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 § 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 § 113.33(b) unless:
(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 § 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 § 113.41, except that calves shall be injected with the equivalent of two doses of vaccine administered as recommended on the label.
(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 § 113.50. Ingredients of animal origin shall meet the applicable requirements provided in § 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 § 113.29.