Emerging trends in nonclinical safety assessment for therapeutics.

Abstract

A major objective of the International Conference on Harmonization (ICH) is the reduction or elimination of unnecessary, obsolete, or redundant regulatory requirements and the development of improved regulatory standards for drug marketing and licensing among the ICH regions. The ICH has served as a motivating force for regulatory agencies and the pharmaceutical industry to assess the utility and effectiveness of current toxicological requirements. The ICH brings together representatives from regulatory authorities from the 3 regions in which most of the pharmaceutical development and manufacturing capacity reside: the European Community or Union (EC), the United States, and Japan. The ICH was organized in 1990 and the first conference (ICH1) was held in Brussels in 199 1. ICH-2 was held in Orlando, Florida in 1993, and ICH-3 will take place in 1995 in Yokohama, Japan. Recent and current ICH nonclinical safety initiatives include: 1. The evaluation of the utility of 6- vs 12-mo ro2. The development of alternatives to the maxi3. Modifications in reproductive toxicity require4. The development of a standard battery for mu5. An assessment of the 2-species rodent carcinoTo obtain the information necessary to address many of these ICH issues, a Food and Drug Administration (FDA)/CDER drug toxicity and carcinogenicity database was developed. The application of this database to the issue of the duration of dent and nonrodent toxicity studies.