Critical assessment of regulatory standards and tests for fish vaccines.

Within the European Economic Area (EU member states plus Norway, Iceland and Liechtenstein), veterinary vaccines must comply with EU regulations and relevant monographs of the European Pharmacopoeia. Since 1996, three European monographs specific for fish have been adopted; concerning oil-adjuvanted, injectable vaccine for salmonids against furunculosis, as well as bacterins against classical vibriosis (Listonella anguillarum) or cold-water vibriosis (Vibrio salmonicida) in salmonids. The regulatory requirements laid down in these monographs include the use of seronegative fish for in vivo safety testing; conduct of vaccination trials in which experimental challenge is administered by injection, and minimum relative protection to be achieved at a given level of control mortality. Several aspects of these requirements are being questioned. This concerns the relevance of injection challenge methods as opposed to waterborne challenge; the validity of relative protection assessed at 60 % control mortality (RPS6) as compared to protection calculated at the endpoint of mortality (RPSendpoint), and poor test power due to low numbers of fish per treatment group. There is a strong need for future efforts to refine the methods for documentation and testing of fish vaccines, and to assure their suitability for the intended purpose.