Details of embryo-fetal development (EFD) studies were compiled for all FDA drug approvals in 2018-19. EFD studies were performed for 82% of approvals (84% of small molecules and 70% of biopharmaceuticals). Rats and rabbits were used for 84% of small molecule (SM) drugs for which EFD studies were submitted. There was at least a 2-fold difference in sensitivity between the rat and the rabbit relative to the human exposure for the majority of drugs (62%, small molecules and biopharmaceuticals combined) tested in both species. On average, however, the rat and rabbit were equally sensitive to developmental toxicity. Over the last 2 years, the use of non-human primates (NHP) for the developmental toxicity testing of biopharmaceuticals has fallen (26% of biologics license applications), with many more biopharmaceuticals now tested in rodents (44% of BLAs). EFD studies were not required for oncology drugs when the mode of action was associated with known developmental risk. One-third of SM non-oncology drugs and two-thirds of SM oncology drugs induced dysmorphogenesis in at least one species. The newly revised ICH S5(R3) guideline will bring about changes to the design of future EFD studies, particularly with respect to high dose selection. The revised guideline will also influence the interpretation of the findings in EFD studies (e.g. fetal morphological variations) and risk assessment.

为 2018-19 年所有 FDA 药物批准编制了胚胎-胎儿发育 (EFD) 研究的详细信息。82% 的批准（84% 的小分子和 70% 的生物制药）进行了 EFD 研究。在提交 EFD 研究的小分子 (SM) 药物中，84% 使用大鼠和兔子。对于在两个物种中测试的大多数药物（62%，小分子药物和生物药物组合），相对于人类暴露，大鼠和兔子之间的敏感性至少有 2 倍的差异。然而，平均而言，大鼠和兔对发育毒性同样敏感。在过去的两年中，使用非人类灵长类动物 (NHP) 进行生物药物发育毒性测试的情况有所下降（占生物制剂许可申请的 26%），现在有更多的生物药物在啮齿动物中进行了测试（占 BLA 的 44%）。当作用方式与已知的发育风险相关时，肿瘤药物不需要 EFD 研究。三分之一的 SM 非肿瘤药物和三分之二的 SM 肿瘤药物导致至少一个物种的畸形发生。新修订的 ICH S5(R3) 指南将改变未来 EFD 研究的设计，特别是在高剂量选择方面。修订后的指南还将影响对 EFD 研究（例如胎儿形态变异）和风险评估结果的解释。新修订的 ICH S5(R3) 指南将改变未来 EFD 研究的设计，特别是在高剂量选择方面。修订后的指南还将影响对 EFD 研究（例如胎儿形态变异）和风险评估结果的解释。新修订的 ICH S5(R3) 指南将改变未来 EFD 研究的设计，特别是在高剂量选择方面。修订后的指南还将影响对 EFD 研究（例如胎儿形态变异）和风险评估结果的解释。