[Federal Register Volume 59, Number 40 (Tuesday, March 1, 1994)]
[Unknown Section]
[Page 0]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 94-4592]


[[Page Unknown]]

[Federal Register: March 1, 1994]


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DEPARTMENT OF AGRICULTURE
9 CFR Parts 101 and 113

[Docket No. 92-201-1]

 

Viruses, Serums, Toxins, and Analogous Products; General 
Requirements for Inactivated Bacterial Products

AGENCY: Animal and Plant Health Inspection Service, USDA.

ACTION: Proposed rule.

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SUMMARY: We are proposing to amend the regulations to include a general 
Standard Requirement for inactivated bacterial products that is 
consistent with the general Standard Requirements for live bacterial 
products, killed virus vaccines, and live virus vaccines. The proposed 
rule would update the current standards and provide uniform, relevant 
criteria for inactivated bacterial products. We are also including 
criteria and tests concerning Master Seed and its identity. Finally, 
the proposed amendment provides a choice of the most appropriate test 
methods, including identity tests, for the broad range of inactivated 
bacterial products available today.

DATES: Consideration will be given only to comments received on or 
before May 2, 1994.

ADDRESSES: Please send an original and three copies of your comments to 
Chief, Regulatory Analysis and Development, PPD, APHIS, USDA, room 804, 
Federal Building, 6505 Belcrest Road, Hyattsville, MD 20782. Please 
state that your comments refer to Docket No. 92-201-1. 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 encouraged to call ahead (202) 690-2817 to 
facilitate entry into the comment reading room.

FOR FURTHER INFORMATION CONTACT: Dr. Richard E. Pacer, Senior Staff 
Veterinarian, Veterinary Biologics, BBEP, APHIS, USDA, room 838, 
Federal Building, 6505 Belcrest Road, Hyattsville, MD 20782, (301) 436-
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.
    General Standard Requirements are currently listed in Title 9, Code 
of Federal Regulations, part 113 for live virus vaccines, killed virus 
vaccines, and live bacterial vaccines. General Standard Requirements, 
however, have not been established for inactivated bacterial products. 
Previously, the general Standard Requirements for live bacterial 
products in Sec. 113.64 have often been applied to inactivated 
bacterial products. The proposed amendments would define the relevant 
criteria for the evaluation of the purity, safety, and identity of 
inactivated bacterial products in proposed Sec. 113.100(a-d). The 
proposed amendments would also define the Master Seed concept in 
proposed Sec. 113.100(c) as it applies to inactivated bacterial 
products. The proposed amendments would provide more specific criteria 
for these inactivated bacterial products in proposed Sec. 113.100(a-d).
    Section 113.100 pertaining to inactivated bacterial products 
currently defines four categories of products: bacterin, toxoid, 
bacterin-toxoid, and bacterial extract. These definitions in current 
Sec. 113.100, paragraphs (a-d) are accurate, but should appear in Part 
101--Definitions. Therefore, the definitions for bacterin, toxoid, 
bacterin-toxoid, and bacterial extract, with minor editorial changes 
for clarity, would be removed from Sec. 113.100 and added to Sec. 101.3 
of the regulations, which defines biological products and related 
terms.
    The general Standard Requirement in proposed new Sec. 113.100 would 
establish criteria for purity, safety, identity of Master Seed, and 
ingredients used in the preparation of inactivated bacterial products.
    The purity of inactivated bacterial products would be based on 
applicable tests in Secs. 113.26 and 113.27(d) of the regulations.
    The safety of inactivated bacterial products would be based on 
mouse or guinea pig safety tests in Secs. 113.33(b) and 113.38 of the 
regulations.
    The identity of the Master Seed Bacteria would be determined to the 
genus and species level according to published criteria. If the Master 
Seed bacteria are characterized as to serotype, serovar, subtype, pilus 
type, strain, or other taxonomic subdivision below the species level, 
adequate testing would be required to distinguish the Master Seed 
bacteria from other bacteria characterized to that level based on 
specified test methods.
    Finally, ingredients used in the growth and preparation of the 
Master Seed bacteria would have to meet specified requirements in 
Secs. 113.50 and 113.53 of the regulations.

Executive Order 12866 and Regulatory Flexibility Act

    The Department is issuing this proposed rule in conformance with 
Executive Order 12866.
    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 
would be considered small entities and would benefit from the adoption 
of this proposed rule. The benefits of the proposed rule would include 
increased efficiency and reduced time and expense in accomplishing the 
steps toward licensure of an inactivated bacterial product. These 
benefits would 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 proposed rule.
    Under these circumstances, the Administrator of the Animal and 
Plant Health Inspection Service has determined that this action would 
not have a significant economic impact on a substantial number of small 
entities.

Executive Order 12778

    This proposed rule has been reviewed under Executive Order 12778, 
Civil Justice Reform. If this proposed rule is adopted: (1) All State 
and local laws and regulations that are in conflict with this rule will 
be preempted; (2) no retroactive effect will be given to this rule; and 
(3) administrative proceedings will not be required before parties may 
file suit in court challenging this rule.

Paperwork Reduction Act

    This proposed 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 and 113 would be amended as follows:

PART 101--DEFINITIONS

    1. The authority citation for part 101 would continue 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, would be 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 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. 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 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. 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 would continue to read as 
follows:

    Authority: 21 U.S.C. 151-159; 7 CFR 2.17, 2.51, and 371.2(d).

    4. Section 113.100, the heading, introductory paragraph, and 
paragraphs (a) through (d) would be 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.
    (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 18th day of February 1994.
Patricia Jensen,
Acting Assistant Secretary, Marketing and Inspection Services.
[FR Doc. 94-4592 Filed 2-28-94; 8:45 am]
BILLING CODE 3410-34-M