[Code of Federal Regulations]
[Title 9, Volume 1]
[Revised as of January 1, 2006]
From the U.S. Government Printing Office via GPO Access
[CITE: 9CFR113.64]

[Page 646-647]
 
                  TITLE 9--ANIMALS AND ANIMAL PRODUCTS
 
  CHAPTER I--ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF 
                               AGRICULTURE
 
PART 113_STANDARD REQUIREMENTS--Table of Contents
 
Sec. 113.64  General requirements for live bacterial vaccines.

    When prescribed in an applicable Standard Requirement or in the 
filed Outline of Production, a live bacterial vaccine shall meet the 
requirements in this section.
    (a) Purity test. Final container samples of completed product from 
each serial and subserial, and samples of 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(b).
    (b) Safety tests. (1) Samples of completed product from each serial 
or first subserial and samples of each lot of Master Seed Bacteria shall 
be tested for safety in young adult mice in accordance with the test 
provided in Sec. 113.33(b) unless:
    (i) The bacteria or agents in the vaccine are inherently lethal for 
mice.
    (ii) The vaccine is recommended for poultry.
    (2) Samples of completed product from each serial or first subserial 
of live bacterial vaccine shall be tested for safety in one of the 
species for which the product is recommended as follows:
    (i) Live bacterial vaccine recommended for use in dogs shall be 
tested as provided in Sec. 113.40, except that dogs shall be injected 
with the equivalent of two doses of vaccine administered as recommended 
on the label.
    (ii) Live bacterial vaccine recommended for use in cattle shall be 
tested as provided in Sec. 113.41, except that calves shall be injected 
with the equivalent of two doses of vaccine administered as recommended 
on the label.
    (iii) Live bacterial vaccine recommended for use in sheep shall be 
tested as provided in Sec. 113.45.
    (iv) Live bacterial vaccine recommended for use in swine shall be 
tested as provided in Sec. 113.44.

[[Page 647]]

    (c) Identity test. At least one of the identity tests provided in 
this paragraph shall be conducted for the Master Seed Bacteria and final 
container samples from each serial or first subserial of completed 
biological product. A known positive control (reference) provided or 
approved by Animal and Plant Health Inspection Service shall be included 
in such tests.
    (1) Fluorescent antibody test. The direct fluorescent antibody 
staining technique shall be conducted using suitable smears of the 
vaccine bacteria. Fluorescence typical for the bacteria concerned shall 
be demonstrated. Fluorescence shall not occur in control smears treated 
with specific antiserum.
    (2) Tube agglutination test. A tube agglutination test shall be 
conducted with a suitable suspension of the vaccine bacteria using the 
constant antigen decreasing serum method with specific antiserum. 
Agglutination typical for the bacteria shall be demonstrated. 
Agglutination shall not occur with negative serum used as a control in 
this test.
    (3) Slide agglutination test. The rapid plate (slide) agglutination 
test shall be conducted with suitable suspensions of the vaccine 
bacteria using the hanging drop, slide or plate method, with specific 
antiserum. Agglutination typical for the bacteria shall be demonstrated 
by microscopic or macroscopic observation. Agglutination shall not occur 
with negative serum used as a control in this test.
    (4) Characterization tests. Applicable biochemical and cultural 
characteristics shall be demonstrated as specified in the filed Outline 
of Production.
    (d) Ingredient requirements. Ingredients used for the growth and 
preparation of Master Seed Bacteria and of live bacterial vaccine shall 
meet the requirements provided in Sec. 113.50. Ingredients of animal 
origin shall meet the applicable requirements provided in Sec. 113.53.
    (e) Moisture content. The maximum percent moisture in desiccated 
vaccines shall be stated in the filed Outline of Production and shall be 
established by the licensee as follows:
    (1) Prelicensing. Data obtained by conducting accelerated stability 
tests and bacterial counts shall be acceptable on a temporary basis.
    (2) Licensed products. Data shall be obtained by determining the 
percent moisture and bacterial count at release and expiration on a 
minimum of 10 consecutive released serials.
    (3) Final container samples of completed product from each serial 
and subserial must be tested for moisture content in accordance with the 
test provided in Sec. 113.29.

[48 FR 33476, July 22, 1983, as amended at 54 FR 19352, May 5, 1989; 56 
FR 66784, Dec. 26, 1991; 68 FR 57608, Oct. 6, 2003]