风险评估在QA审查中的应用

OECDOECDEventEvent,Villa,VillaTuscolanaTuscolana,Frascati(Roma),Italy,,Frascati(Roma),Italy,AprilApril1010––11,11,20082008RiskRiskbasedbasedassessmentassessmentappliedappliedtotoQAGLPQAGLPauditsauditsAlainAlainPitonPitonGaldermaGaldermaR&DR&D,,SophiaSophia--AntipolisAntipolis,France,[e-mail]@galderma.comOECDOECDEventEvent,Villa,VillaTuscolanaTuscolana,Frascati(Roma),Italy,,Frascati(Roma),Italy,AprilApril1010––11,11,20082008RISKBASEDASSESSMENTRISKBASEDASSESSMENTFORGLPAUDITSFORGLPAUDITSINTRODUCTIONSincetheoriginofGLPthestandardplanforQAinspectionsisbasedupontheconceptofstudyandcriticalphases.Theconceptoffacility-basedandprocess-basedinspectionsemergessinceadecade.The“defaultstandard”intheindustryisstilldrivenbythestudiesandtheideathatfacility-basedandprocess-basedshouldbeperformedquarterly.Theconceptofprocesses,broughtbytheISOstandards,andthebusinessneedofoptimizingtheuseofresourcesleadustowardaprocessbasedinspectionconcept,drivenbytherisksassociatedtotheprocessesThispresentationisaimedtosuggesttowhatextentthisapproachisGLPcompatibleOECDOECDEventEvent,Villa,VillaTuscolanaTuscolana,Frascati(Roma),Italy,,Frascati(Roma),Italy,AprilApril1010––11,11,20082008GLPinspectionsGLPinspectionsAuthoritiesrequirementsAuthoritiesrequirements•FDA:Inspecteachnonclinicallaboratorystudyatintervalsadequatetoassuretheintegrityofthestudyandmaintainwrittenandproperlysignedrecordsofeachperiodicinspectionshowingthedateoftheinspection,thestudyinspected,thephaseorsegmentofthestudyinspected,thepersonperformingtheinspection,findingsandproblems,actionrecommendedandtakentoresolveexistingproblems,andanyscheduleddateforreinspection.Anyproblemsfoundduringthecourseofaninspectionwhicharelikelytoaffectstudyintegrityshallbebroughttheattentionofthestudydirectorandmanagementimmediately.•OECD:conductinspectionstodetermineifallstudiesareconductedincompliancewiththesePrinciplesofGoodLaboratoryPractice.InspectionsshouldalsodeterminethatstudyplansandStandardOperatingProcedureshavebeenmadeavailabletostudypersonnelandarebeingfollowed.•InspectionscanbeofthreetypesasspecifiedbyQualityAssuranceProgramStandardOperatingProcedures:–Study-basedinspections,Facility-basedinspections,Process-basedinspections.•Japan:Thequalityassurancemanagershouldimplementbyoneself,ordesignateapersoninchargeofstudytoimplementthefollowing:•(3)confirmthatinspectionsareconductedperiodicallyatintervalsappropriatetoassurethereliabilityofstudyincompliancewiththisordinance;preparerecordsspecifyingthenatureofinspection,inspectionresults,actionstakentosolveproblems,andthedatewhenre-inspectionisscheduledetc.,thenstorethemwithsignatureorsignandseal;•MinistryofHealthandWelfareOrdinanceNo.21,1997OECDOECDEventEvent,Villa,VillaTuscolanaTuscolana,Frascati(Roma),Italy,,Frascati(Roma),Italy,AprilApril1010––11,11,20082008RISKBASEDASSESSMENTRISKBASEDASSESSMENTFORGLPINSPECTIONSFORGLPINSPECTIONSCURRENTSITUATIONINTHEGLPWORLD–Stillalotof“criticalphasesapproach”–Processandfacilitybasedinspectionsdesignunclear–Periodicitydefined(oftenquarterly)–“processes”arefrequentlyperiodicinspectionsof“phases”–FrequentexpectationsbytheauthoritiesoutsideEUtomaintainthestatus-quoOECDOECDEventEvent,Villa,VillaTuscolanaTuscolana,Frascati(Roma),Italy,,Frascati(Roma),Italy,AprilApril1010––11,11,20082008RISKBASEDASSESSMENTRISKBASEDASSESSMENTFORGLPINSPECTIONSFORGLPINSPECTIONSCriticalphasesapproach:Consequences•Studiesarecomparabletoproducts,QAinspectionscouldbelookedatasaQCoftheproduct•Manyphasesareauditedagainandagainwithverylittletonoaddedvalue•Manyinterfacesbetweenphasesarerarelyorneverevaluated•InformationobtainedishardlyusefulforaCAPAoracontinuousimprovementprocessBUT•Studiesare“clean”(productmaybereleased)•ComplianceisgrantedOECDOECDEventEvent,Villa,VillaTuscolanaTuscolana,Frascati(Roma),Italy,,Frascati(Roma),Italy,AprilApril1010––11,11,20082008RISKBASEDASSESSMENTRISKBASEDASSESSMENTFORGLPINSPECTIONSFORGLPINSPECTIONSWhattheprocessesriskbasedassessmentcanprovide?•Avisionoftheactivitythroughprocessesregardlessoftheproduct(inthiscasethestudy)•Aninspectionstrategybasedonactualrisks•AnoptimizedandthoroughuseofQAresources•Theassuranceofoverseeingallactivitiesandinterfaces•InformationforcontinuousimprovementOECDOECDEventEvent,Villa,VillaTuscolanaTuscolana,Frascati(Roma),Italy,,Frascati(Roma),Italy,AprilApril1010––11,11,20082008Howtodefineprocesses•Mainchallenge:findtherightgranularityofprocessmappinganddesign–Lookinginsidetheprocesses:•Drivesthecontentoftheprocessinspection•ApproachusedforQualityriskassessment,processimprovementandriskeliminationandcontrol•Theareasofriskareidentifiedandanalyzed•Theriskiscontrolled–Lookingtheprocessesascomponentsofthesystem:•approachusedforthepurposeoftheinspectionsplanning•Theriskisassessedandmonitored–The2levelsarecomplementaryandsequentialOECDOECDEventEvent,Villa,VillaTuscolanaTuscolana,Frascati(Roma),Italy,,Frascati(Roma),Italy,AprilApril1010––11,11,20082008CategoriesofprocessesCategories•ProductionProcesses•Supportprocesses•ManagementprocessesExampletoxicologys