An Equal Opportunity Provider and Employer

VETERINARY SERVICES MEMORANDUM NO. 800.116 

TO: Veterinary Services Leadership Team

Directors, Center for Veterinary Biologics

Biologics Licensees, Permittees, and Applicants

FROM: Jack A. Shere /s/ B. Healey for J. Shere, August 14, 2017 

Deputy Administrator

SUBJECT: Target Animal Safety Testing Exemption 

I. PURPOSE

This memorandum provides guidance to licensed firms on requesting an exemption 

under title 9, Code of Federal Regulations (9 CFR), part 113.4, to target animal safety 

testing as required in section V.B. of the Outline of Production and 9 CFR 113.64, 

113.100, and 113.300. The Center for Veterinary Biologics (CVB) will consider 

granting an exemption to target animal safety testing for specific products with a 

documented history of acceptable safety results and controlled manufacturing processes 

that have ensured batch-to-batch consistency and sterility. 

II. REPLACEMENT

This memorandum replaces Veterinary Services Memorandum No. 800.116 dated 

July 31, 2013. 

III. BACKGROUND

Safety testing in animals has been a component of the approval process for each serial 

of product released for marketing by the CVB since the program’s inception. This 

release testing provides assurance that each serial of product will not have unfavorable 

results in the target animal. General safety requirements for live bacterial vaccines are 

described in 9 CFR 113.64, inactivated bacterial products in 9 CFR 113.100, killed 

virus vaccines in 9 CFR 113.200, live virus vaccines in 9 CFR 113.300, and antibody 

products in 9 CFR 113.450. 

Depending on the type of product, target animal safety testing may be conducted in the 

cat (9 CFR 113.39), dog (9 CFR 113.40), calf (9 CFR 113.41), pig (9 CFR 113.44), 

sheep (9 CFR 113.45), poultry (9 CFR 113.100(b)(2)), or aquatic species or reptiles 

(9 CFR 113.100(b)(3)). If the Standard Requirement (stipulated in 9 CFR) for a product 

does not specify the animal safety test method, section V.B. in the Outline of 

Production must indicate a method and state the animal species to be used in safety 

testing. With the number of serials produced by all licensed manufacturers, the number 

of target animals used for safety testing can be substantial.

Animal and Plant

Health Inspection

Service

Veterinary Services

1400 Independence

Ave, SW

Washington, DC

20250
VETERINARY SERVICES MEMORANDUM NO. 800.116

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 An Equal Opportunity Provider and Employer

Some products may have established historical data documenting product safety and 

consistency in manufacturing processes, precluding the need for continued target animal 

safety testing. Therefore, a process by which firms could obtain an exemption from target 

animal safety testing is presented below.

USDA’s consideration of an exemption to target animal safety testing is consistent with the 

International Cooperation on Harmonization of Technical Requirements for Registration of 

Veterinary Products (VICH) Steering Committee’s recommendations described in 

“Harmonization of Criteria to Waive Target Animal Batch Safety Testing (TABST) for 

Inactivated Vaccines (TABST; GL50) and “Harmonisation of Criteria to Waive Target 

Animal Batch Safety Testing for Live Vaccines for Veterinary Use” (TABST; GL55), aimed 

to minimize the use of target animal safety tests and the principles of reducing, refining, and 

replacing the use of animals in testing. 

IV. POLICY

A. The CVB will consider exemption requests for all products with documented 

consistency in manufacturing processes and product safety with the exception of 

safety tests associated as precursors to potency tests. 

1. A submitted report should provide an overall assessment of all aspects of the 

product’s safety performance, including serial release and pharmacovigilance data 

(number of years on the market, number of doses sold, frequency and severity of 

adverse event reports). Specific data for 10 serials, or a minimum of 5 serials if 10 

serials are not manufactured within 3 years, should be submitted. The serials 

should be consecutive and from different vaccine bulks. Fallout products of larger 

combinations may be supported by these data. Information on any serials failing 

animal safety testing or deviating from the Outline of Production during this time 

period should be disclosed.

2. To ensure that products exempt from safety testing in animals perform in the field 

as expected, the licensee or permittee must maintain detailed pharmacovigilance 

records for all adverse event reports received for the respective products they 

produce or distribute. For products receiving this exemption, summaries of 

adverse events should be provided to the CVB annually per license restriction.

3. Outlines of Production containing inadequate production details must be revised 

and submitted for review before the CVB can consider the exemption. Adequate 

details include the maximum antigen content based on safety test information, 

historical antigen input, etc. Changes to the Outline of Production open up the 

exemption for reexamination.
VETERINARY SERVICES MEMORANDUM NO. 800.116

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 An Equal Opportunity Provider and Employer

B. Suspension of Safety Testing Exemption and Reissuance

1. If a serial is manufactured with a nonconformance to the Outline of Production, 

the exemption may be suspended. The serial must be tested according to the 

applicable requirements. Reissuance of the exemption will require adequate 

information demonstrating that the production process is controlled, including 

provision of satisfactory safety test results for 10 consecutive serials, or 5 if made 

infrequently. In the event of unfavorable pharmacovigilance report updates, an 

exemption may be suspended. If changes are made to the Outline of Production, 

additional serial safety testing may be requested to continue the exemption.

2. An exemption may be suspended if production nonconformities discovered during 

onsite inspection could have a material effect on the product as determined by the 

Inspection and Compliance staff.

V. IMPLEMENTATION/APPLICABILITY

This change will be effective 30 days from the date of this memorandum.