Veterinary vaccine post-licensing safety testing: overview of current regulatory requirements and accepted alternatives

Abstract Manufacturers of veterinary vaccines frequently incorporate animal-based batch release safety tests into their quality assurance monitoring protocols to meet their internal quality standards and to conform to government regulatory requirements. These tests are conducted by vaccinating target species animals or laboratory animals with a single dose or multiple doses of the test batch, and observing the vaccinated animals for signs of local or systemic adverse reactions. Manufacturers, standard-setting bodies, animal welfare advocacy groups, and regulatory agencies are actively investigating alternative methods to reduce their reliance on animal-based methods for batch release safety testing. Approaches which have been implemented or proposed include harmonizing technical requirements, developing in vitro tests, refining the existing animal tests, improving adverse reaction monitoring (vaccinovigilance), and improving manufacturing methods and quality controls to reduce batch-to-batch variability. An approach, known as the consistency approach, is increasingly being acknowledged as a potentially viable alternative to animal-based batch release tests for vaccines. This paper will provide an overview of currently utilized batch release safety tests for veterinary vaccines, the associated regulatory requirements, and some potentially acceptable alternative approaches for reducing, refining, and replacing the use of animals in these tests.