ICH方法学验证

GuidanceforIndustryQ2BValidationofAnalyticalProcedures:MethodologyNovember1996ICHGuidanceforIndustryQ2BValidationofAnalyticalProcedures:MethodologyAdditionalcopiesareavailablefrom:theDrugInformationBranch(HFD-210),CenterforDrugEvaluationandResearch(CDER),5600FishersLane,Rockville,MD20857(Tel)301-827-4573(HFM-40)CenterforBiologicsEvaluationandResearch(CBER)1401RockvillePike,Rockville,MD20852-1448,(Fax)888-CBERFAXor301-827-3844(VoiceInformation)800-835-4709or301-827-1800U.S.DepartmentofHealthandHumanServicesFoodandDrugAdministrationCenterforDrugEvaluationandResearch(CDER)CenterforBiologicsEvaluationandResearch(CBER)November1996ICHiTableofContentsI.INTRODUCTION.....................................................1II.SPECIFICITY(1).....................................................2A.Identification(1.1)...............................................2B.AssayandImpurityTest(s)(1.2).....................................2III.LINEARITY(2)......................................................3IV.RANGE(3)..........................................................4V.ACCURACY(4)......................................................5A.Assay(4.1).....................................................5B.Impurities(Quantitation)(4.2)......................................6C.RecommendedData(4.3)..........................................6VI.PRECISION(5).......................................................6A.Repeatability(5.1)...............................................7B.IntermediatePrecision(5.2)........................................7C.Reproducibility(5.3)..............................................7D.RecommendedData(5.4)..........................................7VII.DETECTIONLIMIT(6)................................................7A.BasedonVisualEvaluation(6.1)....................................7B.BasedonSignal-to-Noise(6.2)......................................8C.BasedontheStandardDeviationoftheResponseandtheSlope(6.3)........8D.RecommendedData(6.4)..........................................8VIII.QUANTITATIONLIMIT(7)............................................8A.BasedonVisualEvaluation(7.1)....................................9B.BasedonSignal-to-Noise(7.2)......................................9C.BasedontheStandardDeviationoftheResponseandtheSlope(7.3)........9D.RecommendedData(7.4).........................................10IX.ROBUSTNESS(8)...................................................10X.SYSTEMSUITABILITYTESTING(9)...................................10ThisguidancewasdevelopedwithintheExpertWorkingGroup(Quality)oftheInternationalConferenceon1HarmonisationofTechnicalRequirementsforRegistrationofPharmaceuticalsforHumanUse(ICH)andhasbeensubjecttoconsultationbytheregulatoryparties,inaccordancewiththeICHprocess.ThisdocumenthasbeenendorsedbytheICHSteeringCommitteeatStep4oftheICHprocess,November1996.AtStep4oftheprocess,thefinaldraftisrecommendedforadoptiontotheregulatorybodiesoftheEuropeanUnion,JapanandtheUnitedStates.ThisguidancewaspublishedintheFederalRegisteronMay19,1997(62FR27464),andisapplicabletodrugandbiologicalproducts.ThisguidancerepresentstheAgency’scurrentthinkingonthevalidationofanalyticalprocedures.ItdoesnotcreateorconferanyrightsfororonanypersonanddoesnotoperatetobindFDAorthepublic.Analternativeapproachmaybeusedifsuchapproachsatisfiestherequirementsoftheapplicablestatute,regulations,orboth.GUIDANCEFORINDUSTRY1Q2BValidationofAnalyticalProcedures:MethodologyI.INTRODUCTIONThisdocumentiscomplementarytotheICHguidanceentitledTextonValidationofAnalyticalProcedures(ICHQ2A),whichpresentsadiscussionofthecharacteristicsthatshouldbeconsideredduringthevalidationofanalyticalprocedures.Itspurposeistoprovidesomeguidanceandrecommendationsonhowtoconsiderthevariousvalidationcharacteristicsforeachanalyticalprocedure.Insomecases(forexample,demonstrationofspecificity),theoverallcapabilitiesofanumberofanalyticalproceduresincombinationmaybeinvestigatedinordertoensurethequalityofthedrugsubstanceordrugproduct.Inaddition,thedocumentprovidesanindicationofthedatathatshouldbepresentedinanewdrugapplication.Allrelevantdatacollectedduringvalidationandformulaeusedforcalculatingvalidationcharacteristicsshouldbesubmittedanddiscussedasappropriate.Approachesotherthanthosesetforthinthisguidancemaybeapplicableandacceptable.Itistheresponsibilityoftheapplicanttochoosethevalidationprocedureandprotocolmostsuitablefortheirproduct.However,itisimportanttorememberthatthemainobjectiveofvalidationofananalyticalprocedureistodemonstratethattheprocedureissuitableforitsintendedpurpose.Duetotheircomplexnature,analyticalproceduresforbiologicalandbiotechnologicalproductsinsomecasesmaybeapproacheddifferentlythaninthisdocument.Well-characterizedreferencematerials,withdocumentedpurity,shouldbeusedthroughoutthevalidationstudy.Thedegreeofpuritynecessarydependsontheintendeduse.Inaccordancewiththeparentdocument,andforthesakeofclarity,