與制藥工程項目全過程相整合的調(diào)試與確認(rèn)服務(wù)盧浩榮

CHINAANNUALCONFERENCE16th–17thApril2012,BeijingCommissioning&QualificationServicesIntegratedintothePharmaceuticalProjectLifecycle

與制藥工程項目全過程相整合的調(diào)試與確認(rèn)服務(wù)

PresentedbyLu,Haorong盧浩榮ReviewedbyHenkManAgenda

議程Introduction

導(dǎo)言DefinitionandContentsOfI-C&QService

I-C&Q服務(wù)的定義與內(nèi)容ServicesProviderandStakeholders服務(wù)提供商及相關(guān)方Necessity必要性Implementation

實施ReferencesandAcknowledgements

參考文獻與致謝2012ISPECHINAANNUALCONFERENCEIntroduction導(dǎo)言

Concepts

概念GoodEngineeringPractice良好工程規(guī)范Establishedengineeringmethodsandstandardsthatareappliedthroughouttheprojectlifecycletodeliverappropriatedcost-effectivesolution.在項目周期中全程采用已建立的工程方法和標(biāo)準(zhǔn)，以交付合理的、經(jīng)濟有效的解決方案。Commissioning調(diào)試Awellplanned,documentedandmanagedengineeringapproachtothestart-upandturnoveroffacilities,systems,andequipmenttotheEnd-Userthatresultsinasafeandfunctionenvironmentthatmeetsestablisheddesignrequirementsandstakeholderexpectations.采用一套良好計劃的、有文件記錄并受管理的工程方法，對工程設(shè)施、系統(tǒng)和設(shè)備進行試車并交付最終用戶，以建立符合既定設(shè)計要求及股東期望的安全、功能良好的環(huán)境。

2012ISPECHINAANNUALCONFERENCEIntroduction導(dǎo)言

Concepts(cont.)概念（續(xù)）DQ設(shè)計確認(rèn)Thedocumentedverificationthatengineeringdesignofafacility,utilityorequipmentthatcanaffectproductqualityadheretoapprovedUserRequirementanddesignspecifications.對可能影響產(chǎn)品質(zhì)量的設(shè)施、公用工程和設(shè)備的工程設(shè)計進行有文件記錄的查證，確認(rèn)與被批準(zhǔn)的用戶需求和設(shè)計描述一致。IQ安裝確認(rèn)Thedocumentedverificationthatallaspectsofafacility,utilityorequipmentthatcanaffectproductqualityadheretoapprovedspecificationsandarecorrectlyinstalled.對設(shè)施、公用工程和設(shè)備所有可能影響產(chǎn)品質(zhì)量的方面進行有文件記錄的查證，確認(rèn)與被批準(zhǔn)的描述一致并已得到正確的安裝。2012ISPECHINAANNUALCONFERENCEIntroduction導(dǎo)言

Concepts(cont.)概念（續(xù)）OQ操作確認(rèn)Thedocumentedverificationthatallaspectsofafacility,utility,orequipmentthatcanaffectproductqualityoperateasintendedthroughoutallanticipatedranges.對設(shè)施、公用工程和設(shè)備所有可能影響產(chǎn)品質(zhì)量的方面進行有文件記錄的查證，確認(rèn)它們在預(yù)期的操作極限內(nèi)運行正確。PQ性能確認(rèn)Thedocumentedverificationthatallaspectsoffacility,utility,orequipmentthatcanaffectproductqualityperformasintendedmeetingpredeterminedacceptancecriteria.對設(shè)施、公用工程和設(shè)備所有可能影響產(chǎn)品質(zhì)量的方面進行有文件記錄的查證，確認(rèn)其性能符合預(yù)先確定的驗收標(biāo)準(zhǔn)。

2012ISPECHINAANNUALCONFERENCEIntroduction導(dǎo)言

Concepts(cont.)概念（續(xù)）PV工藝驗證Theprocessofestablishingdocumentedevidencewhichprovidesahighdegreeofassurancethataspecificprocesswillconsistentlyproduceaproductmeetingitspre-determinedspecificationsandqualityattributes.建立文件證據(jù)，高度保證在特定生產(chǎn)工藝條件下，可均一地生產(chǎn)符合預(yù)定標(biāo)準(zhǔn)和質(zhì)量屬性的產(chǎn)品的過程。Moreconcepts更多的概念RiskBased–Commensuratewithrisk基于風(fēng)險—與風(fēng)險相適應(yīng)ScienceBased–CQA,CPPs基于科學(xué)—關(guān)鍵質(zhì)量屬性、關(guān)鍵工藝參數(shù)QualitybyDesign–Verifythroughout質(zhì)量源于設(shè)計—全過程的驗證SubjectMatterExpert–DefinedRole學(xué)科問題專家—角色定義2012ISPECHINAANNUALCONFERENCEIntroduction導(dǎo)言

CurrentIssuesRelativetoC&QinChinesePharmaceuticalIndustry當(dāng)前中國醫(yī)藥工業(yè)中調(diào)試與確認(rèn)的相關(guān)問題LimitedresourceandfocusonDQandQBDisnotwellacknowledged.投入資源有限，對設(shè)計確認(rèn)、質(zhì)量源于設(shè)計等的重點未充分認(rèn)識。VeryrareprofessionalC&Qconsultantsalignedwithinternationalstandardandpractice.專業(yè)的、與國際標(biāo)準(zhǔn)、規(guī)范接軌的調(diào)試與確認(rèn)咨詢服務(wù)提供商非常罕見。LackoflocalpresenceofinternationalC&Qconsultingexpertiseandthecorrespondinglocalprofessionalengineersupportiveteam.國際知名調(diào)試與確認(rèn)專家罕有常駐中國本地，同時缺乏與其配套的本地專業(yè)工程師支持團隊。ImportanceofestablishingarealQMSbasedongoodC&Qpracticesisnotwellacknowledgedbyendorsertopmanagement.以良好的調(diào)試與確認(rèn)實踐為基礎(chǔ)建立一個真正的質(zhì)量管理體系的重要性并未被企業(yè)高層管理人員充分認(rèn)識。

2012ISPECHINAANNUALCONFERENCEIntroduction導(dǎo)言

CurrentIssuesRelativetoC&QinChinesePharmaceuticalIndustry（cont.）

當(dāng)前中國醫(yī)藥工業(yè)中調(diào)試與確認(rèn)的相關(guān)問題（續(xù)）Seldomcorrectapplicationsofriskassessmentapproachandover-interpretingofGMPregulationswithoutunderstandingtheirrationalesledtooverinvestmentoftheproject.風(fēng)險分析方法罕有正確應(yīng)用，未能從基本原理上進行理解，若干GMP法規(guī)被過度解讀導(dǎo)致項目過度投資。Seldomsystematicplanningattheverybeginning,mostarecrashjobsinthefinalphaseoftheproject.鮮有在項目開始即進行系統(tǒng)性的策劃，大部分在項目后期進行突擊。FrequentchangeordersduetoissuesexposedinthefinalC&Qphaseledtosignificantcostofremedyanddelay.因最終調(diào)試與確認(rèn)階段暴露的問題而產(chǎn)生的變更導(dǎo)致可觀的索賠及工期延誤。

2012ISPECHINAANNUALCONFERENCEIntroduction導(dǎo)言

CurrentIssuesRelativetoC&QinChinesePharmaceuticalIndustry（cont.）

當(dāng)前中國醫(yī)藥工業(yè)中調(diào)試與確認(rèn)的相關(guān)問題（續(xù)）Unclearinterfacesandpoorcommunicationsofthedifferentprojectpartiesledtoconsiderableoverlappingormissingofprojectworks,commissioningintegrationwithqualificationisrare.不同項目參與方節(jié)點不清，溝通不暢導(dǎo)致相當(dāng)?shù)捻椖抗ぷ髦丿B或漏項,罕有調(diào)試與確認(rèn)進行整合。DuetolackofspecializedC&Qpeople,mostoftheC&Qjobsrelyonsub-contractorsorvendors,thejobs’qualityisnotundercontrol,andtheownerortheEPCcontractorhastopayextrachargesforeachequipmentorsystem.由于缺乏專業(yè)的調(diào)試與確認(rèn)人員，大部分的調(diào)試與確認(rèn)工作依賴于分包商或供應(yīng)商，工作質(zhì)量不可控，而業(yè)主或總承包商不得不為每一設(shè)備或系統(tǒng)付出額外的費用。

2012ISPECHINAANNUALCONFERENCEIntroduction導(dǎo)言

CurrentIssuesRelativetoC&QinChinesePharmaceuticalIndustry（cont.）

當(dāng)前中國醫(yī)藥工業(yè)中調(diào)試與確認(rèn)的相關(guān)問題（續(xù)）ThoughseveralQ&Vconsultantsavailable,thescopeandstandardsofworksareundetermined,andthereforebothquantityandqualityoftheirworksarehardtoevaluate.盡管有數(shù)家確認(rèn)與驗證咨詢服務(wù)提供商，但工作范圍與標(biāo)準(zhǔn)不明確，因而工作的數(shù)量與質(zhì)量都很難評估。

DuetoabsenceofSMEinsomedisciplines,theQ&Vconsultantssometimescanonlyrevealthedefectsintheproject,butfailtopresentthecost-effectivesolutionsforthem,especiallywhentheGMPconflictswithlocalcodes,e.g.firefightingorEHScodes.由于某些專業(yè)的專家欠缺，確認(rèn)與驗證咨詢服務(wù)提供商有時僅能揭示項目的某些缺陷，但不能給出相應(yīng)的經(jīng)濟有效的解決方案，尤其是在GMP與國內(nèi)規(guī)范，如消防、環(huán)保、職業(yè)安全衛(wèi)生規(guī)范發(fā)生沖突時。

2012ISPECHINAANNUALCONFERENCEIntroduction導(dǎo)言言GaptoCurrentGoodPracticesoftheInternationalPharmaceuticalIndustry與當(dāng)前國際醫(yī)醫(yī)藥工業(yè)良好好實踐的差距距Aspects方面China中國International國際MarketingEnvironment市場環(huán)境Obviousdemand,limitedinvestment,developmentrequired需求明顯但投入有限，需要培育Regulardemand,worthtoinvest,matureandnormative需求一般，認(rèn)為投入值得，成熟、規(guī)范Professionals專業(yè)人員Limitedquantity,inexperienced,discipline-absent數(shù)量、經(jīng)驗有限，學(xué)科配套不齊全

Abundant,experienced,completedisciplines，high-cost數(shù)量充足，經(jīng)驗豐富，學(xué)科齊全,費用昂貴Organization機構(gòu)Temporal,projectbased,latelyinvolve臨時、基于項目、后期介入Standing,multi-projects,life-cycleinvolved常設(shè)，多項目，全程Implementation執(zhí)行Random,nostrictprocedure,absentoroverlapping隨意，無嚴(yán)格程序，漏項或重疊Normative,strictprocedure,integrity規(guī)范、程序嚴(yán)格、過程完整Documentation文件Poorintegrity,irregular,non-real-time，referenceabsent完整性差，不規(guī)范，非實時，引用失缺

Goodintegrity,normative,real-time,completereference,credible完整性好，規(guī)范，實時，引用齊全可信Approach方法PartlyfollowsISPEBaselineGuide5僅部分參照ISPE調(diào)試與確認(rèn)指南ASTME250007+ISPEBaselineGuide+GAMP52012ISPECHINAANNUALCONFERENCEDefinition定義Commissioning&qualificationservicesintegratedintothepharmaceuticalprojectlifecycle（I-C&QServices)arethevaluableconsultingservicesprovidedbyaprofessionalC&QconsultanttohelpownerorEPCcontractortoimplementthecommissioningandqualificationsofdesign,installation,operation,performanceoffacilities,systems,andequipments,andfinallytheprocessvalidationofthefacilitiesofapharmaceuticalprojectbyapplyingGEP,GMPprinciplesandengineeringexperiences，beginningwithdevelopingtheOPRandextendingthroughallphasesofprojectdeliveryandintooperationandmaintenance.與制藥工程項項目全過程相相整合的調(diào)試試與確認(rèn)服務(wù)務(wù)(I-C&Q服務(wù)）系由專業(yè)調(diào)試試與確認(rèn)咨詢詢商提供有價價值的咨詢服服務(wù)，應(yīng)用GEP、GMP原則和工程經(jīng)經(jīng)驗，從形成成業(yè)主項目需需求開始擴展展到項目交付付、直到運行行和維護等所所有階段，提提供有價值的的咨詢服務(wù)，，幫助業(yè)主或或總承包商完完成制藥工程程項目中設(shè)施施、系統(tǒng)、設(shè)設(shè)備的調(diào)試以以及設(shè)計、安安裝、運行、、性能等一系系列確認(rèn)乃至至設(shè)施的工藝藝驗證等。DefinitionandContentsofI-C&QServicesI-C&Q服務(wù)的定義與與內(nèi)容Definition(cont.)定義（續(xù)）WhenDoesCommissioningOccur?調(diào)試的時機Commissioningcanbeginduringpre-design,design,constructionorbuildingstart-up.Theprocesscanoffersignificantlygreaterandmorecosteffectivebenefitswhenitbeginsduringpre-designorearlydesign.調(diào)試可從設(shè)計計前、設(shè)計、、施工或開車車的時候開始始。當(dāng)從設(shè)計計前或者設(shè)計計早期開始時時，該過程能能產(chǎn)生更大并并更經(jīng)濟有效效的效益。Commissioningintegrationintoqualification調(diào)試與確認(rèn)的的整合Commissioningcansupportqualificationifperformedwithinaqualificationregime.Inthiscase,itiscriticaltodefinetheover-allscopeofthetestsandverificationstobeperformedforasystem,beforestartinganycommissioningorqualificationwork.當(dāng)按確認(rèn)的制制度來進行時時，調(diào)試可用用以支持確認(rèn)認(rèn)，關(guān)鍵是在在開展調(diào)試與與確認(rèn)工作前前，應(yīng)定義系系統(tǒng)測試與查查證的所有范范圍。13DefinitionandContentsofI-C&QServicesI-C&Q服務(wù)的定義與與內(nèi)容Pre-DesignDesignConstructionStart-UpOperations&MaintenanceTest&BalanceStart-upTestingDefinition(cont.)--CommissioningSpanofControl定義(續(xù))--調(diào)試跨度的控控制Commissioning設(shè)計前調(diào)試開車測試設(shè)計施工開車運行及維護測試及平衡Source（來源）:D.Colburnetal.(2003)I-C&QC&QRiskManagement風(fēng)險管理DesignReview設(shè)計審核ChangeManagement變更管理Product

Knowledge生產(chǎn)知識Regulatory法規(guī)

Company

Quality公司質(zhì)量Process

Knowledge工藝知識GoodEngineeringPractice良好工程規(guī)范范Requirements需求Specification

&Design規(guī)格與設(shè)計Verification確認(rèn)Acceptance

&Release驗收與放行Operations&CI運行及持續(xù)改進ASTME2500-07:StandardsforSpecification,Design&VerificationofPharmaceutical&BiopharmaceuticalManufacturingSystems&EquipmentDefinition(cont.)--FlexibleApproachASTME2500定義(續(xù))--ASTME2500-07柔性方法15ISPEBaselineGuide5–DesignInputs設(shè)計輸入–ImpactAssessment影響評估–DesignQualification設(shè)計確認(rèn)–Commissioning調(diào)試·–MultipleTrialRunstoGetThingsRight多次試運行以以達(dá)標(biāo)–IQ,OQ,PQandAcceptanceCriteriaIQ,OQ,PQ及接受標(biāo)準(zhǔn)–GEPscopeandQAscopeoverlappedGEP和QA范圍重疊–FocusedonDocumentationDeliverables注重關(guān)注文件件–RigidChangeManagement剛性的變更管管理ASTME2500–DesignInputs設(shè)計輸入–DesignReview設(shè)計審核–RiskMitigation降低風(fēng)險–CriticalControlParametersDefineAcceptanceCriteria關(guān)鍵控制參數(shù)數(shù)定義接受標(biāo)標(biāo)準(zhǔn)–VerificationTesting確認(rèn)測試–PerformanceTesting性能測試–GEPscopeandQAscopehaveclearboundaryGEP和QA界限清晰–Process,ProductQualityandPatientSafety工藝，產(chǎn)品質(zhì)質(zhì)量和病人安安全–QualitybyDesign,DesignSpaceandContinuousImprovement質(zhì)量源于設(shè)計計，設(shè)計空間間及持續(xù)改進進DefinitionandContentsofI-C&QServicesI-C&Q服務(wù)的定義與與內(nèi)容Definition(cont.)定義（續(xù)）Source（來源）:ITPharmaValidationEurope(2008)162012ISPECHINAANNUALCONFERENCEContents服務(wù)內(nèi)容Represents““owner“asanobjectiveadvocate作為目標(biāo)宣傳傳者代表業(yè)主主GuidesthedevelopmentofF-URS,URS指導(dǎo)編制設(shè)施施URS及系統(tǒng)URSOrganizesorattendsgapanalysis,impactassessment,riskassessmentandDRorDQ組織或參加偏偏差分析、影影響分析、風(fēng)風(fēng)險評估以及及設(shè)計審核或或設(shè)計確認(rèn)Reviewsstandards/strategiesearlyindesign在設(shè)計階段審審核標(biāo)準(zhǔn)/策略DevelopstheCxPlanandVMP編制調(diào)試計劃劃及驗證總計計劃DefinitionandContentsofI-C&QServicesI-C&Q服務(wù)的定義與與內(nèi)容2012ISPECHINAANNUALCONFERENCEContents(cont.)服務(wù)內(nèi)容（續(xù)續(xù)）DevelopsCxcontractlanguagefortheA/E&Constructioncontracts編制建筑/工程設(shè)計及施施工合同中的的調(diào)試條款GuidestheDevelopmentQualitySystemProgramandImplementationPlan指導(dǎo)編制質(zhì)量量體系程序及及實施方案GuidesthetotalC&Qprocess指導(dǎo)調(diào)試、確確認(rèn)全過程EnsuresimplementationofselectedmeasuresidentifiedintheOPR確保業(yè)主項目目需求中明確確的選擇措施施的實施Verifiesminimumtargetshavebeenmet查證最低目標(biāo)標(biāo)已滿足CompletesfinalC&Qreport完成最終調(diào)試試、確認(rèn)報告告DefinitionandContentsofI-C&QServicesI-C&Q服務(wù)的定義與與內(nèi)容2012ISPECHINAANNUALCONFERENCEContents(cont.)服務(wù)內(nèi)容（續(xù)續(xù)）GuidesComputerSystemValidation指導(dǎo)計算機系系統(tǒng)驗證GuidesAnalyticalInstrumentQualificationandAnalyticalMethodAnalysis指導(dǎo)分析儀器器確認(rèn)與分析析方法驗證GuidesCleaning,Sterilization,andFumigationValidation指導(dǎo)清潔、滅滅菌、熏蒸驗驗證GuidesthePVprocess,completesPVreport指導(dǎo)工藝驗證證過程，完成成工藝驗證報報告Coordinatessystemtestingandoperatortraining協(xié)調(diào)系統(tǒng)測試試和操作人員員培訓(xùn)DefinitionandContentsofI-C&QServicesI-C&Q服務(wù)的定義與與內(nèi)容2012ISPECHINAANNUALCONFERENCEServicePacketsBreakdown服務(wù)工作包分分解GapanalysisandURSdevelopmentguidance偏差分析及設(shè)設(shè)施用戶需求求編制指導(dǎo)GMPreviewGMP審核SystemImpactAssessmentandValidationMasterPlandevelopment系統(tǒng)影響評估估與驗證總計計劃編制QualitysystemprogramandimplementationplandevelopmentGuidance質(zhì)量體系程序序及實施方案案編制指導(dǎo)DefinitionandContentsofI-C&QServicesI-C&Q服務(wù)的定義與與內(nèi)容2012ISPECHINAANNUALCONFERENCEServicePacketsBreakdown(cont.)服務(wù)工作包分分解（續(xù)））RiskAnalysisandS-E/URSSOP,VPdevelopmentguidance風(fēng)險分析及設(shè)設(shè)備/系統(tǒng)用戶需求求、驗證計劃劃編制指導(dǎo)CommissioningPlanandQualificationProtocoldevelopmentguidance調(diào)試計劃和確認(rèn)方方案編制指導(dǎo)導(dǎo)ComponentImpactAssessment,RiskAssessmentguidanceandDQ組件影響分析析、風(fēng)險分析析指導(dǎo)與設(shè)計計確認(rèn)IQ，OP，PQguidance安裝確認(rèn)、運運行確認(rèn)、性性能確認(rèn)指導(dǎo)導(dǎo)ComputerSystemValidationguidance計算機系統(tǒng)驗驗證指導(dǎo)DefinitionandContentsofI-C&QServicesI-C&Q服務(wù)的定義與與內(nèi)容2012ISPECHINAANNUALCONFERENCEServicePacketsBreakdown(cont.)服務(wù)工作包分分解（續(xù)））AnalyticalInstrumentQualificationandAnalyticalMethodValidationGuide分析儀器確認(rèn)認(rèn)與分析方法法驗證指導(dǎo)Cleaning,Sterilization,andFumigationValidationguide清潔、滅菌、、熏蒸驗證指指導(dǎo)ProcessValidationguide工藝驗驗證指指導(dǎo)DefinitionandContentsofI-C&QServicesI-C&Q服務(wù)的的定義義與內(nèi)內(nèi)容2012ISPECHINAANNUALCONFERENCEServicesProviderandStakeholders服務(wù)提提供商商及相相關(guān)方方TheQualifiedServiceTeamStructure合格的的服務(wù)務(wù)團隊隊人員員構(gòu)成成Basedontheprojectscope,resourcerequirements,andthekeystakeholders;取決于于項目目的范范圍、、資源源需求求以及及主要要相關(guān)關(guān)方;Experiencedandprofessionalinindividualfield;在相應(yīng)應(yīng)領(lǐng)域域具有有經(jīng)驗驗和專專業(yè)素素養(yǎng)Needtounderstandtheroles,responsibilities,andlevelsofauthority;應(yīng)能理理解自自身的的角色色、責(zé)責(zé)任以以及權(quán)權(quán)力層層次；；Haveexcellentcommunication,planning,andcoordinationbetweendifferentparties.與不同同的項項目參參與方方間有有很好好的溝溝通、、計劃劃與協(xié)協(xié)調(diào)。。2012ISPECHINAANNUALCONFERENCEServicesProviderandStakeholders服務(wù)提提供商商及相相關(guān)方方TheQualifiedServiceTeamStructure(cont.)合格的的服務(wù)務(wù)團隊隊人員員構(gòu)成成（續(xù)續(xù)）Includingbutnotlimitedto,包括但但不限限于，，Teamleader團隊領(lǐng)領(lǐng)導(dǎo)Complianceandregulatoryexpert合規(guī)和和法規(guī)規(guī)專家家MechanicalC&Qengineer(HVAC,utilities)機械調(diào)調(diào)試與與確認(rèn)認(rèn)工程程師（（暖通通、公公用））Processequipment/systemC&Qengineer工藝設(shè)設(shè)備、、工藝藝系統(tǒng)統(tǒng)調(diào)試試與確確認(rèn)工工程師師2012ISPECHINAANNUALCONFERENCEServicesProviderandStakeholders服務(wù)提提供商商及相相關(guān)方方TheQualifiedServiceTeamStructure(cont.)合格的的服務(wù)務(wù)團隊隊人員員構(gòu)成成（續(xù)續(xù)）Computersystemvalidationengineer(softwareandhardware)計算機機系統(tǒng)統(tǒng)驗證證工程程師AMVengineerandprocessvalidationengineer分析方方法驗驗證工工程師師及工工藝驗驗證工工程師師Cleaning，sterilization,andfumigationvalidationengineer清潔，，滅菌菌，熏熏蒸驗驗證工工程師師Documentcoordinatorandtechnicalwriter文件協(xié)協(xié)調(diào)控控制員員及技技術(shù)文文件編編制人人員2012ISPECHINAANNUALCONFERENCEServicesProviderandStakeholders服務(wù)提提供商商及相相關(guān)方方TheQualifiedServiceTeamStructure(cont.)合格的的服務(wù)務(wù)團隊隊人員員構(gòu)成成（續(xù)續(xù)）Outsourcesupportsubjectmatterexpertsofcomplianceandregulatory,mechanical(HVAC,utilities),process&equipment,cleanfinishing,operation,QC/QA,QMSetc.合規(guī)和和法規(guī)規(guī)、機機械（（暖通通、公公用））、工工藝與與設(shè)備備、潔潔凈裝裝修、、運行行、質(zhì)質(zhì)量控控制與與質(zhì)量量保證證、質(zhì)質(zhì)量管管理體體系等等外部部學(xué)科科問題題支持持專家家。2012ISPECHINAANNUALCONFERENCEOtherProjectParties其它項目目參與方方A/Econsultants工程設(shè)計計Procurement采購Construction施工Projectmanagement項目管理理Commissioningleadersorcoordinatorfromcontractorsandowner承包商、、業(yè)主調(diào)調(diào)試負(fù)責(zé)責(zé)人或協(xié)協(xié)調(diào)員Operations/Production,maintenance,R&D,EHS,QC,QA,Qualification&Validationfromtheowner業(yè)主生產(chǎn)產(chǎn)運行、、維護、、研發(fā)、、環(huán)保及及健康安安全、QC、QA、確認(rèn)與與驗證等等部門ServicesProviderandStakeholders服務(wù)提供供商及相相關(guān)方2012ISPECHINAANNUALCONFERENCETheAuthorities監(jiān)管部門門Food&DrugAdministration食品藥品品監(jiān)督部部門Municipalplanning&constructionadministration規(guī)劃、建建設(shè)管理理部門EnvironmentalProtection環(huán)保部門門Fireauthority消防部門門SafetySupervisionAdministration安全監(jiān)督督部門LaborProtection勞動保護護部門QualitySupervision質(zhì)量監(jiān)督督部門ServicesProviderandStakeholders服務(wù)提供供商及相相關(guān)方2012ISPECHINAANNUALCONFERENCERegulatoryRequirements法規(guī)要求求Necessity必要性Source（來源））:R.E.ChewandD.Petko(2007)EUGMPAnnex15andSFDAGMPChap.7“QualificationandValidation”definetherequirements.歐盟GMP附錄15和中國GMP第七章““確認(rèn)與與驗證””有明確確要求。。RelationshipofASTMStandardtoGMPregulationsandguidancedocumentsASTM標(biāo)準(zhǔn)與GMP法規(guī)和指指南文件件的關(guān)系系日本美國歐盟諸如CFR211.68“設(shè)備應(yīng)應(yīng)按書面面程序進進行校驗驗、檢查查、或核核對以確確保其恰恰當(dāng)性能能”等條條款是確確認(rèn)的基基礎(chǔ)ICHQ9質(zhì)量風(fēng)險險管理可可用來決決定“確確認(rèn)”的的范圍指導(dǎo)如何何執(zhí)行ASTM標(biāo)準(zhǔn)的主主要原理理及基本本原則闡明基于于風(fēng)險的的查證（（或確認(rèn)認(rèn)）的原原理及基基本原則則BenefitstotheOwner為業(yè)主帶帶來的好好處Riskcontrolledearlier風(fēng)險及早早得到控控制Reducetimeandcosttoachieveandmaintaincompliance降低項目目完成所所耗費用用與時間間并維持持項目的的合規(guī)性性Reducechangeordersduringconstruction減少施工工過程的的變更令令Lesswaste&repetition更少的浪浪費與重重復(fù)Reduceprojectdelays較少項目目推遲Shortenbuildingturnoverperiod縮短建筑筑交付周周期ValidationteamandQMSsetup建立驗證證團隊和和質(zhì)量管管理體系系Earlierreleasedandcommercialmanufacture更早地通通過認(rèn)證證并投入入商業(yè)生生產(chǎn)Necessity必要性BenefitstotheOwner(cont.)為業(yè)主帶帶來的好好處(續(xù)）Costeffectiveoperationandmaintenance經(jīng)濟高效效的運行行及維護護Reduceequipmentreplacement減少設(shè)備備更換Betterknowledge,understandingofsystems對系統(tǒng)更更好的認(rèn)認(rèn)識和理理解Bettertrainedoperationsstaff更好地培培訓(xùn)運行行團隊Operationsandmaintenancemanualsarecompleteandsubmittedatprojectturnover.運行及維維護手冊冊完成并并在項目目交付時時提交Necessity必要性BenefitstotheContractors對承包商商的好處處Betterplanningwillresultinimprovedinstallation更好的計計劃可導(dǎo)導(dǎo)致安裝裝的改進進Moreemphasisonqualitycontrolonwhatmatters對質(zhì)量控控制更加加強調(diào)Quickerresolutionofproblems(identifyproblemsduringQC)更快地解解決問題題（在QC過程中界界定問題題）Increaselikelihoodofcompletingprojectonschedule––maximizeprofit提高按時時完成項項目的可可能性—利潤最大大化Reducepost-constructioncallbacks–preserveprofit減少施工工后召回回—保護利潤潤Necessity必要性BenefitstotheAuthorities對監(jiān)管部部門的好好處Genuine,validandsystemicdocumentations文件真實實、有效效、系統(tǒng)統(tǒng)Easyofinspection便于檢查查Genuine,crediblerecordsandtrends真實可信信的記錄錄與趨勢勢Easyofsupervision便于監(jiān)管管Clearmanagementprograms,integralapprovalsinmanufacturer’ssite廠商管理理程序清清晰，審審批完整整Easyofinvestigationafterwards便于事后后追究Necessity必要性ImplementationFlowofPharmaceuticalProject制藥工業(yè)業(yè)項目實實施流程程ProductionStart有效投產(chǎn)產(chǎn)FeasibilityStudy可行性研研究ConceptDesign概念設(shè)計計Procurement采購Construction施工DetailEngineering詳細(xì)設(shè)計計SupportValidation驗證支持持C&Q調(diào)試與確認(rèn)Decision““GO””客戶決定工工程繼續(xù)進行行Basic+Ext.BasicEngineering基本＋擴充充設(shè)計FinalinvestmentDecision客戶做出最最終投資決定定CostEstimate造價估算20%CostEstimate造價估算10%ConceptPhase概念階段DesignPhase設(shè)計階段ExecutionPhase實施階段HandOver交付ValidationPhase驗證階段MaintenanceCustomerService維修/客戶服務(wù)FacilityManagement設(shè)施管理SecondOpinionValueEngineering修改/補充Implementation實施Workflow工作流程Acknowledgement（感謝）:InstructionfromMr.D.W.VincentF(設(shè)施)-URSGA偏差分析BOD設(shè)計基礎(chǔ)VMP驗證總計劃劃RA風(fēng)險分析E/S(設(shè)備/系統(tǒng))-URSVP驗證計劃CSVFD/FS功能設(shè)計/說明DD/DS詳細(xì)設(shè)計/設(shè)計說明CP(FAT,SAT,etc.),Qual.Protocol調(diào)試計劃及及確認(rèn)方案案PQ性能確認(rèn)OQ運行確認(rèn)IQ安裝確認(rèn)Commissioning(FAT/SAT,etc.)Exec.調(diào)試（工廠廠/現(xiàn)場驗收測測試等）執(zhí)執(zhí)行DQ設(shè)計確認(rèn)Procurement&Construction采購施工CV清潔驗證SterilizationValidation滅菌驗證PV工藝驗證MediumFill培養(yǎng)基灌裝裝UtilityQua/Val公用系統(tǒng)確確認(rèn)/驗證FumigationValidation熏蒸驗證AIQ分析儀器確確認(rèn)CSV計算機系統(tǒng)統(tǒng)驗證CSV計算機系統(tǒng)統(tǒng)驗證CSV計算機系統(tǒng)統(tǒng)驗證AMV分析方法驗驗證SIA系統(tǒng)影響評評估GMPRev.GMP審核Implementation實施Workflow工作流程Acknowledgement（感謝）:InstructionfromMr.C.BachofenWorkflow——abriefcasestudy(WFIsystem)工作流程–簡略的案例例分析(注射用水系系統(tǒng)）Specifythefinalusers,capacity,standards，etc.tobefollowedforWFI.systeminF-URS在設(shè)施URS中明確注射射用水系統(tǒng)統(tǒng)的終端用用戶、供應(yīng)應(yīng)能力以及及遵循的標(biāo)標(biāo)準(zhǔn)等。ImplementGAfortherenovatedsystems.對改造的系系統(tǒng)進行偏偏差分析。。DeveloptheschematicdesignofWFIsystem(e.g.MB,PFD，mainequipmentlist)intheBODofthefacility（designconsultant).在設(shè)施的設(shè)設(shè)計基礎(chǔ)中中進行注注射用水系系統(tǒng)的方案案設(shè)計（物物料平衡、、工藝流程程圖,主要設(shè)備表表等）(設(shè)計咨詢方方）。Implementation實施Workflow——abriefcasestudy(WFIsystem)（cont.)工作流程–簡略的案例例分析(注射用水系系統(tǒng)）(續(xù)）ImplementtheIAoftheWFIsystemaccordingtothecriteria.按照判據(jù)進進行注射用用水的影響響評估。。SpecifythelevelofC&Qs(includingCSV)andtherationaleofthesysteminVMP.在驗證總計計劃中闡明明調(diào)試確認(rèn)認(rèn)(包括計算機機系統(tǒng)驗證證）的程度度及原因.DeveloptheURSofthesystem(includingtheC&Qrequirement),VPbasedonRA.在風(fēng)險分析析的基礎(chǔ)上上編制系統(tǒng)統(tǒng)的URS及驗證計劃劃.Implementation實施Workflow——abriefcasestudy(WFIsystem)（cont.)工作流程–簡略的案例例分析(注射用水系系統(tǒng)）(續(xù)）DevelopFS、DSfortheWFIsystem(BD,DD—designconsultantorcontractor).編制注射用用水系統(tǒng)的的功能說明明、設(shè)計說說明（基礎(chǔ)礎(chǔ)設(shè)計、詳詳細(xì)設(shè)計—設(shè)計方或承承包商）。。DeveloptheCommissioning(e.g.FAT/SAT)planandDQ、IQ、OQprotocolsfortheWFIsystemwithaC&Qintegratedapproach.以調(diào)試與確確認(rèn)相整合合的方式編編制調(diào)試（（如FAT/SAT）計劃和DQ、IQ、OQ方案。ImplementtheDQoftheWFIsystemwithstructuralreviewapproachandFEMA(basedonC-IA)采用結(jié)構(gòu)化化審核方式式和建立在在部件影響響評估基礎(chǔ)礎(chǔ)上的潛在在故障形式式和影響分分析（設(shè)計計FMEA)進行注射用用水系統(tǒng)的的設(shè)計確認(rèn)認(rèn)。Implementation實施Workflow——abriefcasestudy(WFIsystem)（cont.)工作流程–簡略的案例例分析(注射用水系系統(tǒng)）(續(xù)）Implementtheconstruction、commissioning、IQ、CSV、OQaccordingtotheapprovedDD、commissioningplanandqualificationprotocolswiththeintegratedapproach采用整合方方式按批準(zhǔn)準(zhǔn)的詳細(xì)設(shè)設(shè)計、調(diào)試試計劃和確確認(rèn)方案實實施注射用用水系統(tǒng)的的施工、調(diào)試、安裝確認(rèn)、計算機系系統(tǒng)驗證、、運行確認(rèn)。ImplementPQ/validation（approvetheSOPs,verifycontrol,verifylong-termcontrol)oftheWFIsystembasedonOQ,andrelativeAIQ、AMV、relativeCV、SV、U-Q/V.在運行確認(rèn)認(rèn)以及相關(guān)關(guān)分析儀器器確認(rèn)、分分析方法驗驗證、清潔潔/消毒驗證，，公用系統(tǒng)統(tǒng)確認(rèn)/驗證的基礎(chǔ)礎(chǔ)上實施PQ或注射用水水系統(tǒng)驗證證(水質(zhì)檢測通通過并批準(zhǔn)準(zhǔn)運行SOP、驗證受控控、驗證長長期受控））。Implementation實施2012ISPECHINAANNUALCONFERENCEInterfaceswithOtherProjectParties與其它項目目參與方的的接口Implementation實施用戶需求規(guī)格（URS）1Contracts,FS,DS采購合同、說明書和規(guī)格2SamplingRecords廠家提供的試樣記錄2FAT/SAT1,I&CRecords廠家安裝和試車4040記錄2ProcessR&DRecords工藝試驗和記錄2設(shè)計確認(rèn)（DQ）1，3安裝確認(rèn)（IQ）1操作確認(rèn)（OQ）1性能確認(rèn)（PQ）1工藝驗證（PV）1SOPofOperation,Clean,MaintainandValidation操作、清潔、維護和驗證管理等SOP1ProductionMasterRecords(CPP,Controllimit,SamplingPlan,etc)生產(chǎn)主記錄（工藝控制點、控制范圍、取樣計劃等）1Formulation&Process

配方和生產(chǎn)工藝4Non-GMPDocuments非GMP文件GMPDocumentsGMP文件Support提供支持1-Reviewed&approvedaccordingtoprocedures,whengapsoccur,shouldexplain,andinvestigatewhennecessary.應(yīng)當(dāng)按一定定程序?qū)徍撕撕团鷾?zhǔn)，，實施過程程中如有偏偏差，應(yīng)解解釋，必要要時進行調(diào)調(diào)查。2-Canbedevelopedanduseddirectly,gapsoccuratimplementationarenotrequiredtoexplain.可直接編寫寫和使用，，不一定需需要解釋實實施過程中中的偏差。。3-DQisaregulatoryrequirementinEU,butnotinUS.在歐盟為法法規(guī)要求，，在美國非非法規(guī)要求求.4-Reviewedandapprovedbyauthority,changeshouldbecontrolledaccordingtoregulatory.由主管當(dāng)局局審核和批批準(zhǔn)，變更更應(yīng)遵循法法定程序。。Vendor/Contractor供應(yīng)商/承包商Owner(+Consultant)業(yè)主(+咨詢方)Owner業(yè)主Owner(+Consultant)業(yè)主(+咨詢方)Owner(+Consultant)業(yè)主(+咨詢方)Source（來源）:Y.Liu(2008)ValidationMasterPlan驗證主計劃劃DesignIntent設(shè)計目的P&ID’s管道儀表流程程圖Specification技術(shù)規(guī)格Drawings圖紙RegulatoryDocuments規(guī)范文件ValidationProtocols驗證方案Start-UpDocuments調(diào)試文件ExecuteValidation執(zhí)行Validationreports驗證報告OperationDocuments操作文件Lists清單FactoryTests工廠測試FieldTestDocuments現(xiàn)場測試文件件InstallationDocuments安裝文件VendorDocuments廠商文件PurchasingDocuments采購文件EngineeringDocuments設(shè)計文件ConstructionDocuments施工文件CommissioningDocuments調(diào)試文件Implementation實施Documentationsystemreflectingthelifecycle反映制藥工業(yè)業(yè)項目周期的的文件系統(tǒng)GoodDocumentationPractices良好記錄規(guī)范范GoodDocumentationPractices(cont.)良好記錄規(guī)范范(續(xù)）Overwrites涂改Errorsindateformatandinitials日期及簽字不不正確Completingformsandrecordinformationafterthefact事后補填表格格與記錄Incompleterecords記錄不完整Backdatinginformation過期信息Crossingoutcalculationsandcriticaldatawithoutjustification無正當(dāng)理由給給計算與關(guān)鍵鍵數(shù)據(jù)打叉Implementation實施GoodDocumentationPractices(cont.)良好記錄規(guī)范范(續(xù)）Transcribinginformation抄寫信息LeavingblankspaceswithoutN/A表格留空，沒沒填“不適用用”Falsifyingdocuments偽造文件Obliteratinginformationi.e.usingwhiteout,doubleormultiplecrossouts用涂改液、雙雙線或多線涂涂去信息Replacingpagesindocumentafteritwasapproved將批準(zhǔn)后的文文件換頁Lackoftraceability缺乏可追溯性性Implementation實施Acknowledgement（感謝）:InstructionfromMr.D.W.Vincent