USP-1663-Extractable

BRIEFING1663AssessmentofExtractablesAssociatedwithPharmaceuticalPackaging/DeliverySystems.Inthe2010–2015cycle,thePackaging,Storage,andDistributionExpertCommitteedeterminedtheneedtoupdategeneralchaptersthatfocusonthequalityofthepackagingsystemsusedtostoredrugproducts.TheExpertCommittee'sinitialfocuswasonthefinalpackagingsystems;however,ithasbeenextendedtoincludepackagingsystemscomponentsandtheirmaterialsofconstruction.Thesuitabilityofapharmaceuticalpackagingsystemforadrugproductcanbeassessedbyextractablesandleachablestesting.Outofthesecharacterizationstudies,specificcontrolsforapackagingsystem,itscomponents,oritsmaterialsofconstructioncanbeestablished.ThesuiteofgeneralchaptersforpackagingsystemsbeginswithPlasticMaterialsofConstruction661.1,whichisusedtocharacterizethematerialsofconstruction,andPlasticPackagingSystemsforPharmaceuticalUse661.2,whichisusedtocharacterizethefinalpackagingsystemand/orcomponent.Otherchaptersthatwillbeproposedinthefuturewilladdressthecharacterizationofplasticmaterialsusedinthemanufacturingprocessandmedicaldevices,PlasticSystemsUsedforManufacturingPharmaceuticalProducts661.3andPlasticMedicalDevicesUsedtoDeliverorAdministerPharmaceuticalProducts661.4.Aspartofthiscontinuation,thePackaging,Storage,andDistributionExpertCommitteeisproposingAssessmentofExtractablesAssociatedwithPharmaceuticalPackaging/DeliverySystems1663,whichpresentsaframeworkforthedesign,justification,andexecutionofanextractablesassessmentforpharmaceuticalpackaginganddeliverysystems.AworkshopwillbeheldonDecember9and10,2013,atUSPinRockville,Marylandtodiscusscommentsonthesuiteofpackaginggeneralchaptersandpotentialfuturerevisions.(GCPS:D.Hunt.)CorrespondenceNumber—C126512Addthefollowing:▪1663ASSESSMENTOFEXTRACTABLESASSOCIATEDWITHPHARMACEUTICALPACKAGING/DELIVERYSYSTEMSPURPOSEThisgeneralinformationchapterpresentsaframeworkforthedesign,justification,andexecutionofanextractablesassessmentforpharmaceuticalpackaginganddeliverysystems.Thechapterestablishescriticaldimensionsofanextractablesassessmentanddiscussespracticalandtechnicalaspectsofeachdimension.Althoughintendedtobehelpfulandgenerallyapplicable,thechapterisforinformationalpurposesanddoesnotestablishspecificextractionconditions,analyticalprocedures,ormandatoryextractablesspecificationsandacceptancecriteriaforparticularpackaginganddeliverysystemsordosageforms;nordoesitdelineateeverysituationinwhichanextractablesassessmentisrequired.Itisnotpossibleforageneraldiscussionofextractablestoanticipateandcoverallsituationswhereanextractablesassessmentmightberequired.Designinganindividualextractablesassessmentisaprocessthatbalancessoundscience,prudentresourceallocation,andeffectiveriskmanagement.Achievingthisbalanceistheresponsibilityandobligationofthedrugproductmanufacturerandassumesdueconsiderationofallapplicablelegalandregulatoryrequirements.Theprinciplesandbestdemonstratedpracticesoutlinedinthisgeneralchapterrepresentaconsensusinterpretationofsoundscienceandcanthereforebeappliedtoanysituationinwhichanextractablesassessmentisrequiredforpharmaceuticalapplication.KEYTERMSThisgeneralchapterusesthefollowingkeytermslistedbelow(1,2;alsoseePackagingandStorageRequirements659).NotethatthetermsPackagingSystem,PackagingComponent,PrimaryPackagingComponent,SecondaryPackagingComponent,andMaterialsofConstructionarealsodefinedin659,andthedefinitionsbelowareintendedforclarificationpurposeswithinthecontextofthischapterandarenotintendedtosupersedethoseprovidedin659.PackagingSystemsarethesumofpackagingcomponentsthattogethercontain,protect,andincertaincasesdeliverthedosageform.PackagingsystemsarealsoreferredtoasContainerClosureSystems.PackagingComponentsaresinglepartsofapackagingsystem.Eachindividualpackagingcomponenthasaparticularfunctionwithinthecontextofcontaining,protecting,anddeliveringthedosageform.AnindividualpackagingcomponentcanbePrimary,meaningthatitisormaybeindirectcontactwiththedosageform;orSecondary,meaningthatitisnotorwillnotbeindirectcontactwiththedosageformbutmayprovideadditionalprotection.PackagingcomponentsareconsideredtobeTertiaryiftheyarenotindirectcontactwiththedosageformbutfacilitatehandlingandtransportinordertopreventdamagefromphysicalhandlingandstorageconditionstowhichthedosageformissubjected.PackagingMaterialsofConstructionaresubstancesusedtomanufacturepackagingcomponents.ThesearealsoreferredtoasRawMaterials.Extractablesareorganicandinorganicchemicalentitiesthatcanbereleasedfromapharmaceuticalpackaging/deliverysystem,packagingcomponent,orpackagingmaterialofconstructionunderlaboratoryconditions.Dependingonthespecificpurposeoftheextractionstudy(discussedbelow),theselaboratoryconditions(e.g.,solvent,temperature,stoichiometry,etc.)mayaccelerateorexaggeratethenormalconditionsofstorageanduseforapackageddosageform.Extractablesthemselves,orsubstancesderivedfromextractables,havethepotentialtoleachintoadrugproductundernormalconditionsofstorageanduse.Leachablesareorganicandinorganicchemicalentitiesthatmigratefromapackaging/deliverysystem,packagingcomponent,orpackagingmaterialofconstructio