Challenges and opportunities for the implementation of the Three Rs in Canadian vaccine quality control.

A case-study approach was used to identify opportunities and challenges to the implementation of the Three Rs in vaccine testing in Canada. Data was obtained through interviews with 16 Canadian stakeholders involved in the production, testing and evaluation of vaccines. Participants identified inconsistent regulatory testing requirements, the lack of biological functionality of some in vitro methods, the benchmarking of in vitro against in vivo assays, and high caution towards method changes as major challenges to implementation. Opportunities to implementation were identified as the desire for and steps taken towards harmonization of test methods between countries, collaborations on new method development, the poor performance of traditional animal methods, the domino effect of one regulatory authority accepting a method after another, and stakeholder concerns for the ethical care and use of animals used in vaccine testing. These results suggest that industry and the Canadian government are open to implementing the Three Rs in vaccine quality control, but methods adopted must be reliable and biologically relevant. Improving the harmonization of regulatory requirements will assist in furthering the implementation of alternative methods.