CFDI发布ICH Q12草案中文版本
翻译：JULIA 来源： Julia法规翻译
CFDI在其期刊（试刊）《国际药品检查动态研究》2018年第2期发布了ICH Q12《药品生命周期管理中的技术和注册考量》草案中文版本。有兴趣者可自行找来阅读。
该草案于2017年11月16日发布于ICH官网，其主要用于指导国家和地区药监机构制订药品注册后生命周期内的变更管理，亦供企业相关人员参考。其中关于变更的控制均为建议形式，比较新的概念主要有3个：EC（established condition)既定条件、PACMP（批准后变更管理方案）以及PLCM（产品生命周期管理）（此处主要指注册资料）。
前言部分内容如下：
1.1 Objectives 目的
The concepts outlined in prior ICH Quality Guidelines (ICH Q8, Q9, Q10 and Q11) provide opportunities for science andrisk-based approaches for drug development and risk-based regulatory decisions.These guidelines are valuable in the assessment of Chemistry, Manufacturing and Controls (CMC) changes across the product lifecycle. ICH Q8 and Q11 guidelines focus mostly on early stage aspects of the product lifecycle (i.e., product development, registration and launch). Experience with implementation of recent ICH guidelines has revealed technical and regulatory gaps that limit the full realisation of more flexible regulatory approaches to post-approval CMC changesas described in ICH Q8 (R2) and Q10 Annex I. This guideline addresses the commercial phase of the product lifecycle (as described in ICH Q10).
之前ICH质量指南（ICH Q8, Q9, Q10和Q11）为基于风险和科学的药品开发方法和基于风险的注册决策提供了机会。这些指南在产品生命周期中评估CMC变更极有价值。ICH Q8和Q11指南主要关注的产品生命周期的早期阶段方面（例如，产品开发、注册和上市）。近年ICH指南实施的经验显示出限制了按ICH (R2)和Q10附录I对上市后CMC变更采用更多灵活注册方法的技术和注册差距。本指南针对的是药品生命周期（如ICH Q10所述）的商业阶段。
A harmonised approach regarding technical and regulatory considerations for lifecycle management will benefit patients,industry, and regulatory authorities by promoting innovation and continual improvement in the biopharmaceutical sector, strengthening quality assurance and improving supply of medicinal products.
技术和注册的生命周期管理考量的协调一致将有助于患者、行业和药监机构，促进生物药品部分的创新的持续改进，加强药品供应的保障和改善。
This guideline provides a framework tofacilitate the management of post-approval CMC changes in a more predictable and efficient manner. It is also intended to demonstrate how increased product and process knowledge can contribute to a reduction in the number of regulatory submissions. Effective implementation of the tools and enablers described in this guideline should enhance industry’s ability to manage many CMC changes effectively under the firm’s Pharmaceutical Quality System (PQS) with less need for extensive regulatory oversight prior to implementation. The extent of operational and regulatory flexibility is subject to product and process understanding (ICH Q8 and Q11), application of risk management principles (ICHQ9), and an effective pharmaceutical quality system (ICH Q10).
本指南提供了一个框架，以帮助采用可预期且高效的方式管理批准后CMC变更。它还旨在展示产品和工艺知识的增加如何有助于减少监管递交的次数。通过对本指南中描述的工具和推动因素的有效应用，提高制药行业在各自企业的药品质量体系（PQS）下有效管理CMC变更的能力，从而减少在实施变更前必须由监管机构评估批准的需求。操作和监管灵活性的程度取决于产品和工艺的掌握程度（ICH Q8和Q11）、风险管理原则的应用（ICH Q9）水平以及药品质量体系（ICH Q10）的可靠程度。
In certain ICH regions, the current ICH Q12 guideline is not fully compatible with the established legal framework with regard to the use of explicit Established Conditions ('EC') referred to in Chapter 3 and with the Product Lifecycle Management ('PLCM') referred to in Chapter 5 as outlined in this guideline. These concepts will, however, be considered when the legal frameworks will be reviewed and, in the interim, tothe extent possible under the existing regulation in these ICH regions.
在特定的ICH地区，当前ICH Q12指南与既定法律框架在使用明确的本指南中第3章所列既定条件（EC）方面以及第5章中所指产品生命周期管理（PLCM）方面并不全面相容。然而，当在这些ICH地区正式或临时审视现有法规时，宜尽量在现有法规框架内考虑这些概念。
1.2 Scope范围
This guideline applies to pharmaceutical drug substances (i.e., active pharmaceutical ingredients) and pharmaceutical drug products, including marketed chemical, and biotechnological/biologicalproducts. The guideline also applies to drug-device combination products that meet the definition of a pharmaceutical or biotechnological/biological product.Changes needed to comply with revisions to Pharmacopoeial monographs are not in scope of this guideline.
本指南适用于药用物质（即原料药）和制剂，包括已上市的化学和生物药品。本指南亦适用于符合药物或生物药品定义的药械组合产品。为符合药典各论修订所需的变更不在此指南范围内。
1.3 ICHQ12 Regulatory Tools and Enablers 注册工具和实现方法
Use of the following harmonised regulatorytools and enablers with associated guiding principles, as described in this guideline, will enhance the management of post-approval changes, and transparency between industry and regulatory authorities, leading to innovationand continual improvement.
使用以下协调后的注册工具和与相关指南原则有关的促进者，正如本指南所述，将加强批准后变更的管理，促进企业与药监当局之间的透明度，引导创新的持续改进。
Categorisation of Post-Approval CMC Changes (Chapter 2) 批准后CMC变更分类（第2章）
Categorisation of Post-Approval CMC Changesis a framework that encompasses a risk-based categorisation for the type of communication expected of the Marketing Authorisation Holder (MAH) with the regulatory authority regarding CMC changes.
批准后CMC变更分类是引导基于风险对MAH与药监当局在CMC变更预期沟通类型的分类框架。
Established Conditions (ECs) (Chapter 3) 既定条件（EC）（第3章）
The concept of ECs provides a clear understanding between the MAH and regulatory authorities regarding the necessary elements to assure product quality and identify the elements that require a regulatory submission, if changed. This guideline describes how ECs are identified as well as what information can be designated as supportive information that would not require a regulatory submission, if changed. Inaddition, guidance is included for managing revisions of the ECs over aproduct’s lifecycle.
EC概念为MAH和药监当局提供关于必需要素方面的清楚理解，以确保产品质量和识别需要执行注册申报的要素（如有变更）。本指南叙述如何识别EC，以及哪些信息可以指定为支持性信息，而不需要法规申报（如有变更）。此外，还包括了EC在产品生命周期中修订管理的指南。
Post-Approval Change Management Protocol (PACMP) (Chapter 4) 批准后变更管理方案（PACMP）（第4章）
The PACMP is a regulatory tool that provides predictability regarding the information required to support a CMC change and the type of regulatory submission based on prior agreement between the MAH and regulatory authority. Such a mechanism enables planning and implementation of future changes to ECs in an efficient and predictable manner.
PACMP是一个注册工具，它提供支持CMC变更所需信息方面可预期性，以及基于MAH和药监当局预订协议的注册申报的类型。此机制使得可以有效和可预期方式规划和实施未来对EC的变更。
Product Lifecycle Management (PLCM) (Chapter 5) 产品生命周期管理（PLCM）（第5章）
The PLCM document serves as a central repository for the ECs and the associated reporting category for changes madeto ECs. The document also captures how a product will be managed during the commercial phase of the lifecycle including relevant post-approval CMC commitments and PACMPs.
PLCM文件用途是作为EC和对EC所做变更的相关报告类型的集中存贮工具。该文件也包括一个产品在生命周期中的商业化阶段如何管理，包括相关批准后CMC承诺和PACMP的信息。
Pharmaceutical Quality System (PQS) and Change Management (Chapter 6) 药物质量体系（PQS）和变更管理（第6章）
An effective PQS as described in ICH Q10and compliance with regional GMPs are necessary for implementation of this guideline. In particular, management of manufacturing changes across the supply chain is an essential part of an effective change management system. This guideline provides recommendations for robust change management across multiple entities involved in the manufacture of a pharmaceutical product.
在ICH Q10中所述的有效PQS和地区GMP合规性在实施本指南时是必须的。尤其是，供应链中生产变更管理是有效管理体系的基础部分。本指南提供对药品生产涉及多个实体的稳健变更管理的建议。
Relationship Between Regulatory Assessment and Inspection (Chapter 7) 注册评审和检查之间的关系（第7章）
This guideline outlines the complementaryroles of regulatory assessment and inspection, and how communication between assessors and inspectors facilitates the use of the tools included herein.
本指南列出了注册评审和检查的互补作用，以及评审员与检查员之间如何沟通，以促进使用此处所包括的工具。
Post-Approval Changes for Marketed Products (Chapter 8) 已上市产品的批准后变更（第8章）
Approaches to facilitate changes to marketed products are outlined. This guideline provides detailed guidance to enable changes to analytical methods to be made with immediate or other post-implementation notification. Science- and risk-based approaches for stability studies in support of the evaluation of CMC changes are also described.
列出了帮助已上市药品变更的方法。本指南提供了执行立即或其它实施后通知的分析方法变更的详细指南。还描述了用于支持CMC变更评估的基于科学和风险的稳定性研究方法。
The tools and enablers described above are complementary and are intended to link different phases of the product lifecycle. Pharmaceutical development activities result in an appropriate control strategy, elements of which are considered to be Established Conditions. All changes to an approved product are managed through a firm’s Pharmaceutical Quality System; changes to ECs must also be reported to the regulatory authority. Where the regulatory system provides for Categorisationof Post-approval CMC Changes for reporting according to risk, the MAH may propose reporting categories for changes to ECs based on risk and knowledge gained through enhanced pharmaceutical development. A system with risk-based reporting categories also facilitates the use of Post-Approval Change Management Protocols, which provide predictability regarding planning for future changes to ECs. The Product Lifecycle Management document is a summary that transparently conveys to the regulatory authority how the MAH plans to manage post-approval CMC changes. The tools and enablers in this guideline donot change the Relationship Between Regulatory Assessment and Inspection;however, collaboration and communication between assessors and inspectors arenecessary for the implementation of this guideline. Finally, this guideline proposes approaches to facilitate Post-Approval Changes to Marketed Products without the need for regulatory review and approval prior to implementation of certain CMC changes.
上述工具和驱动力是互补的，意在关联产品生命周期的不同阶段。药物开发活动产生一个适当的控制策略，其要素要在既定条件中进行考虑。所有对已批准产品的变更通过公司的药物质量体系进行管理，对EC的变更也必须报告给药监当局。当监管系统根据风险对报告的批准后CMC变化进行分类时，MAH可以根据通过增强药物开发获得的风险和知识提出对EC变更的报告类别。具有基于风险的报告类别的系统还便于使用批准后变更管理协议，其提供关于今后EC变更规划的可预测性。产品生命周期管理文件是一次总结，明确清晰地传达给监管机构MAH如何计划管理批准后CMC变更。本指南中的工具和推动因素不改变监管评估和检查之间的关系；然而，评估者和检查员之间的协作和沟通对于实施本指南是必要的。最后，本指南提出了促进上市产品批准后变更的方法，而不需要在实施某些CMC变更之前进行注册审评和批准。