An Equal Opportunity Provider and Employer

VETERINARY SERVICES MEMORANDUM NO. 800.50

TO: Veterinary Services Leadership Team

Directors, Center for Veterinary Biologics

Biologics Licensees, Permittees, and Applicants

FROM: Jack A. Shere

Deputy Administrator

SUBJECT: Basic License Requirements and Guidelines for Submitting Materials in 

Support of Licensure

I. PURPOSE

This memorandum provides guidance regarding the requirements for obtaining a U.S. 

Veterinary Biologics Establishment License, per title 9, Code of Federal Regulations (9 

CFR), section 102.3(a), and a U.S. Veterinary Biological Product License, per 9 CFR 

102.3(b). This memorandum specifies the information and documents an applicant 

must provide to APHIS in order for APHIS to complete licensing actions. 

In addition, this memorandum lists additional regulatory resource documents available 

at the Center for Veterinary Biologics (CVB) Web site at 

https://www.aphis.usda.gov/aphis/ourfocus/animalhealth/veterinary-biologics/biologicsregulations-and-guidance/ct_regs_guidance. The CVB encourages applicants to contact 

CVB’s Policy, Evaluation, and Licensing (CVB-PEL) personnel in order to facilitate 

submission and review of materials.

Although many of the procedures for approving imported products match those 

required for domestically produced products, an applicant for a U.S. Veterinary 

Biological Product Permit (for imported products) should refer to Veterinary Services 

(VS) Memorandum 800.101 for additional guidance.

II. CANCELLATION

This memorandum replaces VS Memorandum 800.50, dated February 9, 2011.

III. BACKGROUND

Veterinary biologics producers in the United States must have both a U.S. Veterinary 

Biologics Establishment License for their facility and a U.S. Veterinary Biological 

Product License for each product produced in their facility. To qualify for an 

establishment license, an applicant also must qualify for at least one product license. If 

an applicant, whether a company or individual, plans to market imported veterinary 

biological products in the United States, the CVB requires the applicant to have a U.S. 

Veterinary Biological Product Permit (Permit for Distribution and Sale).

Animal and Plant

Health Inspection

Service

Veterinary Services

1400 Independence

Ave, SW

Washington, DC

20250
VETERINARY SERVICES MEMORANDUM NO. 800.50

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 An Equal Opportunity Provider and Employer

IV. GUIDELINES FOR SUBMISSIONS

This section describes the materials an applicant must submit for the CVB to consider issuing

establishment and product licenses. The address for submitting paper documents is:

Center for Veterinary Biologics-Policy, Evaluation, and Licensing

1920 Dayton Avenue

Ames, IA 50010

Although the CVB has a portal for Web-based submissions, an applicant must make initial 

submissions on paper. Portal eligibility requirements for new establishments are available on 

the NCAH Portal Guidance page of the CVB website. 

The CVB receives, reviews, and files an applicant’s materials and notifies the applicant in 

writing regarding the acceptability of the submitted materials. If applicable, the CVB-PEL 

provides written comments on any revisions that an applicant must make and/or additional 

data that an applicant must submit. 

A. Application for an Establishment License

1. An applicant must submit:

a. Application for U.S. Veterinary Biologics Establishment License (APHIS 

Form 2001).

b. Articles of incorporation for the applicant and any subsidiaries, if applicable 

(9 CFR 102.3).

c. Water quality statement (9 CFR 108.11). Local water authorities must verify in 

a written statement that the facility is in compliance with effluent waste

regulations.

d. Application for at least one U.S. Veterinary Biological Product License 

(APHIS Form 2003) and applicable supporting documents described in section 

IV.B. below.

e. Qualifications of Veterinary Biologics Personnel, (APHIS Form 2007) for key 

employees (9 CFR 114.7(a)). Licensed establishments must be operated under

competent supervisors and employees (9 CFR 102.4). See VS Memorandum 

800.63 for additional guidance on preparing and submitting APHIS Form 

2007.

f. Facility documents, include blueprints, plot plans, and legends (9 CFR 108.2–

108.5). Refer to VS Memorandum 800.78 for guidance in preparing facility 

documents. An applicant must submit two copies of each document. The 
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 An Equal Opportunity Provider and Employer

CVB’s Inspection and Compliance unit (CVB-IC) reviews and responds to the 

facility document submission. 

2. CVB Actions

a. The CVB-IC inspects the buildings, equipment, personnel and processes to 

determine if an applicant can consistently manufacture the product in compliance 

with the regulations and approved Outlines of Production. Although the CVB-IC 

performs the facility inspection, the CVB-PEL initiates the request for 

inspection. Veterinary Services Memorandum 800.91 provides guidance for 

specific inspection categories. If the CVB-PEL has reviewed the establishment 

license application and supporting documents and an applicant has made 

satisfactory progress toward licensure of at least one product in accordance with 

the approved Outline of Production, the CVB-PEL initiates the request for 

inspection, which occurs before it issues the establishment license/permit.

b. The CVB issues an establishment license only when the CVB qualifies a 

product for licensure that will be made in that establishment.

B. Application for a Product License

1. An applicant must submit:

a. Application for U.S. Veterinary Biological Product License (APHIS Form 

2003).

b. Outline of Production (9 CFR 114.8–114.9) and, if applicable, Special 

Outlines (9 CFR 114.9(b)). See VS Memorandum 800.206 for additional 

guidance regarding preparing and submitting Outlines of Production for select 

product types. Submission procedures described in this memorandum are 

applicable to other biological products that are not currently detailed in VS 

Memorandum 800.206.

c. Master Seed and Cell Reports. For each microorganism (Master Seed) and cell 

stock (Master Cell) used in the production of biological products, an applicant 

must submit a report describing testing performed to evaluate the purity, 

identity, and safety of the seed and cell. An applicant must describe the source 

from which the seed or cell was obtained and all known passage history. VS 

Memorandum 800.109 and the following regulations provide further guidance:

9 CFR 113.27(c & d) Detection of extraneous viable bacteria and 

fungi in Master Seed Virus and Master Seed 

Bacteria
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 An Equal Opportunity Provider and Employer

9 CFR 113.51 Requirements for primary cells used for 

production of biologics

9 CFR 113.52 Requirements for cell lines used for production 

of biologics

9 CFR 113.55 Detection of extraneous agents in Master Seed 

Virus

9 CFR 113.64 General requirements for live bacterial vaccines

9 CFR 113.100

VS Memo 800.113

General requirements for inactivated bacterial 

products

Production, Testing and Storage of Master Seed 

and Cell Stocks at Alternate Locations

9 CFR 113.200 General requirements for killed virus vaccines

9 CFR 113.300 General requirements for live virus vaccines

The 9 CFR Standard Requirements for individual product types provide 

additional organism-specific requirements for Master Seeds. An applicant 

should refer to 9 CFR 113 to determine if a Standard Requirement exists for a 

particular product.

d. Summary Information Formats (SIFs). If an applicant plans to use a Master 

Seed to produce new live biological products or produce a Master Seed using

recombinant DNA technology, the CVB requires additional safety and identity 

data. An applicant must provide this information in a SIF. 

The SIF is an “expandable document,” which is updated as an applicant 

generates applicable data to support the license application. The CVB requires 

a completed SIF before issuing a license. The initial version of the SIF, which 

an applicant should submit concurrently with the Master Seed report described 

in section IV.B.1.c, must provide data that are adequate for the CVB 

laboratory to establish proper biocontainment requirements and conduct 

confirmatory testing. See VS Memorandum 800.205 for additional guidance

and https://www.aphis.usda.gov/aphis/ourfocus/animalhealth/veterinarybiologics/biologics-regulations-and-guidance/ct_vb_sifs for document 

templates.

e. Protocols for studies of host animal immunogenicity/efficacy, safety, 

backpassage, shed/spread, immunological interference, and other applicable 

areas. The CVB strongly recommends that applicants have the CVB review 

their protocol before performing a study. If an applicant would like to have the 

CVB comment on the proposed protocol, an applicant should submit the

protocol at least 60 days before the proposed initiation date. The CVB 

provides additional guidance on study design in the following documents:
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 An Equal Opportunity Provider and Employer

Diagnostic Test Kits VS Memorandum 800.73

Potency Test Validation VS Memorandum 800.112

Inactivation Kinetics VS Memorandum 800.117

Study Practices and Documentation VS Memorandum 800.200

Backpassage VS Memorandum 800.201

Efficacy VS Memorandum 800.202

Component Compatibility VS Memorandum 800.203

Field Safety VS Memorandum 800.204

Target Animal Safety VS Memorandum 800.207

2. CVB Actions

a. Outline of Production or Special Outline

(1) If the CVB determines that an applicant included objectionable features in 

the Outline of Production or that the Outline needs critical or extensive 

changes, the CVB may return the Outline unprocessed. An applicant must 

submit a revised Outline of Production that the CVB determines to be 

accurate and sufficient before licensure.

(2) If the CVB determines that the Outline is satisfactory or requires only 

minimal changes, then the CVB processes the Outline by placing a CVB 

stamp in the lower right corner of each page. The CVB reviewer may make 

corrections to the Outline, which immediately become a part of the 

approved document, and/or may provide comments regarding changes the 

applicant must make before product licensure.

b. Master Seed or Master Cell Reports

(1) If the CVB-PEL determines that the reports are satisfactory and complete, 

the CVB-PEL authorizes the facility to submit samples of Master Seed(s) 

and Master Cell Stock(s) to the CVB laboratory for confirmatory testing. 

Applicants should use an APHIS Form 2070 to request permission to 

submit Seed and Cell samples for testing.

(2) If the CVB determines that the CVB laboratory confirmatory testing of the 

Master Seed is satisfactory, then the CVB-PEL authorizes the applicant to 

produce serials (numbered lots) of product in production facilities.

C. Supporting Data for a Product License Application

1. An applicant must submit, as applicable to the product under consideration, the 

following additional reports and materials:

a. In-process procedures and corresponding validation reports:
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 An Equal Opportunity Provider and Employer

(1) Inactivation procedures for killed products.

(2) Maximum allowable moisture levels for desiccated products.

(3) Other Outline procedures, as appropriate.

b. Host animal immunogenicity/efficacy reports:

(1) Preliminary dose determination studies, if performed.

(2) Master Seed immunogenicity/efficacy studies. The regulations at 9 CFR 

113 describe standard immunogenicity tests for certain organisms. An 

applicant must prepare the serial of product used to demonstrate efficacy 

at the highest allowable passage of the Master Seed being evaluated.

(3) Duration of immunity studies.

(4) Efficacy studies in maternal antibody-positive animals.

(5) Component compatibility studies.

(6) Any other studies needed to support specific product label indications 

and recommendations.

c. Potency test development report. The regulations at 9 CFR 113.8 provide 

additional guidance on developing in vitro potency tests, as does VS 

Memorandum 800.112. If the protocol for the potency test is not codified in 

the CFR and the applicant does not use CVB reagents and procedures, the 

applicant must include in the report, as applicable:

(1) Validation of the dose responsiveness, sensitivity, specificity, and 

reproducibility of the test.

(2) Data showing how the test correlates with (i.e., is sufficiently 

predictive of) host animal protection.

(3) Qualification data for all reference preparations. 

(4) Procedures for monitoring the stability of, and requalifying, the 

reference preparation(s).

d. Product safety reports:

(1) Studies in laboratory animals.
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 An Equal Opportunity Provider and Employer

(2) Studies in host animals under biocontainment, including overdose 

studies.

(3) Data establishing the safety of any new, or significantly different, 

antigen-adjuvant formulation or additive. An applicant must establish 

a slaughter withholding period for products used in domestic animals

if there is an edible portion of the animal which may be used for food 

purposes (9 CFR 112.2(8)). This includes products intended for use in 

horses, with the exception of foals. VS Memorandum 800.51 provides 

guidance for establishing slaughter withholding periods.

(4) Backpassage studies and shed/spread studies for modified live 

products.

(5) Field safety studies. See VS Memorandum 800.204.

e. Stability reports from accelerated or preliminary real-time studies. See VS 

Memorandum 800.300 for specific stability requirements for products 

containing well-characterized proteins, polypeptides, and their derivatives.

f. Veterinary Biologics Production and Test Reports (APHIS Form 2008) for 

three consecutively prepared serials (identified as prelicensing serials) that 

are prepared and tested in accordance with the approved Outline of 

Production. See VS Memorandum 800.53 for guidance on completing 

APHIS Form 2008. 

Each new antigen (i.e., one that has not been previously approved as part of 

a licensed product) must be prepared from a separate antigen production lot 

for each of the prelicense serials. Single lots of previously approved 

antigens may be combined with the new antigen(s). An applicant may use 

one lot of production seed to prepare each prelicense serial; however, an 

applicant must use separate vials of production seed for each lot of antigen 

an applicant prepares. Definitions for seeds are found in 9 CFR 101.7. The 

minimum volume of each serial should approximately equal one-third of an 

average serial, as defined in the Outline of Production.

g. Labels and/or label sketches prepared according to 9 CFR 112 and VS 

Memorandum 800.54. An applicant must provide acceptable scientific data 

to support all label claims.

2. CVB Actions

a. Reports. The CVB-PEL reviews supporting data and provides official 

responses to each submission. 
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 An Equal Opportunity Provider and Employer

b. APHIS Form 2008 for prelicense serials. If the CVB determines that test 

results from the prelicense serials are satisfactory and an applicant 

prepared the serials in the same manner as the serial(s) demonstrating

efficacy and safety, the CVB-PEL authorizes the applicant to submit 

product samples to the CVB laboratory for confirmatory testing. 

Applicants should use APHIS Form 2072 to request permission to submit 

prelicense serial samples. An applicant must select and submit 

representative product samples to the laboratory according to the 

procedures described in 9 CFR 113.3. An applicant must include APHIS 

Form 2020 (Shipment and Receipt of Biological Samples) with all 

shipments.

c. The CVB-IC determines the eligibility for marketing release of the 

prelicense serials and subsequent serials. See VS Memorandum 800.53.

d. Labels and/or Label Sketches.

(1) Finished labels or computer-generated label proofs that have an 

appearance identical to the proposed final label:

(a) If the CVB-PEL determines that the labels are satisfactory, the

CVB-PEL retains the labels until it issues the product license. 

Approved labels are returned to the applicant at the time of 

licensure. An applicant must have an approved final product label 

at the time of licensure. 

(b) If the CVB-PEL determines that the labels are unsatisfactory, the

CVB-PEL processes the labels as sketches and provides 

comments so the applicant can revise them.

(2) Labels submitted to the CVB-PEL as sketches (appearance may or 

may not be identical to that of the proposed finished label): sketches 

are labels which may or may not have an identical appearance to the 

proposed finished label. The CVB-PEL processes such labels as 

sketches, with or without comments, at the time of review.

D. Requests to Conduct Field Studies

An applicant must receive CVB-PEL approval prior to shipping unlicensed 

(experimental) veterinary biological products. The regulations at 9 CFR 103.3 

describe the shipment of product for field safety or field efficacy studies. 

Applicants should use APHIS Form 2071 as a cover for such submissions.
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 An Equal Opportunity Provider and Employer

1. When requesting to ship experimental product for such studies, an applicant 

must include the following:

a. Permit or letter of authorization from proper State or foreign animal health 

authorities for each State or country where the study will be conducted.

b. Tentative list (names and addresses) of proposed recipients and study 

cooperators. An applicant must include the lot identification (serial 

number) and quantity of experimental product to be shipped to each 

individual.

c. Description of the experimental product, including recommendations for 

use and the results of preliminary safety and efficacy studies (if not 

previously submitted). An applicant must specifically address the safety of 

the product in meat-producing animals, if applicable, and describe the 

product according to the appropriate Outline of Production guidelines in 9 

CFR 114.9.

d. Test results of experimental serials. Before an applicant uses an 

experimental serial in field studies, an applicant must complete all serial 

release tests defined in section V of the Outline of Production. At a 

minimum, an applicant must test the serials for purity, completeness of 

inactivation (if applicable), and safety in animals. The CVB may require 

an applicant to perform additional testing.

e. Labels for the experimental product. An applicant must submit a label 

containing the statement “Notice! For experimental use only—not for 

sale” or its equivalent. An applicant must not place the U.S. Veterinary 

License Number (establishment number) on the label. An applicant should 

not submit an APHIS Form 2015 with the experimental product labels and 

should provide two copies if submitting on paper. See VS Memorandum 

800.67 for additional guidance.

f. Study protocol. See VS Memorandum 800.200.

g. Statement from the research investigator or research sponsor agreeing to 

provide additional information concerning each group of meat animals 

involved before moving these animals from the premises where the test is 

to be conducted, when applicable.

h. Environmental release risk assessment. This assessment, to comply with 

National Environmental Protection Act (NEPA) regulations, applies to 

products not exempted by categorical exclusion in 7 CFR 372.5(c). In 

general, this requirement applies to conventionally derived modified live 

products and those derived by recombinant DNA technology. An applicant 
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 An Equal Opportunity Provider and Employer

must submit the information in the SIF described for environmental 

releases. The CVB uses the SIF when evaluating the safety of the product 

in the context of the target environment.

2. CVB Actions

a. Products exempted from environmental risk assessment. If the CVB

determines that the protocol and supporting documents are satisfactory, 

the CVB-PEL authorizes an applicant to ship the experimental product for 

field studies. The CVB-PEL returns a date-stamped copy of the 

experimental label to the applicant. Authorization is effective for not more 

than one year from the date it is given. An applicant must submit a 

summary of the results of each study to the CVB-PEL or notify the CVBPEL if an applicant has not performed a study.

b. Products requiring an environmental release risk analysis. The CVB-PEL 

reviews all risk assessments according to the guidelines outlined in “Risk 

Analysis for Veterinary Biologics” and by NEPA.

(1) If the CVB determines that the risk assessment supports a Finding of 

No Significant Impact (FONSI), then APHIS publishes the risk 

assessment (purged of confidential business information) in the 

Federal Register for comment. At the end of the comment period and 

after APHIS has satisfactorily addressed the public comments, APHIS 

may authorize field studies.

(2) If the CVB determines that the risk assessment indicates that the 

product may have a significant affect on the environment, APHIS 

prepares an Environmental Impact Statement, and the field study must 

meet additional APHIS and NEPA guidelines.

(3) At the conclusion of the field study, the CVB-PEL confirms that the 

study findings support the FONSI of the environmental assessment.

V. EXEMPTION FROM FREEDOM OF INFORMATION ACT

VS considers all submissions confidential, subject to the APHIS Policy Statement on the 

Protection of Privileged or Confidential Business Information (APHIS Notice 85-406). If an 

applicant considers a submission to be exempt from the Freedom of Information Act (5 

U.S.C. 552), the applicant should include a statement in the submission describing the 

specific adverse effects the applicant would experience if any portion of the submission were 

disclosed. VS Memorandum 800.66 contains guidance on identifying confidential 

information in submissions.
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 An Equal Opportunity Provider and Employer

VI. APHIS FORMS

Forms listed in this memorandum are available on the biological forms Web site,

https://www.aphis.usda.gov/aphis/ourfocus/animalhealth/veterinarybiologics/sa_bio_forms/ct_vb_forms. Alternatively, the CVB-PEL provides forms if 

contacted at the address in section IV above.