The international harmonisation of guidelines in the future: a viewpoint from the industry

In the area of safety, 10 completely new toxicology guidelines have been produced up to 1997 under the umbrella of the ICH. Surveys on the use and impact of the ICH guidelines in the pharmaceutical industry in three regions, Europe, the USA and Japan, showed that approximately 80% of the guidelines were utilised and, as expected, the guidelines which had been in place longest were the ones most often used. The work on the different guidelines has initiated a number of specific investigations such as studies on the duration of dosing of male rats to detect adverse effects on male fertility and the duration of chronic toxicity studies in non-rodents. Evaluation of data from various databases on long-term carcinogenicity studies showed that the mouse studies had had very little influence on the outcome of the regulatory decision about the human carcinogenic risk of a specific compound. An important role for the ICH organisation in the future should be to see that changes and amendments to current guidelines are made as soon as they are warranted by the progress of toxicological science. The decision to accept the Common Technical Document as an official ICH topic is important for the industry and will help the industry to reduce the period between drug discovery and regulatory acceptance. In the area of safety there are still topics which could benefit from harmonisation. Such topics are safety pharmacology, clinical pathology, immunotoxicology, juvenile toxicity studies, statistical methods in certain types of toxicity studies, and recommendations for additional short- to medium-term carcinogenicity studies.