Vaccine Pre-clinical Toxicology Testing

Introduction

The coordination of a team with diverse expertise is essential to effectively, efficiently, and successfully translate vaccine candidates from the laboratory to the clinic. Cooperation is necessary among funding agencies, clinicians, scientists, program managers, and experts in regulatory affairs and vaccine manufacturing to facilitate development of a candidate HIV vaccine into a product suitable for human clinical trials.

The purpose of this document is to serve as a reference summary for this process, with particular focus on the pre-clinical toxicology studies to be performed. Flow chart I, Product Development of a Vaccine Candidate, describes the interrelationship between the different parties involved in the development process. With the identification of a potential HIV candidate vaccine, several components of the development process can be initiated. The identification of a suitable manufacturer, capable of GMP, of the vaccine is an important first step. The design of the pre-clinical safety testing protocols and the design of the Phase I clinical trial protocols can occur concurrently and each depends on the other. CBER input may be sought to aid in the filing of the IND by holding a pre-IND meeting between CBER representatives and the vaccine development team. A pre-IND document is submitted to CBER to review and should contain background and justification of efficacy and/or immunogenicity of the proposed candidate vaccine as well as summaries of the manufacturing process (including flowcharts), the proposed pre-clinical safety testing, and the proposed Phase I clinical trial(s). The pre-IND document should also contain a statement of the meeting purpose, a listing of specific objectives or outcomes that the requestor expects, a proposed agenda and list of external attendees and requested CBER participants. Based on CBER's recommendations at the pre-IND meeting, both pre-clinical toxicology and clinical protocols may need to be modified and then pre-clinical safety testing in animals can be initiated with well-characterized vaccine material. Therefore, it is a good idea not to initiate the pivotal or definitive pre-clinical study(ies) until after the pre-IND meeting. Final GLP reports from the pre-clinical safety tests, together with detailed information about the manufacturing process under GMP and detailed clinical protocols should be compiled to form the IND document. This document is submitted to CBER/OVRR. 30 days after CBER receives the IND submission, if CBER has not placed a clinical hold on the study, the Phase I clinical trials can be initiated.