1、BRIEFING1663AssessmentofExtractablesAssociatedwithPharmaceuticalPackagingDeliverySystems.Inthe2010–2015cyclethePackagingStageDistributionExpertCommitteedeterminedtheneedtoupdategeneralchaptersthatfocusonthequalityofthepa

2、ckagingsystemsusedtostedrugproducts.TheExpertCommitteesinitialfocuswasonthefinalpackagingsystemshoweverithasbeenextendedtoincludepackagingsystemscomponentstheirmaterialsofconstruction.Thesuitabilityofapharmaceuticalpacka

3、gingsystemfadrugproductcanbeassessedbyextractablesleachablestesting.Outoftheseacterizationstudiesspecificcontrolsfapackagingsystemitscomponentsitsmaterialsofconstructioncanbeestablished.Thesuiteofgeneralchaptersfpackagin

4、gsystemsbeginswithPlasticMaterialsofConstruction661.1whichisusedtoacterizethematerialsofconstructionPlasticPackagingSystemsfPharmaceuticalUse661.2whichisusedtoacterizethefinalpackagingsystemcomponent.Otherchaptersthatwil

5、lbeproposedinthefuturewilladdresstheacterizationofplasticmaterialsusedinthemanufacturingprocessmedicaldevicesPlasticSystemsUsedfManufacturingPharmaceuticalProducts661.3PlasticMedicalDevicesUsedtoDeliverAdministerPharmace

6、uticalProducts661.4.AspartofthiscontinuationthePackagingStageDistributionExpertCommitteeisproposingAssessmentofExtractablesAssociatedwithPharmaceuticalPackagingDeliverySystems1663whichpresentsaframewkfthedesignjustificat

7、ionexecutionofanextractablesassessmentfpharmaceuticalpackagingdeliverysystems.AwkshopwillbeheldonDecember9102013atUSPinRockvilleMaryltodiscusscommentsonthesuiteofpackaginggeneralchapterspotentialfuturerevisions.(GCPS:D.H

8、unt.)CrespondenceNumber—C126512Addthefollowing:?1663ASSESSMENTOFEXTRACTABLESASSOCIATEDWITHPHARMACEUTICALPACKAGINGDELIVERYSYSTEMSPURPOSEderivedfromextractableshavethepotentialtoleachintoadrugproductundernmalconditionsofst

9、ageuse.Leachablesareganicinganicchemicalentitiesthatmigratefromapackagingdeliverysystempackagingcomponentpackagingmaterialofconstructionintoanassociateddrugproductundernmalconditionsofstageuseduringaccelerateddrugproduct

10、stabilitystudies.Leachablesaretypicallyasubsetofextractablesarederivedfromextractables.Notethatchemicalentitiescanalsoleachfrompackagingdeliverysystemstopatientsviadirectcontact.ExtractionStudiesaretheoveralllabatyproces

11、sesrequiredindertocreateextractablesprofile(s)ofparticularpharmaceuticalpackagingdeliverysystemspackagingcomponentsmaterialsofconstruction.ExtractionstudiesarealsoreferredtoasControlledExtractionStudies.acterizationisthe

12、discoveryidentificationquantitationofeachindividualganicinganicchemicalentitypresentinanextractaboveaspecifiedlevelthreshold.Suchthresholdscanbebasedonpatientsafetyconsiderationsmaterialsconsiderationsthecapabilitiesofan

13、alyticaltechnologyetc.Scoutingistheprocessofacquiringgeneralchemicalinfmationthatprovidesinsightintothenaturemagnitudeofextractables.Discoveryistheprocessofsearchingfultimatelyfindingindividualganicinganicchemicalentitie

14、spresentinanextract.Identificationistheprocessofassigningamolecularstructuretoanganicextractableassigningconstituentelementsinthecaseofaninganicextractable.Quantitationistheprocessofmeasuringthelevelconcentrationofanindi

15、vidualganicinganicchemicalentitycontainedinanextract.ExtractablesProfilesarequalitativequantitativeanalyticalrepresentationsoftheextractablescontentofaparticularextractingmediumsetoflabatyextractionconditions.LeachablesE

16、xtractablesCrelationsareestablishedwhenobserveddrugproductleachablesarelinkedbothqualitativelyquantitativelytoextractablesfromassociatedpackagingdeliverysystemspackagingcomponentsmaterialsofconstruction.SafetyConcernThre

17、shold(SCT)isthethresholdbelowwhichaleachablehasadosesolowthatitpresentsnegligiblesafetyconcernsfromcarcinogenicnoncarcinogenictoxiceffects.Asnotedadditionalterminologyassociateddefinitionsareavailable(12659).SCOPEThescie

18、ntificprinciplesbestpracticesdescribedinthisgeneralchapterareintendedtoapplytoanyextractablesassessmentextractionstudyofpharmaceuticalpackagingdeliverysystemspackagingcomponentsmaterialsofconstructiontheresultsofwhichare

19、intendedfestablishingextractablesprofiles.Extractablesprofilescanbeusedinavarietyofpharmaceuticaldevelopmentmanufacturingapplicationsincludingtheacterizationionqualificationofmaterialsofconstructionpackagingcomponentspac