prasen adya - dcvmn · theore
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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.