臺灣博碩士論文加值系統

近年來隨醫藥產業發展大幅躍進，細胞治療、基因治療及組織工程產品等再生醫療可為傳統醫學無法治療之疾病帶來一線生機，歐美等先進國家之製藥廠紛紛投入此產業發展，並已陸續核准該類產品上市，成為目前醫藥領域研發之趨勢。然該類製劑成分異質性、製程特殊性及治療複雜性，風險管控有別於化學或生物製劑，且其成分使用活細胞，取自於人體或動物來源，可能有外來性病源污染之風險，但因無法最終滅菌，須藉由良好無菌操作、環境管控與品質檢驗層層把關，以降低製程可能遭受之污染及確認製劑品質安全，即所謂製程即是產品概念。如何由製造端至病人施打階段維持該類製劑良好活性與安全性，都將面臨諸多挑戰，各國主管機關為此建立許多規範指引以因應再生醫療領域所面臨之問題，同時協助產業界管控製劑品質。有鑑於國外早已核准多件再生醫療產品，發展相較於我國快速，而我國礙於過去法案尚未完善以致病患無法獲得相關治療方式，為即早滿足國內癌症患者之醫療需求，近期推動再生醫療技術及製劑之雙軌制管理架構，以「特定醫療技術檢查檢驗醫療儀器施行或使用管理辦法」(簡稱特管辦法)管理醫療技術，並以「再生醫療製劑管理條例(草案)｣管理製劑，此條例尚於立法院審議。有鑑於我國尚未有再生醫療製劑上市，相較先進國家管理經驗少，因此本研究考量美國屬再生醫療製劑發展之先導國家之一，並以目前備受討論之CAR-T產品為例，透過研析美國與我國再生醫療製劑管控途徑了解CAR-T產品管理位階，進一步探討其製程管控、品質檢驗、儲存運送、醫院處置等相關規範。經研究顯示，我國再生醫療管理主要參照美國及各國規範，於既定藥品管理規範下，考量再生醫療製劑複雜性與特異性，以個案進行討論，於原則性規範中保有彈性管理空間，而細部處理流程則可藉由汲取美國再生醫療製劑之官方稽查報告、不定期發布之參考文件及專家學者研究文獻等經驗，作為我國管理再生醫療品質之參考，強化品質風險管控，為未來製劑上市預先建立事前準備。

Recently, along with the growth of emerging medical industry, regenerative medical industry includes cell therapy, gene therapy and tissue engineering products, bring hope to cure diseases that current medical can't cure. Therefore, the industry is right on trend in technologically advanced countries like European and the United States, and those countries already approved several regenerative medical products. However, because of the heterogeneity, specificity and complexity of these products, the risk considerations of quality control different from chemical drugs and biological products. Besides, as their ingredients include human or animal living cells, they can’t be sterilized and have potential adventitious agent risks. To prevent potential contamination risks by aseptic operations, environment control and quality tests in every step of the process and the final product is the concept of “processes is products”. Nevertheless, manufacturers and authorities face many challenges with the viability and safety of the product from manufacture to deliver product to patients. Authorities of many countries establish regulations and guidelines to help manufacturers solve these problems. In view of the development of foreign countries, our national authority established two regulatory systems to manage medical technologies and medical products in regenerative medical field to fulfill medical demands in Taiwan. Two regulatory systems include revised “Regulations Governing the Application of Specific Medical Technique and Medical Device” and “Act Governing of Regenerative Medical Preparations” draft, which is unapproved. Considering regenerative medical products haven’t been marketed in Taiwan and lack management experiences, this study analyzed regenerative medical regulation systems and quality control of risk consideration in the United State as references for Taiwan. This study focused on CAR-T products to investigate these products management level and discuss further about manufacturing controls, quality tests, storage, shipping, and handling in hospitals, etc. The results shown that, Taiwan’s regulations/guidelines of regenerative medical products mainly made references to the regulations of America or other countries. Considering the complexity and specialty of regenerative medical products, our national authority maybe use established regulations as a basis to discuss management policies case by case, and leave space to the requirement. Besides, taking FDA and experts experiences to improve quality control system of regenerative medical products in Taiwan, and make well preparations for marketing products in the future.

摘要 I
目次 IV
圖/表目次 V
第一章 緒論 1
第一節 研究背景 1
第二節 緣由與目的 6
第三節 研究範圍 6
第四節 研究方法與架構 6
第二章 再生醫療管理 8
第一節 管理途徑 8
一、國際管理-以美國為例 8
二、我國管理 14
三、第一節討論-比較美國與我國管理架構與途徑 19
第二節 品質管理-以CAR-T產品為例 21
一、原料管控 24
二、製程管控 29
三、品質檢驗 35
四、後端處理 44
五、第二節討論- 美國與我國再生醫療品質管理之比較 51
第三章 結論 57
第四章 參考文獻 58
附錄一、美國已核准上市之再生醫療產品分類 65
附錄二、美國與我國再生醫療品質管理比較表 69

圖/表目次
圖目次
圖 一、歐美日已上市之再生醫療產品 2
圖 二、研究架構 7
圖 三、美國再生醫療管理架構 13
圖 四、人體試驗與臨床醫療之定義 17
圖 五、我國再生醫療管理架構 18
圖 六、彙整美國與我國再生醫療領域管理架構 21
圖 七、CAR-T 產品製程風險流程圖 22

表目次
表 一、美國 CAR-T 產品比較表 3
表 二、我國已核准之細胞治療技術分類 5
表 三、美國與我國針對再生醫療產品品質管制規範 23
表 四、CAR-T 產品品質檢驗項目及規格 (舉例) 36
表 五、不同藥品種類之風險管控比較表 56

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