Recommendations for the preparation, characterization and establishment of international and other biological reference standards (revised 2004), Annex 2, TRS No 932

Overview

The provision of international biological reference standards makes a critically important contribution to high standards of efficacy, quality, purity and safety of many biological medicines used worldwide in the prevention, treatment or diagnosis of disease or conditions. Their use supports the application of the numerous biological and immunological assays used in the standardization and control of a wide range of biologicals including therapeutics, blood-derived products, vaccines and immunological products of traditional types as well as those derived from modern biotechnological approaches. They also have important applications in the standardization of materials and approaches used in medical diagnostics such as diagnosis of disease, monitoring therapy, blood safety and public health applications (e.g. monitoring immune status, screening for disease or susceptibility) or otherwise characterizing biological material from individuals.

This document provides an updated set of recommendations in relation to the development, evaluation, establishment and use of WHO biological reference materials. These Recommendations are divided into in three parts:

• General considerations address the scientific basis of biological standardization and the principles applied to WHO International Standards.
• Part A addresses the background to the need for an international biological reference standard, general considerations about procurement and characterization of suitable material, factors to be taken into account in preparing a batch of a candidate reference standard and assessing its suitability, the testing and collaborative assay of the batch; and the information to be provided to WHO so that appropriate reference standards can be established by the WHO Expert Committee on Biological Standardization. A new section on quality assurance considerations has been included. 
• Part B provides advice and guidance to regional and national regulatory authorities on the preparation and establishment of secondary biological reference standards. Such materials may be assigned values in IUs by assay against the corresponding WHO reference standard. 

The parts of each section printed in smaller type are comments for additional guidance and are intended to provide further explanation of the main text.