Huh Ki Young, Kim Eunwoo, Lee Soyoung, Yoo Hyounggyoon, Yoon Seonghae, Yu Kyung-Sang, Chung Jae-Yong
Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul, South Korea.
Department of Clinical Pharmacology and Therapeutics, CHA University Bundang Medical Center, CHA University School of Medicine, Gyeonggi-do, South Korea.
Front Pharmacol. 2021 May 4;12:651790. doi: 10.3389/fphar.2021.651790. eCollection 2021.
Demonstration of bioequivalence (BE) is mandatory while developing generic drugs. The scientific concept of BE applies equally to different regulatory agencies. However, the application of the concept may differ for each agency, which can affect the design of BE studies. To evaluate the study practices in terms of the BE concept in South Korea, we retrospectively analyzed BE study reports available from Ministry of Food and Drug Safety between 2013 and 2019. Statistical estimation of the pharmacokinetic parameters, including peak concentration and area under the concentration-time curve to the last measurable concentration, as well as study design, number of subjects in a study, study duration, fasting status, and formulation of specific drugs were obtained. The drugs were classified per World Health Organization Anatomical Therapeutic Chemical Classification and Biopharmaceutics Classification System. Post-hoc intrasubject coefficient of variation and corresponding sample sizes were calculated from the 90% confidence intervals of pharmacokinetic parameters. A total of 143 generic drugs in 588 BE studies were analyzed. The largest number of studies were performed in the area of Cardiovascular system (172 studies), followed by Nervous system (143 studies) and Alimentary tract and metabolism (92 studies). Overall, BE studies in South Korea were conducted in accordance with the global guideline despite the differences in details. BE studies were focused on the several therapeutic areas and conducted in a similar manner. The number of subjects was generally larger than that estimated with 90% power.
在开发仿制药时,证明生物等效性(BE)是强制性的。生物等效性的科学概念同样适用于不同的监管机构。然而,每个机构对该概念的应用可能有所不同,这会影响生物等效性研究的设计。为了根据韩国的生物等效性概念评估研究实践,我们回顾性分析了2013年至2019年期间从食品药品安全部获得的生物等效性研究报告。获得了药代动力学参数的统计估计值,包括峰浓度和至最后可测量浓度的浓度-时间曲线下面积,以及研究设计、研究中的受试者数量、研究持续时间、禁食状态和特定药物的剂型。这些药物根据世界卫生组织解剖治疗学化学分类和生物药剂学分类系统进行分类。从药代动力学参数的90%置信区间计算事后受试者内变异系数和相应的样本量。共分析了588项生物等效性研究中的143种仿制药。研究数量最多的领域是心血管系统(共172项研究),其次是神经系统(143项研究)和消化道及代谢(92项研究)。总体而言,尽管在细节上存在差异,但韩国的生物等效性研究是按照全球指南进行的。生物等效性研究集中在几个治疗领域,并以类似的方式进行。受试者数量通常大于以90%检验效能估计的数量。