[Federal Register Volume 60, Number 52 (Friday, March 17, 1995)]
[Rules and Regulations]
[Pages 14353-14355]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 95-6648]
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DEPARTMENT OF AGRICULTURE
Animal and Plant Health Inspection Service
9 CFR Parts 101 and 113
[Docket No. 92-201-2]
Viruses, Serums, Toxins, and Analogous Products; General
Requirements for Inactivated Bacterial Products
AGENCY: Animal and Plant Health Inspection Service, USDA.
ACTION: Final rule.
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SUMMARY: We are amending the regulations to include a general standard
requirement for inactivated bacterial products that is consistent with
the general standard requirements [[Page 14354]] for live bacterial
products, killed virus vaccines, and live virus vaccines. We are also
including criteria and test concerning the identity of master seed.
Finally, the amendment provides a choice of the most appropriate test
methods, including identity tests, for the broad range of inactivated
bacterial products available today. The final rule is necessary to
update the current standards and provide uniform, relevant criteria for
inactivated bacterial products.
EFFECTIVE DATE: April 17, 1995.
FOR FURTHER INFORMATION CONTACT:
Dr. Richard E. Pacer, Senior Staff Veterinarian, Animal and Plant
Health Inspection Service, Biotechnology, Biologics, and Environmental
Protection, Veterinary Biologics, 4700 River Road Unit 148, Riverdale,
MD 20737-1228, (301) 734-8245.
SUPPLEMENTARY INFORMATION:
Background
In accordance with the regulations in 9 CFR part 113, standard
requirements are prescribed for the licensing of veterinary biological
products. A standard requirement consists of specifications,
procedures, and test methods which define the standards of purity,
safety, potency, and efficacy for a given type of veterinary biological
product.
On March 1, 1994, we published in the Federal Register (59 FR 9681-
9682, Docket No. 92-201-1) a proposal to amend the regulations by
revising Sec. 113.100 to include the relevant criteria for evaluation
of the purity, safety, and identity of inactivated bacterial products.
In addition, we proposed to define the master seed concept as it
applies to inactivated bacterial products. This action was intended to
provide specific criteria for these inactivated bacterial products. We
also proposed to move certain definitions from Sec. 113.100 to part
101.
We solicited comments on our proposal for a 60-day period ending
May 2, 1994. We received one comment by that date. This comment was
from a licensed manufacturer of veterinary biological products. The
commenter's only concern was about the manufacture of inactivated
bacterial products for fish.
The commenter sought clarification of our requirement for safety
tests as proposed in Sec. 113.100(b). This requirement states that each
bacterial product shall be evaluated in mice and/or guinea pigs with
the exception that, if the product is specific for poultry, then the
safety test will be performed in poultry. The commenter suggested that
an exception similar to that for poultry should be considered for
products specifically intended for fish. We agree with the rationale of
the commenter because it would be more appropriate to evaluate the
safety of a biological product intended for fish in an aquatic species
than in a mammalian species. In response to the commenter, we have
amended the proposal by adding a new paragraph (b)(3) in Sec. 113.100
concerning fish and including other aquatic species or reptiles which
states: ``The product is recommended for fish, other aquatic species or
reptiles. In such instances, the product shall be safety tested in fish
or other aquatic species or reptiles as required by specific Standard
Requirement or Outline of Production for the product.'' We have also
made a slight change to the definitions to clarify the fact that the
defined products are inactivated bacterial products.
Therefore, with the exception of the above changes, we are adopting
the provisions of the proposal as a final rule.
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 purposes of Executive
Order 12866, and, therefore, has not been reviewed by the Office of
Management and Budget.
There are currently no general requirements for inactivated
bacterial products in the regulations. However, approximately 30
percent of the 114 currently licensed veterinary biologics companies
manufacture inactivated bacterial products. Many of these companies are
considered small entities and will benefit from the adoption of this
rule. The benefits of the rule include increased efficiency and reduced
time and expense in accomplishing the steps toward licensure of an
inactivated bacterial product. These benefits will be realized because
of ready access to clear requirements, uniformity and consistency in
product development, and the alleviation of unnecessary steps in
production of these type of products. These companies should not
experience any additional costs above those which they currently incur
to license an inactivated bacterial product as a result of adoption of
this rule.
Under these circumstances, the Administrator for 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 12778
This rule has been reviewed under Executive Order 12778, Civil
Justice Reform. This rule: (1) Preempts all State and local laws and
regulations that are in conflict with this rule; (2) has no retroactive
effect; and (3) does not require administrative proceedings before
parties may file suit in court challenging this rule.
Paperwork Reduction Act
This rule contains no information collection or recordkeeping
requirements under the Paperwork Reduction Act of 1980 (44 U.S.C. 3501
et seq.).
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.)
List of Subjects
9 CFR Part 101
Animal biologics.
9 CFR Part 113
Animal biologics, Exports, Imports, Reporting and recordkeeping
requirements.
Accordingly, 9 CFR parts 101 ad 113 are amended as follows:
PART 101--DEFINITIONS
1. The authority citation for part 101 continues to read as
follows:
Authority: 21 U.S.C. 151-159; 7 CFR 2.17, 2.51, and 371.2(d).
2. Section 101.3, is amended by adding, at the end of the section,
the following definitions to read as follows:
Sec. 101.3 Biological products and related terms.
* * * * *
(m) Bacterin. An inactivated bacterial product consisting of an
antigenic suspension of organisms or particulate parts of organisms,
representing a whole culture or a concentrate thereof, with or without
the unevaluated growth products, which has been inactivated as
demonstrated by acceptable tests written into the filed Outline of
Production for the product.
(n) Toxoid. An inactivated bacterial product which consists of a
sterile, antigenic toxin or toxic growth product, which has resulted
from the growth of bacterial organisms in a culture medium from which
the bacterial cells have been removed, which has been inactivated
[[Page 14355]] without appreciable loss of antigenicity as measured by
suitable tests, and which is nontoxic as demonstrated by acceptable
tests written into the filed Outline of Production.
(o) Bacterin-toxoid. An inactivated bacterial product which is
either:
(1) A suspension of organisms, representing a whole culture or a
concentrate thereof, with the toxic growth products from the culture
which has been inactivated without appreciable loss of antigenicity as
measured by suitable tests, the inactivation of organisms and toxins
being demonstrated by acceptable tests written into the filed Outline
of Production: Provided, That it shall contain cellular antigens and
shall stimulate the development of antitoxin; or
(2) A combination product in which one or more toxoids or bacterin-
toxoids is combined with one or more bacterins or one or more bacterin-
toxoids.
(p) Bacterial extract. An inactivated bacterial product which
consists of the sterile, nontoxic, antigenic derivatives extracted from
bacterial organisms or from culture medium in which bacterial organisms
have grown.
PART 113--STANDARD REQUIREMENTS
3. The authority citation for part 113 continues to read as
follows:
Authority: 21 U.S.C. 151-159; 7 CFR 217, 2.51, and 371.2(d).
4. In Sec. 113.100, the heading, introductory paragraph, and
paragraphs (a) through (d) are revised to read as follows:
Sec. 113.100 General requirements for inactivated bacterial products.
Unless otherwise prescribed in an applicable Standard Requirement
or in the filed Outline of Production, an inactivated bacterial product
shall meet the applicable requirements in this section.
(a) Purity tests. (1) Final container samples of completed product
from each serial and each subserial shall be tested for viable bacteria
and fungi as provided in Sec. 113.26.
(2) Each lot of Master Seed Bacteria shall be tested for the
presence of extraneous viable bacteria and fungi in accordance with the
test provided in Sec. 113.27(d).
(b) Safety tests. Bulk or final container samples of completed
product from each serial shall be tested for safety in young adult mice
in accordance with the test provided in Sec. 113.33(b) unless:
(1) The product contains material which is inherently lethal for
mice.
In such instances, the guinea pig safety test provided in
Sec. 113.38 shall be conducted in place of the mouse safety test.
(2) The product is recommended for poultry. In such instances, the
product shall be safety tested in poultry as defined in the specific
Standard Requirement or Outline of Production for the product.
(3) The product is recommended for fish, other aquatic species, or
reptiles. In such instances, the product shall be safety tested in
fish, other aquatic species, or reptiles as required by specific
Standard Requirement or Outline of Production for the product.
(c) Identity test. Methods of identification of Master Seed
Bacteria to the genus and species level by laboratory tests shall be
sufficient to distinguish the bacteria from other similar bacteria
according to criteria described in the most recent edition of
``Bergey's Manual of Systematic Bacteriology'' or the American Society
for Microbiology ``Manual of Clinical Microbiology''. If Master Seed
Bacteria are referred to by serotype, serovar, subtype, pilus type,
strain or other taxonomic subdivision below the species level, adequate
testing must be used to identify the bacteria to that level. Tests
which may be used to identify Master Seed Bacteria include, but are not
limited to:
(1) Cultural characteristics,
(2) Staining reaction,
(3) Biochemical reactivity,
(4) Fluorescent antibody tests,
(5) Serologic tests,
(6) Toxin typing,
(7) Somatic or flagellar antigen characterization, and
(8) Restriction endonuclease analysis.
(d) Ingredient requirements. Ingredients used for the growth and
preparation of Master Seed Bacteria and of final product shall meet the
requirements provided in Sec. 113.50. Ingredients of animal origin
shall meet the applicable requirements provided in Sec. 113.53.
* * * * *
Done in Washington, DC, this 13th day of March 1995.
Terry L. Medley,
Acting Administrator, Animal and Plant Health Inspection Service.
[FR Doc. 95-6648 Filed 3-16-95; 8:45 am]
BILLING CODE 3410-34-M