Proposal for international guidelines for reproductive and developmental toxicity testing for pharmaceuticals.

1. A Workshop was organized by the Centre for Medicines Research in London, 13th-15th May 1991 to discuss the current situation concerning tests for reproductive and developmental toxicity required for new drug development, and whether a unified series of guidelines could be developed which would satisfy Regulatory Authorities and Scientists worldwide. 2. The international group of experts invited to participate in this meeting reached a consensus regarding the desirability of developing new and flexible guidelines. An approach was proposed based on the state of the art of scientific knowledge in the field of reproductive and developmental toxicology coupled with the minimum use of experimental animals, and taking into consideration the European proposal for a new guideline which has been open for discussion since 1989. 3. Although time did not permit detailed discussion of all study designs, several which are considered to provide acceptable tests for reproductive and developmental toxicity of new therapeutic candidates have been proposed for further discussion. These include the possibility of considerable reduction in duration and size of studies, and numbers of animals used where there is an indication that a low hazard potential exists. 4. Whichever of the combinations are ultimately used in the premarketing assessment, it is most important that the investigators justify in detail the rationale underlying the choice of studies undertaken. This should take into account the specific properties of the drug molecule and its proposed clinical use. 5. This paper reflects the discussions which took place at the Workshop and its publication has been agreed to by the participants. It is intended that it could be used as the basis for discussions of a harmonized approach to reproductive and developmental toxicity testing of pharmaceuticals. As such, it will be made available to regulatory agencies, trade associations and other appropriate groups for their consideration and acceptance, modification or scientific augmentation.