FDA-industry-Guidance-for-Drug-Substance-CMC-Infor

169GuidanceforIndustryDrugSubstanceChemistry,Manufacturing,andControlsInformationSubmitcommentsonthisguidanceatanytime.SubmitwrittencommentstotheDivisionofDocketsManagement(HFA-305),FoodandDrugAdministration,5630FishersLane,Room1061,Rockville,MD20852.CommentsmayalsobesubmittedelectronicallyontheInternetat(formerly2003D-0571).Forfurtherinformationregardingthisdocument,contactAlemGhiorghis,CenterforVeterinaryMedicine(HFV-143),FoodandDrugAdministration,7500StandishPlace,Rockville,MD20855,[phone],E-mail:[e-mail]idancedocumentmayberequestedfromtheCommunicationsStaff(HFV-12),CenterforVeterinaryMedicine,FoodandDrugAdministration,7519StandishPlace,Rockville,MD20855,andmaybeviewedontheInternetateither://(CVM)August6,2010ContainsNonbindingRecommendationsTABLEOFCONTENTS1I.INTRODUCTION.............................................................................................................1II.BACKGROUND................................................................................................................3A.TheCommonTechnicalDocument—Quality(CTD-Q)Format.............................................3B.ContentofanApplication..............................................................................................................4C.AdditionalGuidance......................................................................................................................4D.ReferencestoOtherApplicationsorMasterFiles(MFs)...........................................................41.OtherApplications...........................................................................................................................42.MasterFiles(MFs)...........................................................................................................................4III.GENERALINFORMATION(S.1)..................................................................................6A.Nomenclature(S.1.1)......................................................................................................................7B.Structure(S.1.2)..............................................................................................................................7C.GeneralProperties(S.1.3)..............................................................................................................7IV.MANUFACTURE(S.2)....................................................................................................8A.Manufacturers(S.2.1)....................................................................................................................8B.DescriptionofManufacturingProcessandProcessControls(S.2.2)........................................91.FlowDiagram..................................................................................................................................92.DescriptionoftheManufacturingProcessandProcessControls.................................................103.Reprocessing,Reworking,Recycling,Regeneration,andOtherOperations.................................13C.ControlofMaterials(S.2.3).........................................................................................................161.StartingMaterials.........................................................................................................................162.Reagents,Solvents,andAuxiliaryMaterials..................................................................................173.Diluents..........................................................................................................................................18D.ControlsofCriticalStepsandIntermediates(S.2.4).................................................................18E.ProcessValidationand/orEvaluation(S.2.5)............................................................................20F.ManufacturingProcessDevelopment(S.2.6).............................................................................21V.CHARACTERIZATION(S.3).......................................................................................21A.ElucidationofStructureandOtherCharacteristics(S.3.1).....................................................211.ElucidationofStructure.................................................................................................................212.PhysicochemicalCharacterization.................................................................................................223.BiologicalandOtherRelevantCharacteristics.............................................................................23B.Impurities(S.3.2)..........................................................................................................................23VI.CO