生物等效性研究的评价标准介绍

Introduction of the evaluation methods for bioequivalence studies

生物等效性(BE)研究是仿制药及创新药上市的重要考量之一,评价方法的选择需要综合考虑药物特点及可行性。同品种药品的不同剂型,其剂量、给药途径、物理化学性质、药代动力学特点并不完全相同,对存在较大药代动力学(PK)差异的一类药物,以某一剂型笼统划定整体的评价方法可能导致药品评价的偏倚。目前,我国对吸收分布代谢途径较为复杂的药品的BE评价尚处起步阶段,通过分析已公布的类似品种药物所推荐的指导原则,可为选择或建立合适的评价标准提供思路。本文综合国家药品监督管理局、美国食品药品监督管理局及欧洲药品管理局针对BE研究的指导原则,系统综述不同制剂BE研究的评价标准,特别聚焦于以药代动力学终点进行BE评价时,评价物质、PK参数及等效界限的考虑,旨在为我国制定特定药品BE评价标准提供建议和参考。

Bioequivalence study is one of the important considerations for the listing of generic drugs and innovative drugs.The selection of evaluation methods requires comprehensive consideration of drug characteristics and feasibilities.The dosage,route of administration,physicochemical properties,and pharmacokinetic characteristics of different dosage forms of the same drug are not exactly the same.For a class of drugs with significant pharmacokinetics(PK)differences,the overall evaluation method defined by a dosage form may lead to bias in drug evaluation.At present,the bioequivalence evaluation of drugs with complex absorption,distribution,and metabolic pathways is still in its infancy in China.By analyzing the published guidelines for similar drugs,it can provide ideas for the selection or establishment of appropriate evaluation standards.This paper integrates the guidelines of National Medical Products Administration,U.S.Food and Drug Administration,and European Medicines Agency for bioequivalence studies,systematically reviews the evaluation criteria for bioequivalence studies of different preparations,especially focusing on evaluating substances and PK parameters when evaluating bioequivalence with pharmacokinetic endpoints and the consideration of the equivalence limits,in order to provide suggestions and references for the development of specific drug bioequivalence evaluation standards in China.