Guideline for the Manufacture of In Vitro Diagnost

ThisguidancewaswrittenpriortotheFebruary27,1997implementationofFDA'sGoodGuidancePractices,GGP's.ItdoesnotcreateorconferrightsfororonanypersonanddoesnotoperatetobindFDAorthepublic.Analternativeapproachmaybeusedifsuchapproachsatisfiestherequirementsoftheapplicablestatute,regulations,orboth.ThisguidancewillbeupdatedinthenextrevisiontoincludethestandardelemntsofGGP's.GuidelinefortheManufactureofInVitroDiagnosticProductsFoodandDrugAdministrationCenterforDevicesandRadiologicalHealthOfficeofComplianceJanuary10,1994PREFACETheFoodandDrugAdministration(FDA)oftenformulatesanddisseminatesguidelinesaboutmatterswhichareauthorizedbythelawsenforcedbytheAgency.Accordingly,FDAismakingavailablethisguideline.ThisguidelineisintendedtobeusedinconjunctionwiththecurrentGoodManufacturingPractice(CGMP)regulation($21CFR820);theLabelingforInVitmDiagnosticProductsregulation($21CFR809.lo),andtheGuidelineonGeneralPrinciplesofProcessValidation.ItisalsointendedtobeusedinconjunctionwiththeinterpretationspublishedintheDeviceGoodManufacturingPracticesManual,MedicalDeviceGMPGuidanceforFDAInvestigatorsManual,andtheGMPWorkshopManualforSterileMedicalDevices.Thenoticeofavailabilityofthedraftguidelinestatedthatitwouldbeissuedunder521CFR10.90@),whichprovidesfortheuseofguidelinestoestablishproceduresorstandardsofgeneralapplicabilitythatarenotlegalrequirementsbutthatareacceptabletotheAgency.TheAgencyisnowintheprocessofconsideringwhethertorevise$21CFR10.90(b).Althoughthatdecisionmakingprocessisnotyetcomplete,theAgencyhasdecidedtopublishthisguideline.However,thisnoticeandthefinalguidelinearenotbeingissuedundertheauthorityof521CFR10.90@),andthefinalguideline,althoughcalledaguideline,doesnotoperatetobindFDAoranyotherpersonin-anyway.TheAgencyadvisesthatthisfinalguidelinerepresentsitscurrentpositionontherequirementsoftheCGMPregulationsforinvitrodiagnosticproducts.Theguidelinemaybeusefultomanufacturersofinvitrodiagnosticproducts.Apersonmayalsochoosetousealternateprocedureseventhoughtheyarenotprovidedforintheguideline.Ifapersonchoosestodepartfromthepracticesandproceduressetforthinthefinalguideline,thatpersonmaywishtodiscussthematterfurtherwiththeAgencytopreventanexpenditureofmoneyandeffortonactivitiesthatmaylaterbedeterminedtobeunacceptablebyFDA.ThisguidelinedoesnotbindtheAgency,anditdoesnotcreateorconferanyrights,privileges,orbenefitsfororonanyperson.CONTENTSSECTIONPAGE1.0SCOPE....................................12.0INTRODUCTION..................................13.0APPLICATIONOFTHEREGULATIONSTOIVDs.............2.........................ProductandProcessSpecifications23.1.1productspecifications............................33.1.2ProcessSpecifications............................4ProcessValidation..................................-6-ProductionandProcessControls..........................73.3.1SterilizationandMicrobiologicalReductionTechniques.......7.................................3.3.2Lyophilization8....................................3.3.3Filtration9...............................3.3.4FillingProcesses10.................3.3.4.1ValidationofFillingProcesses11................................EnvironmentalControl13....................3.4.1AirborneandOtherContamination13..................................3.4.2AirPressure14....................................3.4.3Filtration15....................................PersonnelAttire15..............................CleaningandSanitation:16Components.......................FinishedIVDInspectionandTesting18......................StabilityStudiesandExpirationDating21......................ComplaintsandFailureInvestigations22....................................TrendAnalysis23.................................AppendixI.References-25...................................AppendixI1.Definitions27GuidelinefortheManufactureofInVitroDiagnosticProducts1.0SCOPEInvitrodiagnosticproducts(IVDs),asdefinedin$21CFR809.3(a),arethosereagents,instruments,andsystemsintendedforuseinthediagnosisofdiseaseorotherconditionsincludingadeterminationofthestateofhealth,inordertocure,mitigate,treat,orpreventdiseaseoritssequelae.Suchproductsareintendedforuseinthecollection,preparation,andexaminationofspecimenstakenfromthehumanbody.TheseproduotsaredevicesasdefinedinSection201(h)oftheFederalFood,Drug,andCosmeticAct(theAct),andmayalsobebiologicalproductssubjecttoSection351ofthePublicHealthServiceAct.Thisguidelineisapplicabletomanufacturersofallinvitrodiagnosticreagentsandsystems,butisnotintendedtoapplytomanufacturersofIVDinstrumentation.Assuch,thisguidelineappliestoclinicalchemistryandclinicaltoxicologydevices,hematologyandpathologydevices,andimmunologyandmicrobiologydevices.Thisguidelineprovidesgeneralguidanceontheapplicationofthemedicaldevicegoodmanufacturingpractice(GMP)regulation,$21CFRPart820,toprocessescommonlyusedinthemanufactureofIVDs.ItincludesmethodsandproceduresformeetingrequirementsofthemedicaldeviceGMPregulation.Italsoprovidesgeneralguidanceontheapplicationofthelabelingregulation,$21CFR809.10,forthesedevices.ThisguidelinewillbeusedasareferencebyFDAinvestigator