International safety pharmacology guidelines (ICH S7A and S7B): where do we go from here?

The International Committee for Harmonization (ICH) has issued guidelines (ICH S7A and ICH S7B) for the conduct of safety pharmacology evaluations, which have been accepted in Europe, the United States, and Japan. The present report provides a critical analysis of these guidelines, in particular concerning their implications for studies of the three vital systems: central nervous system (CNS), cardiovascular (CV), and respiratory. The authors suggest that the recommendations should be more specific, and point to the usefulness of particular procedures, for example the evaluation of the convulsive and pain thresholds in CNS and the use of anesthetized dog preparations and physiopathological models in CV and respiratory, for providing a more comprehensive assessment of risk. Further comments are addressed to the timing of safety pharmacology studies, ethical and animal welfare issues, and statistical evaluation. Drug Dev Res 64:83–89, 2005. © 2005 Wiley‐Liss, Inc.