The WHO Expert Committee on Biological Standardization met in Geneva from 17 to 21 November 2003. The technical specifications and reagents developed by the Committee define international regulatory expectations for the quality, safety and efficacy of biological pharmaceutical products, including vaccines, blood products, biological therapeutics and in vitro diagnostic devices. This information is targeted to national regulatory authorities and manufacturers. A full report of the Committee’s decisions is in preparation and will be published in the WHO Technical Report Series. In the meantime, a pre-publication document has been posted onto the WHO website to provide early notice of content (1).

The Committee recommended establishment of the following new documents.

Guidelines on nonclinical evaluation of vaccines: regulatory expectations

A broad range of novel vaccines are under development and there is a need for guidance on the type and extent of their nonclinical evaluation since this forms an essential part of the quality assessment of a vaccine candidate. The guidelines are intended to set out principles for nonclinical evaluation of vaccines and provide information and guidance to vaccine manufacturers, and recommendations for national regulatory authorities concerning evaluation and assessment. The document is intended to complement WHO Guidelines for clinical evaluation of vaccines: regulatory expectations (2).

Recommendations for the production biological and quality control of pneumococcal conjugate vaccines

Infections caused by Streptococcus pneumoniae, are responsible for substantial morbidity and mortality, particularly in the very young and elderly. Several pneumococcal vaccines containing polysaccharide conjugated to protein carriers are now available or at an advanced stage of development. Controlled clinical trials with these vaccines have demonstrated that such conjugates are both safe and highly immunogenic. Differences in the incidence of serotypes causing disease from one continent to another has lead to the development of pneumococcal vaccine formulations consisting of increasing numbers of conjugated components. Experience gained with identification of reference levels of antibodies supporting successful licensing of a product in a number of countries will guide the review of clinical trial data from other countries and with other products.

Recommendations for the production and quality control of pneumococcal conjugate vaccines takes account of the large number of serotypes of S. pneumoniae and the need to allow flexibility in recommendations to cover different conjugation chemistries and carrier proteins.

Production and quality control of inactivated influenza vaccine

Guidelines on production and quality control of inactivated influenza vaccine have been updated following an informal WHO Consultation in July 2003. Significant development in influenza vaccines has taken place since the last revision of the document. Subunit and split vaccines are now widely used and the effective dose of haemag-glutinin has been established. In addition, vaccines containing adjuvants have been developed and approved. The danger exists of pandemics caused by the appearance of novel and highly pathogenic strains of virus and this danger presents a number of challenges for production and administration of suitable vaccines. The new recommendations reflect these and other developments.

Diphtheria, tetanus, pertussis and combination vaccines

Developments have taken place in methods of assay of diphtheria and tetanus vaccines directed to overcoming difficulties in potency testing including a number of in vitro assays. A series of reviews and meetings held during 1999-2000 resulted in proposals for amendment of the WHO Requirements but the technical details could not be finalized at that time. Further discussion resulted in a recommendation to move to a harmonized and simplified batch release assay using guinea pigs. The main changes to the present requirements constitute an updating of the sections on reference materials and separation of sections on potency into two, addressing licensing and batch release respectively.

Use of animal cells for the in vitro production of biologicals

The WHO Requirements for the use of animal cells as in vitro substrates for the production of biologicals (3) provide information on a WHO cell bank of Vero cells. These cells were designated as a master cell bank in 1998 making cultures of the cells available to manufacturers and national control authorities. Possible deficiencies in the records relating to the cell bank might have regulatory implications for establishment of master cell banks, and so a revision of the requirements was proposed. The Committee endorsed a recommendation from a WHO Cell Bank Monitoring Group that the 10-87 Vero cell bank should not be considered as a master cell bank for direct use in manufacturing processes. Rather, the 10-87 bank should be regarded as a Cell Seed qualified by scientific analytical consensus from which master cell banks may be established for thorough re-qualification.