Harmonization of Reproductive Guidelines: Perspective from the International Federation of Teratology Societies

Abstract

The International Federation of Teratology Societies (IFTS) consists of the Australian, European, Japanese, and American Teratology Societies. A Committee on International Regulation was designated to interact with the European Economic Community (EEC) on development of the document “Guideline on Detection of Toxicity to Reproduction for Medicinal Products (Draft 11).” Professor Rolf Bass (BGA) coordinated input from multiple international regulatory agencies and professional organizations. The 1991 IFTS Scientific Program held in June 1991, was designated as a focus for distribution and discussion. Presentations were given by representatives of EEC; FDA; academia; and American, Japanese, and European pharmaceutical industries. Key points in the proposed draft are: (1) flexibility in protocol designs based on scientific justification; (2) mutual acceptance of scientifically justified protocol designs; (3) use of pharmacokinetic data to justify dose selection; and (4) potential protocol designs including: (a) a multigeneration design (agents of low toxicity); (b) the Japanese Segment I combined with EEC Segments II and III; and (c) current EEC, Japanese or U.S. guidelines. Behavioral evaluations may be included in a multigeneration test, a combined Segments II and III test, or in separate Segment II and III tests. Potential reduction of the male exposure period depends upon the design selected. The male Segment I exposure period may be shortened to two weeks, if subchronic data identify no adverse effects on the testes (histopathology) or sperm parameters (motility, morphology, concentration). The need to use noninvestigator-biased automated behavioral tests of learning and memory and elimination of physical landmark tests was emphasized.