质量体系--有效质量管理体系的关键--奥星公司验证总监2011.10上海ISPE

ISPE-CCPIE CHINA CONFERENCE 2011 Quality System Key to the effective Quality Management System 质量体系有效质量管理体系的关键 Anwarul Haque, Validation Director, Austar 奥星公司验证总监 ISPE October 25-28 2011 Shanghai 1 Regulatory Perspective 法规问题 The holder of a Manufacturing Authorisation (MA) must manufacture medicinal products ensuring that: 生产许可证（MA）的持有人所生产的药品必须保证： Fit for their intended use符合预期用途 comply with the requirements of the MA符合MA中的要求 Do not place patients at risk due to inadequate safety, quality or efficacy.不会因安全性、质量或功效不当而对患者造成风险 Senior Management holds the responsibility for Quality objective (stated above) 高级管理层担负着质量目标的责任(如上所述) In attaining the objectives it requires participation and commitment by all stake holders to the company 在达到目标方面要求公司内的所有利益相关方的参与和承 诺 ISPE-CCPIE CHINA CONFERENCE 2011 Regulatory Perspective Contd 法规问题-续 To achieve the quality objective reliably there must be a comprehensively designed and correctly implemented system of QA incorporating GMP 为可靠地达到质量目标，必须有经过综合设计和正 确实施且集成了GMP的质量保障系统。 Quality objectives fully documented and its effectiveness monitored 质量目标应有完整的文件记录并对其有效性进行监 控。 All parts of the Quality Assurance system should be adequately resourced 质量保证系统的所有部分均应配备有充分的资源。 ISPE-CCPIE CHINA CONFERENCE 2011 Regulatory Findings 监管检查问题 Zhang Aiping (Director of Center for Certification of Drug, SFDA) 国家食品药品监督管理局药品认证管理中心主任张爱萍: “ We found that the defects are concentrated in the effectiveness of such quality systems as the QC system and the QA system. The problems are mainly in insufficient understanding, inaccurate grasping and the inexperience in using the elements of the quality assurance system. Especially that there are such problems as insufficiently established procedures or failures in completing corresponding activities as required in the established procedures in such areas as change control, deviation handling and corrective and preventive actions (CAPA). They are inflexible in implementing such new concepts as trend analysis, alert limits, action limits, annual product quality review, etc. . They are still at an early stage in the use of quality risk management and they are not fully combined with their own experiences or the actual production situations. These defects have reflected that the enterprises have not integrated GMP concepts into each of the steps of their quality system management activities and product quality risk management has not been effectively implemented.” 张爱萍：我们对已进行现场检查的企业和进行模拟检查的企业做了分析对比发现，缺陷比较 集中地体现在质量控制与质量保证等质量体系有效性方面，问题突出体现在对质量保证体系 构成要素理解不清楚，把握不准确，使用不熟练等。特别是对变更控制、偏差处理、纠正和 预防措施（CAPA)方面，存在程序制定不够完善，或者未按照制定的程序要求完成相应工作 的情况；对于趋势分析、警戒线、纠偏线、年度产品质量回顾分析等新概念的应用较为机械 ，存在生搬硬套的情况，没有与自己实际情况结合起来；对于质量风险管理的使用尚处于初 期，没有完全与自己已有的经验以及产品或生产的实际情况结合。这些缺陷反映出目前企业 尚未完全将药品GMP的精髓有机地融入到其质量体系管理的各个环节中，产品质量的风险 管理还未得到有效贯彻。 ISPE-CCPIE CHINA CONFERENCE 2011 Quality Management System 质量管理系统 QMS A quality management system (QMS) is an organizational structure implemented by a company and consists of procedures, processes and resources used for quality management. QMS is designed to increase performance and quality within an organization 质量管理系统（QMS）是公司为进行质量管理而实施的一种组织结构 ，包括规程、工艺和资源。 QMS设计用于提高组织内部的业绩和质 量。 Purpose目的 A QMS is implemented to promote quality and efficiency within a company. QMSs rely on creating procedures for the processes used in producing a product or service. QMS的实施目的是为了提高公司内部的质量和效率。 QMS依赖于为 用于生产产品或提供服务的工艺流程制定相应规程。 ISPE-CCPIE CHINA CONFERENCE 2011 Product Lifecycle 产品生命周期 There are 4 phases of product lifecycle: 产品生命周期有4个阶段： Pharmaceutical Development制药研发 Technology Transfer技术转移 Commercial Manufacturing商业化生产 Product Discontinuation产品停产 For each of the above phases the QMS needs to be appropriate for that phase 需针对上述每个阶段制定适宜的规定 QMS ISPE-CCPIE CHINA CONFERENCE 2011 Quality Risk Management 质量风险管理 Quality risk management is integral to an effective QMS 质量风险管理是有效QMS中不可分 割的一部分。 It provides a proactive approach 它提供了一种积极主动的方法 It facilitates continual improvement of process performance and product quality throughout the product lifecycle. 它有助于在产品的整个生命周期过 程中对工艺性能和产品质量进行持 续改进。 ISPE-CCPIE CHINA CONFERENCE 2011 The Objectives of QMS QMS的目的 Achieve Product Realisation 实现产品生产 Establish and Maintain a State of Control 建立并维持受控状态 Facilitate Continual Improvement 帮助进行持续改进 ISPE-CCPIE CHINA CONFERENCE 2011 The Objectives of QMS QMS的目的 实现 Achieve Product Realisation 产品生产It should allow the delivery of products with the quality attributes appropriate to meet the needs of: 应使得可以生产出符合如下方面要 求的质量属性的产品： - patients 患者要求 - health care professionals医疗保健 专业人员的要求 - regulatory authorities法规当局的 要求 - internal and external customers内 部及外部客户的要求 ISPE-CCPIE CHINA CONFERENCE 2011 The Objectives of QMS (contd) QMS的目的（续） Establish and Maintain a State of 建立并维持受控状态 Control Develop and use effective monitoring and control systems for process performance and product quality 制定并使用用于监控工艺性能和产品质 量的有效监视和控制系统 Quality risk management can be useful in identifying the monitoring and control systems. 质量风险管理在确定监视和控制系统方 面非常有用。ISPE-CCPIE CHINA CONFERENCE 2011 The Objectives of QMS (contd) QMS的目的（续） 帮助进 Facilitate Continual Improvement 行持续改进 Identify and implement appropriate product quality improvements, process improvements, variability reduction, innovations and quality system enhancements 确定并实施适宜的产品质量改进、工艺改进 、可变因素缩减、创新和质量系统改进措施 Again quality risk management can be useful for identifying and prioritising areas for continual improvement. 同样，质量风险管理在确定持续改进区域并 确定其优先级别方面非常有用。ISPE-CCPIE CHINA CONFERENCE 2011 Design of QS QS的设计 The design, organisation and documentation of the QMS should be well structured and clear QMS的设计、组织和文件编制应具有良好的组织结构且非常明确 QS should reflect the size and complexity of the companys activities QS应反映公司业务的规模和复杂性 Risk management principles should applied to the design 设计中应采用风险管理的原则 QMS aspects can be company-wide and or some aspects can be site-specific QMS的某些方面可以是全公司范围的而某些方面则可以是针对具体厂 区的 Note: Effectiveness of the pharmaceutical quality system is normally demonstrated at the site level. 备注：制药质量系统的有效性通常是在厂区层次进行证明的 ISPE-CCPIE CHINA CONFERENCE 2011 Content of QS QS的内容 Appropriate processes, resources and 适宜的流程、资源和职责 responsibilities 管理职责 Management responsibilities QMS includes the following elements: QMS包括如下成分： process performance and product quality monitoring工艺性能和产品质量监控 CAPA change management变更管理 management review管理审查 Performance indicators性能指标 ISPE-CCPIE CHINA CONFERENCE 2011 Management Responsibilities 管理职责 Design, implementation, monitor and maintain the QS QS的设计、实施、监控和维护 Quality Policy质量方针 Quality Planning质量计划 Ensure QS implementation throughout the organisation 保证QS在全公司范围内的实施 Provide escalation process to raise quality issues in a timely manner 提供逐级汇报流程及时报告质量 问题 ISPE-CCPIE CHINA CONFERENCE 2011 Management Responsibilities (contd) 管理职责（续） Define roles, responsibilities & at all levels 界定所有级别的职责、职能 Review process performance and product quality and the QMS 对工艺性能、产品质量和QMS进行 审查 Manage purchased materials 管理所购置物料 Manage outsourced activities 管理外包工作 Provide appropriate resources 提供适宜的资源 ISPE-CCPIE CHINA CONFERENCE 2011 Quality Manual质量手册 Quality Manual (QM) should contains description of the QS as well as: 质量手册（QM）中应包括有关QS的描 述以及： The quality policy 质量方针 The scope of the quality system 质量系统的范围 Identification of the QMS processes QMS流程的确定 Management responsibilities 管理职责 ISPE-CCPIE CHINA CONFERENCE 2011 Quality Policy质量方针 Quality Policy should describes the overall intentions and direction of the company related to quality 质量方针应对公司与质量相关的整体目 的和方向进行描述 States compliance with applicable regulatory requirements 说明所符合的适用法规要求 Provides mechanism for CI of the quality system 提供质量系统CI的机制 Understood by all stakeholders of the company 为公司的所有利益相关方所理解 Reviewed periodically 定期审查 ISPE-CCPIE CHINA CONFERENCE 2011 Quality Planning质量计划 Quality objectives should be defined and communicated 应制定处质量目标并对其进 行沟通 All stake holders should buy in to Quality objectives 质量目的应获得所有利益相 关方的同意 ISPE-CCPIE CHINA CONFERENCE 2011 Quality Planning (contd) 质量计划（续） Aligns quality objectives with the companys strategies and be consistent with the quality policy 使质量目标与公司的策略相符并与质量方针保持一致 Appropriate resources and training arrangement 适宜的资源和培训安排 Set performance indicators against quality objectives established, monitored & published 针对所建立、监控和公布的质量目标设定性能指标 Extend the QS to the control and review of any outsourced activities and quality of purchased materials 扩展QS至任何外包工作的控制和审查及外购原料的质量。 ISPE-CCPIE CHINA CONFERENCE 2011 QS Elements QS的成分 The elements of QS are: QS的成分为： Process performance and product quality monitoring system 工艺性能和产品质量监控系统 Corrective action and preventive action (CAPA) system 纠正和预防措施（CAPA）系统 Change management system 变更管理系统 Review of process performance and product quality 工艺性能和产品质量的审查 ISPE-CCPIE CHINA CONFERENCE 2011 Process performance and product quality 工艺性能和产品质量 Process performance and product quality to ensure a state of control is maintained 工艺性能和产品质量以保证保持 受控状态 Provide tools for measurement and analysis of parameters and attributes 提供测量工具和参数及属性分析 Analyse parameters and attributes to verify state of control 对参数和属性进行分析以检查确 认控制状态 ISPE-CCPIE CHINA CONFERENCE 2011 Process performance and product quality 工艺性能和产品质量 Continual improvement activities - reduce or control variation 持续改进工作降低或控制可变性 Feedback mechanism on product quality 产品质量的反馈机制 Enhance process understanding 促进对工艺的理解 Enable innovative approaches to process validation 启用工艺验证的创新型方法 ISPE-CCPIE CHINA CONFERENCE 2011 Corrective Action and Preventive Action (CAPA) System 纠正和预防措施（CAPA）系统 CAPA resulting from the investigation of: CAPA是因如下情况的调查研究而导致的： Complaints投诉 product rejections产品剔除 non-conformances不符合 Recalls召回 Deviations偏差 Audits审计 Regulatory inspections and findings法规检查和检查结果 Trends from process performance and product quality monitoring 工艺性能和产品质量监控的趋势 The level of effort, formality, and documentation of the investigation should be commensurate with the level of risk 调查工作量、程序和文件的程度应与风险的程度相匹配 ISPE-CCPIE CHINA CONFERENCE 2011 Change Management System 变更管理系统 An effective change management system should provide a high degree of assurance there are no unintended consequences of the change 有效的变更管理系统应能高度保证 变更不会导致预期之外的后果。 Oversight of CM by the quality unit 由质量部门对变更管理进行监管 Change assessment should be science and risk based 应以科学和风险为基础进行变更评 估 ISPE-CCPIE CHINA CONFERENCE 2011 Process Performance and Product Quality Review 工艺性能和产品质量的审查 Management of process performance and product quality to be reviewed over the lifecycle of the product 应在产品的整个生命周期过程中对工艺性能和产品质量的 管理进行审查 Should be a formal process 应是一种正式的流程 Should be done periodically 应定期进行 Review includes but not limited to: 审查范围包括但并不仅限于： Measurement of achievemen