質(zhì)量體系的分析研究2024/3/11質(zhì)量體系的分析研究AgendaSessionObjectivesQualityManagementSystemOverviewTraditionalChallengesRe-definingCAPAImplementingaQualityManagementSoftwareSolutionConclusionQ&A質(zhì)量體系的分析研究SessionObjective DiscusscriticalcomponentsofaneffectiveQualityManagementSystem(QMS),challengeswithcurrentsystems,andsolutionstoovercomethesechallengesbyimplementingaholisticQualityManagementSoftwaresolution.質(zhì)量體系的分析研究GeneralIntroduction質(zhì)量體系的分析研究DefiningCAPA–ISO13485:20038.5.2CorrectiveAction–Correctiveactionsshallbeappropriatetotheeffectsofthenonconformitiesencountered.Adocumentedprocedureshallbeestablishedtodefinerequirementsforreviewingnonconformities(includingcustomercomplaints)determiningthecauseofnonconformitiesevaluatingtheneedforactiontoensurethatnonconformitiestonotrecurdeterminingandimplementingactionneeded,including,ifappropriate,updatingdocumentationrecordingoftheresultsofanyinvestigationandofactiontaken,andreviewingthecorrectiveactiontakenanditseffectiveness質(zhì)量體系的分析研究DefiningCAPA–ISO13485:20038.5.3Preventiveaction–Theorganizationshalldetermineactiontoeliminatethecausesofpotentialnonconformitiesinordertopreventtheiroccurrence.Preventiveactionsshallbeappropriatetotheeffectsofthepotentialproblems.Itisalsodeterminepotentialnonconformitiesandtheircausesevaluatingtheneedforactiontopreventoccurrenceofnonconformitiesdeterminingandimplementingactionneededrecordingoftheresultsofanyinvestigationsandofactiontaken,andreviewingpreventiveactiontakenanditseffectiveness質(zhì)量體系的分析研究QualityRegulation21CFR820.100U.S.FoodandDrugAdministration’sregulationgoverningmedicaldevicemanufacturersqualitysystems:(a) Eachmanufacturershallestablishandmaintainproceduresforimplementingcorrectiveandpreventiveaction:analyzingprocesses,workoperations,concessions,qualityauditreports,qualityrecords,servicerecords,complaints,returnedproducts,andothersourcesofqualitydatatoidentifyexistingandpotentialcausesofnonconformingproduct,orotherqualityproblemsinvestigatingthecauseofnonconformitiesrelatingtoproduct,processes,andthequalitysystemidentifyingtheactionsneededtocorrectandpreventrecurrenceofnonconformingproductandotherqualityproblemsverifyingorvalidatingthecorrectiveandpreventiveactionImplementingandrecordingchangesinmethodsandproceduresneededtocorrectandpreventidentifiedqualityproblemsEnsuringthatinformationrelatedtoqualityproblemsornonconformingproductisdisseminatedtothosedirectlyresponsibleforassuringthequalityofsuchproductorthepreventionofsuchproblems;andSubmittingrelevantinformationonidentifiedqualityproblems,aswellascorrectiveandpreventiveactions,formanagementreview質(zhì)量體系的分析研究QualityRegulation21CFR211.22VerysimilaristheU.S.FDA’sregulationforpharmaceuticalmanufacturers21CFRPart211.22(QualityControlUnit)…responsibilitiesofaqualitycontrolunit...toassurethatnoerrorshaveoccurredor,iferrorshaveoccurred,thattheyhavebeenfullyinvestigated.Thequalitycontrolunitshallhavetheresponsibilityforapprovingorrejectingallproceduresorspecificationsimpactingontheidentity,strength,quality,anpurityofthedrugproduct…andinPart211.92(ProductionRecordReview)Anyunexplaineddiscrepancy…orthefailureofabatchoranyofitscomponentstomeetanyofitsspecificationsshallbethoroughlyinvestigated…Theinvestigationshallextendtootherbatchesofthesamedrugproductandotherdrugproductsthatmayhavebeenassociatedwiththespecificfailureordiscrepancy.Awrittenrecordoftheinvestigationshallbemadeandshallincludetheconclusionsandfollow-up.

質(zhì)量體系的分析研究QuotesfromCurrentFDAWarningLettersEachmanufacturershallestablishproceduresforqualityauditsandconductsuchauditstoassurethatthequalitysystemisincompliancewiththeestablishedqualitysystemrequirementsandtodeterminetheeffectivenessofthequalitysystem.Qualityauditsshallbeconductedbyindividualswhodonothavedirectresponsibilityforthemattersandshallbetakenwhennecessary.Areportoftheresultsofeachqualityaudit,andreaudit(s)wheretaken,shallbemadeandsuchreportsshallbereviewedbymanagementhavingresponsibilityforthemattersaudited.Thedatesandresultsofqualityauditsandreauditsshallbedocumentedasrequiredby21CFR820.22.internalqualityauditsconductedbyyourfirmfailedtoverifythatthequalitysystemwaseffectiveinfulfillingqualitysystemobjectives(FDA483,Item#2).質(zhì)量體系的分析研究QuotesfromCurrentFDAWarningLettersYourfirmfailstoimplementandmaintaincorrectiveandpreventiveaction(CAPA)proceduresthatincluderequirementsforanalyzingprocesses,workoperations,concessions,qualityauditreports,qualityrecords,servicerecords,complaints,returnedproduct,andothersourcesofqualitydatatoidentifyexistingandpotentialcausesofnonconformingproduct,orotherqualityproblemsasrequiredby21CFR820.100(a)(1).Yourfirmfailstoestablishandimplementcorrectiveandpreventiveaction(CAPA)proceduresthatincluderequirementsforidentifyingtheaction(s)neededtocorrectandpreventrecurrenceofnon-conformingproductandotherqualityproblemsasrequiredby21CFR820.100(a)(3)Allactivitiesrequiredby21CFR820.100mustbeverifiedorvalidatedtoensurethatsuchactioniseffectiveanddoesnotadverselyaffectfinisheddevices,andtheresultsoftheseactivitiesshallbedocumentedasrequiredby21CFR820.100(a)(4)and(b).Yourfirm'sCAPAproceduresfailtodocumenthowanalysisisdoneandfailstorequireverification/validationthatCAPAdoesnotadverselyaffectfinisheddevices(FDA483,Item#8).質(zhì)量體系的分析研究CommissionDirective2003/94/EC

PreambleHavingregardtotheTreatyestablishingtheEuropeanCommunity,Allmanufacturersshouldoperateaneffectivequalitymanagementsystemoftheirmanufacturingoperations,whichrequirestheimplementationofapharmaceuticalqualityassurancesystem.

Article13-ComplaintsAnycomplaintconcerningadefectshallberecordedandinvestigatedbythemanufacturer…

Article14-InspectionsThemanufacturershallconductrepeatedself-inspections…inordertomonitortheimplementationandrespectofgoodmanufacturingpracticeandtoproposeanynecessarycorrectivemeasures.Recordsshallbemaintainedofsuchself-inspectionsandanycorrectiveactionsubsequentlytaken.質(zhì)量體系的分析研究Morethanjustcorrectiveactions…CAPAismuchmorethanjust“correctiveactions”and“preventiveactions”.AnyopportunitytoimprovequalityinyourorganizationisaCAPA!質(zhì)量體系的分析研究HolisticQMSDefinesCAPASourcesComplaintsInternalInspectionsSupplierAuditsRegulatoryAuditsNon-conformanceDeviationsOutofSpecificationOutofSpecificationAdverseTrendsAdverseEventsIncomingInspectionsAndmore…NumeroussourceareasforCAPAScopeof“problems”thatdriveCAPAsgobeyondnonconformingproductAnyprocessthataffectsproductqualityisincluded質(zhì)量體系的分析研究CAPAProcess–bestpracticesVerifyEffectivenessImplementActionsReview&ApprovePlanInvestigate,RootCause,ActionPlanIdentify&TriageRegardlessofwheretheproblemoriginates,orwhattypeitis,itmustfollowaprocessIdentifyproblemAssessimpactQuality/Regulatory/ManagementNotificationInvestigationProcess?CompleteInvestigationDetermineRootCauseProposedCorrective/PreventiveActionsPlaneffectivenessAssesschangesEnsurenoimpacttoproductqualityConsensusfromSMEsApprovalImplementActionsVerifycompletedInformstakeholdersMeasuretoensureproblemhasbeenresolvedMonitortoensureitisnotre-occurringChangeControlMetricsandReporting質(zhì)量體系的分析研究AddressingQMSChallenges質(zhì)量體系的分析研究TypicalQMSChallengesChallengesinProblemIdentificationMissingviewofthebigpictureLackofownershipandaccountabilityInabilitytolinkrelatedproblemsInsufficienttoolsfortrendingandanalysisChallengesinInvestigationQualityofinvestigationsispoorMissing&incompleteinformationInabilitytoeasilyreviewsimilarpastinvestigationsInconsistentinvestigationprocess&RootCauseNotdeterminingrootcausePastdueinvestigations,notbeingclosed,getlostProblemIdentificationIdentify&InvestigateRootCauseCreateActionPlanChallengesinPlanningVaguerootcauseanalysisConfusionoverwhatis“corrective”andwhatis“preventive”actionInabilitytorelatecorrectiveactionstosourceproblemsLackofintegrationtoChangeControlSystem質(zhì)量體系的分析研究TypicalQMSChallenges(cont.)VerifyEffectivenessImplementActionsChallengesinImplementationNowaytotrackissuesthroughworkflowLackofvisibilitytoopenitemsLackofvisibilitytorelateditemsChangestoplanmid-streamComplianceriskChallengesinEffectivenessEasyto“forget”tomeasureeffectivenessDifficulttogathernecessarymetricsNomeanstogeneratemetricsInabilitytomeasureeffectivenessdoesnotgiveusanyassuranceifweareaddressingtherootcauseoftheproblemsReview&ApprovePlanChallengesinReview&ApprovalNotsurewhoneedstoapproveApprovalsinserial,notparallelApprovalprocesstakeslongtimeLackofkeystakeholderinput質(zhì)量體系的分析研究SolutionHolisticApproachtoQualityManagementGlobalize(harmonize)aroundacommonphilosophyandapproachtoCAPAandsourceEventsObtainfullcompliancewithcGxPs,aswellasregulatory&customerexpectationsUsequalitymetricsasabasisforcontinuousimprovementsTrending–ProblemAnalysisThoroughInvestigationsandRootCauseAnalysisEnsuringCAPAeffectivenessBringattentiontoriskareastopreventproblemsImplementacentralizedQualityManagementSystem:ManagesallinputsandoutputsaswellastheactualactionsScalabletobedeployedonaglobalbasisFunctionality/Flexibilitytomeetbusinessrequirements質(zhì)量體系的分析研究Re-definingCAPA質(zhì)量體系的分析研究Re-definingCAPADefinitionsStandardizedefinitionsacrosstheorganizationTermslike““deviation”,“event”,“nonconformance”,correction”,“correctiveaction”,“preventiveaction”,“discrepancy”mustbeconsistentforeachoperatingunitThesametermshouldhavethesamemeaningeverywhere,anddrivethesameprocessCAPAsourcesinclude:Complaints,AuditsObservations,TrendscanfeedCAPADetermine,scopeidentification&impactofnewsystemWheredoestheprocessneedtochange?Whowillthesystemaffect?Whatexistingpoliciesmaychange?Understandthedifferencebetweenthe“what”andthe“who”質(zhì)量體系的分析研究DefinetheInputs&Process質(zhì)量體系的分析研究RecordtheEventCaptureallrelateddataofanyeventregardlessofthetypeSourceDate&TimeofEventTypeDescriptionDepartmentForissuessurroundingEvents,utilizeaqualityevaluation:QualityEventonlyQualityEvent+CAPAQualityEvent+Investigation+CAPA+ChangeControlLogobservations/trendstoimplementpro-activechanges質(zhì)量體系的分析研究PerformAssessment&InvestigationAssignInvestigatorUse“Push”or“Pull”conceptAssessimpact,considerdecisiontreeapproachCreateInvestigationPlanUseParent-Childconcepts–trackeachinvestigation“task”UseInvestigationTemplatesTrack&CompleteInvestigationsUseworkflow,duedatesandremindersEscalationofpastdueinvestigationsSearch&ReportingUserDashboardsAnalyzeRootCauseStructureRootcauseAnalysisTreeUseRootCausetoDriveCAPAprocess質(zhì)量體系的分析研究CAPAPlan&ApprovalReviewcurrentlyinprogressCAPAsCreateCAPAsandlinktorootcauseIfmultipleCAPAsidentifywhichonesresolvewhichrootcause?Whichactionsmustbeclosedtoclosethedeviation?CreateanEffectivenessPlanatthistimeDetermineApproversUsepre-setapproverfunctionsifpossibleRouteInvestigation&CAPAplanforapprovalEmailalerts,remindersDashboardsObtainApprovalAbilitytorejecttovariouspreviousworkflowstates質(zhì)量體系的分析研究ImplementingCAPA&EffectivenessEachCAPArecordshouldhaveitsownrecordandworkflowUseParent-childrelationshipstobreakuptheprocessinto“smallerbites”ActionItemTrackingTrackcompletionandverificationofeachCAPAUseworkflow,duedatesandremindersEscalationofpastdueinvestigationsSearch&ReportingUserDashboardsMeasureeffectivenessaccordingtotheplan->evidencethatrootcausehasbeeneliminated質(zhì)量體系的分析研究ImportantQMSRequirements質(zhì)量體系的分析研究HighLevelRequirementsCentralizeddatabaseHandlesallprocessareas-modularWorkflowdrivenProactiveusernotificationandescalationActionitemsmanagementQuerying&ReportingElaboratesecuritybyuser-groupDefiningtheRequirementsManagementreportsPerformanceMetrics&TrendingPart11Compliance質(zhì)量體系的分析研究ManagementofallDataModularapproachtohandlingallsourceareasbutmaintainsindividualrequirementMultiple“RecordTypes”tohandleallprocessareasAbilitytocreateuserdefinedfieldsConfigurabledataentryformsValidationandbusinessrulesIntegrationtoexternalsystemsE.g.,CreatedeviationsautomaticallyfromERPE.g.,CreateOOSInvestigationfromLIMSMasterdata(customer,product/item,etc.)ExternalSystemsDataManagement質(zhì)量體系的分析研究WorkflowManagementConfigurableworkflowAutomatereviewandapprovalprocessbasedonmetadataBusiness-rulebasedworkflowsParallelApprovalsProcesschangingactivityE-mailnotificationsIntegratedsourceareasprocesstoCorrectiveActionprocessParent–childrelationshipsCrossreferencingWorkflowExternalSystemsDataManagement質(zhì)量體系的分析研究EscalationsandBusinessRulesBusinessrulesenforcementDateDue,MilestoneDatesAutomaticallyassigninginvestigators,reviewers,approversAutomaticallyschedulingtasksbasedontypeofRecordEscalation“Reminders”oftasksreachingexpectedcompletiondateEscalationofCAPApastdueWorkflowExternalSystemsDataManagementBusinessRules&Escalation質(zhì)量體系的分析研究Query,Reporting,TrendingWorkflowExternalSystemsDataManagementBusinessRules&EscalationSearch,Report,TrendQueryingAbilitytoqueryonallfieldsFulltext/searchenginefunctionalityAbilitytosavesearchesReportingCustomizablereportformatOnscreenview,print,email,saveStatusreportingTrendingAcrossallsitesAcrossallsourceareasRootcauseanalysisIdentifyoccurrenceratedecrease/increaseAbilitytodetecttrendsautomatically質(zhì)量體系的分析研究CompliancewithPart11Doesthesystemconformwithyourfirm’sPart11requirements?Hasthesoftware“passed”thetest,I.e.,hasitgonethroughFDAauditsatanotherfirm?Canitbevalidated?Howconfidentareyouintheaboveassessment?FullaudittrailReportingfeaturesConfigurablesecuritygroupsCompleterecordofcreatedandmodifieddataEnforcedworkflowsequencingPasswordcompositionrulesElectronicSignaturesmadeupoftwouniquecomponentsPasswordaging/expirationCannotre-usepreviouspasswordAccountLockingandAdminNotificationafterfailedlog-inAttemptsSessiontime-outRequirementof“reason”fordatamodificationAdministrator/ConfigurationAuditTrail質(zhì)量體系的分析研究ImplementSolution質(zhì)量體系的分析研究Quality,Operations,ITStructuredProjectOrganizationCustomer–SystemAdministratorImplementationConsultantProjectManagementCustomerExecutiveSponsorSr.Mgmt.SupportBusiness&ITProjectMgr.VendorProjectManagerProjectTeamChangeManagementValidationPartnersOperationsmanagementVendorSMEsQA&CustomerSatisfactionTechnicalSupportLAN/WANDBAServersCustomerITSponsorMedtronicLeads:MedtronicLeads:Customer.OwnerTeamCAPAComplaintsAuditsRMAsOthersSteeringCommitteeInternalComputerSystemsValidationVendor3rdParty(recommended)ValidationTeamVendorAdministrativeResources質(zhì)量體系的分析研究RapidROI-PhasedApproachCriticalSystemsPrioritizationPhase-1:FIRSTQMSConfigure,Prototype,TrainValidationPhase-2:AdditionalQSImplementation,Configure,Prototype,TrainDATAMigration&SystemsIntegrationReducedValidationviaMigrationtoolFullyintegratedCAPAInitialROI/BusinessandcomplianceBenefitsRollout–ProductionAdditionalQSYesNoPrioritizedQMSListandimplementationProjectPlanG