing responsibility. When the radioimmunoassay method
for hepatitis B surface antigen testing is performed by personnel other
than those of the facility collecting the blood, plasma, or serum, as
provided in paragraph (b) of this section, it shall not be considered as
divided manufacturing as described in Sec. 610.63, provided the
following conditions are met:
(1) The collecting facility has obtained a written agreement that
the testing laboratory will permit authorized representatives of the
Food and Drug Administration to inspect its testing procedures and
facilities during reasonable business hours.
(2) The testing laboratory will participate in any proficiency
testing programs undertaken by the Center for Biologics Evaluation and
Research, Food and Drug Administration.
(f) The information collection requirements in paragraph (d) of this
section were approved by the Office of Management and Budget and
assigned OMB control number 0910-0136.
(Information collection requirements contained in paragraph (b)(4) were
approved by the Office of Management and Budget under control number
0910-0168)
[40 FR 29710, July 15, 1975, as amended at 48 FR 23181, May 24, 1983; 49
FR 23834, June 8, 1984; 49 FR 26718, June 29, 1984; 51 FR 15607, Apr.
25, 1986; 55 FR 11013 and 11014, Mar. 26, 1990]
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