Issue 3-Policy Considerations for 

Different Product Types

Product--Specific

Considerations, e.g. Viral Vaccines

(live, killed, vectored), Bacterins,

Bacterial Extracts, Toxoids

David M. Dusek

Staff Reviewer

Center for Veterinary Biologics/USDA

Ames, Iowa
What is this issue about?

Should the potency requirements of different 

veterinary biologicals (vaccines and 

therapeutics) be treated the same or 

different based on:

Category

Virus or bacterial or parasite

Live or inactivated

Toxoids

Recombinant

Immunomodulator
Is it this simple?

Some factors to consider

 Species treated

 Production animal (bovine, porcine, poultry, minor species)

 Companion animal (canine, feline, equine)

 Adjuvanted vs none

 Type of adjuvant

 Single fraction vs multi-fraction 

 Purpose–Herd immunity versus individual protection

 Disease agent (e.g. Canine Coronavirus vs Rabies)
Is it this simple?

Study design (Experimental clinical vs Field 

efficacy)

Representative of the disease transmission in the 

field vs artificial but convenient

Number of animals

Effectiveness of challenge strain

Route of challenge

Primary outcome

Case definition
What is the Typical Study 

Design?

Pivotal efficacy studies are conducted with small numbers of 

animals using firm devised/CVB reviewed protocols or the 9CFR 

Standard Requirements. 

 Typically 20 treated and 20 controls 

 Experimental clinical study

 Usually no dose titrations

 Naïve animals, at youngest age

 Sometimes immunocompromised

 CD/CD

 Steroids

 Challenge/route procedure varies

 Natural vs Convenient
What is the typical efficacy serial 

and How is it tested?

Production serial or bench-top in 

R&D or in process development

One serial or one of many, 

evaluated for potency in a validated 

or un-validated assay

Maybe the result of a series of 

proof-of-concept studies or not
Is it this simple? Probably not!
Current release and throughout dating 

specifications

 Quantal assays e.g. titrations of live virus 

products are set at ≈16X’s (+1.2log10) the 

efficacy serial and must maintain ≈5X’s 

(+0.7log10) is required throughout dating.

 Quantitative counts e.g. live bacteria must 

maintain 2x the CFU of the efficacy serial 

throughout the dating of the product 

 Inactivated products the efficacy, release, 

and throughout dating are traditionally the 

same.
Why are they treated differently?

History?

 History is indeed the witness of the times, 

the light of truth. (Cicero)

 Seemed like a good idea at the time 

(anonymous)
The reason for revisiting our potency 

policy and evaluation of stability 

monitoring and the rationale for setting 

expiration dates

A long term process 

CVB is in the early stages 
Should there be Product-Specific 

considerations for setting release and 

throughout dating potency specifications?

 Perhaps certain categories could be established based on 

product type, according to some rational criteria.

 But note that the divisions are complex because of the 

diversity of the products

 Possibilities?

 Risk-based? (What does this mean?)

 Category within a species e.g. Bovine

Dairy 

Passive immunity products

Feed lot

 Companion animal (Canine, Feline, Equine)
How do you bring consistency to the 

situation?

Regardless of possible divisions a common starting point 

is essential:

 Validated potency assays...... regardless of the product.

 Take into account the variation in the potency assay, 

manufacturing process, the vial-to-vial variation and 

the product stability.......... regardless of the type of 

product.

 This is essentially what is proposed by the VSM Draft 

DOC No. 440.

 A science based approach in line with the plan initiated 

in 2004 as part of CVB’s long term comprehensive 

approach to potency testing.
Questions?