Regulatorypathways

DrSureshJadhavDrNoraDellepiane

Uniquesitua6on

•  AvaccinebeingmadebyadevelopingcountrymanufacturerforSub-SaharanAfrica.

•  Thiswasunprecedented•  Posedquiteafewchallenges

VaccinemadeinIndia+TrialsinAfrica=LicenseinIndia???

Challenges

•  WhywillIndianNCLreleaselots?•  TheprotocolsofAfricantrialsnotapprovedbyDCGI

•  Howwilltheyreviewthisdata?•  AfricanNRAsnotexperiencedinreviewoftrialprotocols.

•  WillIndiantrialdataberelevanttoAfrica?

Lotrelease

•  AllvaccinelotsmadeinIndiamustbereleasedbyNCLi.e.CDL,Kasauli,India

•  Thelabdidn’thavetheexper6se•  CDLfolkstraveledtoPoPersBar,UKfortrainingatNIBSC.

•  SeveralR&DlotswerethentestedbothatNIBSCandCDL

•  ThefirstGMPlotwasproducedbySIIandthenreleasedbyCDLin2004!

Interac6onswithDCGI

•  Beginningin2004,severalmee6ngswereheldwithDCGI,toreviewtheen6reprojectandthe6melines.

•  TheoverallclinicalplanthatincludedaPhaseIstudyinIndiawasapprovedbyDCGI

•  withonesugges6onthataPhase2studyin2-10yearoldsalsobedoneinIndia.

Onthewaytolicensure

•  RegulatorydossiersubmiPedtoDCGIinApril2009.

•  ButDCGIwasunderreviewbyWHOtocon6nueasafunc6onalNRA

Onthewaytolicensure

•  HealthCanadasteppedintoassistDCGIinreviewofthedossier.

•  Inaddi6on,WHOappliedafasttrackPQprocedurebyreviewingthedossierinparalleltoDCGI&HCandbuiltonthereviewbytheauthori6estobasetheirPQdecision.

•  Ajointinspec6onofproduc6onfacili6esbyDCGIandHealthCanadain2009.

Facilita6ngregistra6oninusercountries•  WHOinvitedthethreeearlyintroducingcountries(Niger,BurkinaFasoandMali)toperformtheirevalua6onoftheproductinGenevaandprovidedaccesstoallWHO/PQassessmentreports.

•  ForallothercountriesWHOorganized–  TrainingandJointreviewmee6ngswithanglophoneandfrancophonecountries(26par6cipa6ngcountries)andsharedwiththemtheWHO/PQassessmentreports.

– Advocatedforadop6onoftheexpeditedprocedureforreviewofimportedprequalifiedvaccines.

–  EmphasizedontheneedtorelyontheworkperformedbytheIndianandCanadianNRAsandWHO/PQandtobasetheirdecisionsonthereviewofabbreviatedinforma6onplusthePQassessmentreportstoensure6melyintroduc6onofthevaccineincountries.

Somehurdle…

•  Onemajorfindingoftheinspec6on-changeinthesiteofproduc6onforpolysaccharide.

•  ClinicaldataindossieronSynCoBioPartnersmaterial(Netherlands)whilelicenseaskedforSIILmaterial(India)

•  notacceptedbyDCGI.

Resolu6on…

•  TheproblemdiscussedintenselybyDCGI,SIIL,PATH,andWHO.

•  Thenewvaccineshouldundergoanimaltoxicitystudies.

•  Animalstudiesshowednotoxicity

Alliswellthatendswell…

•  Thevaccinewaslicensedon24December2009solelyforuseinAfrica!!!

•  WHOPQinJune2010!!!

Many“new”sintheproject

•  IndiancompanymakingvaccineonlyforAfrica•  IndianNCLgehngtrainedonlotrelease•  AfricanNRAsgehngtrainedtoreviewclinicaltrialapplica6ons

•  IndianNRAundercloudatthesame6me

Many“new”sintheproject

•  Cri6calrawmaterial(polysaccharide)changedmid-way(wehadnochoiceJ)

•  AhighlyregulatedcountryNRA(HealthCanada)reviewinganIndiandossier

•  Exportonlylicense•  WHOPQforavaccinenotsoldinthecountryoforigin

Keylearnings…

•  Pre-INDmee6ngwithNRAishighlyvaluable•  Constantdialoguewithregulatorscansolvemostoftheissues

•  Keepingtheminloop– AfricantrialprotocolsweresubmiPedtoDCGIeventhoughtheydidnotapprovethem

•  Bereadyforsurprises…– Thepolysaccharideissuepushedlicensureby1year

Keylearnings…

•  Helpthemhelpyourself– TrainingstoIndianandAfricanNRAswaspivotal

•  TimingmaPers!– NigeriaepidemicsforcedWHOforparallelreview

•  Crea6vesolu6onshelp–  remember“exportonlylicense”?

•  Collabora6on,andnotconfronta6onisamustforsuccessofaproject!

Thankyou!