Alternative methods and strategies to reduce, refine, and replace animal use for veterinary vaccine post-licensing safety testing: state of the science and future directions

NICEATM and ICCVAM convened an international workshop to review the state of the science of human and veterinary vaccine potency and safety testing methods and to identify opportunities to advance new and improved methods that can further reduce, refine, and replace animal use. Six topics were addressed in detail by speakers and workshop participants and are reported in a series of six reports. This workshop report, the last in the series, addresses methods and strategies for veterinary vaccine post-licensing safety testing that can reduce, refine, and replace animal use (the 3Rs). It also provides recommendations for priority research and other activities necessary to advance the development and/or implementation of 3Rs methods for veterinary vaccine post-licensing safety testing. Workshop participants gave priority for future efforts to vaccines that (1) use large numbers of animals per test, (2) produce large numbers of serials annually, (3) use additional animals for safety testing. They also prioritized poultry vaccines for which in vivo extraneous agent testing is still performed, adjuvanted vaccines that cause a site reaction, and vaccines that are well characterized. Vaccines identified as the highest priorities were those for avian diseases, rabies, Clostridium spp., and subunit protein and DNA vaccines, in addition to modified live viral products that do not contain excipients. Workshop participants recommended priority research, development, and validation activities to address critical knowledge and data gaps, including opportunities to apply new science and technology. Recommendations included further assessment of the need for a general safety test; expanded application of primary cell culture and polymerase chain reaction (PCR) techniques to replace in vivo chicken tests for extraneous agents; development of in-process safety testing to verify detoxification of selected vaccines; and further investigation of cell-based assays to measure residual toxicity. Implementation of the workshop recommendations is expected to advance alternative methods for veterinary vaccine post-licensing safety testing that will benefit animal welfare and reduce or replace animal use while ensuring continued protection of human and animal health.