The successful development of vaccines is a lengthy process, requiring input from different expertises, such as research and development, quality control, quality assurance, production, regulatory affairs, and marketing and sales. A cornerstone in vaccine development is the availability of a panel of high-quality assays that can reduce the risk of failure in clinical trials and licensure. This review highlights the quality-control issues and approaches in vaccine development from different viewpoints: discovery, process development, assay development, clinical development and the postlicensing phase.

The antigenicity of alum-adsorbed diphtheria toxoid (DTd) was determined in combination vaccines, containing DTd, tetanus toxoid and inactivated poliovirus. A panel of monoclonal antibodies was used, covering five epitopes, distributed over the antigen. The resulting antigenic fingerprint of DTd demonstrates consistency of adsorption at antigen level in final product combination vaccines. The antigenic quality of DTd alone, adsorbed to aluminium phosphate, was also determined and compared with pre-adsorbed toxoid (starting material as well as toxoid desorbed from aluminium phosphate). Some epitopes became less accessible after adsorption, while others became relatively better exposed. Some epitopes disappeared almost completely upon adsorption, but were re-established after desorption of the antigen. The results indicate that DTd is adsorbed to aluminium phosphate in a preferred orientation and not randomly.

This is the 61st report of a series of workshops organised by the European Centre for the Validation of Alternative Methods (ECVAM). The main goal of ECVAM, as defined in 1993 by its Scientific Advisory Committee, is to promote the scientific and regulatory acceptance of alternative methods which have scientific relevance and which reduce, refine or replace the use of laboratory animals. One of the first priorities set by ECVAM was the implementation of procedures that would enable it to become well informed about the stateof-the-art of non-animal test development and validation, and the potential for the possible incorporation of alternative tests into regulatory procedures. It was decided that this would be best achieved by the organisation of ECVAM workshops on specific topics, at which groups of invited experts would review the current status of non animalbased tests and their potential uses, and make recommendations about the best ways forward (1).The workshop on the potential of physicochemical and immunochemical assays to replace animal tests in the quality control of toxoid vaccines was held at ECVAM on 14-15 April 2005, under the cochairmanship of Coenraad Hendriksen and Gideon Kersten. The objectives of the workshop were: a) to review the state-of-the-art of physicochemical, biochemical and immunochemical tests for the quality control of diphtheria and tetanus toxoid vaccines; and b) to identify possibilities for and limitations to their use in the regulatory framework, i.e. for replacing the use of in vivo tests. The outcome of the discussions and the recommendations of the workshop participants are summarised in this report.

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