[Federal Register Volume 61, Number 121 (Friday, June 21, 1996)]
[Rules and Regulations]
[Pages 31822-31823]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 96-15854]



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DEPARTMENT OF AGRICULTURE
Animal and Plant Health Inspection Service

9 CFR Part 113

[Docket No. 95-012-2]


Viruses, Serums, Toxins, and Analogous Products; Rabies Vaccine, 
Killed Virus and Rabies Vaccine, Live Virus

AGENCY: Animal and Plant Health Inspection Service, USDA.

ACTION: Final rule.

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SUMMARY: We are amending the standard requirements for establishing the 
immunogenicity of Rabies Vaccine, Killed Virus and Rabies Vaccine, Live 
Virus. The amendment changes and clarifies alternate test procedures 
which may be used in animals other than carnivores. Under the rule, 
when a reduced number of challenge animals is used in a rabies 
immunogenicity test, all vaccinates must survive challenge. If one or 
more of the challenged vaccinates die of rabies, all of the remainder 
of the vaccinates will have to be challenged or the test will be deemed 
unsatisfactory and terminated.
    This action corrects a problem associated with rabies 
immunogenicity tests in the regulations and makes other changes deemed 
necessary for clarity and consistency.

EFFECTIVE DATE: July 22, 1996.

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

SUPPLEMENTARY INFORMATION:

Background

    The regulations in 9 CFR part 113 pertain to standard requirements 
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 (APHIS) 
to determine that a veterinary biological product is pure, safe, 
potent, and efficacious and not worthless, dangerous, contaminated, or 
harmful.
    The standard requirements for Rabies Vaccine, Killed Virus, and for 
Rabies Vaccine, Live Virus, appear in Secs. 113.209 and 113.312, 
respectively. Sections 113.209(b)(4) and 113.312(b)(4) provide for an 
alternative immunogenicity test, for domestic species other than dogs 
and cats, that reduces the number of animals that must be challenged.
    On November 16, 1995, we published in the Federal Register (60 FR 
57549-57550, Docket No. 95-012-1) a proposed rule to amend the standard 
requirements for Rabies Vaccine, Killed Virus and Rabies Vaccine, Live 
Virus. The amendments specify: (1) that for an immunogenicity study in 
non-carnivores to be satisfactory, all animals must survive challenge 
when less than 25 vaccinates are challenged, and (2) that a reduced 
number of challenge animals may only be used for non-carnivores. The 
rule more clearly

[[Page 31823]]

defines which animals must be challenged when a reduced number of 
vaccinates is used.
    We solicited comments for a 60-day comment period ending January 
16, 1996. One comment was received by that date. The comment was from a 
licensed manufacturer of veterinary biological products. The comment 
addressed which animals should be challenged and the percent survival 
required for a reduced challenge. The commenter recommended that less 
than 100 percent survival be acceptable for a reduced challenge. The 
commenter requested that this be accomplished through a wording change 
to the rule.
    In response to the commenter, APHIS believes that when the number 
of challenged animals is reduced, survival of less than 100 percent of 
the animals of the lowest titer would not provide adequate assurance 
that animals of higher titer would be protected against challenge. 
Because of this, 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 proposal 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 amending Secs. 113.209 and 113.312 is necessary to 
clarify the regulations regarding the rabies immunogenicity test. The 
amendment clarifies which animals are to be challenged in a reduced 
immunogenicity study and the procedures to follow when one or more of 
the vaccinates die of rabies. The amendment requires that additional 
vaccinates be challenged if one of the low titer vaccinates succumbs to 
rabies. In 7 of the last 10 rabies challenge tests of non-carnivores, 
firms elected to challenge 25 or more animals. In the remaining three 
cases in which a reduced number of animals were challenged in 
accordance with current Sec. 113.209 or Sec. 113.312, paragraph (b)(4), 
no additional animals were challenged and no additional animals would 
have been challenged under the amendment. The amendment, therefore, 
will have minimal economic effect.
    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 12778

    This 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 rule contains no new information collection or record keeping 
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. Section 113.209 is amended by revising paragraph (b)(4) to read 
as follows:


Sec. 113.209  Rabies Vaccine, Killed Virus.

* * * * *
    (b) * * *
    (4) An alternative to challenging all surviving test animals in 
accordance with paragraph (b)(3)(iv) of this section may be used when 
the test animals are of species other than carnivores. Vaccinates shall 
be challenged at 1 year postvaccination. These shall include five 
vaccinates with the lowest SN titers at the 270th-day bleeding, five 
vaccinates with the lowest SN titers at the 365th-day bleeding, and all 
vaccinates with SN titers below 1:10 by the mouse SN test or below 1:16 
by the rapid-fluorescent-focus-inhibition test at any bleeding. At 
least five SN-negative controls of each species shall be challenged at 
the same time as the vaccinates. All SN titers shall be titrated to an 
endpoint. All of the challenged vaccinates must remain well for a 
period of 90 days, and at least 80 percent of the controls must die of 
rabies for a satisfactory test without further challenge. If one or 
more of the vaccinates die from rabies, all the remaining vaccines, 
regardless of titer, along with the five controls shall be challenged. 
The cumulative results from the two challenges shall be evaluated for 
acceptance as specified in paragraph (b)(3)(v) of this section.
* * * * *
    3. Section 113.312 is amended by revising the section heading and 
paragraph (b)(4) to read as follows:


Sec. 113.312  Rabies Vaccine, Live Virus.

* * * * *
    (b) * * *
    (4) an alternative to challenging all surviving test animals in 
accordance with paragraph (b)(3)(iv) of this section may be used when 
the test animals are of species other than carnivores. Vaccinates shall 
be challenged at 1 year postvaccination. These shall include five 
vaccinates with the lowest SN titers at the 270th-day bleeding, five 
vaccinates with the lowest SN titers at the 365th-day bleeding, and all 
vaccinates with SN titers below 1:10 by the mouse SN test or below 1:16 
by the rapid-fluorescent-focus-inhibition test at any bleeding. At 
least five SN-negative controls of each species shall be challenged at 
the same time as the vaccinates. All SN titers shall be iterated to an 
endpoint. All of the challenged vaccinates must remain well for a 
period of 90 days, and at least 80 percent of the controls must die of 
rabies for a satisfactory test without further challenge. If one or 
more of the vaccinates die from rabies, all the remaining vaccinates, 
regardless of titer, along with the five controls shall be challenged. 
The cumulative results from the two challenges shall be evaluated for 
acceptance as specified in paragraph (b)(3)(v) of this section.
* * * * *
    Done in Washington, DC, this 17th day of June 1996.
Lonnie J. King,
Administrator, Animal and Plant Health Inspection Service.
[FR Doc. 96-15854 Filed 6-20-96; 8:45 am]
BILLING CODE 3410-34-M