[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]
BILLING CODE 4310-12-P