An Equal Opportunity Provider and Employer 

VETERINARY SERVICES MEMORANDUM NO. 800.210 

TO: Veterinary Services Leadership Team 

 Directors, Center for Veterinary Biologics 

 Biologics Licensees, Permittees, and Applicants 

 

FROM: Jack A. Shere 

 Deputy Administrator 

SUBJECT: Manufacturing Deviations Identified Prior to Marketing Release 

I. PURPOSE 

This memorandum provides guidance to licensees and permittees regarding processes 

to follow prior to marketing release when product preparation does not agree with a 

filed Outline of Production or the regulations. This document does not cover noncompliance with any statutory requirements of the Virus-Serum-Toxin Act. These 

procedures do not apply to contamination events or to products containing rabies virus 

or derived from select agents. 

II. CANCELLATION 

This memorandum replaces Veterinary Services Memorandum No. 800.210, dated 

December 22, 2010. 

III. BACKGROUND 

The Virus-Serum-Toxin Act protects veterinary biologics users from worthless, 

contaminated, dangerous, or harmful products. Title 9, Code of Federal Regulations (9 

CFR), part 102.5(c)(1) requires producers of licensed biological products prepare them 

as required by the regulations and in accordance with a filed Outline of Production. 

Producers must conform to the Outline of Production to consistently prepare quality 

products. Products may be considered worthless, contaminated, dangerous, or harmful 

when not prepared in accordance with the filed Outline of Production or the regulations. 

The Center for Veterinary Biologics (CVB) acknowledges that deviations may occur 

during the manufacturing of biological products. The CVB may consider products 

manufactured with inadvertent deviations eligible for marketing release if the licensee 

or permittee discovers and thoroughly investigates and analyzes the deviations before 

marketing release. Products not evaluated appropriately may be considered worthless, 

contaminated, dangerous, or harmful. 

The CVB may also need to determine whether certain deviations would cause harm to 

the public interest; and, if the licensee or permittee releases the product to the market, if 

the public should be aware of the circumstances. Evaluation of the product by the 

 Animal and Plant 

 Health Inspection 

 Service 

 Veterinary Services

 1400 Independence

 Ave, SW 

 Washington, DC 

 20250

JACK 

SHERE

Digitally signed 

by JACK SHERE 

Date: 2018.05.31 

10:22:34 -04'00'
VETERINARY SERVICES MEMORANDUM NO. 800.210 

Page 2 

 An Equal Opportunity Provider and Employer 

Outline of Production testing alone will not satisfy the criteria for the evaluation and risk 

assessment. The evaluation should provide scientific justification for the conclusion. The 

licensee or permittee keeps the documentation and must provide it for CVB review upon 

request. 

If the licensee or permittee discovers it did not prepare the product in accordance with the 

Outline of Production or the regulations after submitting APHIS Form 2008 or the CVB 

marketing release, it must follow the procedures in 9 CFR 116.5(b), as defined in Veterinary 

Services Memorandum No. 800.57. 

IV. PROCEDURES 

A. If a licensee or permittee discovers a manufacturing deviation before submitting 

APHIS Form 2008, it can evaluate whether the deviation has adversely affected the 

product, the testing of the product, and the shelf life of the product. The licensee or 

permittee must have a systematic, documented procedure in place to address 

deviations. 

B. Documentation of the investigation by the licensee or permittee shall include: 

1. A detailed systematic process-driven investigation of the incident, including a 

root cause and risk analysis, possible previous occurrences, the effect on the 

product, and similar incidence in other products or processes. 

2. If the licensee or permittee has several manufacturing sites, an analysis to 

address the impact of licensed/permitted products at the different 

licensed/permitted sites, as well as the communication of the deviation and 

investigation to other sites. 

3. All associated copies of testing or other materials to support the disposition of 

the product. 

4. Corrective and preventive actions, including a review process for effectiveness. 

C. The results of an investigation supporting that the product performs as intended 

throughout shelf life, despite not being prepared in accordance with the Outline of 

Production or the regulations may be considered eligible for consideration for 

market release. 

D. The licensee or permittee must dispose of product determined to be unsatisfactory 

according to 9 CFR 114.15. 

E. CVB may consider the licensee or permittee’s failure to adequately investigate, 

document, or institute appropriate corrective or preventive actions when the licensee 

or permittee produces a product not in accordance with the Outline of Production or 

the regulations and releases it to the market willful or harmful and not in the public 
VETERINARY SERVICES MEMORANDUM NO. 800.210 

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 An Equal Opportunity Provider and Employer 

interest. The CVB may take regulatory action against the licensee/permittee in 

accordance with 9 CFR 105.1, 105.2, or 105.3. 

F. APHIS may revoke without prior review a licensee or permittee’s privilege to 

determine a product’s eligibility for consideration for marketing release. 

V. IMPLEMENTATION/APPLICABILITY 

This change is effective immediately.