FDA QC实验室检查指南.docx

FDA QC实验室检查指南.docx

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FDAQC实验室检查指南

GUIDETOINSPECTIONSOFPHARMACEUTICALQUALITYCONTROLLABORATORIES

Note:

ThisdocumentisreferencematerialforinvestigatorsandotherFDA

personnel.ThedocumentdoesnotbindFDA,anddoesnoconferanyrights,

privileges,benefits,orimmunitiesfororonanyperson（s）.

1.INTRODUCTION

Thepharmaceuticalqualitycontrollaboratoryservesoneofthemost

importantfunctionsinpharmaceuticalproductionandcontrol.Asignificant

portionoftheCGMPregulations（21CFR211）pertaintothequalitycontrol

laboratoryandproducttesting.Similarconceptsapplytobulkdrugs.

Thisinspectionguidesupplementsotherinspectionalinformationcontained

inotheragencyinspectionalguidancedocuments.Forexample,Compliance

Program7346.832requiringpre-approvalNDA/ANDAinspectionscontains

generalinstructionstoconductproductspecificNDA/ANDAinspectionaudits

tomeasurecompliancewiththeapplicationsandCGMPrequirements.This

includespharmaceuticallaboratoriesusedforin-processandfinished

producttesting.

2.OBJECTIVE

Thespecificobjectivewillbespelledoutpriortotheinspection.The

laboratoryinspectionmaybelimitedtospecificissues,ortheinspection

mayencompassacomprehensiveevaluationofthelaboratory'scompliancewith

CGMP's.Asaminimum,eachpharmaceuticalqualitycontrollaboratoryshould

receiveacomprehensiveGMPevaluationeachtwoyearsaspartofthe

statutoryinspectionobligation.

Ingeneraltheseinspectionsmayinclude

--thespecificmethodologywhichwillbeusedtotestanewproduct

--acompleteassessmentoflaboratory'sconformancewithGMP's

--aspecificaspectoflaboratoryoperations

3.INSPECTIONPREPARATION

FDAInspectionGuidesarebasedontheteaminspectionapproachandour

inspectionofalaboratoryisconsistentwiththisconcept.Aspartofour

efforttoachieveuniformityandconsistencyinlaboratoryinspections,we

expectthatcomplex,highlytechnicalandspecializedtestingequipment,

proceduresanddatamanipulations,aswellasscientificlaboratory

operationswillbeevaluatedbyanexperiencedlaboratoryanalystwith

specializedknowledgeinsuchmatters.

Districtmanagementmakesthefinaldecisionregardingtheassignmentof

personneltoinspections.Nevertheless,weexpectinvestigators,analysts

andotherstoworkasteamsandtoadvisemanagementwhenadditional

expertiseisrequiredtocompleteameaningfulinspection.

Teammembersparticipatinginapre-approvalinspectionmustreadandbe

familiarwithComplianceProgram7346.832,Pre-Approval

Inspections/Investigations.RelevantsectionsoftheNDAorANDAshouldbe

reviewedpriortotheinspection;butiftheapplicationisnotavailable

fromanyothersource,thisreviewwillhavetobeconductedusingthe

company'scopyoftheapplication.

Teammembersshouldmeet,ifpossible,priortotheinspectiontodiscuss

theapproachtotheinspection,todefinetherolesoftheteammembers,and

toestablishgoalsforcompletionoftheassignment.Responsibilitiesfor

developmentofallreportsshouldalsobeestablishedpriortothe

inspection.ThisincludesthepreparationoftheFDA483.

TheCenterforDrugEvaluationandResearch（CDER）mayhaveissued

deficiencyletterslistingproblemsthatthesponsormustcorrectpriorto

theapprovalofNDA/ANDA'sandsupplements.Theinspectionteamisexpected

toreviewsuchlettersonfileatthedistrictoffice,andtheyareexpected

toasktheplantforaccesstosuchletters.Theteamshouldevaluatethe

repliestotheseletterstoassurethatthedataareaccurateandauthentic.

Completetheinspectioneventhoughtherehasbeennoresponsetothese

lettersorwhentheresponseisjudgedinadequate.

4.INSPECTIONAPPROACH

A.General

InadditiontothegeneralapproachutilizedinadrugCGMPinspection,the

inspectionofalaboratoryrequirestheuseofobservationsofthe

laboratoryinoperationandoftherawlaboratorydatatoevaluate

compliancewithCGMP'sandtospecificallycarryoutthecommitmentsinan

applicationorDMF.Whenconductingacomprehensiveinspectionofa

laboratory,allaspectsofthelaboratoryoperationswillbeevaluated.

Laboratoryrecordsandlogsrepresentavitalsourceofinformationthat

allowsacompleteoverviewofthetechnicalabilityofthestaffandof

overallqualitycontrolprocedures.SOPsshouldbecompleteandadequateand

theoperationsofthelaboratoriesshouldconformtothewrittenprocedures.

Specificationsandanalyticalproceduresshouldbesuitableand,as

applicable,inconformancewithapplicationcommitmentsandcompendial

requirements.

Evaluaterawlaboratorydata,laboratoryproceduresandmethods,laboratory

equipment,includingmaintenanceandca