Assessment of menstrual cycle length in cynomolgus monkeys as a female fertility endpoint of a biopharmaceutical in a 6 month toxicity study.

According to ICH S6(R1), mating studies are not practical for assessing effects on female fertility of biopharmaceuticals that are pharmacologically active only in non-human primates (NHPs). Instead, fertility should be assessed by evaluating histopathology and organ weights of the reproductive tract in studies of at least 3 months dosing duration using sexually mature NHPs. An assessment of the menstrual cycle in females can be included if there is cause for concern based on pharmacological mode of action or relevant findings in previous studies.

Follow-up actions from positive results of in vitro genetic toxicity testing.

Appropriate follow-up actions and decisions are needed when evaluating and interpreting clear positive results obtained in the in vitro assays used in the initial genotoxicity screening battery (i.e., the battery of tests generally required by regulatory authorities) to assist in overall risk-based decision making concerning the potential effects of human exposure to the agent under test.