Reproduction and Teratology Studies

The Thalidomide tragedy demonstrated the need to evaluate new drugs in reproductive toxicology studies. Some of the earliest guidelines were issued by the US FDA (the 'Goldenthal guidelines'). An ICH guideline now covers the performance of these studies (Federal Register September 22 1994), as amended in 1995 to address possible effects on male reproduction.

In general, there are three phases of the reproductive process that are evaluated. The first phase (historically referred to as Segment I study, and now under ICH as Stage A) evaluates the effect of the new drug on fertility and the early implantation stages of embryogenesis. In these studies, breeding animals of one species (usually rats or rabbits) of both sexes will be treated for 2 or more weeks prior to mating, and then the females will be further dosed until day 6 of gestation. The second stage (historically Segment II, now ICH Stage B) is the teratology study (sometimes termed 'the developmental toxicity study') and is done in both of the same two species. The third stage (Segment III or ICH Stage C) evaluates treatment during late gestation, parturition, and lactation. Behavioral and neurodevelopmental assessments in the offspring are often made in Segment III studies. In some cases, two of the studies can be combined and still satisfy the ICH guideline.

The period in the drug development process at which results of these studies are required varies somewhat from country to country, and is discussed in the ICH guideline. Hoyer (2001) reviews the current situation, and provides additional perspective.

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