An Equal Opportunity Provider and Employer

CENTER FOR VETERINARY BIOLOGICS NOTICE NO. 23-08

TO: Biologics Licensees, Permittees, and Applicants

 Directors, Center for Veterinary Biologics 

 Veterinary Services Leadership Team

FROM: Dr. David White 

 Acting Director

SUBJECT: Update for Documenting Appropriate Details for Potency Tests

I. PURPOSE

The purpose of this Notice is to remind industry of the expectations for the level of 

detail required in Section V.C. of Outlines of Productions (OPs) and associated 

Special Outlines (SOs). Although most of the information described below is 

specific to vaccines or immunotherapies administered to animals, the general 

concepts are applicable to all products under CVB’s jurisdiction. This Notice is not 

intended to require modifications to assays described in OPs or SOs but rather 

clarify the current assay procedures being used. 

CVB Notice 20-11 was published in 2020 with the same intent as the current 

document. After discussions internally and with industry, it has been determined that 

additional details are required to clarify CVB’s expectations. The CVB intends to 

update Veterinary Services Memorandum (VSM) 800.206 to address these 

clarifications more appropriately. The following Notice states the CVB’s expectation 

of OPs and SOs and specifies some of what will be further clarified in VSM 

800.206. 

The current notice replaces Notice 20-11 which has been removed from the Center 

for Veterinary Biologics’ (CVB) Website. 

II. BACKGROUND

Title 9, Code of Federal Regulations, part 113.5 (a) requires satisfactory completion 

of potency testing of all serials of biological products before they are considered for

release to the marketplace. 9 CFR 113.6 authorizes CVB to examine and test serials 

for purity, potency, safety, or efficacy as a part of the market release process. Part 

114.9 (c) – (f) lists the OP requirements for different types of products and each of 

these sections say that tests must be described in detail within the appropriate testing 

section of the OP. Veterinary Services Memorandum No. 800.206, Appendix I, 

Section V. states that OPs should “Include stepwise procedures in sufficient detail so 

a laboratory technician experienced in general laboratory techniques could perform 

the assay.” Descriptions will vary based on the test, but the expected level of detail 

includes the specific reagents required, the number of vials or samples tested, the 

Animal and Plant

Health Inspection

Service

Veterinary Services

Center for Veterinary 

Biologics

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PO Box 844

Ames, IA 50010

(515) 337-6100
CENTER FOR VETERINARY BIOLOGICS NOTICE NO. 23-08

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 An Equal Opportunity Provider and Employer

testing performed on each, objective decision-making step(s) for selecting subsets of 

wells/dilutions/plates/etc. used in later steps, validity criteria and calculations required to 

determine potency in a way that the reader could reproduce the results from the licensee 

or permittee. Analogous information for diagnostics would include the number of 

plates/devices/wells that are used, any calculations that are required to determine the 

classification, and any cutoffs or controls that are required for serial release that may not 

be in the insert or used by the end user.

CVB should be able to independently verify the results and validity of a test with 

documents that are on hand rather than having to request current use information for a 

given test. When test procedures are not fully described in documents that are on file at 

CVB, review and testing time may be increased due to the need to request missing 

information.

III. ACTION 

During the annual reviews, as required by 9CFR 114.8(d), OPs and SOs should be 

reviewed for clarity and updated to consider including additional details at the level an 

independent laboratory could reproduce the test in the same manner it is conducted by the 

firm.

The following list reflects some examples of common situations where clarity could be 

improved. These have been written to apply to all assay types, so not all information will 

be applicable to a given assay, but analogous information should be provided for all 

potency tests at a similar level of detail:

1. The number of vials, or the number of samples if taken from bulk, used for 

conducting the potency test for the test serials, controls, reference and any other 

preparation used in the assay. 

2. Specify all level of detail for a given vial for each preparation. Examples include 

dilution factors, number of dilution series created, number of plates/wells per 

dilution, countable range, etc. Include decision processes for selecting dilutions 

within the series or plates within a set, where applicable. Specify all calculation 

methods for each vial. 

3. If a single potency measurement is derived from multiple vials, the OP or SO

should indicate the method for combining results across vials (i.e., arithmetic or 

geometric mean) and clearly specify the derived value is used for serial release. 

Do not alter current release or expiration potency specifications. 

4. Consider including a sample calculation in the file documentation to help the 

reader fully understand the described procedure.
CENTER FOR VETERINARY BIOLOGICS NOTICE NO. 23-08

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 An Equal Opportunity Provider and Employer

5. Clearly and objectively state any validity criteria or inclusion criteria, such as 

methods for selecting a single dilution or determining countable ranges, in the OP.

Additional expectations for test controls and validity criteria will be addressed in 

a VSM 800.206 update.

6. Critical reagents will be further defined in the VSM 800.206 update. CVB 

considers those to be any reagents that effect or change the architecture of the test. 

Changing a critical reagent will require validation according to VSM 800.112. It 

is noted that critical reagents will vary across assay methods which will also be 

discussed further in the memo. Lot changes for critical reagents will still only 

require demonstration of equivalence as described in VSM 800.112 Appendix III 

Section 2.4.6.2 for relative potency ELISAs.

IV. IMPLEMENTATION/ APPLICABILITY

CVB will comment on missing information in Outlines and Special Outlines. Items 

specific to the VSM 800.206 update will have implementation addressed when that 

memo is updated.