Regulatory acceptance and use of serology for inactivated veterinary rabies vaccines.

In April 2013 the mouse antibody serum neutralization test (SNT) was formally incorporated into European Pharmacopoeia monograph 0451 for potency testing of inactivated veterinary rabies vaccines. The SNT is designed to replace the highly variable and pain and distress causing NIH mouse rabies challenge assay. The adoption of the SNT meets the European ambition (i.e., EC and CoE) to replace, reduce and/or refine laboratory animal testing. However, regulatory acceptance and use of 3R models, such as the SNT, remains challenging. This paper aims at clarifying the process of acceptance and use of the SNT. For this purpose it reconstructs the process and reveals barriers and drivers that have been observed by involved stakeholders to have played a role. In addition it extracts lessons to stimulate regulatory acceptance in similar future processes. The incorporation of the SNT into the monographs went relatively quick due to a thorough test development and pre-validation phase, commitment and cooperation of relevant stakeholders and a strong project coordination of the international validation study. The test was developed by the Paul Ehrlich Institut; a leading European OMCLs. This facilitated its European regulatory use. The use by industry is in a critical phase. At this stage product specific validation and the question whether the SNT will be accepted outside Europe are important influencing factors.