THE QUALITY OF GENOTOXICITY TESTING OF DRUGS - EXPERIENCES OF A REGULATORY AGENCY WITH NEW AND OLD COMPOUNDS

The state of the art of mutagenicity testing of drugs based upon new entities submitted for registration in the Federal Republic of Germany is reviewed for the period between 1986 and 1989. In the initial phase of registration 50 out of 107 new compounds were tested insufficiently, thus making safety assessment for therapeutic use difficult. The main shortcomings applied to both missing as well as insufficiently performed mutagenicity tests. In some cases indications for a genotoxic activity were obtained due to inadequate testing giving rise to a suspicion of a mutagenic potential which had to be clarified. Upon additional testing during the subsequent phases of the registration procedure almost all insufficiencies and unclarified suspicions could be eliminated. Several examples on this point are discussed. When evaluating data for 'old compounds' regulatory authorities are confronted with considerable problems. This publication gives some practical advice for judging the plausibility and relevance of published data. Two examples (quercetin and malathion) for which published data are summarized, illustrate that even extensive literature data may not be sufficient to draw a definitive conclusion, if the relevance of most of the results is questionable.