WHO manual for the establishment of national and other secondary standards for vaccines

Overview

Biological reference standards are used in qualifying or validating test procedures to ensure uniformity in the designation of potency or activity of biological preparations including vaccines. These are required to ensure lot to lot consistency of production and to minimize systematic deviation of assay. The WHO recommendations for the preparation, characterization and establishment of International Standards (IS) and other biological reference standards were revised in 2004 (1) and includes a section on the preparation of National Standards. However, reference standards used on a regional basis or even just within a single laboratory are also calibrated against the IS.

The terminology used in this document to cover all standards developed by regional or national authorities, or by other organisations and calibrated against the IS is secondary standards. Such secondary standards are designed to provide national, regional and other organisations with greater quantities of calibrated and accredited material used in batch control and other product development activities, for which the International Standard may not be available due to limited supply.

This document is primarily aimed at secondary standards which will be used in the potency testing of vaccines but many of the principles considered would apply to antisera or other biologicals. Reagents such as the challenge bacteria, virus or toxin used in vaccine potency assays are not covered by this manual as they are not standards by definition.