Prasen Adya

Mycobacteriumtuberculosis:leadingcauseofhumandiseaseanddeathindevelopingcountries.

Firstusedtoimmunisehumansin1921.

WHOintroducedBCGvaccina<onaspartofEPIsince1974.

Globalcoveragerates>80%incountriesendemicforTB.

BCGVaccine

DifferentStrains

Atpresentabout100miochildrenreceiveBCGvaccineeveryyear.

Globaldemandpeggedat260miodosesperannum.

CurrentvaccinestrainsarealldescendantsoftheoriginalM.bovisisolatethatCalmeIe&Guerinpassagedthroughnumerouscyclesduringthe13yearperiod1909-1921.(Ref.:WeeklyEpidemiologicalRecord,No.4,23January2004P34)

Subsequentpassagesunderdifferentlaboratorycondi<onsresultedinphenotypicandgenotypicdifferences.(Ref.:WeeklyEpidemiologicalRecord,No.4,23January2004P34)

ThegenealogyofBCGvaccinestrains,displaystheoriginalvirulentancestorstrainM.bovisandthesubsequentseriesofgenomicaltera<onincludingdele<onsofregionsofdifference(RD),andsomestrain-specificinser<on.

Source:www.nature.com

DifferentStrains

Asarou<ne,BCGvaccineandBCGforBladderCancer–manufacturedfromthesamebulk.

Theformula<onisdifferent.

Theore<cally,OnedoseofBCGforBladdercancerequals240vialsofBCGvaccinei.e.4800dosesofBCGvaccine!

BCG:ImmunisaHon,BladderCancer

BCG:ImmunisaHon,BladderCancer

BCGforBladderCancer BCGVaccine1Dose 4800Doses

1Vial 240Vials

OnePa<entmayrequire27dosesofONCO-BCGforBladderCancer.*

*:Lamm’sprotocol

ListofWHOPQBCGsuppliers

Suppliers Presenta<on

10/20dosevial

JapanBCGLaboratory 20doseamp

IntervaxLtd 10/20doseamp

20dosevial

10dosevial

DCVMNmemberscurrentlysupplymorethan50%of

theGlobalDemand.

SUCCESSSTORY

2013-15:GlobalAvailabilityofBCGvaccine

ShortagesreportedbyUNagencies,EU,US,ANZ,SAfrica,severalothercountries.

UNagencies&countriesundertookstrategiestomi<gatetheeffectscausedduetoshortage.

StudiesreportedimpactofshortagesonGlobalPaed.Mortality.(Ref.:Thepoten<alimpactofBCGvaccinesupplyshortagesonglobalpaediatrictuberculosismortality:RebeccaCetal,BMCMedicine201614:138).

2013-15:GlobalAvailabilityofBCGvaccine

SIIPLfacilityunderrefurbishment

JapanBCGfacilityunderrefurbishment

SSI:upgrada<on

SanofiCanadaplantunderrenova<on

ShortageSituaHon

reportedshortagesasfollows:

Year Shortages

2013 8miodoses

2014 23miodoses

2015 17miodoses

Source:wwwthelancet.com/respiratoryVol4April2016PP251

FacilityRefurbishment–OnlyReasonforShortage

Cannotbe!!!

Clarityonstocksrequired.

NonavailabilityofBCGforCaBladderaggravatedthesitua<on–Capaci<esweredivertedtomanufactureBCGforBladdercancer.

BCGforBladderCancer

BladderCancer:ExtremelySmallGlobalMarket.

Incidencemoreinthedevelopedcountries.

Fewsuppliersglobally.

BCGforBladderCancer

Majorsupplierhadmfg.issues.

ResultedinGlobalshortageofthatbrand.

Increasedpressureonotherbrands.

Exis<ngcapaci<esgotdiverted.

Planning&Forecasts

Beforeshutdown,ManufacturersdidmanufacturestocksforOrdersinHand!

Provisionwasalsomadeforan<cipatedorders.

Stocksnotavailableforunplannedorders.

Toaddtopressure,therewasashortageofBCGforBladdercancer.

Insomecases,capaci<esgotdiverted.

TheIssue

BCGmanufacturingtakesalongHme.

Bulkmanufacturingrequiresalmost60days.

FollowedbyfillfinishandQCrelease–another90–120days.

NRArelease-another45days!

RegulatoryChallenges!

Registra<oninIndividualcountries–alongprocess!

Documenta<ondesiredinCTDformat!

Auditaspartofregistra<onrequirementbyseveralcountries–DespitehavingWHOPQ.

Somecountriesinsistonlocalclinicalstudies.

Lotreleaseforeachbatch–MfgcountryNRAaswellasexportedcountryNRAfore.g.India,Thailand,Indonesia,Malaysia.

CurrentSituaHon

UNICEFLTA’s:2016-18:400miodoses:4suppliers.(Ref.BCGvaccinesupply&demandoutlookDecember2015)

SIIhasresumedproduc<on.

JapanBCGresumesproduc<on.*

MerckincreasescapacityfortheirBladdercancerBCG.

WHOPQgrantedtonewmanufacturer:GreenSignal.

*:Noconformalinforma<onavailableinpublicdomain

Isallwell?

Notreally!!!

SanofiannouncesplanstoshutdowntheirCanadaplant.

DemandforBCGforBladdercancerislikelytosurge.

Capaci<esarelikelytobedivertedtomeetthisincreaseddemandforOncoBCG.

Againtheore<cally:1doseofOncoBCGconsumescapacityof4800dosesofBCGvaccine!

SoluHon

AccurateForecas<ng!!!

Conver<ngforecastsintoConfirmedOrderswithinanappropriate<me.

Suppliersadheretotheprescribedsupplyschedule.