生物类似药证据链完备性的合成P值法评估（英文）

发布时间：2018-05-12 15:59

本文选题：生物相似性 + 证据链完备性　；参考：《药物分析杂志》2015年05期

【摘要】：最近几年,许多生物制药/生物技术公司对研发生物类似药物的兴趣越来越强。根据生物类似药物的研发需求,美国药监局(FDA)在2012年颁布了3个相关指导原则草案。FDA在这3个指导原则中表示,对于生物类似药物的注册申请的全部提交资料采用"证据链完备性(totality-of-the-evidence)"的方法来审查,并鼓励研发企业使用"逐步递进法stepwise"来找出与原研产品相比,仿制生物制品在每一工艺步骤中的残余不确定度,进而在后续的研发步骤中设法解决这些残余不确定度。尽管要获得"具有较小不确定度的充足证据链完备性"这样的概念可以理解,但是,如何根据提交的所有注册申请信息客观地评价"证据链完备性",以及如何基于已有信息确定下一步研发步骤的程度和范围仍然是需解决的具体操作问题。本研究探索了费舍尔合成P值的概念(Fisher,1932)在等效性检验设置中的应用,更具体地说,在一个生物类似药物的临床研究中,根据"逐步递进法"和"临床证据完备性"的概念,用它来设计和分析2个生物类似药物的临床相似性。
[Abstract]:In recent years, many biopharmaceutical / Biotech Corp have become increasingly interested in developing biological similar drugs. According to the needs of research and development of biological similar drugs, the United States Drug Administration (FDA) issued 3 draft guidelines in 2012,.FDA, in these 3 guidelines, all submissions for registration applications for biological similar drugs. The material is reviewed with the "totality-of-the-evidence" method and encourages R & D enterprises to use "step by step method stepwise" to find out the residual uncertainty of biologics in each process compared with the original research products, and then try to solve these residual uncertainties in the subsequent R & D steps. The concept of "sufficient evidence chain completeness with smaller uncertainty" can be understood, but how to objectively evaluate the "completeness of evidence chain" based on all the information submitted for registration and how to determine the range and scope of the next step of research and development based on the existing information is still a specific operation problem to be solved. The application of Fisher's concept of P value (Fisher, 1932) in the equivalence test setting was explored, and more specifically, in a clinical study of a biological similar drug, the clinical similarity of 2 biological similar drugs was designed and analyzed in accordance with the concept of "progressive approach" and "clinical evidence completeness".

【作者单位】： Amgen
【分类号】：R95

【共引文献】