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May 11, 2007 

CENTER FOR VETERINARY BIOLOGICS NOTICE NO. 07-06 

Subject: Preparation and Testing of Experimental Biological Products that are 

 Derived from Biotechnology 

To: Biologics Licensees, Permittees, and Applicants 

 Veterinary Services Management Team 

 Directors, Center for Veterinary Biologics 

 Area Veterinarians in Charge, VS 

 State Veterinarians 

I. PURPOSE 

 

The purpose of this notice is to inform biologics firms of the expectations of the Center 

for Veterinary Biologics (CVB) regarding conditions for research and development of 

biotechnology-derived products. 

II. BACKGROUND 

Title 9, Code of Federal Regulations (9CFR), Part 103.1, indicates that preparation of 

experimental biological products must not result in contamination of licensed products. 

It further specifies that each request for permission to prepare an experimental biological 

product on licensed premises shall indicate the nature of the unlicensed product, 

designate facilities to be used, and specify precautions which will be taken to prevent 

contamination of licensed products. 

In 1994, the National Institutes of Health published “Guidelines for Research Involving 

Recombinant DNA Molecules” (NIH Guidelines). Numerous amendments have been 

made since then. The NIH Guidelines provide for oversight by an Institutional Biosafety 

Committee (IBC), a group of diverse individuals knowledgeable about the NIH 

Guidelines and its ranking of the human health risks posed by specific pathogens. They 

also make physical containment recommendations for large-scale use of organisms 

containing recombinant DNA molecules. These recommendations, designated as 

Biosafety Level 1, 2, 3, or 4, refer to the degree of human health risk, not to animal health 

or environmental risk. Federal laboratories (including the CVB laboratory) as well as 

many academic and other non-Federal laboratories operate under these guidelines. 

A comprehensive biosafety risk assessment also requires characterization of hazards to 

animal health. In 2004 the World Health Organization (WHO) established their 

classification of infective microorganisms using 4 risk groups for animal and human 

disease based on pathogenicity, modes of transmission, and host range of the organism. 

United States 

Department of 

Agriculture

Animal and Plant 

Health Inspection 

Service 

Veterinary Services 

Center for Veterinary 

Biologics 

510 S. 17th Street, 

Suite 104 

Ames, IA 50010 

(515) 232-5785 

FAX (515) 232-7120 
Center for Veterinary Biologics Notice No. 07-06 2 

The National Environmental Policy Act (NEPA) was passed in 1969. It requires that 

environmental impact be evaluated prior to release of an agent. Where adverse 

environmental effects might be anticipated, alternative options or at least sufficient 

mitigation of the negative effects must be explored. 

Deliberate release of any organism containing recombinant DNA into the environment is 

subject to review and approval by appropriate Federal agencies. Under normal 

husbandry and laboratory practices, injected veterinary biologicals are not considered to 

be released into the environment, provided that the vaccine organism is not shed after 

vaccination. Any microbial agents that are shed are considered to be released into the 

environment. 

 

III. POLICY

When making a request to the CVB for permission to prepare an experimental biological 

product on licensed premises, per 9CFR Part 103.1, firms should indicate the nature of 

the unlicensed product (including if it is biotechnology-derived), designate the facilities 

to be used, and specify precautions which will be taken to prevent contamination of 

licensed products. Food animals vaccinated with an experimental biotechnology-derived 

product cannot enter the human food chain unless a risk analysis is conducted and 

approved by the CVB. This is in addition to the usual pre-slaughter considerations 

regarding whether the adjuvant is approved for use in the species of animals vaccinated, 

the appropriate withdrawal time has been observed (per 9CFR Part 112.2(a)(8) and VS 

Memorandum 800.51), and animals are not diseased or unhealthy following the 

conclusion of a vaccination/challenge study. 

The CVB strongly recommends that biologics firms working with experimental 

biotechnology-derived products comply with NEPA and provide appropriate containment 

to ensure low risk to human and animal health and to the environment. Research on 

recombinant organisms should be evaluated and approved by the firm’s IBC or an 

equivalent body. The evaluation by an IBC or an equivalent body should be conducted 

for research facilities that are entirely separate and apart from production facilities of a 

licensed establishment, as well as for research facilities that are on the same premises as 

the production facilities. 

Firms may wish to ship experimental biotechnology-derived products for testing in 

animals. Required documentation to request authorization to ship experimental product 

is described in 9CFR Part 103.3 and VS Memorandum 800.67. In addition, the firm 

proposing to ship the biological product should provide a description of the recombinant 

and its construction (including any vectors used) and documentation of evaluation and 

approval by the IBC or an equivalent body of the institution conducting the testing. 

/s/Richard E. Hill, Jr. 

Richard E. Hill, Jr. 

Director 

Center for Veterinary Biologics