ICH-Q3D-2015最新版

Q3DElementalImpuritiesGuidanceforIndustryU.S.DepartmentofHealthandHumanServicesFoodandDrugAdministrationCenterforDrugEvaluationandResearch(CDER)CenterforBiologicsEvaluationandResearch(CBER)September2015ICHQ3DElementalImpuritiesGuidanceforIndustryAdditionalcopiesareavailablefrom:OfficeofCommunications,DivisionofDrugInformationCenterforDrugEvaluationandResearchFoodandDrugAdministration10001NewHampshireAve.,HillandaleBldg.,4thFloorSilverSpring,MD20993Phone:[phone]or301-796-3400;Fax:[phone]Email:[e-mail]:[e-mail](CDER)CenterforBiologicsEvaluationandResearch(CBER)September2015ICHContainsNonbindingRecommendationsiTABLEOFCONTENTSI.INTRODUCTION(1).......................................................................................................1II.SCOPE(2)..........................................................................................................................2III.SAFETYASSESSMENTOFPOTENTIALELEMENTALIMPURITIES(3).........2A.PrinciplesoftheSafetyAssessmentofElementalImpuritiesforOral,ParenteralandInhalationRoutesofAdministration(3.1)...................................................................................2B.OtherRoutesofAdministration(3.2)..........................................................................................4C.JustificationforElementalImpurityLevelsHigherThananEstablishedPDE(3.3).............4D.ParenteralProducts(3.4)..............................................................................................................5IV.ELEMENTCLASSIFICATION(4)...............................................................................5V.RISKASSESSMENTANDCONTROLOFELEMENTALIMPURITIES(5)........7A.GeneralPrinciples(5.1).................................................................................................................7B.PotentialSourcesofElementalImpurities(5.2)..........................................................................7C.IdentificationofPotentialElementalImpurities(5.3)................................................................8D.RecommendationsforElementstobeConsideredintheRiskAssessment(5.4)...................10E.Evaluation(5.5)............................................................................................................................10F.SummaryofRiskAssessmentProcess(5.6)...............................................................................11G.SpecialConsiderationsforBiotechnologicallyDerivedProducts(5.7)...................................12VI.CONTROLOFELEMENTALIMPURITIES(6)......................................................13VII.CONVERTINGBETWEENPDESANDCONCENTRATIONLIMITES(7)........13VIII.SPECIATIONANDOTHERCONSIDERATIONS(8).............................................16IX.ANALYTICALPROCEDURES(9).............................................................................16X.LIFECYCLEMANAGEMENT(10)............................................................................16GLOSSARY.................................................................................................................................16REFERENCES............................................................................................................................18APPENDIX1:METHODFORESTABLISHINGEXPOSURELIMITS...........................19APPENDIX2:ESTABLISHEDPDESFORELEMENTALIMPURITIES........................22APPENDIX3:INDIVIDUALSAFETYASSESSMENTS.....................................................24APPENDIX4:ILLUSTRATIVEEXAMPLES.......................................................................72ContainsNonbindingRecommendations1Q3DElementalImpuritiesGuidanceforIndustry1ThisguidancerepresentsthecurrentthinkingoftheFoodandDrugAdministration(FDAorAgency)onthistopic.ItdoesnotestablishanyrightsforanypersonandisnotbindingonFDAorthepublic.Youcanuseanalternativeapproachifitsatisfiestherequirementsoftheapplicablestatutesandregulations.Todiscussanalternativeapproach,contacttheFDAstaffresponsibleforthisguidanceaslistedonthetitlepageofthisguidance.I.INTRODUCTION(1)2Elementalimpuritiesindrugproductsmayarisefromseveralsources;theymayberesidualcatalyststhatwereaddedintentionallyinsynthesisormaybepresentasimpurities(e.g.,throughinteractionswithprocessingequipmentorcontainer/closuresystemsorbybeingpresentincomponentsofthedrugproduct).Becauseelementalimpuritiesdonotprovideanytherapeuticbenefittothepatient,theirlevelsinthedrugproductshouldbecontrolledwithinacceptablelimits.Therearethreepartsofthisguidance:•theevaluationofthetoxicitydatafo