与制药工程项目全过程相整合的调试与确认服务卢浩荣

Commissioning&Qualification Services Integrated into the Pharmaceutical Project Lifecycle 与制药工程项目全过程相整合的调试与确认服务Presented by Lu,Haorong 卢浩荣Reviewed by Henk Man Agenda议程 Introduction 导言 Definition and Contents Of I-C&Q Service I-C&Q服务的定义与内容 Services Provider and Stakeholders 服务提供商及相关方 Necessity必要性 Implementation 实施 References and Acknowledgements 参考文献与致谢2012 ISPE CHINA ANNUAL CONFERENCEIntroduction 导言导言 Concepts 概念概念Good Engineering Practice良好工程规范良好工程规范Established engineering methods and standards that are applied throughout the project lifecycle to deliver appropriated cost-effective solution.在项目周期中全程采用已建立的工程方法和标准，以交付合理的、经济有效的解决方案。Commissioning调试调试A well planned,documented and managed engineering approach to the start-up and turnover of facilities,systems,and equipment to the End-User that results in a safe and function environment that meets established design requirements and stakeholder expectations.采用一套良好计划的、有文件记录并受管理的工程方法，对工程设施、系统和设备进行试车并交付最终用户，以建立符合既定设计要求及股东期望的安全、功能良好的环境。2012 ISPE CHINA ANNUAL CONFERENCEIntroduction 导言导言 Concepts(cont.)概念（续）概念（续）DQ设计确认设计确认The documented verification that engineering design of a facility,utility or equipment that can affect product quality adhere to approved User Requirement and design specifications.对可能影响产品质量的设施、公用工程和设备的工程设计进行有文件记录的查证，确认与被批准的用户需求和设计描述一致。IQ安装确认安装确认 The documented verification that all aspects of a facility,utility or equipment that can affect product quality adhere to approved specifications and are correctly installed.对设施、公用工程和设备所有可能影响产品质量的方面进行有文件记录的查证，确认与被批准的描述一致并已得到正确的安装。2012 ISPE CHINA ANNUAL CONFERENCEIntroduction 导言导言 Concepts(cont.)概念（续）概念（续）OQ操作确认操作确认The documented verification that all aspects of a facility,utility,or equipment that can affect product quality operate as intended throughout all anticipated ranges.对设施、公用工程和设备所有可能影响产品质量的方面进行有文件记录的查证，确认它们在预期的操作极限内运行正确。PQ性能确认性能确认The documented verification that all aspects of facility,utility,or equipment that can affect product quality perform as intended meeting predetermined acceptance criteria.对设施、公用工程和设备所有可能影响产品质量的方面进行有文件记录的查证，确认其性能符合预先确定的验收标准。2012 ISPE CHINA ANNUAL CONFERENCEIntroduction 导言导言 Concepts(cont.)概念（续）概念（续）PV工艺验证工艺验证The process of establishing documented evidence which provides a high degree of assurance that a specific process will consistently produce a product meeting its pre-determined specifications and quality attributes.建立文件证据，高度保证在特定生产工艺条件下，可均一地生产符合预定标准和质量属性的产品的过程。More concepts 更多的概念更多的概念 Risk Based Commensurate with risk 基于风险与风险相适应 Science Based CQA,CPPs 基于科学关键质量属性、关键工艺参数 Quality by Design Verify throughout 质量源于设计全过程的验证 Subject Matter Expert Defined Role 学科问题专家角色定义2012 ISPE CHINA ANNUAL CONFERENCEIntroduction 导言导言Current Issues Relative to C&Q in Chinese Pharmaceutical Industry 当当前中国医药工业中调试与确认的相关问题前中国医药工业中调试与确认的相关问题 Limited resource and focus on DQ and QBD is not well acknowledged.投入资源有限，对设计确认、质量源于设计等的重点未充分认识。Very rare professional C&Q consultants aligned with international standard and practice.专业的、与国际标准、规范接轨的调试与确认咨询服务提供商非常罕见。Lack of local presence of international C&Q consulting expertise and the corresponding local professional engineer supportive team.国际知名调试与确认专家罕有常驻中国本地，同时缺乏与其配套的本地专业工程师支持团队。Importance of establishing a real QMS based on good C&Q practices is not well acknowledged by endorser top management.以良好的调试与确认实践为基础建立一个真正的质量管理体系的重要性并未被企业高层管理人员充分认识。2012 ISPE CHINA ANNUAL CONFERENCEIntroduction 导言导言Current Issues Relative to C&Q in Chinese Pharmaceutical Industry（cont.）当前中国医药工业中调试与确认的相关问题当前中国医药工业中调试与确认的相关问题 （续）（续）Seldom correct applications of risk assessment approach and over-interpreting of GMP regulations without understanding their rationales led to overinvestment of the project.风险分析方法罕有正确应用，未能从基本原理上进行理解，若干GMP法规被过度解读导致项目过度投资。Seldom systematic planning at the very beginning,most are crash jobs in the final phase of the project.鲜有在项目开始即进行系统性的策划，大部分在项目后期进行突击。Frequent change orders due to issues exposed in the final C&Q phase led to significant cost of remedy and delay.因最终调试与确认阶段暴露的问题而产生的变更导致可观的索赔及工期延误。2012 ISPE CHINA ANNUAL CONFERENCEIntroduction 导言导言Current Issues Relative to C&Q in Chinese Pharmaceutical Industry（cont.）当前中国医药工业中调试与确认的相关问题当前中国医药工业中调试与确认的相关问题 （续）（续）Unclear interfaces and poor communications of the different project parties led to considerable overlapping or missing of project works,commissioning integration with qualification is rare.不同项目参与方节点不清，沟通不畅导致相当的项目工作重叠或漏项,罕有调试与确认进行整合。Due to lack of specialized C&Q people,most of the C&Q jobs rely on sub-contractors or vendors,the jobs quality is not under control,and the owner or the EPC contractor has to pay extra charges for each equipment or system.由于缺乏专业的调试与确认人员，大部分的调试与确认工作依赖于分包商或供应商，工作质量不可控，而业主或总承包商不得不为每一设备或系统付出额外的费用。2012 ISPE CHINA ANNUAL CONFERENCEIntroduction 导言导言Current Issues Relative to C&Q in Chinese Pharmaceutical Industry（cont.）当前中国医药工业中调试与确认的相关问题当前中国医药工业中调试与确认的相关问题 （续）（续）Though several Q&V consultants available,the scope and standards of works are undetermined,and therefore both quantity and quality of their works are hard to evaluate.尽管有数家确认与验证咨询服务提供商，但工作范围与标准不明确，因而工作的数量与质量都很难评估。Due to absence of SME in some disciplines,the Q&V consultants sometimes can only reveal the defects in the project,but fail to present the cost-effective solutions for them,especially when the GMP conflicts with local codes,e.g.fire fighting or EHS codes.由于某些专业的专家欠缺，确认与验证咨询服务提供商有时仅能揭示项目的某些缺陷，但不能给出相应的经济有效的解决方案，尤其是在GMP与国内规范，如消防、环保、职业安全卫生规范发生冲突时。2012 ISPE CHINA ANNUAL CONFERENCEIntroduction 导言导言Gap to Current Good Practices of the International Pharmaceutical Industry 与当前国际医药工业良好实践的差距与当前国际医药工业良好实践的差距Aspects 方面方面China 中国中国International 国际国际Marketing Environment市场环境Obvious demand,limited investment,development required需求明显但投入有限，需要培育Regular demand,worth to invest,mature and normative需求一般，认为投入值得，成熟、规范Professionals专业人员Limited quantity,inexperienced,discipline-absent 数量、经验有限，学科配套不齐全 Abundant,experienced,complete disciplines，high-cost 数量充足，经验丰富，学科齐全,费用昂贵Organization机构Temporal,project based,lately involve 临时、基于项目、后期介入Standing,multi-projects,life-cycle involved 常设，多项目，全程Implementation执行Random,no strict procedure,absent or overlapping随意，无严格程序，漏项或重叠Normative,strict procedure,integrity 规范、程序严格、过程完整Documentation文件Poor integrity,irregular,non-real-time，reference absent 完整性差，不规范，非实时，引用失缺 Good integrity,normative,real-time,complete reference,credible完整性好，规范，实时，引用齐全可信2012 ISPE CHINA ANNUAL CONFERENCE Definition 定义定义Commissioning&qualification services integrated into the pharmaceutical project lifecycle（I-C&Q Services)are the valuable consulting services provided by a professional C&Q consultant to help owner or EPC contractor to implement the commissioning and qualifications of design,installation,operation,performance of facilities,systems,and equipments,and finally the process validation of the facilities of a pharmaceutical project by applying GEP,GMP principles and engineering experiences，beginning with developing the OPR and extending through all phases of project delivery and into operation and maintenance.与制药工程项目全过程相整合的调试与确认服务与制药工程项目全过程相整合的调试与确认服务(I-C&Q(I-C&Q服服务）务）系由专业调试与确认咨询商提供有价值的咨询服务，应用GEP、GMP原则和工程经验，从形成业主项目需求开始扩展到项目交付、直到运行和维护等所有阶段，提供有价值的咨询服务，帮助业主或总承包商完成制药工程项目中设施、系统、设备的调试以及设计、安装、运行、性能等一系列确认乃至设施的工艺验证等。Definition and Contents of I-C&Q Services I-C&QI-C&Q服务的定义与内容服务的定义与内容Definition(cont.)定义（续）定义（续）When Does Commissioning Occur?调试的时机调试的时机Commissioning can begin during pre-design,design,construction or building start-up.The process can offer significantly greater and more cost effective benefits when it begins during pre-design or early design.调试可从设计前、设计、施工或开车的时候开始。当从设计前或者设计早期开始时，该过程能产生更大并更经济有效的效益。Commissioning integration into qualification调试与确认的整合调试与确认的整合Commissioning can support qualification if performed within a qualification regime.In this case,it is critical to define the over-all scope of the tests and verifications to be performed for a system,before starting any commissioning or qualification work.当按确认的制度来进行时，调试可用以支持确认，关键是在开展调试与确认工作前，应定义系统测试与查证的所有范围。13Definition and Contents of I-C&Q Services I-C&QI-C&Q服务的定义与内容服务的定义与内容Test&BalanceStart-up Testing Definition(cont.)-Commissioning Span of Control 定义定义(续续)-)-调试跨度的控制调试跨度的控制Commissioning 设计前调试开车测试设计施工开车运行及维护测试及平衡Source（来源）:D.Colburn et al.(2003)I-C&QC&QRisk Management 风险风险管理管理Design Review 设计审设计审核核Change Management 变变更管理更管理Good Engineering Practice良好工程良好工程规规范范ASTM E2500-07:Standards for Specification,Design&Verification of Pharmaceutical&Biopharmaceutical Manufacturing Systems&Equipment Definition(cont.)-Flexible Approach ASTM E2500 定义定义(续续)-ASTM E2500-07)-ASTM E2500-07柔性方法柔性方法15ISPE Baseline Guide 5 Design Inputs设计输入 Impact Assessment 影响评估 Design Qualification 设计确认 Commissioning 调试 Multiple Trial Runs to Get Things Right 多次试运行以达标 IQ,OQ,PQ and Acceptance Criteria IQ,OQ,PQ及接受标准 GEP scope and QA scope overlapped GEP和QA范围重叠 Focused on Documentation Deliverables 注重关注文件 Rigid Change Management刚性的变更管理ASTM E2500 Design Inputs设计输入 Design Review设计审核 Risk Mitigation降低风险 Critical Control Parameters Define Acceptance Criteria 关键控制参数定义接受标准 Verification Testing确认测试 Performance Testing 性能测试 GEP scope and QA scope have clear boundary GEP和QA界限清晰 Process,Product Quality and Patient Safety工艺，产品质量和病人安全 Quality by Design,Design Space and Continuous Improvement质量源于设计，设计空间及持续改进Definition and Contents of I-C&Q Services I-C&QI-C&Q服务的定义与内容服务的定义与内容Definition(cont.)定义（续）定义（续）Source（来源）:IT Pharma Validation Europe(2008)162012 ISPE CHINA ANNUAL CONFERENCE Contents服务内容服务内容Represents“owner“as an objective advocate 作为目标宣传者代表业主Guides the development of F-URS,URS 指导编制设施URS及系统URSOrganizes or attends gap analysis,impact assessment,risk assessment and DR or DQ组织或参加偏差分析、影响分析、风险评估以及设计审核或设计确认Reviews standards/strategies early in design 在设计阶段审核标准/策略Develops the Cx Plan and VMP编制调试计划及验证总计划Definition and Contents of I-C&Q Services I-C&QI-C&Q服务的定义与内容服务的定义与内容2012 ISPE CHINA ANNUAL CONFERENCE Contents(cont.)服务内容（续）服务内容（续）Develops Cx contract language for the A/E&Construction contracts 编制建筑/工程设计及施工合同中的调试条款Guides the Development Quality System Program and Implementation Plan 指导编制质量体系程序及实施方案Guides the total C&Q process 指导调试、确认全过程Ensures implementation of selected measures identified in the OPR 确保业主项目需求中明确的选择措施的实施Verifies minimum targets have been met 查证最低目标已满足Completes final C&Q report 完成最终调试、确认报告Definition and Contents of I-C&Q Services I-C&QI-C&Q服务的定义与内容服务的定义与内容2012 ISPE CHINA ANNUAL CONFERENCE Contents(cont.)服务内容（续）服务内容（续）Guides Computer System Validation指导计算机系统验证 Guides Analytical Instrument Qualification and Analytical Method Analysis指导分析仪器确认与分析方法验证 Guides Cleaning,Sterilization,and Fumigation Validation指导清洁、灭菌、熏蒸验证 Guides the PV process,completes PV report 指导工艺验证过程，完成工艺验证报告 Coordinates system testing and operator training 协调系统测试和操作人员培训Definition and Contents of I-C&Q Services I-C&QI-C&Q服务的定义与内容服务的定义与内容2012 ISPE CHINA ANNUAL CONFERENCE Service Packets Breakdown 服务工作包分解服务工作包分解Gap analysis and URS development guidance偏差分析及设施用户需求编制指导GMP review GMP审核System Impact Assessment and Validation Master Plan development 系统影响评估与验证总计划编制Quality system program and implementation plan development Guidance 质量体系程序及实施方案编制指导Definition and Contents of I-C&Q Services I-C&QI-C&Q服务的定义与内容服务的定义与内容2012 ISPE CHINA ANNUAL CONFERENCE Service Packets Breakdown(cont.)服务工作包分解服务工作包分解 （续）（续）Risk Analysis and S-E/URS SOP,VP development guidance 风险分析及设备/系统用户需求、验证计划编制指导Commissioning Plan and Qualification Protocol development guidance调试计划和确认方案编制指导Component Impact Assessment,Risk Assessment guidance and DQ 组件影响分析、风险分析指导与设计确认IQ，OP，PQ guidance安装确认、运行确认、性能确认指导Computer System Validation guidance计算机系统验证指导Definition and Contents of I-C&Q Services I-C&QI-C&Q服务的定义与内容服务的定义与内容2012 ISPE CHINA ANNUAL CONFERENCE Service Packets Breakdown(cont.)服务工作包分解服务工作包分解 （续）（续）Analytical Instrument Qualification and Analytical Method Validation Guide分析仪器确认与分析方法验证指导Cleaning,Sterilization,and Fumigation Validation guide 清洁、灭菌、熏蒸验证指导Process Validation guide工艺验证指导Definition and Contents of I-C&Q Services I-C&QI-C&Q服务的定义与内容服务的定义与内容2012 ISPE CHINA ANNUAL CONFERENCEServices Provider and Stakeholders 服务提供商及相关方服务提供商及相关方The Qualified Service Team Structure 合格的服务团队人员构成合格的服务团队人员构成Based on the project scope,resource requirements,and the key stakeholders;取决于项目的范围、资源需求以及主要相关方;Experienced and professional in individual field;在相应领域具有经验和专业素养Need to understand the roles,responsibilities,and levels of authority;应能理解自身的角色、责任以及权力层次；Have excellent communication,planning,and coordination between different parties.与不同的项目参与方间有很好的沟通、计划与协调。2012 ISPE CHINA ANNUAL CONFERENCEServices Provider and Stakeholders 服务提供商及相关方服务提供商及相关方The Qualified Service Team Structure(cont.)合格的服务团队人员构成（续）合格的服务团队人员构成（续）Including but not limited to,包括但不限于，pTeam leader 团队领导pCompliance and regulatory expert 合规和法规专家pMechanical C&Q engineer(HVAC,utilities)机械调试与确认工程师（暖通、公用）pProcess equipment/system C&Q engineer 工艺设备、工艺系统调试与确认工程师2012 ISPE CHINA ANNUAL CONFERENCEServices Provider and Stakeholders 服务提供商及相关方服务提供商及相关方The Qualified Service Team Structure(cont.)合格的服务团队人员构成（续）合格的服务团队人员构成（续）pComputer system validation engineer(software and hardware)计算机系统验证工程师pAMV engineer and process validation engineer 分析方法验证工程师及工艺验证工程师pCleaning，sterilization,and fumigation validation engineer 清洁，灭菌，熏蒸验证工程师pDocument coordinator and technical writer文件协调控制员及技术文件编制人员 2012 ISPE CHINA ANNUAL CONFERENCEServices Provider and Stakeholders 服务提供商及相关方服务提供商及相关方The Qualified Service Team Structure(cont.)合格的服务团队人员构成（续）合格的服务团队人员构成（续）pOutsource support subject matter experts of compliance and regulatory,mechanical(HVAC,utilities),process&equipment,clean finishing,operation,QC/QA,QMS etc.合规和法规、机械（暖通、公用）、工艺与设备、洁净装修、运行、质量控制与质量保证、质量管理体系等外部学科问题支持专家。2012 ISPE CHINA ANNUAL CONFERENCEOther Project Parties 其它项目参与方其它项目参与方p A/E consultants 工程设计pProcurement 采购pConstruction 施工pProject management 项目管理pCommissioning leaders or coordinator from contractors and owner 承包商、业主调试负责人或协调员 pOperations/Production,maintenance,R&D,EHS,QC,QA,Qualification&Validation from the owner 业主生产运行、维护、研发、环保及健康安全、QC、QA、确认与验证等部门Services Provider and Stakeholders 服务提供商及相关方服务提供商及相关方2012 ISPE CHINA ANNUAL CONFERENCEThe Authorities 监管部门监管部门pFood&Drug Administration食品药品监督部门 pMunicipal planning&construction administration规划、建设管理部门pEnvironmental Protection环保部门pFire authority消防部门pSafety Supervision Administration安全监督部门pLabor Protection 劳动保护部门pQuality Supervision 质量监督部门 Services Provider and Stakeholders 服务提供商及相关方服务提供商及相关方2012 ISPE CHINA ANNUAL CONFERENCERegulatory Requirements 法规要求法规要求 Necessity必要性必要性Source（来源）:R.E.Chew and D.Petko(2007)pEU GMP Annex 15 and SFDA GMP Chap.7“Qualification and Validation”define the requirements.欧盟GMP附录15和中国GMP第七章“确认与验证”有明确要求。pRelationship of ASTM Standard to GMP regulations and guidance documentsASTMASTM标准与标准与GMPGMP法规和指南文件的关系法规和指南文件的关系日本美国欧盟诸如CFR 211.68“设备应按书面程序进行校验、检查、或核对以确保其恰当性能”等条款是确认的基础ICH Q9 质量风险管理可用来决定“确认”的范围指导如何执行ASTM标准的主要原理及基本原则阐明基于风险的查证（或确认）的原理及基本原则 Benefits to the Owner 为业主带来的好处为业主带来的好处 Risk controlled earlier 风险及早得到控制 Reduce time and cost to achieve and maintain compliance降低项目完成所耗费用与时间并维持项目的合规性 Reduce change orders during construction 减少施工过程的变更令 Less waste&repetition 更少的浪费与重复 Reduce project delays 较少项目推迟 Shorten building turnover period 缩短建筑交付周期 Validation team and QMS set up 建立验证团队和质量管理体系 Earlier released and commercial manufacture 更早地通过认证并投入商业生产 Necessity必要性必要性 Benefits to the Owner(cont.)为业主带来的好处为业主带来的好处(续）续）Cost effective operation and maintenance经济高效的运行及维护 Reduce equipment replacement 减少设备更换 Better knowledge,understanding of systems 对系统更好的认识和理解 Better trained operations staff 更好地培训运行团队 Operations and maintenance manuals are complete and submitted at project turnover.运行及维护手册完成并在项目交付时提交Necessity必要性必要性 Benefits to the Contractors对承包商的好处对承包商的好处 Better planning will result in improved installation 更好的计划可导致安装的改进 More emphasis on quality control on what matters 对质量控制更加强调 Quicker resolution of problems(identify problems during QC)更快地解决问题（在QC过程中界定问题）Increase likelihood of completing project on schedule maximize profit 提高按时完成项目的可能性利润最大化 Reduce post-construction callbacks preserve profit 减少施工后召回保护利润Necessity必要性必要性 Benefits to the Authorities 对监管部门的好处对监管部门的好处 Genuine,valid and systemic documentations 文件真实、有效、系统 Easy of inspection 便于检查 Genuine,credible records and trends 真实可信的记录与趋势 Easy of supervision 便于监管 Clear management programs,integral approvals in manufacturers site 厂商管理程序清晰，审批完整 Easy of investigation afterwards便于事后追究Necessity必要性必要性Implementation Flow of Pharmaceutical Project制药工业项目实施流程制药工业项目实施流程Production Start有效投产Feasibility Study可行性研究Concept Design概念设计Procurement采购Construction 施工Detail Engineering详细设计SupportValidation验证支持 C&Q 调试与确认Decision“GO”客户决定工程继续进行Basic+Ext.Basic Engineering基本扩充设计Final investment Decision 客户做出最终投资决定Cost Estimate造价估算 20%Cost Estimate造价估算 10%Concept Phase 概念阶段 Design Phase 设计阶段Execution Phase 实施阶段 Hand Over交付Validation Phase验证阶段MaintenanceCustomer Service维修/客户服务Facility Management设施管理Second Opinion Value Engineering 修改/补充Implementation 实施实施 Workflow 工作流程工作流程Acknowledgement（感谢）:Instruction from Mr.D.W.Vincent F(设施)-URSGA偏差分析BOD设计基础VMP验证总计划RA风险分析E/S(设备/系统)-URSVP验证计划CSVFD/FS功能设计/说明DD/DS详细设计/设计说明CP(FAT,SAT,etc.),Qual.Protocol 调试计划及确认方案PQ性能确认OQ运行确认IQ安装确认Commissioning(FAT/SAT,etc.)Exec.调试（工厂/现场验收测试等）执行DQ设计确认Procurement&Construction采购施工CV清洁验证Sterilization Validation灭菌验证PV工艺验证Medium Fill培养基灌装Utility Qua/Val公用系统确认/验证Fumigation Validation熏蒸验证AIQ分析仪器确认CSV计算机系统验证CSV计算机系统验证CSV计算机系统验证AMV分析方法验证SIA系统影响评估GMP Rev.GMP审核Implementation 实施实施 Workflow 工作流程工作流程 Acknowledgement（感谢）:Instruction from Mr.C.Bachofen Workflowa brief case study(WFI system)工作流程工作流程 简略的案例分析简略的案例分析(注射用水系统）注射用水系统）p Specify the final users,capacity,standards，etc.to be followed for WFI.system in F-URS 在设施URS中明确注射用水系统的终端用户、供应能力以及遵循的标准等。p Implement GA for the renovated systems.对改造的系统进行偏差分析。p Develop the schematic design of WFI system(e.g.MB,PFD，main equipment list)in the BOD of the facility（design consultant).在设施的设计基础中进行 注射用水系统的方案设计（物料平衡、工艺流程图,主要设备表等）(设计咨询方）。Implementation 实施实施 Workflowa brief case study(WFI system)（cont.)工作流程工作流程 简略的案例分析简略的案例分析(注射用水系统）注射用水系统）(续）续）p Implement the IA of the WFI system according to the criteria.按照判据进行注射用水的影响评估。p Specify the level of C&Qs(including CSV)and the rationale of the system in VMP.在验证总计划中阐明调试确认(包括计算机系统验证）的程度及原因.p Develop the URS of the system(including the C&Q requirement),VP based on RA.在风险分析的基础上编制系统的URS及验证计划.Implementation 实施实施 Workflowa brief case study(WFI system)（cont.)工作流程工作流程 简略的案例分析简略的案例分析(注射用水系统）注射用水系统）(续）续）p Develop FS、DS for the WFI system(BD,DDdesign consultant or contractor).编制注射用水系统的功能说明、设计说明（基础设计、详细设计设计方或承包商）。p Develop the Commissioning(e.g.FAT/SAT)plan and DQ、IQ、OQ protocols for the WFI system with a C&Q integrated approach.以调试与确认相整合的方式编制调试（如FAT/SAT）计划和 DQ、IQ、OQ方案。p Implement the DQ of the WFI system with structural review approach and FEMA(based on C-IA)采用结构化审核方式和建立在部件影响评估基础上的潜在故障形式和影响分析（设计FMEA)进行注射用水系统的设计确认。Implementation 实施实施 Workflowa brief case study(WFI system)（cont.)工作流程工作流程 简略的案例分析简略的案例分析(注射用水系统）注射用水系统）(续）续）p Implement the construction、commissioning、IQ、CSV、OQ according to the approved DD、commissioning plan and qualification protocols with the integrated approach采用整合方式按批准的详细设计、调试计划和确认方案实施注射用水系统的施工、调试、安装确认、计算机系统验证、运行确认。p Implement PQ/validation（approve the SOPs,verify control,verify long-term control)of the WFI system based on OQ,and relative AIQ、AMV、relative CV、SV、U-Q/V.在运行确认以及相关分析仪器确认、分析方法验证、清洁/消毒验证，公用系统确认/验证的基础上实施PQ或注射用水系统验证(水质检测通过并批准运行SOP、验证受控、验证长期受控）。Implementation 实施实施 2012 ISPE CHINA ANNUAL CONFERENCEInterfaces with Other Project Parties 与其它项目参与方的接口与其它项目参与方的接口 Implementation 实施实施 用户需求规格（URS）1Contracts,FS,DS采购合同、说明书和规格2Sampling Records厂家提供的试样记录2FAT/SAT1,I&C Records厂家安装和试车4040记录2Process R&D Records工艺试验和记录2设计确认（DQ）1，3安装确认（IQ）1操作确认（OQ）1性能确认（PQ）1工艺验证（PV）1SOP of Operation,Clean,Maintain and Validation 操作、清洁、维护和验证管理等SOP1Production Master Records(CPP,Control limit,Sampling Plan,etc)生产主记录（工艺控制点、控制范围、取样计划等）1Formulation&Process 配方和生产工艺4Non-GMP Documents非非GMP文件文件GMP DocumentsGMP文件文件Support 提供支持提供支持1-Reviewed&approved according to procedures,when gaps occur,should explain,and