藥品上市後變更-製程變更之法規比較   全文下載

Comparison of the Laws and Regulations on Pharmaceutical Post-Marketing Manufacturing Process Changes

在藥品之生命週期期間，化學、製造與管制（Chemistry, manufacturing, and controls, CMC）變更，是不可避免的，無論是因應藥品管理法規要求更新、新發現或持續改進，或是基於各種不同的需求，所有變更皆應進行風險評估，並遵循正確的法規管理路徑完成申請程序。2019年ICH Q12：藥品生命週期管理之技術與法規考量指引正式公告，鼓勵與要求各藥品法規管理單位（ICH法規會員），就其所轄將該指引納入藥品上市後變更相關管理規範，基於科學與風險的生命週期管理，提供合理的管理上彈性。對於上市後變更，不論是事先核准（Prior approval, PA）亦或通報（Notification），在實際執行時，還是有相當的模糊地帶，需要主管機關的明確說明與業者確實落實風險管理，提交適當文件供監管單位審查。本文主要針對美國聯邦法規21 CFR第314.70條、歐盟委員會第1234/2008號條例，及相關指引文件，進行藥品上市後製程變更之法規比較與分析，以供法規單位與業界參考。

During drug’s lifecycle, post-approval changes (PACs) of chemistry, manufacturing and controls (CMC) for pharmaceutical product is inevitable. These changes are necessitated by regulatory updates, new findings, unceasing improvements, or various other needs. Marketing authorization holders (MAHs) are requested to undergo risk assessment of all changes and follow the appropriate regulatory path to submit. The 2019 ICH Q12 guideline on Technical and Regulatory Considerations of Drug Life Cycle Management was officially announced, encouraging and requiring ICH regulatory members to incorporate this guideline into their post-marketing manufacturing process changes. This guideline aims to provide reasonable regulatory based on science and risk-based lifecycle management. For a PAC, whether it is a prior approval (PA) or notification, there are still gray areas in practice that require clear PAC definitions from the regulatory agency, risk supervision implementation by industry stakeholders, and submission of adequate documentation for authority review. This article compares and analyzes the regulations regarding post-marketing manufacturing process changes for pharmaceuticals under the US Code of Federal Regulations (CFR) 21 CFR Part 314.70, Regulation (EC) No 1234/2008 of the European Commission, and related thematic guidance documents, providing a reference for regulatory authorities and the industry.