In general, modified-live virus (MLV) vaccines for Bovine Rhinotracheitis (IBR) and Bovine Viral Diarrhea (BVD) need to carry a warning against use in pregnant cows or in calves nursing pregnant cows. Vaccine companies can however, obtain a label claim for use of those MLV vaccines in pregnant cows and nursing calves if they conduct appropriate research trials and provide data demonstrating safety.
This week, the USDA’s Animal and Plant Health Inspection Service (APHIS) issued a memorandum providing guidance on the research methods and data needed to obtain an exemption and label their MLV vaccines for use in pregnant cows and nursing calves.
Guidelines for research trials include the following:
· Only heifers and cows that are confirmed pregnant should be included in the study.
· All animals should be vaccinated with an appropriate single or multifraction test vaccine.
· Animals must be vaccinated in accordance with product labeling, including, if recommended, a pre-breeding vaccination. If vaccination prior to breeding is not required, all animals must be seronegative for virus prior to administration of the test vaccine.
· Studies that involve only the vaccination of calves that are nursing pregnant heifers or cows will not be acceptable for claiming the exemption.
· Clinical studies should be conducted in accordance with VS Memorandum No. 800.301.
· At least 1,200 pregnant heifers and cows must be included in the study. Animals should be divided into three groups of 400 animals each on the basis of stage of pregnancy; i.e., the first, second, or third trimester. Three separate studies may be conducted; however, at least 400 animals are needed for each stage of pregnancy.
· All animals included in the study must be followed through parturition.
· Researchers must randomly divide each group (trimester) into two groups (vaccinates and controls), each containing 200 animals, inoculate animals in the vaccinate group with the modified live virus test vaccine and inoculate animals in the control group with inactivated vaccine or phosphate buffered saline.
· The groups should be adequately separated so as to prevent the controls from being exposed to vaccinates that may be shedding vaccine virus.
· The vaccine used in the study should be formulated in accordance with the filed Outline of Production. If vaccination prior to breeding is recommended, the identity of the vaccine used for the pre-breeding vaccination should be specified in the report and on the labeling.
The memorandum also specifies data collection and statistical analysis, and notes that exemptions could be denied if the rate of abortion due to IBRV or BVDV exceeds 0.5% in any trimester group, or if serum testing in calves born from second- and third-trimester groups reveals any fetal infection with type 1 or type 2 BVD virus.
When a vaccine company obtains an exemption the vaccine label should include a statement that the vaccine may be used in pregnant cows and calves nursing pregnant cows, with a brief description of the study and a summary of the results. If vaccination prior to breeding is required, the recommended product and dose should be specified on the label. Wording acceptable to the APHIS Center for Veterinary Biologics is “This vaccine may be used in pregnant cows or calves nursing pregnant cows provided they were vaccinated, pre-breeding, with (insert product name).”
It is important to note that a label approval does not mean zero risk in using MLV vaccines in pregnant cows. South Dakota State University veterinarian Chris Chase, DVM, PhD, points out a statement from the memorandum specifying that labeling must also bear the following statement concerning residual risk; see also 9 CFR 112.7(e)(3): “Fetal health risks associated with the vaccination of pregnant animals with this vaccine cannot be unequivocally determined during clinical trials conducted for licensure. Appropriate strategies to address the risks associated with vaccine use in pregnant animals should be discussed with a veterinarian.”
That statement reinforces the importance of the veterinarian-client-patient relationship (VCPR) in setting vaccination protocols. Even when a vaccine company meets the safety requirements for labeling, Chase notes the veterinarian remains liable and needs to discuss potential risks with clients.