Chow Shein-Chung, Liu Jen-Pei
Duke University School of Medicine, Durham, North Carolina, USA.
J Biopharm Stat. 2010 Jan;20(1):10-30. doi: 10.1080/10543400903280266.
Biological products or medicines are therapeutic agents that are produced using a living system or organism. Access to these life-saving biological products is limited because of their expensive costs. Patents on the early biological products will soon expire in the next few years. This allows other biopharmaceutical/biotech companies to manufacture the generic versions of the biological products, which are referred to as follow-on biological products by the U.S. Food and Drug Administration (FDA) or as biosimilar medicinal products by the European Medicine Agency (EMEA) of the European Union (EU). Competition of cost-effective follow-on biological products with equivalent efficacy and safety can cut down the costs and hence increase patients' access to the much-needed biological pharmaceuticals. Unlike for the conventional pharmaceuticals of small molecules, the complexity and heterogeneity of the molecular structure, complicated manufacturing process, different analytical methods, and possibility of severe immunogenicity reactions make evaluation of equivalence (similarity) between the biosimilar products and their corresponding innovator product a great challenge for both the scientific community and regulatory agencies. In this paper, we provide an overview of the current regulatory requirements for approval of biosimilar products. A review of current criteria for evaluation of bioequivalence for the traditional chemical generic products is provided. A detailed description of the differences between the biosimilar and chemical generic products is given with respect to size and structure, immunogenicity, product quality attributed, and manufacturing processes. In addition, statistical considerations including design criteria, fundamental biosimilar assumptions, and statistical methods are proposed. The possibility of using genomic data in evaluation of biosimilar products is also explored.
生物制品或药物是利用生命系统或生物体生产的治疗剂。由于成本高昂，获得这些救命生物制品的机会有限。早期生物制品的专利将在未来几年内到期。这使得其他生物制药/生物技术公司能够生产生物制品的仿制药，美国食品药品监督管理局（FDA）称其为后续生物制品，欧盟（EU）的欧洲药品管理局（EMEA）则称其为生物类似药。具有同等疗效和安全性的高性价比后续生物制品之间的竞争可以降低成本，从而增加患者获得急需生物药品的机会。与传统小分子药物不同，生物类似药分子结构的复杂性和异质性、复杂的生产工艺、不同的分析方法以及严重免疫原性反应的可能性，使得评估生物类似药产品与其相应创新产品之间的等效性（相似性）对科学界和监管机构来说都是一个巨大的挑战。在本文中，我们概述了目前生物类似药产品批准的监管要求。提供了对传统化学仿制药生物等效性评估现行标准的综述。从大小和结构、免疫原性、产品质量属性和生产工艺等方面详细描述了生物类似药与化学仿制药之间的差异。此外，还提出了包括设计标准、基本生物类似药假设和统计方法在内的统计考量。还探讨了在生物类似药产品评估中使用基因组数据的可能性。
