The incidence of spontaneous pregnancy/infant losses is highly variable in long-tailed macaques (cynomolgus monkey), making it potentially difficult to ascertain test item-related effects in developmental toxicity studies. Therefore, pregnancy normograms had been developed by Jarvis et al. [1] to aid in the distinction of normal (e.g. test facility background) versus non-normal pregnancy outcomes. These normograms were mostly derived from embryo-fetal development studies and from PPND studies with a postnatal phase limited to seven days. However, the enhanced pre- and postnatal developmental (ePPND) study paradigm has essentially replaced these former study types. This work aims at providing enhanced normograms (e-normograms) in the context of regulatory ePPND studies. Survival functions for the prenatal phase (286 control pregnancies) and the postnatal phase (222 live infants) were estimated using the Kaplan-Meier estimator. Normograms were generated from survival curves and pseudo-study simulations. Data were available from two test facilities with comparable EU-compliant animal husbandry.
Assessment of developmental and reproductive toxicity (DART) is commonly done in rodents (mice and rats) and in rabbits (mainly developmental toxicity). However, depending on the metabolism, target organ, and specificity of the test item, nonhuman primate (NHP) species may also be needed for DART evaluation. In recent years, the demand for developmental toxicity studies in NHPs has considerably increased since NHPs are frequently the clinically relevant species during biopharmaceutical drug development. This holds particularly true for the development of monoclonal antibodies for which it is reported that over 70% of compounds have the cynomolgus monkey .