計算機(jī)化系統(tǒng)驗(yàn)證要點(diǎn)分析

目錄TableofContents3.新建及遺留計算機(jī)化系統(tǒng)驗(yàn)證示例分析CaseStudyforValidationofNewandLegacyComputerizedSystems2.新建計算機(jī)化系統(tǒng)驗(yàn)證流程介紹

IntroductiontoValidationProcessofNewComputerizedSystem目錄TableofContents1.計算機(jī)化系統(tǒng)相關(guān)法規(guī)ComputerizedSystemRelatedRegulations計算機(jī)化系統(tǒng)驗(yàn)證要點(diǎn)分析

Key-PointAnalysisofComputerizedSystemValidationAnwar奧星設(shè)備與工藝系統(tǒng)事業(yè)部驗(yàn)證總監(jiān)計算機(jī)化系統(tǒng)相關(guān)法規(guī)ComputerizedSystemRelatedRegulations第一部分Part1相關(guān)法規(guī)和指南總覽

RelevantRegulationsandGuidelines(USFDA)21CFRPart11美國聯(lián)邦法規(guī)21篇第11部分電子記錄與電子簽名(USFDA)21CFRPart11:Electronicrecordandelectronicsignature(USFDA)工業(yè)指南11部分

電子記錄與電子簽名-范圍和應(yīng)用(USFDA)GuidanceforIndustry,Part11Electronicrecordandelectronicsignature–scopeandapplication

(USFDA)聯(lián)邦法規(guī)第21篇第210211部分，成品藥的現(xiàn)行生產(chǎn)質(zhì)量管理規(guī)范(USFDA)21CFRPart210and211,cGMPforfinishedpharmaceuticals

(ISPE)良好自動化生產(chǎn)實(shí)踐指南，遵從GxP計算機(jī)化系統(tǒng)監(jiān)管的風(fēng)險管理方法(ISPE)GAMP,Arisk-basedapproachtoaGxPcompliantComputerizedsystem(ISPE)GAMPGPG良好實(shí)踐指南，GAMP架構(gòu)下的系列良好實(shí)踐指南(ISPE)GAMPGPG,GPGundertheframeworkofGAMP(EU)歐盟藥事法規(guī)第4卷GMP，附錄11《計算機(jī)化系統(tǒng)》

EUGuidelinestoGoodManufacturingPractice:(Volume4),annex11ComputerizedSystem

(PIC/S)GMP指南，藥用產(chǎn)品良好生產(chǎn)實(shí)踐指南(TGA)GMP，藥用產(chǎn)品良好生產(chǎn)實(shí)踐指南(PIC/S)在“GxP”監(jiān)管環(huán)境下的計算機(jī)化系統(tǒng)良好實(shí)踐（檢查官指南）PIC/SComputerizedsystemgoodpracticesunderGxPregulation(Inspectorguideline)(WHO)

GMP2003,Annex4(WHOTechnicalReportSeries,No.908)(CFDA)2010年版GMP及征求意見稿《計算機(jī)化系統(tǒng)》CFDAGMP-2010and“ComputerizedSystem”(draftforcomment)(CFDA)GSP附錄二附錄三《藥品經(jīng)營企業(yè)計算機(jī)系統(tǒng)》《溫濕度自動監(jiān)測》(CFDA)GSPAnnex2andAnnex3“ComputerizedSystemofPharmaceuticalTradingEnterprises”and“AutomaticTemperatureandHumidityMonitoring”CFDAGMP及附錄CFDAGMPandAnnexes第一百六十三條使用電子數(shù)據(jù)處理系統(tǒng)的，只有經(jīng)授權(quán)的人員方可輸入或更改數(shù)據(jù)，更改和刪除情況應(yīng)當(dāng)有記錄；應(yīng)當(dāng)使用密碼或其他方式來控制系統(tǒng)的登錄；關(guān)鍵數(shù)據(jù)輸入后，應(yīng)當(dāng)由他人獨(dú)立進(jìn)行復(fù)核。用電子方法保存的批記錄，應(yīng)當(dāng)采用磁帶、縮微膠卷、紙質(zhì)副本或其他方法進(jìn)行備份，以確保記錄的安全，且數(shù)據(jù)資料在保存期內(nèi)便于查閱。Article163 Ifanelectronicdataprocessingsystemisused,onlyauthorizedpersonscaninputorchangedata,thechangeanddeletionrecordsshallbekept,thesystem’slogginginshallbecontrolledbythewayofinputtingapasswordorothermethods;afterinputtingkeydata,itshallbedoublecheckedbyanotherpersonindependently.Thebatchrecordstoredelectronicallyshallbebackedupwithamagnetictape,amicrofilm,apaperduplicateorothermethods,toensurethesafetyoftherecordandtheconveniencetoreviewduringthepreservationperiod.附錄1第七十條采用自控和監(jiān)測系統(tǒng)的，應(yīng)當(dāng)經(jīng)過驗(yàn)證，保證符合關(guān)鍵工藝的要求。Article70,Annex1Whereautomationandmonitoringsystemsareusedfortheseapplicationstheyshouldbevalidatedtoensurethatcriticalprocessrequirementsaremet.CFDAGMP征求意見稿《計算機(jī)化系統(tǒng)》

CFDADraftforcomment“Computerizedsystem”第四條應(yīng)使用科學(xué)的風(fēng)險評估方法來決定計算機(jī)化系統(tǒng)驗(yàn)證的范圍與程度。應(yīng)當(dāng)將驗(yàn)證看作計算機(jī)化系統(tǒng)“生命周期”的一個組成部分。Article4Sciencebasedriskassessmentapproachesshallbeusedtodeterminethescopeandextentofcomputerizedsystemvalidation.Thevalidationshallbeconsideredasapartofthe“l(fā)ifecycle”ofacomputerizedsystem.第七條軟件是計算機(jī)化系統(tǒng)的重要組成部分。軟件的使用者應(yīng)當(dāng)根據(jù)風(fēng)險評估的結(jié)果，對于所采用軟件進(jìn)行分級管理（如針對軟件供應(yīng)商的審計），保證軟件的編制過程符合質(zhì)量保證系統(tǒng)的要求。Article7Softwareisanimportantpartofacomputerizedsystem.Usersofsoftwareshallperformdifferentiatedmanagement(suchasforauditstosoftwaresuppliers)tothesoftwareusedbasedontheriskassessmentresults,toensuretheprogrammingprocessofsoftwareconformstotherequirementsofthequalityassurancesystem.第十條數(shù)據(jù)的輸入或修改只能由經(jīng)許可的人員進(jìn)行。杜絕未經(jīng)許可的人員輸入數(shù)據(jù)的手段有：使用鑰匙、密碼卡、個人密碼和限制對計算機(jī)終端的訪問。Article10Onlyanauthorizedpersonisallowedtoinputorchangedata.Meanstopreventunauthorizedpersonnelfrominputtingdataincludes:key,ciphercard,personalpasswordandrestrictiontoaccesstocomputerterminals.EUGMP

Annex11《計算機(jī)化系統(tǒng)》4.6定制計算機(jī)系統(tǒng)的驗(yàn)證，應(yīng)有一個適當(dāng)?shù)倪^程保證在系統(tǒng)所有生命周期的階段進(jìn)行正式的評估和質(zhì)量和性能測試的報告。4.6Forthevalidationofcustomizedcomputerizedsystemsthereshouldbeastepinplacethatensurestheformalassessmentandreportingofqualityandperformancemeasuresforallthelife-cyclestagesofthesystem9.審計跟蹤AuditTrails9.應(yīng)該基于風(fēng)險評估來考慮給系統(tǒng)加入一種可以生成記錄的功能，來記錄所有與GMP相關(guān)的變更和刪除（系統(tǒng)生成的“審計跟蹤”）。Considerationshouldbegiven,basedonriskassessment,tobuildingintothesystemafunctionforthecreationofarecordofallGMP-relevantchangesanddeletions(an"audittrail"generatedbythesystem).12.1應(yīng)該使用物理和/或邏輯控制來嚴(yán)格控制計算機(jī)系統(tǒng)的權(quán)限，其權(quán)限只給經(jīng)過授權(quán)的人。12.1Physicaland/orlogicalcontrolsshouldbeinplacetorestricttheaccesstoacomputerizedsystemonlytoauthorizedpersons.US21CFRPart211211?68自動化設(shè)備、機(jī)械化設(shè)備和電子設(shè)備應(yīng)對計算機(jī)或有關(guān)系統(tǒng)采取適當(dāng)控制，以確保生產(chǎn)及控制主記錄或其它記錄由授權(quán)人員制定變更內(nèi)容。配方、其它記錄或數(shù)據(jù)在計算機(jī)或有關(guān)系統(tǒng)輸入和輸出時，應(yīng)核查其準(zhǔn)確性。211?68Automationequipment,mechanicalequipmentandelectronicequipmentAppropriatecontrolsshallbeusedforacomputerortherelatedsystemstoassurethatchangesinthemasterproductionandcontrolrecordsorotherrecordsareinstitutedonlybyauthorizedpersonnel.Inputtoandoutputfromthecomputerortherelatedsystemofformulasorotherrecordsordatashallbecheckedforaccuracy.US21CFRPart11SubB//11.10/a系統(tǒng)的驗(yàn)證以保證準(zhǔn)確、可靠、穩(wěn)定地預(yù)期性能，有能力識別無效的和被改變的記錄。

SubB//11.10/aValidationofsystemstoensureaccuracy,reliability,consistentintendedperformance,andtheabilitytodiscerninvalidoralteredrecords.SubB//11.10/e使用安全的、計算機(jī)產(chǎn)生的、時間印記的審計跟蹤以便獨(dú)立地記錄操作者登錄和建立、修改、或刪除電子記錄的行為的日期和時間。)

SubB//11.10/eUseofsecure,computer-generated,time-stampedaudittrailstoindependentlyrecordthedateandtimeofoperatorentriesandactionsthatcreate,modify,ordeleteelectronicrecords.Recordchangesshallnotobscurepreviouslyrecordedinformation.SubB//11.10/g使用驗(yàn)證檢查以保證只有被授權(quán)用戶才可以使用系統(tǒng)，以電子方式簽署記錄，使用操作或計算機(jī)系統(tǒng)的輸入輸出設(shè)備，改變記錄或手工執(zhí)行操作。SubB//11.10/gUseofauthority

checkstoensurethatonlyauthorizedindividualscanusethesystem,electronicallysignarecord,accesstheoperationorcomputersysteminputoroutputdevice,alterarecord,orperformtheoperationathand.WHOGMP15.9使用電子數(shù)據(jù)處理系統(tǒng)的，只有經(jīng)授權(quán)的人員方可輸入或更改數(shù)據(jù)，更改和刪除情況應(yīng)當(dāng)有記錄；應(yīng)當(dāng)使用密碼或其他方式來控制系統(tǒng)的登錄；關(guān)鍵數(shù)據(jù)輸入后，應(yīng)當(dāng)由他人獨(dú)立進(jìn)行復(fù)核。用電子方法保存的批記錄，應(yīng)當(dāng)采用磁帶、縮微膠卷、紙質(zhì)副本或其他方法進(jìn)行備份，以確保記錄的安全，且數(shù)據(jù)資料在保存期內(nèi)便于查閱。15.9Ifelectricdataprocessingsystemisused,onlyauthorizedpersoncouldinputorchangedata,thechangeanddeletionrecordsshallbekept;thesystem’slogginginshallbecontrolledbythewayofinputtingpasswordorothermethods;afterinputtingkeydata,itshallbedoubleexaminedbyotherpersonindependently.Thebatchrecordstoredinelectronicmethodshallbebackedupwithmagnetictape,microfilm,paperduplicateorothermethods,toensurethesafetyoftherecordanditisconvenienttoreviewdataduringthepreservationperiod.ISPEGAMPGAMP5（GoodAutomatedManufacturingPractice-Rev5）GAMP是由國際制藥工程協(xié)會主編的針對計算機(jī)化系統(tǒng)合規(guī)的實(shí)踐指南。旨在提供一套基于現(xiàn)有行業(yè)規(guī)范的行之有效的方法，使計算機(jī)化系統(tǒng)符合預(yù)定用途并滿足現(xiàn)有法規(guī)的要求。自90年代以來，不斷改版的《良好自動化生產(chǎn)實(shí)踐指南》已被廣泛使用并得到國際監(jiān)管部門的公認(rèn)。它是計算機(jī)化系統(tǒng)驗(yàn)證的指導(dǎo)方針。GAMP5是目前的最新版本，于2008年2月發(fā)布。GAMPispracticeguidelineeditedbyISPEaimingtoregulatorycomplianceofcomputerizedsystem.GAMPguidanceaimstoachievecomputerizedsystemsthatarefitforintendeduseandmeetcurrentregulatoryrequirements,bybuildinguponexistingindustrygoodpracticeinanefficientandeffectivemanner.Since1990s,constantlyrevisedGMAPhasbeenwidelyusedandrecognizedbyinternationalregulatoryauthorities.Itistheguidelinetocomputerizedsystemvalidation.SinceitsissuanceinFebruary2008,GMAP5isthelatestversionuptonow.五個關(guān)鍵概念Fivekeyconcepts：基于質(zhì)量管理體系的生命周期方法LifecycleapproachwithinaQMS可增減的生命周期活動Scaleablelifecycleactivities流程和產(chǎn)品的理解.Productandprocessunderstanding基于科學(xué)的質(zhì)量風(fēng)險管理Sciencebasedqualityriskmanagement充分利用供應(yīng)商活動.Leveragingsupplierinvolvement法規(guī)、GMP、驗(yàn)證相關(guān)術(shù)語

Regulations,GMP,Validationrelatedglossary術(shù)語Abbr.名稱NameCFDAChinaFoodandDrugAdministration國家食品藥品監(jiān)督管理總局WHOWorldHealthOrganization世界衛(wèi)生組織EUEuropeanUnion歐洲聯(lián)盟（歐盟）PIC/SPharmaceuticalInspectionConventionandPharmaceuticalInspectionCo-operationScheme藥品檢查合作計劃(藥品檢查協(xié)會）FDAU.S.FoodandDrugAdministration美國食品藥品監(jiān)督管理局ICHInternationalConferenceonHarmonizationofTechnicalRequirementsforRegistrationofPharmaceuticalsforHumanUse國際人用藥品注冊和醫(yī)藥技術(shù)協(xié)調(diào)會議ISPEInternationalSocietyForPharmaceuticalEngineering國際制藥工程協(xié)會RARiskAssessments

風(fēng)險評估SIASystemImpactAssessment

系統(tǒng)影響性評估術(shù)語Abbr.名稱NameCCAComponentCriticalityAssessment部件關(guān)鍵性評估FAT/SATFactoryAcceptanceTest/SiteAcceptanceTest工廠/現(xiàn)場驗(yàn)收測試DQ/IQ/

OQ/PQDesign/Installation/Operational/PerformanceQualification設(shè)計/安裝/運(yùn)行/性能確認(rèn)CPPCriticalProcessParameter關(guān)鍵工藝參數(shù)CQACriticalQualityAttribute關(guān)鍵質(zhì)量屬性ERESElectronicRecord;ElectronicSignature電子記錄與電子簽名計算機(jī)化系統(tǒng)驗(yàn)證常見術(shù)語1

CommonGlossaryforComputerizedSystemValidation1名稱縮寫英文驗(yàn)證主計劃VMPValidationMasterPlan質(zhì)量及項(xiàng)目計劃QPPQualityandProjectPlan用戶需求說明URSUserRequirementSpecification功能說明FSFunctionSpecification硬件設(shè)計說明HDSHardwareDesignSpecification軟件設(shè)計說明SDSSoftwareDesignSpecification軟件模塊說明SMSSoftwareModuleSpecification設(shè)計確認(rèn)DQDesignQualification源代碼審核SCRSourceCodeReview軟件模塊測試SMTSoftwareModuleTest工廠驗(yàn)收測試FATFactoryAcceptanceTest現(xiàn)場驗(yàn)收測試SATSiteAcceptanceTest安裝確認(rèn)IQInstallationQualification運(yùn)行確認(rèn)OQOperationQualification性能確認(rèn)PQPerformanceQualification計算機(jī)化系統(tǒng)驗(yàn)證常見術(shù)語2

CommonGlossaryforComputerizedSystemValidation12名稱縮寫Abbr.英文可追溯矩陣TMTraceabilityMatrix驗(yàn)證總結(jié)報告VSRValidationSummaryReport國際制藥工程協(xié)會ISPEInternationalSocietyOfPharmaceuticalEngineering良好自動化生產(chǎn)實(shí)踐指南GAMPGoodAutomatedManufacturingPractice質(zhì)量管理系統(tǒng)QMSQualityManagementSystem可編程邏輯控制器PLCProgrammableLogicController集散控制系統(tǒng)DCSDistributedControlSystem數(shù)據(jù)采集與監(jiān)視系統(tǒng)SCADASupervisoryControlAndDataAcquisition企業(yè)資源計劃ERPEnterpriseResourcePlanning實(shí)驗(yàn)室信息管理系統(tǒng)LIMSLaboratoryInformationManagementSystem生產(chǎn)執(zhí)行系統(tǒng)MESManufacturingExecutionSystems樓宇管理系統(tǒng)BMSBuildingManagementSystem環(huán)境監(jiān)視系統(tǒng)EMSEnvironmentMonitoringSystem計算機(jī)系統(tǒng)驗(yàn)證CSVComputerSystemValidation不間斷電源UPSUninterruptiblePowerSupply新建計算機(jī)化系統(tǒng)驗(yàn)證流程介紹IntroductiontoValidationProcessofNewComputerizedSystem第二部分Part2CSV經(jīng)典V-Model圖及其總流程CSVclassicV-Modelandgeneralflowchart流程逐一步驟的良好實(shí)踐Goodpracticesofprocesssteps計算機(jī)化系統(tǒng)驗(yàn)證生命周期V-Model

V-Modelofcomputerizedsystemvalidationlifecycle驗(yàn)證生命周期文件架構(gòu)

Lifecycledocumentationframework計算機(jī)化系統(tǒng)驗(yàn)證總流程

Generalflowofcomputerizedsystemvalidation確認(rèn)計算機(jī)化系統(tǒng)Computerizedsystemdefinition初步系統(tǒng)評估確定系統(tǒng)影響，判定GxP系統(tǒng)Performinitialsystemassessmentanddeterminesystemimpacts,andGxPsystem供應(yīng)商評估確定其能力及參與評估點(diǎn)Performsupplierassessmentanddeterminetheircapacityandinvolvementassessmentpoints軟硬件分類評估確定其復(fù)雜性和新穎性Performhardwareandsoftwarecategorizationassessmentanddeterminetheircomplexityandnovelty.結(jié)合供應(yīng)商能力，系統(tǒng)復(fù)雜性和新穎性、GxP影響制定適宜V-ModelMakeanappropriateV-Modelinconjunctionwithsuppliercapacity,systemcomplexityandnoveltyandGxPimpacts按照既定的V-Model實(shí)施確認(rèn)PerformverificationasestablishedintheV-Model流程良好實(shí)踐1-1ProcessGoodPractices通過網(wǎng)絡(luò)結(jié)構(gòu)圖，找到接口界面“云圖”的方式劃分界定系統(tǒng)Definesystemsthroughnetworkstructurechart,andinterface“cloudpicture確認(rèn)計算機(jī)化系統(tǒng)Computerizedsystemdefinition流程良好實(shí)踐1-2ProcessGoodPractices1-2確認(rèn)計算機(jī)化系統(tǒng)ComputerizedsystemdefinitionWhennetworkarchitecture

diagramisnotavailablefornosupplierperformssecondarydevelopmentattheinitialstage,thecomputerizedsystemsummarylistisconsideredasthebasisfordefiningsystems.項(xiàng)目初期沒有供應(yīng)商二次開發(fā)無法得到網(wǎng)絡(luò)架構(gòu)圖時，可考慮采用計算機(jī)化系統(tǒng)清單匯總作為界定劃分系統(tǒng)的依據(jù)流程良好實(shí)踐2ProcessGoodPractices2SelectGxPcriticalsystemsthroughGxPriskassessmentquestions

通過GxP評估問題篩選出GxP關(guān)鍵系統(tǒng)PerforminitialriskassessmentanddetermineGxPcriticalsystems初步風(fēng)險評估判定GxP關(guān)鍵系統(tǒng)Doesthesystemgenerate,manipulateorcontroldatasupportingregulatorysafetyandefficacysubmissions?系統(tǒng)是否生成、處理或控制用于支持法規(guī)安全性和功效提交文件的數(shù)據(jù)？Doesthesystemcontrolcriticalparametersanddatainpreclinical,clinical,development,ormanufacturing?系統(tǒng)是否控制臨床前、臨床、開發(fā)或生產(chǎn)相關(guān)關(guān)鍵參數(shù)和數(shù)據(jù)？Doesthesystemcontrolorprovidedataorinformationforproductrelease?系統(tǒng)是否控制或提供有關(guān)產(chǎn)品放行的數(shù)據(jù)或信息？Doesthesystemcontroldataorinformationrequiredincaseofproductrecall?系統(tǒng)是否控制與產(chǎn)品召回相關(guān)要求的數(shù)據(jù)或信息？系Doesthesystemcontroladverseeventorcompliantrecordingorreporting?統(tǒng)是否控制不良事件或投訴的記錄或報告？Doesthesystemsupportpharmacovigilance?系統(tǒng)是否支持藥物安全監(jiān)視？Criticalsystemsaresubjecttovalidation,andnon-criticalsystemsaresubjecttoGEPcommissioningonly.

關(guān)鍵系統(tǒng)做驗(yàn)證，非關(guān)鍵系統(tǒng)GEP調(diào)試即可流程良好實(shí)踐3供應(yīng)商評估確定其能力及參與平衡點(diǎn)對每一受GxP監(jiān)管的計算機(jī)化系統(tǒng)和服務(wù)的供應(yīng)商進(jìn)行正式的評估，來確認(rèn)計算機(jī)系統(tǒng)能夠以高標(biāo)準(zhǔn)滿足他們的技術(shù)、商業(yè)及法規(guī)要求，同時確認(rèn)能夠充分利用供應(yīng)商的知識、經(jīng)驗(yàn)和文件。通過供應(yīng)商審計來識別供應(yīng)商QMS以及其能力水平方面的風(fēng)險，被監(jiān)管公司對計算機(jī)系統(tǒng)和服務(wù)供應(yīng)商的質(zhì)量和可靠性進(jìn)行確認(rèn)，要求有文件化的證據(jù)來證明該計算機(jī)系統(tǒng)能夠如所預(yù)期的持續(xù)運(yùn)行，并確保軟件結(jié)構(gòu)和功能的完整性。ProcessGoodPractices3PerformsupplierassessmentanddeterminetheircapacityandinvolvementbalancepointFormalassessmentisperformedtoeachsupplierofcomputerizedsystemandserviceundertheregulationofGxP,toverifythatthecomputerizedsystemcanmeettheirtechnical,commercialandregulatoryrequirements,andatthesametimemakethebestuseofsupplier’sknowledge,experienceanddocuments.Risksofsupplier’sQMSandcapacityareidentifiedthroughasupplieraudit.Thecompanyundertheregulationverifythequalityandreliabilityofsupplierofcomputerizedsystemandservices,anddocumentedevidenceisrequiredtoprovethecomputerizedsystemcanruncontinuouslyasintended,andensuretheintegrityofsoftwarestructureandfunction.流程良好實(shí)踐4-1軟硬件分類評估確定其復(fù)雜性和新穎性硬件分2類軟件分4類通過識別軟硬件類別來識別復(fù)雜性和新穎性帶來的風(fēng)險，從而確定出適宜的可增減周期策略ProcessGoodPractices4-1Performhardwareandsoftwarecategorizationassessmentanddeterminetheircomplexityandnovelty.Hardwareisdividedintotwocategories.Softwareisdividedintofourcategories.Identifyrisksfromcomplexityandnoveltythroughidentifyinghardwareandsoftwarecategories,todetermineproperextendablelifecyclestrategy.流程良好實(shí)踐4-2硬件類別類別典型方法1,標(biāo)準(zhǔn)硬件部件通過文件記錄下生產(chǎn)廠家或供應(yīng)商的詳情、序列號和版本號確認(rèn)正確的安裝適用配置管理和變更控制2,定制制造的硬件部件上述內(nèi)容再加上：設(shè)計說明驗(yàn)收測試適用配置和變更控制ProcessGoodPractices4-2HardwareCategoriesCategoryTypicalApproach1.StandardHardwareComponentsDocumentmanufacturerorsupplierdetail,serialnumberandversionnumberCorrectinstallationtobeverifiedConfigurationManagementandChangecontrolapply2.CustomBuiltHardwareComponentsTheaboveplus:DesignspecificationAcceptancetestingConfigurationandChangecontrolapply流程良好實(shí)踐4-3硬件類別硬件類別第二類定制制造部件第一類標(biāo)準(zhǔn)部件ProcessGoodPractices4-3HardwareCategoriesHardwareCategoryCategory2CustomBuiltHardwareComponentsCategory1StandardHardwareComponents流程良好實(shí)踐4-4軟件類別ProcessGoodPractices4-4SoftwareCategoriesTypeGAMP5GAMP51OperatingsystemInfrastructureSoftware2FirmwareOutofuse3StandardsoftwarepackageNon-configured4ConfiguredsoftwarepackageConfigured5Custom(reserved)softwareCustom流程良好實(shí)踐4-5

軟件類別類別說明典型示例典型方法1,基礎(chǔ)設(shè)施軟件分層式軟件用于管理操作環(huán)境的軟件操作系統(tǒng)數(shù)據(jù)庫引擎中間件編程語言電子制表軟件版本控制給你工具網(wǎng)絡(luò)監(jiān)控工具記錄版本號，按照所批準(zhǔn)的安裝規(guī)程驗(yàn)證正確的安裝方式。3,非配置軟件可以輸入并儲存運(yùn)行參數(shù)，但是并不能對軟件進(jìn)行配置以適合業(yè)務(wù)流程基于固件的應(yīng)用程序COTS軟件簡化的生命周期法URS用戶需求說明基于風(fēng)險的供應(yīng)商審計/評估記錄版本號，驗(yàn)證正確的安裝方式基于風(fēng)險進(jìn)行測試有用于維持系統(tǒng)符合性的規(guī)程ProcessGoodPractices4-5SoftwareCategoriesCategoryDescriptionTypicalexamplesTypicalApproach1.InfrastructureSoftwareLayeredsoftwareSoftwareusedtomanagetheoperatingenvironmentOperatingsystemsDatabaseenginesMiddlewareProgramminglanguagesSpreadsheetsVersioncontroltoolsNetworkmonitoringtoolsRecordversionnumber,verifycorrectinstallationbyfollowingapprovedinstallationprocedure3.Non-configuredRuntimeparametersmaybeenteredandstored,butthesoftwarecannotbeconfiguredtosuitthebusinessprocessFirmwarebasedapplicationsCOTssoftwareCOTSAbbreviatedLifecycleapproachURSRiskbasedapproachtosupplierassessmentRecordversionnumber,verifycorrectinstallationRiskbasedtestProcedureinplaceformaintainingcompliance流程良好實(shí)踐4-6

軟件類別類別說明典型示例典型方法4,可配置這種軟件通常非常復(fù)雜，可以由用戶來進(jìn)行配置以滿足用戶具體業(yè)務(wù)流程的特殊要求。這種軟件的編碼不能更改。SCADADCSBMSHMILIMSERPClinicaltrailmonitoring生命周期法基于風(fēng)險的供應(yīng)商審計/評估供應(yīng)商的質(zhì)量管理系統(tǒng)記錄版本號，驗(yàn)證正確的安裝方式在測試環(huán)境中根據(jù)風(fēng)險進(jìn)行測試在業(yè)務(wù)流程中根據(jù)風(fēng)險進(jìn)行測試具有維持符合性的規(guī)程5,定制定制設(shè)計和編碼以適于業(yè)務(wù)流程的軟件內(nèi)部和外部開發(fā)的IT應(yīng)用程序內(nèi)部和外部開發(fā)的工藝控制應(yīng)用程序定制功能邏輯定制固件電子制表軟件（宏）與第4類相同，再加上更嚴(yán)格的公用設(shè)施評估，包括進(jìn)行供應(yīng)商審計完整的生命周期設(shè)計和源代碼回顧ProcessGoodPractices4-6SoftwareCategoriesCategoryDescriptionTypicalexamplesTypicalApproach4.ConfiguredSoftware,oftenverycomplex,thatcanbeconfiguredbytheusertomeetthespecificneedsoftheuser’sbusinessprocess.Softwarecodeisnotaltered.DAQsystemsSCADADCSBMSHMILIMSERPClinicaltrailmonitoringLifecycleapproachRiskbasedapproachtosupplierassessmentSupplierQMSRecordversionnumber,verifycorrectinstallationRiskbasedtestinginatestenvironmentRiskbasedtestingwithinthebusinessprocessProcedureinplaceformaintainingcompliance5.CustomSoftwarecustomdesignedandcodedtosuitthebusinessprocess.Internally,externallydevelopedITapplications.Internally,externallydevelopedprocesscontrolapplications.CustomladderlogicCustomfirmwareSpreadsheet(macro)Sameascat4plusMorerigoroussupplierassessment,withpossiblesupplierauditPossessionoffulllifecycleDesignandsourcecodereview流程良好實(shí)踐5GxP評估—患者安全、產(chǎn)品質(zhì)量、數(shù)據(jù)完整性—做與不做驗(yàn)證—定范圍軟硬件分類評估—復(fù)雜性和新穎性—可增減的策略1—定深度或程度供應(yīng)商評估—供應(yīng)商能力水平帶來的風(fēng)險—可增減的策略2—定工作參與平衡點(diǎn)結(jié)合供應(yīng)商能力、系統(tǒng)復(fù)雜性新穎性、GxP影響制定適宜V-Model規(guī)范階段基于風(fēng)險可增減確認(rèn)階段基于風(fēng)險可增減ProcessGoodPractices5GxP

assessment—PatientSafety,ProductQualityandDataIntegrity—Validationrequiredornot—definescope

Softwareandhardwareclassificationassessment—complexityandnovelty—expandablestrategy1—definedepthorextentSupplierassessment—risksfromsuppliercapacitylevel—expandablestrategy2—defineworkinvolvementbalancepointMakeanappropriateV-Modelinconjunctionwithsuppliercapacity,systemcomplexityandnoveltyandGxPimpactRegulationstagebasedonriskscalablityVerificationstagebasedonriskscalablity流程良好實(shí)踐6按照既定的V-Model實(shí)施確認(rèn)驗(yàn)證ProcessGoodPractices6PerformverificationbasedontheestablishedV-Model新建及遺留計算機(jī)化系統(tǒng)驗(yàn)證示例分析CaseStudyofNewandLegacyComputerizedSystemValidation第三部分Part3示例分析1-確定系統(tǒng)（參考）接口界面面的選擇取決于供應(yīng)商施工接口及科學(xué)的經(jīng)驗(yàn)CaseStudy1-Systemdefinition

(reference)Interfaceselectiondependsonsupplier’sconstructioninterfaceandscientificexperience.示例分析2-確定GxP系統(tǒng)（參考）YNNNYYorNY/N判定結(jié)果取決于其真實(shí)用途是否涉及GxP相關(guān)功能CaseStudy2-DetermineGxPsystems（reference)YNNNYYorNY/NdependsonwhetheritsrealuseinvolvesanyGxPrelatedfunctions.示例分析3-確定軟硬件類別（參考）項(xiàng)目軟件名稱軟件描述軟件分類操作員站W(wǎng)INXPSP3計算機(jī)操作系統(tǒng)1WinCCV7.0西門子人機(jī)界面軟件1配置軟件TTBMS_WINCC項(xiàng)目文件4S7314PLC不可配置軟件PLC卡件3配置軟件TTBMS_PLC項(xiàng)目文件4項(xiàng)目硬件名稱硬件描述硬件分類操作員站電腦主機(jī)及顯示器用于操作員人機(jī)交互1控制站接線配置用于提供電力或信號2軟件分類需要結(jié)合供應(yīng)商的經(jīng)驗(yàn)以及系統(tǒng)的定制程度CaseStudy3-Softwareandhardwarecategorization（reference）Project

SoftwareDescription

CategoryOperatorstationWINXPSP3Operatingsystem1WinCCV7.0SimensHMIsoftware1ConfiguratedsoftwareTTBMS_WINCCprojectdocument4S7314PLCNon-configuratedsoftwarePLCcard3ConfiguratedsoftwareTTBMS_PLCprojectdocument4Project

HardwareDescription

CategoryOperatorstationHostcomputerandmonitorForhuman-computerinteraction1ControlstationWiringconfigurationForsupplyofpowerandsignal2Softwareiscategorizedinconjunctionwithsupplier’sexperienceandsystemcustomizationdegree.示例分析4-確定供應(yīng)商的能力（參考）供應(yīng)商質(zhì)量體系工程技術(shù)能力GxP合規(guī)能力分值評價AAA710724待定，加強(qiáng)GMPBBB46616＜20，直接否決CCC84719＜20，直接否決DDD97925待定，加強(qiáng)GEP通過審計打分的方法，甄別合適的供應(yīng)商，同時找到關(guān)注重點(diǎn)及工作參與平衡點(diǎn)CaseStudy4-determinesuppliercapacity（reference）SupplierQSEngineeringtechnicalcapacityGxP

compliancecapacityScoreComment

AAA710724Undetermined,GMPcapacityshallbestrengthened.BBB46616＜20，rejectCCC84719＜20，rejectDDD97925Undetermined,GEPcapacityshallbestrengthened通過審計打分的方法，甄別合適的供應(yīng)商，同時找到關(guān)注重點(diǎn)及工作參與平衡點(diǎn)Identifyappropriatesupplierbymeansofauditingandscoring,findfocusandworkinvolvementbalancepoint.示例分析5質(zhì)量風(fēng)險管理五步流程CaseStudy5QualityRiskManagementProcess示例分析5功能性風(fēng)險評估功能性風(fēng)險評估確定其GxP關(guān)鍵功能1.識別系統(tǒng)使用到的功能（或部件）2.通過問題判定的方式識別GxP關(guān)鍵功能（或部件）3.實(shí)施FMEA，分析功能（或部件）的優(yōu)先級RPN14.識別控制措施并實(shí)施5.實(shí)施FMEA，分析優(yōu)先級RPN2審查風(fēng)險是否可接受RPN風(fēng)險優(yōu)先級CaseStudy5FunctionalRiskAssessmentFunctionalriskassessmentisperformedtodetermineGxPcriticalfunctions.1.Identifyfunctions(orcomponents)usedinthesystem2.IdentifyGxPcriticalfunctions(orcomponents)throughaseriesofstandardquestions3.ImplementFMEA

toanalyzeRPN1offunctions(orcomponents)4.Identifyandimplementcontrolmeasures5.ImplementFMEA

toanalyzeRPN1reviewriskisacceptableornot.RPNreferstoriskprioritynumber示例分析6確定適宜的生命周期URSFSHDSSCS配置FATSAT-IOQVSRVPQPP公司QMSTMCCDMPart11RA支持包含風(fēng)險管理整個過程結(jié)合示例分析3和4的結(jié)果，我們定義如下參考的周期：一個四類系統(tǒng)的模型假定以分值高低最終選擇了DDD供應(yīng)商，我們需要加強(qiáng)現(xiàn)場施工技術(shù)方面的監(jiān)管及設(shè)計審查，文件和合規(guī)方面可充分利用供應(yīng)商的活動CaseStudy6DetermineAppropriateLifecycleURSFSHDSSCS配置FATSAT-IOQVSRVPQPP公司QMSTMCCDMPart11RA支持包含風(fēng)險管理整個過程CombiningresultsofCaseStudy3and4,wedefinethefollowinglifecycleforreference:amodelforacategory4system.SupposetheDDDsupplerisfinallychosenasperscores,weneedtoenhancethesupervisionanddesignreviewregardingsiteconstructiontechnique,asfordocumentandregulatorycompliance,supplier’sactivitiescanbefullyused.示例分析

7支持流程Part11符合性

SystemName系統(tǒng)名稱

SystemNo.系統(tǒng)編號SIADocNo.系統(tǒng)評估文件號21CFRPart11–ApplicabilityReview適用性審核:StatementApplicable

是否適用聲明

(Yes/No/N/A):Thesystemmaintainsrecordsthatarerequiredbypredicate

rules(e.g.21CFRPart210,211,etc.),inelectronicformat(e.g.informationstoredwithinSQLdatabase)inplaceofpaperformat.

系統(tǒng)用以維持規(guī)定規(guī)則（例如21CFRPart210,211等）所要求的，用于替代紙質(zhì)版格式文件的電子版格式（例如在SQL數(shù)據(jù)庫中所存儲信息）的記錄。Note:Permanentcopiesofrecordsmaintainedelectronicallyinapaperequivalentformat(e.g.PDF)arenotconsideredelectronicrecords.

備注：以與紙質(zhì)版等同的電子版格式（例如PDF）維護(hù)的永久性記錄復(fù)件并不被認(rèn)定為是電子記錄。Thesystemmaintainsrecordsthatarerequiredbypredicaterulesinelectronicformat,inadditiontopaperformat,andarereliedupontoperformregulatedactivities.

系統(tǒng)用于維持規(guī)定規(guī)則所要求的，除了以紙質(zhì)格式還需以電子格式維持，并需要據(jù)其執(zhí)行法規(guī)要求工作的記錄。Note:Ifthesystemgeneratespaperrecordswhicharethentheonlyrecordsusedtoperformregulatedactivities,thenthisstatementdoesnotapply.

備注：如果系統(tǒng)會生成紙質(zhì)版記錄，而這種記錄是用于進(jìn)行法規(guī)要求工作的唯一記錄，那么此項(xiàng)聲明并不適用。ThesystemmaintainsrecordssubmittedelectronicallytoFDAunderpredicaterules.

系統(tǒng)用于維持根據(jù)規(guī)定規(guī)則要求需要以電子版形式提交給FDA的記錄。Note:Statementappliesregardlessiftherecordisspecificallyidentifiedinagencyregulationsornot.

備注：無論在FDA法規(guī)中是否具體列出了這種記錄此項(xiàng)聲明均適用。Note:Usingarecordingeneratingasubmissiondoesnotinferapplicabilityofpart11tothatrecord.

備注：在編寫一份提交文件是用到了某記錄，并不會使得該記錄需要適用part11的要求。Thesystemmaintainselectronicsignaturesthatareintendedtobetheequivalentofhandwrittensignatures,initials,andothergeneralsigningsrequiredbypredicaterules.

系統(tǒng)用于維持預(yù)期等同于規(guī)定規(guī)則所要求的手寫簽名、首字母簽名和其它一般簽名的電子簽名。Result結(jié)果:Iftheanswertostatements1–4is“No”thentheequipmentisnotwithinthescopeof21CFRPart11.

如果對第1-4號聲明的回答均是“否”，那么該設(shè)備不適用于21CFRPart11的范圍。NoIftheanswertoanyoftheabovestatementsis“Yes”,thentheequipmentiswithinthescopeof21CFRPart11.

如果對第1-4號聲明中任何一項(xiàng)的回答是“是”，那么該設(shè)備適用于21CFRPart11的范圍。N/A評估系統(tǒng)是否適用Part11-----適用ER，適用ER&ES,還是均不適用？CaseStudy7,SupportingProcess

Part11

Compliance

SystemName系統(tǒng)名稱

SystemNo.系統(tǒng)編號SIADocNo.系統(tǒng)評估文件號21CFRPart11–ApplicabilityReview適用性審核:StatementApplicable

是否適用聲明

(Yes/No/N/A):Thesystemmaintainsrecordsthatarerequiredbypredicate

rules(e.g.21CFRPart210,211,etc.),inelectronicformat(e.g.informationstoredwithinSQLdatabase)inplaceofpaperformat.

系統(tǒng)用以維持規(guī)定規(guī)則（例如21CFRPart210,211等）所要求的，用于替代紙質(zhì)版格式文件的電子版格式（例如在SQL數(shù)據(jù)庫中所存儲信息）的記錄。Note:Permanentcopiesofrecordsmaintainedelectronicallyinapaperequivalentformat(e.g.PDF)arenotconsideredelectronicrecords.

備注：以與紙質(zhì)版等同的電子版格式（例如PDF）維護(hù)的永久性記錄復(fù)件并不被認(rèn)定為是電子記錄。Thesystemmaintainsrecordsthatarerequiredbypredicaterulesinelectronicformat,inadditiontopaperformat,andarereliedupontoperformregulatedactivities.

系統(tǒng)用于維持規(guī)定規(guī)則所要求的，除了以紙質(zhì)格式還需以電子格式維持，并需要據(jù)其執(zhí)行法規(guī)要求工作的記錄。Note:Ifthesystemgeneratespaperrecordswhicharethentheonlyrecordsusedtoperformregulatedactivities,thenthisstatementdoesnotapply.

備注：如果系統(tǒng)會生成紙質(zhì)版記錄，而這種記錄是用于進(jìn)行法規(guī)要求工作的唯一記錄，那么此項(xiàng)聲明并不適用。ThesystemmaintainsrecordssubmittedelectronicallytoFDAunderpredicaterules.

系統(tǒng)用于維持根據(jù)規(guī)定規(guī)則要求需要以電子版形式提交給FDA的記錄。Note:Statementappliesregardlessiftherecordisspecificallyidentifiedinagencyregulationsornot.

備注：無論在FDA法規(guī)中是否具體列出了這種記錄此項(xiàng)聲明均適用。Note:Usingarecordingeneratingasubmissiondoesnotinferapplicabilityofpart11tothatrecord.

備注：在編寫一份提交文件是用到了某記錄，并不會使得該記錄需要適用part11的要求。Thesystemmaintainselectronicsignaturesthatareintendedtobetheequivalentofhandwrittensignatures,initials,andothergeneralsigningsrequiredbypredicaterules.

系統(tǒng)用于維持預(yù)期等同于規(guī)定規(guī)則所要求的手寫簽名、首字母簽名和其它一般簽名的電子簽名。Result結(jié)果:Iftheanswertostatements1–4is“No”thentheequipmentisnotwithinthescopeof21CFRPart11.

如果對第1-4號聲明的回答均是“否”，那么該設(shè)備不適用于21CFRPart11的范圍。NoIftheanswertoanyoftheabovestatementsis“Yes”,thentheequipmentiswithinthescopeof21CFRPart11.

如果對第1-4號聲明中任何一項(xiàng)的回答是“是”，那么該設(shè)備適用于21CFRPart11的范圍。N/AEvaluatewhetherthesystemappliestoPart11-----appliestoERorER&ES,orneitherERES相關(guān)知識探討57/100記錄三種形式“純”紙質(zhì)記錄保證三種要求如：手寫的報表人工介入的電子記錄123123如：打印的電子數(shù)據(jù)報表“純”電子記錄如：存儲在電腦中的純電子報表文件安全性完整性可追溯性如：訪問控制如：變更控制如：審計跟蹤ERES均不適用適用ER，ES不適用ERES均適用DiscussiononERESKnowledge58/100Record3types“Pure”paperrecordAssurance3requirementsSuchas：handwrittenreportE-recordwithhumanintervention123123Suchas：printedelectronicdatareport“Pure”e-recordSuchas：pureelectronicreportssavedinthecomputerSafetyIntegrityTraceabilitySuchas：AccesscontrolSuchas：ChangecontrolSuchas：audittraceNeitherERnorESappliesER