新冠肺炎疫苗供應(yīng)鏈如何出現(xiàn)-彼得森國際經(jīng)濟(jì)研究所-2021.8-60正式版

WORKINGPAPER21-12HowCOVID-19vaccinesupplychainsemergedinthemidstofapandemicChadP.BownandThomasJ.BollykyAugust2021ABSTRACTManymonthsafterCOVID-19vaccineswerefirstauthorizedforpublicuse,stilllimitedsuppliescouldonlypartiallyreducethedevastatinglossoflifeandeconomiccostscausedbythepandemic.Couldadditionalvaccinedoseshavebeenmanufacturedmorequicklysomeotherway?Wouldalternativepolicychoiceshavemadeadifference?Thispaperprovidesasimpleanalyticalframeworkthroughwhichtoviewthecontoursofthevaccinevaluechain.ItthencreatesanewdatabasethatmapstheCOVID-19vaccinesofPfizer/BioNTech,Moderna,AstraZeneca/Oxford,Johnson&Johnson,Novavax,andCureVactotheproduct-andlocation-specificmanufacturingsupplychainsthatemergedin2020and2021.Itdescribesthechoppyprocessthroughwhichdozensofothercompaniesatnearly100geographicallydistributedfacilitiescametogethertoscaleupglobalmanufacturing.Thepapercataloguesmajorpandemicpolicyinitiatives—suchastheUnitedStates’OperationWarpSpeed—thatarelikelytohaveaffectedthetimingandformationofthosevaccinesupplychains.Giventhedata,afinalsectionidentifiesfurtherquestionsforresearchersandpolicymakers.JEL:F13Keywords:Vaccines,COVID-19,subsidies,exportrestrictions,supplychains

ChadP.BownistheReginaldJonesSeniorFellowatthePetersonInstituteforInternationalEconomics.ThomasJ.Bollykyisdirectoroftheglobalhealthprogramandseniorfellowforglobalhealth,economics,anddevelopmentattheCouncilonForeignRelations(CFR).Afterthispaperwaswrittenbutbeforeitwaspublished,BollykybecameaseniorconsultantfortheCoalitionforEpidemicPreparednessInnovations(CEPI).Note:ArevisedversionofthispaperwillbepublishedinTheWorldEconomy.Forhelpfulcommentsandsuggestions,theauthorsthankChrisAdams,DavidGreenaway(theeditor),AnnaIsaac,SoumayaKeynes,JacobKirkegaard,SamLowe,JimMiller,ChrisRogers,KadeeRuss,DaveVanness,andPrashantYadav.HexuanLiandYilinWangprovidedoutstandingresearchassistance.MelinaKolb,WilliamMelancon,andOliverWardassistedwithgraphics.Anyerrorsareauthors’own.1750MassachusettsAvenue,NW|Washington,DC20036-1903USA|+1.202.328.9000|每日免費(fèi)獲取報告1、每日微信群內(nèi)分享7+最新重磅報告；2、每日分享當(dāng)日華爾街日報、金融時報；3、每周分享經(jīng)濟(jì)學(xué)人4、行研報告均為公開版，權(quán)利歸原作者所有，起點(diǎn)財經(jīng)僅分發(fā)做內(nèi)部學(xué)習(xí)。掃一掃二維碼關(guān)注公號回復(fù)：研究報告加入“起點(diǎn)財經(jīng)”微信群。。WP21-12|AUGUST20212?1.INTRODUCTIONPfizer.Moderna.AstraZeneca.Johnson&Johnson.In2021,vaccinesassociatedwiththesecompaniesbecamethesymbolofhopeforaworlddesperatetoendtheCOVID-19pandemic.Theworkofthesefirmslikelysavedmillionsofpeople’slivesandreducedthesufferingofhundredsofmillionsmore.Yet,oneofthemostimportantretrospectivequestionstoaskiswhethervaccinemakerscouldhavedonebetter.Giventhenatureofthepandemicandthestateoftheworldin2020,couldmorevaccinedoseshavebeenmanufacturedmorequickly?Wouldalternativegovernmentpolicychoiceshavemadeadifference?ThispaperdetailstheprocessbywhichanumberofCOVID-19vaccinesweremanufactured.Itshowshowcomplexglobalsupplychainsemergedbehindthescenes—inmanyinstancesnearlyfromscratch—toproducethebillionsofdosesofvaccinesthathavebecomehouseholdnames.Itisorganizedasfollows.Thesecondsectionprovidesasimpleanalyticalframeworkthroughwhichtoviewthevaccinevaluechain.Itidentifiesthefivemainstepscriticaltogettinganewvaccinefromstarttofinish:researchanddevelopment;clinicaltrials;productionofthedrugsubstanceanditsformulationintodrugproduct;“fillandfinish,”ortheassembly-lineprocessofputtingavaccineintomillionsoftinyvials;andthendistribution.Thecostseparabilityofthosefirstfourfunctionsaffectedhowthepharmaceuticalindustrywasorganizedheadingintothepandemic.Splittingapartthethirdandfourthstepsinparticular—theheartofthevaccinemanufacturingsupplychain—ultimatelyaffectedhowmanydoseswereproduced,where,andhowquickly.ThethirdsectionmapssixkeyCOVID-19vaccinecandidates—thefouridentifiedaboveplusNovavaxandCureVac—toessentialelementsofthemanufacturingsupplychainsthatemerged.Doingsorequiresthecreationofanewdatabasethatlinkseachvaccinetothefirms,plants,andgeographiclocationsusedtoproduceit,aswellastothetimingofmatchesandotherimportantevents.1SupplychainsformostCOVID-19vaccineswerenotpre-determined—theyevolvedovertime,withrelationshipsoftensetbetweenfirmsatarm’slength,throughaverychoppyprocess.Behindthevaccinebrands,dozensofother,lesser-knowncompaniesatnearly100geographicallydispersedfacilitiesplayedcriticalroles.Section4cataloguespolicyinitiativesduringthepandemicthatarelikelytohaveaffectedtheformationofthosesupplychains.Understandingpolicydetailsiscriticalforevaluatingtheirimpact.Forexample,theUnitedStatesmadeconsiderablepublicinvestmentstoacceleratethescaling-upofmanufacturingsupplychains“atrisk”(i.e.,inadvanceofanyvaccinecandidateclearingregulatoryhurdlesandforwhichtheremighthavebeenzeropayoff).Unlikeothers,theUSapproachalsotargetedmanymoreupstreamelementsofthevaccinemanufacturingsupplychain,subsidizingcapacityexpansionofkeyinputsuppliers,notsimplydownstreamvaccineproductionfacilities.Furthermore,policysurelyaffectedthedecisionofmanyvaccinemakerstoestablishparallelsupplychainsindifferentlocations.Forexample,thehighlysubsidizedcontractsthatvaccinemakerssignedwiththeUSadministrationinmid-2020madeclearthattheywouldneedtoestablishmanufacturingfacilitiesoutsidetheUnitedStatesiftheywantedtosimultaneouslysupplyCOVID-19vaccinestotherestoftheworld.

ThispaperdetailstheprocessbywhichanumberofCOVID-19vaccinesweremanufactured.Foreaseofexposition,thispapersometimesreferstothesesixas“vaccines”eventhough,asofJuly2021,thosefromNovavaxandCureVactechnicallyshouldbereferredtoas“candidates,”sinceneitherwasyet(andmightnoteverbe)authorizedbyregulatorsforpublicuse.WP21-12|AUGUST20213?Giventhatdemandforthiscompletelynewvaccinemightreach14billiondoses,couldthemanufacturingscale-uphaveproceededmorequicklyoronalargerscalein2020and2021?2Thefifthsectionofthepaperraisesnewquestionsforresearcherstoinvestigate,especiallyoncemoredetaileddatabecomeavailable.Weretheat-riskpublicinvestmentssufficient?Didpandemic-erapolicyinterventionsmisssubsidizingexpansionofsuppliesofcriticalrawmaterialsandequipment?Inthefaceofextremescarcity,wereinputsandproductioncapacityefficientlyallocatedand,inlightofnewlyemergingregulatoryinformationonanyparticularvaccine,reallocated?Throughwhichchannelsandhowquicklydid“l(fā)earning-by-doing”byvaccinemanufacturerstakeplace?Didthefactthatsupplychainscrossedbordersmakecoordinationmoredifficult?Didinternationalinterdependencepreventvaccinenationalismfrombeingworsethanitwas?Beforecontinuing,itisimportanttonotethatthisanalysisdoesnotaddressthecriticalissuesofvaccinedemandanddistribution,whicharementionedonlybrieflyintheconcludingsection6.Otherresearchhasdescribedtheglobalpublichealthandglobaleconomicbenefitsofanequitablevaccineallocationscheme,prioritizinghealthcareworkersandvulnerablepopulations,asthroughtheCOVID-19VaccinesGlobalAccess(COVAX)regime.COVAXwasdevelopedinearly2020bytheWorldHealthOrganization(WHO),Gavi(theVaccineAlliance),andCEPI(theCoalitionforEpidemicPreparednessInnovations)andaimedtocoordinatevaccinemanufacturingparticipantsandtofinanceandprocureenoughCOVID-19vaccinedosestoadministerto20percentoftheglobalpopulation,includingtheworld’spoorestcountries.3Throughmid-2021,theongoingeffectsofthepandemicmeantthatgloballimitstovaccinedemandwereunlikelytobeabindingconstraintonthemainmanufacturingsupplychainissuesoffocushere.4

Manufacturingvaccinesisdifferentfromproductionofmanyofthesmall-moleculedrugsprovidedbythepharmaceuticalindustry.2.INDUSTRYORGANIZATIONHEADINGINTOTHEPANDEMICManufacturingvaccinesisdifferentfromproductionofmanyofthesmall-moleculedrugsprovidedbythepharmaceuticalindustry.5Unlikedrugsgiventosickpatients,vaccinesaretypicallyprovidedtohealthyindividuals.Everyyear,vaccinesaregiventomorethanabillionpeople,necessitatingtheirrigorousoversight.Sponsorsmustestablishtheirsafetyandefficacyinmultipleroundsofclinicaltesting.Workingwithmanufacturers,theymustdemonstratetonationalregulatoryauthoritiesthatmultiplesetsofpersonnelcanproducethevaccineconsistently,accordingtoclearanddocumentedprocedures,withmultiplesourcesofequipmentand“It’lltakemonths—orevenyears—tocreate7billiondoses(orpossibly14billion,ifit’samulti-dosevaccine),”wroteBillGates,co-chairoftheBillandMelindaGatesFoundation,oneofthefoundationalgroupsseekingtoaccelerateCOVID-19vaccines,earlyinthepandemic(BillGates,“WhatyouneedtoknowabouttheCOVID-19vaccine,”GatesNotes,April30,2020).Importantly,atwo-doseregimenwasrequiredforallofthevaccinesdescribedbelow,withtheexceptionofJohnson&Johnson(onedose),implyingtheneedforcloserto14billiondosesthan7billion.COVAXsigneduptotheprogrammostoftheworld’spoorestcountries,aswellaslower-middle-incomeeconomies.Ithadtroublemeetingitsearlygoals,however,mostlybecausethevaccine-manufacturingcountriesrefusedtosharesufficientdoseswiththeprogram.SeeBollykyandBown(2020a,2020b)andBownandBollyky(2021).See,forexample,Castilloetal.(2021),Cakmaklietal.(2021),Gagnon,Kamin,andKearns(2021),andHafneretal.(2020)forestimatesoftheeconomiccostsoffailingtoscaleupvaccinemanufacturing.Forresearchonadvancemarketcommitmentsfornewvaccines,seeKremer,Levin,andSnyder(2020).Smallmoleculedrugs—e.g.,aspirinorpenicillin—arerelativelysimpleandcanbemanufacturedbychemicalsynthesis.Incontrast,biologicalproductssuchasvaccinesarecomplexmixturesthatarenoteasilyidentifiedorcharacterized.WP21-12|AUGUST20214?rawmaterials,foranextendedperiodoftimewithoutfailureorinterruption.Furthermore,thesafety,effectiveness,andqualityofthevaccinecontinuestobecloselyregulatedevenafterregulatoryapproval.Whereastheintellectualpropertyforasmall-moleculedrugmightbeadequatelycapturedbyachemicalcompoundalone,thetechnologyforvaccinesisequalparttheproductionprocess.Gettinganewvaccinefrombeginningtoend—fromconcepttodeliveringshotsintothepublic’sarms—requiresfivestepsassociatedwithfive,largelyseparable,setsoffixedcosts(figure1).Figure1Vaccinemanufacturingisamulti-stageprocessthatoftenrequiresextensivecollaborationNote:Selectstagesandinputsdepictedillustrategeneralvaccineproductionprocessandarenotcomprehensive.Source:Constructedbytheauthors.Thefirstarethecostsassociatedwiththepreclinicalstageofresearchanddevelopment.Buildingondecadesofscientificresearchandpreviousdiscovery,aswellasnewmethods,scientistssoughtantigens—foreignsubstancesthat,WP21-12|AUGUST20215?whenintroducedintothebody,induceanimmunereaction—thattriggeredthesamereactionasthevirusdoes.Itnormallytakesyearstoidentifyvaccines.ButthingsmovedextraordinarilyquicklyinresponsetoCOVID-19.Chinasharedthegeneticsequenceofthenovelcoronavirus,namedSARS-CoV-2,withtheWHOinearlyJanuary2020.ByFebruary24,2020,forexample,ModernahadalreadybeguntoshipitsvaccinecandidateoffforPhase1clinicaltrials.ByearlyApril,BioNTech,Oxford,Janssen,Novavax,andmanyothercompanieshadallidentifiedtheirleadingCOVID-19vaccinecandidates.Thesecondstepinvolvedmultipleroundsofclinicaltrials,whichalsoproceededatunprecedentedspeed.Trialsstartwithrelativelysmallnumbersofhealthypeople—45inthecasesofPfizerandModerna—toestablishthesafetyofthecandidatevaccine,aswellasinformationastowhetheritwastriggeringthedesiredimmuneresponse.Subsequentstagesinvolveincreasinglylargernumbersofpeople,inordertogeneratepreliminaryestimatesofsafety,efficacy,dosage,andadversereactions.ThecriticalPhase3trialrequiresrecruitingtensofthousandsofpeople—whoarerandomlyallocated(randomized)tobeadministeredeitherthecandidatevaccineoracontrol(aknowncomparatorproduct,oftenaplacebo)—andthentrackingthemovertimetodeterminewhetherthevaccinewassafeandeffective.Theseclinicaltrialsareperformedaccordingtoprotocolsapprovedandoverseenbynationalregulatoryagenciesandethicscommittees.Smallerentities—suchasbiotechcompaniesoruniversities—oftenlackthecapacitytocompletethecostlylate-stageclinicaltrialsnecessarytosupportapplicationsformarketingapproval(licensure).BeforeCOVID-19,clinicaldevelopmentofanovelvaccinehadneverbeencompletedinlessthanfouryears,anditoftentookmorethanadecade.DevelopmentofsomeCOVID-19vaccinesoccurredinamatterofmonths,thankstoinnovativetrialdesigns;theactivesupportofnationalregulatoryagencies,suchastheUSFoodandDrugAdministration(FDA);andfinancingandcoordinationsupportfromtheUSNationalInstitutesofHealth(NIH),theWHO,andothers.InearlyDecember2020,lessthanayearafterpublicreportsofSARS-CoV-2emerged,regulatoryagencies—startingwiththeMedicinesandHealthcareproductsRegulatoryAgency(MHRA)intheUnitedKingdomandtheFDAintheUnitedStates—authorizedthefirstCOVID-19vaccinesforexpandedpublicuse.Manufacturingcomesnext,intwooftenseparablesteps.Thefirstphaseofmanufacturingwascreationofthedrugsubstanceanditsformulationintoadrugproduct.6Scalingupproductionforthepandemicrequiredplantscapableofgeneratingtensofmillions,ifnothundredsofmillions,ofdosesayear.Thefixedcostsofsuchproductionfacilitiesincludedcreatingandmaintaininghyper-cleanrooms,acquiringspecializedcapitalequipmentsuchasbioreactorsandfiltrationpumps,andemployingskilledpersonnelabletotransferthetechnologybehindthevaccinefromalaboratorytesttubetodedicatedmass-productionlines.Thesefacilitiesalsorequiredanumberofcriticalandspecializedvariableinputs,includingsingle-usebioreactorbags,filters,andcellularmaterial.Theprocessultimatelycombinedthedrugsubstancewithotherpharmaceuticalingredients,suchasexcipients,adjuvants,andpreservatives,dependingonthevaccine,toformulate

Itnormallytakesyearstoidentifyvaccines.ButthingsmovedextraordinarilyquicklyinresponsetoCOVID-19.6 Forcostaccountingforvaccinemanufacturing,seePlotkinetal.(2017)andKisetal.(2021).WP21-12|AUGUST20216?adrugproduct.Massvolumesofsomespecializedingredientswereneededfromotherpharmaceuticalcompanies,throughseparatenodesofasupplychain.Thefourthstepoftheentireprocesstypicallyinvolvedaseparatemanufacturingfacilitycapableofreceivingthedrugproductinorderto“fill”(squirtdosesintovials)and“finish”(capthevialswithstoppersandthenlabelandpackage)thevaccine,sothatitwasreadyfordistribution.Thefill-and-finishplantsrequiredspecializedassembly-linecapitalequipment,inadditiontovariableinputslikeglassvialsandstoppers.Materialswerealsoneededforpackagingandshipping,sometimesincludingcoldstorage.Thefifthandfinalstagewasdelivery.Uponreceiptoftheglassvialscontainingthevaccineatadistributioncenter,skilledpersonnelwouldalsoneedaccesstoneedles,syringes,antisepticwipes,andsometimesadditionalpharmaceuticalingredients.Somevaccineswereshippedfrozenandinconcentratedform,requiringon-sitedilution.Onlyaftertheappropriatediluentswereaddedcouldhealthcareworkerssafelyadministertheappropriatedosageintothearmsofpeoplewaitingtobeinoculated.Headingintothepandemic,thepharmaceuticalindustryemployedarangeofbusinessmodels.Atoneextremewerelegacy,integratedpharmaceuticalcompanies,potentiallyperformingeachofthosefirstfourstepsthemselves.Table1liststhetop10pharmaceuticalfirmsbysalesrevenueoverthelastfourdecades.Althoughsomecompanieswerecriticaltocertainsupplychainsduringthepandemic,theintegratedapproachwashardlythedominantmodel.Thebusinessmodelthatmuchofthepharmaceuticalindustryhadshiftedtowardovertheprevious25yearsinvolvedfragmentation.Astariffsandothertradebarriershadfallenglobally,informationandcommunicationstechnology(ICT)developed,shippingandlogisticsefficiencyincreased,andprotectionofintellectualpropertyrightssteadilyimproved.Thefactthattradecouldplayagreaterroleindistributingpharmaceuticalproductsgloballymeantthatcompaniescouldoperatefewerplantsbutatalargerscale.Atthesametime,separabilityofthesefixedcostscontributedtobreakingapartthevaccineproductionprocess.Firmscouldspecializeinonestep,leavingtheremaindertobedonebyotherfirmsthrougharm’slengthcontracts.Furthermore,theboomincreasedtheavailabilityofventurecapital.Thegenomeprojectandotherscientificadvancementsprovidedsmallbiotechcompaniesanduniversityresearcherswithastartingpoint,which,coupledwiththeavailabilityofexternalfinancing,meantthattheirnewdruginnovationscouldcompetewiththoseattheintegratedpharmaceuticalcompanies.7Capitalizingonthoseinventionsalsobecamelessandlessconstrainedbytheneedforscientistsandinnovatorstohaveaccesstotheirownmanufacturingfacilities.Contractdevelopmentandmanufacturingorganizations(CDMOs)couldbehiredtohandlejusttheproduction,coveringthethirdorfourthstepsoftheprocessshowninfigure1.

Thebusinessmodelthatmuchofthepharmaceuticalindustryhadshiftedtowardoverthepreviousyearsinvolvedfragmentation.Althoughnotafocushere,contractresearchorganizations(CROs)alsoemergedtohelpmanagetheclinicaltrialprocessandinteractionswithregulators,andclinicaltrialsthemselveswereincreasinglyconductedabroadoracrossmultiplecountries.Forthegovernanceofclinicaltrials,seeOECD(2013).WP21-12|AUGUST20217?Table1Top10globalpharmaceuticalfirms,bysalesrevenue,1990–2020Ranking19902000201020202020revenues(billionsofdollars)1Merck&Co.PfizerPfizerJohnson&82.6Johnson2Bristol-MyersGlaxoSmithKlineNovartisRoche62.1Squibb3GlaxoMerck&Co.SanofiNovartis48.74SmithKlineAstraZenecaMerck&Co.Merck&Co.48.0Beecham5Ciba-GeigyBristol-MyersGlaxoSmithKlineAbbVie45.8Squibb6AmericanHomeNovartisRocheGlaxoSmithKline43.8Products7HoechstJohnson&AstraZenecaBristol-Myers42.5JohnsonSquibb8Johnson&AventisJohnson&Pfizer41.9JohnsonJohnson9BayerPharmaciaEliLillySanofi41.110RocheAmericanHomeAbbottTakeda29.2ProductsSources:Pharmtechfor1990and2000,Statistafor2010,andFiercePharmafor2020.CompaniesshadedingreyareinvolvedinCOVID-19vaccinesdescribedbelow.Table2liststhetopCDMOsbyrevenuein2020.Therevenuesofthelargestfirmshavegrownovertime,albeitremainingsmallerthanthoseofthetoppharmaceuticalcompanies(seetable1).SomeCDMOshavebecomeglobal,operatingplantsinmultiplecountriesandhandlingvariouspartsofpharmaceuticalproduction.Despitetheirrelativeanonymity,companieslikeLonzaandCatalentplayedincrediblyimportantrolesinmanufacturingCOVID-19vaccinesduringthepandemic.Finally,somemajorpharmaceuticalcompanieslistedintable1—likePfizerandGlaxoSmithKline(GSK)—hadalsodevelopedbusinessoperationstoofferCDMO–likeservicestootherfirms,tobettermanagetheirowncapacity.8Thefragmentationofthepharmaceuticalindustryandtheriseincontractmanufacturerssharesomesimilaritieswiththeglobalsemiconductorindustry(Bown2020).Formoreonglobalvaluechainsmorebroadlyandthepandemic,seeAntràs(2020).WP21-12|AUGUST20218?Table2Topcontractdevelopmentandmanufacturingorganizations(CDMOs),bysalesrevenuein2020Revenues(millionsofdollars)/firmsHeadquarters3,000–5,000LonzaSwitzerlandCatalentUnitedStatesThermoFisherScientific(Patheon)UnitedStates1,000–3,000FarevaFranceRecipharmSwedenWuxiAppTec/BioChinaSiegfriedSwitzerlandDelpharmFrance750–1,000CambrexUnitedStatesAlbanyMolecularResearch(AMRI)UnitedStatesVetterGermanyAenovaGroupGermanyBoehringer-IngelheimGermanyFUJIFILMDiosynthBiotechnologies(FDB)Japan500–750AjinomotoJapanAlmacGroupUnitedKingdomBaxterBiopharmaSolutionsUnitedStatesSource:ConstructedbytheauthorswithdataprovidedbyJimMilleratDrug,Chemical&AssociatedTechnologies(Miller2021).CompaniesshadedingreyareinvolvedintheCOVID-19vaccinesdescribedbelow.WP21-12|AUGUST20219?3.SETTINGUPVACCINESUPPLYCHAINSINTHEMIDSTOFAPANDEMICCEPIconductedasurveyofglobalvaccinemanufacturingcapacityearlyinthepandemic,inanattempttomapthelandscapeoftheresourcesthatmightbetapped(CEPI2020).ByJune2020,itsmaintakeawaywasthatexistingvaccinemanufacturingcapacitywasconcentratedinIndia,Europe,andNorthAmerica(dataforChinawereunavailable).Thesupplychainsthatemergedoverthefollowingyearreflectedthisconcentration.AccordingtotheWHO,291COVID-19vaccinecandidateswereinthepipelineasofJuly2021,including184inpre-clinicaldevelopmentand107inclinicaldevelopment.9Sixvaccines—Pfizer/BioNTech,Moderna,AstraZeneca/Oxford,Johnson&Johnson(Janssen),Sinopharm,andSinovac—hadreceivedregulatoryapprovalforemergencyusefromtheWHO,theFDA,MHRA,and/ortheEuropeanUnion’sEuropeanMedicinesAgency(EMA)andwereinwidespreaddeploymentaroundtheworld(table3).Oneothercandidate—Novavax—seemedclose(forthatandotherreasons,itisincludedintheanalysis).Ahandfulofothervaccinecandidates—especiallyfromIndia(BharatBiotech)andRussia(SputnikV)—hadalreadybeenputintocirculationdomesticallyandinselectedcountriesevenbeforetheyreceivedWHOemergencyuselisting.WiththeexceptionofJohnson&Johnson,eachofthesevaccinesinvolvedatwodoseregimen.Otherattempts—includingbymajorindustryplayerssuchasMerckandSanofi/GSK,aswellasCureVac—didnotclearclinicaltrials.Thatsomanycandidatesmadeitthroughsoquicklyisascientificanomaly.Thegeographicconcentrationofvaccineproductionwasonereasonwhytradewouldplayasubstantialroleininoculatingmuchoftheglobalpopulation.MostofSub-SaharanAfrica,forexample,aswellaslow-andmiddle-incomecountrieselsewhere,relyonimports,astheyhadlittlepre-pandemicexperiencemanufacturingvaccineslocally.Tradewasalsocriticalbecauseofthecross-bordernatureofmanyvaccinesupplychainsthatemergedduringthepandemic,includingtradeinspecializedinputs,themanufacturingofwhichwasalsocharacterizedbythegeographicconcentrationofsuppliers.ProductionofmostoftheCOVID-19vaccinesinvolvedtheestablishmentofmultiplesupplychains,partlyoutoffearsthatgovernmentswouldresortto“vaccinenationalism”—i.e.,refusaltoexportdoses,atleastuntiltheirpopulationshadbeenfullyserved.10Thepossibilityofthisoutcomewasmadeobvioustopharmaceuticalcompaniesearlyinthepandemic,whentheTrumpadministrationdemandedcontractualtermsthatvaccinesmanufacturedintheUnitedStatesremainthere,asthepropertyoftheUSgovernment.TheUnitedStateswasnotalone:TheUKgovernmentpubliclyadoptedasimilarstrategy.11Companiesthusquicklylearnedthatprovidingvaccinestoothermarketsmeantalsomanufacturingthemfromothermarkets.

ProductionofmostoftheCOVID-19vaccinesinvolvedtheestablishmentofmultiplesupplychains,partlyoutoffearsthatgovernmentswouldresortto“vaccinenationalism.”WHO.2021.COVID-19VaccineTrackerandLandscape,lastaccessedonJuly9,2021.Forearlywarnings,seeBollykyandBown(2020a,2020b).See,forexample,UKNationalAuditOffice(2020,p.25).WP21-12|AUGUST202110?Table3DateskeyregulatorsauthorizedemergencyuseforvariousvaccinesVaccineFDAEMAMHRADCGIChinaRussiaWHO(US)(EU)(UK)(India)Pfizer/BioNTechDecemberDecemberDecemberNANANADecember11,202021,20202,202031,2020ModernaDecemberJanuary6,January8,June29,NANAApril30,18,20202021202120212021Johnson&FebruaryMarch11,May28,NANANAMarch12,Johnsona27,2021202120212021AstraZenecaNAJanuary29,DecemberJanuary3,NANAFebruary202130,2020202115,2021bSinopharmNANANANAFebruary5,NAMay7,20212021SinovacNANANANAAugust31,NAJune1,20202021SputnikVNANANAApril20,NADecemberNA20212,2020BharatBiotechNANANAJanuary3,NANANA2021NovavaxNANANANANANANACureVacNANANANANANANANote:DatesareasofJuly15,2021.FDA=FoodandDrugAdministration,EMA=EuropeanMedicinesAgency,MHRA=MedicinesandHealthcareproductsRegulatoryAgency,DCGI=DrugsControllerGeneralofIndia,WHO=WorldHealthOrganization.NA=Notauthorized.Hyperlinksprovideoriginalsources.a.Johnson&Johnson’svaccinewasonedose,theotherswereallatwo-doseregimen.b.TheWHOultimatelyissuedanemergencyuselicensefortheAstraZenecavaccinefromthreesources:SerumInstituteofIndia,SKbioscience,andfacilitiesinEurope.Source:Constructedbytheauthors.Someofthesevaccinesalsorequiredadditionalnodesofproduction—separatemini-supplychains—feedingintothemainmanufacturingsupplychainillustratedinfigure1.Pfizer/BioNTechandModerna,forexample,requiredmassivevolumesoflipidnanoparticles,andNovavaxrequiredaspecializedadjuvant,aproductthathelpsboostthebody’simmuneresponsetotheantigen.Finally,companieswouldcomplainaboutlimitedavailabilityofcriticalinputsthroughoutthepandemic.Attimesthereweretoofewsingle-usebioreactorbags,filtrationpumps,filters,skilledworkers,financialcapital,andevenpartnercompanieswithidlecapacitytoquicklyscaleuptheirproductionprocesses.a.Pfizer/BioNTechBioNTech—abiotechfirmlocatedinMainz,Germanyfoundedby