European Regulatory Requirements for Veterinary Vaccine Safety and Potency Testing and Recent Progress Towards Reducing Animal Use

AbstractEuropean technical requirements for veterinary vaccines are laid down in Annex 1, Title II, to Directive 2001/82/EC, as amended by Directive 2009/9/EC, and the European Pharmacopoeia (Ph. Eur.). Safety tests carried out on each batch are generally overdosage studies carried out in at least one of the most sensitive target species and by at least the recommended route of administration that poses the greatest risk. The dose administered should preferably be twice the standard dose for inactivated vaccines and ten times the standard dose for live vaccines. Each batch must also be tested to show that it will contain the appropriate potency or titer to ensure its safety and efficacy. Live vaccines are usually tested by in vitro titration, while serological or challenge tests in vaccinated animals are commonly used for inactivated vaccines, although alternative methods are encouraged if satisfactorily validated. Several amendments have been introduced into the Ph. Eur. to facilitate reduction in the severity of tests and the numbers of animals used, including: the ability to waive the batch safety test when consistency of production has been established; in vitro methods to test for extraneous viruses in live poultry vaccines; and humane endpoints for rabies vaccine potency tests. This report discusses some preliminary conclusions concerning how these changes have affected the numbers of animals used during batch control testing of vaccines released via the UK batch release scheme