文件將質(zhì)量變更分為重大質(zhì)量變更、中等質(zhì)量變更、微小質(zhì)量變更和無影響質(zhì)量變更：
重大質(zhì)量變更：對產(chǎn)品核心質(zhì)量屬性（如鑒別、效價(jià)、純度等）有顯著影響，可能改變產(chǎn)品臨床特性的變更。例如，生產(chǎn)工藝關(guān)鍵變更、產(chǎn)品成分 / 規(guī)格變更、生產(chǎn)場地重大變更等。
中等質(zhì)量變更：對產(chǎn)品質(zhì)量有一定影響，但通過現(xiàn)有數(shù)據(jù)可驗(yàn)證一致性，無需大規(guī)模臨床數(shù)據(jù)支持的變更。例如，細(xì)胞庫 / 種子庫變更、工藝參數(shù)微調(diào)、原料 / 輔料供應(yīng)商變更、質(zhì)量控制方法變更等。
微小質(zhì)量變更：對產(chǎn)品質(zhì)量、安全、 有效性影響極小，通過常規(guī)驗(yàn)證即可確認(rèn)一致性的變更。例如，設(shè)備更換 / 優(yōu)化、質(zhì)量標(biāo)準(zhǔn)微調(diào)、場地 / 設(shè)施優(yōu)化等。
無影響的質(zhì)量變更：對產(chǎn)品質(zhì)量、安全、 有效性無任何潛在影響，僅涉及行政或文件層面的變更。例如，文件糾錯(cuò)、非產(chǎn)品接觸變更、合規(guī)性更新等。WHO要求這類變更按 GMP 要求留存相關(guān)記錄，供監(jiān)管機(jī)構(gòu)檢查時(shí)核查，無需主動向監(jiān)管機(jī)構(gòu)報(bào)備。
Quality changes with no impact
無影響的質(zhì)量變更
Quality changes that have no impact on product quality, safety or efficacy may be implemented by the marketing authorization holder without prior review by the NRA. Information on such changes must be retained as part of the manufacturer’s GMP records or marketing authorization holder’s product records, as applicable. These changes must comply with the applicable GMP requirements and must be available for review during GMP inspections. Examples of such changes include, but are not limited to:
對產(chǎn)品質(zhì)量、安全性或有效性無影響的質(zhì)量變更，MAH可在不經(jīng)國家監(jiān)管機(jī)構(gòu)事先審查的情況下實(shí)施。此類變更的相關(guān)信息應(yīng)適當(dāng)作為制造商的GMP記錄或MAH的產(chǎn)品記錄予以保存。這些變更必須符合適用的GMP要求，并在GMP檢查時(shí)可提供審查。此類變更示例包括但不限于：
non-critical changes to the licensed application, including spelling corrections and editorial clarifications made to documents (such as validation summaries and/or reports, analytical procedures, standard operating procedures or production documentation summaries) that have no impact on the quality, safety and efficacy of the product;
對許可申請的非關(guān)鍵性變更，包括對文件（如驗(yàn)證總結(jié)和/或報(bào)告、分析程序、標(biāo)準(zhǔn)操作規(guī)程或生產(chǎn)文件摘要）的拼寫修正和編輯性說明，且該變更對產(chǎn)品質(zhì)量、安全性和有效性無影響；
replacement of equipment with identical equipment; or change in the process equipment that does not directly come into contact of the product;
用相同設(shè)備替換原有設(shè)備；或變更不直接接觸產(chǎn)品的工藝設(shè)備；
change in specifications for a compendial or non-critical raw material, a compendial excipient or a compendial container closure component to comply with an updated pharmacopoeial standard/monograph;
為符合藥典標(biāo)準(zhǔn)/各論更新，變更藥典級或非關(guān)鍵性原料、藥典級輔料或藥典級容器密封組件的質(zhì)量標(biāo)準(zhǔn)；
change in the in-process controls performed at non-critical manufacturing steps;
變更非關(guān)鍵生產(chǎn)步驟的過程控制；
addition of a new GMP storage warehouse for raw materials, master and working cell banks, and drug substance;
新增符合藥品GMP的原輔料、主細(xì)胞庫、工作細(xì)胞庫和原料儲存?zhèn)}庫；
installation of non-process-related equipment or rooms to improve the facility, such as warehousing refrigerators or freezers;
安裝與工藝無關(guān)的設(shè)備或房間以改善設(shè)施（如倉儲用冰箱或冰柜）；
addition of time point(s) into the post-approval stability protocol;
在獲批后穩(wěn)定性方案中新增時(shí)間點(diǎn)；
deletion of time point(s) from the post-approval stability protocol beyond the approved shelf-life;
從獲批后穩(wěn)定性方案中刪除超過批準(zhǔn)有效期的時(shí)間點(diǎn)；
change in tertiary packaging material.
變更三級包裝材料。
京公網(wǎng)安備11010802046783號
