[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]
-----------------------------------------------------------------------
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.
-----------------------------------------------------------------------
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
