Review of embryo-fetal developmental toxicity studies performed for pharmaceuticals approved by FDA in 2024 and 2025.

The FDA approved 96 novel drugs between 2024 and 2025. Of these approvals, 49 were designated for orphan indications. EFD studies were conducted for 78% of approvals. Rats and rabbits were the most common species used (48% and 41% of studies, respectively). For the testing of biopharmaceuticals, non-human primates (40% of EFD studies), rodents (33%) and rabbits (27%) were all used. Most (75%) biopharmaceuticals intended to treat cancer were approved without EFD studies. Amongst the 51 drugs for which both rat and rabbit EFD studies were performed, the rabbit appeared more sensitive species of the two to both maternal toxicity and developmental toxicity (39% and 37% of drugs, respectively, versus 16% and 18% for the rat). About half of drugs (55%) showed more than a 2-fold difference in the LOAEL for developmental toxicity between the rat and rabbit. EFD studies were not required for drugs with a mode of action known to pose a clear hazard for pregnancy. Further EFD studies were generally not performed when clinically relevant developmental effects had already been observed in one species or in a preliminary EFD study. Several drug labels showed minor deviations from the PLLR rule: the metric used to calculate exposure margins and the presence or absence of maternal toxicity were not always specified. These omissions, however, are of little significance for the prescriber. The five reviews in this series now show compiled information on EFD studies for small molecule pharmaceuticals approved since 2014 and for all therapeutic monoclonal antibodies approved to date.