過程確認及方法概述專家講座

ProcessValidation&ApproachOverview

過程確認及方法概述WallyWang

ParagonMedicalDeviceChangzhou

王新化派瑞格醫(yī)療器械（常州）有限企業(yè)過程確認及方法概述專家講座第1頁Agenda/Topics

日程/主題WhatisProcessValidation?什么是過程確認？Briefhistoryofvalidation確認簡明歷史Whoconcernsaboutvalidation? 誰關心確認？Expectations期望Definitions/Compliance定義/符合性ValidationEconomics確認經(jīng)濟意義ExamplesofWarningLetters警告信案例ElementsofProcessValidation 過程確認要素WhentoValidate何時確認ValidationMasterPlans確認主計劃WhatisRequiredtoBeOutstandinginProcessValidation?確認中需要強調(diào)什么？StepstoValidationofaProcess過程確認步驟Protocoldevelopment方案編制

IQ安裝判定OQ操作判定PQ性能判定TheFinalReport最終匯報Revalidation 再確認Monitoring 監(jiān)控過程確認及方法概述專家講座第2頁WhyArewediscussthis?

為何我們要討論？Validationmaybenew

可能確認對你來說是一個全新概念Youneedarefresher

你需要更新知識Youhavespecificquestions

你有一些詳細問題Youmaybeundera483(orworse,awarningletter!)

可能你已經(jīng)收到了483（或更糟，警告信?。┻^程確認及方法概述專家講座第3頁WhatisProcessValidation(FDA)?

什么是過程確認(FDA)？Processvalidationisestablishingdocumentedevidencewhichprovidesahighdegreeofassurancethataspecificprocesswillconsistentlyproduceaproductmeetingitspredeterminedspecificationsandqualitycharacteristics

過程確認就是建立一套能證實特定過程能夠以高度信心連續(xù)地生產(chǎn)出滿足預定規(guī)格和質(zhì)量特征產(chǎn)品書面證據(jù)。GuidelinesonGeneralPrincipleofProcessValidation,GMPManual,May1987過程確認總標準指導，1987年5月，GMP手冊，

過程確認及方法概述專家講座第4頁WhatisProcessValidation(GHTF)?

什么是過程確認(GHTF)?

Processvalidation:establishingbyobjectiveevidencethataprocessconsistentlyproducesaresultorproductmeetingitspredeterminedrequirements.

過程確認：有客觀證據(jù)支持，即過程將連續(xù)地產(chǎn)出符合預定要求結果或產(chǎn)品。

GHTF

過程確認及方法概述專家講座第5頁HistoryofValidation

確認簡明歷史Before1978….noFDAregulations 1978年之前….沒有FDA法規(guī)CurrentGMPbecamelawin1978

當前GMP是在1978年成為法規(guī)1987…GlobalHarmonizationTaskForcereleased:QualityManagementSystems-ProcessValidationGuidance 1987年…醫(yī)療器械全球協(xié)調(diào)行動組織公布：質(zhì)量管理體系-過程確認指導1987…FDArelease:GuidelineonGeneralPrinciplesofProcessValidation 1987年…公布FDA：過程確認總標準指導1999…GlobalHarmonizationTaskForceupdate:QualityManagementSystems-ProcessValidationGuidance 1999年…醫(yī)療器械全球協(xié)調(diào)行動組織更新了：質(zhì)量管理體系-過程確認指導…GlobalHarmonizationTaskForceupdate:QualityManagementSystems-ProcessValidationGuidance

年…醫(yī)療器械全球協(xié)調(diào)行動組織更新了：質(zhì)量管理體系-過程確認指導過程確認及方法概述專家講座第6頁

Whoconcernsaboutvalidation?

誰關心確認？Medicaldevicemanufacturingandqualitymanagementregulatory醫(yī)療器械生產(chǎn)質(zhì)量管理規(guī)范FDAPreambleFDA導言ISO13485：；YY0287：21CFR820-FDARegulation 21CFR820-FDA法規(guī)GlobalHarmonizationTaskForce全球醫(yī)療器械協(xié)調(diào)行動組織Companywhohopestoconsistentlyproduceaproductmeetingitspredeterminedspecificationsandqualitycharacteristics

希望能連續(xù)地生產(chǎn)出滿足預定規(guī)格和質(zhì)量特征產(chǎn)品企業(yè)

過程確認及方法概述專家講座第7頁TheExpectation

期望Oneoftheprinciplesonwhichthequalitysystemsregulationisbasedisthatallprocessesrequiresomedegreeofqualification,verification,orvalidation,andmanufacturersshouldnotrelysolelyoninspectionandtestingtoensureprocessesareadequatefortheirintendeduse.

質(zhì)量體系法規(guī)建立基本標準之一是：全部過程都要求進行一定程度認證、驗證、或確認，制造商不應該僅僅依靠檢驗和測試來確保其過程能充分地滿足其預期要求。Pre-amble#41,pg.52612過程確認及方法概述專家講座第8頁DoesYourCompanyNeedtoDoProcessValidation?

你們企業(yè)需要做過程確認嗎？Yes,ifyouareproducingamedicaldevice(itisthelaw!!!)

是，假如你們生產(chǎn)醫(yī)療器械，需要做過程確認（這是法規(guī)要求?。。。￤hatareclassesofmedicaldevices?

醫(yī)療器械類別ClassI一類ClassII二類ClassIII三類過程確認及方法概述專家講座第9頁DoesYourCompanyNeedtoDoProcessValidation?

你們企業(yè)需要做過程確認嗎？

Areanyclassesofmedicaldevicesexempt?

哪個類別醫(yī)療器械不需要做過程確認？No!UnlessspecificallystatedinMedicalDeviceExemptions510(k)andGMPRequirements

沒有！除非醫(yī)療器械豁免510(k)和GMP要求中有尤其申明。/scripts/cdrh/cfdocs/cfpcd/315.cfm過程確認及方法概述專家講座第10頁Definitions

定義UnderstandingdefinitionsisimportantinmakingsureweallareonthesamepageespeciallywhenitcomestotalkingwiththeFDA.

了解定義對于確保我們有相同了解是非常主要，尤其當我們與FDA討論時。YourdefinitionofhowatermisinterpretedisnotasimportantasknowinghowtheFDAinterpretsit!

對于一個條款解釋，你個人解釋沒有了解FDA解釋主要。過程確認及方法概述專家講座第11頁ObjectiveEvidence

客觀證據(jù)Objectiveevidenceisinformationthatcanbeprovedtrue,basedonfactsthroughobservation,measurement,testorothermeans.

客觀證據(jù)是能夠經(jīng)過觀察、測量、測試或其它方法被證實為真實信息。ISO84022.19Astheoldsayinggoes,“Ifyoudidn’tdocumentit,youdidn’tdoit!”正如老話所說“假如你沒有做統(tǒng)計，就等于你什么也沒做”。過程確認及方法概述專家講座第12頁Verification

驗證Confirmationbyexaminationandprovisionofobjectiveevidencethatspecifiedrequirementshavebeenfulfilled.

經(jīng)過檢驗并提供客觀證據(jù)來證實已經(jīng)滿足特定要求。820.3(aa)過程確認及方法概述專家講座第13頁ProcessValidationProtocol

過程確認方案Adocumentstatinghowvalidationwillbeconducted,includingtestparameters,productcharacteristics,manufacturingequipment,anddecisionpointsonwhatconstitutesacceptabletestresults.

說明怎樣實施確認文件，包含了測試參數(shù)、產(chǎn)品特征、生產(chǎn)設備和由什么組成可接收測試結果判斷關鍵點。GHTFSometimesvalidationrequiresyoustartwiththeacceptancecriteriaandworkbackwards.

有時候，過程確認要求你首先從確定接收標準開始，逆向實施確認。過程確認及方法概述專家講座第14頁Installationqualification(IQ)安裝判定（IQ）

Establishingbyobjectiveevidencethatallkeyaspectsoftheprocessequipmentandancillarysysteminstallationadheretothemanufacturer’sapprovedspecificationandthattherecommendationsofthesupplieroftheequipmentaresuitablyconsidered.用客觀證據(jù)來支持證實，所安裝過程設備和輔助系統(tǒng)關鍵安裝方面，能滿足制造商已同意技術規(guī)范，且供給商提議也被恰當考慮了。

》GHTF過程確認及方法概述專家講座第15頁Operationalqualification(OQ)操作判定（OQ）Establishingbyobjectiveevidenceprocesscontrollimitsandactionlevelswhichresultinproductthatmeetsallpredeterminedrequirements用客觀證據(jù)確定能夠生產(chǎn)出滿足全部預定要求產(chǎn)品過程控制極限和行動標準?！稧HTF

過程確認及方法概述專家講座第16頁Performancequalification(PQ)性能判定（PQ）establishingbyobjectiveevidencethattheprocess,underanticipatedconditions,consistentlyproducesaproductwhichmeetsallpredeterminedrequirements.用客觀證據(jù)確定，在預期條件下，過程能連續(xù)地產(chǎn)出符合全部預定要求產(chǎn)品?！稧HTF過程確認及方法概述專家講座第17頁ValidationEconomics

確認經(jīng)濟意義Whatisthecostofvalidatingaprocess?進行過程確認所付出成本是什么？Whatisthecostofnotvalidatingaprocess?不進行過程確認所付出成本是什么？過程確認及方法概述專家講座第18頁ValidationEconomics

確認經(jīng)濟意義Increasedoutput(processvelocity)

產(chǎn)量提升（過程速度）Fewerproductnon-conformances

更少不合格產(chǎn)品Lessscrapandrework

更少許報廢和重新加工Fewercomplaints

更少投訴Theprocessbecomescharacterized

過程變得特征化Processbecomesmorepredictable

過程變得更可預測Lesschanceofrecalls更少召回可能性Regulatorycompliance符正當規(guī)要求

過程確認及方法概述專家講座第19頁ExamplesfromWarningLetters

來自警告信中案例Thislotwasnotproducedusingthemanufacturingprocessdiscussedinthevalidationstudyprotocol.

這批產(chǎn)品沒有按照確認方案中討論制造過程生產(chǎn)。Themoldingoperationwaschangedtoimprovethevisibilityofthebiohazardsymbolonthecap;theinterlockofthecapintothetubewaschangedtoimprovethepullstrengthtesting;andshortcapswereaddedtoaccommodatedifferentsizesyringes.Verificationsand/orvalidations,designreviews,designreleases,anddesignapprovalswerenotperformedforanyofthesechanges.

….對于這些變更沒有實施確認和/或確認，設計評審，設計公布，以及設計同意。Specifically,recordswerenotavailabletoshowthatthebursttestonlot31255wasperformedatthemaximumsterilizationdose.

尤其是，沒有統(tǒng)計能夠表明批號為31255產(chǎn)品按照最大滅菌劑量進行了爆裂測試。Yourfirmfailedtoverify/validateseveralprocessdeviationsasrequiredby21CFR820.75.

你們沒有按照21CFR820.75要求進行驗證/確認過程偏差。過程確認及方法概述專家講座第20頁SomeFDAComplianceOfficerComments

FDA符合官員一些評論“Specificationsneedtobedevelopedbeforeyougettothevalidationstage.” “進行確認之前，需要制訂技術規(guī)范?！薄癕anufacturerssometimesmissthestepofcompletingadequateprotocolsbeforeproceedingwithvalidationactivities.” “制造商有時會忘記在開始確認之前完成充分方案?！薄癕anufacturerssometimesfailtorevisitthevalidationprocesswhenmodificationsaremadeinproductsorprocesses.” “當發(fā)生產(chǎn)品或過程變更時，制造商有時沒有重新進行過程確認?！边^程確認及方法概述專家講座第21頁SoWhyDon’tCompaniesJustDoIt?

為何我們不能馬上進行過程確認呢？Misunderstandingoftheregulation

對法規(guī)誤解Lackofknowledgeinexecution

缺乏實施知識Lackofresourcestoexecute

缺乏實施資源Fearoffailure

害怕失敗Lackofmanagementsupport

缺乏管理層支持Fearofdelaytomarket

擔心延誤了上市Inhibitsprocesschange

隱藏了過程改變過程確認及方法概述專家講座第22頁過程確認要素確認安裝判定操作判定性能判定開發(fā)過程確認及方法概述專家講座第23頁何時確認A過程輸出可驗證嗎？B驗證是充分及成本可接收嗎？C驗證并控制過程D確認E重新設計產(chǎn)品和/或過程過程確認及方法概述專家講座第24頁ProcessesWhichShouldBeValidated

需要確認過程

Sterilization 滅菌Cleanroomambientconditions

凈化室周圍環(huán)境Asepticfillingprocesses無菌填充過程Sterilepackagingsealingprocesses

無菌包裝密封過程Lyophilizationprocess（低壓）凍干過程Heattreatingprocesses

熱處理過程Plasticinjectionmoldingprocess

注塑成型過程……GHTF過程確認及方法概述專家講座第25頁ProcessesThatMayBeVerified

能夠驗證過程Manualcuttingprocesses

手動切割過程Testingforcolor,turbidity,totalpHforsolutions

測試溶液顏色，混濁度，總pH值Visualinspectionofprintedcircuitboards

印制電路板目視檢驗Manufacturingandtestingofwiringharnesses電纜線束制造和測試GHTF過程確認及方法概述專家講座第26頁WhatisaValidationMasterPlan?

什么是確認主計劃（VMP）Amastervalidationplanidentifiesthoseprocessestobevalidated,thescheduleforvalidations,interrelationshipsbetweenprocessesrequiringvalidationandtimingforrevalidations.Oncethesehavebeenestablished,andthepurposeandscopeforvalidationsareclearlystatedandknown,protocoldevelopmentcancommence確認主計劃用以明確哪些過程要確認，確認（過程）進度表，要求確認過程和再確認（過程）時間選定上相互關系。一旦確定了上述內(nèi)容、清楚地要求確認目標和范圍并對外通知，方案編制便能夠著手進行了。Itdocumentsspecificallythevalidationofequipment,processes,software,facilities,etc.

它統(tǒng)計了要被確認設備、過程、軟件、設施等。Itsamapoftheprocessvalidationprocessfortheteamtofollow.它是團體要恪守過程確認根本圖。AVMPisanindexthatFDAcanfollowinunderstandingyourvalidations.

確認主計劃是FDA用來了解你確實認索引

過程確認及方法概述專家講座第27頁WhyUseaValidationMasterPlan?

為何要用確認主計劃AlthoughthesearenotrequiredbytheFDAregulationsitisoneofthefirstthingsthatanauditormayaskforduringaninspection.

盡管這不是FDA法規(guī)所要求，不過它是審核員在檢驗過程中所要求首要東西之一。IfacompanyholdstruetoitsVMPanditsdocumentedevidence,credibilityisestablishedandFDAwillhavemoreconfidenceinone’soutcomes.

假如企業(yè)能夠按照VMP做而且統(tǒng)計了證據(jù)，信任就建立起來了，F(xiàn)DA對其結果就會更有信心。過程確認及方法概述專家講座第28頁WhyUseaValidationMasterPlan?

為何要用確認主計劃Allowsonetobeproactiveratherthanreactive.

考慮前瞻性而不是事后反應Providesdefinition,scopecreep,andcommitmenttoresponsibilities.

提供了定義、范圍以及對職責承諾Itprovidesamaporguidetotheauditordefininghowthecompanyistyingtheirconcepttorealityinordertosuccessfullyachieveuserrequirements.它為審核員提供了企業(yè)為了成功滿足用戶要求而怎樣將企業(yè)觀念和實際聯(lián)絡在一起路線圖或指導方向過程確認及方法概述專家講座第29頁ComponentsofaValidationMasterPlan?

確認主計劃組成Definitionoftheproject項目定義Strategyorapproachtotheproject項目標策略或方法Scopeoftheproject項目標范圍Whatprocesseswillbevalidated?將被確認過程Whatprocesseswillbeverified?將被驗證過程Responsibilities職責過程確認及方法概述專家講座第30頁ComponentsofaValidationMasterPlan?

確認主計劃組成Arethereanyspecialconsiderations?

是否有任何特殊考慮？Keymilestones

關鍵里程碑Validationprotocolnumbers確認方案編號AVMP,perse,isnotthesameasaprojectplan!過程確認及方法概述專家講座第31頁WhatisinaValidationMasterPlan?

確認主計劃是什么

確認方案編號.編號EVAPVA計劃開始日期計劃完成日期實際完成日期EN是否完成了？責任人備注IQOQPOOQPQ設備過程

過程確認及方法概述專家講座第32頁WhatisRequiredtoBeOutstandinginProcessValidation?

過程確認中需要強調(diào)什么？Planning

計劃CrossfunctionalteamTHATCANWORKTOGETHER!!!

相關職能部門，一起合作Profoundprocessknowledge

淵博過程知識Havingalongtermcommitment

長久承諾Roadmapreflectingregulatoryguidelines

能反應法規(guī)指導路標圖Metricstomapprogress

進展指標Passionforexcellence

追求卓越激情過程確認及方法概述專家講座第33頁StepstoValidationofaProcess

過程確認步驟Formamulti-disciplinaryteam組建一個多功效小組Plantheapproachanddefinerequirements制訂步驟并定義要求Identifyanddescribetheprocess識別和描述過程Specifyprocessparametersanddesiredoutput要求過程參數(shù)和希望輸出Decideonverificationandorvalidation就驗證和（或）確認做出決定CreateaValidationMasterPlan制訂一個主要確認方案過程確認及方法概述專家講座第34頁StepstoValidationofaProcessSelectmethodsandtoolsforvalidations選擇確認方法和工具Createvalidationprotocols編制確認方案PerformIQ,OQ,PQanddocumentresults執(zhí)行IQ、OQ、PQ并將結果形成文件Determinecontinuousprocesscontrols確定連續(xù)過程控制Controltheprocesscontinuously連續(xù)地控制過程過程確認及方法概述專家講座第35頁Protocoldevelopment方案編制

Processvalidationprotocolsshouldincludethefollowingelements:過程確認方案應該包含以下元素：Completedescriptionoftheprocess過程完整描述Identificationoftheprocesstobevalidated要確認過程標識Selecttheworstcase

選擇最差條件（產(chǎn)品）Identificationofdevice(s)tobemanufacturedusingthisprocess在這個過程下產(chǎn)出器械標識Objectiveandmeasurablecriteriaforasuccessfulvalidation一個成功確認目標和可測量標準Lengthanddurationofthevalidation確認用時和使用期限Shifts,operators,equipmenttobeusedintheprocess過程中采取輪班制、操作人員和設備Identificationofutilitiesfortheprocessequipmentandqualityoftheutilities過程設備中使用器具(utilities)標識和質(zhì)量Identificationofoperatorsandrequiredoperatorqualification操作員識別和要求操作員資格（證）

過程確認及方法概述專家講座第36頁Protocoldevelopment方案編制

、Relevantspecificationsthatrelatetotheproduct,components,manufacturingmaterials,etc產(chǎn)品、元件、生產(chǎn)材料等相關規(guī)格Anyspecialcontrolsorconditionstobeplacedonprecedingprocessesduringthevalidation在（過程）確認中，對先發(fā)生過程所設置任何特殊控制或條件Processparameterstobemonitored,andmethodsforcontrollingandmonitoring要監(jiān)控過程參數(shù)和監(jiān)控方法Productcharacteristicstobemonitoredandmethodformonitoring監(jiān)視產(chǎn)品特征和方法Anysubjectivecriteriausedtoevaluatetheproduct用來評定產(chǎn)品主觀標準Definitionofwhatconstitutesnon-conformanceforbothmeasurableandsubjectivecriteria對于可測量標準和主觀標準，定義什么是不合格Statisticalmethodsfordatacollectionandanalysis數(shù)據(jù)搜集和分析統(tǒng)計方法Considerationofmaintenanceandrepairsofmanufacturingequipment生產(chǎn)設備保養(yǎng)和修理方面考慮IQ、OQ&PQ

Criteriaforrevalidation再確認標準過程確認及方法概述專家講座第37頁Protocoldevelopment方案編制

Forallthreephases,IQ,OQ,andPQ,basedonproduct/processrequirements:對于三個階段，IQ、OQ和PQ都要基于產(chǎn)品或過程要求：Determinewhattoverify/measure決定驗證或測量什么Determinehowtoverify/measure決定怎樣驗證或測量Determinehowmanytoverify/measure,i.e.statisticalsignificance決定驗證或測量多少，如統(tǒng)計量Determinewhentoverify/measure決定何時驗證或測量Defineacceptance/rejectioncriteria要求接收或拒絕標準Definerequireddocumentation要求要求文件Remember:protocolmustbereviewedandapprovedbeforeexecution記住，在實施前，方案必須被評審和同意。過程確認及方法概述專家講座第38頁Protocoldevelopment方案編制

Generally,protocolincludes4sections:普通來講，方案可分為四大部分：The1stsection:validationoverview,includingvalidationscope,processdescription,background,worstcases,lengthanddurationofthevalidation,objectiveetc.第一部分：確認概述部分，包含確認范圍，過程描述，背景介紹，最差條件挑選，確認用時和使用期限，目標

等等；The2ndsection:qualificationreadiness,includingtherequirementsforman,machine,material,method,environment,testandlabel&traceability,PFMEAetc.第二部分：判定準備階段，包含全部人、機、料、法、環(huán)、測及標志和追溯,PFMEA等要求和準備；The3rdsection:qualification(IQ,OQ&PQ),includingqualificationplananddeviationdisposaletc.第三部分：判定階段(IQ,OQ&PQ)，包含判定計劃及偏差處理等；The4thsection:documentrequirements，includingtheinputandoutputdocumentsrequiredbythisprotocol.第四部分：文件要求，包含本方案所需文件及輸出文件要求。過程確認及方法概述專家講座第39頁QualificationTypes

判定類型Howdorequirementsapply?怎樣應用這些要求QualificationType判定類型Application應用IQ

Gagecalibration量具校準Verificationofinstallationitems（EIQ，EOQ&EPQ）安裝項目驗證（EIQ，EOQ&EPQ）OQGageR&RDOESamplingplans抽樣計劃Otherstatisticaltechniques其它統(tǒng)計技術PQ

ControlCharts控制圖Cp/CpkstudiesSamplingplans抽樣計劃過程確認及方法概述專家講座第40頁TheImportanceofGaging

量具主要性Yourmeasurementmethodismostimportantindeterminingyourprocessparameters.

在確定你過程參數(shù)過程中，你測量方法是最主要。Gagesmeasurevariationandprovidesignalsforchangesinvariation.

量具用來測量變差并提供變差改變信號。Gagesarethecompasstohelpnavigatethroughthevalidationprocess.量具是整個確認過程中幫助我們導航羅盤。過程確認及方法概述專家講座第41頁InstallationQualification(IQ)

安裝判定（IQ）Establishingbyobjectiveevidencethatallkeyaspectsoftheprocessequipmentandancillarysysteminstallationadheretothemanufacturer’sapprovedspecificationandthattherecommendationsofthesupplieroftheequipmentaresuitablyconsidered.用客觀證據(jù)來支持證實，所安裝過程設備和輔助系統(tǒng)關鍵安裝方面，能滿足制造商已同意技術規(guī)范，且供給商提議也被恰當考慮了。GHTF過程確認及方法概述專家講座第42頁InstallationQualification(IQ)

安裝判定（IQ）“Istheequipmentinstalledcorrectly?”設備已經(jīng)正確安裝了嗎？IQGoal：IQ目標Verifyandproveallkeyaspectsoftheprocessequipmentandancillarysysteminstallationadheretothemanufacturer’sapprovedspecificationandthattherecommendationsofthesupplieroftheequipmentaresuitablyconsidered.驗證并證實所安裝過程設備和輔助系統(tǒng)關鍵安裝方面，能滿足制造商已同意技術規(guī)范，且供給商提議也被恰當考慮了。TheIQreducesriskbyreducingthenumberofrootcausessuspectedwhentroubleoccursintheOQandPQ.IQ經(jīng)過消減在OQ和PQ過程中出現(xiàn)麻煩可疑原因數(shù)量來降低風險Makesureequipmentstomeetintendeduse.

確保設備滿足預期用途

過程確認及方法概述專家講座第43頁InstallationQualification(IQ)

安裝判定（IQ）

Reviewintendeduse&Manufacturerequirements評審預期用途及制造商要求Definetheacceptancecriteria定義接收標準DefineIQitems定義IQ項目DevelopIQprotocol開發(fā)IQ方案ExecuteIQprotocol執(zhí)行ＩＱ方案EvaluateIQ評定IQ過程確認及方法概述專家講座第44頁InstallationQualification(IQ)

安裝判定（IQ）Importantconsiderationsare:IQ考慮事項：Equipmentdesignfeatures(constructionmaterials,cleanability)設備設計特點（如清潔裝置結構材料等）Installationconditions(wiring,utilities)安裝條件（布線、實用性、功效性等）Calibration,PreventiveMaintenance,cleaningschedules校準、預防性保養(yǎng)、清潔計劃Safety安全特征Supplierdocumentation供給商文件Softwaredocumentation軟件文件Sparepartslist零部件清單Environmentalconditions(temperature,humidity)環(huán)境條件（如清潔室要求、溫度和濕度）GHTF過程確認及方法概述專家講座第45頁AcceptanceCriteria

接收標準Considerations考慮點:Makethemclearandobjective清楚、客觀Bedescriptive可描述Attributesshouldreferenceastandardwhenpossible.可能時，定性參數(shù)應該作為參考標準Specificationscanbeatolerance,maximumorminimum規(guī)格應該有公差，最大或最小Theymustmakesense，必須能講清楚TheymustkeeptheOQandPQinmind必須一直把OQ和PQ記在心里

Acceptancecriteriaarecreatedbeforetheprotocolisapprovednotafterward接收標準要在方案同意之前制訂出來而不是之后制訂出來過程確認及方法概述專家講座第46頁InstallationQualification(IQ)

安裝判定（IQ）Protocolcomponents:方案組成Purpose目標Equipmentdescription設備描述Scope范圍Processdescription過程描述Itemstobeverifiedineachinstallationcategory在每個安裝類別里所要驗證項目過程確認及方法概述專家講座第47頁OperationalQualification(OQ)

操作判定（OQ）Establishingbyobjectiveevidenceprocesscontrollimitsandactionlevelswhichresultinproductthatmeetsallpredeterminedrequirements用客觀證據(jù)確定能夠生產(chǎn)出滿足全部預定要求產(chǎn)品過程控制極限和行動標準。

GHTF過程確認及方法概述專家講座第48頁OperationalQualification(OQ)

操作判定（OQ）OQGoal：OQ目標：TheOQisintendedtocreateaprocessscope(limits)

withinwhichanoperatorcontrolstheprocess.Thiswillchallengetheworstcase(Limits)OQ用于創(chuàng)建過程范圍(極限）,操作工可在此過程范圍內(nèi)控制過程。它將會挑戰(zhàn)過程最差條件按（極限）。Usinggoodscienceisessentialtoestablishingreliableprocessparameters.

使用正確科學知識是建立可靠地過程參數(shù)基本條件。過程確認及方法概述專家講座第49頁OperationalQualification(OQ)

操作判定（OQ）Reviewproductintendeduse&process/product

requirements評審預期用途及過程/產(chǎn)品要求Definetheacceptancecriteriaforproduct定義產(chǎn)品接收標準Defineprocessparameters定義過程參數(shù)DevelopOQplan開發(fā)OQ方案ExecuteOQprotocolandgetlimits&Nominal執(zhí)行OＱ方案,取得極限和中值EvaluateOQ,limitsarecapable評定OQ,極限是有能力Sometime,limitscanbegottenherefromexperienceandothersourceinadvance有時，此處可由經(jīng)驗或其它起源預先取得極限。過程確認及方法概述專家講座第50頁OperationalQualification(OQ)

操作判定（OQ）Importantconsiderationsare:主要考慮點：Processparameterscontrollimits過程參數(shù)控制線Defineproductionrunsbatchqty/productqtyandsequenceforeachgroupofparameters

確定每組參數(shù)生產(chǎn)批次/產(chǎn)品數(shù)量以及次序Acceptancecriteria接收標準Gagingortestmethods測量或測試方法Rawmaterials原材料Processchangecontrol過程變更控制

ThelimitsandconditionsestablishedintheOQwillbethesamelimitsandconditionsusedinthePQ.

在OQ中建立極限和條件將是用在PQ中所使用極限和條件相同。過程確認及方法概述專家講座第51頁OperationalQualification(OQ)

操作判定（OQ）Importantconsiderations:主要考慮點：Training培訓Methodfordeterminingshorttermstabilityandcapabilityofprocess確定短期穩(wěn)定性和過程能理方法Potentialfailuremodes,actionlevels,andworstcaseconditions可能故障狀態(tài)、作用程度和最壞情況條件UseofstatisticaltechniquestoidentifykeyprocessvariablesandDOEforoptimization統(tǒng)計學有效技術使用來識別關鍵過程變差及用DOE進行優(yōu)化過程確認及方法概述專家講座第52頁OperationalQualification(OQ)

操作判定（OQ）TheOQmusttestproductattheworsecaseprocessconditions.OQ必須測試在最差過程條件中生產(chǎn)產(chǎn)品Theworsecaseconditionsmustalsoincludeworsecaseproductwhenmorethanoneproductisinvolved(i.e.aproductfamily).當包括到不止一個產(chǎn)品時（比如一個產(chǎn)品族）最差條件也要包含最差條件產(chǎn)品。TheprocessparametersestablishedintheOQwillestablishtherevalidationcriteria.OQ中建立過程參數(shù)要建立再確認標準。過程確認及方法概述專家講座第53頁DeterminationofProcessScope

過程范圍確實定Conventionalapproach:Usebesttechnicaljudgmentstodeterminekeyparametersandoperatingscope傳統(tǒng)方法：使用最好技術判斷來決定關鍵參數(shù)和操作范圍。Enhancedapproach:UseDesignofExperimentstodetermineoperationalscope

先進方法：使用DOE來確定操作范圍。過程確認及方法概述專家講座第54頁AdditionalOQConsiderations

額外OQ考慮點Thisisthetimetofindthelimitsofyourprocess這是發(fā)覺你們過程極限時間。Thisisalsothetimetodemonstrateyouknowhowchangesininputswilleffectyourkeyprocesscharacteristics這是證實你們知道當輸入怎樣改變時會影響你們關鍵過程特征時間。 Remember:Oncethekeyprocesscontrolsareestablishedtheycannotbeviolatedbytheoperatorortheengineerwithoutrevalidation!記?。阂坏┙⒘岁P鍵過程控制，假如沒有再確認，任何操作工或工程師都不能違反他們。過程確認及方法概述專家講座第55頁PerformanceQualification(PQ)

性能判定（PQ）establishingbyobjectiveevidencethattheprocess,underanticipatedconditions,consistentlyproducesaproductwhichmeetsallpredeterminedrequirements.用客觀證據(jù)確定，在預期條件下，過程能連續(xù)地產(chǎn)出符合全部預定要求產(chǎn)品。GHTF過程確認及方法概述專家講座第56頁PerformanceQualification(PQ)

性能判定（PQ）PQGoal：

PQ目標：establishingbyobjectiveevidencethattheprocess,underanticipatedconditions,consistentlyproducesaproductwhichmeetsallpredeterminedrequirements.用客觀證據(jù)確定，在預期條件下，過程能連續(xù)地產(chǎn)出符合全部預定要求產(chǎn)品。

Normally,anticipatedconditionsarethebestconditions(NominalParameters).

通常情況下，預期條件就是最好條件（名義參數(shù)）過程確認及方法概述專家講座第57頁PerformanceQualification(PQ)

性能判定（PQ）

Inthisphasethekeyobjectiveistodemonstratetheprocesswillconsistentlyproduceacceptableproductundernormaloperatingconditions.

在此階段，要用關鍵目標來證實在正常操作條件下過程能連續(xù)生產(chǎn)出可接收產(chǎn)品。GHTFThePQmustbeperformedbytheoperator!PQ必須要由操作工來執(zhí)行！過程確認及方法概述專家講座第58頁PerformanceQualification(PQ)

性能判定（PQ）

WhileFDAbelievesthatthreeproductionrunsduringprocessvalidationistheacceptedstandard,FDArecognizesthatallprocessesmaynotbedefinedintermsoflotsorbatches.Thenumberthreeis,however,currentlyconsideredtobetheacceptablestandard.FDA相信在過程確認中三個生產(chǎn)循環(huán)是可接收標準，F(xiàn)DA認識到全部過程不可能依據(jù)批次來進行定義。然而，三這個數(shù)字當前被認為是可接收標準。FDAPreamble過程確認及方法概述專家講座第59頁Reviewproductintendeduse&process/productrequirements評審預期用途及過程/產(chǎn)品要求Definetheacceptancecriteriaforproduct定義產(chǎn)品接收標準Definenominalprocessparameters定義名義過程參數(shù)DevelopPQplan開發(fā)PQ方案ExecutePQprotocol執(zhí)行PＱ方案EvaluatePQ,nominalarecapable評定PQ,名義參數(shù)是有能力PerformanceQualification(PQ)

性能判定（PQ）過程確認及方法概述專家講座第60頁PQconsiderationsinclude:PQ應該考慮：ActualproductandprocessparametersandproceduresestablishedinOQOQ階段真實產(chǎn)品、過程參數(shù)和建立程序Acceptabilityoftheproduct產(chǎn)品可接收性AssuranceofprocesscapabilityasestablishedinOQ就像OQ階段那樣建立對過程能力確保Processrepeatability,longtermprocessstability過程重復能力和長久過程穩(wěn)定能力PerformanceQualification(PQ)

性能判定（PQ）過程確認及方法概述專家講座第61頁PQExecution

PQ實施1.Manufacturethepredeterminednumberoflots.生產(chǎn)預先確定批次數(shù)量產(chǎn)品2.Collectdataoneachlot.搜集每一批數(shù)據(jù)3.Analyzethedataapplyingtheproperstatisticaltechnique.使用恰當統(tǒng)計方法分析數(shù)據(jù)4.Documentallfindings.統(tǒng)計全部發(fā)覺5.Dispositiontheprotocol.方案處理

Note:Alllotsmustpasstoconsidertheprocessvalidated!注意：全部批次必須經(jīng)過將要被確認過程！過程確認及方法概述專家講座第62頁TheFinalReport

最終匯報Prepareatendofvalidationactivities

在確認活動最終準備Summarizethefindingsandanydeviationstotheprotocol.總結發(fā)覺和任何對方案偏離Includeallattachmentsrisenfromprotocol.包含由方案所引發(fā)全部附件ConsiderwhethertheOQisstillvalid.考慮是否OQ依然有效Deriveconclusionsregardingthevalidationstatusoftheprocess.應得出關于過程確認狀態(tài)結論Obtainfinalapprovalsignatures.取得最終同意簽字Releaseprocesstomanufacturing.將過程放行給生產(chǎn)過程過程確認及方法概述專家講座第63頁FailedStudy

失效研究Summarizethereport.

總結匯報Investigateanddocumenttherootcauses.

調(diào)查并統(tǒng)計根本原因DeterminewhethertheOQparametersaretherootcause.

確定是否OQ參數(shù)是根本原因DeterminewhethertheOQneedstobere-run.決定是否要重新進行OQDeterminewhetherthePQwillberunagain.決定是否再進行PQ過程確認及方法概述專家講座第64頁FailedStudy

失效研究Deviationsfromtheprotocol對方案偏離Deviationscanbeacceptable.

偏離是否是可接收Statethedeviation.

陳說偏離Statehowitdoesnotaffecttheprotocol

陳說偏離不影響方案Havethedeviationapproved.

讓偏離取得同意過程確認及方法概述專家講座第65頁DiscussionQuestions

問題討論Whathappensiftwooutofthreelotsfailduetooperatorerror?Caneachlotbedispositionedoneatatime?Candifferentproductsberunin-betweeneachvalidationlot?Whathappensiftheparametersneedtobetemporarilychangedduetoarawmaterialchange?Doesanewoperatorrequiretheprocesstoberevalidated?Whenequipmentismovedtoanewlocationdoesthepr