Refalo Nathaniel, Chetcuti Daniel, Tanti Amy, Serracino-Inglott Anthony, Borg John Joseph
Medicines Authority, Sir Temi Żammit Buildings, Malta Life Sciences Park, San Ġwann, Malta.
Medicines Authority, Sir Temi Żammit Buildings, Malta Life Sciences Park, San Ġwann, Malta; Department of Pharmacy, Faculty of Medicine and Surgery, University of Malta, Msida, Malta.
Saudi Pharm J. 2017 Feb;25(2):280-289. doi: 10.1016/j.jsps.2016.07.005. Epub 2016 Jul 29.
The selection of a robust bioequivalence (BE) study designs for registering a generic product remains still a hard task. This task is still challenging despite the fact that generic products are much needed by health care providers in economical terms. Thus, BE study designs could be a means to allow companies to reduce costs and reach the market earlier. We therefore investigated whether different approaches in various products assessed by the European Medicines Agency during the approval phase resulted in a reduction in resources required to show bioequivalence for different medicinal products.
European Public Assessment Reports (EPARs) for off-patent medicinal products authorised within the European Union (EU) through the centralised procedure during the period 2007-2015 were retrieved and reviewed to identify the clinical studies that resulted in fewer number of subjects, the number of centres or trial duration versus the two-period crossover design.
7 studies out of 108 were considered as having benefitted from having a different design. Differences noted included having a different dose allocation scheme, having a different number of dosing periods, having a different number of treatment arms, and having one study evaluating different strengths. Benefits noted included a decrease in the number of subjects and centres required, decreases in study duration and a reduced number of studies required to demonstrate bioequivalence.
Bioequivalence studies can be designed in a specific manner to require fewer resources to carry out. Fewer resources required to register a medicinal product, could impart an advantage to companies (such as to be first on the market) or could even translate to making medicines more accessible (such as cheaper) to patients.
为仿制药注册选择稳健的生物等效性（BE）研究设计仍然是一项艰巨的任务。尽管从经济角度来看，医疗保健提供者非常需要仿制药，但这项任务仍然具有挑战性。因此，BE研究设计可能是一种让公司降低成本并更早进入市场的手段。我们因此调查了欧洲药品管理局在审批阶段评估的各种产品中，不同方法是否能减少证明不同药品生物等效性所需的资源。
检索并审查了2007 - 2015年期间通过集中程序在欧盟（EU）获得批准的非专利药品的欧洲公共评估报告（EPAR），以确定与两期交叉设计相比，导致受试者数量、中心数量或试验持续时间更少的临床研究。
108项研究中有7项被认为受益于不同的设计。注意到的差异包括采用不同的剂量分配方案、不同的给药周期数、不同的治疗组数量，以及有一项研究评估不同强度。注意到的益处包括所需受试者和中心数量减少、研究持续时间缩短以及证明生物等效性所需的研究数量减少。
生物等效性研究可以以特定方式设计，以减少开展所需的资源。注册药品所需资源减少，可能会给公司带来优势（例如率先上市），甚至可能转化为使患者更容易获得药品（例如更便宜）。
