经口吸入药物生物等效性研究的科学基础与法规挑战  

Scientific Rationale and Regulatory Challenges for Bioequivalence Study of Orally Inhaled Drug Products

作　　者：周璇 喻勇 侯曙光 ZHOU Xuan;YU Yong;HOU Shuguang(Sichuan Purity Pharmaceutical Co.,Ltd.,Chengdu 610041;School of Pharmacy,Chengdu University of Traditional Chinese Medicine,Chengdu 611137)

机构地区：[1]四川普锐特药业有限公司,四川成都610041 [2]成都中医药大学药学院,四川成都611137

出　　处：《中国医药工业杂志》2021年第9期1131-1141,共11页Chinese Journal of Pharmaceuticals

摘　　要：经口吸入药物制剂属于药物与装置组合的产品,是治疗哮喘、慢性阻塞性肺疾病(COPD)等呼吸系统疾病的首选药物。吸入药物的研发不仅具有技术挑战,欧美法规要求也存在争论和差别。本文从体外药学研究、体内药代动力学(PK)研究和药效学(PD)研究三方面对吸入仿制药研发的欧美法规指南进行了系统比较和解析,并讨论了其科学基础。吸入仿制药与原研药的体外药学研究是制剂一致性的前提基础;PK研究灵敏客观,可进一步确保吸入仿制药物的一致性;PD研究的意义和必要性则存在争论,有待进一步证实。我国吸入仿制药研发和申报应以国家药品监督管理局药品审评中心(CDE)发布的指导原则为基础,结合药物性质、制剂类别和最新法规进展,科学设计体外和体内的评价方法。Orally inhaled drugs are drug-device combination products,and have been widely used as the first option for treatment of respiratory diseases such as asthma and chronic obstructive pulmonary disease(COPD).The development of inhaled drug products is not only full of technical challenges,but also has disputes and discrepancies between USA and European regulatory agents.This paper compares and analyzes the FDA and EMA guidelines for the development of generic inhaled drug products on in vitro equivalence study,pharmacokinetic(PK)and pharmacodynamic(PD)bioequivalence studies,and discusses the scientific rationale.The in vitro equivalence for a generic inhaled drug is the essential requirement.For in vivo studies,PK study shows sensitive and objective as an indicator of bioequivalence,however,disputes exist for PD study,which needs more studies.In China,the development of generic inhaled drugs should be based on CDE guidelines,together with investigations of drug properties,dosage forms and updated regulations,to scientifically design the in vitro and in vivo evaluation studies.

关 键 词：吸入药物 肺部递送 生物等效性 法规要求 

分 类 号：R944.9[医药卫生—药剂学]