Nonhuman primates reproductive/developmental toxicity studies

Review of the reproductive/developmental toxicity studies that have been conducted in support of the approved biopharmaceuticals have shown that historically a flexible case-by-case approach has been applied. For biopharmaceuticals that cross-react only with nonhuman primates a limited reproductive toxicity testing strategy has been employed based on the patient population, the indication, and the proposed clinical use. The studies that have been performed have been sufficient to inform the patient populations of potential risk to the fetus. 

For most of the other monoclonal antibodies, species cross-reactivity has been limited to nonhuman primates. For these molecules the need to conduct reproductive and developmental studies has to be carefully considered on a case-by-case basis. S5A states that nonhuman primates are best used when the objective of the study is to characterize a relatively certain reproductive toxicant, rather than detect a hazard. The nonhuman primate reproductive toxicity studies are not powered to detect infrequent events. 

For most pharmaceuticals, developmental toxicity studies are conducted in rodents and rabbits. However, for certain pharmaceuticals, the nonhuman primate is the only relevant species in which developmental toxicity studies can be conducted. This is particularly the case for many human therapeutic proteins that bind only to human and nonhuman primate receptors or antigens, and consequently developmental studies conducted in other species are not relevant for assessing human risk (see Chapter 6). Therefore, in order to evaluate potential adverse effects of these human therapeutic proteins on reproduction and development, nonhuman primate models have been developed that can address various aspects of the reproductive process (Vogel and Bee, 1999 Hendrickx et al., 2002,2005 Weinbauer, 2002). 

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