Since the first approval of a biosimilar medicinal product in 2006, scientific understanding of the features and development of biosimilar medicines has accumulated. This review scrutinizes public information on development programs and the contribution of the clinical studies for biosimilar approval in the European Union (EU) and/or the United States (US) until November 2019. The retrospective evaluation of the programs that eventually obtained marketing authorization and/or licensure revealed that in 95% (36 out of 38) of all programs, the comparative clinical efficacy studies confirmed similarity. In the remaining 5% (2 out of 38), despite meeting efficacy outcomes, the biosimilar candidates exhibited clinical differences in immunogenicity that required changes to the manufacturing process and additional clinical studies to enable biosimilar approval. Both instances of clinical differences in immunogenicity occurred prior to 2010, and the recurrence of these cases is unlikely today due to state-of-the-art assays and improved control of process-related impurities. Biosimilar candidates that were neither approved in the EU nor in the US were not approved due to reasons other than clinical confirmation of efficacy. This review of the development history of biosimilars allows the proposal of a more efficient and expedited biosimilar development without the routine need for comparative clinical efficacy and/or pharmacodynamic studies and without any compromise in quality, safety, or efficacy. This proposal is scientifically valid, consistent with regulation of all biologics, and maintains robust regulatory standards in the assessment of biosimilar candidates. Note: The findings and conclusion of this paper are limited to biosimilar products developed against the regulatory standards in the EU and the US.

中文翻译：

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通向量身定制的生物仿制药开发之路。

自从2006年首次批准生物仿制药产品以来，对生物仿制药的特性和发展的科学认识不断积累。这项审查仔细审查了有关开发计划的公开信息，以及在2019年11月之前在欧盟（EU）和/或美国（US）进行生物仿制药批准的临床研究的贡献。对最终获得营销许可和/或许可表明，在所有程序中的95％（38个中的36个）中，比较的临床疗效研究证实了相似性。在剩下的5％（38个中的2个）中，尽管达到了疗效结果，生物仿制药的候选药物在免疫原性方面表现出临床差异，这需要改变制造工艺和进行其他临床研究才能获得生物仿制药的批准。免疫原性的两种临床差异均发生在2010年之前，由于最新的检测方法和对过程相关杂质的改进控制，今天这些病例的复发不太可能发生。既未在欧盟也未在美国批准的生物仿制药候选者，由于除临床确认疗效以外的原因未获批准。回顾生物仿制药的发展历史，可以提出更高效，更快速的生物仿制药开发的建议，而无需常规的比较临床功效和/或药效学研究，并且在质量，安全性或功效上没有任何妥协。该建议在科学上是有效的，与所有生物制剂的法规一致，并且在评估生物仿制药候选药物时保持了强有力的法规标准。注意：本文的发现和结论仅限于根据欧盟和美国的监管标准开发的生物仿制药产品。