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 Pha rmaceuticals'. The most important element in the new guidance was the accep tability of only one life-time carcinogenicity study in a rodent species (p referably the rat). In addition a choice could be made to test the pharmace utical in one of the newly developed models, i.e, the newborn mouse assay o r one of the various transgenic mouse assays. In the present paper the stre ngths and weaknesses of various models are discussed from a regulatory poin t of view. The aim of the new animal models would eventually be replacing a nimal life-span studies without compromizing human safety. Such studies sho uld supplement the life-span studies and provide additional information not readily available from the long-term assay. At present there is insufficie nt information to predict or offer guidance on which of the models may be t he most suitable. New models are not useful to test the carcinogenic potent ial of biotechnological products. (C) 2000 Elsevier Science Ireland Ltd. Al l rights reserved.