Abstract
The Pharmaceutical Manufacturers Association (PMA) and the International Federation of Pharmaceutical Manufacturers Association (IFPMA) have taken a leading role in the current harmonization efforts, which also include issues on quality assurance and clinical efficacy, although these subjects will not be addressed here. Important preclinical testing issues were identified by industry and regulatory expert working groups in Europe, Japan, and the United States. The most critical issues were then selected, and regulatory agencies in each country were encouraged to address the possible resolution of national differences. The issues under discussion include acceptable requirements for single-dose testing in rodents and nonrodents; clarification of no-effect, delayed-effect, and toxic-effect dose levels in repeated-dose toxicity studies; 6-versus 12-month requirements for chronic toxicity studies; clarification and harmonization of requirements for developmental toxicity studies; standards/issues for biotechnology safety studies; and the timing of toxicity studies versus the conduct of clinical trials. Final resolutions and agency positions were presented during the First International Conference on Harmonization held November 5–7 in Brussels, Belgium.