First exposure in man: Toxicological considerations

The safety of a volunteer/patient who participate in the very first human t rial relies on data from animal experimentation and on the design of the tr ial. Recommendations on the type and extent of preclinical safety studies t hat should be conducted prior to first dose in man have been developed by t he International Conference on Harmonisation, and the European Committee fo r Proprietary Medicinal Products. These recommendations include studies des igned to characterise local tolerance and general toxicity of the drug cand idate as well as its genotoxic potential and ability to interfere with repr oduction. For trials which can be categorised as low dose PK screening tria ls and trials with products where rodent and non-rodent (primarily dog) mod els do not show any biological response (e.g. some biotechnology-derived ho rmones and cytokines) other testing paradigms should be used. The present r ecommendations for preclinical testing have had an important impact on the documented impressive safety record of phase I clinical trials. In this spi rit we extend our warmest and sincerest thanks to Professor Jens S. Schou f or his long and deep engagement in European and International harmonisation of preclinical test recommendations. His efforts have had a substantial im pact on the present testing recommendations, which are of obvious benefit t o the safely of the patient.