FDAcGMP检查-hora.ppt
《FDAcGMP检查-hora.ppt》由会员分享,可在线阅读,更多相关《FDAcGMP检查-hora.ppt(47页珍藏版)》请在装配图网上搜索。
FDAcGMPInspectionsPekingUniversity2005 RobertC Horan PhDFDAPharmaceuticalInspectorateNewYorkDistrict FDAInspections Periodic biennial comprehensivecGMPPre ApprovalInspection PAI Forcause Inspectionmayinvolvemorethanoneassignmentandwillverifycorrectionstopreviousinspections AllinspectionscoverGMPs ForeignInspectionsbyCountryinFY2004 ForeignInspectioninFY2004byFirmType FDAcGMPsfor21stCenturyInitiative Announced8 2002 objectivesinclude EncourageadoptionofnewtechnologiesPromoteindustryuseofmodernqualitysystemapproachesEncouragerisk basedapproacheswhichfocusoncriticalelementsEnsureFDAreview complianceandinspectionpoliciesbasedonstate of artpharmaceuticalscience FDAcGMPsfor21stCenturyInitiative SystemsBasedInspectionsRisk BasedApproachtoManufacturingandRegulationPharmaceuticalInspectoratePATGuidancedocument PATTeamQualitySystemsGuidancedocumentProcessValidation CompliancePolicyGuiderevised Guidancebeingrevised 21CFRPart11ElectronicRecordsGuidance risk based gearedtowardGMPdocuments PharmaceuticalInspectorate CadreofmostexperiencedinvestigatorswhoarededicatedtodruginspectionsIntensivelytrainedalongwithqualityreviewersandcompliancestaffinFDAheadquarters HQ OverallgoalistohavePIworkcloselywithHQpersonnel moreefficientlyintegratereviewandinspectionfunctions PharmaceuticalInspectorate FDAReviewstaff ComplianceOfficersandPIcandidatesattendedtrainingmoduleswhichfocusedon CurrentRegulatoryProgramsAdvancedQualitySystemsPATandModernPharmaceuticalTechnologyRiskManagement PharmaceuticalInspectorate FieldInvestigators 18 fromacrossU S makeupthePharmaceuticalInspectorateScreeningprocesswithcertificationboardCompletedtrainingwithHQpersonnelOnemonthdetailworkingwithHQstaffLevelIIIcertification highestlevel ConductPAIs complexdruginspections ProcessAnalyticalTechnology PATisasystemfordesigning analyzingandcontrollingmanufacturingthrough realtime measurementsofcriticalqualityattributesofrawandin processmaterialsandprocesses withthegoalofensuringfinalproductquality SeeFDAGuidancedocumentonPAT ProcessAnalyticalTechnology ExamplesofPATapplications Continuousrealtimemeasurementsofcontentuniformityoftabletsduringproduction usingnearInfra Red NearIRmeasurementofmoisturelevelduringAPIdryingprocesstodetermineactualendofoperationforeachbatch ProcessAnalyticalTechnology Aprocessisgenerallyconsideredwellunderstoodwhen AllcriticalsourcesofvariabilityareidentifiedandexplainedVariabilityismanagedbytheprocess Qualitycannotbetestedintoproducts itshouldbebuilt inorshouldbebydesign ProcessValidation LifeCycleApproachProcessvalidationbeginswithprocessdevelopmentandcontinuesbeyondtheinitial validation batchesforaslongasproductismanufactured marketedSourcesofcriticalvariabilityidentifiedandcontrolledQualitySystemroleinmaintainingvalidatedstate qualitybuiltin nottestedintoproduct ProcessValidation FDACompliancePolicyGuide ProcessValidationRequirementsforDrugProductsandActivePharmaceuticalIngredientsCPG7132c 08 revisiondate12March2004FDAIndustryGuidelineonProcessValidation currentlybeingrevised SystemInspections QualityFacilitiesandEquipmentMaterialsProductionPackaging LabelingLaboratoryControls MostCommonGMPDeficienciesbySystem API DosageInspectionsfor2004 5 StateofControl Detailedinspectionofasystemsothatthefindingsreflectthestateofcontrolinthatsystemforeveryproduct profile classIfoneofthesixsystemsisoutofcontrol thefirmisconsideredoutofcontrolAsystemisconsideredoutofcontrolbasedonGMPdeficiencieswhichsuggestlackofassuranceofquality QualitySystem QualitymustbebuiltintotheprocessQualityisnottestedintotheproductAssuranceofQualitycomesfrom Designofrobustprocessbasedonthoroughknowledgeofthatprocessandthesourcesofvariability EffectiveQualitySysteminplace RoleofManagementinQS Managementisresponsiblefor OrganizationalstructureAllProcessesAllProceduresFacilities ResourcesInshort everythingtoinsureproductquality customersatisfactionandcontinuousimprovement QualitySystemResponsibilities AssuresoverallcompliancewithcGMPsReviewandapprovaldutiesfor ProductQualityReviews atleastannually ComplaintreviewsDiscrepancy failureinvestigationsChangeControlCAPA CorrectiveAndPreventiveAction Qualitysystem continued 6 Reprocess Rework7 Validation Revalidation8 Rejects9 StabilityFailures Outoftrenddata10 Quarantineproducts11 DocumentedGMP JobRelatedTraining LaboratoryControlSystem AdequatelabfacilitiesundertheQualityUnitwhichisindependentfromProductionAdequatelystaffedlaboratories supervisoryandbenchpersonnel Writtenspecificationsforrawmaterials intermediates APIs labels packagingWrittenproceduresforsampling testing approvalorrejectionofmaterialsandfortherecordingandstorageofdataChangecontrolforwrittenproceduresMethodvalidation revalidation LaboratoryControlSystem ReferenceStandards primary secondary EquipmentQualificationCalibration writtenprocedures schedule documentationValidationandSecurityforcomputerizedhandlingoftestresultsandrelateddata systemforassuringintegrityofalllabdataLaboratorycontrolsfollowedanddocumented LaboratoryControlSystem Writtenprocedure SOP coveringoutofspecification oos resultsInvestigationof oos resultsconductedinatimelymannerasperSOPanddocumented completerecordsmaintained Conclusionsfrom oos investigationsdocumentedandcorrectiveactions needforadditioninvestigationidentifiedandimplemented oos reviewincludedinProductQualityReviews LaboratoryControlRecords DescriptionofsamplesIdentificationofmethodusedRawdataforsample standardpreparation reagentsCompleterecordofalldatafromtestingRecordofallcalculationsStatementofthetestresults howcomparewithestablishedacceptancecriteriaSignatureofthepersonwhoperformedeachtest datestestsperformedDate signatureofsecondqualifiedpersonwhoreviewedoriginaltestrecordsforaccuracy completenessandcompliancewithestablishedstandards ProductionSystem Training documented job related MasterproductionandcontrolrecordsBatchproductionandcontrolrecordsChangecontrolprocedureContemporaneous accurateandcompletebatchproductiondocumentationImplementationanddocumentationofin processcontrols tests andexaminations Productionsystem continued Adequatewrittenprocedures practiceforcharge inofmaterialsIdentificationofequipmentwithcontents stageofmanufacturing statusEquipmentcleaningrecordsEstablishedtimelimitsforcompletionofproductionsteps stages Productionsystem continued DeviationsinvestigatedanddocumentedcontemporaneouslywithinvestigationProcessvalidationbasedonknowledgeofprocess scientificbasisforidentifyingcriticalsteps criticalprocessparameters controlpoints Justificationandconsistencyofin processspecificationsandfinalproductspecificationsData informationdocumentedandavailabletoQualityUnitforreview trending investigationsetc Facilities EquipmentSystem FACILITIESLocation design constructionappropriatetofacilitatecleaning maintenance operationsLayoutandairhandlingdesignedandconstructedtopreventcross contaminationFlowofmaterials personneldesignedtopreventmix upsorcontamination Facilities EquipmentSystem Definedareasorothercontrolsystemstopreventmix upsorcontaminationIncomingmaterials id quarantine Samplingarea preventcontamination Quarantine intermediates APIs ReleasedmaterialsRejection Facilities EquipmentSystem EQUIPMENTAppropriatedesign size location non reactiveproductcontactsurfacesIdentificationclearlymarkedQualification DQ IQ OQ PQ CalibrationPreventiveMaintenancescheduleandproceduresCleaningproceduresandvalidationRecordsofuse cleaning maintenance Facilities EquipmentSystem Lubricants heatingfluidsorcoolants notcontact alterproductquality ClosedorcontainedequipmentInspectionpriortouse Separatefacilitiesorcontainmentwhereneeded penicillins highlypotentcompoundsetc Utilities Qualifiedandappropriatelymonitored drawingsshouldbeavailableDesignedandconstructedtopreventcontaminationorcross contaminationRecirculatedairtoproduction sameconcern PermanentlyinstalledpipeworkshouldbeappropriatelyidentifiedDrainsofadequatesizewithairbreak Water ProcesswateratminimummeetingWHOguidelinesforpotablewaterJustifyqualityofwaterusedtoachievestatedAPIqualityandestablishspecificationsWatertreatmentfacilitiesvalidatedAPItobeusedforincorporationintosteriledosageform waterusedinlaterstagesshouldbemonitoredandcontrolledfortotalmicrobialcounts objectionableorganismsandendotoxins MaterialsSystem Writtenproceduresforreceipt identification quarantine storage handling sampling testingandapprovalorrejectionofmaterialsSystemtoevaluatesuppliers criticalmaterials PurchasedagainstagreedspecificationChangecontrolprocessforchangingsuppliersUponreceiptcheckforcorrectlabeling sealsBeforeco minglingbulkmaterial id testAssurancesobtainedfromnon dedicatedtankers MaterialsSystem Identificationonlargestoragecontainersandassociatedmanifolds fillinganddischargelinesCodegiventoreceivedbatches statusidentityAtminimum aspecificidentitytestonincomingbatches COASupplierevaluationshouldincludethreefullytestedbatches onefullytestedbatch yearWrittensamplingplanwithjustificationPreventcontaminationofsampledcontainers MaterialsSystem Storedinmannertopreventdegradation contamination noadverseeffectonqualityDrums bags boxesoffthefloorFirstin firstoutRejectedmaterialsidentifiedandcontrolledunderaquarantinesystemEstablishedre test re evaluationperiods Packaging LabelingSystem Writtenproceduresforreceipt identification quarantine sampling examinationand ortestingPifre used cleaned labelingdefaced Labeling AccesstolabelstoragearealimitedWrittenproceduresforreconciliation investigationifdiscrepancyAllexcesslabelswithbatch destroyedObsoletelabelsdestroyedPrintingdevicescontrolledtoinsureaccuracyoflabel againstbatchrecord Printlabelscheckedagainstmasterandacopyplacedintothebatchrecord Packaging LabelingOperations Documentedprocedurestoassurecorrectpackagingmaterials labelsusedOperationsdesignedtopreventmix upsLabels APIname batch storageconditionsShippedAPI Name addressmanufacturer specialtransportconditions expiry retestdateDocumentedclearancebeforeoperationsPackaged labeledintermediatesorAPIsexaminedaspartofpackaging documented Sealemployedtoassurepackageintegrity APIsareDrugSubstances FDAFood DrugandCosmeticActdefinitionofdrugincludes articlesintendedforuseinthediagnosis cure mitigation treatmentorpreventionofdiseaseinmanorotheranimals nodistinctionbetweenAPIs dosageforms BeforeICHQ7A FDAuseddosagedrugregulationsasguidanceforAPIinspectionStilltrue seenextslide however ICHQ7AprovidesguidanceontheapplicationofthosecGMPstoAPIs FromcurrentFDAComplianceProgram56002forDrugManufacturingInspections ThisisthecomplianceprogramforFDAInvestigators thisrevisionintroducedSystemsInspections ThecGMPregulationsarenotdirectrequirementsformanufactureofAPIs buttheyareguidanceforcGMPinAPImanufacture CurrentFDAComplianceGuideonProcessvalidation FromFDACompliancePolicyGuide ProcessValidationRequirementsforDrugProductsandActivePharmaceuticalIngredientsCPG7132c 08 revisiondate12March2004 ValidationofmanufacturingprocessesisarequirementoftheCurrentGoodManufacturingPractice cGMP regulationsforfinishedpharmaceuticals andisconsideredanenforceableelementofcurrentgoodmanufacturingpracticeforactivepharmaceuticalingredients APIs underthebroaderstatutorycGMPprovisionsoftheFederalFood Drug andCosmeticAct DifferencesAPI DosageForm APIsinvolvepurificationstepsGMPcontrolstighterforlaterAPIstepsAPIimpurityprofileiscriticalfocusandstepswhichproduceorremoveimpuritiesrequiregreatercontrolandvalidationDosageformsdonotinvolvepurification SimilaritiesAPIs DosageForms RequiredemonstratedknowledgeofprocessandapplicationofappropriateGMPcontrolstoassuresafety identity strength qualityandpurity SystemsincontroltobeincomplianceLifeCycleApproachtoValidation beyondtheinitial conformancebatches Similaritiesinclude Processesforspecificproductsvaryincomplexity eitherAPIordosagecaninvolvecomplexorsimpleprocesses In ProcessControlsFinishedProductControlsCriticalSteps CriticalProcessParametersProcessValidationQualityAssuranceforconsumerisbasedonunderstanding ControlofSourcesofProcess ProductVariability MoreSimilarities SciencebasedapproachfortheestablishmentofprocessesKnowledgeofprocessbasedonProcessDevelopmentworkDesignOfExperiments DOE QualitySystem review trending ContinuousImprovementpossiblewithinwellcharacterizedprocess- 配套讲稿:
如PPT文件的首页显示word图标,表示该PPT已包含配套word讲稿。双击word图标可打开word文档。
- 特殊限制:
部分文档作品中含有的国旗、国徽等图片,仅作为作品整体效果示例展示,禁止商用。设计者仅对作品中独创性部分享有著作权。
- 关 键 词:
- FDAcGMP 检查 hora
装配图网所有资源均是用户自行上传分享,仅供网友学习交流,未经上传用户书面授权,请勿作他用。
关于本文