生物相似性藥品的評估－統計觀點

Evaluation of Biosimilars-Statistical Perspectives

鄒小蕙(Hsiao-Hui Tsou)

《中國統計學報》 53卷1期 (2015/03) Pp. 11-22

摘要

近年來，許多暢銷的生物藥品（Biologics）之專利紛紛到期，發展成本較為低廉的生物相似性藥品（biosimilars/Follow-onbiologics）已經引起生技產業的關注。然而，不論在美國FDA公佈的指導草案、歐盟EMA的生物相似性藥品指引、亦或是台灣的審查重點表中，都沒有建議明確的統計方法來評估生物相似性藥品的生物相似性。至今，發表於國際期刊、用來評估生物相似性的統計方法學的論文仍然相當少。本文說明「評估生物相似性」的統計考量，並介紹一些最近發展出來、用來評估生物相似性藥品和原廠的生物藥品之間的生物相似性的統計方法，從統計的觀點來說明生物相似性藥品的考量重點。

關鍵字

生物相似性藥品 ； 預測機率密度函數 ； 一致性基準 ； 再現性機率 ； 生物相似性指標

並列摘要

Recently, biosimilars have attracted much attention from sponsors and regulatory authorities while patents on early biological products will soon expire in the next few years. The regulatory agencies in many countries such as tFDA of Taiwan, FDA of USA, EMA of EU have published guidelines or draft guidance to assist sponsors in demonstrating that a proposed follow-on biological product is biosimilar to a reference products on similar biological medicinal products for approval of the proposed products. In those guideline or draft guidance, however, no specific statistical methods for assessment of biosimilarity were mentioned. The standard statistical methods for the assessment of average bioequivalence may not be appropriate for the assessment of biosimilarity of follow-on biologics due to fundamental differences between small-molecule drug products and biological (large-molecule) drug products. Other statistical methodologies for evaluation of biosimilarity from different approaches are recommended. This article introduces some new statistical methodologies published recently for evaluation of biosimilarity. The statistical considerations in the design and evaluation of biosimilar clinical trials are also provided.

並列關鍵字

biosimilars ； predictive probability function ； consistent criterion ； reproducibility ； biosimilarity index

參考文獻

97年11月21日衛署藥字第0970333017號公告之「藥品查驗登記審查準則─生物相似性藥品之查驗登記」

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