KeithWatts.April2016
WhitePaper
Corporate Citizenship, Expanded Access, and
Ethical Pre-License Drug Sales
CorporateCitizenship,ExpandedAccess,andEthicalPre-LicenseDrugSales 2
Abstract
Highpublicexpectationsforcorporatesocialresponsibility(CSR)andaccountabilityhavedirectedpharmaceuticalindustrypracticestoinfluencepositivechangelocallyandglobally.Drugcompaniesoftenrespondtoissuesaffectingpatientwell-beingfollowingcommercializationofnewproducts.Today,pharmaceuticalcompaniesareheldtohigherstandardsascorporatecitizensandmustnowconsiderhowtoimplementthisrolethroughoutaproduct’slife-cycle.Channelsthatallowaccesstomedicinestotreatserious,life-threateninganddebilitatingdisordersmustbebalancedwiththeinterestofallstakeholders.Today,thisbalancingacttakesplaceearlierintheproductlife-cycle,oftenbeforecommercialization,attheend,andeveninthoseinstanceswheremarketauthorizationisnotsought.Therearevariousethicalchannelsavailabletoprovideneededmedicationstopatientswithnoalternatives.Some
ofthesechannelsincludeEarlyandExpandedAccessPrograms(EAP),NamedPatientPrograms(NPP),CompassionateUse(CU),andPre-LicenseSales(PLS).Confusionexistsbecausethesetermscanhavevaryingmeaningsthroughouttheglobe.ItisimportantthatthesechannelsarefullyunderstoodbypharmaceuticalcompaniestoupholdCSR,lessenrisks,andpreservepatientsafety.Clearerdefinitionsofthesedifferentchannelsareneeded,asisunderstandingandexpertisetoethicallyandcompliantlyleveragethesepathwaystobenefitthosearoundtheworldwithrare,serious,andoftenlife-threateningdisorders.Whilethiswillsurelybeadifficulttask,clarifyingunderstandingofthesepathwayswilleventuallyharmonizemanufacturers,distributors,andpatients.
WhitePaper
CorporateCitizenship,ExpandedAccess,andEthicalPre-LicenseDrugSales 3
CorporateCitizenship,ExpandedAccess,andEthicalPre-LicenseDrugSales
whichroughlyonly5%aretreatablewithmedicinesapprovedbytheUSFoodandDrugAdministration(FDA).Araredisease,asdefinedbytheOrphanDrugsActof1983,affectsnomorethan200,000patients.TheUSwasthefirstcountrytosetuplegislationthatprovidedformarketingexclusivityandpaymentincentivesfororphandrugs(Gammieetal.,2015).Inthe1990’sJapanandAustraliafollowedtheUSincraftingorphandruglegislationthatprovidedincentivestodevelopandmarketdrugsforrarediseases;theEuropeanUnion(EU)followedin2000withspecificorphandruglegislation(Gammieetal.,2015).Manycountrieshavesetuporphandruglegislationthatincludesvaryingrangesofreimbursement.Forexample,theNetherlandsorphandruglegislationallowsforpre-licenseaccesstoorphandrugsandreimburses100%ofthecostforapprovedorphandrugs(Gammieetal.,2015).Attheotherendofthecontinuum,India,acountrywithoverone-billionpeople,hasnoorphandruglegislationandpaymentoftencomesfromself-fundedfoundationsorfundedout-of-pocketbythepatient(Gammieetal.,2015).
Source:Phrmawebsite:NewReportHighlightsaDecadeofInnovationinRareDiseases.Accessed4/11/16.Availableat:http://catalyst.phrma.org/new-report-highlights-a-decade-of-innovation-in-rare-diseases
Countriesaroundtheworldhavesetupregulatorymechanismsforethicalaccesstoorphanandnon-orphandrugsatvaryingstagesoftheproductlife-cycle.Earlyandexpandedaccessareonlytwoofthemanynamesusedtodescribeaccesschannelsoutsidethemorefamiliartraditionalsupplychain.Providers,patients,andadvocacygroupsareleveragingearlyaccesschannelstoensurepotentialinterventionsforlife-threateningandlife-alteringdisordersreachthosepatientswithoutviabletreatmentalternatives.Legislationexistsforinnovationstotreatraredisordersthatprovideincentivesmakingitcommerciallyfeasibleformanufacturerstotaketheextraordinaryrisksassociatedwithdevelopingdrugsforsmallpatientpopulations.AdvocacygroupsandinternationalorganizationssuchastheNationalOrganizationforRareDisorders(NORD)intheUnitedStates(US)andtheEuropeanOrganisationforRareDiseases(EURODIS),areinfluentialdriversoforphandruglegislation(Gammie,Lu,&Babar,2015).Thereisanestimated350millionpeoplearoundtheworldwhosufferfromroughly7,000differentrarediseases("Rarediseases:Factsandstatistics,"n.d.),of
CorporateCitizenship,ExpandedAccess,andEthicalPre-LicenseDrugSales 4
ThisarticlediscussesCSRasitconvergeswithchallengesalongvarioussupplychannelsthatexistatvaryingstagesofadrug’slife-cycle.
Consideringallrelevantstakeholdersisimportantwhendecidingwhetheraddressingglobaldemandforearlyaccessisconsistentwithacompany’sCSRinitiatives.Thedecisionismorecomplicatedandriskyduringearlystagesofaproduct’slife-cycle.Safety,efficacy,andamyriadofstrategicconsiderationsinthemidtolatedevelopmentandpost-researchphasesmustdirectresponsibledecisionmaking.Pre-approvalandpost-approvalpre-licensephasesincountrieswithestablishedethicalearlyaccesslegislation,ifcompetentlymanaged,mayprovidethegreatestsocietalandcorporatebenefit.
ThisarticlediscussesCSRasitconvergeswithchallengesalongvarioussupplychannelsthatexistatvaryingstagesofadrug’slife-cycle.ThesechannelshavemanylabelsincludingEAP,post-approvalPLS,NPP,amongothers.Thesechannelsrepresentethicalpathwayssetupbyhostcountriestoaddresstheissuesfacingthosepatientsawaitingadrug’scommercialapprovalormarketingauthorizationtotreatalife-threateningorlife-alteringdisorder.
CorporateSocialResponsibilityPharmaceuticalcompaniesarebecomingawarethatintentionalinitiativestosupportCSRcanimprovetheircompetitiveadvantage.CSRaffectsmanystakeholdersacrosssociocultural,political,economic,andregulatoryenvironments.Inthepast,amediumtolargepharmaceuticalcompanycoulddonatetovariouscharitiesandclaimtobeagoodcorporatecitizen(Matten,Crane,&Chapple,2003).Companiesarenowexpectedtoengageinprogramsthataffectthehealthandwell-beingofpatientsaswellasinfluencesustainablepositivechangeinlocalandglobalcommunities.Companyreputationandpublicopinionimproveswhendecisionsaredirectedbytransparentdeterminantsusedtoguideproductaccessthroughethicalpathwaysdesignedtomeetunmetmedicalneeds.SaltonandJones(2015)arguedthatpharmaceuticalcompaniesshouldbeheldtohigherstandardsofethical
socialbehavior.Pharmaceuticalandbiotechfirmssharethecommonpurposeofimprovingthehealthandqualityoflifeforpeoplearoundtheworld(Salton&Jones,2015).Itiscriticaltobalancethispurpose,andtheextraordinarypossibilitytopositivelyaffectlivesagainstthepossiblenegativeconsequencesflowingfrommisdirectedorpoorlyconsideredproductaccessimplementation.Ensuringthesecurityandintegrityofthesupplychainiscriticalwhenmakingtheseaccessdecisionsandtheprocessbeginswithchoosingtherightdistributionpartnerfortherightstageofaproduct’slife-cycle.
EAPexisttoprovideneededmedicinestopatientswithspecialcircumstancesincountrieswithestablishedregulatorymechanismsforaccessbeforemarketauthorization.Somecompaniessetupextensiveprogramstoprovidedrugsoutsideclinicaltrialsifconvincedtheremaybesomebenefittopatientsandcliniciansbeforeseekingmarketauthorization.Therearepharmaceuticalfirmsthathavesetuppoliciesdenyingorignoringtheneedforearlyaccesstomedicationsincountrieswheretheydonotintendtoseekmarketauthorization.Thereasonforrestrictivepoliciesincludelackofproductsupply,uncertaintyofthesupplychannelregulations,andotherreasonsthatcouldbeaddressedbycollaboratingwiththerightstrategicpartner.Thesepoliciesoftenexisteveninthepresenceofhostcountryregulatorymechanismsallowingaccessandreimbursementforneededdrugsapprovedinanothercountry.RisksofnegativepublicopinionandfailureofCSRarehighwhenacompanyrefusestoengagetheproperearlyaccesschanneltohelppatientsinneed.Therisksofnegativeperceptionishigherwhenthereisnofinancialorregulatoryrisktothecompany.Licensed,professional,anddedicateddistributioncompaniesexistwiththesolebusinessmissiontoethicallyaddressearlyaccessneedsofpatientsaroundtheworld,commerciallyorbyCU,whilesecuringthesupplychainandprotectingstakeholderinterests.Thesmallnumberofcompaniesdedicatedtothisbusinessmodel,suchasOneWorld,Inc.(OWI)canprofessionallyaddressthecommonissuesgivenforwithholdingproductfromsmallerlesscommerciallyattractiveregionsaroundtheworld.
CorporateCitizenship,ExpandedAccess,andEthicalPre-LicenseDrugSales 5
“A small number of companies, such as One
World, Inc. (OWI), can address the common issues given for
withholding product from smaller, less commercially
attractive regions around the world.“
RisksofnegativepublicopinionandfailureofCSRarehighwhenacompanyrefusestoengagetheproperearlyaccesschanneltohelppatientsinneed.
Drugsupplyforecastsforapproveddrugseligibleforearlyaccessareusuallymorerobustandcanaccommodatechanneldemandmoreeasilythanresearchstagesupply.CompaniessuchasOWIcanhelpwithestimatesoftreatmentdemandinvariousregions,andbysecuringthesupplychainfromsecondarywholesalersandspecialtypharmacieslikelysellingintothoseregionswithneitheraccountabilityorthemanufacturer’sknowledge.Clinicalandmarketinsightsfromreal-lifeexperiencescommunicatedbyprovidersandkeynetworkpartners,whereallowedbyexistingregulatorymechanisms,canbeobtainedforstrategicusetohelpguidecommercialization.DelaysinmarketauthorizationalsocreatedisadvantagesforpatientsoutsidetheUSthatcanbegreatlyreducedbyauthorizedspecialtydistributorsknowledgeableinEAPregulations.Forexample,intheEU,onceadrugapplicationisfiled,ittakesanaverageof418daysforthedrugtoreceiveEMAapproval(Adesetal.,2014).PatientsintheUStypicallyhavemorerapidaccesstonewproducts,possiblybecauseofexpeditedreviewprocessesavailableinthestates(Adesetal.,2014).Patientswithlife-threateningandlife-alteringdisordersareplacedatextremedisadvantageandriskwhenmanufacturerswithholdavailableproductfromanapproved,licensedandcompliantspecialtydistributorthatcanethicallyaccessregulatedchannelswherethedrugisawaitingmarketauthorization,butisapprovedforearlyaccess.
Diversionanddrugcounterfeitingisanongoingconcernthatriskspatientsafetyandlives(Hintlian&Kelly,2014).Diversionappearstobemorecommonasamechanismtomeettheinternationaldemandforneededmedicationsininstanceswheremanufacturershavedecidedtowithholdproduct,pre-andpost-approval,fromterritorieswherenocommercializationisplanned.Thisisoftenthecase,evenwhenethicaldistributionpartnersspecializingincompliancedrivensupplyofunlicensedandpre-licensemedicationsusingestablishedregulatorymechanismsoffertoassumefinancialrisk.Drugdiversionbysecondarywholesalersalsoservingdomesticmarketsfurthercomplicatestheethicalaccesstoneededmedicinesandthatleadtohighercostsandriskpatientsafety(Hintlian&Kelly,2014;WorldHealthOrganization,2014).Unauthorizedcompaniesenteringtheinternationaldistributionchainwithpoorqualitymanagementalsocreaterisksfromdiversionandcounterfeitproduct(Kohler,Mitsakakis,Saadat,Byng,&Martinez,2015;Wilcock&Boys,2014).
Keith Watts
CorporateCitizenship,ExpandedAccess,andEthicalPre-LicenseDrugSales 6
Unauthorizedcompaniesenteringtheinternationaldistributionchainwithpoorqualitymanagementalsocreaterisksfromdiversionandcounterfeitproduct.
Theserisksincludenegligentenvironmentalcontrolsandmonitoringcombinedwithpoorlyimplementedexport-importstrategiesthatruncountertoregulatoryrequirementsandriskpatientssafety(Hintlian&Kelly,2014).Thesesituationsexistwhenmanufacturers’policiesignorelegitimatepathwaysthatcanbelegitimatelyaccessedbyworkingwithcompaniessuchasOWItoreachpatientswherecommercializationisdelayedornotplanned.Providersandpatientsareforcedtosourceneededmedicationsoutsidelegitimatesupplychainchannelswhenmanufacturersrefuseforfailtouseethicalandregulatedchannelsbyworkingwithspecialtydistributorstosupplypre-licensedandunlicensedmedicines.Unauthorizeddistributioncreatesanenvironmentwherepatientseitherdonotreceivethedrug,ormustpayveryhighpricesforaccesstodrugswithnotraceability,educationalsupport,orrecallprocedureofferedbytheunauthorizedseller.Furtherriskstopatientsafetyoccurwhentherearenoassurancesthatenvironmentalrequirementshavebeenmet(Hintlian&Kelly,2014).
CSRisevaluatedtodaybasedontheGlobalReportingInitiative(GRI)thatisrobust,butdoesnottargetissuesspecificallyrelevanttothepharmaceuticalindustry.Offivemajorpharmaceuticalcompaniesevaluated,Johnson&JohnsonandRochereachedthehighestCSRscoresachieving65%and64%GRIguidelinecoverage,respectively(Salton&Jones,2015).Sanofi,GlaxoSmithKlineachieved58%and44%GRIcoverage,followedbyPfizerat28%(Salton&Jones,2015).Somecompaniesfocusmoreheavilyononeortwoofthe10GRImeasures,thereby,understatingtheircontributiontosocietyinthebroadermeasures,asreportedintheSaltonandJones(2015)study.DespitetheratingsfromGRI,Pfizerisconsideredagoodcorporatecitizenandhasdevotedsignificantresourcestosettingupregulatorycompliantearlyaccessforneededmedicinesbeforeregulatoryapproval.
SomecompanieswilldevotesignificantresourcestoengageinROWCSRinitiatives.MerckcreatedauniquesupplychainmodeltosupplycontraceptivesinSenegalthatisreplicableforotherproductsinterritoriesthatcouldproducecommercialvaluewhileaddressinghumanneed(Wright,2016).Merck’sinitiativeisagreatexampleofCSR.OtherlargepharmaceuticalcompaniesfocusondifferentCSRinitiativeswithnoattentiongiventoproductaccessincountrieswherenomarketauthorizationisplanned.Patientswithlife-threateningdiseaseslivinginregionswithnoexistingorexpectedcommercializationvaluefacesignificantdisadvantageunlessmanufacturerspartnerwithcompaniessuchasOWItoensureethicalaccesstoneededmedications.
OWIisamongafewcompaniesdedicatedtoensuringaccess,nomatterhowsmallordifficultthechallengesandcanhelpsupportCSRforcompaniesablebutunwillingtoservethesemarkets.Thereareclearlysupplychainissueskeepingneededdrugsfrompatientsinhardtoreachorcommerciallyunattractivemarkets(Wright,2016),butcompetentdistributionpartnersspecializinginEAPandPLScansupportmanagedaccessinitiativesaroundtheworld.TheEUcanbechallengingforthoseunfamiliarwithearlyaccesswherereimbursementpoliciesdifferandmarketauthorizationlagtimesvaryamongmembernations(Adesetal.,2014;Gammieetal.,2015;Hohmanetal.,2015).Companiesoftenignoretheseterritories,becausenomarketauthorizationissoughtorregulatoryexpertiseismissingtoensureproperdistribution.Merck,Pfizer,andothermanufacturerscanhelpexpandcompliantglobalaccesstoneededmedicationsthroughouttheproductlife-cycleinregionswithsmallpatientpopulationsanduniqueregulatorymechanismsbypartneringwithdedicateddistributorsspecializinginthesesupplychannels.
CorporateCitizenship,ExpandedAccess,andEthicalPre-LicenseDrugSales 7
AproductcanreceiveregulatoryapprovalinonecountryandbeavailableforCUorPLSpriortomarketauthorizationinothercountries.
EthicalAccesstoNeededMedicinesDefiningethicalEAPandtryingtoapplythedefinitionuniformlyacrosscontinentscanbecomplicated.Itisoccasionallyunclearononecontinentacrossmultipleindustryparticipants.IntheUSthetermEAPandCUprogramscanbeusedinterchangeably,whileinEuropethetermsdonothavethesamemeaning(Iudicello,Alberghini,Benini,&Mosconi,2016).CUtypicallyreferstoaprocesswhereapharmaceuticalmanufacturertemporarilyallowsaccesstotreatmentforapatientwhohasrunoutofalternativetreatments(Hyry,Manuel,Cox,&Roos,2015).AproductcanreceiveregulatoryapprovalinonecountryandbeavailableforCUorPLSpriortomarketauthorizationinothercountries.Somecompaniesofferthedrugatnochargewhileothersseekoutpaymentprograms(Hyryetal.,2015).CUoftenrepresentsacommitmenttoCSRthatcanbuildearlymarketpresenceyieldingusefulrealworlddataassociatedwiththeexpandedaccessprogram(Hyryetal.,2015).ManufacturersworryaboutallowingCU,mainlybecausetheywanttoavoidcreatingexpectationsoffreeproduct.
TheUSandEMAdefinitionsforEAParesimilar;however,thedifferencesareenoughtorequireregulatoryspecializationwhencarryingoutEAPatvaryingstagesofdevelopmentandapproval.Open-labelextension,whichisclearlydelineatedfromEAPintheUSdefinition,butisnotsoclearwithintheEMA,cancauseconfusion(Iudicelloetal.,2016).ApharmaceuticalmanufacturermayuseCUtocarryoutspecificinternalprogramsdesignedtoprovidesomeformofearlyaccesstoaninvestigationaltreatment.CUmayalsobetiedtoapatientassistanceprogram,NPP,oranynumberofotherprogramsfittingoutsidethenormalsupplychain.Theseprogramsareoftenunfamiliartopharmaceuticalmanufacturersincertaindecisionmakingroles.FearoftheEAPandPLSchannelsoftenstemsfromdifferingregulatoryconstraintsandrequirementsforthesechannelscomparedtothoseofthecommercialsupply
chain.TheEMAallowscompaniesthatmakepromisingmedicinestorunCUstoallowearlyaccesstotheirmedicineandtoextendusetopatientswhocanbenefitfromit.TheEUregulatoryenvironmenthasmanynuancesthatvaryamongmembernations.Thesedifferencesmeritdiscussion,butarebeyondthisarticle’sscope.Futurearticleswilladdresssomeofthedifferencesbetweenopen-labelstudiesandEAPintheEU.
TheBrazilianUniversalHealthSystem(SUS),withguidancefromtheMinistryofHealth,hasauniquesystemwiththegoalofprovidingneededmedicinesfree-of-chargetocloseto75%ofitspopulation(Bertoldi,Helfer,Camargo,Tavares,&Kanavos,2012).Differentmeaningsfortermsthatdescribelegislatedaccesstounapprovedinvestigationaldrugs,post-researchpre-approvaldrugs,andunlicensedmedicinesawaitingauthorizationhaspersuadedresearchersoftheneedforclaritythroughcommondefinitionsforproperaccessmechanisms(Iudicelloetal.,2016).ClearerdefinitionsthatdistinguishEAPfromclinicaltrialsshouldreduceconfusionforpatients,providers,andcompaniesdealingwiththesecomplextopics.AglobaldefinitionisatallorderasthechallengeistocoordinatealltermsassociatedwithvariousEAPs.Claritywillhelpdirectsupportofaccesstoneededmedicationsatvaryingstagesoftheproductlife-cycle(Iudicelloetal.,2016).
Pre-LicenseSalesPre-licenseaccessallowsimportationoforphandrugsavailableinothercountriesbutcurrentlyunauthorizedinthehostcountry(Gammieetal.,2015).NPPisoftenusedtodescribepre-licensingaccessandisoftenthemostcommonmethodforpatientsaccessingorphandrugsinmanycountries(Gammieetal.,2015).NPPscanoccurthroughapprovedpre-licensedsale(PLS)ofaproductaccessgrantedtoanindividualoragroupofpatientswithaseriousorlife-threateningdisorderincaseswhereexistingtreatmentalternativeshavebeenexhausted.Pre-licenseregulatorymechanismsforproductaccesstypicallyrequireaphysician
CorporateCitizenship,ExpandedAccess,andEthicalPre-LicenseDrugSales 8
CompanieswithdedicatedEAP/PLSmodelscansupportPLSandCUchannelsininstanceswhereapharmaceuticalmanufacturerisnotseekingmarketauthorizationinspecifiedcountries.
responsibleforthepatient’scaretoassesstheneedandopenarequestforadrug,onbehalfofthepatient(Gammieetal.,2015).Amanufacturer,orcooperationbetweenthemanufacturerandacompetentEAP/PLSdistributionpartner,willassesswhethertohonortherequestforaccess,basedonfixedguidelinesfromthemanufacturer.Aregulatorymechanismforpre-licenseaccessmaygrantethicalaccess,although,reimbursementbypublicpayersmaynotbetherule(Gammieetal.,2015).Turkeyisauniquecontraryexampleofacountrywithoutorphandruglegislationthathasanationalreimbursementprogramallowingimportationandaccesstoorphandrugsinapre-licensesettingwherethesedrugsareunavailableorunauthorized(Gammieetal.,2015).
CompanieswithdedicatedEAP/PLSmodels,suchasOWI,cansupportPLSandCUchannelsininstanceswhereapharmaceuticalmanufacturerisnotseekingmarketauthorizationinspecifiedcountries.Incountrieswheredemandforunavailablemedicinesexists,butmarketauthorizationstrategiesareunattractiveforpharmaceuticalcompanies;anexperienceddistributionpartnercansupportethicalaccesstotheseproducts.Supplychainqualitymanagementbythesespecialtydistributorsisimportanttoprotectagainstcounterfeiting,diversion,andunauthorizedproductsales(Kohleretal.,2015;Wilcock&Boys,2014).Specialtydistributorsmustreturnvaluetomanufacturersintheformofsupplychainsecurityandintegrity,RWD(inregulatorycompliance),marketinsightsandprovidereducation.Incertaincases,RWD,marketinsights,andpatientreportedoutcomes(PRO)cansupportlabelclaimsapprovedbyUSandEuropeanregulatoryagencies.TheEMAmorecommonlyallowsPRO-basedclaimsthantheUSFDA(Wilcock&Boys,2014).TheEMAgenerallywillgranthigherorderclaims,suchashealthrelatedqualityoflifeandphysicalfunctioning,fromPRO(DeMuroetal.,2013).TheFDAmainlyallowssymptomrelatedclaimsfromPRO(DeMuroetal.,2013).Thetwoagenciestendtoalignonsymptomswhere,forexample,patientreportedpainsymptomscansupportlabelclaims(DeMuroetal.,2013).Knowingwhattoexpectfromdifferentregulatorybodies
mayhelpidentifykeyRWDelementswhencollectionofsuchdataisallowed.
Manycompanieshaveastatedpolicyofwithholdingearlyaccessincountriesthatarenotconsideredformarketauthorizationorcommercialization.Thesecountriesarechallengingandsomecompanies,manufacturers,andEAPdistributors,areeithernotequippedorprefernottodevoteresourcestohandlerequestsfromthesedifficultregions.IntheUSafewspecializedcompaniesexistwhosesolebusinessasalicensedexportdistributorcentersonethicallyservingrest-of-world(ROW)pre-licenseproductneedsthroughexistingregulatorymechanisms.Specialiststendtobeexceedinglycapableandenthusiastictoservethosechallengingregions,whethertherearetwoor200patients.AnethicalpharmaceuticaldistributorwithastrongPLSmodel,havingadevelopednichepresenceandcompetenceinsecuringEAPsupplychainsinROWmarkets,canbeastrongallyofthepharmaceuticalmanufacturer.Itisimportantthedistributionpartnerthoroughlyunderstandsthehostcountryregulatoryandrelatedissuesfacingmanufacturersandpatients.TheneedsofpatientscanbeefficientlyservedbyanexperiencedspecialtyPLSdistributorthatsimultaneouslyprotectstherelatedinterestsofpharmaceuticalmanufacturers.
APLSbusinessmodeldoesnotexcludeservicingaCUorEAP,butitisbesttoseparateoneserviceproviderfromanothertoavoidconflictsofinterestandsupplychainconfusion.Interritorieswhereanavailablereimbursementorpaymentmechanismforunlicensedmedicineexists,andwheremarketauthorizationisnotpractical,acompetentspecialtydistributorcanhelpethicallysupplyneededproducts.Thesespecialistscannavigatethecomplexitiesofservingthischannelefficientlywithinavailableregulatorymechanisms,andwithoutrisktomanufacturers’globalplans.AcompanywithasoundandrobustPLSmodelcansupportsociallyresponsibledistributionofproductstoprovidersandpatientswithnoviabletreatmentalternatives.Thisisdonebyassumingfinancialandreimbursementrisksofproductacquisition,providercredentialing,shipmentsecurity,tracking,andconfirmation
CorporateCitizenship,ExpandedAccess,andEthicalPre-LicenseDrugSales 9
withfollow-upreporting,whereindicatedandallowedbyahostcountry.Insomecountries,reimbursementoforphandrugsisbasedontherapeuticvalue,impactonclinicalpracticeandbudgetimpact(Gammieetal.,2015).
PLSchannelmanagementforethicalaccesstoneededmedicationsrequiresaspecializeddistributionpartnerwithstrongunderstandingofthischannel.Unauthorizedandunmonitoredsalesbysecondarywholesalersnotversedintheregulatoryenvironmentofmanydifferentcountriesrisksafetyandsecurityofpatients,whetheritbeoneormany(Mackey&Liang,2012;Wilcock&Boys,2014).Itisalsoanadvantagetoworkwithapartnerwhosemodelleveragesunderstandingoftheissuesfacingmanufacturers,providers,payers,andpatients.
ManufacturerCSRthatsupportsEAP,CU,andPLS,oftenreliesoninternaldepartmentsdevotedtoconnectingneededtreatmentstoprovidersofpatientswhohaveexhaustedexistingtherapeuticregimens.Settingupaninternalsystemrequiresresourcestodevelopnetworksandglobalregulatoryexpertise.Acost-effectivealternativetyingupinternalresourcesistoengageacompanylikeOWItobridgethatgapforpatientswhocannototherwiseaccessaproductbeforemarketauthorizationorwherecommercializationisnotplanned.AnethicalPLSprogramestablishedwithatrusteddistributionpartnerexperiencedinmulti-nationalregulatoryrequirementsofthischanneloffersanefficientalternativetoin-housemanagementofthisrole.CompaniesengagedinclinicaltrialsandresearchphaseEAPsshoulduseaseparateproviderforthissupplychanneltoclearlyseparatefromtheirCUandrelatedpre-approvalEAP.
PLSandCUareimportantaccesschannelsforneededproducts,butitisnotaseparatemarketingchannel.Thereisnomarketingallowedforaproductbeforemarket.Ethicalandexperienceddistributionpartnersunderstandthisandhavepoliciesinplacedefiningtheirroletoserveanexistingunmetmedicalneedandtoavoidmarketingaproductapprovedforpre-licensedsales.Onceaproductreceivesmarketauthorization,thePLSdistributionpartner’sjobistohelptransitiontoappointedaffiliatesofthemanufacturerforcommercialization.
“PLS channel management for ethical access to needed medications requires a specialized distribution
partner with strong understanding of this
channel.”
CorporateCitizenship,ExpandedAccess,andEthicalPre-LicenseDrugSales 10
Paymentfororphanandnon-orphandrugsintheEUissubjecttoindividualcountrypolicies.
RegulatoryMechanismsItisimportantthatmanufacturersoforphandrugsandspecialtydistributorsunderstandtheregulatoryframeworkinplacetoaddressproductaccessandreimbursementaroundtheworld.TheregulatorymechanismsinplaceintheUSandEUdirectingorphandrugmarketingauthorizationandearlyaccessaresimilartonon-orphanregulatorymechanisms(Gammieetal.,2015).Asimilarregulatoryenvironmentexistsinnon-EUcountries(Gammieetal.,2015).TheCommitteeforOrphanMedicinalProducts(COMP)oftheEMAisresponsiblefordecisionstoawardanorphandruglabel,althoughmarketingauthorizationdecisionsaretheresponsibilityoftheCommitteeforMedicinalProductsforHumanUse(CHMP).
Paymentfororphanandnon-orphandrugsintheEUissubjecttoindividualcountrypolicies.IndividualEUcountriesareresponsibleforfixingearlyaccesspolicymechanismspre-andpost-marketauthorization.IndividualEUcountriesalsomustsetreimbursementmechanismsthatalignpayersandregulatorymechanismsforearlyaccesstodrugsforraredisordersthataresustainableovertime(Gutierrez,Patris,Hutchings,&Cowell,2015;Hyryetal.,
2015).Manycountriesrequirecosteffectivenessanalysistosupportreimbursementofhighcostorphandrugsandtheuseofmanagedentryagreementsarebecomingmorecommonforbothorphanandnon-orphandrugreimbursement(Gammieetal.,2015).Reimbursementpoliciesforneededmedicationsvarysignificantlyaroundtheworld.
InBrazil,25%ofthehouseholdspayforprivateinsurancewhile75%ofthepopulationrelyontheBrazilianUniversalHealthSystemeventhoughonlyroughly60%ofneededmedicinesareavailablewhenneeded(Bertoldietal.,2012).Brazilhasthreechannelsthatallowaccesstounapprovedorpre-licensepharmaceuticalandbiotechproducts,twoofwhicharesubjecttoapprovalbytheNationalHealthSurveillanceAgency(ANVISA).Humanitarianuse,whichisCUforimportingfreeproductaftermeetingseveralconditions,isacommonchannelforaccesstounapprovedmedicines.TheEAPinBrazilallowsacohortofpatientstoreceiveproductwithoutcharge,subjecttospecificconditionsandrequiressubmissionofasummaryreportonalltreatedpatients.Finally,NPPsinBrazilallowforpersonaluseofanunapprovedproductbasedoffaprescriptionfromthetreatingdoctor-noANVISAapprovalisrequired.
CorporateCitizenship,ExpandedAccess,andEthicalPre-LicenseDrugSales 11
ReferencesAdes,F.,Zardavas,D.,Senterre,C.,deAzambuja,E.,Eniu,A.,Popescu,R.,...Parent,F.(2014).Hurdlesanddelaysinaccessto
anti-cancerdrugsinEurope.Ecancermedicalscience,8(474-494),482.doi:10.3332/ecancer.2014.482
Bate,A.,Juniper,J.,Lawton,A.M.,&Thwaites,R.M.A.(2015).Designingandincorporatingarealworlddataapproachtointernationaldrugdevelopmentanduse:Whattheukoffers.DrugDiscoveryToday.doi:http://dx.doi.org/10.1016/j.drudis.2015.12.002
Berger,M.L.,Lipset,C.,Gutteridge,A.,Axelsen,K.,Subedi,P.,&Madigan,D.(2015).Optimizingtheleveragingofreal-worlddatatoimprovethedevelopmentanduseofmedicines.ValueinHealth,18(1),127-130.doi:10.1016/j.jval.2014.10.009
Bertoldi,A.D.,Helfer,A.P.,Camargo,A.L.,Tavares,N.U.,&Kanavos,P.(2012).Isthebrazilianpharmaceuticalpolicyensuringpopulationaccesstoessentialmedicines?GlobalHealth,8,6.doi:10.1186/1744-8603-8-6
Blommestein,H.M.,Franken,M.G.,&Uyl-deGroot,C.A.(2015).Apracticalguideforusingregistrydatatoinformdecisionsaboutthecosteffectivenessofnewcancerdrugs:Lessonslearnedfromthepharosregistry.Pharmacoeconomics,33(6),551-560.doi:10.1007/s40273-015-0260-4
DeMuro,C.,Clark,M.,Doward,L.,Evans,E.,Mordin,M.,&Gnanasakthy,A.(2013).Assessmentofprolabelclaimsgrantedbythefdaascomparedtotheema(2006-2010).ValueinHealth,16(8),1150-1155.doi:10.1016/j.jval.2013.08.2293
Gammie,T.,Lu,C.Y.,&Babar,Z.U.(2015).Accesstoorphandrugs:Acomprehensivereviewoflegislations,regulationsandpoliciesin35countries.PloSOne,10(10),e0140002.doi:10.1371/journal.pone.0140002
Gutierrez,L.,Patris,J.,Hutchings,A.,&Cowell,W.(2015).PrinciplesforconsistentvalueassessmentandsustainablefundingoforphandrugsinEurope.OrphanetJournalofRareDiseases,10(1),53.doi:10.1186/s13023-015-0269-y
Hintlian,J.T.,&Kelly,R.(2014).Aroadmapforriskyterritory.PharmaceuticalProcessing,29(8),18-20.
Hohman,R.,Shea,M.,Kozak,M.,Roberts,S.,Allen,J.,&Sigal,E.(2015).Regulatorydecision-makingmeetstherealworld.ScienceTranslationalMedicine,7(313),313fs346.doi:10.1126/scitranslmed.aad5233
Hyry,H.I.,Manuel,J.,Cox,T.M.,&Roos,J.C.P.(2015).Compassionateuseoforphandrugs.OrphanetJournalofRareDiseases,10(1),1.
Iudicello,A.,Alberghini,L.,Benini,G.,&Mosconi,P.(2016).Expandedaccessprogramme:Lookingforacommondefinition.Trials,17(1),21.doi:10.1186/s13063-015-1108-0
Kohler,J.C.,Mitsakakis,N.,Saadat,F.,Byng,D.,&Martinez,M.G.(2015).Doespharmaceuticalpricingtransparencymatter?Examiningbrazil'spublicprocurementsystem.GlobalHealth,11(1),34.doi:10.1186/s12992-015-0118-8
Mackey,T.K.,&Liang,B.A.(2012).Combatinghealthcarecorruptionandfraudwithimprovedglobalhealthgovernance.BMCInternationalHealthandHumanRights,12.doi:10.1186/1472-698X-12-23
Matten,D.,Crane,A.,&Chapple,W.(2003).Behindthemask:Revealingthetruefaceofcorporatecitizenship.Givingvoiceinacultureofsilence.fromacultureofcompliancetoacultureofintegrity,45(1/2),109-120.
Rarediseases:Factsandstatistics.(n.d.).RetrievedMarch18,2016,fromhttp://globalgenes.org/rare-diseases-facts-statistics/
Salton,R.,&Jones,S.(2015).Thecorporatesocialresponsibilityreportsofglobalpharmaceuticalfirms.BritishJournalofHealthcareManagement,21(1),21-2525p.
Wilcock,A.E.,&Boys,K.A.(2014).Reduceproductcounterfeiting:Anintegratedapproach.BusinessHorizons,57(2),279-288.doi:http://dx.doi.org/10.1016/j.bushor.2013.12.001
CorporateCitizenship,ExpandedAccess,andEthicalPre-LicenseDrugSales 12
WorldHealthOrganization.(2014).Medicinesquality.WHODrugInformation,28(3),317-323317p.
Wright,R.(2016).Howmerckbalancesthebusinessofcorporatesocialresponsibility.LifeScienceLeader,8(1),18-23.
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Appendix:TableofAbbreviationsANVISA AgênciaNacionaldeVigilânciaSanitária
COMP CommitteeforOrphanMedicinalProducts
CSR Corporatesocialresponsibility
CU CompassionateUse
EAP Earlyandexpandedaccessprogram
EMA EuropeanMedicinesAgency
EU EuropeanUnion
EURODIS EuropeanOrganisationforRareDiseases
FDA FoodandDrugAdministration
GRI GlobalReportingInitiative
NORD NationalOrganizationforRareDisorders
NPP Namedpatientprogram
OWI OneWorld,Inc.
PLS Pre-licensesales
PRO Patientreportedoutcomes
ROW Rest-of-world
SUS BrazilianUniversalHealthSystem
US UnitedStates
CorporateCitizenship,ExpandedAccess,andEthicalPre-LicenseDrugSales 14
OneWorld,Inc.Tucker,GA30084
Author:KeithWattsPresident/CEOKGPharmaceuticals.BoardMember,OneWorld,Inc.AdjunctFaculty,OhioChristianUniversityHealthCareAdministrationHealthcareEconomicsandBusinessStrategyLecturerCorrespondingauthorat:OneWorld,Inc.,4920NorthRoyalAtlantaDrive,Tucker,GA30084.Tel.:404-371-1745Ext312;fax:404-371-1774;email:[email protected]