[Federal Register Volume 60, Number 227 (Monday, November 27, 1995)]
[Proposed Rules]
[Pages 58255-58256]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 95-28764]



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DEPARTMENT OF AGRICULTURE
Animal and Plant Health Inspection Service

9 CFR Part 113

[Docket No. 93-128-1]


Viruses, Serums, Toxins, and Analogous Products; 
Encephalomyelitis Vaccine, Eastern, Western, and Venezuelan, Killed 
Virus

AGENCY: Animal and Plant Health Inspection Service, USDA.

ACTION: Proposed rule.

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SUMMARY: We are proposing to amend 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 
encephalomyelitis vaccines. The effect of the proposed amendment would 
be to require the use of Vero 76 cells in the test to evaluate the 
potency of Encephalomyelitis Vaccine, Eastern, Western, and Venezuelan, 
Killed Virus, and to 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.

DATES: Consideration will be given only to comments received on or 
before January 26, 1996.

ADDRESSES: Please send an original and three copies of your comments to 
Docket No. 93-128-1, Regulatory Analysis and Development, PPD, APHIS, 
Suite 3C03, 4700 River Road Unit 118, Riverdale, MD 20737-1238. Please 
state that your comments refer to Docket No. 93-128-1. Comments 
received may be inspected at USDA, room 1141, South Building, 14th 
Street and Independence Avenue SW., Washington, DC, between 8 a.m. and 
4:30 p.m. Monday through Friday, except holidays. Persons wishing to 
inspect comments are requested to call ahead (202)-690-2817 to 
facilitate entry into the comment reading room.

FOR FURTHER INFORMATION CONTACT: Dr. David Espeseth, Deputy Director, 
Veterinary Biologics, BBEP, APHIS, 4700 River Road Unit 148, Riverdale, 
MD 20737-1237, (301) 734-8245.

SUPPLEMENTARY INFORMATION:

Background

    In accordance with the regulations contained in 9 CFR part 113, 
standard requirements are prescribed for the preparation of veterinary 
biological products. A standard requirement consists of test methods, 
procedures, and criteria established by the Animal and Plant Health 
Inspection Service to help ensure that veterinary biological products 
are pure, safe, potent, and efficacious.
    The standard requirement for Encephalomyelitis Vaccine, Eastern and 
Western, Killed Virus, in Sec. 113.207, specifies minimum potency 
requirements for such products. A serial of Eastern and Western equine 
encephalomyelitis vaccine must induce at least minimum antibody titers 
in guinea pigs specific for each fraction. The current standard 
requirement states that titers are to be determined in a plaque 
reduction, serum neutralization test but does not specify the cell type 
to be employed in the test. Primary duck embryo fibroblasts (DEF) were 
once considered the cells of choice; however, difficulties in producing 
acceptable DEF cultures are often encountered and results obtained with 
such cultures are not always consistent. These problems are not seen 
with cells of the Vero (African green monkey kidney) 76 cell line.
    This proposed rule would revise the standard requirement in 
Sec. 113.207 to require that cells of the Vero 76 cell line be used in 
encephalomyelitis vaccine potency tests. It would also revise the 
standard requirement by changing the minimum specific antibody titers 
from 1:4 to 1:40 for Eastern equine encephalomyelitis virus (EEV) and 
1:32 to 1:40 for Western EEV. Extensive correlation work performed by 
the National Veterinary Services Laboratories (NVSL) indicates these 
new minimum specific antibody titers as measured using Vero 76 cells 
are equivalent to those currently specified in the standard requirement 
as measured with DEF.
    In addition, the proposed rule would revise the standard 
requirement to establish standard test requirements for 
Encephalomyelitis Vaccine, Venezuelan, Killed Virus, and set 1:4 as the 
minimum specific antibody titer such vaccines must obtain to pass the 
potency test. The Agency has determined that a product that induces an 
anti-Venezuelan equine encephalomyelitis virus titer (as measured using 
Vero 76 cells) in guinea pigs of 1:4 or greater should protect horses 
against disease caused by that virus.
    This proposed rule would establish uniform test requirements for 
all killed vaccines for the prevention of Venezuelan equine 
encephalomyelitis and would revise the current potency test to make it 
more reliable and consistent. Executive Order 12866 and Regulatory 
Flexibility Act
    This proposed rule has been reviewed under Executive Order 12866. 
The rule has been determined to be not significant for purposes of 
Executive Order 12866, and, therefore, has not been reviewed by the 
Office of Management and Budget.
    This proposed rule would revise 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 proposed 
rule would revise 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 
proposed 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.
    Under these circumstances, the Administrator of the Animal and 
Plant Health Inspection Service has determined that this action would 
not 

[[Page 58256]]
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 12778

    This proposed rule has been reviewed under Executive Order 12778, 
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 which must be exhausted 
prior to a judicial challenge to the provisions of this rule.

Paperwork Reduction Act

    This proposed 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 would be amended as follows:

PART 113--STANDARD REQUIREMENTS

    1. The authority citation for part 113 would continue to read as 
follows:

    Authority: 21 U.S.C. 151-159; 7 CFR 2.17, 2.51, 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) would be 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 20th day of November 1996.
Terry L. Medley,
Administrator, Animal and Plant Health Inspection Service.
[FR Doc. 95-28764 Filed 11-24-95; 8:45 am]
BILLING CODE 3410-34-P