PF-Online-1790-注射剂目视检查visual-inspection-of-injecti

2015年1月16日PFOnline(GCDF:D.Hunt.)CorrespondenceNumber—C118966Commentdeadline:March31,2015Addthefollowing:1790VISUALINSPECTIONOFINJECTIONS1.Scope1.1Introduction1.2RelatedChapters1.3DefectPrevention2.Introduction2.1InspectionProcessCapability2.2PatientRisk2.3HistoryofInspectionStandards3.TypicalInspectionProcessFlow3.1100%Inspection3.2AcceptanceSamplingandTesting3.3RemediationandAlternativePractices4.InspectionLife-Cycle4.1CommonSourcesofAddedParticulates4.2PreventionofParticulates4.3ParticulateRemovalbyComponentWashing4.4Trending5.InterpretationofInspectionResults5.1DefectClassification5.2UniqueProductandContainerConsiderations6.InspectionMethodsandTechnologies6.1ManualVisualInspection(MVI)6.2Semi-AutomatedVisualInspection6.3AutomatedVisualInspection(AVI)7.QualificationandValidationofInspectionProcesses7.1Standards7.2PreparingDefectStandards7.3ParticleTypes7.4RejectionProbabilityDetermination7.5TestSets7.6TypesofTestSets7.7TrainingandQualificationofHumanInspectors7.8InspectorQualificationRequirements7.9Requalification8.ConclusionsandRecommendations9.References1.SCOPE1.1IntroductionThischapterprovidesguidanceontheinspectionofinjectionsforvisibleparticles.Thetermsparticle,particulates,andparticulatematterareequivalentanddonothavedifferentmeaningwhenusedinthischapter.Individualvisibleparticlesaregenerallygreaterthan50µmindiameter,andthethresholdforroutine,reliabledetection(70%probability)isoftennear150µmforsinglesphericalparticlesinclearsolutionscontainedinclearglassvials[1].Themethodsdiscussedinthischapterarealsoapplicabletothedetectionofothervisibledefects.Theseinclude,butarenotlimitedto,containerintegritydefectssuchascracks,misplacedstoppers,orincompleteseals,anyofwhichmaycompromisethesterilityoftheproduct.Additionalcontainerdefects[2],aswellasotherproductcharacteristicssuchasfilllevel,arealsodetectedduringvisualinspection,andnon-conformingunitsshouldberejectedusingthemethodsdescribedinthischapter.Inspectionfortheseotherqualityattributesoftenoccursatthesametimeastheinspectionforparticles.Theprimaryfocusofthischapterisamanualreferenceinspectionmethod;however,semi-automatedandautomatedmethodsarealsodiscussed.1.2RelatedChaptersThegeneralchapterInjectionsandImplantedDrugProducts(Parenterals)—ProductQualityTests1providesanoverviewofinjectabledosageformsandthequalitytestsassociatedwiththem.Anothergeneralchapter,VisibleParticulatesinInjections790,hasbeenaddedtotheU.S.Pharmacopeia–NationalFormulary(USP–NF)toprovideacleardefinitionofroutineinspectionproceduresforinjectableproducts;thegoalistocomplywiththeexpectationthatproductsbeessentiallyfreeofvisibleparticulatematter.Additionally,informationonthedetectionofsubvisibleparticulatesisprovidedingeneralchaptersSubvisibleParticulateMatterinTherapeuticProteinInjections787,ParticulateMatterinInjections788,andParticulateMatterinOphthalmicSolutions789.ThegeneralchapterMethodsfortheDeterminationofParticulateMatterinInjectionsandOphthalmicSolutions1788providesadditionalsupportinginformationonmeasurementmethodsforsubvisibleparticles.1.3DefectPrevention2015年1月16日PFOnline[3]incriticalareas.Thisapproachbeginswithdevelopingqualityattributesbasedonincomingcomponentspecifications,followedbycomponent-levelacceptancetesting.Itextendstocomponentpreparationandproduct-fillingprocedures,followedby100%in-processinspectionoffilledproduct,andconcludingwithfinalacceptancesamplingandtestingofthefinishedproduct.Theapproachmustextendtopurchased,ready-to-usecomponentssuchascontainersorclosures,wherethereisnoopportunityforsubsequentparticleremovalafterreceiptandbeforefilling.Stabilityandretentionsampleinspection,customercomplainthandling,andin-houseinvestigativeproceduressupportthisintegratedprocess.Theinspectionlife-cycleiscomposedof,andsupportedby,sub-cyclesinvolvingqualification,maintenance,personneltraining,defectcharacterization,andtheuseofstandardswithineachofthecriticalareas.Thefinalelementofthelife-cycleisafeedbackloopoftrendinganddatareviewfromeachoftheseprocessareas,resultinginamechanismthatsupportscontinuousprocessimprovement.2.INTRODUCT