Reproductive toxicity testing for pharmaceuticals under ICH

Reproductive toxicity testing of drugs is performed as a 2- or 3-segment package. The choice of species for routine studies with small molecule drugs is essentially limited to the rat, rabbit, mouse and minipig. The lack of alternative species is a threat to the successful screening of drugs for teratogenicity. A proposed revision of the ICH M3 guideline addresses contradictions concerning the timing of the various reproductive and juvenile studies. This M3 draft, however, raises questions concerning the confidence that can be attributed to preliminary embryotoxicity studies with as few as six females per group. The detection of reproductive hazards could be improved by implementing methods in routine use for the testing of chemicals, such as double staining of fetuses and primordial follicle counts. Modern imaging techniques hold promise for application in the morphological examination of fetuses. An assessment of developmental immunotoxicity should be included in any future revision of the reproductive toxicity guidelines.