[Safety of medications]

Safety evaluation is an essential part for the registration of new drugs. Animal studies are performed to assess toxicity by single and repeated dose administration, potential effects on reproduction, genotoxicity, carcinogenic potential and local tolerance. Guidelines have been harmonized in the European Union since 1975, but there is no comparison in a world-side view-point, because many differences exist between the European Union, USA and Japan. This situation is very detrimental for industry, inducing the need for duplicate studies (with a waste of time and money) and to construct new files. From an ethical view point, this situation also induces overuse of laboratory animals. For all theses reasons, more or less successful harmonization of the guidelines for the safety evaluation of new products has developed since 1991. Prior to the 4th International Conference on Harmonization, important problems were still not resolved (duration of repeated dose studies in non-rodent species). Moreover, a more flexible and less complex system must be developed in the near future for better efficacy.