Introductory Session-Historical 

Perspective on Regulation of Potency 

(testing) of USDA Regulated Vaccines

David M. Dusek

Staff Reviewer

Center for Veterinary Biologics

USDA

Ames, Iowa
History? Various Opinions

o History is indeed the witness of the 

times, the light of truth. (Cicero)

o Those who cannot remember the 

past are condemned to repeat it. 

(Santayana)

o History is more or less bunk. (Henry 

Ford) 
Overview of Relevant Events

–VSTA

–Vaccination:challenge only (1913)

–Live virus titrations in lieu of live animal tests (1969)

–In vitro tests in lieu of live animal tests and live bacterial counts (1984)

–SAM 318 Relative potency ELISA (1992)

– Revised 9CFR 113.8 add in vitro potency; VSM 800.90 (1997 and 1998)

–3R’s meeting- (2004)

–VSM 800.112 validation (2008)

–VSM 800.112 ELISA validation Ap III (2011)

–VSM Draft DOC 440 (2011-2014); VSM 800.115 Contract Testing (2013) 

–Before Assay Validation

1910

–Assay validation

1960197019801990200020102020
Summary

1913 VSTA -For the first 60 years exclusively animal 

potency tests with some changes.

o Shift from host animal to laboratory animal

o Shift from vaccination/challenge to 

vaccination/serology

1969

o Virus titrations in lieu of animal testing

1984

o In vitro tests in lieu of animal tests for immunogenicity

o Counts for live bacterial vaccines
Summary

1992

o SAM 318 Relative potency method for enzyme 

immunoassays (revised 7/9/2001)

1997 Publication of revised 9CFR 113.8 

o Regulation describing criteria for a relative potency 

immunoassay

1998

o VSM 800.90: Guidelines for Veterinary Biological 

Relative Potency Assays and Reference Preparations 

Based on ELISA Antigen Quantification
Summary

2003-2004 Review of potency testing policy

o Animal welfare concerns –reduce, refine, replace 

(3R’s) in vivo potency testing 

o Guidelines for developing test methods 

o Consistency across products

o Adopt new technology

2004 Meeting Ames, Iowa “Technology and 

Approaches to Reduce, Refine, and Replace Animal 

Testing” 

oProposed changes for potency testing.

oPresentation on various types of bio-analytical 

methods
Proposed Policy Changes 

Common policy for ALL potency tests, that 

included clearly defined requirements for

o Validated assay methods

o Quality assurance programs for assays and 

references 

o Develop criteria for evaluation of product and 

reference stability and expiration dating

o Reemphasize direct antigen quantification 

(μg/mL versus relative potency)
Proposed Policy Changes 

o Real-time stability studies –stability 

indicating assays

o Contract testing

o Non-protective surrogate antigen 

correlated to efficacy in lieu of 

measuring protective antigen
Overview of Relevant Events

–VSTA

–Vaccination:challenge only (1913)

–Live virus titrations in lieu of live animal tests (1969)

–In vitro tests in lieu of live animal tests and live bacterial counts (1984)

–SAM 318 Relative potency ELISA (1992)

– Revised 9CFR 113.8 add in vitro potency; VSM 800.90 (1997 and 1998)

–3R’s meeting- (2004)

–VSM 800.112 validation (2008)

–VSM 800.112 ELISA validation Ap III (2011)

–VSM Draft DOC 440 (2011-2014); VSM 800.115 Contract Testing (2013) 

–Before Assay Validation

1910

–Assay validation

1960197019801990200020102020
Summary

2008-VS Memorandum 800.112 Guidelines for Validation of 

In Vitro Potency Assays 

o Detailed guidance for validating potency testing 

methods developed in collaboration with industry

2011-VS Memorandum 800.211 Guidelines for Master 

Reference Qualification and Requalification

o Extended useful dating period of Master References

o Response to industry concerns about resources 

committed to Master Reference qualification studies

2011-VS Memorandum 800.112 Guidelines for Validation of 

In Vitro Potency Assays Appendix III (ELISA validation) 

o Requested by and developed in collaboration with 

industry.
Summary 

2011-2014 VSM Draft Doc #440 Guidelines for 

Determining Release and Throughout-Dating 

Potency Specifications ,

o Several drafts for public comment.

2013 VS Memorandum 800.115 Potency Testing 

by Unlicensed Facilities (June 21, 2013)

o Potency testing by contract labs
Overview of Relevant Events

–VSTA

–Vaccination:challenge only (1913)

–Live virus titrations in lieu of live animal tests (1969)

–In vitro tests in lieu of live animal tests and live bacterial counts (1984)

–SAM 318 Relative potency ELISA (1992)

– Revised 9CFR 113.8 add in vitro potency; VSM 800.90 (1997 and 1998)

–3R’s meeting- (2004)

–VSM 800.112 validation (2008)

–VSM 800.112 ELISA validation Ap III (2011)

–VSM Draft DOC 440 (2011-2014); VSM 800.115 Contract Testing (2013) 

–Before Assay Validation

1910

–Assay validation

1960197019801990200020102020
A Dichotomy: Before

Validation vs After 

Validation
Why is this important?

o The majority of potency tests have not been validated

o Not stability indicating assays

o Not good measures of product potency or stability

o New assays will be stability indicating assays and will 

be valuable for evaluating stability and product dating.

o Guidance is in place to improve or replace older 

assays resulting in relevant measures of product 

potency and stability

o Proposed guidance indicates how we can apply this to 

have consistent measures of product dating and 

release values that are science based and data driven
Why is this important?

o Industry needs consistency and 

predictability

o Regulators need to be consistent and have 

sound basis for policy and decisions

o Both need to be adaptable to changing 

technology and the scientific knowledge 

base

o CVB continues to be on its journey for 

upgrading potency and other assays to 

support serial release and stability of 

product and references
o History is indeed the witness of the times, 

the light of truth. (Cicero)

o History is more or less bunk. (Henry Ford)

o Those who cannot remember the past are 

condemned to repeat it. (Santayana)

o Don’t know much about history.....what a 

wonderful world this would be. (Sam 

Cooke, 1959)

What version of History do you 

subscribe to?
Questions?