臺灣博碩士論文加值系統

近年來生醫產業之醫療器材領域不斷應用人工智慧、創新技術研究發展創新醫材，故相關之法規標準與依據隨之產生，為使創新醫療器材在創新領域法規要求領域中符合安全與有效性，則需有賴更多相關臨床前測試、實質相等試驗，以及臨床試驗等相關測試且在合理的範圍內進行驗證，而醫療器材產品從開發至商品化過程，需經過產品設計、產品相關確效作業、臨床評估(必要時須執行臨床試驗)、製造、品質檢驗、法規要求等，為使產品能於各國上市進行銷售則需透過醫療器材的安全性與有效性，並達到各國之醫療器材產品上市法規要求，以及國內醫療器材查驗登記與國際間產品的認證核可上市，並從中規劃出商品最佳化法規途徑，以提升醫療器材上市率以及產品國際競爭力。
本研究以「專利技術-減少人工關節摩擦之潤滑組合物及其使用方法」為例，對於此人工關節潤滑組合物產品特性為植入人體可能超過30天、市面上無相關已上市產品之相關產品特性，依據台灣醫療器材法規分類分級定義判定為創新、植入性等之高風險醫療器材，並歸類於第三等級醫療器材產品，此等級醫材需經過臨床試驗相關規範確認其安全與有效性驗證後才可上市，而在技術之設計開發、測試、製造之標準於台灣尚無相關規定，故本研究以此專利技術與市面上應用於退化性關節炎使用注射玻尿酸減少關節間摩擦進行相似領域產品應用之設計、材料特性、製造過程、功效及治療使用目的的分析比較進行臨床前測試項目的研究，並依生物相容性、滅菌試驗(滅菌確效)、物化試驗、功效性試驗等方面著手，欲擬定出相關臨床前測試方式參考依據，並依據本研究產品特性研究一系列商品化過程以及與各國醫療器材上市途徑比較，提供一生醫材料延長人工關節置換率之生物潤滑分子臨床前測試項目之參考與最佳化上市法規途徑的研究。

In recent years, artificial intelligence and innovative technology have been continually applied to develop innovative medical devices for the biomedical industry. Accordingly, related regulations and standards have been stipulated. To ensure that innovative medical devices comply with safety- and effectiveness-related regulations for the innovative fields, related testing such as preclinical testing, substantial-equivalence testing, and clinical trials must be performed to yield results within a rational range. From product development to commercialization, medical devices undergo product design, product validation, clinical assessment (clinical trials are conducted when necessary), product manufacturing, quality inspection, and regulatory review. For medical devices manufactured in Taiwan to be sold in local and foreign markets, they must be inspected for registration in Taiwan, comply with local laws and regulations regarding safety and effectiveness in the target market, and obtain international certification. In addition, the optimal method for product legalization must be determined to enhance the sales of the medical devices and their international competitiveness.
In this study, a lubricating composition for reducing artificial joint friction was used as an example. The artificial-joint lubricating composition can be implanted in human body for more than 30 days, and no related products on the market have this feature. According to the regulations for medical devices in Taiwan, this product is classified as an innovative, implantable, highly risky, and third-grade medical device. This type of medical device must undergo clinical trials and meet related requirements to confirm its safety and effectiveness before being marketed. However, in Taiwan, no related regulations have been formulated for the design, development, testing, and production of related technology. Therefore, to investigate preclinical testing, this study analyzed and compared the product design, material characteristics, production processes, product efficacy, and therapeutic purposes between this patented technology and hyaluronic acid—a similar commercially-available product that is used to reduce joint friction in patients with in degenerative arthritis. In addition, biocompatibility, sterilization (sterilization validation), physiochemical, and efficacy testing were performed to provide references for developing related preclinical testing methods. Moreover, according to the characteristics of the product investigated in this study, a series of product commercialization processes and methods used in other countries for selling medical devices were compared in order to provide a reference for investigating preclinical testing for biolubricants (i.e., biomedical materials that can enhance the lifespan of artificial joint replacement) and to identify the optimal method for formulating regulations regarding product sales.

摘要 i
ABSTRACT iii
誌 謝 v
目 錄 vi
表目錄 ix
圖目錄 x
第一章 緒論 1
1.1研究背景與動機 1
1.1.1法規面 1
1.1.2 技術面 2
第二章 文獻回顧 3
2.1 醫療器材產業個論 3
2.1.1 全球醫療器材市場 3
2.1.2 全球骨科醫療器材市場 5
2.2 醫療器材法規與管理模式 8
2.2.1 法源依據與定義 8
2.2.2 醫療器材優良製造規範GMP 17
2.2.3 醫療器材上市管理流程-查驗登記 20
2.2.4 創新醫材管理規範 26
2.2.5 醫療器材品質管理制度ISO 13485:2016 28
2.2.6 上市後監督管理制度 30
2.3 醫療器材產品技術面 35
2.3.1 玻尿酸(Hyaluronic acid,HA) 35
2.3.2 海藻酸鈉(Na-Alginate,AA) 37
2.3.3 角叉藻二醣(Carrageenan,CRG) 40
第三章 專利技術-減少人工關節摩擦之潤滑組合物及其使用方法 42
3.1 背景沿革 42
3.2 技術與發展 44
3.3 專利技術測試方法與結果 44
3.3.1 實例 44
3.3.2 測試流程方法與結果 46
3.4 相關小節與建議 49
第四章 研究目的與流程 50
4.1 研究目的 50
4.2 研究方法與流程 50
第五章 研究成果與內容 51
5.1 生物潤滑分子現有應用 51
5.2 產品設計管制流程 52
5.3 醫療器材查驗登記 56
5.3.1 安全性試驗 56
5.3.2 功效性試驗 73
5.3.3 臨床試驗 78
第六章 結論 84
參考文獻 87

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55.ISO 11137-2 Sterilization of health care products -- Radiation -- Part 2: Establishing the sterilization dose
56.ISO 11137-3 Sterilization of health care products -- Radiation -- Part 3: Guidance on dosimetric aspects of development, validation and routine control
57.ISO 11135-1:2007 Sterilization of health care products -- Ethylene oxide -- Part 1: Requirements for development, validation and routine control of a sterilization process for medical devices
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