Statistical Methodology, Novartis Pharma AG, 4056, Basel, Switzerland.
Department of Clinical Pharmacology, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria.
Br J Clin Pharmacol. 2018 Jul;84(7):1415-1431. doi: 10.1111/bcp.13586. Epub 2018 Apr 27.
Sponsors and regulators have more than 10 years of experience with the development of biosimilars in Europe. However, the regulatory pathway is still evolving. The present article provides an update on biosimilar development in practice by reviewing the clinical development programmes of recently approved biosimilars in Europe.
We used the European public assessment reports (EPARs) which are published by the European Medicines Agency (EMA) for a comparison of the clinical development programmes of the 37 approved biosimilars in Europe. Here, we present novel strategies in the development of biosimilars by focusing specifically on the 17 biosimilars that have gained approval in the last year, but we also compare additional key characteristics for all approved biosimilars.
The high variability of the clinical development strategies that we found previously was confirmed in the present analysis. Compared with earlier biosimilar applications, more nonstandard development strategies have been used recently. This includes, for example, applications without any studies in patients, and more complex study designs. During this study, we found that the EPARs for biosimilars seem to be improving; however, we identified important details which were still often missing. We provide a proposal for a checklist of the minimum information that should be included in biosimilar EPARs for giving the general public insights into the rationale for the approval of biosimilars.
European regulators still seem to be open to consider approaches that differ from the guidelines or previous applications, as long as justification is provided.
在欧洲，赞助商和监管机构在生物类似药的开发方面拥有超过 10 年的经验。然而，监管途径仍在不断发展。本文通过回顾欧洲最近批准的生物类似药的临床开发计划，提供了生物类似药开发实践的最新情况。
我们使用了欧洲药品管理局（EMA）发布的欧洲公共评估报告（EPAR），对欧洲批准的 37 种生物类似药的临床开发计划进行了比较。在这里，我们通过特别关注过去一年中获得批准的 17 种生物类似药，展示了生物类似药开发中的新策略，但我们也比较了所有获得批准的生物类似药的其他关键特征。
我们之前发现的临床开发策略的高度可变性在本分析中得到了证实。与早期的生物类似药应用相比，最近更多地使用了非标准的开发策略。例如，应用中没有任何患者研究，以及更复杂的研究设计。在这项研究中，我们发现生物类似药的 EPAR 似乎在不断改进；然而，我们发现了一些重要的细节，这些细节仍然经常缺失。我们提出了一份生物类似药 EPAR 中应包含的最低信息清单的建议，以便公众了解批准生物类似药的基本原理。
只要有充分的理由，欧洲监管机构似乎仍然愿意考虑与指南或以前的应用不同的方法。
