与制药工程项目全过程相整合的调试与确认服务卢浩荣

CHINAANNUALCONFERENCE16th–17thApril2012,BeijingCommissioning&QualificationServicesIntegratedintothePharmaceuticalProjectLifecycle

与制药工程项目全过程相整合的调试与确认服务

PresentedbyLu,Haorong卢浩荣ReviewedbyHenkManAgenda

议程Introduction

导言DefinitionandContentsOfI-C&QService

I-C&Q服务的定义与内容ServicesProviderandStakeholders服务提供商及相关方Necessity必要性Implementation

实施ReferencesandAcknowledgements

参考文献与致谢2012ISPECHINAANNUALCONFERENCEIntroduction导言

Concepts

概念GoodEngineeringPractice良好工程规范Establishedengineeringmethodsandstandardsthatareappliedthroughouttheprojectlifecycletodeliverappropriatedcost-effectivesolution.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Awellplanned,documentedandmanagedengineeringapproachtothestart-upandturnoveroffacilities,systems,andequipmenttotheEnd-Userthatresultsinasafeandfunctionenvironmentthatmeetsestablisheddesignrequirementsandstakeholderexpectations.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。

2012ISPECHINAANNUALCONFERENCEIntroduction导言

Concepts(cont.)概念（续）DQ设计确认Thedocumentedverificationthatengineeringdesignofafacility,utilityorequipmentthatcanaffectproductqualityadheretoapprovedUserRequirementanddesignspecifications.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Thedocumentedverificationthatallaspectsofafacility,utilityorequipmentthatcanaffectproductqualityadheretoapprovedspecificationsandarecorrectlyinstalled.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。2012ISPECHINAANNUALCONFERENCEIntroduction导言

Concepts(cont.)概念（续）OQ操作确认Thedocumentedverificationthatallaspectsofafacility,utility,orequipmentthatcanaffectproductqualityoperateasintendedthroughoutallanticipatedranges.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Thedocumentedverificationthatallaspectsoffacility,utility,orequipmentthatcanaffectproductqualityperformasintendedmeetingpredeterminedacceptancecriteria.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。

2012ISPECHINAANNUALCONFERENCEIntroduction导言

Concepts(cont.)概念（续）PV工艺验证Theprocessofestablishingdocumentedevidencewhichprovidesahighdegreeofassurancethataspecificprocesswillconsistentlyproduceaproductmeetingitspre-determinedspecificationsandqualityattributes.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。Moreconcepts更多的概念RiskBased–Commensuratewithrisk基于风险—与风险相适应ScienceBased–CQA,CPPs基于科学—关键质量属性、关键工艺参数QualitybyDesign–Verifythroughout质量源于设计—全过程的验证SubjectMatterExpert–DefinedRole学科问题专家—角色定义2012ISPECHINAANNUALCONFERENCEIntroduction导言

CurrentIssuesRelativetoC&QinChinesePharmaceuticalIndustry当前中国医药工业中调试与确认的相关问题LimitedresourceandfocusonDQandQBDisnotwellacknowledged.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。VeryrareprofessionalC&Qconsultantsalignedwithinternationalstandardandpractice.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。LackoflocalpresenceofinternationalC&Qconsultingexpertiseandthecorrespondinglocalprofessionalengineersupportiveteam.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。ImportanceofestablishingarealQMSbasedongoodC&Qpracticesisnotwellacknowledgedbyendorsertopmanagement.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。

2012ISPECHINAANNUALCONFERENCEIntroduction导言

CurrentIssuesRelativetoC&QinChinesePharmaceuticalIndustry（cont.）

当前中国医药工业中调试与确认的相关问题（续）Seldomcorrectapplicationsofriskassessmentapproachandover-interpretingofGMPregulationswithoutunderstandingtheirrationalesledtooverinvestmentoftheproject.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。Seldomsystematicplanningattheverybeginning,mostarecrashjobsinthefinalphaseoftheproject.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。FrequentchangeordersduetoissuesexposedinthefinalC&Qphaseledtosignificantcostofremedyanddelay.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。

2012ISPECHINAANNUALCONFERENCEIntroduction导言

CurrentIssuesRelativetoC&QinChinesePharmaceuticalIndustry（cont.）

当前中国医药工业中调试与确认的相关问题（续）Unclearinterfacesandpoorcommunicationsofthedifferentprojectpartiesledtoconsiderableoverlappingormissingofprojectworks,commissioningintegrationwithqualificationisrare.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。DuetolackofspecializedC&Qpeople,mostoftheC&Qjobsrelyonsub-contractorsorvendors,thejobs’qualityisnotundercontrol,andtheownerortheEPCcontractorhastopayextrachargesforeachequipmentorsystem.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。

2012ISPECHINAANNUALCONFERENCEIntroduction导言

CurrentIssuesRelativetoC&QinChinesePharmaceuticalIndustry（cont.）

当前中国医药工业中调试与确认的相关问题（续）ThoughseveralQ&Vconsultantsavailable,thescopeandstandardsofworksareundetermined,andthereforebothquantityandqualityoftheirworksarehardtoevaluate.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。

DuetoabsenceofSMEinsomedisciplines,theQ&Vconsultantssometimescanonlyrevealthedefectsintheproject,butfailtopresentthecost-effectivesolutionsforthem,especiallywhentheGMPconflictswithlocalcodes,e.g.firefightingorEHScodes.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。

2012ISPECHINAANNUALCONFERENCEIntroduction导言言GaptoCurrentGoodPracticesoftheInternationalPharmaceuticalIndustry与当前国际医医药工业良好好实践的差距距Aspects方面China中国International国际MarketingEnvironment市场环境Obviousdemand,limitedinvestment,developmentrequired需求明显但投入有限，需要培育Regulardemand,worthtoinvest,matureandnormative需求一般，认为投入值得，成熟、规范Professionals专业人员Limitedquantity,inexperienced,discipline-absent数量、经验有限，学科配套不齐全

Abundant,experienced,completedisciplines，high-cost数量充足，经验丰富，学科齐全,费用昂贵Organization机构Temporal,projectbased,latelyinvolve临时、基于项目、后期介入Standing,multi-projects,life-cycleinvolved常设，多项目，全程Implementation执行Random,nostrictprocedure,absentoroverlapping随意，无严格程序，漏项或重叠Normative,strictprocedure,integrity规范、程序严格、过程完整Documentation文件Poorintegrity,irregular,non-real-time，referenceabsent完整性差，不规范，非实时，引用失缺

Goodintegrity,normative,real-time,completereference,credible完整性好，规范，实时，引用齐全可信Approach方法PartlyfollowsISPEBaselineGuide5仅部分参照ISPE调试与确认指南ASTME250007+ISPEBaselineGuide+GAMP52012ISPECHINAANNUALCONFERENCEDefinition定义Commissioning&qualificationservicesintegratedintothepharmaceuticalprojectlifecycle（I-C&QServices)arethevaluableconsultingservicesprovidedbyaprofessionalC&QconsultanttohelpownerorEPCcontractortoimplementthecommissioningandqualificationsofdesign,installation,operation,performanceoffacilities,systems,andequipments,andfinallytheprocessvalidationofthefacilitiesofapharmaceuticalprojectbyapplyingGEP,GMPprinciplesandengineeringexperiences，beginningwithdevelopingtheOPRandextendingthroughallphasesofprojectdeliveryandintooperationandmaintenance.与制药工程项项目全过程相相整合的调试试与确认服务务(I-C&Q服务）系由专业调试试与确认咨询询商提供有价价值的咨询服服务，应用GEP、GMP原则和工程经经验，从形成成业主项目需需求开始扩展展到项目交付付、直到运行行和维护等所所有阶段，提提供有价值的的咨询服务，，帮助业主或或总承包商完完成制药工程程项目中设施施、系统、设设备的调试以以及设计、安安装、运行、、性能等一系系列确认乃至至设施的工艺艺验证等。DefinitionandContentsofI-C&QServicesI-C&Q服务的定义与与内容Definition(cont.)定义（续）WhenDoesCommissioningOccur?调试的时机Commissioningcanbeginduringpre-design,design,constructionorbuildingstart-up.Theprocesscanoffersignificantlygreaterandmorecosteffectivebenefitswhenitbeginsduringpre-designorearlydesign.调试可从设计计前、设计、、施工或开车车的时候开始始。当从设计计前或者设计计早期开始时时，该过程能能产生更大并并更经济有效效的效益。Commissioningintegrationintoqualification调试与确认的的整合Commissioningcansupportqualificationifperformedwithinaqualificationregime.Inthiscase,itiscriticaltodefinetheover-allscopeofthetestsandverificationstobeperformedforasystem,beforestartinganycommissioningorqualificationwork.当按确认的制制度来进行时时，调试可用用以支持确认认，关键是在在开展调试与与确认工作前前，应定义系系统测试与查查证的所有范范围。13DefinitionandContentsofI-C&QServicesI-C&Q服务的定义与与内容Pre-DesignDesignConstructionStart-UpOperations&MaintenanceTest&BalanceStart-upTestingDefinition(cont.)--CommissioningSpanofControl定义(续)--调试跨度的控控制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.Colburnetal.(2003)I-C&QC&QRiskManagement风险管理DesignReview设计审核ChangeManagement变更管理Product

Knowledge生产知识Regulatory法规

Company

Quality公司质量Process

Knowledge工艺知识GoodEngineeringPractice良好工程规范范Requirements需求Specification

&Design规格与设计Verification确认Acceptance

&Release验收与放行Operations&CI运行及持续改进ASTME2500-07:StandardsforSpecification,Design&VerificationofPharmaceutical&BiopharmaceuticalManufacturingSystems&EquipmentDefinition(cont.)--FlexibleApproachASTME2500定义(续)--ASTME2500-07柔性方法15ISPEBaselineGuide5–DesignInputs设计输入–ImpactAssessment影响评估–DesignQualification设计确认–Commissioning调试·–MultipleTrialRunstoGetThingsRight多次试运行以以达标–IQ,OQ,PQandAcceptanceCriteriaIQ,OQ,PQ及接受标准–GEPscopeandQAscopeoverlappedGEP和QA范围重叠–FocusedonDocumentationDeliverables注重关注文件件–RigidChangeManagement刚性的变更管管理ASTME2500–DesignInputs设计输入–DesignReview设计审核–RiskMitigation降低风险–CriticalControlParametersDefineAcceptanceCriteria关键控制参数数定义接受标标准–VerificationTesting确认测试–PerformanceTesting性能测试–GEPscopeandQAscopehaveclearboundaryGEP和QA界限清晰–Process,ProductQualityandPatientSafety工艺，产品质质量和病人安安全–QualitybyDesign,DesignSpaceandContinuousImprovement质量源于设计计，设计空间间及持续改进进DefinitionandContentsofI-C&QServicesI-C&Q服务的定义与与内容Definition(cont.)定义（续）Source（来源）:ITPharmaValidationEurope(2008)162012ISPECHINAANNUALCONFERENCEContents服务内容Represents““owner“asanobjectiveadvocate作为目标宣传传者代表业主主GuidesthedevelopmentofF-URS,URS指导编制设施施URS及系统URSOrganizesorattendsgapanalysis,impactassessment,riskassessmentandDRorDQ组织或参加偏偏差分析、影影响分析、风风险评估以及及设计审核或或设计确认Reviewsstandards/strategiesearlyindesign在设计阶段审审核标准/策略DevelopstheCxPlanandVMP编制调试计划划及验证总计计划DefinitionandContentsofI-C&QServicesI-C&Q服务的定义与与内容2012ISPECHINAANNUALCONFERENCEContents(cont.)服务内容（续续）DevelopsCxcontractlanguagefortheA/E&Constructioncontracts编制建筑/工程设计及施施工合同中的的调试条款GuidestheDevelopmentQualitySystemProgramandImplementationPlan指导编制质量量体系程序及及实施方案GuidesthetotalC&Qprocess指导调试、确确认全过程EnsuresimplementationofselectedmeasuresidentifiedintheOPR确保业主项目目需求中明确确的选择措施施的实施Verifiesminimumtargetshavebeenmet查证最低目标标已满足CompletesfinalC&Qreport完成最终调试试、确认报告告DefinitionandContentsofI-C&QServicesI-C&Q服务的定义与与内容2012ISPECHINAANNUALCONFERENCEContents(cont.)服务内容（续续）GuidesComputerSystemValidation指导计算机系系统验证GuidesAnalyticalInstrumentQualificationandAnalyticalMethodAnalysis指导分析仪器器确认与分析析方法验证GuidesCleaning,Sterilization,andFumigationValidation指导清洁、灭灭菌、熏蒸验验证GuidesthePVprocess,completesPVreport指导工艺验证证过程，完成成工艺验证报报告Coordinatessystemtestingandoperatortraining协调系统测试试和操作人员员培训DefinitionandContentsofI-C&QServicesI-C&Q服务的定义与与内容2012ISPECHINAANNUALCONFERENCEServicePacketsBreakdown服务工作包分分解GapanalysisandURSdevelopmentguidance偏差分析及设设施用户需求求编制指导GMPreviewGMP审核SystemImpactAssessmentandValidationMasterPlandevelopment系统影响评估估与验证总计计划编制QualitysystemprogramandimplementationplandevelopmentGuidance质量体系程序序及实施方案案编制指导DefinitionandContentsofI-C&QServicesI-C&Q服务的定义与与内容2012ISPECHINAANNUALCONFERENCEServicePacketsBreakdown(cont.)服务工作包分分解（续））RiskAnalysisandS-E/URSSOP,VPdevelopmentguidance风险分析及设设备/系统用户需求求、验证计划划编制指导CommissioningPlanandQualificationProtocoldevelopmentguidance调试计划和确认方方案编制指导导ComponentImpactAssessment,RiskAssessmentguidanceandDQ组件影响分析析、风险分析析指导与设计计确认IQ，OP，PQguidance安装确认、运运行确认、性性能确认指导导ComputerSystemValidationguidance计算机系统验验证指导DefinitionandContentsofI-C&QServicesI-C&Q服务的定义与与内容2012ISPECHINAANNUALCONFERENCEServicePacketsBreakdown(cont.)服务工作包分分解（续））AnalyticalInstrumentQualificationandAnalyticalMethodValidationGuide分析仪器确认认与分析方法法验证指导Cleaning,Sterilization,andFumigationValidationguide清洁、灭菌、、熏蒸验证指指导ProcessValidationguide工艺验验证指指导DefinitionandContentsofI-C&QServicesI-C&Q服务的的定义义与内内容2012ISPECHINAANNUALCONFERENCEServicesProviderandStakeholders服务提提供商商及相相关方方TheQualifiedServiceTeamStructure合格的的服务务团队队人员员构成成Basedontheprojectscope,resourcerequirements,andthekeystakeholders;取决于于项目目的范范围、、资源源需求求以及及主要要相关关方;Experiencedandprofessionalinindividualfield;在相应应领域域具有有经验验和专专业素素养Needtounderstandtheroles,responsibilities,andlevelsofauthority;应能理理解自自身的的角色色、责责任以以及权权力层层次；；Haveexcellentcommunication,planning,andcoordinationbetweendifferentparties.与不同同的项项目参参与方方间有有很好好的沟沟通、、计划划与协协调。。2012ISPECHINAANNUALCONFERENCEServicesProviderandStakeholders服务提提供商商及相相关方方TheQualifiedServiceTeamStructure(cont.)合格的的服务务团队队人员员构成成（续续）Includingbutnotlimitedto,包括但但不限限于，，Teamleader团队领领导Complianceandregulatoryexpert合规和和法规规专家家MechanicalC&Qengineer(HVAC,utilities)机械调调试与与确认认工程程师（（暖通通、公公用））Processequipment/systemC&Qengineer工艺设设备、、工艺艺系统统调试试与确确认工工程师师2012ISPECHINAANNUALCONFERENCEServicesProviderandStakeholders服务提提供商商及相相关方方TheQualifiedServiceTeamStructure(cont.)合格的的服务务团队队人员员构成成（续续）Computersystemvalidationengineer(softwareandhardware)计算机机系统统验证证工程程师AMVengineerandprocessvalidationengineer分析方方法验验证工工程师师及工工艺验验证工工程师师Cleaning，sterilization,andfumigationvalidationengineer清洁，，灭菌菌，熏熏蒸验验证工工程师师Documentcoordinatorandtechnicalwriter文件协协调控控制员员及技技术文文件编编制人人员2012ISPECHINAANNUALCONFERENCEServicesProviderandStakeholders服务提提供商商及相相关方方TheQualifiedServiceTeamStructure(cont.)合格的的服务务团队队人员员构成成（续续）Outsourcesupportsubjectmatterexpertsofcomplianceandregulatory,mechanical(HVAC,utilities),process&equipment,cleanfinishing,operation,QC/QA,QMSetc.合规和和法规规、机机械（（暖通通、公公用））、工工艺与与设备备、洁洁净装装修、、运行行、质质量控控制与与质量量保证证、质质量管管理体体系等等外部部学科科问题题支持持专家家。2012ISPECHINAANNUALCONFERENCEOtherProjectParties其它项目目参与方方A/Econsultants工程设计计Procurement采购Construction施工Projectmanagement项目管理理Commissioningleadersorcoordinatorfromcontractorsandowner承包商、、业主调调试负责责人或协协调员Operations/Production,maintenance,R&D,EHS,QC,QA,Qualification&Validationfromtheowner业主生产产运行、、维护、、研发、、环保及及健康安安全、QC、QA、确认与与验证等等部门ServicesProviderandStakeholders服务提供供商及相相关方2012ISPECHINAANNUALCONFERENCETheAuthorities监管部门门Food&DrugAdministration食品药品品监督部部门Municipalplanning&constructionadministration规划、建建设管理理部门EnvironmentalProtection环保部门门Fireauthority消防部门门SafetySupervisionAdministration安全监督督部门LaborProtection劳动保护护部门QualitySupervision质量监督督部门ServicesProviderandStakeholders服务提供供商及相相关方2012ISPECHINAANNUALCONFERENCERegulatoryRequirements法规要求求Necessity必要性Source（来源））:R.E.ChewandD.Petko(2007)EUGMPAnnex15andSFDAGMPChap.7“QualificationandValidation”definetherequirements.欧盟GMP附录15和中国GMP第七章““确认与与验证””有明确确要求。。RelationshipofASTMStandardtoGMPregulationsandguidancedocumentsASTM标准与GMP法规和指指南文件件的关系系日本美国欧盟诸如CFR211.68“设备应应按书面面程序进进行校验验、检查查、或核核对以确确保其恰恰当性能能”等条条款是确确认的基基础ICHQ9质量风险险管理可可用来决决定“确确认”的的范围指导如何何执行ASTM标准的主主要原理理及基本本原则阐明基于于风险的的查证（（或确认认）的原原理及基基本原则则BenefitstotheOwner为业主带带来的好好处Riskcontrolledearlier风险及早早得到控控制Reducetimeandcosttoachieveandmaintaincompliance降低项目目完成所所耗费用用与时间间并维持持项目的的合规性性Reducechangeordersduringconstruction减少施工工过程的的变更令令Lesswaste&repetition更少的浪浪费与重重复Reduceprojectdelays较少项目目推迟Shortenbuildingturnoverperiod缩短建筑筑交付周周期ValidationteamandQMSsetup建立验证证团队和和质量管管理体系系Earlierreleasedandcommercialmanufacture更早地通通过认证证并投入入商业生生产Necessity必要性BenefitstotheOwner(cont.)为业主带带来的好好处(续）Costeffectiveoperationandmaintenance经济高效效的运行行及维护护Reduceequipmentreplacement减少设备备更换Betterknowledge,understandingofsystems对系统更更好的认认识和理理解Bettertrainedoperationsstaff更好地培培训运行行团队Operationsandmaintenancemanualsarecompleteandsubmittedatprojectturnover.运行及维维护手册册完成并并在项目目交付时时提交Necessity必要性BenefitstotheContractors对承包商商的好处处Betterplanningwillresultinimprovedinstallation更好的计计划可导导致安装装的改进进Moreemphasisonqualitycontrolonwhatmatters对质量控控制更加加强调Quickerresolutionofproblems(identifyproblemsduringQC)更快地解解决问题题（在QC过程中界界定问题题）Increaselikelihoodofcompletingprojectonschedule––maximizeprofit提高按时时完成项项目的可可能性—利润最大大化Reducepost-constructioncallbacks–preserveprofit减少施工工后召回回—保护利润润Necessity必要性BenefitstotheAuthorities对监管部部门的好好处Genuine,validandsystemicdocumentations文件真实实、有效效、系统统Easyofinspection便于检查查Genuine,crediblerecordsandtrends真实可信信的记录录与趋势势Easyofsupervision便于监管管Clearmanagementprograms,integralapprovalsinmanufacturer’ssite厂商管理理程序清清晰，审审批完整整Easyofinvestigationafterwards便于事后后追究Necessity必要性ImplementationFlowofPharmaceuticalProject制药工业业项目实实施流程程ProductionStart有效投产产FeasibilityStudy可行性研研究ConceptDesign概念设计计Procurement采购Construction施工DetailEngineering详细设计计SupportValidation验证支持持C&Q调试与确认Decision““GO””客户决定工工程继续进行行Basic+Ext.BasicEngineering基本＋扩充充设计FinalinvestmentDecision客户做出最最终投资决定定CostEstimate造价估算20%CostEstimate造价估算10%ConceptPhase概念阶段DesignPhase设计阶段ExecutionPhase实施阶段HandOver交付ValidationPhase验证阶段MaintenanceCustomerService维修/客户服务FacilityManagement设施管理SecondOpinionValueEngineering修改/补充Implementation实施Workflow工作流程Acknowledgement（感谢）:InstructionfromMr.D.W.VincentF(设施)-URSGA偏差分析BOD设计基础VMP验证总计划划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调试计划及及确认方案案PQ性能确认OQ运行确认IQ安装确认Commissioning(FAT/SAT,etc.)Exec.调试（工厂厂/现场验收测测试等）执执行DQ设计确认Procurement&Construction采购施工CV清洁验证SterilizationValidation灭菌验证PV工艺验证MediumFill培养基灌装装UtilityQua/Val公用系统确确认/验证FumigationValidation熏蒸验证AIQ分析仪器确确认CSV计算机系统统验证CSV计算机系统统验证CSV计算机系统统验证AMV分析方法验验证SIA系统影响评评估GMPRev.GMP审核Implementation实施Workflow工作流程Acknowledgement（感谢）:InstructionfromMr.C.BachofenWorkflow——abriefcasestudy(WFIsystem)工作流程–简略的案例例分析(注射用水系系统）Specifythefinalusers,capacity,standards，etc.tobefollowedforWFI.systeminF-URS在设施URS中明确注射射用水系统统的终端用用户、供应应能力以及及遵循的标标准等。ImplementGAfortherenovatedsystems.对改造的系系统进行偏偏差分析。。DeveloptheschematicdesignofWFIsystem(e.g.MB,PFD，mainequipmentlist)intheBODofthefacility（designconsultant).在设施的设设计基础中中进行注注射用水系系统的方案案设计（物物料平衡、、工艺流程程图,主要设备表表等）(设计咨询方方）。Implementation实施Workflow——abriefcasestudy(WFIsystem)（cont.)工作流程–简略的案例例分析(注射用水系系统）(续）ImplementtheIAoftheWFIsystemaccordingtothecriteria.按照判据进进行注射用用水的影响响评估。。SpecifythelevelofC&Qs(includingCSV)andtherationaleofthesysteminVMP.在验证总计计划中阐明明调试确认认(包括计算机机系统验证证）的程度度及原因.DeveloptheURSofthesystem(includingtheC&Qrequirement),VPbasedonRA.在风险分析析的基础上上编制系统统的URS及验证计划划.Implementation实施Workflow——abriefcasestudy(WFIsystem)（cont.)工作流程–简略的案例例分析(注射用水系系统）(续）DevelopFS、DSfortheWFIsystem(BD,DD—designconsultantorcontractor).编制注射用用水系统的的功能说明明、设计说说明（基础础设计、详详细设计—设计方或承承包商）。。DeveloptheCommissioning(e.g.FAT/SAT)planandDQ、IQ、OQprotocolsfortheWFIsystemwithaC&Qintegratedapproach.以调试与确确认相整合合的方式编编制调试（（如FAT/SAT）计划和DQ、IQ、OQ方案。ImplementtheDQoftheWFIsystemwithstructuralreviewapproachandFEMA(basedonC-IA)采用结构化化审核方式式和建立在在部件影响响评估基础础上的潜在在故障形式式和影响分分析（设计计FMEA)进行注射用用水系统的的设计确认认。Implementation实施Workflow——abriefcasestudy(WFIsystem)（cont.)工作流程–简略的案例例分析(注射用水系系统）(续）Implementtheconstruction、commissioning、IQ、CSV、OQaccordingtotheapprovedDD、commissioningplanandqualificationprotocolswiththeintegratedapproach采用整合方方式按批准准的详细设设计、调试试计划和确确认方案实实施注射用用水系统的的施工、调试、安装确认、计算机系系统验证、、运行确认。ImplementPQ/validation（approvetheSOPs,verifycontrol,verifylong-termcontrol)oftheWFIsystembasedonOQ,andrelativeAIQ、AMV、relativeCV、SV、U-Q/V.在运行确认认以及相关关分析仪器器确认、分分析方法验验证、清洁洁/消毒验证，，公用系统统确认/验证的基础础上实施PQ或注射用水水系统验证证(水质检测通通过并批准准运行SOP、验证受控控、验证长长期受控））。Implementation实施2012ISPECHINAANNUALCONFERENCEInterfaceswithOtherProjectParties与其它项目目参与方的的接口Implementation实施用户需求规格（URS）1Contracts,FS,DS采购合同、说明书和规格2SamplingRecords厂家提供的试样记录2FAT/SAT1,I&CRecords厂家安装和试车4040记录2ProcessR&DRecords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）1SOPofOperation,Clean,MaintainandValidation操作、清洁、维护和验证管理等SOP1ProductionMasterRecords(CPP,Controllimit,SamplingPlan,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-GMPDocuments非GMP文件GMPDocumentsGMP文件Support提供支持1-Reviewed&approvedaccordingtoprocedures,whengapsoccur,shouldexplain,andinvestigatewhennecessary.应当按一定定程序审核核和批准，，实施过程程中如有偏偏差，应解解释，必要要时进行调调查。2-Canbedevelopedanduseddirectly,gapsoccuratimplementationarenotrequiredtoexplain.可直接编写写和使用，，不一定需需要解释实实施过程中中的偏差。。3-DQisaregulatoryrequirementinEU,butnotinUS.在欧盟为法法规要求，，在美国非非法规要求求.4-Reviewedandapprovedbyauthority,changeshouldbecontrolledaccordingtoregulatory.由主管当局局审核和批批准，变更更应遵循法法定程序。。Vendor/Contractor供应商/承包商Owner(+Consultant)业主(+咨询方)Owner业主Owner(+Consultant)业主(+咨询方)Owner(+Consultant)业主(+咨询方)Source（来源）:Y.Liu(2008)ValidationMasterPlan验证主计划划DesignIntent设计目的P&ID’s管道仪表流程程图Specification技术规格Drawings图纸RegulatoryDocuments规范文件ValidationProtocols验证方案Start-UpDocuments调试文件ExecuteValidation执行Validationreports验证报告OperationDocuments操作文件Lists清单FactoryTests工厂测试FieldTestDocuments现场测试文件件InstallationDocuments安装文件VendorDocuments厂商文件PurchasingDocuments采购文件EngineeringDocuments设计文件ConstructionDocuments施工文件CommissioningDocuments调试文件Implementation实施Documentationsystemreflectingthelifecycle反映制药工业业项目周期的的文件系统GoodDocumentationPractices良好记录规范范GoodDocumentationPractices(cont.)良好记录规范范(续）Overwrites涂改Errorsindateformatandinitials日期及签字不不正确Completingformsandrecordinformationafterthefact事后补填表格格与记录Incompleterecords记录不完整Backdatinginformation过期信息Crossingoutcalculationsandcriticaldatawithoutjustification无正当理由给给计算与关键键数据打叉Implementation实施GoodDocumentationPractices(cont.)良好记录规范范(续）Transcribinginformation抄写信息LeavingblankspaceswithoutN/A表格留空，没没填“不适用用”Falsifyingdocuments伪造文件Obliteratinginformationi.e.usingwhiteout,doubleormultiplecrossouts用涂改液、双双线或多线涂涂去信息Replacingpagesindocumentafteritwasapproved将批准后的文文件换页Lackoftraceability缺乏可追溯性性Implementation实施Acknowledgement（感谢）:InstructionfromMr.D.W.Vincent