国际上不同分析方法验证准则概述.ppt

国际上不同分析方法验证的准则概述 7 8 2010 蔡磊明 分析方法验证是论证某一分析方法适用于其用途的过程 Analyticalmethodvalidationistheprocesstoconfirmthattheanalyticalprocedureemployedforaspecifictestissuitableforitsintendeduse 分析方法验证MethodValidation 7 8 2010 Slide3 CriteriaforMethodValidation LimitofdetectionLimitofquantitationPrecision Intermediateprecision AccuracyLinearity RangeSelectivity SpecificityRuggednessRobustness Actualvalidationeffortdependsontheanalysisproblem Proofsuitabilityforintendeduse DefinitionMethodScope DefineValidationCriteria Test DefineRoutineTests ValidationofAnalyticalMethods SamplematrixCompoundsEquipment Location OptimizemethodparametersDefineperformancecharacteristicsAcceptancecriteria DeveloptestcasesPreliminarytestsFinaltests SOPsSystemSuitabilitytestsAnalyticalqualitycontrol ValidationPlan ValidationReport Slide5 ScopeoftheMethod Compounds SamplematrixQualitative quantitativeinformationOperatingrange concentration PerformancecharacteristicsInstrument specificbrand producte g Agilent1200Series Location specificlab specificsite global Specificregulatory standardsrequirements e g part21CFRPart11 ISO17025 InternationalregulatorybodiesandtheirguidelinesondifferentaspectsofMV ExamplesofMethodsThatRequireValidationDocumentation ChromatographicMethods HPLC GC TLC GC MS etc PharmaceuticalAnalysis InsupportofCMC BioanalyticalAnalysis InsupportofPK PD ClinicalStudies SpectrophotometricMethods UV VIS IR NIR AA NMR XRD MSCapillaryElectrophoresisMethods Zone IsoelectricFocusingParticleSizeAnalysisMethods Laser Microscopic Sieving SEC etc AutomatedAnalyticalMethods Robots AutomatedAnalysis 7 7 8 2010 ConsiderationsPriortoMethodValidation SuitabilityofInstrumentStatusofQualificationandCalibrationSuitabilityofMaterialsStatusofReferenceStandards Reagents PlaceboLotsSuitabilityofAnalystStatusofTrainingandQualificationRecordsSuitabilityofDocumentationWrittenanalyticalprocedureandproperapprovedprotocolwithpre establishedacceptancecriteria 8 7 8 2010 ValidationStep Definetheapplication purposeandscopeofthemethod Analytes Concentration Samplematrices Developaanalyticalmethod Developavalidationprotocol Qualificationofinstrument Qualify trainoperatorQualificationofmaterial Performpre validationexperiments Adjustmethodparametersand oracceptancecriteriaifnecessary Performfullvalidationexperiments DevelopSOPforexecutingthemethodinroutineanalysis Documentvalidationexperimentsandresultsinthevalidationreport 9 7 8 2010 PurposeofMethodValidation IdentificationofSourcesandQuantitationofPotentialerrorsDeterminationifMethodisAcceptableforIntendedUseEstablishProofthataMethodCanbeUsedforDecisionMakingSatisfyRegulatoryRequirements ValidationReport typeofcompoundsandmatrixdetailedchemicals reagents referencestandardsandcontrolsamplepreparationsproceduresforqualitychecksofstandardsandchemicalsusedsafetyconsiderationsmethodparameterscriticalparametersindicatedfromrobustnesstestinglistingofequipmentanditsfunctionalandperformancerequirements e g celldimensions baselinenoise columntemperaturerangedetailedconditionsonhowtheexperimentswereconducted includingsamplepreparationstatisticalproceduresandrepresentativecalculationsproceduresforqualitycontrolintheroutine e g systemsuitabilitytests representativeplots e g chromatograms spectraandcalibrationcurvesmethodacceptancelimitperformancedatatheexpecteduncertaintyofmeasurementresultscriteriaforrevalidationpersonwhodevelopedandinitiallyvalidatedthemethodsummaryandconclusions USFDAValidationGuidelines FDAGuidanceforIndustry AnalyticalProceduresandMethodsValidation DRAFT August2000FDAPolicyguide RequestingMethodsValidationforAbbreviatedNewDrugApplications ANDAs May1998FDAGuidanceforIndustry BioanalyticalMethodValidation May2001FDAGuidance Mass SpectrometryforConfirmationoftheIdentityofAnimalDrugResidues Draft FDAGuidance GuidelineforSubmittingSamplesandAnalyticalDataforMethodsValidationFDAGuidance ProtocolfortheConductofMethodTransferforTypeCMedicatedFeedAssayMethods May2007 USFDAValidationGuidelines FDAGuidanceforIndustry AnalyticalProceduresandMethodsValidation DRAFT August2000FDAPolicyguide RequestingMethodsValidationforAbbreviatedNewDrugApplications ANDAs May1998FDAGuidanceforIndustry BioanalyticalMethodValidation May2001FDAGuidance Mass SpectrometryforConfirmationoftheIdentityofAnimalDrugResidues Draft FDAGuidance GuidelineforSubmittingSamplesandAnalyticalDataforMethodsValidationFDAGuidance ProtocolfortheConductofMethodTransferforTypeCMedicatedFeedAssayMethods May2007 ICHValidationGuidelines ICH GuidanceforIndustry Q2A TextonValidationofAnalyticalProceduresICH GuidanceforIndustry Q2B ValidationofAnalyticalProcedures Methodology EUValidationGuidelines EURACHEMTheFitnessforPurposeofAnalyticalMethodsProbablythemostdetailedofficialdocumentformethodvalidation 1998EMEAGuideResidues Guidanceforgeneratingandreportingmethodsofanalysisinsupportofpre registrationdatarequirementsforAnnexII partA Section4 andAnnexIII partA Section5 ofDirective91 414 Nov 2000 AustralianValidationGuidelines TGAGuide Australia StartingMaterialAnalyticalProcedureValidationforComplimentaryMedicines March2006NATATechnicalNote 17 GuidelinesfortheValidationandVerificationofChemicalTestMethods April2009 USEPAValidationGuidelines USEPAGuidetoMethodFlexibilityandApprovalofEPAWaterMethods40CFRPart136GuidelinesEstablishingTestProceduresfortheAnalysisofPollutants AnalyticalMethodsforBiologicalPollutantsinAmbientWater FinalRule Jan 31 200340CFRParts136and503GuidelinesEstablishingTestProceduresfortheAnalysisofPollutants AnalyticalMethodsforBiologicalPollutantsinWastewaterandSewageSludge March26 2007USEPA GuidanceformethodsdevelopmentandmethodsvalidationfortheResourceConservationandRecoveryAct RCRA Program Washington 1995 ValidationGuidelines IUPACTechnicalReport HarmonizedGuidelinesforSingleLaboratoryValidationofMethodsofAnalysisPureAppl Chem Vol 74 No 5 pp 835 855 2002AOAC HowtoMeetISO17025RequirementsforMethodVerification PreparedbyAOACINTERNATIONAL481N FrederickAve Suite500 2007UnitedStatesPharmacopeia ValidationofCompendialMethods e g XXVI Rockville MD 20022149 2152 Chapter1225 1999 RegulatoryandComplianceRequirementsReview FDAregulationssuchasGMP GLPandGCPandqualitystandardssuchasISO17025requireanalyticalmethodstobevalidatedbeforeandduringroutineuse TherearenospecificregulationsonmethodvalidationsbuttheFDA otheragenciesandindustrytaskforceshavedevelopedguidelinesformethodvalidation ValidationRequirements Parameters ICH USPValidationRequirements Parameters SpecificityLinearityRangeAccuracyPrecisionRepeatabilityIntermediatePrecisionReproducibilityLimitofDetectionLimitofQuantitation ICH SpecificityLinearityandRangeAccuracyPrecisionLimitofDetectionLimitofQuantitationRuggednessRobustness USP USPCategories Category1 QuantitationofmajorcomponentsoractiveingredientsCategory2 DeterminationofimpuritiesordegradationproductsCategory3 Determinationofperformancecharacteristics USPDataElementsRequiredForAssayValidation Mayberequired dependingonthenatureofthespecifictest ICHValidationCharacteristicsvs TypeofAnalyticalProcedure AOACCategoriesofChemicalMethods Category1 ConfirmationofIdentityCategory2 QuantifyingananalyteatalowconcentrationCategory3 Determiningifananalyteispresentaboveorbelowaspecified lowconcentration oftencalledaLimitTest ThespecifiedconcentrationisclosetotheLOQ Category4 QuantifyingananalyteatahighconcentrationCategory5 Determiningifananalyteispresentaboveorbelowaspecified highconcentration oftencalledaLimitTest ThespecifiedconcentrationissubstantiallyabovetheLOQ Category6 Qualitativetest AOACValidationCharacteristicsvs TypeofAnalyticalProcedure AOACValidationCharacteristics Analyteconcentrationversusprecisionwithinorbetweendays AOACValidationCharacteristics Analyterecoveryatdifferentconcentrations HowdoweKnowtheexpectationsoftheFDA FDAForm483FDAWarningLettersPersonalExperiences 483Observations Therewasinadequatemethodvalidationspecificitydatatodemonstratethateachmethodwascapableofdistinguishingtheactiveingredientfromitsimpurit