Current status and use of short/medium-term models for assessment of carcinogenicity of human pharmaceuticals: regulatory perspectives.

In the summer of 1997 international governmental organizations and industry partners agreed upon a new document on 'Testing for Carcinogenicity of Pharmaceuticals'. The most important element in the new guidance was the acceptability of only one life-time carcinogenicity study in a rodent species (preferably the rat). In addition a choice could be made to test the pharmaceutical in one of the newly developed models, i.e. the newborn mouse assay or one of the various transgenic mouse assays. In the present paper the strengths and weaknesses of various models are discussed from a regulatory point of view. The aim of the new animal models would eventually be replacing animal life-span studies without compromizing human safety. Such studies should supplement the life-span studies and provide additional information not readily available from the long-term assay. At present there is insufficient information to predict or offer guidance on which of the models may be the most suitable. New models are not useful to test the carcinogenic potential of biotechnological products.