IntegratedSummariesofImmunogenicity:AnFDAReviewer’sWishListDisclaimerImmunogenicityattheFDAOfficeofBiotechnologyProducts(OBP)FDAImmunogenicityGuidancesCDERImmunogenicityReviewCommitteeCDERImmunogenicityReviewCommitteeFDAregulatoryperspectivesFDAregulatoryperspectivesExpectationsforImmunogenicityAssessmentExpectationsforImmunogenicityAssessmentRisk-basedApproachtoImmunogenicityAssayDevelopmentForOtherProductsCurrentChallengesforFDAreviewersCurrentChallengesforFDAReviewersOBPReviewer’sPerspectiveRegardingImmunogenicityRegardingimmunogenicityPossibleModelPossibleModelImmunogenicityRiskAssessmentProposedImmunogenicityTieredStrategyandMethodologyClinicalStudyDesignandSamplingStrategyClinicalStudyDesignandSamplingStrategy(cont)ClinicalImmunogenicityDataAnalysisClinicalImmunogenicityDataAnalysis(cont)ConclusionsandRiskMitigationPost-Aproval/life-cyclemanagementClosingremarksCurrentlythedatarelevanttotheassessmentofimmunogenicityaredispersedthroughoutdifferentlocationsoftheeCTDincluding2.7.4SummaryofClinicalSafety,5.3.1.4ReportsonBiopharmaceuticalStudiesand5.3.5ReportsofEfficacyandSafetyStudies.ForyourBLAweencourageyoutoprovideanIntegratedSummaryofImmunogenicitythatincludes:Animmunogenicityriskassessmentspecifictoyourproduct,Detailsonthetieredimmunogenicitystrategythatyoufollowedinyourclinicalprogram,andvalidationsummariesforthevariousimmunogenicityassaymethodsyoudevelopedinyourprogramLinkstomethoddevelopmentandvalidationreportsforalltheimmunogenicityassaysusedinyourclinicalstudies,particularlythoseusedtotestimmunogenicitysamplesfromyourpivotalclinicalstudy(ies)Immunogenicitysamplingplan(s)forallclinicalstudiesthathadimmunogenicityassessmentperformedSummaryresultsofimmunogenicityanalysisforallclinicalstudieshavingimmunogenicitycomponent,includingtheresultsofyourcorrelationanalysisbetweenanti-drugantibodystatusandtiterswithPK/PD/efficacy/safety(adverse-events)dataTraceabilityofdrugproductlotsusedinallyourclinicalstudiesTheIntegratedsummarymaybesubmittedineCTDsection2