Guidance-for-Industry-Bioavailability-and-Bioequiv

GuidanceforIndustryBioavailabilityandBioequivalenceStudiesforOrallyAdministeredDrugProducts—GeneralConsiderationsU.S.DepartmentofHealthandHumanServicesFoodandDrugAdministrationCenterforDrugEvaluationandResearch(CDER)March2003BPRevision1GuidanceforIndustryBioavailabilityandBioequivalenceStudiesforOrallyAdministeredDrugProducts—GeneralConsiderationsAdditionalcopiesareavailablefrom:DivisionofDrugInformation,HFD-240CenterforDrugEvaluationandResearchFoodandDrugAdministration5600FishersLaneRockville,MD20857(Tel)301-827-4573(CDER)March2003BPRevision1TABLEOFCONTENTSBIOAVAILABILITYANDBIOEQUIVALENCESTUDIESFORORALLYADMINISTEREDDRUGPRODUCTS—GENERALCONSIDERATIONS......................1I.INTRODUCTION.................................................................................................................1II.BACKGROUND...................................................................................................................2A.General............................................................................................................................................2B.Bioavailability.................................................................................................................................3C.Bioequivalence................................................................................................................................4III.METHODSTODOCUMENTBAANDBE......................................................................6A.PharmacokineticStudies...............................................................................................................6B.PharmacodynamicStudies............................................................................................................9C.ComparativeClinicalStudies.......................................................................................................9D.InVitroStudies............................................................................................................................10IV.COMPARISONOFBAMEASURESINBESTUDIES.................................................11V.DOCUMENTATIONOFBAANDBE.............................................................................11A.Solutions........................................................................................................................................12B.Suspensions...................................................................................................................................12C.Immediate-ReleaseProducts:CapsulesandTablets................................................................12D.Modified-ReleaseProducts.........................................................................................................14E.MiscellaneousDosageForms......................................................................................................17VI.SPECIALTOPICS.............................................................................................................17A.Food-EffectStudies......................................................................................................................17B.MoietiestoBeMeasured.............................................................................................................17C.LongHalf-LifeDrugs..................................................................................................................19D.FirstPointCmax..........................................................................................................................19E.OrallyAdministeredDrugsIntendedforLocalAction............................................................20F.NarrowTherapeuticRangeDrugs.............................................................................................20ATTACHMENT:GENERALPHARMACOKINETICSTUDYDESIGN.........................21ANDDATAHANDLING...........................................................................................................21ContainsNonbindingRecommendations1GuidanceforIndustry1BAandBEStudiesforOrallyAdministeredDrugProducts—GeneralConsiderationsThisguidancerepresentstheFoodandDrugAdministration's(FDA's)currentthinkingonthistopic.ItdoesnotcreateorconferanyrightsfororonanypersonanddoesnotoperatetobindFDAorthepublic.Analternativeapproachmaybeusedifsuchapproachsatisfiestherequirementsoftheapplicablestatutesandregulations.I.INTRODUCTIONThisguidanceisintendedtoproviderecommendationstosponsorsand/orapplicantsplanningtoincludebioavailability(BA)andbioequivalence(BE)informationfororallyadministereddrugproductsininvestigationalnewdrugapplications(INDs),newdrugapplications(NDAs),abbreviatednewdrugapplications(ANDAs),andtheirsupplements.ThisguidancecontainsadviceonhowtomeettheBAandBErequirementssetforthinpart320(21CFRpart320)astheyapplytodosageformsintendedfororaladministration.2Theguidanceisal