Abstract：
103 novel drugs were approved by the FDA in 2020-2021. Embryofetal development (EFD) studies were conducted for 76 % of these approvals. For the majority of drugs, EFD studies were conducted in rats and rabbits. Both species were equally sensitive to developmental toxicity, but the rabbit was slightly more sensitive to maternal toxicity at the same systemic exposure level. Nonetheless, 68 % of drugs showed more than a 2-fold difference in the low adverse effect level for developmental toxicity between the rat and rabbit. Previous reviews in this series compiled information on EFD studies for all small molecule pharmaceuticals approved since 2014 and for all therapeutic monoclonal antibodies approved to date. The use of non-human primates for the developmental toxicity testing of biopharmaceuticals has fallen over recent years (22 % of biologics license applications (BLAs) for 2020-2021, compared with 62 % for 2002-2015), with more biopharmaceuticals now tested in rodents (37 % of BLAs for 2020-2021). While the Pregnancy and Lactation Labeling Rule (PLLR), adopted in 2014, has brought consistency to the presentation of EFD data in drug labels, prescribers complain that the pregnancy section of current drug labels is neither concise nor clear. The FDA has pledged to address the concerns of clinicians in a future revision of the PLLR rule. The recommendations on risk assessment in the recently revised ICHS5(R3) guideline could be incorporated into the PLLR rule to remove extraneous nonclinical details from the label with the aim of facilitating rapid understanding by the practitioner.
摘要：
在2020-2021年，FDA批准了103种新药。胚胎发育（EFD）研究进行了76％的批准。对于大多数药物来说，在大鼠和兔中进行EFD研究。这两个物种对发育毒性同样敏感，但是在相同的全身暴露水平下，兔子对母体毒性稍敏感。尽管如此，68％的药物在大鼠和兔之间的发育毒性的低不良反应水平上显示出超过2倍的差异。本系列先前的评论汇编了自2014年以来批准的所有小分子药物以及迄今为止批准的所有治疗性单克隆抗体的EFD研究的信息。近年来，非人类灵长类动物在生物制药发育毒性测试中的使用有所下降（2020-2021年生物制品许可申请（BLAs）占22％，而2002-2015年为62％）。现在在啮齿动物中测试了更多的生物制药（2020-2021年占BLA的37%）。虽然怀孕和哺乳标签规则（PLLR），2014年采用，为药物标签中EFD数据的呈现带来了一致性，开处方者抱怨当前药物标签的怀孕部分既不简洁也不清楚。FDA已承诺在未来修订PLLR规则时解决临床医生的担忧。最近修订的ICHS5（R3）指南中关于风险评估的建议可以纳入PLLR规则，以从标签中删除无关的非临床细节，以促进从业者的快速理解。
