[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]



=======================================================================
-----------------------------------------------------------------------

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.

-----------------------------------------------------------------------

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