FDA/HC/EMA/PMDA/CFDA对口服固体制剂中窄治疗指数药物的仿制药人体生物等效性研究要求

The requirements for in vivo bioequivalence studies for solid products of oral drugs with narrow therapeutic indexes by FDA,HC,EMA,PMDA and CFDA

窄治疗指数(narrow therapeutic index,NTI)药物的特性决定其仿制药人体生物等效性(bioequivalence,BE)研究必须要有更加科学的研究设计和判定标准。目前国际上主要药品监管机构对NTI药物的BE研究要求各不相同,而且也没有全球统一的NTI药物目录。此外,部分剂量-效应关系陡峭并且用药安全性风险较高的药物没有被列入已有的NTI药物目录中。本文综述了美国食品药品监督管理局(FDA),加拿大卫生部(HC)、欧洲药品监督管理局(EMA)、日本药品和医疗器械管理局(PMDA)以及中国食品药品监督管理总局(CFDA)对NTI药物仿制药人体生物等效性研究的基本要求,并收集这些药品监管机构已认可的NTI药物目录,希望对我国的NTI药品仿制药BE研究的优化有借鉴意义。

Scientific consideration on study design and more strict bioequivalence （BE） acceptance limits are essential for in vivo BE studies of generic narrow therapeutic index （NTI） drugs, which is decided by the characteristics of NTI drugs. Currently, there are differences in the BE study requirements of NIT drugs among the main drug administration agencies, and there is no globally harmonized NTI list. Moreover, some drugs with steep dose-response relationship and high risk in use are not defined as NTI drugs. In this review, we summed up the requirements for in vivo BE studies of NTI drugs by FDA, HC, EMA, PMDA and CFDA, and collected the official NTI lists from those countries and regions, which will be helpful to optimize the BE studies of NTI drugs in China.