Reproductive/developmental toxicity studies monoclonal antibodies

Omalizumab and adalimumab are examples of monoclonal antibodies, developed for chronic non-life-threatening indication, that showed cross-reactivity to cynomolgus macaques as well as to humans. This broader species cross-reactivity allowed for a more thorough preclinical safety evaluation of the human monoclonal antibody developed for human use in the cynomolgus macaque. In the case of omalizumab, fertility studies and developmental tox-icitiy studies were conducted in macaques in addition to the chronic toxicity studies. For adalimumab, no reproductive and developmental toxicity studies were conducted. The value of conducting fertility and developmental studies in macaques with monoclonal antibodies is described in Chapter 17. 

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. 

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