Last updated: December 6, 2007

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The US Department of Agriculture (USDA) is broadly responsible for “protecting American agriculture.” Within the context of regulatory toxicology, the USDA Center for Veterinary Biologics (CVB), a division of the Animal and Plant Health Inspection Service (APHIS), “regulates veterinary biologics (vaccines, bacterins, antisera, diagnostic kits, and other products of biological origin) to ensure that the veterinary biologics available for the diagnosis, prevention, and treatment of animal diseases are pure, safe, potent, and effective.”

 

Regulatory Authority

The Virus Serum Toxin Act (21 USC § 151-159 et seq.) proscribes the preparation or sale of “any worthless, contaminated, dangerous, or harmful virus, serum, toxin, or analogous product intended for use in the treatment of domestic animals” and establishes a legal basis for the licensing and inspection of veterinary biologics and for the USDA’s creation and enforcement of implementing regulations.

USDA regulations concerning biological products are codified under Title 9 of the Code of Federal Regulations (9 CFR § 101-123). Especially significant are the “standard requirements” laid out in Part 113, which prescribe extensive in vivo toxicological testing for each batch product and stipulate that “[n]o biological product shall be released prior to the completion of tests prescribed … for the product to establish the product to be pure, safe, potent, and efficacious.” In addition, the regulations permit APHIS itself to conduct duplicative purity, safety, potency, and/or efficacy studies for confirmation purposes. The following are the principal categories of animal tests that may be required:

• Target species safety test (e.g., dog, cat, mouse, calf, swine, sheep)
• Live bacterial vaccines (e.g., Brucella, Anthrax, Pasteurella, Chlamydia)
• Inactivated bacterial products (e.g., Leptospira, Clostridium, Tetanus)
• Live virus vaccines (e.g., avian pox, bluetongue, measles, Newcastle disease)
• Killed virus vaccines (e.g., canine distemper, rabies, parvovirus)
• Antibody products (e.g., tetanus and clostridium antitoxins)

Further to the regulations themselves, USDA has published an extensive series of Veterinary Service Memorandums and public notices that provide companies with additional detailed guidance concerning product- and agent-specific testing, licensing, and other regulatory requirements.

 

Alternatives Policies & Actions

Between 1998 and 2003, CVB published several memoranda providing guidelines concerning the use of in vitro methods under certain circumstances for the testing of veterinary vaccines. Examples include:

• Memorandum No. 800.90 – Guidelines for veterinary biological relative potency assays and reference preparations based on ELISA antigen quantification
• Memorandum No. 800.92 – In vitro tests for serial release
• Memorandum No. 800.99 – Guidelines for using in vitro relative potency tests to determine the antigen content of inactivated bovine rhinotracheitis vaccine
• Memorandum No. 800.102 – Exemption from Leptospira bacterin testing in hamsters
• Memorandum No. 800.104 – In vitro serial release potency test for completed product containing Clostridium chauvoei

In 2004, CVB held a conference entitled Technology and Approaches to Reduce, Refine, and Replace Animal Testing. The USDA is also a proactive member of the US Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM).