An Equal Opportunity Provider and Employer

VETERINARY SERVICES MEMORANDUM 800.213 

TO: Veterinary Services Leadership Team

Directors, Center for Veterinary Biologics

Biologics Licensees, Permittees, and Applicants

FROM: Jack A. Shere

Deputy Administrator 

SUBJECT: Licensing Guidelines for Production Platform Technology-Based, NonReplicating, Nonviable Vaccines

I. PURPOSE

This memorandum provides guidance to licensees, permittees, and applicants for 

licensing non-replicating, nonviable biological veterinary vaccines. Such vaccines are 

prepared for use in the target species by means of production platform-based Master 

Seeds and Sequences with a standardized method of veterinary biological manufacture. 

II. CANCELLATION

This memorandum replaces Veterinary Services (VS) Memorandum No. 800.213 dated 

April 29, 2015. 

III. BACKGROUND

A production platform is a manufacturing process that relies on a single vector or

expression system (“backbone”) and a standard process for inserting a gene or genes of 

interest (GOI) into the system to generate different recombinant Master Seeds or 

Sequences, which are then used to produce product following a standardized method 

for manufacture. These production platforms may be based on, but are not limited to, 

RNA expression systems, DNA cloning vectors, or various virus, plant, insect, or 

bacterial expression vectors. The GOI may consist of one or more complete or partial 

gene sequences. Platform-based Seeds, Sequences, or antigens are blended with 

excipients in a fixed formulation to manufacture completed products with certain 

defined properties. Examples of completed products include vaccines containing viruslike particles, nucleic acid, a killed agent, or a subunit protein or proteins prepared from 

an expression vector. 

The Center for Veterinary Biologics (CVB) will consider streamlined regulatory 

requirements for licensing platform-based, standardized products resulting in nonreplicating, nonviable completed products once an applicant has successfully licensed 

one product using the same platform and product formulation. 

Animal and Plant

 Health Inspection 

 Service 

 Veterinary Services 

 1400 Independence 

Ave, SW

Washington, DC

 20250 for
VETERINARY SERVICES MEMORANDUM NO. 800.213

Page 2

 An Equal Opportunity Provider and Employer

IV. DEFINITIONS

A. Vector or Expression System (VES). System used to express the GOI, whether in 

vivo or in vitro, e.g., a baculovirus system, a nucleic acid delivery system, or a virus 

that is itself an immunological fraction.

B. Gene of Interest (GOI). Full or partial gene coding for the targeted antigen, e.g., the 

influenza hemagglutinin (HA) gene.

C. GOI Variant. A nucleotide sequence variant from the initial GOI, e.g., Orf2 from 

strain A or strain B.

D. Construct. Combination of VES and GOI (or GOIs).

E. Platform Product. Any one or several of a group of products that are based on the 

following components:

1. The VES, including all reagents, seeds, sequences, and cells to propagate the 

final construct.

2. The inserted GOI, including a defined procedure for creating new VES/GOI

constructs with different sequence variants of the GOI.

3. Standardized manufacturing system for consistency in the manufacture and 

formulation of biological product.

4. Efficacy data for the initial VES/GOI construct (minimum age, dose volume, 

specific route of administration, specific species, minimum antigenic dose).

5. Maximum antigenic content - the total amount of antigenic material per dose in a 

completed serial, as determined by a measurable quantity (titer, μg, etc.).

6. Field safety data for the initial VES/GOI construct (minimum age, dose volume, 

specific route of administration, specific species, maximum antigenic content).

F. Initial Product. A fully-licensed product that establishes the product platform, 

including the standardized method of manufacture, maximum antigenic content, 

permissible species for use, minimal age, dose, and route of administration.
VETERINARY SERVICES MEMORANDUM NO. 800.213

Page 3

 An Equal Opportunity Provider and Employer

V. GUIDELINES

A. Licensing Requirements

1. To establish the platform, an applicant is required to have a full product license 

for each specific GOI, with a defined standardized manufacturing process, and 

claims for use of the product administered by the given dose and route in the 

given species at the recommended age. Requirements typically include, but are 

not limited to, submission of a Category IV Summary Information Format (SIF) 

and Risk Assessment for the VES/GOI construct; confirmatory testing of the 

Master Seed (MS), Master Sequence (MSQ), and/or Master Cell Stock (MCS) by 

the CVB; an inactivation kinetics study; efficacy studies for each label claim; 

dilution of preservative study; potency assay; confirmatory testing of prelicense 

serials by the CVB; and a full field safety study. Specific requirements will 

depend on the VES system that is used. The applicant must fully describe the 

production method and location for generating the recombinant Master Seed or 

Sequence in the Outline of Production or Special Outline. The applicant cannot 

initiate the field safety study until the CVB has evaluated the VES/GOI construct 

for compliance with the National Environmental Policy Act (NEPA) and reaches

a finding of no significant impact (FONSI).

Once the applicant has established a production platform and the initial product 

has been licensed, licensure of products containing GOI sequence variants can 

typically be streamlined based on some of the studies conducted with the initial 

product, provided there are no changes in manufacture. Subsequent constructs

must be produced with the identical VES, using the exact method documented in 

the Outline of Production for the initial product. There should be no changes to 

the manufacturing process or maximum antigenic content (as determined by preinactivation titer or other measurable quantification of antigen), and the product

label claims will be for the same species, age, and route of administration. Any 

change to the standardized method of manufacture, regardless of perceived 

impact, must be evaluated by the CVB prior to incorporation of the change and 

may require the establishment of a new Initial Product.

Each subsequent VES/GOI construct should be identical to the initial product

construct, with the exception of the sequence of the GOI. If the initial product 

does not contain the full GOI, subsequent VES/GOI constructs should include a 

comparable region of the sequence. For approval of each new sequence variant, 

the CVB will require, at a minimum, evidence of field relevance, demonstration 

of a reasonable expectation of efficacy, submission of a Category IV SIF with the 

sequence to the CVB, and confirmatory testing of the new variant GOI MS or 

MSQ by the CVB. All safety and efficacy studies must have been conducted 

using product manufactured in accordance with the currently approved Outline of 

Production. Reevaluation for compliance with NEPA, an inactivation kinetic 

study, and a field safety trial are generally not needed.
VETERINARY SERVICES MEMORANDUM NO. 800.213

Page 4

 An Equal Opportunity Provider and Employer

If the applicant demonstrates efficacy of a construct containing a new GOI 

variant, the CVB will issue a full product license for the new variant. In contrast, 

if the applicant demonstrates a reasonable expectation of efficacy, a conditional 

product license will be issued. A GOI variant that is initially marketed under a 

conditional license can be converted to a full product license at a later date if 

pivotal efficacy is subsequently demonstrated and a validated potency assay is

approved.

2. In cases where a full license already exists, if the applicant demonstrates that the 

production platform requirements are met as stated above, the CVB may allow 

that product to serve as the initial product establishing the platform for the defined 

VES/GOI.

3. The CVB considers the substitution of either a different GOI from the same initial 

pathogen or a GOI from a different pathogen into a VES that is used in a licensed 

product to be a new platform; therefore, the CVB requires a new full license to 

establish that VES/GOI combination. Depending on the components of the new

platform, abbreviated studies for licensure may be allowed, including, but not 

limited to, reduced field safety requirements.

4. The CVB will subject the applicant’s request for additional claims for use of a

licensed platform product, either in a different species or for a different age or 

route of administration in the same species, to the same considerations as any 

traditionally licensed product, and will require efficacy and field safety studies.

5. Licensing and eligibility requirements for conditional licenses are set forth in title 

9, Code of Federal Regulations (9 CFR), part 102.6, and in VS Memorandum No. 

800.75. Platform products are subject to the same eligibility rules as any other 

product. In contrast to non-platform products, if the platform product meets an 

urgent need, then the CVB may issue or reissue a conditional license for a 

production platform product, even though a full license has been granted for a 

similar product. Products containing any of the approved sequence variants for the 

same GOI, for which a reasonable expectation of efficacy has been demonstrated,

can be manufactured under a single conditional license.

6. The CVB may issue both conditional and full licenses for platform products 

containing multiple fractions based on the same VES, provided there is no 

immunological interference between the fractions.
VETERINARY SERVICES MEMORANDUM NO. 800.213

Page 5

 An Equal Opportunity Provider and Employer

7. Split manufacturing between two or more licensed firms is acceptable under the 

guidelines of VS Memorandum No. 800.61. In this case, the initial platform 

product must be licensed under the split manufacturing arrangement; a production 

platform that has been established by a single firm cannot subsequently be 

produced under a split manufacturing arrangement. Likewise, a production 

platform that has been established under a split manufacturing arrangement 

cannot subsequently be transferred to one of the firms as the sole manufacturer.

8. A licensee is prohibited from sublicensure of an established platform to another 

Establishment. Each manufacturer must establish the production platform

independently through full licensure.

9. The CVB subjects platform products to the same license restrictions as analogous,

traditionally licensed products.

B. Manufacturing Considerations

1. The CVB requirements for MSs, MSQs, and MCSs involved in a platform 

product are the same as those for traditional products and encompass testing by or 

for the firm, submission of a report documenting the test procedures and results,

and confirmatory testing by the CVB. In addition, the CVB may need 

confirmatory testing by the CVB for the VES and/or additional seeds, sequences, 

or cells used in the generation of new VES/GOI constructs. The applicant must 

submit a Category IV SIF for each final construct and should include an 

electronic file of the sequence of the inserted GOI and flanking region. Each

construct should be given a running number for that specific VES/GOI and should 

be identified with the file name “Est No._Product Code_FirmIdentity_xxx”.

2. The applicant must make all VES/GOI constructs in facilities located within the 

United States, the District of Columbia, the Territories, or any place under the 

regulatory jurisdiction of the United States. Constructs may be made within a 

licensed facility, in a firm’s research and development facility, or by a third party, 

as long as an acceptable, consistent method for the generation of new constructs is 

used that has been approved by the CVB.

C. Outlines of Production

1. In section I of the Outline of Production (or a cited Special Outline) for the initial 

product, the applicant should include a detailed description of how and where new 

constructs containing sequence versions of the GOI are made and the testing that 

is done on each new construct.
VETERINARY SERVICES MEMORANDUM NO. 800.213

Page 6

 An Equal Opportunity Provider and Employer

2. In Outlines of Production for subsequent VES/GOI versions, the applicant should 

identify the product that was used to establish the platform and should describe 

how each new construct was made in section I. In the Outline, the applicant may 

cite the Outline of the initial product for the manufacturing processes. The CVB 

does not allow deviations in manufacture.

3. In section I of the Outline of Production for VES/GOI versions that are 

conditionally licensed, the applicant should list each approved construct, the 

sequence designation, and the date and Mail Log No. of the approval. The 

applicant should identify each construct based on that VES/GOI by a running 

number. In addition, the applicant should provide a table in section VI.C. listing 

the identity number of the construct, the claims that were approved for that 

construct, and the date and Mail Log No. of the approval(s).

4. The applicant should include annotated maps of all vectors that are used in the 

production platform in an appendix to the Outline of Production.

D. Final Product Testing

1. The applicant must provide a validated potency assay for the initial product 

VES/GOI and for any subsequent VES/GOI sequence variant for which a full 

license is issued. A suitable test for batching consistency is acceptable for 

conditionally licensed products for which a reasonable expectation of efficacy has 

been demonstrated.

2. The applicant must provide an identity test to confirm that the correct VES/GOI 

sequence version is in the completed serial; this may be part of the potency assay

(or batching consistency test) or may be an independent assay. For products that 

contain two or more different VES/GOI fractions, the identity test should confirm 

that each of the desired fractions is present in the final product. Depending on the 

nature of the product, the identity test may be conducted on the final product or on 

the bulk.

E. Labeling

1. The CVB requires that labels for all products that have a full license (the product 

that established the production platform, and subsequent VES/GOI sequence 

variants for which full efficacy was demonstrated and a validated potency assay 

has been approved) conform to 9 CFR 112 and the guidance provided in VS

Memorandum No. 800.54. The product compilation summary that is published on 

productdata.aphis.usda.gov must contain the efficacy data that was approved for 

the specific construct and the field safety data for the initial product that 

established the platform.
VETERINARY SERVICES MEMORANDUM NO. 800.213

Page 7

 An Equal Opportunity Provider and Employer

2. The CVB requires that labels for the products that have a conditional license 

(subsequent VES/GOI sequence variants for which only a reasonable expectation 

of efficacy was demonstrated) conform to 9 CFR 112 and the guidance provided 

in VS Memorandum No. 800.54. Since serials containing different conditionally 

licensed sequence variants may be produced under the same product license, the 

applicant should place the statement “Sequence Variant No. ___” directly under 

the True Name. This number is the running identification number for the given 

VES/GOI sequence variant, and this is a fillable field to communicate to the end 

user which GOI variant is in the serial. If desired, the applicant may submit 

individual labels for specific VES/GOI sequence variants that contain information 

related to that specific sequence variant; in this case, the mounting sheet must 

identify the sequence variant for which that label would be used. The product 

compilation summary that is published on productdata.aphis.usda.gov will 

reference the field safety data for the initial product that established the platform 

and will include a statement that the product was licensed based on a production 

platform.

VI. IMPLEMENTATION/APPLICABILITY

This policy applies to all non-replicating and nonviable biological vaccines based on a

platform product. The CVB reserves the right to determine the suitability of the proposed 

platform product and its use. The CVB will base its consideration on the disease agent; 

animal and public health concerns; and, the impact on the environment, disease surveillance, 

and commerce.

This memorandum is effective immediately.