An Equal Opportunity Provider and Employer

VETERINARY SERVICES MEMORANDUM NO. 800.214 

TO: Veterinary Services Leadership Team

Directors, Center for Veterinary Biologics

Biologics Licensees, Permittees, and Applicants

 

FROM: Jack A. Shere

 Deputy Administrator 

SUBJECT: Prescription Platform Product Biologics 

I. PURPOSE

The Center for Veterinary Biologics (CVB) allows biologics manufacturers to use

advanced technologies to license products manufactured with a standardized production 

platform (PP). Detailed guidance for platform products is provided in Veterinary 

Services (VS) Memorandum Number (No.) 800.213. VS Memorandum No. 800.214 

provides additional guidance to licensees, permittees, and applicants wishing to 

distribute customized (prescription) non-replicating, nonviable biological products 

using production platform-based technology. Unless specified otherwise in this 

memorandum, guidance in VS Memorandum No. 800.213 applies to prescription 

products as well.

II. BACKGROUND

The prescription platform product biologic (RxPP) is based on a written prescription 

from a veterinarian, for administration to animals within the context of a VeterinarianClient-Patient Relationship (VCPR). Prescription platform biologics have no 

demonstrated claim of efficacy but are tested for safety and purity. 

III. DEFINITIONS

A. Production platform (PP)

A production platform utilizes a single “backbone” vector or expression system 

(VES) and a standard process for inserting a gene(s) of interest (GOI) into the 

backbone to generate different recombinant Seeds or Sequences (constructs), 

which are then used to produce product following a standardized method for 

manufacture. The final product is non-replicating and nonviable. Refer to VS 

Memorandum No. 800.213. 

Animal and Plant

Health Inspection

 Service 

Veterinary Services

1400 Independence

Ave, SW

Washington, DC

20250 for
VETERINARY SERVICES MEMORANDUM NO. 800.214

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 An Equal Opportunity Provider and Employer

B. Prescription Platform Product biologic (RxPP)

Custom veterinary biological product prepared for an individual animal or animals 

under a prescription written by a licensed veterinarian. Serials are manufactured 

based upon a licensed production platform.

C. Initial Product

A fully licensed biological product that establishes the product platform; the 

standardized method of manufacture; the maximum total antigen content; the 

permissible species for use, minimum animal age, dose, and route of administration 

(i.e., use specifications); and, safety for the RxPP. See VS Memorandum 800.213 for 

additional detail regarding an Initial Product.

D. Total Antigenic Content

Total amount of antigenic material in a completed serial when the input of all 

fractions is combined. RxPP serials must not exceed the maximum total antigenic 

content defined in the Outline of Production. This establishes the upper limit for 

product safety.

E. Use specifications

The minimum age of the permissible species for use at the maximum total antigenic 

content per dose volume by a specific route of administration for the Initial Product.

F. Veterinarian-Client-Patient Relationship (VCPR)

VCPR is defined by title 9, Code of Federal Regulations (CFR), part 107.1 and the 

Principles of Veterinary Medical Ethics of the American Veterinary Medical 

Association. Prescribing veterinarians are responsible for ensuring a legitimate VCPR 

exists with the end user(s) of the RxPP.

IV. POLICY

A. Prerequisite for an Initial Product

The CVB will consider license applications for a RxPP once an Initial Product is fully 

licensed. Refer to VS Memorandum No. 800.213 for guidance on licensing an Initial 

Product. The CVB will not license a RxPP based on a conditionally licensed platform 

product.
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 An Equal Opportunity Provider and Employer

B. Licensure of Prescription Product

The initial license for a RxPP will be granted upon approval of the first exchanged 

GOI of the Initial Product. The applicant must produce constructs for the GOI 

exchange with the identical VES, using the exact method documented in the Outline 

of Production for the Initial Product and without any changes to the manufacturing 

process. The completed product must have the same use specifications as the Initial 

Product. 

C. Selection of GOIs

Under an RxPP license, the applicant may use constructs containing a variety of GOIs 

from different pathogens to manufacture serials for administration under the approved 

use specifications. This differs from nonprescription platform products, where the 

applicant may only substitute gene variants of the original GOI. The prescribing 

veterinarian may submit relevant microbial isolates or sequences from which the 

licensee or manufacturer will derive a GOI, or the prescribing veterinarian may select 

a GOI in consultation with the applicant. 

To ensure that the use of RxPP biologics does not interfere with animal disease 

surveillance and control/eradication programs or pose other health risks, APHIS 

restricts the use of GOIs from certain microorganisms. The applicant must not 

produce RxPP serials from restricted organisms without authorization of the APHIS 

Administrator. 

Currently, APHIS considers the following to be restricted:

• Diseases under Cooperative State/Federal/Industry Animal Disease Control 

and/or Eradication Programs, if APHIS determines that products may interfere 

with disease surveillance and/or control/eradication efforts.

• Diseases under the National List of Reportable Animal Diseases (NLRAD). 

See the National Animal Health Reporting System (NAHRS) Reportable 

Disease List.

• Biological agents and toxins under the U.S. Federal Select Agent Program.

• Foreign Animal Diseases (FADs).

• Any other diseases/antigens not endemic to the United States in which 

products may endanger the animal agriculture of the United States.
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 An Equal Opportunity Provider and Employer

D. Approval to Use New GOI

The CVB must approve each GOI used in an RxPP serial, and the GOI must be listed 

in the Outline of Production or Special Outline before the applicant manufactures a 

serial containing the GOI. The CVB expects applicants to consider and address each 

of the following aspects or points in their submissions for a request to begin 

manufacture of a new GOI:

• Field relevance of the GOI in the intended animal species. Include the

geographic origin of the GOI and geographic location for product use. 

• Potential safety impact of the new GOI when combined with the VES. Are 

there any characteristics resulting from this combination that might affect 

product safety in target and non-target animals?

• Inactivation method of the Initial Product. Is it reasonable to expect that the 

same method will be sufficient for this construct? What would be the impact if 

the expression product of the GOI was not fully inactivated by the current 

method? Conversely, could the immunogenicity of the expression product 

(e.g., a toxin) be adversely impacted by the current inactivation method?

• Public health safety considerations for the GOI.

• The CVB may require the applicant to provide additional studies and to 

perform confirmatory testing on potential new constructs prior to filing the 

Outline of Production or Special Outline.

E. Manufacturing

The applicant must make all constructs in facilities located within the United States or 

any place under the regulatory jurisdiction of the United States. Refer to VS 

Memorandum No. 800.213 for additional information.

The CVB allows split manufacturing, based on the established manufacturing of the 

Initial Product, but the CVB does not allow sublicensure to another Establishment. 

See VS Memorandum No. 800.213 for details.

The CVB handles requests to make changes in manufacturing of a licensed RxPP, as

described in VS Memorandum No. 800.213. The CVB must evaluate any change to 

the standardized method of manufacture, regardless of perceived impact, prior to 

incorporation of the change. Material or manufacturing changes may require the 

establishment of a new Initial Product and, subsequently, a new RxPP license. 
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 An Equal Opportunity Provider and Employer

F. Changes to Use Specifications

The CVB requires supporting field safety studies if there is a change in any of the use 

specifications of a licensed RxPP. The applicant must submit a proposal stating the 

intended modification, an updated Category IV Summary Information Format, and a 

field safety study protocol for approval prior to conducting the study. 

G. Creating Multi-Valent Serials

The CVB determines the number of GOIs allowable in one construct based on the 

construct approved by the CVB for use in the Initial Product. The CVB allows the 

number of GOIs in an individual serial to be increased by creating product fractions, 

each fraction containing a different GOI. The CVB restricts the allowable fractions in 

a serial by the maximum total antigenic content for which safety has been 

demonstrated.

H. Testing

The Outline of Production must contain at least the following, so that product 

consistency can be evaluated: 

1. Batching consistency method. An objective in-process, per-dose measure of the 

amount of a single construct harvest (fraction) blended into a serial. Describe the 

method(s) in section IV. Cite the section IV testing in section V and include 

results on the APHIS Form 2008 to fulfill serial release requirements.

2. Analytical quantification method. This determines total antigenic content in the 

completed serial and is intended to ensure the serial contains no more antigen than 

has been demonstrated safe. The applicant must describe this test method, with 

applicable validation criteria, in section V.C. Examples of possible assay methods 

include, but are not limited to, immunoassays, liquid chromatography, and total 

protein analysis.

3. Identity testing. This confirms the completed serial contains the correct 

construct(s). The applicant must provide an identity test for each fraction.

Depending on the nature of the product, the identity test may be conducted on 

completed product or on the bulk antigen. Describe the method(s), with applicable 

validation criteria, in section V.E. and include results on the APHIS Form 2008 to 

fulfill serial release requirements.

4. Final product testing for sterility and safety (9 CFR 113.100(a) and (b)). The CVB 

requires testing as established by the Initial Product.
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 An Equal Opportunity Provider and Employer

I. Product Dating

Applicants should propose and justify an appropriate means for establishing serial 

expiration dating, based on the manufacture date of the earliest bulk harvest of the 

GOI and the storage conditions for that bulk. The CVB will evaluate the proposal and 

set product dating accordingly.

J. Serial and Sample Submission/Retention

Veterinary Biological Product Samples are selected, authenticated, and submitted 

according to 9 CFR 113.3 and VS Memorandum No. 800.59. 

Based on the number of containers produced, the licensee should allocate samples as 

follows: 

1. For serials with <50 containers, the licensee selects 2 government reserve samples 

only. 

2. For serials with ≥50 containers, the licensee selects 10 government submission 

samples but is only required to submit 2 samples. After the serial has been 

released to the market, the licensee may return 6 samples to salable inventory and 

maintain 2 government reserve samples. 

K. Outlines of Production

The applicant must include the following in the designated sections of the Outline of 

Production for an RxPP:

1. General. All information as required for platform products per VS Memorandum 

No. 800.213 and VS Memorandum No. 800.206; methods must match the 

methods described in the Outline for the Initial Product. 

2. Section I. The method(s) for determining the identity of a submitted isolate or 

sequence from which a GOI will be obtained, and a detailed description of how 

each GOI is introduced into the VES and subsequent testing to confirm purity and 

identity.

3. Section IV.I. State the maximum permissible total antigenic content.

4. Section V. Information for product testing, as stated in section IV.H of this 

memorandum.

5. Section VI.B. Information on serial sampling per section IV.J of this 

memorandum.
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 An Equal Opportunity Provider and Employer

L. Serial Release

The CVB allows release in accordance with 9 CFR 113.3, 113.6, and 116.7, with 

additional guidance listed in VS Memorandum No. 800.53, Release of Biological 

Products. 

The applicant must report the following additional information on the APHIS Form 

2008:

1. The identity (licensee’s internal identification) of each GOI in the serial. 

2. Biological agent of each GOI.

3. Date of Manufacture for each GOI bulk in the serial (to determine expiry dating).

4. Host animal species and route of administration for which the product is intended.

M. Labels

Applicants must prepare labels according to 9 CFR 112 and VS Memorandum No. 

800.54.

The applicant must structure labels as required for conditional licensed products;

however, the claim statement must include the following: “For vaccination against the 

organisms and strains listed. This product is a prescription platform veterinary 

biologic to be used under the supervision of a licensed veterinarian. Efficacy and 

potency have not been demonstrated.”

N. Packaging

Licensees must package RxPPs consistent with requirements for other licensed 

products. All vaccine fractions must be packaged in a single container; however, 

diluent or adjuvant may be provided in a separate container. Refer to VS 

Memorandum No. 800.74 for information regarding sterile diluents.

O. Marketing and Promotional Materials

The CVB limits product advertising and marketing to notification of availability of 

prescription platform product biologics. The CVB does not permit advertising that 

compares products, or infers or claims efficacy or potency. The CVB must review all 

promotional and advertising materials prior to publication or distribution. 
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 An Equal Opportunity Provider and Employer

P. License Restrictions

The CVB issues RxPP licenses with several restrictions. The restrictions will read:

• This license will expire in 2 years. The license may be renewed upon request 

by the firm and at the discretion of APHIS based on manufacturing 

consistency and inspections by the Center for Veterinary Biologics. For use by 

veterinary prescription by and under the supervision of a licensed veterinarian. 

• Trade names shall not be used with this product. 

• Marketing and promotional materials must be reviewed by the CVB prior to 

publication or distribution. 

• Distribution in each State shall be limited to authorized recipients designated 

by proper State officials—under such additional conditions as these 

authorities may require. 

• Export distribution shall be limited to authorized recipients designated by 

proper animal health regulatory officials—under such additional conditions as 

these authorities may require. 

• This license does not authorize production, distribution, or shipment of a 

vaccine/bacterin for foot-and-mouth disease, rinderpest, any H5 or H7 subtype 

of avian influenza, any subtype of avian influenza in chickens, swine vesicular 

disease, Newcastle disease, African swine fever, classical swine fever, 

Brucella abortus, vesicular stomatitis, and rabbit hemorrhagic disease or any 

other disease that the Administrator determines may pose a risk to animal or 

public health. 

• Unusual conditions or adverse events linked to vaccinated animals are to be 

reported to the CVB quarterly. 

• Disposition records, maintained according to 9 CFR 116.2, shall be prepared 

in a format acceptable to APHIS and submitted to the CVB at intervals 

determined by APHIS.

With regard to the final restriction listed above, licensees must submit a report to the 

CVB quarterly including the number of doses produced and destroyed for each serial, 

and indicating GOI and animal species for use. 
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 An Equal Opportunity Provider and Employer

V. IMPLEMENTATION/APPLICABILITY

This policy applies to all non-replicating and nonviable prescription platform product

biologics derived from production platform product biologics. The CVB reserves the right to 

determine the suitability of the proposed production platform and its use. The CVB will base 

its consideration on the disease agent, the animal and public health concerns, and the impact 

on the environment, disease surveillance, and commerce.

This policy is effective immediately.