Embryofetal development studies

Because the type I interferons produced no adverse effects on embryofetal development and the early abortifacient effect could be predicted based on a measurement of female endocrine changes, the need to conduct additional macaque embryofetal development studies for type I interferons in nonhuman primates was considered unnecessary. Therefore, for the second-generation pegylated versions of the alpha interferons, only hormonal analysis was conducted in macaques. This is the only known example of where mechanistic studies have been accepted in place of developmental studies in accordance with ICH S6 guidance. 

The macaque embryofetal development study design has been shown to be appropriate for detecting the teratogenic effects of the small molecular weight drugs thalidomide and isotretinoin [35,36]. For large molecular weight biopharmaceuticals that do not cross the placenta the standard macaque... 

Fuchs A, Weinbauer G. Feasibilty of embryofetal development studies in the marmoset (Callithrix jacchus). In Weinbauer G,VogelF,eds.NovelApproaches towards Primate Toxicology. Muenster Waxmann 2006 110-22. 

For most biotherapeutics that do not cross-react with rodents or rabbits, an embryofetal development study in macaques is generally conducted during clinical development to support the inclusion of women of childbearing potential in clinical trials. However, postnatal development studies in nonhuman primates have not routinely been conducted. Consequently, the protocols and the end points are less well established for evaluation of postnatal effects on the immune system. 

TABLE 9.2-1 Antibodies with Positive Immune Reactivity to Macaque Antigens Used to Identify Specific Cell Population in Macaque during Embryofetal Development Studies... 

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