ICH-Q3A-impurities-in-new-drug-substances

GuidanceforIndustryQ3AImpuritiesinNewDrugSubstancesU.S.DepartmentofHealthandHumanServicesFoodandDrugAdministrationCenterforDrugEvaluationandResearch(CDER)CenterforBiologicsEvaluationandResearch(CBER)June2008ICHRevision2GuidanceforIndustryQ3AImpuritiesinNewDrugSubstancesAdditionalcopiesareavailablefrom:OfficeofTrainingandCommunicationDivisionofDrugInformationCenterforDrugEvaluationandResearchFoodandDrugAdministration10903NewHampshireAve.Bldg.51,Room2201SilverSpring,MD20993-0002(Tel)301-796-3400://:1-888-CBERFAXor301-827-3844(Tel)800-835-4709or301-827-1800U.S.DepartmentofHealthandHumanServicesFoodandDrugAdministrationCenterforDrugEvaluationandResearch(CDER)CenterforBiologicsEvaluationandResearch(CBER)June2008ICHRevision2TABLEOFCONTENTSI.INTRODUCTION(1).......................................................................................................1II.CLASSIFICATIONOFIMPURITIES(2).....................................................................2III.RATIONALEFORTHEREPORTINGANDCONTROLOFIMPURITIES(3)....3A.OrganicImpurities(3.1)................................................................................................................3B.InorganicImpurities(3.2).............................................................................................................3C.Solvents(3.3)...................................................................................................................................4IV.ANALYTICALPROCEDURES(4)................................................................................4V.REPORTINGIMPURITYCONTENTOFBATCHES(5)..........................................4VI.LISTINGOFIMPURITIESINSPECIFICATIONS(6)..............................................5VII.QUALIFICATIONOFIMPURITIES(7)......................................................................6GLOSSARY...................................................................................................................................9ATTACHMENT1:THRESHOLDS........................................................................................11ATTACHMENT2:ILLUSTRATIONOFREPORTINGIMPURITYRESULTSFORIDENTIFICATIONANDQUALIFICATIONINANAPPLICATION...................12ATTACHMENT3:DECISIONTREEFORIDENTIFICATIONANDQUALIFICATION................................................................................................13ContainsNonbindingRecommendationsGuidanceforIndustry1Q3AImpuritiesinNewDrugSubstancesThisguidancerepresentstheFoodandDrugAdministration's(FDA's)currentthinkingonthistopic.ItdoesnotcreateorconferanyrightsfororonanypersonanddoesnotoperatetobindFDAorthepublic.Analternativeapproachmaybeusedifsuchapproachsatisfiestherequirementsoftheapplicablestatutesandregulations.Ifyouwanttodiscussanalternativeapproach,contacttheFDAstaffresponsibleforimplementingthisguidance.IfyoucannotidentifytheappropriateFDAstaff,calltheappropriatenumberlistedonthetitlepageofthisguidance.I.INTRODUCTION(1)Thisdocumentisintendedtoprovideguidanceforregistrationapplicationsonthecontentandqualificationofimpuritiesinnewdrugsubstancesproducedbychemicalsynthesesandnotpreviouslyregisteredinaregionormemberstate.Impuritiesinnewdrugsubstancesareaddressedfromtwoperspectives:•Chemistryaspectsincludeclassificationandidentificationofimpurities,reportgeneration,listingofimpuritiesinspecifications,andabriefdiscussionofanalyticalprocedures•Safetyaspectsincludespecificguidanceforqualifyingthoseimpuritiesthatwerenotpresent,orwerepresentatsubstantiallylowerlevels,inbatchesofanewdrugsubstanceusedinsafetyandclinicalstudies.ThisisthesecondrevisionoftheQ3Aguidance,whichwaspublishedin1996andrevisedin2003.Inrevision2,Attachment2isretitled“IllustrationofReportingImpurityResultsforIdentificationandQualificationinanApplication”andincludesclarifyinginformationandanadditionalexample.1ThisguidancewasdevelopedwithintheExpertWorkingGroup(Quality)oftheInternationalConferenceonHarmonisationofTechnicalRequirementsforRegistrationofPharmaceuticalsforHumanUse(ICH)andhasbeensubjecttoconsultationbytheregulatoryparties,inaccordancewiththeICHprocess.ThisdocumenthasbeenendorsedbytheICHSteeringCommitteeatStep4oftheICHprocess(October2006).AtStep4oftheprocess,thefinaldraftisrecommendedforadoptiontotheregulatorybodiesoftheEuropeanUnion,Japan,andtheUnitedStates.ArabicnumbersreflecttheorganizationalbreakdowninthedocumentendorsedbytheICHSteeringCommitteeatStep4oftheICHprocess,October2006.1ContainsNonbindingRecommendationsThisguidanceisnotintendedtoapplytonewdrugsubstancesusedduringtheclinicalresearchstageofdevelopment.Thefollowingtypesofdrugsubstancesarenotcoveredinthisguidance:•biological/biotechnological•peptide•oligonucleotide•radiopharmaceutical•fermentationproductsandsemisyntheticproductsderivedtherefrom•herbalproducts•crudeproductsofan