fdaqclab

第1页共12页2004年11月23日GUIDETOINSPECTIONSOFPHARMACEUTICALQUALITYCONTROLLABORATORIESNote:ThisdocumentisreferencematerialforinvestigatorsandotherFDApersonnel.ThedocumentdoesnotbindFDA,anddoesnoconferanyrights,privileges,benefits,orimmunitiesfororonanyperson(s).1.INTRODUCTIONThepharmaceuticalqualitycontrollaboratoryservesoneofthemostimportantfunctionsinpharmaceuticalproductionandcontrol.AsignificantportionoftheCGMPregulations(21CFR211)pertaintothequalitycontrollaboratoryandproducttesting.Similarconceptsapplytobulkdrugs.Thisinspectionguidesupplementsotherinspectionalinformationcontainedinotheragencyinspectionalguidancedocuments.Forexample,ComplianceProgram7346.832requiringpre-approvalNDA/ANDAinspectionscontainsgeneralinstructionstoconductproductspecificNDA/ANDAinspectionauditstomeasurecompliancewiththeapplicationsandCGMPrequirements.Thisincludespharmaceuticallaboratoriesusedforin-processandfinishedproducttesting.2.OBJECTIVEThespecificobjectivewillbespelledoutpriortotheinspection.Thelaboratoryinspectionmaybelimitedtospecificissues,ortheinspectionmayencompassacomprehensiveevaluationofthelaboratory'scompliancewithCGMP's.Asaminimum,eachpharmaceuticalqualitycontrollaboratoryshouldreceiveacomprehensiveGMPevaluationeachtwoyearsaspartofthestatutoryinspectionobligation.Ingeneraltheseinspectionsmayincludethespecificmethodologywhichwillbeusedtotestanewproductacompleteassessmentoflaboratory'sconformancewithGMP'saspecificaspectoflaboratoryoperations3.INSPECTIONPREPARATIONFDAInspectionGuidesarebasedontheteaminspectionapproachandourinspectionofalaboratoryisconsistentwiththisconcept.Aspartofourefforttoachieveuniformityandconsistencyinlaboratoryinspections,weexpectthatcomplex,highlytechnicalandspecializedtestingequipment,proceduresanddatamanipulations,aswellasscientificlaboratoryoperationswillbeevaluatedbyanexperiencedlaboratoryanalystwithspecializedknowledgeinsuchmatters.Districtmanagementmakesthefinaldecisionregardingtheassignmentofpersonneltoinspections.Nevertheless,weexpectinvestigators,analystsandotherstoworkasteamsandtoadvisemanagementwhenadditionalexpertiseisrequiredtocompleteameaningfulinspection.Teammembersparticipatinginapre-approvalinspectionmustreadandbefamiliarwithComplianceProgram7346.832,Pre-ApprovalInspections/Investigations.RelevantsectionsoftheNDAorANDAshouldbereviewedpriortotheinspection;butiftheapplicationisnotavailablefromanyothersource,thisreviewwillhavetobeconductedusingthecompany'scopyoftheapplication.第2页共12页2004年11月23日Teammembersshouldmeet,ifpossible,priortotheinspectiontodiscusstheapproachtotheinspection,todefinetherolesoftheteammembers,andtoestablishgoalsforcompletionoftheassignment.Responsibilitiesfordevelopmentofallreportsshouldalsobeestablishedpriortotheinspection.ThisincludesthepreparationoftheFDA483.TheCenterforDrugEvaluationandResearch(CDER)mayhaveissueddeficiencyletterslistingproblemsthatthesponsormustcorrectpriortotheapprovalofNDA/ANDA'sandsupplements.Theinspectionteamisexpectedtoreviewsuchlettersonfileatthedistrictoffice,andtheyareexpectedtoasktheplantforaccesstosuchletters.Theteamshouldevaluatetherepliestotheseletterstoassurethatthedataareaccurateandauthentic.Completetheinspectioneventhoughtherehasbeennoresponsetotheselettersorwhentheresponseisjudgedinadequate.4.INSPECTIONAPPROACHA.GeneralInadditiontothegeneralapproachutilizedinadrugCGMPinspection,theinspectionofalaboratoryrequirestheuseofobservationsofthelaboratoryinoperationandoftherawlaboratorydatatoevaluatecompliancewithCGMP'sandtospecificallycarryoutthecommitmentsinanapplicationorDMF.Whenconductingacomprehensiveinspectionofalaboratory,allaspectsofthelaboratoryoperationswillbeevaluated.Laboratoryrecordsandlogsrepresentavitalsourceofinformationthatallowsacompleteoverviewofthetechnicalabilityofthestaffandofoverallqualitycontrolprocedures.SOPsshouldbecompleteandadequateandtheoperationsofthelaboratoriesshouldconformtothewrittenprocedures.Specificationsandanalyticalproceduresshouldbesuitableand,asapplicable,inconformancewithapplicationcommitmentsandcompendialrequirements.Evaluaterawlaboratorydata,laboratoryproceduresandmethods,laboratoryequipment,includingmaintenanceandcalibration,andmethodsvalidationdatatodeterminetheoverallqualityofthelaboratoryoperationandtheabilitytocomplywithCGMPregulations.Examinechromatogramsandspectraforevidenceofimpurities,poortechnique,orlackofinstrumentcalibration.Mostmanufacturersusesystemsthatprovidefortheinvestigationoflaboratorytestfailures.Thesearegenerallyrecordedinsometypeoflog.Asktoseeresultsofanalysesforlotsofproductthathavefailedtomeetspecificationsandreviewtheanalysisoflotsthathavebeenretested,rejected,orreworked.Evaluatethedecisiontoreleaselotsofproductwhenthelaboratoryresultsindicatethatthelotfailedtomeetspecificationsanddeterminewhoreleasedthem.B.Pre-ApprovalDocumentsrelatingtotheformulationoftheproduct,synthesisofthebulkdrugsubstance,productspecifications,analysisoftheproduct,andothersareexaminedduringthereviewprocessinheadquarters.However,thesereviewsandevaluationsdependonaccurateandauthenticdatathatt