The in vivo rodent test systems for assessment of carcinogenic potential.

A Drug Information Association (DIA) workshop was held in May 2001 to discuss the outcome of the International Life Sciences Institute-Health and Environmental Sciences Institute (ILSI-HESI) project on alternative models for carcinogenicity assessment such as the P53(+/-) and XPA(+/-) knockout mouse models, the RasH2 and Tg.AC transgenic mouse models, and the neonatal mouse model. The "ICH Guideline S1B on Testing for Carcinogenicity of Pharmaceuticals" advocates that carcinogenicity testing of pharmaceuticals, when needed, might be carried out choosing one 2-year rodent carcinogenicity study (rat) plus one other study that supplements the 2-year study and providing additional information that is not readily available from the 2-year study: either (1) a short- or medium-term in vivo rodent test system or (2) a 2-year carcinogenicity study in a second rodent species (mouse). Another topic of discussion was pros and cons of the short- and medium-term models being evaluated by the ILSI-HESI project, in particular the usefulness of the models in relation to results of genotoxicity assays. Further discussions were advised following publication of the ILSI-HESI database, which is expected before the end of 2001. The use of the short- and medium-term rodent test systems were not considered appropriate for the assessment of carcinogenic potential of biotechnology-derived medicinal products.