[Federal Register Volume 61, Number 249 (Thursday, December 26, 1996)]
[Rules and Regulations]
[Pages 67929-67930]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 96-32725]
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DEPARTMENT OF AGRICULTURE
9 CFR Part 113
[Docket No. 93-128-2]
Viruses, Serums, Toxins, and Analogous Products;
Encephalomyelitis Vaccine, Eastern, Western, and Venezuelan, Killed
Virus
AGENCY: Animal and Plant Health Inspection Service, USDA.
ACTION: Final rule.
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SUMMARY: We are amending the standard requirement for Encephalomyelitis
Vaccine, Eastern and Western, Killed Virus, by specifying requirements
for killed Venezuelan equine encephalomyelitis vaccines and revising
the standard potency test for Eastern and Western equine
encephalomyelitis vaccines. The amendments require the use of Vero 76
cells in the test to evaluate the potency of Encephalomyelitis Vaccine,
Eastern, Western, and Venezuelan, Killed Virus, and establish minimum
antibody titers which must be elicited by each of the indicated
fractions, as determined by a plaque reduction, serum neutralization
assay in which Vero 76 cells are used.
EFFECTIVE DATE: January 27, 1997.
FOR FURTHER INFORMATION CONTACT: Dr. David A. Espeseth, Director,
Licensing and Policy Development, Center for Veterinary Biologics, VS,
APHIS, 4700 River Road Unit 148, Riverdale, MD 20737-1237, (301) 734-
8245.
SUPPLEMENTARY INFORMATION:
Background
In accordance with the regulations in 9 CFR part 113, standard
requirements are prescribed for the preparation of veterinary
biological products. A standard requirement consists of specifications,
procedures, and test methods that define the standards of purity,
safety, potency, and efficacy for a veterinary biological product.
Where a standard requirement for a product has not been established,
production procedures and specifications for purity, safety, and
potency of a biological product are provided in an Outline of
Production filed with the Animal and Plant Health Inspection Service
(APHIS).
On November 27, 1995, we published in the Federal Register (60 FR
58255-58256, Docket No. 93-128-1) a proposed rule to amend the
regulations in Sec. 113.207 by providing requirements for killed
Venezuelan equine encephalomyelitis vaccines and amending the potency
test provisions for killed Eastern and Western equine encephalomyelitis
vaccines. The proposed amendments required the use of Vero 76 cells in
the test to evaluate the potency of Encephalomyelitis Vaccine, Eastern,
Western, and Venezuelan, Killed Virus and establish minimum antibody
titers which must be elicited by each of the indicated fractions, as
determined by a plaque reduction, serum neutralization assay in which
Vero 76 cells are used.
We solicited comments concerning our proposal for 60 days ending
January 26, 1996. We received two comments by that date from a
manufacturer of veterinary biological products and a veterinary
biologics industry consultant. They are discussed below.
One commenter expressed support for the rule provided adequate data
are available to justify the proposed revisions. Adequate data are
available to support the revisions. Antibody titers in guinea pigs, as
measured by duck embryo fibroblasts, were correlated with protection in
horses. Antibody titers in guinea pigs measured by Vero 76 cells were,
in turn, correlated with those measured by duck embryo fibroblasts.
Therefore, the Agency believes that there is justification for the
proposed revisions. No changes to the regulations are made in response
to this comment.
The other commenter, who claimed to have considerable experience
with the plaque reduction, serum neutralization assay in which Vero
cells are used, stated that ``less than 1:10'' rather than ``less than
1:4'' should be set as the acceptable titer for control guinea pigs in
the tests for the Eastern and Western type fractions because
nonspecific titers up to 1:10 are commonly encountered. In response to
the commenter, the Agency notes that the correlative studies to support
the rule were conducted with guinea pigs with prevaccination titers of
less than 1:4. APHIS believes that extrapolation of the results of the
studies to a situation where the sera of test animals prior to
vaccination are negative at a 1:10 dilution but positive at a 1:4
dilution is inappropriate. No change to the regulations is made in
response to this comment.
The second commenter also requested that, in proposed
Sec. 113.207(b)(4), ``three or four vaccinate serum samples'' instead
of ``two or three vaccinate serum samples'' be specified to ``be
consistent with the initial tests being satisfactory if 80 percent of
the vaccinates show protective titers.'' In response to the commenter,
APHIS notes that the proposed ``two or three vaccinate serum samples''
does not differ from the requirement specified under the current
regulations. Moreover, paragraph (b)(6) of Sec. 113.207 of the current
regulations not proposed for amendment specifies that four or more
failures is a basis for an unsatisfactory test, and that for a given
fraction, at least 9 of the 10 vaccinated guinea pigs, or 90 percent,
must have an acceptable titer for a satisfactory first-stage test.
Therefore, ``three or four vaccinate serum samples'' and ``80 percent
of the vaccinates show[ing] protective titers'' would be inconsistent
with current regulations. No change to the regulations is made in
response to this comment.
Therefore, based on the rationale set forth in the proposed rule
and in this document, we are adopting the provisions of the proposed
rule as a final rule without change.
Executive Order 12866 and Regulatory Flexibility Act
This rule has been reviewed under Executive Order 12866. The rule
has been determined to be not significant for the purposes of Executive
Order 12866 and, therefore, has not been reviewed by the Office of
Management and Budget.
This rule revises the standard requirement in Sec. 113.207 for
Encephalomyelitis Vaccine, Eastern and Western, Killed Virus, by
specifying a different cell type for use in the potency test assay and
specifying different minimum specific antibody titers that must be
achieved for a satisfactory test. In addition, the rule revises the
standard requirement so that it would also apply to Encephalomyelitis
Vaccine, Venezuelan, Killed Virus. The Agency believes the titers given
in the standard requirement are adequately correlated with claimed
efficacy and that they would be readily obtained by all relevant
vaccines currently licensed. We do not expect any increase in cost to
the biologics manufacturers affected by this rule. The changes should
actually decrease costs for most impacted manufacturers, since fewer
repeat tests will be needed and obtaining Vero 76 cells should prove
less expensive than procuring primary DEF.
[[Page 67930]]
Under these circumstances, the Administrator of the Animal and
Plant Health Inspection Service has determined that this action will
not have a significant economic impact on a substantial number of small
entities. Executive Order 12372
This program/activity is listed in the Catalog of Federal Domestic
Assistance under No. 10.025 and is subject to Executive Order 12372,
which requires intergovernmental consultation with State and local
officials. (See 7 CFR part 3015, subpart V.)
Executive Order 12988
This final rule has been reviewed under Executive Order 12988,
Civil Justice Reform. It is not intended to have retroactive effect.
This rule would not preempt any State or local laws, regulations, or
policies, unless they present an irreconcilable conflict with this
rule. There are no administrative procedures that must be exhausted
prior to a judicial challenge to the provisions of this rule.
Paperwork Reduction Act
This rule contains no new information collection or recordkeeping
requirements under the Paperwork Reduction Act of 1995 (44 U.S.C. 3501
et seq.).
List of Subjects in 9 CFR Part 113
Animal biologics, Exports, Imports, Reporting and recordkeeping
requirements.
Accordingly, 9 CFR part 113 is amended as follows:
PART 113--STANDARD REQUIREMENTS
1. The authority citation for part 113 continues to read as
follows:
Authority: 21 U.S.C. 151-159; 7 CFR 2.22, 2.80, and 371.2(d).
2. In Sec. 113.207, the section heading, the introductory text, the
introductory text of paragraph (b), and paragraphs (b)(2), (b)(3),
(b)(4), and (b)(5) are revised to read as follows:
Sec. 113.207 Encephalomyelitis Vaccine, Eastern, Western, and
Venezuelan, Killed Virus.
Encephalomyelitis Vaccine, Eastern, Western, and Venezuelan, Killed
Virus, shall be prepared from virus-bearing cell culture fluids. Each
serial or subserial shall meet the requirements prescribed in this
section and the general requirements prescribed in Sec. 113.200, except
those in Sec. 113.200(d). Any serial or subserial found unsatisfactory
by a prescribed test shall not be released.
* * * * *
(b) Potency test. Bulk or final container samples of completed
product from each serial shall be tested for potency in accordance with
the two-stage test provided in this paragraph. For each fraction
contained in the product--Eastern type, Western type, or Venezuelan
type--the serological interpretations required in this test shall be
made independently. A serial or subserial found unsatisfactory for any
of the fractions shall not be released.
(1) * * *
(2) Fourteen to 21 days after the second injection, serum samples
from each vaccinate and each control shall be tested by a plaque
reduction, serum neutralization test using Vero 76 cells.
(3) If the control serum samples show a titer of 1:4 or greater for
any fraction, the test is inconclusive for that fraction and may be
repeated: Provided, That, if four or more of the vaccinate serum
samples show a titer of less than 1:40 for the Eastern type fraction,
less than 1:40 for the Western type fraction, or less than 1:4 for the
Venezuelan type fraction, the serial or subserial is unsatisfactory
without further testing.
(4) If two or three of the vaccinate serum samples show a titer of
less than 1:40 for the Eastern type fraction, less than 1:40 for the
Western type fraction, or less than 1:4 for the Venezuelan type
fraction, the second stage of the test may be used for the relevant
fraction(s): Provided, That, if a fraction is found acceptable by the
first stage of the test, the second stage need not be conducted for
that fraction.
(5) If the second stage is used and four or more of the vaccinate
serum samples show a titer of less than 1:40 for the Eastern type
fraction or the Western type fraction, or less than 1:4 for the
Venezuelan type fraction, the serial or subserial is unsatisfactory.
* * * * *
Done in Washington, DC, this 16th day of December 1996.
A. Strating.
Acting Administrator, Animal and Plant Health Inspection Service.
[FR Doc. 96-32725 Filed 12-24-96; 8:45 am]
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