CENTER FOR VETERINARY BIOLOGICS NOTICE NO. 19-03

TO: Biologics Licensees, Permittees, and Applicants

Directors, Center for Veterinary Biologics

Veterinary Services Leadership Team

American Veterinary Medical Association

FROM: Byron Rippke

Director

SUBJECT: New Extraneous Agent Testing Requirement for Equine-Origin 

Antibody, Antitoxin, Serum, and Plasma Products Regulated by 

APHIS 

I. PURPOSE

This Notice informs interested parties of a new testing requirement for donor horses 

and completed APHIS-regulated antibody, antitoxin, serum, and plasma products of 

equine origin for freedom from equine parvovirus-hepatitis. 

II. BACKGROUND

Recently published research describes equine parvovirus-hepatitis as a probable cause 

of equine serum hepatitis.

1, 2, 3 The research indicates that the virus is present in, and 

can be spread by, administration of equine serum and/or plasma. 

Title 9, Code of Federal Regulations, part 113.450(c)(2) states: “An animal that tests 

positive for an infectious disease shall not be used in the manufacture of antibody 

products.” The presence of equine parvovirus-hepatitis in licensed veterinary 

biologicals poses a newly identified and unacceptable risk, requiring regulatory 

action. 

III. ACTION

A. Donor Horses

All horses used as donor animals for the manufacture of APHIS-regulated antibody, 

antitoxin, serum, and plasma products must test negative for the presence of equine 

parvovirus-hepatitis in blood samples, by test methods acceptable to APHIS. Donor 

herds must be tested annually, and all additions to the donor herd must test negative 

prior to sharing physical space or being allowed contact to donor animals. If a 

negative animal in the herd subsequently tests positive, contact the Center for 

Veterinary Biologics (CVB) for guidance on additional requirements.

Animal and Plant

Health Inspection

Service

Veterinary Services

Center for Veterinary

Biologics

1920 Dayton Avenue

PO Box 844

Ames, IA 50010

(515) 337-6100
CENTER FOR VETERINARY BIOLOGICS NOTICE 19-03

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B. Serial Release Testing

In addition, each completed serial of APHIS-regulated antitoxin, antibody, serum, or 

plasma product labeled for use in equines must test negative for equine parvovirushepatitis by test methods acceptable to APHIS, as listed in the respective Outline of 

Production. Test results must be reported on APHIS Form 2008 in accordance with 

the Outline of Production. Exemptions to the serial testing requirements may be 

considered if data acceptable to APHIS demonstrate that production methods prohibit 

the presence of the infectious virus in the completed product. 

C. Product Labeling

1. Labeling of products licensed for use in equines must bear a caution statement 

indicating that use of equine serum and plasma products has been associated 

with hepatitis (Theiler’s Disease). 

2. Labeling of products of equine origin licensed for use in species other than 

equine must bear a caution statement stating “Do not use in equine species.” 

This statement may be removed once donor herd testing described in Section 

III.A is fully implemented.

3. Once in compliance with Sections III.A and B, equine product labeling may 

bear a statement affirming the product has tested free of equine parvovirus. 

Additional statements indicating freedom from other specific viruses with less

definitive associations to equine hepatic disease4 may be considered by the 

CVB with submission of an acceptable test and test validation data. The 

caution statement for Theiler’s Disease must remain. 

IV. IMPLEMENTATION/ APPLICABILITY

The policy applies to prelicense and licensed equine-origin antibody, antitoxin, 

serum, and plasma products, regardless of animal species for administration. Policy 

regarding the use of equine-origin serum in the production of other biologicals such 

as vaccines is currently being reviewed and will be addressed separately.

Products must be in compliance with Sections III.A and B within 18 months of the 

publication date of this notice. Labels must be in compliance with Parts 1 and 2 of 

Section III.C within 6 months of the publication date of this notice. Outlines of 

Production must be updated with applicable testing and labeling changes as they are 

implemented.
CENTER FOR VETERINARY BIOLOGICS NOTICE 19-03

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V. REFERENCES

1. Divers TJ, Tennant BC, Kumar A, McDonough S, Cullen J, Bhuva N, Jain K, 

Chauhan LS, Scheel TKH, Lipkin WI, Laverack M, Trivedi S, Srinivasa S, Beard L, 

Rice CM, Burbelo PD, Renshaw RW, Dubovi E, Kapoor A. New Parvovirus 

Associated with Serum Hepatitis in Horses after Inoculation of Common Biological 

Product. Emerg Infect Dis. 2018; 24(2):303-310. 

2. Tomlinson JE, Tennant BC, Struzyna A, Mrad D, Browne N, Whelchel D, Johnson 

PJ, Jamieson C, Löhr CV, Bildfell R, McKenzie EC, Laverack M, Renshaw RW, 

Dubovi E, Kapoor A, Meirs RS, Belgrave R, Engiles J, Van de Walle GR, Divers TJ.

Viral testing of 10 cases of Theiler's disease and 37 in-contact horses in the absence 

of equine biologic product administration: A prospective study (2014-2018). J Vet 

Intern Med. 2019: Jan; 33(1) 258-265.

3. Tomlinson JE, Kapoor A, Kumar A, Tennant BC, Laverack MA, Beard L, Delph K, 

Davis E, Schott II H, Lascola K, Holbrook TC, Johnson P, Taylor SD, McKenzie E, 

Carter-Arnold J, Setlakwe E, Fultz L, Brakenhoff J, Ruby R, Trivedi S, Van de Walle 

GR, Renshaw RW, Dubovi EJ, Divers TJ. Viral testing of 18 consecutive cases of 

equine serum hepatitis: A prospective study (2014-2018). J Vet Intern Med. 2019: 

Jan;33(1) 251-257.

4. Chandriani S, Skewes-Cox P, Zhong W, Ganem DE, Divers TJ, Van Blaricum AJ,

Kistler AL. (2013). Identification of a previously undescribed divergent virus from 

the Flaviviridae family in an outbreak of equine serum hepatitis. Proceedings of the 

National Academy of Sciences of the United States of America, 110(15), E1407–

E1415.