平行檢定法於生物製劑學名藥對等性評估之應用

On Study of Applications of the Parallel Line Assays to Evaluation of Biosimilar Drug Products

林亞靚(Ya-Chimg Lin)

指導教授 ： 劉仁沛

國立臺灣大學/生物資源暨農學院/農藝學研究所/碩士(2010年)

https://doi.org/10.6342/NTU.2010.01401

摘要

近年來生物製劑的市場逐漸增加，但所開發的成本太高。所以在生物製劑的專利期到期之後，許多藥廠紛紛投入生物製劑學名藥的開發。但生物製劑有別於一般傳統的小分子學名藥，所以評估生物製劑學名藥的方法可能不同。生技原廠認為生物製劑學名藥須執行臨床試驗才能被核准。但若生物製劑學名藥須執行大型臨床試驗，則生物製劑學名藥的研發則與發展新的生物製劑相同，而不能達到降低成本造福病患的目的。所以本論文以平行檢定的方法評估生物製劑學名藥是否必須進行大型臨床試驗及提出生物製劑學名藥與原廠生物製劑藥品相似的方法，執行模擬評估所提出方法之第一型錯誤機率和檢定力，並以數值例子來介紹提出方法之應用。

關鍵字

生物製劑 ； 生物製劑學名藥 ； 平行檢定 ； 生物相等性 ； 外插

並列摘要

In recent years, biologics market increases rapidly, but the development costs are also very high. Therefore, after the patent of biological products expires, many pharmaceutical companies have invested in the development of biosimilar drug products. But biological products are different from traditional small molecule drug products. Therefore the methods for assessment of biosimilar drug products are also different. Innovators ask for clinical trials to provide the efficacy and safety data to approve biosimialr drug products. However if approval of biosimilar products requires clinical trials, then development cost of biosimilar products will be the same as that of the innovators. As a result, it cannot achieve the goal of cost reduction. Therefore we try to apply the method of the parallel line assay to test whether the approval of the biosimilar should require clinical trials and to evaluate the similarity between the biosimilar products and innovator’s biological products. The results of type I error and power from the simulation studies are presented. A numerical example is used to illustrate the application of the proposed method.

並列關鍵字

Biological products ； Biosimilar ； Parallel line assay ； Bioequivalence ； Extrapolation

參考文獻

Chow, S. C. and Liu, J. P. (2008). Design and Analysis of Bioavailability and Bioequivalence Studies. 3rd ed. Marcel Dekker, Inc. New York.

Chow, S. C. and Liu, J. P. (2010). Statistical Assessment of Biosimilar Products. Journal of Biopharmaceutical Statistics 20:10-30

ICH (2005). Q5E Guideline on Comparability of Biotechnological/Biological Products Subject to Changes in Their Manufacturing Process. Center for Drug Evaluation and Research, Center for Biologics Evaluation and Research, the US Food and Drug Administration, Rockville, Maryland, USA

Schellekens, H. (2004). How similar do ‘biosimilar’ need to be? Nat Biotechnol, 22, 1357-1359.

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