Q10 药物质量体系20080604(中英文).doc

Q10 药物质量体系20080604（中英文） INTERNATIONAL CONFERENCE ON HARMONISATION OF TECHNICAL REQUIREMENTS FOR REGISTRATION OF PHARMACEUTICALS FOR HUMAN USE ICH HARMONISED TRIPARTITE GUIDELINE ICH三方协调指南PHARMACEUTICAL QUALITY SYSTEM 药物质量体系Q10 Current Step 4 version dated 4 June 2008 This Guideline has been developed by the appropriate ICH Expert Working Group and has been subject to consultation by the regulatory parties, in accordance with the ICH Process. At Step 4 of the Process the final draft is recommended for adoption to the regulatory bodies of the European Union, Japan and USA.Q10 Document History 文件历史Code History Date Q10Approved by the Steering Committee under Step 2 and release for public consultation.9 May 2007Current Step 4 versionCode History Date Q10Approved by the Steering Committee under Step 4 and recommendation for adoption to the three ICH regulatory bodies.4 June 2008PHARMACEUTICAL QUALITY SYSTEM ICH Harmonised Tripartite Guideline Having reached Step 4 of the ICH Process at the ICH Steering Committee meeting on 4 June 2008, this guideline is recommended for adoption to the three regulatory parties to ICH TABLE OF CONTENTS 1. PHARMACEUTICAL QUALITY SYSTEM.1 1.1 Introduction.1 1.2 Scope.1 1.3 Relationship of ICH Q10 to Regional GMP Requirements, ISO Standards and ICH Q7.2 1.4 Relationship of ICH Q10 to Regulatory Approaches.2 1.5 ICH Q10 Objectives.2 1.5.1 Achieve Product Realisation.2 1.5.2 Establish and Maintain a State of Control.3 1.5.3 Facilitate Continual Improvement.3 1.6 Enablers: Knowledge Management and Quality Risk Management.3 1.6.1 Knowledge Management.3 1.6.2 Quality Risk Management.3 1.7 Design and Content Considerations.3 1.8 Quality Manual.4 2. MANAGEMENT RESPONSIBILITY.4 2.1 Management Commitment.4 2.2 Quality Policy.5 2.3 Quality Planning.5 2.4 Resource Management.5 2.5 Internal Communication.6 2.6 Management Review.6 2.7 Management of Outsourced Activities and Purchased Materials.6 2.8 Management of Change in Product Ownership.6 3. CONTINUAL IMPROVEMENT OF PROCESS PERFORMANCE AND PRODUCT QUALITY.7 3.1 Lifecycle Stage Goals.7 3.1.1 Pharmaceutical Development.7 3.1.2 Technology Transfer.7 3.1.3 Commercial Manufacturing.7 3.1.4 Product Discontinuation.7 3.2 Pharmaceutical Quality System Elements.7 3.2.1 Process Performance and Product Quality Monitoring System.8 3.2.2 Corrective Action and Preventive Action (CAPA) System.9 3.2.3 Change Management System.10 3.2.4 Management Review of Process Performance and Product Quality.11 4. CONTINUAL IMPROVEMENT OF THE PHARMACEUTICAL QUALITY SYSTEM.11 4.1 Management Review of the Pharmaceutical Quality System.11 4.2 Monitoring of Internal and External Factors Impacting the Pharmaceutical Quality System.12 4.3 Outcomes of Management Review and Monitoring.12 5. GLOSSARY.13 Annex 1:Potential Opportunities to Enhance Science and Risk Based Regulatory Approaches .16Annex 2:Diagram of the ICH Q10 Pharmaceutical Quality System Model.17 1制药质量体系11绪论12范围13ICHQ10与地方GMP要求，ISO标准与ICHQ7之间的关系14ICHQ10与法规方法间的关系15ICHQ10目的151产品实现152控制状态的建立和实现153 持续改进16支持者：知识管理和质量风险管理161知识管理162质量风险管理17设计和内容方面的考虑18质量手册2管理职责21管理承诺22质量方针23质量策划24资源管理25内部沟通26管理评审27外包活动和物料采购的管理28产品所有权变更管理3工艺性能和产品质量的持续改进31生命周期阶段目标311物料研发312技术转移313商业化生产314产品终止32制药质量体系原理321工艺性能和产品质量监控体系322纠正预防体系323变更管理体系324工艺性能和产品质量的管理评审4制药质量体系的持续改进41制药质量体系的管理评审42制药质量体系的内外部影响因素的监控43管理评审和监控成果5术语附件1：基于法规方法对科学和风险进行改进的潜在机会附件2：ICH Q10 制药质量体系模型图PHARMACEUTICAL QUALITY SYSTEM药物质量体系1. PHARMACEUTICAL QUALITY SYSTEM 药物质量体系1.1 Introduction 介绍 This document establishes a new ICH tripartite guideline describing a model for an effective quality management system for the pharmaceutical industry, referred to as the Pharmaceutical Quality System. Throughout this guideline, the term “pharmaceutical quality system” refers to the ICH Q10 model. 本文确立了新的ICH三方指南，叙述了制药工业有效质量管理体系的一个模型，被称之为制药质量体系。在这个指南中，术语“制药质量体系”是指ICH Q10模型。ICH Q10 describes one comprehensive model for an effective pharmaceutical quality system that is based on International Standards Organisation (ISO) quality concepts, includes applicable Good Manufacturing Practice (GMP) regulations and complements ICH Q8 “Pharmaceutical Development” and ICH Q9 “Quality Risk Management”. ICH Q10 is a model for a pharmaceutical quality system that can be implemented throughout the different stages of a product lifecycle. Much of the content of ICH Q10 applicable to manufacturing sites is currently specified by regional GMP requirements. ICH Q10 is not intended to create any new expectations beyond current regulatory requirements. Consequently, the content of ICH Q10 that is additional to current regional GMP requirements is optional. ICHQ10叙述了基于ISO质量概念的有效的制药管理体系的综合模型，包括了适用的GMP法规，并与ICH Q8（药物研发）和ICH Q9（质量风险管理）相辅相成。ICH Q10这一制药质量体系模型是可以应用于产品生命周期的各个阶段的。ICH Q10目的不在于创立超越现行法规要求的新期望。因此，ICH Q10中多于现行的各地的GMP要求的内容是可选的。ICH Q10 demonstrates industry and regulatory authorities support of an effective pharmaceutical quality system to enhance the quality and availability of medicines around the world in the interest of public health. Implementation of ICH Q10 throughout the product lifecycle should facilitate innovation and continual improvement and strengthen the link between pharmaceutical development and manufacturing activities. ICH Q10论述了行业和药政管理机构为了公众健康而对有效制药质量体系的支持以提高世界范围内药品的质量和获得性。在整个产品生命周期内实施了ICH Q10有助于创新和持续改进，并加强了药物研发和生产活动间的联系。1.2 Scope 范围This guideline applies to the systems supporting the development and manufacture of pharmaceutical drug substances (i.e., API) and drug products, including biotechnology and biological products, throughout the product lifecycle. 本指南适用于药用物质（API）和制剂的研发和生产系统，包括生物技术和生物产品的整个产品生命周期。The elements of ICH Q10 should be applied in a manner that is appropriate and proportionate to each of the product lifecycle stages, recognising the differences among, and the different goals of each stage (see Section 3). ICH Q10要素的应用需与产品生命周期的各个阶段相适应，应认识到和个阶段目标的差异（见第3节）。For the purposes of this guideline, the product lifecycle includes the following technical activities for new and existing products: 本指南中，新老产品的产品生命周期包括如下的技术活动：? Pharmaceutical Development: 药物研发：o Drug substance development; 药用物质的研发o Formulation development (including container/closure system); 配方研发（包括容器/密闭系统）o Manufacture of investigational products; 研究用产品的生产o Delivery system development (where relevant); 给药系统研发（如相关的话）o Manufacturing process development and scale-up; 生产工艺开发和放大o Analytical method development. 分析方法开发? Technology Transfer: 技术转移o New product transfers during Development through Manufacturing; 新产品从研发转移至生产o Transfers within or between manufacturing and testing sites for marketed products. 市售产品生产和检测地点内部或之间转移? Commercial Manufacturing: 商业化生产o Acquisition and control of materials; 原料的获得和控制o Provision of facilities, utilities, and equipment; 厂房，公用设施和设备的准备o Production (including packaging and labelling); 生产（包括包装和贴签）o Quality control and assurance; 质量控制和保证o Release; 放行o Storage; 储存o Distribution (excluding wholesaler activities). 发放（不包括批发商活动）? Product Discontinuation: 产品终止o Retention of documentation; 文件保留o Sample retention; 留样o Continued product assessment and reporting. 产品持续评估和报告1.3 Relationship of ICH Q10 to Regional GMP Requirements, ISO Standards and ICH Q7 ICH Q10与地方性GMP要求,ISO标准和ICH Q7的关系Regional GMP requirements, the ICH Q7 Guideline, “Good Manufacturing Practice Guide for Active Pharmaceutical Ingredients”, and ISO quality management system guidelines form the foundation for ICH Q10. To meet the objectives described below, ICH Q10 augments GMPs by describing specific quality system elements and management responsibilities. ICH Q10 provides a harmonised model for a pharmaceutical quality system throughout the lifecycle of a product and is intended to be used together with regional GMP requirements. 地区GMP要求，ICH Q7及ISO质量管理体系是是ICH Q10的基础。为了满足下述目的，ICHQ10通过叙述具体的质量体系要素和管理职责加强了GMP。ICH Q10为产品生命周期的制药质量体系提供了一致的模型并预期与地区的GMP要求一同使用。The regional GMPs do not explicitly address all stages of the product lifecycle (e.g., Development). The quality system elements and management responsibilities described in this guideline are intended to encourage the use of science and risk based approaches at each lifecycle stage, thereby promoting continual improvement across the entire product lifecycle. 地区的GMP没有明确列出产品生命周期的所有阶段（如，研发）。此指南描述的质量体系基础和管理职责用于鼓励在每个生命周期阶段使用科学和风险管理方法，因而在全部的产品生命周期中促进持续改进。1.4 Relationship of ICH Q10 to Regulatory Approaches ICH Q10与法规方法的关系Regulatory approaches for a specific product or manufacturing facility should be commensurate with the level of product and process understanding, the results of quality risk management, and the effectiveness of the pharmaceutical quality system. When implemented, the effectiveness of the pharmaceutical quality system can normally be evaluated during a regulatory inspection at the manufacturing site. Potential opportunities to enhance science and risk based regulatory approaches are identified in Annex 1. Regulatory processes will be determined by region. 特定产品或生产车间的法规方法应与产品和工艺的理解水平，质量风险管理结果和制药质量体系效果相对应。一旦实施，制药质量体系的有效性一般会在生产现场的官方审计过程中得到评价。基于法规方法对科学和风险进行改进的潜在机会如附件所示。法规程序由各地区确定。1.5 ICH Q10 Objectives ICH Q10的目标Implementation of the Q10 model should result in achievement of three main objectives which complement or enhance regional GMP requirements. Q10模型的执行应该导致三个主要目标的完成，补充或提升地区GMP要求。1.5.1 Achieve Product Realisation获得产品实现To establish, implement and maintain a system that allows the delivery of products with the quality attributes appropriate to meet the needs of patients, health care professionals, regulatory authorities (including compliance with approved regulatory filings) and other internal and external customers. 建立，实施和维护一体系以允许产品的交付合适地满足患者，保健专业人员，药政机构（包括符合批准的法规）和其它内部和外部的顾客。1.5.2 Establish and Maintain a State of Control 控制状态的建立和维护To develop and use effective monitoring and control systems for process performance and product quality, thereby providing assurance of continued suitability and capability of processes. Quality risk management can be useful in identifying the monitoring and control systems. 开发和使用工艺性能和产品质量的有效监控和控制体系，以此为工艺持续适宜性和性能提供保证。质量风险管理有助于监控和控制体系的确定。1.5.3 Facilitate Continual Improvement 有助于持续改进To identify and implement appropriate product quality improvements, process improvements, variability reduction, innovations and pharmaceutical quality system enhancements, thereby increasing the ability to fulfil quality needs consistently. Quality risk management can be useful for identifying and prioritising areas for continual improvement. 确定和实施适宜的产品质量改进，工艺改进，变动减少，创新和制药质量体系改进，以此提高持续满足需求的能力。质量风险管理有助于改进领域的确定和优先排序。1.6 Enablers: Knowledge Management and Quality Risk Management 支持者：知识管理和质量风险管理Use of knowledge management and quality risk management will enable a company to implement ICH Q10 effectively and successfully. These enablers will facilitate achievement of the objectives described in Section 1.5 above by providing the means for science and risk based decisions related to product quality. 知识管理和质量风险管理的使用将使公司有效并顺利地执行ICH Q10。 它们有助于实现上述1.5章节所述的目的，为与产品质量相关的基于科学和风险的决定提供方法。1.6.1 Knowledge Management 知识管理Product and process knowledge should be managed from development through the commercial life of the product up to and including product discontinuation. For example, development activities using scientific approaches provide knowledge for product and process understanding. Knowledge management is a systematic approach to acquiring, analysing, storing and disseminating information related to products, manufacturing processes and components. Sources of knowledge include, but are not limited to prior knowledge (public domain or internally documented); pharmaceutical development studies; technology transfer activities; process validation studies over the product lifecycle; manufacturing experience; innovation; continual improvement; and change management activities. 产品和工艺知识管理应从开发一直到产品的商业生命，并包括产品终止。比如，研发活动通过科学的方法为产品和工艺理解提供知识。知识管理是获得，分析，保存和公布产品制造，工艺和组分相关信息的系统方法。知识来源包括，但不限于，先前知识（公共领域或内部文件），药物开发研究，技术转移活动，产品生命周期内的工艺验证，生产经验，持续改进和变更管理活动。1.6.2 Quality Risk Management 质量风险管理Quality risk management is integral to an effective pharmaceutical quality system. It can provide a proactive approach to identifying, scientifically evaluating and controlling potential risks to quality. It facilitates continual improvement of process performance and product quality throughout the product lifecycle. ICH Q9 provides principles and examples of tools for quality risk management that can be applied to different aspects of pharmaceutical quality. 质量风险管理是有效的制药质量体系的不可分割的部分。它能提供确定，科学评价和控制潜在质量风险的前摄性方法。它有助于产品生命周期内工艺性能和产品质量的持续改进。ICH Q9提供了用于制药质量不同方面的质量风险管理工具的原则和例子。1.7 Design and Content Considerations 设计和内容考虑(a) The design, organisation and documentation of the pharmaceutical quality system should be well structured and clear to facilitate common understanding and consistent application. 制药质量体系的设计，组织和文件应清晰，并有良好的结构，能有助于共识和持续应用。(b) The elements of ICH Q10 should be applied in a manner that is appropriate and proportionate to each of the product lifecycle stages, recognising the different goals and knowledge available for each stage. ICH Q10要素的应用需与产品生命周期的各个阶段相适应，应认识到各个阶段的不同目标和有用的知识。(c) The size and complexity of the companys activities should be taken into consideration when developing a new pharmaceutical quality system or modifying an existing one. The design of the pharmaceutical quality system should incorporate appropriate risk management principles. While some aspects of the pharmaceutical quality system can be company-wide and others site-specific, the effectiveness of the pharmaceutical quality system is normally demonstrated at the site level. 在开发新的制药质量体系或对现有体系进行改进时，应考虑到公司活动的规模和复杂性。制药质量体系的设计应适当地与风险管理原则相结合。当制药质量体系的有些方面是公司范围的而其它的是场地特定的，则制药质量体系效果一般来说应在场地这个水平上进行阐述。(d) The pharmaceutical quality system should include appropriate processes, resources and responsibilities to provide assurance of the quality of outsourced activities and purchased materials as described in Section 2.7. 制药质量体系应包括适当的工艺，资源和职责，按2.7章节描述的为外包活动和采购物料提供质量保证。(e) Management responsibilities, as described in Section 2, should be identified within the pharmaceutical quality system. 制药质量体系中应确定第2章节中所叙述的管理职责。(f) The pharmaceutical quality system should include the following elements, as described in Section 3: process performance and product quality monitoring, corrective and preventive action, change management and management review. 制药质量体系应包括第3章节所述的如下要素：工艺性能和产品质量监控，纠正和预防措施，变更管理和管理评审。(g) Performance indicators, as described in Section 4, should be identified and used to monitor the effectiveness of processes within the pharmaceutical quality system. 应当确认第4章节描述的性能指标，并用于监控制药质量体系内程序的有效性。1.8 Quality Manual 质量手册 A Quality Manual or equivalent documentation approach should be established and should contain the description of the pharmaceutical quality system. The description should include: 应建立质量手册或相当的文件，质量手册应包括制药质量体系的叙述。叙述应包括(a) The quality policy (see Section 2); 质量方针（见章节2）(b) The scope of the pharmaceutical quality system; 制药质量体系的范围(c) Identification of the pharmaceutical quality system processes, as well as their sequences, linkages and interdependencies. Process maps and flow charts can be useful tools to facilitate depicting pharmaceutical quality system processes in a visual ma