本文選題：生物相似性 + 證據(jù)鏈完備性�。� 參考：《藥物分析雜志》2015年05期

【摘要】：最近幾年,許多生物制藥/生物技術(shù)公司對研發(fā)生物類似藥物的興趣越來越強。根據(jù)生物類似藥物的研發(fā)需求,美國藥監(jiān)局(FDA)在2012年頒布了3個相關(guān)指導原則草案。FDA在這3個指導原則中表示,對于生物類似藥物的注冊申請的全部提交資料采用"證據(jù)鏈完備性(totality-of-the-evidence)"的方法來審查,并鼓勵研發(fā)企業(yè)使用"逐步遞進法stepwise"來找出與原研產(chǎn)品相比,仿制生物制品在每一工藝步驟中的殘余不確定度,進而在后續(xù)的研發(fā)步驟中設(shè)法解決這些殘余不確定度。盡管要獲得"具有較小不確定度的充足證據(jù)鏈完備性"這樣的概念可以理解,但是,如何根據(jù)提交的所有注冊申請信息客觀地評價"證據(jù)鏈完備性",以及如何基于已有信息確定下一步研發(fā)步驟的程度和范圍仍然是需解決的具體操作問題。本研究探索了費舍爾合成P值的概念(Fisher,1932)在等效性檢驗設(shè)置中的應(yīng)用,更具體地說,在一個生物類似藥物的臨床研究中,根據(jù)"逐步遞進法"和"臨床證據(jù)完備性"的概念,用它來設(shè)計和分析2個生物類似藥物的臨床相似性。
[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".

【作者單位】： Amgen
【分類號】：R95

【共引文獻】

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