臺灣與先進國家再生醫療製劑監製人制度之比較分析與發展建議

Abstract

再生醫療近年來快速發展，再生醫療製劑的安全性受到高度重視，各國對於確保產品品質與法規遵循的關鍵角色的資格要求與職責設定不盡相同。臺灣現行制度依《再生醫療製劑條例》，明文要求再生醫療製劑製造業者設置具藥師資格之專任監製人，駐廠負責整體製程、品質管理、GMP制度執行與產品放行。監製人同時承擔製造與品質系統的監督責任，並對法規遵循負最終責任。 美國未設置如臺灣監製人或歐盟QP般具明確法定職稱之人員，依《公共衛生服務法（PHS）》第351條，高風險生物製劑須申請IND與BLA，並全面適用21 CFR第210與211部分cGMP規定。符合PHS 351條文之產品，其製造過程須遵守21 CFR § 211.22所列品質管制規範，由品質單位（Quality Unit）負責法規遵循與產品放行並承擔品質管理與放行責任。 歐盟設有法定職位合格人員（Qualified Person, QP），為先進醫療產品（ATMPs）最終放行前的品質與法規把關者。其法律依據為《Directive 2001/83/EC》第48至51條，規定QP須具備藥學、化學、生物學等背景與兩年以上實務經驗，並確認每批產品符合GMP及相關法規 而日本依據《薬機法》規定，製造販售業者須設置「総括製造販売責任者」（總括製造販售責任人），負責管理產品的品質與安全，需具備藥學或科學背景及實務經驗，職責與臺灣監製人相近。此核心職位，連同依GQP省令設置「品質保證責任者」，及依據GVP省令設置「安全管理責任者」，這三個角色的管理人員合稱「三役」。此外，GCTP省令另外要求製造廠需任命具備細胞生物學等專業的「製造管理者」，以專職監督第一線的製造流程。 本研究採用文獻分析法與比較法，對臺灣、美國、歐盟、日本之相關法規、官方指引及制度背景進行分析，探討臺灣再生醫療製劑監製人資格之現行制度與國際法規之間的差異。儘管2014年TFDA已提出制度改革的建議，但目前僅於2019年以行政指導方式推動部分功能導向的品質被授權人（AP）制度，尚未全面法制化落實。本研究在既有文獻基礎上，進一步分析再生醫療製劑的特性，指出現行制度在專業能力與執行面存在的顯著差異，並透過與先進國家的法規制度比較，提出更具體且深化的制度改革建議與配套措施，以提升臺灣再生醫療製劑的品質安全與國際競爭力。

In recent years, regenerative medicine has rapidly advanced, and the safety of regenerative medicinal products has become a major concern. However, the qualifications and responsibilities of key personnel responsible for ensuring product quality and regulatory compliance vary across countries. Under Taiwan’s current system, the Regenerative Medicinal Products Act explicitly requires manufacturers of regenerative medicinal products to appoint a full-time Responsible Person with a pharmacist license. This person must be stationed at the manufacturing site and is responsible for overseeing the entire production process, quality management, GMP implementation, and product release. The Responsible Person holds supervisory responsibility over both the manufacturing and quality systems and is ultimately accountable for regulatory compliance. In the United States, there is no statutory position equivalent to Taiwan’s Responsible Person or the EU’s QP. However, under Section 351 of the Public Health Service Act, high-risk biological products are required to undergo IND (Investigational New Drug) and BLA (Biologics License Application) procedures and must fully comply with GMP regulations stipulated in 21 CFR Parts 210 and 211. The manufacturing of products under PHS 351 must adhere to the quality control requirements outlined in §211.22, with the Quality Unit responsible for regulatory compliance and product release. According to 21 CFR §211.22, the Quality Unit essentially assumes responsibilities equivalent to those of quality management and release authorization. In the European Union, a statutory position known as the Qualified Person (QP) is established to ensure the quality and regulatory compliance of Advanced Therapy Medicinal Products (ATMPs) prior to product release. According to Articles 48 to 51 of Directive 2001/83/EC, QPs must have academic qualifications in pharmacy, chemistry, or biology, along with at least two years of relevant practical experience, and are responsible for verifying that each batch complies with GMP and applicable regulations. In Japan, under the Pharmaceuticals and Medical Devices Act (PMD Act, Law No. 145 of 1960), manufacturers are required to appoint a Marketing Director of Regenerative Medicine Products, who is responsible for the overall management of product quality and safety. This person must possess a background in pharmacy or science and relevant experience, and their role is functionally similar to that of Taiwan’s Responsible Person. This key position, along with a Quality Assurance Manager (per GQP regulations) and a Safety Management Manager (per GVP regulations), constitutes the "San-yaku" management system. Furthermore, GCTP regulations require the appointment of a separate Manufacturing Manager at the manufacturing site, who must have expertise in areas like cell biology, to specifically supervise the production process. This study employs document analysis and comparative methodologies to examine the relevant regulations, official guidelines, and institutional frameworks of Taiwan, the United States, the European Union, and Japan. It aims to explore the disparities between Taiwan’s current system for qualifying the responsible person for the manufacturing of regenerative medicinal products and the regulatory frameworks of advanced countries. Although a 2014 study by the Taiwan Food and Drug Administration (TFDA) proposed recommendations for institutional reform, only a partially function-oriented Authorized Person (AP) system has been promoted through administrative guidance since 2019, without full legal implementation. Building upon the existing literature, this study further analyzes the unique characteristics of regenerative medicinal products and identifies significant gaps in professional competencies and practical execution under the current system. By comparing international regulatory systems, the study puts forward more concrete and in-depth recommendations for institutional reform and supporting measures to enhance the quality, safety, and global competitiveness of Taiwan’s regenerative medicinal products.