在开发仿制药时,必须证明生物等效性(BE)。BE的科学概念同样适用于不同的监管机构。然而,每个机构的概念应用可能不同,这可能会影响BE研究的设计。为了评估韩国BE概念的研究实践,我们回顾性分析了2013年至2019年食品药品安全部提供的BE研究报告.药代动力学参数的统计估计,包括到最后可测量浓度的浓度-时间曲线下的峰浓度和面积,以及研究设计,研究中的受试者数量,研究持续时间,空腹状态,并获得了特定药物的配方。根据世界卫生组织解剖治疗化学分类和生物药剂学分类系统对药物进行分类。根据药代动力学参数的90%置信区间计算受试者体内变异系数和相应的样本量。共分析了588项BE研究中的143种仿制药。在心血管系统领域进行的研究最多(172项研究),其次是神经系统(143项研究)和消化道和代谢(92项研究)。总的来说,尽管细节存在差异,但韩国的BE研究仍按照全球指南进行。BE研究集中在几个治疗领域,并以类似的方式进行。受试者的数量通常大于90%功率的估计。
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.