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November 14, 2011 

VETERINARY SERVICES MEMORANDUM NO. 800.212 

TO: VS Management Team (VSMT) 

 Directors, Center for Veterinary Biologics 

 Biologics Licensees, Permittees, and Applicants 

FROM: John R. Clifford /s/ John R. Clifford 

Deputy Administrator 

SUBJECT: Licensing Considerations: Vaccine Claims for Protection of the Fetus 

Against Bovine Virus Diarrhea Virus 

I. PURPOSE 

This memo provides guidance to licensees, permittees, and applicants concerning vaccine 

claims for protection against the reproductive effects of Bovine Virus Diarrhea Virus 

(BVDV). Historically, BVDV vaccines have been licensed based on respiratory 

challenge, as described in title 9, Code of Federal Regulations (9 CFR), sections 113.215 

and 113.311. As knowledge of BVDV pathogenesis has increased, interest in obtaining 

label claims to include the reproductive effects of the disease has also increased. Infection 

with BVDV can cause a wide array of reproductive sequelae, including abortion, 

persistently infected calves, unthrifty or stunted calves, and congenital anomalies. The 

Center for Veterinary Biologics (CVB) allows label claims for the reproductive effects of 

BVDV. Additional studies must be performed, however, to support label claims 

regarding the reproductive effects of BVDV. As per 9 CFR, section 112.1(b), no label 

shall include statements that are false or misleading. Similarly, as per 9 CFR, 

section 102.4(b)(3), biologics shall not be advertised as to mislead or deceive the 

purchaser, and packages or containers in which biologics are marketed shall not bear any 

statement, design, or device which is false or misleading. This memo clarifies the type of 

data that is needed to support various label claims and promotional materials against the 

reproductive effects of BVDV. 

II. BACKGROUND 

Licensing Considerations provide guidance to licensees, permittees, and applicants 

concerning the submission of documents to support licensure and label claims. This 

guidance assists CVB Policy, Evaluation, and Licensing with maintaining uniformity and 

consistency in the review of license applications and associated label claims. It also 

provides guidance for conducting studies to support label claims against the reproductive 

effects of BVDV. Conducting these studies supports label claims and supports associated 

promotional materials regarding the reproductive effects of BVDV. The complexity of 

United States 

Department of 

Agriculture

Animal and Plant 

Health Inspection 

Service 

Veterinary Services 

Washington, DC 

20250 
VETERINARY SERVICES MEMORANDUM NO. 800.212 

Page 2 

the disease, including the effect of persistently infected calves on herd health, requires 

certain clarifications to be included on the labeling. 

III. POLICY 

A. Types of Claims. Label claims for BVDV reproductive effects are divided into 

claims for fetal protection and claims for abortion (which may be due to 

maternal, as well as fetal, causes). The claims are type-specific (i.e., BVDV 

Type 1 or Type 2). Each claim must be directly supported by acceptable data that 

have been approved by and filed with CVB. Three categories have been 

identified: 

1. Abortion. Claims for efficacy against abortion due to BVDV must be 

supported by studies in which abortions occur in an acceptable proportion of 

the nonvaccinated control cattle. Since many strains of BVDV do not 

routinely cause abortion, appropriate challenge strains must be used. 

Alternatively, acceptable field studies, using natural exposure to BVDV, may 

be performed. 

2. Persistently infected calves. Claims for efficacy against the development of 

persistently infected calves may be supported by challenging pregnant cattle at 

50 to 100 days of gestation and performing virus isolation procedures on 

tissues from all fetuses on or after 150 days of gestation. Those fetuses from 

which BVDV is isolated are considered to be persistently infected. 

3. Fetal infection. Claims for efficacy against fetal infection by BVDV (e.g., 

“aids in the prevention of fetal infection” or “aids in the prevention of fetal 

infection, including persistently infected calves”) may be supported by 

generating data to support a claim for persistently infected calves AND 

challenging a separate group of pregnant cattle at approximately 180 days of 

gestation, and evaluating the fetuses (or calves) at or after ≥220 days of 

gestation. Serology and virus isolation procedures must be performed. Fetuses 

(or calves) are considered to be protected from infection if they are 

seronegative for BVDV antibodies, and negative for BVDV using virus 

isolation techniques. 
VETERINARY SERVICES MEMORANDUM NO. 800.212 

Page 3 

B. Labels and Promotional Materials 

1. Product labels should not be more specific than what can be supported by the 

filed data (e.g., should not make a specific label claim for congenital 

anomalies if the efficacy study did not produce calves with congenital 

anomalies in the nonvaccinated control group). 

2. Labeling for products that have label claims for BVDV reproductive effects 

should include a description of the efficacy study results. Promotional 

materials for BVDV products with reproductive claims should be appropriate 

for the label claim. Products with claims for persistently infected calves or 

fetal infection should not be promoted as being effective against abortion or 

fetal loss. Promotional materials for products with claims for fetal infection 

may discuss the possible sequelae of fetal infection (e.g., congenital 

anomalies, unthrifty calves), but should not imply that protection against these 

conditions has been directly proven unless supported by acceptable data. 

3. Promotional materials for BVDV products with reproductive claims should be 

appropriate for the label claim. Products with claims for persistently infected 

calves or fetal infection should not be promoted as being effective against 

abortion or fetal loss. Promotional materials for products with claims for fetal 

infection may discuss the possible sequelae of fetal infection (e.g., congenital 

anomalies, unthrifty calves), but should not imply that protection against these 

conditions has been directly proven unless supported by acceptable data. 

V. IMPLEMENTATION/APPLICABILITY 

This change is effective immediately. This policy applies to BVDV products with 

reproductive claims.