11 March 2025  2025 年 3 月 11 日
EMA/INS/GMP/48771/2025
GMP/GDP Inspectors Working Group (GMP/GDP IWG) Concept paper on the revision of Part IV Guidelines on Good Manufacturing Practice specific to Advanced Therapy Medicinal Products
GMP/GDP 检查员工作组（GMP/GDP IWG） 关于修订第四部分 "先进疗法药物产品良好生产规范指导原则 "的概念文件

The proposed guideline will replace:
拟议准则将取代

Those participating in the public consultation are asked to please submit comments via the EU Survey tool at the following link
请参与公众咨询的人士通过欧盟调查工具提交意见，链接如下

This concept paper aims to outline the rationale, objectives, and proposed changes for updating Part IV - GMP specific to ATMP of the good manufacturing practice (GMP) guide Eudralex Volume 4 following the revision of Annex 1 which came into operation in August 2023. As the Part IV is an EU standalone guideline and that the sector is to abide solely for reference, it should be revised independently to address recent developments in the manufacture of sterile medicinal products.
本概念文件旨在概述良好生产规范（GMP）指南 Eudralex 第 4 卷第 IV 部分--ATMP 专用 GMP（附件 1 已于 2023 年 8 月修订生效）的基本原理、目标和修订建议。由于第 IV 部分是欧盟的独立指南，该部门仅作为参考而遵守，因此应进行独立修订，以应对无菌药品生产的最新发展。

Since the introduction of the revised GMP Annex I for the manufacture of sterile products has modified and clarified some requirements compared to the current ATMP guideline, the proposed revision of the ATMP guideline is to align with the current Annex 1 while maintaining a flexible approach for the production of ATMPs.
由于修订后的无菌产品生产 GMP 附件 I 与现行的 ATMP 指南相比，修改并明确了一些 要求，因此，拟议的 ATMP 指南修订旨在与现行的附件 1 保持一致，同时保持生产 ATMP 的灵活方法。

Part IV was developed under the initiative of the European Commission according to Art 5 of the Regulation (EC) No 1394/2007 and was adopted on November 22, 2017. After extensive consultations with the stakeholders, the European Commission had deemed it necessary to reflect the entire requirements for the manufacture of ATMPs in one single guideline, moving away from the former Annex 2 Manufacture of Biological active substances and Medicinal Products for Human Use, and all pertinent chapters of the Eudralex Volume 4 guideline. The rationale was to allow academia, developers and manufacturers to achieve the consistent production of high-quality ATMPs across the European Union.
第四部分由欧盟委员会根据（EC）第 1394/2007 号法规第 5 条倡议制定，于 2017 年 11 月 22 日通过。在与利益相关方进行广泛磋商后，欧盟委员会认为有必要在单一指南中反映 ATMP 生产的全部要求，摒弃原附件 2《生物活性物质和人用医药产品的生产》以及 Eudralex 第 4 卷指南的所有相关章节。这样做的目的是让学术界、开发商和制造商能够在整个欧盟范围内一致地生产高质量的 ATMP。
Since the release of the revised Annex 1, the incorporation of relevant ICH concepts (such as Quality Risk Management (QRM) and Pharmaceutical Quality System (PQS)), the introduction of Contamination Control Strategy (CCS), and recent technological advancements are not yet reflected in the current ATMP GMP guideline.
自修订版附件 1 发布以来，ICH 的相关概念（如质量风险管理 (QRM) 和药品质量体系 (PQS)）、污染控制策略 (CCS) 的引入以及最新的技术进步尚未反映在当前的 ATMP GMP 指南中。
EudraLex Part IV contains only requirements for applying a risk-based approach in all the sections of the guidance, however the revised Annex 1 is referring to Quality Risk Management (QRM) principles with reference to ICH Q9 concepts that offer a more systematic approach to quality risk management, and to ICH Q10 which describes a modern pharmaceutical quality system (PQS) which allows to establish and maintain a state of control of product quality and to facilitate continual improvement over the entire life cycle, which is also the basis for the Contamination Control Strategy (CCS).
EudraLex 第 IV 部分仅要求在指南的所有章节中应用基于风险的方法，但修订后的附件 1 提及了质量风险管理 (QRM) 原则，并参考了 ICH Q9 概念，该概念为质量风险管理提供了更系统的方法，还参考了 ICH Q10 概念，该概念描述了现代药品质量体系 (PQS)，可建立和保持产品质量控制状态，并促进整个生命周期内的持续改进，这也是污染控制策略 (CCS) 的基础。
In addition, the current ATMP guideline does not reflect the advances of new technologies in the manufacture of advanced medicinal products; the proposed revision will give further clarifications on the expectations how to qualify, control and manage clean rooms and closed systems (isolators and Restricted Access Barriers Systems (RABS) in order to prevent detrimental impact on product but it will maintain open to the use of biosafety cabinets due to of the numerous manual manipulations associated with the individualized batches .
此外，现行的 ATMP 指南没有反映先进医药产品生产中新技术的进步；拟议的修订将进一步明确如何鉴定、控制和管理洁净室和封闭系统（隔离器和限制进入屏障系统（RABS）），以防止对产品造成有害影响，但由于与个性化批次相关的大量手工操作，它将继续开放生物安全柜的使用。
The proposed revision will embrace the use of new technologies that are not currently covered in the current version (e.g. automated advanced technology, (closed) single use systems, fast rapid microbiological testing methods).
拟议的修订将包括目前版本未涵盖的新技术的使用（如自动化先进技术、（封闭式）一次性使用系统、快速微生物检测方法）。

Following the publication of a new regulation on standards of quality and safety for substances of human origin intended for human application there is also a need to update legal references and definitions for the starting material of human origin.
在新的《人类原产物质质量和安全标准条例》发布后，还需要更新人类原产物质的法律参考资料和定义。

It is noted that the current revision will only focus on the sterile manufacture sections related to the updated version of the Annex 1 and not to update any other topics/sections outside of that scope.
需要指出的是，本次修订仅关注与附件 1 更新版有关的无菌生产部分，而不更新该范围之外的任何其他主题/部分。

The working group action plan was presented to the GMP/GDP Inspector’s working group on the ${26}^{\text{th}}$${26}^{\text{th }}$26^("th ")26^{\text {th }} of November 2024. The GMP/GDP Inspectors Working Group recommends that the current version of ATMP guideline is revised to align with the recent revised Annex 1.
工作组行动计划已于 2024 年 11 月 ${26}^{\text{th}}$${26}^{\text{th }}$26^("th ")26^{\text {th }} 日提交给 GMP/GDP 检查员工作组。GMP/GDP 检查员工作组建议修订当前版本的 ATMP 准则，使其与最近修订的附件 1 保持一致。
The new guideline should clarify how manufacturers can take advantage of new possibilities deriving from the application of an enhanced process understanding by using innovative tools as described in the ICH Q9 and Q10 guidelines.
新指南应阐明生产商如何利用 ICH Q9 和 Q10 指南中描述的创新工具，通过加强对工艺的理解来利用新的可能性。
The revised guideline will seek to remove ambiguity and inconsistencies and will take account of advances in technologies.
修订后的准则将力求消除模糊和不一致之处，并将考虑到技术的进步。
The working group action plan was also presented to the BWP and the CAT on the ${22}^{\text{nd}}$${22}^{\text{nd }}$22^("nd ")22^{\text {nd }} of January 2025.
工作组行动计划还于 2025 年 1 月 ${22}^{\text{nd}}$${22}^{\text{nd }}$22^("nd ")22^{\text {nd }} 提交给了生物武器公约和禁止酷刑委员会。

Preparation of draft concept paper - January 2025
编写概念文件草案 - 2025 年 1 月
Approval of draft concept paper - $15{}^{\text{th}}$$15{}^{\text{th }}$15^("th ")15{ }^{\text {th }} April 2025
批准概念文件草案 - $15{}^{\text{th}}$$15{}^{\text{th }}$15^("th ")15{ }^{\text {th }} 2025 年 4 月
Released for consultation - $8{}^{\text{th}}$$8{}^{\text{th }}$8^("th ")8{ }^{\text {th }} May 2025
发布征求意见稿 - $8{}^{\text{th}}$$8{}^{\text{th }}$8^("th ")8{ }^{\text {th }} 2025 年 5 月
Deadline for stakeholders’ comments - $8^{\text{th}}$$8^{\text{th }}$8^("th ")8^{\text {th }} July 2025
利益相关者提出意见的截止日期 - $8^{\text{th}}$$8^{\text{th }}$8^("th ")8^{\text {th }} 2025 年 7 月
Proposed date for release of draft guideline - September 2026
准则草案的拟议发布日期 - 2026 年 9 月
Deadline for stakeholders comments - December 2026
利益相关者提出意见的截止日期 - 2026 年 12 月
Adoption in GMDP IWG - March 2027
2027 年 3 月全球机制发展计划 IWG 通过

A drafting group has been established, with a kick-off meeting held on the ${30}^{\text{th}}$${30}^{\text{th }}$30^("th ")30^{\text {th }} of November 2024. Meetings are schedule every 2 weeks in order to closely monitor the progress on work. Regular feedback will be provided to the GMP/GDP IWG. Feedback from CAT will be requested once the first draft is available.
起草小组已经成立，并于 2024 年 11 月 ${30}^{\text{th}}$${30}^{\text{th }}$30^("th ")30^{\text {th }} 召开了启动会议。每两周召开一次会议，以密切监督工作进展。将定期向 GMP/GDP IWG 提供反馈。一旦初稿完成，将要求 CAT 提供反馈意见。

There is no anticipated adverse impact on the industry in terms of resources or costs. However, clarifying the use of new systems may necessitate gradual modifications to certain facilities, equipment, and processes over time.
预计在资源或成本方面不会对该行业产生不利影响。不过，要明确新系统的使用，可能需要随着时间的推移逐步修改某些设施、设备和流程。

Revision of the guideline will facilitate a better understanding of expectations which will lead to more consistent and improved manufacture of ATMPs.
修订该指南将有助于更好地理解人们的期望，从而使 ATMP 的生产更加一致和改进。

EMA (GMP/GDP Inspectors Working Group, Committee for Advanced Therapy, Biologics Working party), national competent authorities of EU/EEA member states, stakeholders.
欧洲药品管理局（GMP/GDP 检查员工作组、先进疗法委员会、生物制剂工作组）、欧盟/欧洲经济区成员国的国家主管机构、利益相关者。