International regulatory requirements for vaccine safety and potency testing: a WHO perspective&

The World Health Organization (WHO) has played a key role for over 50 years in establishing the international biological reference preparations necessary to standardize vaccines and other biological substances as well as developing WHO guidelines and recommendations (written standards) on the production, control, nonclinical and clinical evaluation of biological products. These norms and standards, based on scientific consensus achieved through international consultations, assist WHO Member States in ensuring the quality, efficacy and safety of biological medicines and related in vitro biological diagnostic tests worldwide. The Organization accomplishes this work through the WHO Collaborating Centres and the WHO Expert Committee on Biological Standardization. This also involves collaboration with the international scientific and professional communities, regional and national regulatory authorities, manufacturers and expert laboratories worldwide. Through these activities, WHO has supported the concept of replacement, reduction and refinement in use of animals for developing, producing, testing and characterizing vaccines for human use. WHO has implemented the 3Rs principles by their adoption in certain WHO written standards (e.g. nonclinical evaluation, lot release), establishing well-characterized cell banks (e.g. Vero, MRC-5) that allow replacing primary animal cells for vaccine production, and coordinating international collaborative studies on the suitability of reference standards and reagents. WHO also updates written standards for vaccines based on available state-of-art knowledge and scientific evidence. The concept of consistency of production has been introduced for final lot release testing for a number of vaccines in WHO written standards and implementation of the concept has the potential to reduce animal use worldwide. The recently developed WHO guidelines on independent vaccine lot release encourage the national control laboratories to (1) apply 3Rs principles to minimize the use of animals and (2) to pursue mutual recognition or collaborative agreement to accept animal testing performed in the exporting country's national control laboratory.