Harmonization of guidelines for toxicity testing of pharmaceuticals by 1992

Abstract

In the past there has been considerable disagreement between various regulatory authorities regarding the type and design of animal tests that should be required before a new medicine can be used ethically and safely in the clinic. However, regulatory variations have largely been removed within politically and geographically similar regions (e.g., the U.S.A., the European Community, the Nordic countries) and there now appears to be a consensus regarding the value of harmonizing international requirements. In order to assist the process of harmonization, a detailed table of preclinical toxicity requirements in the U.S.A., Canada, Japan, and the European Community for each test (acute, subacute, chronic, carcinogenicity, mutagenicity, reproduction) has been compiled. This has been circulated to the relevant regulatory authorities to ensure that it accurately reflects current requirements. The major differences between authorities were found to be the duration of chronic, repeated-dose tests and the design of reproduction studies. International pharmaceutical companies were asked to complete a questionnaire, indicating how they design their preclinical testing program to comply with varying regulatory requirements. Most of the respondent companies indicated that chronic tests of longer than 6 months were conducted solely to comply with some regulatory requirements. Many companies repeat reproduction studies in order to comply with Japanese requirements. This emphasizes the need to harmonize these guidelines and discussions are currently underway to attempt to develop protocols acceptable to the FDA, the EC, and the Japanese Ministry of Health and Welfare.