Assay Development for Immunogenicity Testing of Th

GuidanceforIndustryAssayDevelopmentforImmunogenicityTestingofTherapeuticProteinsDRAFTGUIDANCEThisguidancedocumentisbeingdistributedforcommentpurposesonly.Commentsandsuggestionsregardingthisdraftdocumentshouldbesubmittedwithin60daysofpublicationintheFederalRegisterofthenoticeannouncingtheavailabilityofthedraftguidance.SubmitcommentstotheDivisionofDocketsManagement(HFA-305),FoodandDrugAdministration,5630FishersLane,rm.1061,Rockville,MD20852.AllcommentsshouldbeidentifiedwiththedocketnumberlistedinthenoticeofavailabilitythatpublishesintheFederalRegister.Forquestionsregardingthisdraftdocumentcontact(CDER)SusanKirshnerat301-827-1731,or(CBER)OfficeofCommunication,Outreach,andDevelopmentat301-827-1800.U.S.DepartmentofHealthandHumanServicesFoodandDrugAdministrationCenterforDrugEvaluationandResearch(CDER)CenterforBiologicsEvaluationandResearch(CBER)December2009CMCGuidanceforIndustryAssayDevelopmentforImmunogenicityTestingofTherapeuticProteinsAdditionalcopiesareavailablefrom:OfficeofCommunicationDivisionofDrugInformation,WO51,Room2201CenterforDrugEvaluationandResearchFoodandDrugAdministration10903NewHampshireAve.SilverSpring,MD20993(Tel)301-796-3400;(Fax)[e-mail]@fda.hhs.gov(Tel)800-835-4709or301-827-1800U.S.DepartmentofHealthandHumanServicesFoodandDrugAdministrationCenterforDrugEvaluationandResearch(CDER)CenterforBiologicsEvaluationandResearch(CBER)December2009CMCContainsNonbindingRecommendationsDraft—NotforImplementationTABLEOFCONTENTSI.INTRODUCTION.............................................................................................................1.33.3.4.4.4.4.6.7.7.7.7.8.9.9.9.910.10.10.10.10.10.11.11.11.11.12.12II.DISCUSSION....................................................................................................................1A.General......................................................................................................................................1B.ImmunogenicityTestingDuringProductDevelopment.......................................................2C.PrinciplesofImmunogenicityTestingDuringProductDevelopment................................2III.APPROACHTOASSAYDEVELOPMENT................................................................A.OverviewofDesignElements..................................................................................................1.Multi-tieredApproach..........................................................................................................2.AspectsofAssayDevelopment............................................................................................B.ScreeningAssay.......................................................................................................................1.SelectionofFormat..............................................................................................................2.SelectionofAssayandReagents..........................................................................................3.InterferenceandMatrix.......................................................................................................4.DefiningaPositiveResult....................................................................................................C.NeutralizationAssay...............................................................................................................1.SelectionofFormat..............................................................................................................2.ActivityCurve......................................................................................................................3.Interference..........................................................................................................................4.ConfirmationofNeutralizingAntibodies.............................................................................5.CutPointofNeutralizingAntibodiesAssays.......................................................................6.MultipleFunctionalDomains..............................................................................................IV.CLINICALASPECTSOFASSAYVALIDATION..........................................................A.CriticalConsiderationsandCaveats....................................................................................B.DeterminingtheMinimalDilution......................................................................................1.Importance.........................................................................................................................2.Approach................................................