The timing of toxicological studies to support clinical trials : proceedings of a CMR discussion meeting held at Nutfield Priory, Nutfield, UK, May 1994

Over the past twelve years, the Centre for Medicines Research has held a series of Workshops on a number of topics related to the drug discovery and development process. The major objective of these Workshops has been to provide an international forum for regula­ tory, academic and industry representatives to debate together, and suggest solutions to, specific problems. The meeting reported in this volume represents a departure from this approach, in that the par­ ticipants were drawn largely from the pharmaceutical industry. Senior clinicians, pharmacologists and toxicologists from companies in Europe, the USA and Japan met in May 1994 to discuss a scientific rationale for the conduct of toxicity studies to support the clinical development of new medicines, and to begin to work towards an industry consensus. Achievement of such a consensus is seen as an important step in the process leading towards international harmon­ isation of the recommendations on the timing of toxicity studies in relation to clinical trials. Front Matter....Pages i-xvi Front Matter....Pages 1-1 The application of toxicological investigations in the safe development of medicines....Pages 3-16 Review of international recommendations on animal toxicity studies and their relation to clinical exposure....Pages 17-25 International survey on the timing of toxicity studies in relation to clinical trials....Pages 27-39 Considerations for implementing a toxicity testing strategy....Pages 41-49 Front Matter....Pages 51-51 Phase I clinical trials: what is the minimum preclinical package necessary for initiating single-dose studies in man? — a toxicologist’s opinion....Pages 53-60 Phase I clinical trials: what is the minimum preclinical package necessary for initiating single-dose studies in man? — a clinical pharmacologist’s opinion....Pages 61-65 The duration of toxicity studies required to support repeated dosing in clinical investigation — a toxicologist’s opinion....Pages 67-74 The duration of toxicity studies required to support repeated dosing in clinical investigation — a clinician’s opinion....Pages 75-83 Reproductive and developmental toxicity studies required to support the inclusion of women and children in clinical trials — a toxicologist’s opinion....Pages 85-93 Front Matter....Pages 95-98 The minimum non-clinical package for initiating Phase I clinical trials....Pages 99-108 The duration of toxicity studies required to support repeated dosing in humans in clinical investigation....Pages 109-114 The timing of reproductive toxicity studies in relation to clinical trials....Pages 115-125 The way forward....Pages 127-131 Input to ICH....Pages 133-139 Back Matter....Pages 141-150 The timing of toxicological studies in relation to the clinical evaluation of new medicines is a key topic for strategic planners in the industry and those involved with harmonisation. Resolving the anomalies between different regulatory authorities should eliminate redundant testing on animals and improve the efficiency of the developmental process by encouraging single international strategies. To aid industry in reaching a consensus, the Centre for Medicines Research brought together representatives of the pharmaceutical industry from Europe, Japan and the U.S.A., to give a comprehensive account of current international industry positions on the subject. The contributions review the situation and address the clinical and strategic requirements of the preclinical programme. Personal and consensus proposals on the toxicity studies required to initiate clinical investigations, the timing of reproductive toxicity tests and the duration of repeat-dose studies to support clinical development are provided.