Controlled Human Infection Studies: Proposals for guidance on how to design, develop and produce a challenge strain.

There is an increasing need to establish quality principles for designing, developing and manufacturing challenge agents as currently these agents are classified differently by various jurisdictions. Indeed, considerations for challenge agent manufacturing vary between countries due to differences in regulatory oversight, the categorization of the challenge agent and incorporation into medicinal/vaccine development processes. To this end, a whitepaper on the guidance has been produced and disseminated for consultation to researchers, regulatory experts and regulatory or advisory bodies. This document is intended to discuss fundamental principles of selection, characterization, manufacture, quality control and storage of challenge agents for international reference. In the development phase, CMC documentation is needed for a candidate challenge agent, while standard operating procedure documentation is needed to monitor and control the manufacturing process, followed by use of qualified methods to test critical steps in the manufacturing process, or the final product itself. These activities are complementary: GMP rules, which intervene only at the time of the routine manufacturing of batches, do not contribute to the proper development and qualification of the candidate product. Some considerations regarding suitability of premises for challenge manufacturing was discussed in the presentation dedicated to "routine manufacturing".

Implementation workshop of WHO guidelines on evaluation of malaria vaccines: Current regulatory concepts and issues related to vaccine quality, Pretoria, South Africa 07 Nov 2014.

The current World Health Organization (WHO) guidelines on the quality, safety and efficacy of recombinant malaria vaccines targeting the pre-erythrocytic and blood stages of Plasmodium falciparum were adopted by the WHO Expert Committee on Biological Standardization in 2012 to provide guidance on the quality, nonclinical and clinical aspects of recombinant malaria vaccines. A WHO workshop was organised to facilitate implementation into African (national/regional) regulatory practices, of the regulatory evaluation principles outlined in the guidelines regarding quality aspects. The workshop was used also to share knowledge and experience on regulatory topics of chemistry, manufacturing and control with a focus on vaccines through presentations and an interactive discussion using a case study approach. The basic principles and concepts of vaccine quality including consistency of production, quality control and manufacturing process were presented and discussed in the meeting. By reviewing and practicing a case study, better understanding on the relationship between consistency of production and batch release tests of an adjuvanted pre-erythrocytic recombinant malaria vaccine was reached. The case study exercise was considered very useful to understand regulatory evaluation principles of vaccines and a suggestion was made to WHO to provide such practices also through its Global Learning Opportunities for Vaccine Quality programme.