Challenges in the evaluation and licensing of new pneumococcal vaccines, 7–8 July 2008, Ottawa, Canada

Abstract The introduction of seven valent pneumococcal conjugate vaccine (7vPnC) into immunization programmes has led to a significant reduction in invasive disease due to Streptococcus pneumoniae. New conjugate pneumococcal vaccine formulations containing additional serotypes are at advanced stages of clinical development and are expected to be available in the near future. There are also a number of on-going initiatives to facilitate the introduction of pneumococcal conjugate vaccines into the immunization programmes of developing countries. These initiatives are dependent upon the vaccines being satisfactorily licensed and subsequently pre-qualified by the WHO for use by UN agencies. Recommendations for the production and control of pneumococcal conjugate vaccines were established by WHO in 2003 and have served as a basis for national requirements for the evaluation and licensing of these products. Much progress has been made since that time and a consultation held in Ottawa, Canada, in July 2008 aimed to provide regulators and manufacturers with further guidance on the criteria for evaluating and licensing of new pneumococcal conjugate vaccines taking account of recent developments. The principal conclusion of the meeting was that the current WHO recommendations, in which the demonstration of immunological non-inferiority to the licensed 7vPnC vaccine is proposed as the main basis for approval, continue to provide a solid basis for the evaluation of pneumococcal conjugate vaccines and may be referred to when assessing new vaccines for licensure and pre-qualification. Uncertainties regarding serological criteria for assessing the efficacy of new conjugate vaccines against invasive pneumococcal disease were discussed in detail and proposals made for handling complex data. In particular, it was emphasized that all relevant immunological data should be taken into account when comparing new pneumococcal conjugate vaccines with licensed 7vPnC vaccine. These include the measurement of the total amount of anticapsular IgG as well as the demonstration of functionality of vaccine-induced antibodies, by verifying their ability to opsonize and promote the killing of pneumococcal serotypes, and the demonstration of immunological priming. It was agreed that new information on assay performance and on the effectiveness of currently licensed 7vPnC vaccine, as assessed in routine mass immunization programmes, should both be included in any update of the WHO recommendat