United States

Department of

Agriculture

Marketing and 

Regulatory 

Programs 

Animal and Plant 

Health Inspection 

Service 

Veterinary Services 

Center for Veterinary

Biologics 

Suite 104 

510 South 17th Street 

Ames, IA 50010

(515) 232-5785 

FAX (515) 232-7120 

September 12, 2003 

CENTER FOR VETERINARY BIOLOGICS NOTICE NO. 03-13 

Subject: Detection of Avian Lymphoid Leukosis Virus 

in Veterinary Biological Products 

To: Biologics Licensees, Permittees, and Applicants 

Veterinary Services Management Team

Directors, Center for Veterinary Biologics 

I. PURPOSE 

The purpose of this notice is to inform interested parties that the Center for Veterinary 

Biologics (CVB) is aware that certain veterinary biological products may contain a 

contaminating virus not easily detected by current routine test methods and to describe 

actions to address this issue. 

II. BACKGROUND 

Six subgroups of avian leukosis virus (ALV), also known as lymphoid leukosis virus 

(LLV), are currently recognized. These are retroviruses known to infect chickens and 

can significantly lower production and increase susceptibility to other diseases. Five of 

these subgroups (designated A, B, C, D, and J) are transmitted as infectious viral particles 

and known as exogenous ALVs. Genetic elements of Subgroup E ALVs are integrated in 

the normal genome of nearly all chickens either as complete or incomplete viral genomes 

and known as endogenous ALV. Typically, exogenous ALV are associated with tumor 

formation and production problems while endogenous ALV are not. Because both forms 

of ALV can be transmitted vertically, chicken embryos and tissue cultures used as 

ingredients or substrates for the production of veterinary biological products may harbor 

exogenous or endogenous ALV. 

The CVB, under authority of the Virus-Serum-Toxin Act and the Code of Federal 

Regulations (9 CFR), requires that all veterinary biological products be tested and shown 

to be free of contaminating agents to ensure purity. While suppliers of fertile eggs or 

tissue for use in veterinary biological product production are not regulated by the CVB, 

Veterinary Services (VS) Memorandum No. 800.65 specifies that fertile eggs or tissue 

intended for use in the production of veterinary biological products be free of specified 

disease agents, including ALV. In addition, the 9 CFR 113.31 specifies that prior to 

release for sale, all live virus veterinary biological products must be tested by the 

complement fixation test for avian leukosis (COFAL), which detects the presence of 

exogenous ALV. 

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Center for Veterinary Biologics Notice No. 03-13 2 

Information has recently come to the attention of the CVB suggesting the presence of 

ALV in certain veterinary biological products intended for use in poultry which was not 

detected by the required routine testing specified in VS Memorandum No. 800.65 and 

9 CFR 113.31. The reason for the failure of the required tests to detect this 

contamination is unclear at this time, but may be related to the presence of both 

endogenous (Subgroup E) and exogenous (Subgroup A) ALV in the tested samples. The 

source of the contaminating virus has not been unequivocally determined, but evidence 

suggests a common source of fertile eggs used in the manufacture of the contaminated 

products as the origin. 

III. ACTION 

The CVB is issuing this notice to ensure that members of the veterinary biological 

product industry who use fertile eggs or tissues derived from them in their production 

processes are aware of this issue and can exercise appropriate safeguards to prevent 

contamination of their products. 

Veterinary biologics manufacturers are required to report the results of all testing for 

ALV by any method used by the firm, including and in addition to the test required by 

9 CFR 113.31. These results shall be included on APHIS Form 2008 for each product 

serial when submitted to the CVB for authorization to release the serial (9 CFR 116.7). 

The CVB is further addressing this issue in cooperation with representatives from

industry, academia, and other government agencies through the following steps: 

• We are currently evaluating the COFAL test as specified in 9 CFR 113.31, as well 

as modifications to this test and alternative procedures, to enhance the ability to 

detect ALV contamination of products. We expect that this evaluation will result 

in proposals to modify ALV test procedures from those currently prescribed by 

regulation or pending implementation. 

• Validated results will be communicated to industry representatives as they 

become available. 

Veterinary biologics manufacturers are encouraged to continue to assist the CVB by 

providing valuable information and adopting recommendations in a timely fashion to 

ensure the highest quality of veterinary biological products. 

/s/ Richard E. Hill, Jr. 

Richard E. Hill, Jr. 

Director

Center for Veterinary Biologics