113.200—General requirements for killed virus vaccines.
When prescribed in an applicable Standard Requirement or in the filed Outline of Production, a killed virus vaccine shall meet the applicable requirements in this section.
(a) Killing agent.
The vaccine virus shall be killed (inactivated) by an appropriate agent. The procedure involved may be referred to as inactivation. Suitable tests to assure complete inactivation shall be written into the filed Outline of Production.
(b) Cell culture requirements.
If cell cultures are used in the preparation of the vaccine, primary cells shall meet the requirements in § 113.51 and cell lines shall meet the requirements in § 113.52.
(c) Purity tests—
(1) Bacteria and fungi.
Final container samples of completed product from each serial shall be tested as prescribed in § 113.26.
(2) Avian origin vaccine.
Bulk pooled material or final container samples from each serial shall also be tested for:
(3) Mycoplasma.
If the licensee cannot demonstrate that the agent used to kill the vaccine virus would also kill mycoplasma, each serial of the vaccine shall be tested for mycoplasma as prescribed in § 113.28, prior to adding the killing agent. Material found to contain mycoplasma is unsatisfactory for use.
(4) Extraneous viruses.
Each lot of Master Seed Virus used to prepare killed virus vaccine recommended for animals other than poultry shall meet the requirements for extraneous viruses as prescribed in § 113.55.
(d) Safety tests.
Final container samples of completed product from each serial shall be tested for safety in guinea pigs as prescribed in § 113.38 and for safety in mice as prescribed in § 113.33: Provided, That, vaccines recommended for use only in poultry are exempt from this requirement.
(e) Viricidal activity test.
Only serials tested for viricidal activity in accordance with the test provided in § 113.35 and found satisfactory by such test shall be packaged as diluent for desiccated fractions in combination packages.
(f) Formaldehyde content.
If formaldehyde is used as the killing agent, the residual free formaldehyde content must not exceed 0.74 grams per liter (g/L) as determined using the ferric chloride test. 3 Firms currently using tests for residual free formaldehyde content other than the ferric chloride test have until July 14, 2004 to update their Outline of Production to be in compliance with this requirement.
Code of Federal Regulations
Footnote(s): 3 The procedures for performing the ferric chloride test for residual free formaldehyde may be obtained from USDA, APHIS, Center for Veterinary Biologics-Laboratory, 1800 Dayton Road, P.O. Box 844, Ames, IA 50010.