Future Perspectives on Toxicokinetics: A Regulator's View

This paper focuses on the desirable future developments in toxicokinetics as seen from the regulator's point of view. The main points of interest discussed are biopharmaceutics and interspecies extrapolation. With respect to biopharmaceutical development of study formulations, important factors such as possible routes of administration, physical and chemical properties of compounds, the influence of biological factors, and the fate of a substance in the organism have to be accounted for. These factors are discussed and examples from personal experience are provided. Considering interspecies interpolation and extrapolation to the human situation, experience in the evaluation of dossiers indicates that interspecies scaling is rarely used in pharmaceutical safety evaluations. To achieve a better integration of toxicokinetics in safety evaluation, strong multidisciplinary collaboration with well-defined autonomy is required. In many companies, this means that traditional barriers need to be crossed routinely.