FDA-cGMP检查--英文

FDAFDAcGMPcGMPInspectionsInspectionsPekingUniversity2005PekingUniversity2005RobertC.Horan,PhDRobertC.Horan,PhDFDAPharmaceuticalInspectorateFDAPharmaceuticalInspectorateNewYorkDistrictNewYorkDistrictFDAInspectionsFDAInspections„„Periodic(biennial)comprehensivePeriodic(biennial)comprehensivecGMPcGMP„„PrePre--ApprovalInspection(PAI)ApprovalInspection(PAI)„„““ForcauseForcause””„„InspectionmayinvolvemorethanoneInspectionmayinvolvemorethanoneassignmentandwillverifycorrectionstoassignmentandwillverifycorrectionstopreviousinspections.previousinspections.„„AllinspectionscoverAllinspectionscoverGMPsGMPsForeignInspectionsbyForeignInspectionsbyCountryinFY2004CountryinFY2004India14%Germany14%Italy10%China7%UnitedKingdom7%Canada7%France5%Japan5%Switzerland4%Spain4%Ireland4%Others19%ForeignForeignInspectioninFY2004InspectioninFY2004byFirmTypebyFirmTypeAPI51%Dosage27%Intermediates10%ControlLab2%BothAPIandDosage9%Micronizer1%FDAFDAcGMPscGMPsfor21for21ststCenturyCenturyInitiativeInitiativeAnnounced8/2002Announced8/2002;;objectivesincludeobjectivesinclude::„„EncourageadoptionofnewtechnologiesEncourageadoptionofnewtechnologies„„PromoteindustryuseofmodernqualitysystemPromoteindustryuseofmodernqualitysystemapproachesapproaches„„EncourageriskEncouragerisk--basedapproacheswhichfocusbasedapproacheswhichfocusoncriticalelementsoncriticalelements„„EnsureFDAreview,complianceandinspectionEnsureFDAreview,complianceandinspectionpoliciesbasedonstatepoliciesbasedonstate--ofof--artpharmaceuticalartpharmaceuticalsciencescienceFDAFDAcGMPscGMPsfor21for21ststCenturyCenturyInitiativeInitiative„„SystemsBasedInspectionsSystemsBasedInspections„„RiskRisk--BasedApproachtoManufacturingandRegulationBasedApproachtoManufacturingandRegulation„„PharmaceuticalInspectoratePharmaceuticalInspectorate„„PATGuidancedocument/PATTeamPATGuidancedocument/PATTeam„„QualitySystemsGuidancedocumentQualitySystemsGuidancedocument„„ProcessValidation(CompliancePolicyGuiderevised;ProcessValidation(CompliancePolicyGuiderevised;Guidancebeingrevised)Guidancebeingrevised)„„21CFRPart11ElectronicRecordsGuidance(risk21CFRPart11ElectronicRecordsGuidance(risk--based;gearedtowardGMPdocuments)based;gearedtowardGMPdocuments)PharmaceuticalInspectoratePharmaceuticalInspectorate„„CadreofmostexperiencedinvestigatorswhoareCadreofmostexperiencedinvestigatorswhoarededicatedtodruginspectionsdedicatedtodruginspections„„IntensivelytrainedalongwithqualityreviewersIntensivelytrainedalongwithqualityreviewersandcompliancestaffinFDAheadquarters(HQ)andcompliancestaffinFDAheadquarters(HQ)„„OverallgoalistohavePIworkcloselywithHQOverallgoalistohavePIworkcloselywithHQpersonnelpersonnel––moreefficientlyintegratereviewmoreefficientlyintegratereviewandinspectionfunctionsandinspectionfunctionsPharmaceuticalInspectoratePharmaceuticalInspectorate„„FDAReviewstaff,ComplianceOfficersandFDAReviewstaff,ComplianceOfficersandPIcandidatesattendedtrainingmodulesPIcandidatesattendedtrainingmoduleswhichfocusedon:whichfocusedon:¾¾CurrentRegulatoryProgramsCurrentRegulatoryPrograms¾¾AdvancedQualitySystemsAdvancedQualitySystems¾¾PATandModernPharmaceuticalTechnologyPATandModernPharmaceuticalTechnology¾¾RiskManagementRiskManagementPharmaceuticalInspectoratePharmaceuticalInspectorate„„FieldInvestigators(18)fromacrossU.S.FieldInvestigators(18)fromacrossU.S.makeupthePharmaceuticalInspectoratemakeupthePharmaceuticalInspectorate¾¾ScreeningprocesswithcertificationboardScreeningprocesswithcertificationboard¾¾CompletedtrainingwithHQpersonnelCompletedtrainingwithHQpersonnel¾¾OnemonthdetailworkingwithHQstaffOnemonthdetailworkingwithHQstaff¾¾LevelIIIcertification(highestlevel)LevelIIIcertification(highestlevel)¾¾ConductConductPAIsPAIs,complexdruginspections,complexdruginspectionsProcessAnalyticalTechnologyProcessAnalyticalTechnology„„PATisasystemforPATisasystemfordesigningdesigning,,analyzinganalyzingandandcontrollingcontrollingmanufacturingthroughmanufacturingthrough““realrealtimetime””measurementsofcriticalmeasurementsofcriticalqualityattributesofrawandinqualityattributesofrawandin--processprocessmaterialsandprocesses,withthegoalofmaterialsandprocesses,withthegoalofensuringfinalproductquality.ensuringfinalproductquality.„„SeeSeeFDAGuidancedocumentonPATFDAGuidancedocumentonPATProcessAnalyticalTechnologyProcessAnalyticalTechnologyExamplesofPATapplications:ExamplesofPATapplications:„„ContinuousrealtimemeasurementsofContinuousrealtimemeasurementsofcontentuniformityoftabletsduringcontentuniformityoftabletsduringproduction(usingnearInfraproduction(usingnearInfra--Red)Red)„„NearIRmeasurementofmoisturelevelNearIRmeasurementofmoisturelevelduringAPIdryingprocesstodetermineduringAPIdryingprocesstodetermineactualendofoperationforeachbatchactualendofoperationforeachbatchProcessAnalyticalTechnologyProcessAnalyticalTechnology„„AprocessisgenerallyconsideredwellAprocessisgenerallyconsideredwellunderstoodwhen:understoodwhen:¾¾AllcriticalsourcesofvariabilityareidentifiedAllcriticalsourcesofvariabilityareidentifiedandexplainedandexplained¾¾Variabilityismanaged