Statistical Assessment of Biosimilar Products
Statistical Assessment of Biosimilar Products
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DOI：
10.1080/10543400903280266
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发表时间：
2010-01-01
影响因子：
1.1
通讯作者：
Liu, Jen-pei
中科院分区：
文献类型：
--
作者：
Chow, Shein-Chung;Liu, Jen-pei
生物制品或药物是使用生命系统或生物体生产的治疗剂。由于成本昂贵，获得这些救生生物产品的机会有限。早期生物制品的专利将在未来几年内到期。这允许其他生物制药/生物技术公司生产生物制品的仿制药，这些生物制品被美国食品药品监督管理局（FDA）称为后续生物制品，或被欧盟（EU）的欧洲药品管理局（EMEA）称为生物仿制药。具有同等疗效和安全性的具有成本效益的后续生物制品的竞争可以降低成本，从而增加患者获得急需的生物药品的机会。与传统的小分子药物不同，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生物类似药产品与其相应的创新产品之间的等效性（相似性）评价对于科学界和监管机构来说都是一个巨大的挑战。在本文中，我们概述了当前批准生物仿制药产品的监管要求。本文对传统化学仿制药的生物等效性评价标准进行了综述。详细描述了生物类似药和化学仿制药在大小和结构、免疫原性、产品质量属性和生产工艺方面的差异。此外，还提出了统计学考虑因素，包括设计标准、基本生物类似药假设和统计方法。还探讨了使用基因组数据评价生物类似药产品的可能性。
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.