strategic plan 2010â€“2020 - - world health organization

The InITIaTIve for vaccIne research

strategic plan 2010–2020

InITIaTIve for vaccIne researchDepartment of Immunization,

vaccines and BiologicalsWorld health organization1211 Geneva 27, switzerlande-mail: [email protected]/IvB/10.02

www.who.int/vaccine_research

Progress in public health depends on innovation. some of the greatest strides forward for health have followed the development and introduction of new medicines and vaccines.

Dr Margaret chan, Director-General of the World health organizationconference on Intellectual Property and Public Policy Issues,

Geneva, 14 July 2009

This publication is available at www.who/int/vaccine_research/documents/en/

Copies may be requested from:

World Health OrganizationDepartment of Immunization, Vaccines and Biologicals1211 Geneva 27Switzerlande-mail: [email protected]

Ordering code: WHO/IVB/10.02

© World Health Organization 2010

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Cover image: The world in a petri dish (Image Source/gettyimages).

Design and layout: Alessandra Bonrruquer.

Printed in India.

IVRVIsIon

IVR’s vision is a world in which vaccines and related technologies are developed and effectively used to protect all people at risk against infectious diseases of public health importance, particularly in developing countries.

MIssIon

IVR’s mission is to accelerate the development and optimal use of safe and effective vaccines and related technologies.

Table of ConTenTs

aCRonyMs .............................................................................................................................. iv

exeCuTIVe suMMaRy ...............................................................................................................1

The added value of IVR in 2010–2020 .................................................................................................................. 1

strategic functions .................................................................................................................................................2

Priority areas and lead projects ...........................................................................................................................2

Implementing the strategic Plan ..........................................................................................................................3

1. InTRoduCTIon ...................................................................................................................4

1.1 Realizing the potential of vaccines .....................................................................................................................4

1.2 Producing vaccines and technologies that meet developing country needs ................................................5

2. PosITIonIng IVR In a ChangIng global enVIRonMenT ..........................................8

2.1 IVR strategic Plan 2006–2009.............................................................................................................................. 8

2.2 how is the IVR strategic Plan 2010–2020 different? ...........................................................................................9

2.2.1 Who/unICef global Immunization Vision and strategy ....................................................................... 10

2.2.2 Who strategy on research for health ...................................................................................................... 10

2.2.3 Who global strategy on public health, innovation and intellectual property .................................... 10

3. The IVR sTRaTegIC Plan MaTRIx ...................................................................................12

3.1 strategic functions ............................................................................................................................................... 13

3.1.1 Identification of vaccine and vaccination research priorities ............................................................... 14

3.1.2 development of research standards and guidelines ............................................................................ 15

3.1.3 strengthening research and product development capacity .............................................................. 15

3.1.4 Translation of research results into policy and practice ....................................................................... 17

3.2 Priority areas and lead projects......................................................................................................................... 18

3.2.1 Vaccination as an element of health security ........................................................................................ 18

3.2.2 Vaccination strategies for all age groups ............................................................................................... 19

3.2.3 Vaccines against poverty-related diseases ............................................................................................ 21

3.3 summary of the IVR strategic Plan matrix ....................................................................................................... 22

4. IMPleMenTIng The sTRaTegIC Plan ...........................................................................24

4.1 Working with partners ......................................................................................................................................... 24

4.2 Monitoring and evaluation ................................................................................................................................. 25

iv

aCRonyMs

AAVP AfricanAIDSVaccineProgramme

EPI ExpandedProgrammeonImmunization

GIVS GlobalImmunizationVisionandStrategy

HIV/AIDS human immunodeficiencyvirus/acquiredimmunodeficiencysyndrome

HPV humanpapillomavirus

IVAC IVRVaccineAdvisoryCommittee

IVB WHO Department of Immunization,VaccinesandBiologicals

IVR InitiativeforVaccineResearch

MDG MillenniumDevelopmentGoal

PDP productdevelopmentpartnership

R&D researchanddevelopment

SAGE WHOStrategicAdvisoryGroupofExpertsonimmunization

TB tuberculosis

TDR UNICEF/UNDP/World Bank/WHOSpecial Programme for Research andTraininginTropicalDiseases

TPP targetproductprofile

UNAIDS JointUnitedNationsProgrammeonHIV/AIDS

UNDP UnitedNationsDevelopmentProgramme

UNICEF UnitedNationsChildren'sFund

WHO WorldHealthOrganization

1

exeCuTIVe suMMaRy

Vaccinesareoneofthemosteffectivepublichealthtoolsandprotectmillionsofliveseachyearfrominfectiousdiseases.Assuch,theyarealsocriticaltoreachtheMillenniumDevelopmentGoals (MDGs),particularlythegoalstoreduceinfantandchildmortality(MDG4)andtocombatHIV/AIDS,malariaandotherdiseases(MDG6).Progressoverthelastdecadestoincreasethepotentialofvaccinesandsavemorelives,frombothcurrentandemergingdiseases,hasbeenencouraging.Yetanestimatedfourmillionpeoplestilldieeachyearfromdiseasesforwhichvaccinesareavailable,andmillionsmoredieorsufferwhilewaitingforvaccinesto becomeavailable, such as againstmalaria anddengue. In addition, the potential of vaccinationcouldbeenhancedconsiderablyifexpandedbeyondpaediatricpopulations.

Hence,continuedeffortsareneededtodevelopnewandimprovedvaccinesandtoassuretheirsafeandeffectiveimplementation.However,theintroductionofanewvaccinefacesmanyhurdlesand,increasingly,depends on post-licensure research, comparativeassessments and tools to inform policy-makers.Developing countries suffer not only froma lack ofresearchcarriedoutondiseasesthatafflictprimarilytheirpopulations;inaddition,vaccinesproducedfordevelopedcountrymarketsmayhavecharacteristicsmaking them less suitable for thedevelopingworld.Slow,butsteadyprogressisbeingmadetoaddressthese issues, aswell as to improve implementationresearchcapacity,notablythroughnewpublic–privatepartnershipsthatfocusdirectlyondevelopingcountryneeds.

TheWHO Initiative forVaccine Research (IVR)wasestablished in 1999 as the Organization's unifiedentity forvaccineresearch,andhasbeensuccessfulin driving many major projects forward. Since itsinception,theglobalvaccineresearchanddevelopment(R&D)environmenthassignificantlyevolved.Withtheinjectionofnewfunding,primarilyfromphilanthropicorganizations, several new, largely disease-focusedinitiatives have emerged that aim to develop andaccelerateaccesstoaffordablevaccinesforallthosewhoneedthem.

The added Value of IVR In 2010–2020

Buildingonadecadeofexperience,IVRhasformulateda long-termStrategic Plan that takes account of theevolvingvaccineR&D landscape,andof the strongleadership role it canplayas theWHO integratedvaccineresearcharm.ThemuchwelcomednewplayersinthevaccineR&Dpipelineaccentuatetheneedforincreased global coordination and normative andtechnicalsupporttocountries,rolesthatareattheheartofIVR’smandate.

TheStrategicPlan2010–2020hasamatrixapproachthatusesfourstrategicfunctionsandasetofpriorityareas to address public health priorities, and it isherethatIVRhasmostsignificantlyevolvedsincethepreviousstrategy.Thematrix isdirectlyalignedwithWHO’s corporate strategyandpolicies to stimulateinnovation in health research, as well as with theglobalimmunizationagendaoftheOrganization.This

2 initiative for vaccine research : strategic plan 2010–2020

harmonizationwillfurtherstrengthensynergiesbetweenresearch-anddisease-focusedprogrammes.

sTRaTegIC funCTIons

ThefourstrategicfunctionsthatwillguidethecoreworkofIVRoverthenext10yearsare:

i) identificationofvaccineandvaccinationresearchpriorities;

ii) the development of research standards andguidelines;

iii)the strengthening of research and productdevelopmentcapacity;

iv) the translationof researchresults intopolicyandpractice.

Identification of vaccine and vaccination research priorities.Asthenumberofdonorsandtechnical actors supporting the development anduse of vaccines increases, so does the demand foran independentevaluationofneeds,anassessmentofpriorities, and coordinationof efforts tooptimizeefficiencyandalignmentofactivities.IVR’sroleintheseactivitieswillbetoidentifyresearchgapsofparticularrelevancetolow-andmiddle-incomecountries;establishtechnicalagendastoaddressthesegaps;stimulatetheimplementationofthetechnicalagendas;andsynergizeitsportfolioofactivitieswiththoseofitspartners.

Development of research standards and guidelines. Thesecond IVRstrategic function is todevelop and support standards and guidelines forresearchintovaccinesandvaccination.Theseactivitiesinformtheestablishmentofnewregulatorystandards,harmonizedmethods,andtoolsthatpermitacomparisonofresearchresults.Thisisparticularlyrelevantfornewvaccinecandidatesastheirmechanismsofactionaremorecomplexthanthoseofexistingvaccines,andoften

target diseaseswithmultiple clinicalmanifestations.In addition, IVR will continue to develop practiceguidelinesfortheappropriateandethicalconductofresearchindevelopingcountries,therebyencouragingpublicconfidenceandparticipationinresearch.

Strengthening research and product develop-ment capacity.Asaminimum,allcountriesshouldbe able to assess their immunization needs, assessorcarryoutvaccineevaluationsanddecidewhetherto introduce a new vaccine into their immunizationprogrammes. In addition, an increasing number ofcountriesareinterestedinestablishingthetechnologybasetodevelopandproducevaccinesofassuredqual-ity.Tomeettheseneeds,IVRwillstrengthencapacityindevelopingcountriesasanintegralpartofitsprojects.Examplesof thissupportareprovidingguidanceongoodclinicalpractice;facilitatingtechnologytransfertovaccinemanufacturersforproductdevelopment;andsupporting thedevelopmentof technologyhubsandresearchnetworks.

Translation of research results into policy and practice.Atthegloballevel,IVRwillgenerateand/or analyse the scientific data to enable theoverarchingWHOadvisory body on vaccines andimmunization – the Strategic Advisory Group ofExpertsonimmunization(SAGE)–tomakeevidence-based recommendations. IVRwill help develop theknowledge base for local deployment of vaccines,and vaccination strategies and schedules.Attentionwill be given to the development and validation oftoolstoinformvaccinationpolicybygathering,whererelevant, country representative epidemiological,socialoreconomicdataanddemonstratingtheiruseindecision-makingatcountrylevel.

PRIoRITy aReas and lead PRojeCTs

Applyingthestrategicfunctionsdescribedabove,IVRwillinitiallyfocusonthefollowingthreepriorityareas

3executive summary

–eachwithaleadproject– thatcanhaveamajorimpactonpublichealth:

i) vaccinationasanelementofhealthsecurity;

ii) vaccinationstrategiesforallagegroups;

iii)vaccinesagainstpoverty-relateddiseases.

Vaccination as an element of health security.ThepotentialofemergingdiseasesandpandemicstothreatenworldhealthonanunprecedentedscalehasledWHOtostepupitseffortsinglobalhealthsecurity.IVRactivitieswillincludethedevelopmentofsimplifiedvaccineproductionandadministration,computationalmodelling, and scenario development for vaccinedeployment.Theleadprojectunderthispriorityareaistoassistdevelopingcountrymanufacturerstoproduceinfluenzavaccine.

Vaccination strategies for all age groups.Expansionoftheagescopeforvaccinationbeyondthetraditionalpaediatricsegmentiscriticaltomaximizethebenefitsofvaccination,andaprominentelementoftheWHOGlobalImmunizationVisionandStrategy.1Drivenbychangingepidemiologicalpatternsandtheavailabilityofnewvaccines,reachingolderchildrenandadolescentsbecomesaprogrammaticpriority.Inolderagegroups,infectiousdiseasescausesignificantmorbidity and mortality, but existing vaccines arethoughttohavelimitedeffectiveness.Definingthetrueburdenofinfectiousdiseasesintheelderly,particularlyin developing countries, and exploring strategies to

increasetheimmuneresponsivenessofthisagegrouptovaccineswillbe importantactivitiesof IVR's leadprojectonvaccinesfortheelderly.

Vaccines against poverty-related diseases.Three killer diseases –HIV/AIDS, tuberculosis andmalaria–remainleadingpublichealthprioritiesformanylow-andmiddle-incomecountries.IVRwilladvocatefortheaccelerateddevelopmentofvaccinesagainstthesediseasesinthecontextofexistingpreventivemeasures,andparticularlythroughitsleadproject,theHIVVaccineInitiativewhich itwill continue to host. IVRwill alsocoordinateactivities related to thedevelopment andevaluationofvaccinesagainstotherdiseases–especiallyneglected tropical diseases – that disproportionatelyaffectpoorandmarginalizedpopulations.

IMPleMenTIng The sTRaTegIC Plan

IVRwillcontinuetofunctionasasmall,highlyskilledand experienced group collaborating with a widerange of partners to achieve its goals. Periodicmonitoring, evaluation and risk assessments willexamine the priority areas and lead projects forrelevance, feasibility, progress and the impact thatIVRcaneffect.Theresultsofthesereviewswillinformdecisionsonthecontinuationofprojects.However,itisunderlinedthatwhetherornotpriorityareasorprojectsaremodifiedtomeettheneedsofcountriesortomatchscientificadvances,thestrategicfunctionswillremainconstantthroughouttheperiodoftheStrategicPlan.

4

1. InTRoduCTIon

Vaccinationhasproventobeamongthemostefficientand cost-effective ways of reducing mortality andmorbidityfrominfectiousdiseasesworldwide.Yetanestimated fourmillionpeopledie each year fromavaccine-preventable disease, and some50%of allchild deaths and an average25%of adult deaths(15–59years)arestillattributedtoinfectiousdiseases.In fact, adult deaths from infectiousdiseases rise toa staggering55% in theAfrican regiondue to thetollofHIV/AIDS.2Recognizingthesechallenges,theWorldHealthAssemblyendorsedanambitiousandcomprehensiveplan,theGlobalImmunizationVisionandStrategy(GIVS)1coveringtheperiod2006–2015,tofightcommunicablediseasesthroughimmunization.Improvingaccess to immunization is also critical toachievetheMillenniumDevelopmentGoals(MDGs),andwillparticularlycontributetotheMDGtargetstoreducechilddeathsandtocombatHIV/AIDS,malariaandotherdiseases.3

1.1 RealIzIng The PoTenTIal of VaCCInes

WithregardtothetraditionalEPIvaccines,onegoaloftheGIVSisthatfrom2010,atleast90%ofchildrenacrosstheglobewillbereceivingtheirthirddoseofdiphtheria-tetanus-pertussisvaccine.WhilethistargethasbeenmetinseveralWHOregions,coveragevariessignificantlyandinsomecasesremainsbelow70%.Infact,coveragegapstranslateintomorethan23 millionchildrennot,oronlypartiallybeingvaccinatedwithbasicEPIvaccines.

Inparallel,theintroductionofnewvaccinespromisestoreducesignificantlytheburdenofinfectiousdiseases.Several new vaccines already recommended forintroduction indevelopingcountries could, together,savethelivesofuptoamillionchildrenayear,includingpneumococcalvaccine,whichpreventspneumoniaandmeningitis,and rotavirusvaccineagainstdiarrhoealdisease.Inaddition,thehumanpapillomavirus(HPV)vaccine has the potential to prevent most cervicalcancersinwomen.

However, new vaccine introduction is complex andfinancial considerations are not the only constraint.Thedecisiontointroduceanewvaccineintoacountryneeds to be based on a broad set of factors thatoften intertwine. Experience with the Haemophilus influenzatypebvaccine,forexample,showedalaginintroductioninlow-andmiddle-incomecountriesduetodelayedtranslationofresearchfindingsintopolicyandpractice, inparticular in relation to theburdenof disease, the cost of the vaccine and ineffectivecommunicationandadvocacyefforts.

Learningfromtheselessons,implementationresearchisneededtoprovidecriticalinformationandtools,andtounderstandfactorsthatinfluencecoverageorslowuptakeofvaccine.Analysesmayincludethestudyofgenderissueshinderingcoverage,andresearchintopredicting the impactofnewvaccines. Increasingly,decisions will rely on comparative assessments tomakechoicesbetweenvaccinesoralternativehealthinterventionsagainsta targetdiseaseor tocombinethem in a more effective manner. Tools and data

51. introduction

arerequiredtoassistcountrydecision-makersinthisprocess,aswellasmoderninformationtechnologytogather,transferandmanagedata.

Otherresearchprioritiesaretoenhanceimmunizationschedules and thereby improve vaccine deliverystrategies and the impact of vaccination.AlthoughWHO periodically revisits schedules of individualpaediatric vaccines,4 a review is needed of thecombined immunization schedules developed overthreedecadesago.IVRwillcarryoutthiscomprehensivereview toensure that thedeliveryof traditionalandnew vaccines are appropriate to country diseaseepidemiologyandhealthinfrastructure.ThedeliveryofnewvaccinessuchasHPVtoyounggirlsprovidesanopportunitytodevelopschedulesanddeliverystrategiesbeyondthechildagegroup.Thereisalsothepotentialtoexpandtheintegrateddeliveryofvaccineswithnon-immunizationhealthservicesinordertoimprovechild,adolescentandmaternalhealth.

Lookingtothefuture,severalnovelvaccinesareinanadvancedstageofdevelopment.Inthenextfewyears,for instance, vaccines against bacterial meningitisgroupA,malariaanddengue,alongwithimprovedvaccinesagainstcholera,Japaneseencephalitisandtyphoidfevermaybecomeavailableforintroductioninto immunizationprogrammesandprotectabroadrange of ages. On the other hand, diseases suchas EnterotoxigenicEscherichia coli, shigellosis andstreptococcusgroup Awillprobablylackaneffectivevaccineforsometime.

Of themortality caused by infectious diseases thatyetlackaneffectivevaccine,40%iscausedbyHIV,tuberculosisandmalariaalone.Whileafirst-generationmalariavaccineislikelytobeavailableinthenextfewyears, improved tuberculosis vaccines have severalmoreyearstogotolicensure.HIVvaccineresearchisstillfacingmajorchallenges,despiteencouragingresults

fromaprime-boostclinicaltrialthatdemonstratedforthefirsttimesomeefficacyinpreventingHIVinfection.

ThepotentialofexistingandfuturevaccinesinrelationtothemortalitycausedbyinfectiousdiseasescanbeseeninFigure1.

1.2 PRoduCIng VaCCInes and TeChnologIes ThaT MeeT deVeloPIng CounTRy needs

Typically,morethan10yearsarerequiredfromconcepttolicensureofavaccine,anduptoafurther10yearsto introduction and use of the vaccine in nationalimmunizationprogrammes.WHOactively facilitateseachstepalongthepathwaywiththeaimofacceleratingtheprocess (Figure2). The cost of the researchandprocessdevelopment for a single vaccine candidateisinthehundredsofmillionsofUSdollars,andasthetechnologicalcomplexityofvaccinecandidatesandtheensuing regulatory requirements increase, sowill thecost.Therateofattritionduringthedevelopmentprocessishigh,andcandidatesmayevenfailatalatestageofclinicaldevelopment.Thesecostsneedtobeoffsetandthussignificantcapital,highlyskilled labourandknow-howarerequiredtobringavaccinetolicensure.

Unfortunately,thosewhomostneedthevaccinesareoftentheleastabletoaffordordevelopthem.Inaddi-tion,researcheffortslargelyfocusondiseasesthataffectindustrialized countrypopulations. Even if the samediseaseoccursinadevelopedanddevelopingcountry,theircharacteristicsareoftendifferent.Forexample,pneumococcaldiseaseiscausedbyadifferentsetofserotypesinAfricaandAsiatothoseinNorthAmericaandWesternEurope,resultinginavaccinetargetedatindustrializedcountrieshavingreducedeffectivenessinmanydevelopingcountries.Aclearunderstandingoftheburdenofdiseaseandtargetedproductdevelop-mentcanhelptoaddressthesedifferences.


fIg. 1. The PoTenTIal of VaCCInes

Area of circles is proportional to the number of deaths (2008 data). Shaded areas are proportional to the number of deaths prevented by vaccination.

Adapted from Serdobova I, Kieny MP. Assembling a Global Vaccine Development Pipeline for Infectious Diseases in the Developing World. American Journal of Public Health, 2006, 96(9):1554–1559.

Anumberofresearchpartnershipsandmarketincentivemechanismshavebeencreatedtoaddresstheneedsof low- and middle-income countries. These effortsinject new funds into researchand involveboth thepublicsector,includingWHO,andtheprivatesector,particularly thevaccine industry.Afewexamplesof

public–privatepartnershipsfocusingonaspecificdis-easearetheInternationalAIDSVaccineInitiative,theMalariaVaccineInitiative,thePediatricDengueVaccineInitiativeandtheAerasGlobalTBVaccineFoundation.Inaddition,severalnon-profitinitiativesarenowbeingestablished todevelopnewvaccines fordeveloping

HIV/AIDS

TuberculosisMalaria

DengueMeningitis (conjugate)Human papillomavirus

Rotavirus

Pneumococcus (conjugate)Cholera

Typhoid

Haemophilus in�uenzae type b

Hepatitis B

RubellaJapanese encephalitis

In uenza

Yellow fever

MeaslesPolioTetanus

PertussisDiphtheria

1960 1980 2000

Futurevaccines

Underutilizedvaccines

TraditionalEPI vaccines

71. introduction

WHO priority focus

Best practice guidelines

Pre-normative researchNorms and standards Implementation and

translational researchRecommendations

for use

Non-clinical research Clinical research Vaccine licensure Effectiveness studies Large-scale vaccine introduction

Moving towards programmatic introduction of vaccines

fIg. 2. CRITICal sTePs In VaCCIne deVeloPMenT and eValuaTIon

countries against a broader rangeof diseases. TheMerck-WellcomeTrustHillemanLaboratoriesinIndia,establishedin2009,isthelatestofthese.

Nonetheless,manydiseases,suchasleishmaniasis,arecurrentlyunabletoattracttheresourcesandleadershiptobringavaccinetomarket.RecentanalysishasshownthatR&Dfundingstreamsstillpoorlymatchpublichealthpriorities.5MechanismssuchastheAdvanceMarketCommitment have been designed to createmarketincentivestopushforwardvaccinedevelopmentforthepoorestcountriesbycommittingfundsforaspecifiedtarget product profile. Their capacity to vitalizeinvestmentintoearlier-stagecandidatesremainstobedemonstrated.

Besides product development partnerships, researchfundingandmarket incentivemechanisms,acritical

nextsteptowardsvaccineavailabilityandaffordabilityis tostrengthenresearchandproductioncapacityincountriesor regionswhere theburdenofdisease ishigh.Typically,emergingsuppliershave focusedontraditional vaccines,oftenwith limitedmargins, thattheycanproduceinlargevolumesformiddle-and/or low-incomecountries. In the last fewyears,somecompanies in these countries have acquired know-how and technologies allowing them to developinnovativeproducts.Ensuringtechnologytransfer,orconnecting competency already available in targetcountries, combinedwith humanand technologicalcapacitystrengtheningformanufacturerswithinasolidregulatoryframework,areessentialtoincreaseaccessto vaccines in developing countries and strengthenhealthsecurity.

8

IVRwasformedin1999tofacilitatethedevelopmentofvaccinesagainstinfectiousdiseasesofmajorpublichealthimportance,toimprovevaccinationtechnologiesandtoensurethattheseadvancesaremadeavailabletothosewhoneedthemmost.ItsthreeconstituenciesaretheSpecialProgrammeforResearchandTrainingin TropicalDiseases (TDR), the JointUnitedNationsProgrammeonHIV/AIDS(UNAIDS)andWHO.IVRactsasthefocalpointwithinWHOforvaccineR&Dand is the interlocutor with external partners andorganizationsthatworkontheglobalvaccinepipeline.Asof2010,IVRcomprises25staff.

2.1 IVR sTRaTegIC Plan 2006–2009

TheStrategicPlanunderwhichIVRoperatedfrom2006to2009 useda three-tiered framework of researchcategories, namely: (i) knowledge management,guidance and advocacy to accelerate innovationfor new and improved vaccines and technologies;(ii)supporttoresearchandproductdevelopmentforpriority products; and (iii) implementation researchand development of tools to support policies andstrategiesforoptimaluseofvaccinesandtechnologies.Thisholisticapproachwasadeliberateefforttomovebeyond a largely product development perspectivetowardsabroadervisionofvaccinationasapublichealthpriority.

Duringthisperiod,IVR’sleadershipmovedanumberofprojectsforward,someofwhichareoutlinedinTable 1.TheseprojectshavebeensuccessfulbecauseIVRwasable to identify a public health need and proposetechnologysolutions,conceptualizeandoperatewithin

partnershipsthatcombinethestrengthsofitsindividualmembers,mobilize the best technical and scientificexpertise,andbuildconsensusoncomplexmatters.

Anexternal reviewconducted in2008 reflectedonIVR'sachievementsandthehurdlesithadfaced,aswellastherolesitshouldplaywithintheglobalvaccineR&Darenaoverthenextdecade.ThestrongleadershipofIVRanditsneutralWHOhallmarkwererecognizedasmajorassets.Atthesametime,thereviewemphasizedthataperiodicappraisalofprogrammeprioritiesshouldhighlight research areas that no longer justify IVR'sproactive involvement. The key recommendations oftheexternalreviewwereasfollows:

Focus on “landmark” projects that have a clearpublichealthgoal.

Spotlight activities that build on IVR corecompetenciesandthecomparativeadvantagesofWHOasaconvener, facilitator,and interlocutorwithdevelopingcountries.

Increase the involvement of developing countriesin product development partnerships, research,training and institutional capacity strengthening,bothinvaccineclinicaltrialsandimplementationresearch.

Build on WHO's normative role to guide andfacilitatevaccinedevelopmentandevaluation.

Developa long-term strategic plan to provide adurableframeworkforinteractionwithpartnersandfirmlypositionIVRintheevolvingglobalvaccineresearcharena.

2. PosITIonIng IVR In a ChangIng global enVIRonMenT

92. positioning ivr in a changing global environment

Project description Status at January 2010

The Meningitis Vaccine Project is a public–private partnership to develop a conjugate meningococcal A vaccine to eliminate epidemics in the sub-Saharan meningitis belt. IVR and PATH co-manage this development effort, including collaboration among the vaccine manufacturer, trial sites, laboratories and ministries of health; adherence to international standards; and capacity strengthening for vaccine trials and regulatory competence in African countries.

The vaccine is expected to be licensed and available to countries of the African meningitis belt in 2010.

The Measles Aerosol Vaccine Project, jointly overseen by WHO, the American Red Cross and the US Centers for Disease Control and Prevention, aims to develop an aerosolized measles vaccine in partnership with a major vaccine manufacturer and device companies. IVR manages the project with input from the best technical experts. The aerosolized vaccine will allow administration by non-medically trained personnel and avoid injection-related safety problems, especially in resource-poor settings and during vaccination campaigns.

The vaccine is expected to be registered as early as 2011.

The Pandemic Influenza Vaccine Production project seeks to increase influenza vaccine production capacity in low- and middle-income countries to bridge the considerable gap between current capacity and potential pandemic influenza demand. IVR has brought together significant funding, technical expertise and capable developing country vaccine manufacturers.

The domestic pandemic influenza vaccine production capacity of 11 developing country manufacturers is now being strengthened.

2.2 hoW Is The IVR sTRaTegIC Plan 2010–2020 dIffeRenT?

Instrivingtoachievesustained,high-impactresults,fourstrategicfunctionsandalimitedsetofpriorityareasandprojectsdescribedinthenextSectionwillconstituteIVR’s framework of operations for the next decade.While theareasofworkandprojectsmayneed tobemodifiedas scientific advances or new contextsdictate,thestrategicfunctionswillstillbeshapingIVRprioritiesin2020.

IVRpaidparticularattentiontotherecommendationsof the external reviewdescribedabove, aswell as

thoseoftheIVRVaccineAdvisoryCommittee(IVAC)inthedevelopmentofitsStrategicPlan2010–2020.IVR will strengthen its collaboration and synergieswiththeresearch-ledprogrammesatWHOandwiththeglobalvaccineresearchcommunitytoensurethelong-termrelevanceandimpactofitsworkandsecureaproductiveinterfacewithitspartners.

Most importantly, the IVR Strategic Plan is directlyalignedwiththeWHO/UNICEFGlobalImmunizationVision and Strategy,1 and WHO’s policies andprocessestostimulateresearch,innovationandaccesstointerventiontoolstargetedatdevelopingcountries.

Table 1. hIghlIghTs of IVR-dRIVen VaCCIne deVeloPMenT PRojeCTs


2.2.1 Who/unICef global IMMunIzaTIon VIsIon and sTRaTegy

TheGlobalImmunizationVisionandStrategy2006–2015 seeks to accelerate progress to reachglobalhealthanddevelopmentgoalsthroughimmunization.IVR focuses particularly on theGIVS Strategy8 onvaccineR&D,whoseconcreteactivitiesareto:generateandanalysecountry-contextualdata;defineresearchagendas;strengthencapacityindevelopingcountriestocarryoutvaccineevaluationsandclinicaltrials;fosterinnovationinvaccineR&D;andupdateevidence-basedimmunizationschedulesasnewtechnologiesbecomeavailable.

2.2.2 Who sTRaTegy on ReseaRCh foR healTh

TheWHOstrategyonresearchforhealth,endorsedbytheExecu-tiveBoardinJanuary2009,6isaframeworkofstrategicgoalsthatharmonizestheresearcheffortsoftheOrganizationwithitsmandateandmission, and complementsthoseof itspartners. It seeks toimproveandbettercommunicateWHO’sroleinsupportingMem-ber States to strengthen healthresearchcapacity,andtopositionthe Organization as a strongleaderand championof healthresearchwithinan increasinglycomplex global architecture ofresearchinitiatives.IVR'sstrategicfunctionsmirrorthegoalsoftheWHOstrategyonresearchforhealth,illus-tratedinFigure3,andprovideabasisformoreefficientcollaborationamongWHOresearchprogrammes.

2.2.3 Who global sTRaTegy and Plan of aCTIon on PublIC healTh, InnoVaTIon and InTelleCTual PRoPeRTy

Recognizingthecriticalrolethatdevelopingcountriesthemselvesshouldplayingeneratingrelevantresearchandinnovation,theWorldHealthAssemblyadoptedtheGlobalStrategyandPlanofActiononPublicHealth,InnovationandIntellectualProperty7in2008aimingtostimulatenewthinkingonaccesstohealth-careproducts.Theplanofaction−thefruitofanintergovernmentalworkinggroup− sets out a framework of activitiesbased on eight strategic elements that cover thedevelopmentof researchagendas; thepromotionof

healthresearch,innovationandproductR&Dcapacityin developing countries; the transfer of technology;intellectualpropertymanagement;andactivities thatfocusontranslatingresearchresultsintopractice.

PRIORITIESChampion research

that addresses priorityhealth needs

CAPACITYSupport the

development of robust national health

research systems

STANDARDSPromote good

research practice

TRANSLATIONStrengthen links

between research, policy and practice

ORGANIZATIONStrengthen the research culture across WHO

MISSIONWHO, Member States and partners work together to harness knowledge, science

and technology to produce research evidence and tools to improve health

VISIONdecisions and

actions to improve health and enhance health equity are

grounded in evidence for research

fIg. 3. Who sTRaTegy on ReseaRCh foR healTh

112. positioning ivr in a changing global environment

IVR goals and activities during 2010–2020 willcontributetoeachofthestrategicelementsoftheGlobalStrategyandPlanofAction,andaseriesofprojectswillbeimplementedinconjunctionwiththeplan.Movingbeyondthetraditionalconceptofbilateralcollaboration

betweendevelopedanddevelopingcountries, thereis great potential for research networks within thedevelopingworld to consolidate competencies anddevelopvaccinesadaptedtoregionalneeds.

12

IVR'smission is to accelerate the development andoptimaluseofsafeandeffectivevaccinesandrelatedtechnologies. The four strategic functionswhere IVRconsidersithasastrongcomparativeadvantage,andwhichwill therefore serve as an umbrella for IVR’sprogrammeofworkasfrom2010,are:

the identification of vaccine and vaccination re-searchpriorities;

thedevelopmentofresearchstandardsandguide-lines;

thestrengtheningofresearchandproductdevelop-mentcapacity;and

the translationof researchresults intopolicyandpractice.

Withinthisframework,IVRhasselectedthreeprioritypublic health areas that require concerted globalcooperation, andwhere IVR involvement can driveprogressforward,namelyvaccinationasanelementofhealthsecurity;vaccinationstrategiesforallagegroups;and vaccines against poverty-related diseases. ThematrixapproachIVRwillembraceisshowninTable2.

3. The IVR sTRaTegIC Plan MaTRIx

Table 2. IVR sTRaTegIC Plan MaTRIx

STRATEGIC fuNCTIONS

Researchpriorities

Research standards

Capacity strengthening

Translation of research results

PRIO

RITY

ARE

AS

Vaccination for health security

Vaccination for all ages

Vaccines for diseases of poverty

133. the ivr strategic plan matrix

3.1 sTRaTegIC funCTIons

3.1.1 IdenTIfICaTIon of VaCCIne and VaCCInaTIon ReseaRCh PRIoRITIes

Inanincreasinglycomplexlandscapeofglobalhealthresearch, and a growing number of players in thefield,itisimportantthatactualpublichealthneedsareassessedthroughatransparentandinclusiveprocess.Theneedtoassessgapsinknowledge,andtoanalyseandidentifyR&DprioritiesfordiseasesofpovertyhasbeenrecognizedbyWHOMemberStates,theoutcomeofwhichwillbecriticallyrelevantforcountryresearchplans,majorresearchfundersandtheprivatesector,andwillensurethatnewresearchactionswilltargetwhereitisneededmost.

IVRhasextensiveexperience in identifyingresearchgapsandalong-termrecordofadvisingtheresearchcommunitythroughitsscientificandtechnicalcommitteesandexpertgroups.IVRalsoconsidersdiseasecontrol

efforts other than vaccines when conducting gapanalysesandprioritizationand, in this context,willcontinuetocollaboratewithprogrammesworkinginthisarea,suchasTDR’sthematicanddiseasereferencegroups.

Ofparticularimportanceistheelaborationoftechnicalagendassuchastargetproductprofiles(TPPs)toinformandguidethedevelopmentofdesirablenewvaccinesand related technologies adapted to developingcountry needs. Moreover, highly specific technicalagendashavethepotentialtofocusscarceresourcesonpriorityissuesandtherebymaximizeimpact.TPPsenable WHO to determine research and productneeds through an evidence-based, transparent andconsultative process and convey them to theglobalresearchcommunity.ThisprioritysettingfunctionbuildsontheneutralbrokerpositionofWHOandhasbeensuccessful for the development of essential productcharacteristicsofnovelpneumococcalvaccines(Box1).Suchprioritizationactivitiesareassessedregularlyto

box 1. exaMPle of a VaCCIne ReseaRCh PRIoRITIzaTIon aCTIVITy: TaRgeT PRoduCT PRofIles

IVR developed the TPP for pneumococcal conjugate vaccines with the help of a dedicated advisory committee, extensive stakeholder consultations and special studies to develop criteria for maximum vaccine impact in target populations. Once a manufacturer supplies a product requested by developing countries that is judged to meet the TPP characteristics, funds pledged by donors to the Advance Market Commitment can be released to purchase the product at a pre-arranged price. Since the TPP is a formal eligibility criterion for funding, this mechanism stimulates industry investment in vaccines that are appropriate for developing countries. The official adoption by SAGE and the GAVI Alliance of this TPP is a powerful example of the public sector guiding private sector product development.

guaranteetheirrelevanceandvalidity.Irrespectiveofspecificincentivemechanisms,TPPsareconsideredasuitableapproachtoshapeandfocusR&Deffortsforothervaccinesandrelatedtechnologies,andwillbedevelopedbyIVRforpriorityneeds.

Inaddition, IVRwill conductassessments to identifysuitable technologiesandmethods tobeapplied tovaccinedevelopment,productionandadministration.Oncepromisingtechnologieshavebeenevaluated,IVRwillanalyserelevantintellectualpropertypositionsin


ordertoprovidethebestadvicetodevelopingcountryvaccinemanufacturers.

Insummary,IVRwill:

develop and apply rigorous scientific reviewprocesses,includingsystematicreviewsandmetho-dologies,andprioritizetheresearchgapsidentified;

developtechnicalagendassuchastargetproductprofiles;

conductassessments toscreenforpromisingandaccessiblevaccinetechnologies;

conveneadhocadvisorycommitteesattherequestofMemberStatesorWHOpolicy-formingbodiestoinformresearchagendasandpolicies.

3.1.2 deVeloPMenT of ReseaRCh sTandaRds and guIdelInes

Establishingnorms,standardsandguidelinesforhealtharepartofWHO’scoremandate.Appliedtovaccineresearch,standardshelptoachieveaconsistentlyhighlevelofquality,ensurecomparabilityofresults,providenationalauthoritieswithguidancefortheevaluationofproductsand,intheformofgoodpracticeguidelines,ensurethatresearchisconductedefficientlyandtothehighest ethical principles. They also help to protectresearchparticipantsandtomaintainpublicconfidence.

Forregulatorystandards,IVRidentifies,initiatesandcoordinatespre-normativeresearch,i.e.researchthatmayleadtotheestablishmentofregulatorystandardsfortheevaluationandqualitycontrolofvaccinesandbiologicalsbyotherteamsatWHO.Ultimately,theseregulatorystandardsareendorsedandpublishedintheWHOTechnicalReportSeriesasstandardsforvaccineprequalification.

The pre-normative research typically emerges fromvaccine research projects that require advanced

methodologies to measure immunogenicity andsafety, and usually requires evaluation of novellaboratorymethodsandtechnologies,theircomparativeassessmentandthedevelopmentofstandardprotocolsfor their furtherevaluation.Ofparticular importanceareapproachesandlaboratoryassaysthatmayhelpto establish correlates of protection, as theygreatlyfacilitate the prediction of vaccine impact and theevaluationandlicensureofsecondgenerationvaccines.

IVRwillcontinuetodevelopguidelinesfortheclinicalevaluationofvaccines.Forvaccinestargetingdiseaseswith complex pathologies and multiple clinicalmanifestations, IVR has initiated, coordinated andfacilitated researchand consensus-buildingactivitiesthatresultedinguidelinesonbasictrialdesign,andevaluationcriteriasuchasclinicalendpointstoassessthesafetyofcandidatevaccines.Suchguidelines,ashavealreadybeenproducedformalariaanddengue,8providevaluable information forvaccinedevelopersandnationalregulatoryauthorities,andfacilitatethecomparativeevaluationofvaccinecandidates(Box 2).

Withregardtogoodpracticeguidelinesforvaccineandvaccination research, IVRwillparticularly focusontheprotectionofvulnerablepopulationsenrolledinclinicaltrials,andonresearchareasthatlargelylack

WHO guide for standardization

of economic evaluations of

immunization programmes

WHO/IVB/08.14 ORIGINAL: ENGLISH

Immunization, Vaccines and Biologicals

Guidelines for the clinical evaluation of

dengue vaccines in endemic areas

WHO/IVB/08.12 ORIGINAL: ENGLISH

Immunization, Vaccines and Biologicals

Selected IVR guidelines


box 2. exaMPle of a VaCCIne ReseaRCh sTandaRds aCTIVITy: Consensus ReCoMMendaTIons foR The desIgn and eValuaTIon of MalaRIa

VaCCIne ClInICal TRIals

With malaria vaccines entering pivotal phase 3 evaluation, the standardization of methods and reporting practices in controlled trials of preventive interventions became a high priority. IVR convened advisory groups to define measures of efficacy as consensus recommendations on the choice of endpoints, clinical case definitions, sample size, duration and nature of follow-up, as well as on key trial design and analysis issues. IVR will facilitate priority research into the statistical methods for estimating efficacy against the overall community burden of clinical malaria. In addition, IVR will synthesize the wealth of information on malaria vaccine performance as an aid to policy-makers and as a bridge between scientific proof-of-principle endpoints and the public health impact of malaria vaccines. Analogous approaches will be tailored to HIV, tuberculosis and dengue vaccines, among others, as they reach the pivotal phase 3 evaluation stage.

harmonizedmethods,suchashealtheconomics.IVRwillalsosupporttheimplementationofgoodpracticeguidelinesthroughitstrainingandcapacitystrengthen-ingactivitiesforimprovedefficiencyandharmonized,qualityresearch,incollaborationwithTDR.

Insummary,IVRwill:

identifyandprioritizeneedsforresearchstandardsdevelopment,andconductpre-normativeresearchtoidentifyandimprovesuitablemethodsandmea-surementtechnologies;

conduct comparative studies to informbiologicalstandardsdevelopment;

developconsensusandguidelinesfortheevaluationof complex vaccines and related technologies,basedonbroadconsultationsandspecialstudies;

developgoodpracticeguidelinesinareaswhereitiscriticaltoprotectresearchsubjects,ortoadvancetherelevanceandcomparabilityofresearch;

develop,disseminateandimplementgoodpracticeguidelinesinconjunctionwithtrainingandcapacity

strengtheningeffortsandwithWHOcollaboratingcentres.

3.1.3 sTRengThenIng of ReseaRCh and PRoduCT deVeloPMenT CaPaCITy

Strengtheningcountrycapacityforcontextualresearchservesastheirscientificbasistoinformhealthpolicyandassuresthattechnicalcompetencyisdeveloped.In addition, an increasing number of countries areinterestedinestablishingthetechnologybasetodevelopandproducevaccinesofassuredquality.TheMexicoMinisterialSummitonHealthResearch9calledforallcountriestoinvestsystematicallyasmallpercentageoftheirhealthbudgetintoresearchtoaddresstheirmostpressingpublic health needs.While some countrieshavemadeprogressindevelopingresearchcapacity–bothinthepublicandprivatesectors–othersarelaggingconsiderablybehind.

Some programmes, notably TDR, have a specificmandate for training, career development andinstitutionalcapacitystrengtheningforhealthresearch.IVR, in contrast, strengthens capacityasan integral


componentofitsresearchprojectsandclinicaltrials.Bothprogrammesjoinforcesforspecifictrainingactivitiessuchasongoodclinicalpracticestoensurethatclinicaltrialsare conducted to thehighest international standards.Similarly,IVRsupportstrainingandgoodpracticesinresearchethics jointlywithUNAIDSand the TDR-ledStrategicInitiativefortheDevelopmentofCapacityforEthical Review,whichare important opportunities toimplementanddisseminategoodpracticeguidelines.

IVRwillplacespecificemphasisonvaccinetechnologycapacity development in linewith the objectives ofthe Global Strategy and Plan of Action on PublicHealth, Innovationand Intellectual Property. IVRwillassess intellectual property and freedom to operateforcriticalvaccinetechnologies,identifyappropriatemanufacturingtechnologiesandtechnologyproviders,andcommissionmarketanalysestofacilitatetechnologytransfertodevelopingcountries.Technologynetworkswill also be set up within and among developingcountries to maximize the sharing of knowledgetowardsregionalorcountrycompetencyforvaccinedevelopmentandproduction.TheAfricanNetworkforDrugsandDiagnosticsInnovationisonesuchmodel,whereapartnershipofAfricaninstitutionshasformedtostrengthenR&Dcapacitythroughoutthecontinent.10

Followingthesuccessfulestablishmentofatechnologytransferhubtosupporttheacquisitionandenhancementof influenza vaccineproduction capacity in low- ormiddle-income countries, the concept of technologyhubswillbefurtherdeveloped.Thesehubswillserveascompetencycentrestoadvisedevelopingcountrymanufacturersontheselectionandimplementationofnovelproductiontechnologiesforothervaccinesofhighpublichealthvalue.

IVR has identified limited knowledge on vaccineformulation and the lack of access to innovativeadjuvantsasmajorimpedimentstomanyvaccineR&Dprojects.AGlobalAdjuvantDevelopment Initiativewill enable the vaccine research community,and inparticulardevelopingcountries,toaccessadjuvants,criticaldataontheseproducts,andtechnicaladviceandtraininginrelationtovaccineformulation(Box 3).

Insummary,IVRwill:

enhancethecompetenciesneededforIVR-sponsoredresearch projects, and exploit opportunitiesofferedbytrainingschemesdevelopedbypartnerprogrammes;

usetrainingefforts todisseminateandimplementgoodpracticeguidelines;

box 3. exaMPle of a CaPaCITy sTRengThenIng aCTIVITy: TRansfeRRIng knoW-hoW on adjuVanTs

The development of new vaccines will benefit from improved access to a range of novel technologies, especially adjuvants. IVR has initiated a number of activities, collectively referred to as the Global Adjuvant Development Initiative, that aim to facilitate the development of adjuvants and antigen delivery systems, and to supply these and know-how on their use to the public sector. It is envisioned that over the next 10 years the project will expand to include technology transfer to developing country research and manufacturing centres. Activities include: preparing, evaluating and supplying generic versions of known adjuvants; maintaining and making available databases of toxicology and clinical studies with adjuvants; training researchers in adjuvant formulation; and undertaking technology transfer to developing country vaccine manufacturers.


seeksuitableprojectsandstrategiesfortechnologytransfer;

encouragetheset-upofresearchnetworksbyandfordevelopingcountries;

participateinresearchplatformsthataimtoestablishresearchcapacityatcountrylevel;

furtherdeveloptheconceptoftechnologyhubsascompetencycentrestoassistwithtechnologytransfertodevelopingcountryvaccinemanufacturesandrelatedpublicsectorinstitutions.

3.1.4 TRanslaTIon of ReseaRCh ResulTs InTo PolICy and PRaCTICe

Movingresearchfindingsmorequicklyintopolicyandpracticehasbeenrecognizedasamajoravenuetoharvestthebenefitsofinnovation.ThisneedwasmostrecentlyhighlightedintheBamakoCalltoActiononResearch forHealth,11which reiterated the valueofresearchresultstodevelopevidence-informedpolicies.

Toaddresstranslationalobstaclesinimmunization,IVRsupportsimplementationresearchalongseveralaxesthataimtoprovidecountriesandtheglobalcommu-nitywithrelevant information fordecision-makingorpolicydevelopment, suchas for the optimizationofimmunizationschedules.ThisresearchwillbecarriedoutinclosealignmentwithteamsatWHOthatsup-portnationalimmunizationprogrammesindevelopingcountries,notablythoseoftheDepartmentofImmuniza-tion,VaccinesandBiologicals(IVB).Thedevelopmentandvalidationoftoolstosupportvaccinationpolicywillincludeananalysisoffactorsleadingtoeffectivevaccineimplementation,withattentiontogenderandvulnerablepopulationswhererelevant;thegatheringof country representative epidemiological, social oreconomicdata;anddemonstrating theuseof thesedataindecision-making.

IVRwillalsoreviewestablishedvaccinationpracticesandassesstheirpotentialforimprovement.Ofparticularimportance is to fully implement a comprehensivereviewofpaediatricimmunizationschedules(Box 4),

box 4. exaMPle of a TRanslaTIon ReseaRCh aCTIVITy: oPTIMIzIng IMMunIzaTIon sChedules

The paediatric immunization schedule established by WHO more than 35 years ago still serves as the basis of most countries' immunization programmes. While individual vaccine schedules have been updated, no combined review of all major paediatric vaccine schedules has been conducted. Yet the vaccines, epidemiological situations and immunization programmes have evolved. Some vaccines exert population effects that have not been considered sufficiently when designing vaccination schedules. The need to introduce an increasing number of new paediatric vaccines provides the opportunity for a comprehensive assessment of immunization schedules. The optimization of immunization schedules has therefore been identified as a landmark activity for IVR. The project will review the existing evidence, taking due consideration of epidemiological, economical and operational aspects. The project will also identify and prioritize areas for research to fill critical data needs in relation to vaccine scheduling. The final product will be an analytic framework to assist countries on optimal programmatic vaccine decision-making.


through the establishment of a transparent set ofmethodsanddecision-makingapproaches,areviewofpublishedandunpublisheddata,targetedresearchanddemonstrationprojects.

IVRwillsupportorassessprojectsthatevaluatenewproducts or interventions for their effectiveness andoptimal use in field conditions. This research alsoassures thatproductand tooldevelopmentmeet theneedsoftheultimateuserandaretailoredtoreal-lifesettingsindevelopingcountries.

Finally, serving as the research arm of the WHOStrategicAdvisoryGroupofExpertsonimmunization,IVRreviewsandanalysesscientificevidencetoinformglobal policy recommendations. For the purpose ofassuringthehigheststandardsinquantitativeresearch,IVRwill be assisted by theAdvisoryCommittee onQuantitativeResearchinImmunization.

Insummary,IVRwill:

develop tools for decision-making informed bycountry-relevant,contextualdata;

supportstudiesthatexaminevaccineeffectivenessandeconomicimpactinrelevantcountryscenarios;

conductacomprehensivereviewofimmunizationschedules;

conductsystematicanalysesofavailableevidenceandsynthesizetheknowledgeintoguidanceandtechnical advice to Member States and globalpartners;

serve as the research arm for vaccines on theWHO Strategic Advisory Group of Experts onimmunization;

assureexcellenceand impartiality inquantitativeresearch through the involvementofadedicatedadvisorycommittee.

3.2 PRIoRITy aReas and lead PRojeCTs

TheimplementationofIVR’sStrategicPlan,basedonthefourstrategicfunctionsdescribedabove,willfocusonareasofglobalpublichealthimportance.InnovationwillbeatthecentreofIVR’sactivitiesandinnovationpotentialacriterionfortheselectionofprojects.ItiswithintheInitiative’smissiontochallengethestatusquoandlookatwaysforvaccinestobedevelopedanddeployeddifferently–andbetter.Effectivelyfosteringinnovation requires looking beyond vaccine andvaccination research and examining other scientificdisciplinesandbusinessareasforvaluableinput.IVRwillconductperiodicscreeningforinnovationpotentialtobeappliedfromoutsidethefieldofimmunization.

Tolaunchthe10-yearStrategicPlan,threepriorityareashavebeenidentified,namelyvaccinationasanelementof health security, vaccination strategies for all agegroupsandvaccinesagainstpoverty-relateddiseases.Withinthesemajorpublichealthissues,leadprojectsthatneedurgentactionorthatholdparticularpotentialforinnovationwillbepursued.Thesepriorityareasandleadprojects,describedbelow,wereselectedbasedon an analysis of IVR successes and comparativeadvantages, and following broad consultationwithpartners.

3.2.1 VaCCInaTIon as an eleMenT of healTh seCuRITy

Emergingdiseases, humanitarian emergencies, andhealth risks from the effects of climate change orenvironmentaldegradationareamongtheacutehealththreatsthathavebecomemajorpublichealthprioritiestoday.Framedbytheinternationalhealthregulations,12globalhealthsecurityisthefirstlineofdefenceagainsthealthcatastrophesthatcandevastatepeople,societiesandeconomiesworldwide.Exemplifiedbythepotentialofinfluenzapandemicstocauseharmataglobalscale,


infectiousdiseaseoutbreakscannotbetreatedaspurelynationalissues.

WHO has stepped up its operational capacity toidentifyandrespondtodiseaseoutbreaksthroughtheGlobalOutbreakAlertandResponseNetwork13andrelated efforts. In parallel, theGroupof Eight (G8)has created a global health security initiative,withWHOasanadvisor,whichsetoutaseriesofglobalactionsaimedat facilitatingresponsecapacity,suchasresearchintovaccineformulationsandregulatoryframeworksfortheirdevelopment.

WhilemanyexistingorpipelinevaccinessuchasthenewvaccineagainstmeningitisAcouldbeconsideredastoolstosupporthealthsecurity,specialmeasures,e.g.specificclinicaltrialschemesandregulatorystrategies,areneededtodevelopeffectivevaccinesagainstfuturehealththreats.Thedevelopmentofsimplifiedvaccineproductiontechnologiesmayalsoallowamoreflexiblesupplyinfrastructureforsporadically-neededvaccines.

Basedonexperiencegainedwithcholeraandinfluenzavaccines,IVRwillworkwiththeresearchcommunityto develop relevant computational modelling andsocioeconomic research for vaccine deploymentscenariosforprophylaxisoroutbreakresponse.

Simplifying vaccineadministration could reduce theneedforhighlytrainedhealth-careworkersandenableafasterandbroaderdeploymentofvaccines.Thisincludestechnologies suchas skinpatches,oralor sublingualwafersandnasalsprays.Other technologiessuchasthermostable formulations could reduce the need forthecoldchain. IVRhasalreadyplayedakeyroleinthis field through the continued screeningofdeliverydevices,theevaluationofintradermaldeliveryofpoliovaccinebyneedle-freeinjectionandthedevelopmentofanaerosolizedmeaslesvaccinedeliverysystem.

Asaleadproject,IVRwillcontinuetosupportpandemicinfluenzavaccinepreparednessandproduction(Box 5).Involvedinthisactivitysince2006,IVRsupportsthe

improvement of available vaccines, promotes andfacilitatesthescaling-uporaccelerationofvitalvaccineproductionandadviseson thedevelopmentofnewformulations.

3.2.2 VaCCInaTIon sTRaTegIes foR all age gRouPs

One goal of the Global Immunization Visionand Strategy1 is to protect more people throughimmunization, andamajor strategy to achieve thisentails the expansion of immunization beyond thetraditionaltargetgroupofchildrenbelowtheageofone.Indeed,overthepastyears,immunizationneedsaswell as opportunities for older agegroups havebecomeapparent:vaccineboostershavebeenstudiedandrecommendationsissued,andneworunderutilizedvaccines are now available against diseases thatcauseburdenbeyondinfancy.ThemostrecentoftheseopportunitiesistheuseofHPVvaccineinadolescentgirls toprevent cervical cancer.Other vaccines thatmaybedeliveredoutsidethepaediatricagesegment

Aerosolized delivery of measles vaccine

Phot

o:Ji

mL

in


includetyphoidanddengue.Developingstrategiesandpoliciestoachievebroadcoverageofthesepopulationswillrequiresignificantresearch.

Infectiousdiseaseshavehugepublichealthimplicationsin theelderly,evenifdirectmortality frominfectionsismuch less than from noncommunicable diseases:hospitalizationratesforinfluenzaandpneumoniaareintherangeof500–2500per100 000populationabove65years,whichissimilartothatforcardiovascularorischemicheartdisease.14

The population older than65 years is predicted toquadrupleoverthenextfewdecadeswhenitwillexceed25%ofthetotalpopulation.Aspeoplegrowoldertheirimmune systemweakens (immune senescence) andtheybecomeincreasinglysusceptibletoinfections,inparticularfrominfluenza,pneumococciandrespiratorysyncytialvirus,butalso fromopportunistic infectionsandtheresurgenceofchronicinfectionssuchasherpes

zoster.Moreover,immunesenescencediminishestheefficacyofvaccinationinthispopulation.

Indevelopingcountries,wherethepopulationisageingrapidlywithoutconcomitanthealthcare, theburdenof infectiousdisease is likely tobemuchhigher.Sofar,veryfewstudieshavedocumentedtheinfectiousdisease burden in this group, and no studies haveevermeasured the immunefunction in theelderly indeveloping countries.Although the exact causes ofimmune senescence remainpoorly understood, andasyetnotreatmentcanreverseit,protectiveimmunitymight be induced in this population by developingand using special vaccines (e.g. those containingappropriateadjuvantsoradministeredbyalternativeroutes)and/orbyimmunizingadultspriortotheonsetofimmunesenescence.

IVR has thus identified vaccines for the ageingpopulationasa leadproject (Box6). Itwill seek to

box 5. PRIoRITy aRea lead PRojeCT: faCIlITaTIng deVeloPIng CounTRy ManufaCTuReRs To PRoduCe Influenza VaCCIne

At the peak of the pandemic threat from the H5N1 avian influenza virus, the world was faced with the immense gap between the potential availability of a pandemic vaccine and the actual global need. Since H5N1 showed an extraordinarily high case–fatality rate, WHO conceptualized the Global Pandemic Action Plan to Increase Vaccine Supply. Building new vaccine production capacity, especially in developing countries where no such capacity existed, was a key goal of the action plan.

In response, IVR established a programme, in collaboration with donors, that provides seed funds for award recipient manufacturers and a technology transfer hub with a public sector institution to provide a turnkey process and training to potential manufacturers. More than 10 manufacturers are benefiting from training and technical support, or funding for physical plants, equipment, and preclinical and clinical trials with candidate influenza vaccines produced in these new manufacturing sites. In the coming years, it will be crucial to sustain technical and financial support to the new manufacturers, and to assess how many more projects should be initiated, in which part of the world and based on which technology.

The project exemplifies how shortfalls in vaccine production capacity and access to technology in the developing world can be improved through successful coordination. The overall strategy will be applied to other vaccines of public health importance.


understandbetterthemagnitudeoftheissueandthefactorsleadingtoimmunesenescence,suchastheageatwhichonsetoccursindifferentpopulations.Thiswillbeparticularly important in respect to the effects ofageingon immune responses indevelopingcountrypopulations where frequent exposure to infectiousagentsmayleadtodifferentonsetpatterns.

3.2.3 VaCCInes agaInsT PoVeRTy-RelaTed dIseases

Diseasesofpovertyarethosethataremoreprevalentinpoorerthaninwealthierpopulations,oraremorelikelytodriveaffectedpeopleandtheirfamiliesintopoverty.Socioeconomicfactorscanplayamajorroleinaggravatingcertaindiseases.ThebulkofthediseaseburdenofHIV,tuberculosisandmalariaaloneoccursin low-andmiddle-incomecountries,andcontrolof

thesediseasesremainstheleadingpublichealthpriorityformanyMember States. Recognizing the complexinteractionsbetweenthesediseases,theirpublichealthimpactisincreasinglyconsideredtogether.

Poverty-relateddiseases suchas pneumococcal andsomediarrhoealdiseasesarealsoimportanttomention,someofwhichhavebenefitedfromthedevelopmentofpowerfulinterventiontools.Others,oftenreferredtoasneglectedtropicaldiseases,suchasschistosomiasis,trachoma and leishmaniasis, figure among thoseagainst which no efficient preventive tools are yetavailableorbeingused.

ForHIV,tuberculosisandmalaria,IVRwillsupportthedevelopmentofvaccinesthroughitsguidelinesontheevaluationandcomparativeassessmentofcandidatevaccines.Guidelinesarealsodevelopedandwidelydisseminatedon standards for vaccine efficacyand

box 6. PRIoRITy aRea lead PRojeCT: assessIng The PoTenTIal of VaCCInes To PReVenT InfeCTIous dIseases In The

eldeRly

IVR will carry out the following activities in this area:

Gather reliable, valid and comparable data on infectious disease burden in older adult populations in representative developing countries.

Measure the immunogenicity and, where appropriate, efficacy of vaccines in the elderly in developing countries, and compare this to age-matched cohorts in industrialized countries. This will provide information on the effectiveness of existing and improved vaccines in developing country populations, whether they experience a comparable process of immune senescence, or whether this is modified by environmental factors.

Promote an evaluation and understanding of how vaccination earlier in adulthood could impact the immune function in later life and delay hypo-responsiveness. The implementation of schedules beyond childhood is already taking shape in some developing countries and may provide preliminary data on immune functions and the challenges to reaching adult populations.

Support the development of policies for the use of vaccines in adults and the elderly.


safety,andonethicalandsocialmeasurestoaccom-panyclinicaltrials.

IVRservesasthekeyfacilitatorforprioritizationoftheessentialimmunologicalmeasuresforleadcandidatesenteringefficacytrialsandforenablingaccesstore-agents,controlsandconsensus-harmonizedstandardoperatingproceduresforthegenerationofclinicaldata.Theoutcomeoftheseactivitiesandultimatelythede-velopmentofcorrelatesofprotectionwillbehallmarksfor the accelerated evaluation of vaccines. Target

productprofilesmaybedevelopedforsomevaccinesinordertoguideresearchtowardsproductswiththehighestexpectedpublichealthimpact.

For neglected poverty-related diseases, where theutility of a vaccine has been clearly identified, IVRwilldevelopresearchagendasandpromoteproductdevelopmentpartnerships.

TheleadprojectwillbesupporttotheWHO–UNAIDSHIVVaccineInitiative(Box 7).Theeffortsoftheleadprojectwillfollowthreemainavenues:(i)maintaina

box 7. PRIoRITy aRea lead PRojeCT: sTRaTegIC PlannIng, eThICs and CoMMunITy InVolVeMenT In VaCCIne TRIals

There are significant logistic challenges in conducting HIV vaccine trials in less developed countries to acceptable scientific and ethical standards. To address this, IVR has supported these countries to develop National AIDS Vaccine Plans and to strengthen their clinical trial capacities. This includes political support, clearly defined legal, ethical and regulatory frameworks, media and community involvement, and scientific, human resource, epidemiological and clinical trial infrastructures. As of January 2010, 10 African countries had adopted National AIDS Vaccine Plans, some of which now have the capacity to carry out all stages of clinical trials. The next steps are to expand the strategy to clinical trials of other vaccines of public health importance, such as malaria and tuberculosis.

favourableglobalenvironment forHIVvaccineR&Dthroughadvocacy, promotion of effective collabora-tion and support to regional networks; (ii) developand facilitate implementation of polices, normsandstandards related tovaccineevaluationandaccess;and(iii)supportsustainablecapacitystrengtheningofclinicaltrialsitesthatareintegratedintootherpreven-tionefforts,inparticularformalariaandtuberculosis.

3.3 suMMaRy of The IVR sTRaTegIC Plan MaTRIx

The IVRStrategicPlan2010–2020matrix, showingthestrategicfunctionsasthefourpillarsofIVR’swork,alongwithcross-cuttingpriorityareasandexamplesofprojects,isrepresentedinTable 3.


STRATEGIC fuNCTIONS

Researchpriorities

Research standards

Capacity strengthening


PRIO

RITY

ARE

AS

Vaccination for health security

Technology transfer platforms

Tools for decision-making

Vaccination for all ages

Vaccines for the elderly

Immunization schedules

Vaccines for diseases of poverty

Target product profiles

Clinical trial design and evaluation

HIV Vaccine Initiative

Table 3. IVR sTRaTegIC MaTRIx WITh seleCTed PRojeCTs*

* A comprehensive list of IVR projects will be established within the WHO core biennial workplan process.

24

As of January 2010, IVR comprised 25 full-timeemployees. Over the course of the Strategic Plan2010–2020, IVRwill remaina small teamworkingeffectivelywithconsultantsandpartnersasneededtoachieveitsgoals.Tothisend,IVRwillcontinuetoholdregularcutting-edgescientificconferences.

4.1 WoRkIng WITh PaRTneRs

Asasmallprogramme,IVR’ssuccessandtheultimateimpactofitsworkwilldependtoaconsiderableextentonassuringconstructiveinterfaceswithglobalresearchefforts.IVR’sfirst10yearsofexperienceshowedthatcollaborationwithpartnerscanbehighlyproductiveifbuiltonthemutualstrengthsofeachconstituent.Withitsstrategicfunctionsclearlydefined,IVR’sinteractionwithpartnersisexpectedtobeevenmoretransparentanditsplanningprocessmoreefficient.

Within WHO, IVR constitutes the unified entity forvaccine researchand thus collaborates closelywithawiderangeofprogrammesatglobalandregionallevels.Forexample,researchonnormsandstandardsforbiologicalsandontranslationalresearchiscarriedoutwithteamsintheWHODepartmentofImmunization,VaccinesandBiologicals.IVR’sleadprojectsrequirestrong alignment with disease control programmesandthosethataddresshealthatdifferentstagesofthelife course. IVRworksparticularly closelywithotherresearch-ledprogrammesofWHOontheprioritizationand coordination of research efforts, aswell as onstrengtheningcapacityindevelopingcountries,notablywithitsconstituentsTDRandUNAIDS.

WithregardtocollaborationoutsidetheOrganization,IVRhasprivilegedinteractionasaWHOprogrammewith governments and governmental institutions,particularlyindevelopingcountries.Inthiscontext,itcanprovideindependentadvicetoMemberStates.Thisrolealsoappliestoitsuniquecontactswithregulatoryentitiesinthedevelopmentofstandards.ItalsoallowsIVR to function as broker or neutral participant indiscussionsofinterestedpartiesandstakeholders.

Productdevelopmentpartnerships(PDPs)haveemergedoverthelastyearsasimportantplayers,andIVRisoftenrepresentedontheiradvisoryboardsasasourceofindependentadviceorasacollaboratorforspecificprojects. IVRwill encourage increasing developingcountryrepresentationintherelevantPDPs.

IVR relies on the technical input and services fromacademiaandWHOcollaboratingcentresinsupportofitsactivities.

Finally,thevaccineindustryisanimportantstakeholderfor IVR. While mostly involved in projects withdeveloping country vaccine manufacturers and thebiotechnologyindustrytobroadenthevaccinesupplybase,IVRalsointeractswithmultinationalmanufacturersalongwell-definedprojects that serve global publichealthneeds.Inthisrespect,IVRsolicitstechnicaladviceanddatafromthevaccineindustryasneeded.

OnemajoravenueforIVRinteractionwiththebroadervaccine research community is theGlobal VaccineResearchForum,convenedbyIVRevery18months;anotheristhroughtheIVRVaccineAdvisoryCommittee,

4. IMPleMenTIng The sTRaTegIC Plan

254. implementing the strategic plan

whichprovidesoverallstrategicandtechnicaladvicetotheInitiative.Itsmembershipcomprisesarangeofpartnersthatrepresentthepublicandprivatesectors:nationalandinternationalresearchinstitutions,donor

anddevelopmentagencies,UnitedNationssisteror-ganizationsaswellasthevaccineindustry.Figure4summarizestheroleandcontributionofIVRwithitsdiverserangeofpartners.

4.2 MonIToRIng and eValuaTIon

In compliancewithWHO’s planning process, two-yearworkplanswillbedevelopedthatsetoutspecificactivities,milestonesandoutcomesforIVR’swork.ThisprocesswillalsousetheWHOresults-basedbudgeting,managementandmonitoringapproach.Itshouldbenotedthat,whiletheIVRStrategicPlan2010–2020focusesonstrategicfunctions,priorityareasandleadprojects,itistheWHObiennialworkplansthatwilloutlinethefulllistanddescriptionofallIVRactivitiesandrelatedresources.

IVR’s priority areas, flagship projects and ongoingactivitieswill be regularlymonitoredand evaluatedtoassesstheircontinuedrelevanceagainstthelatestscientific developments and public health priorities.TheprocessforthedevelopmentofIVRproductsandservicesinvolvesIVAC,SAGEandotherindependentevaluationmechanisms,andthusprovidesthequalityassuranceofIVR'swork.Assessmentsofbothexistingandpotentialprojectswillbebasedoncriteriasuchaswhethertheprojectstandstocontributetoimprovingpublichealth,particularlyindevelopingcountries,and

fIg. 4. IVR InTeRaCTIon WITh key sTakeholdeRs

WHO programmes Outside WHO

vaccine implementation

norms and standards

capacity strengthening

disease control efforts

provision of expertise and membership on advisory bodies

research institutes and governments

standards and clinical guidelines PDPs

research prioritization academia

evaluation of new technologies industry

IVr


whethertheinvolvementofIVRwilladdsignificantvaluetotheproject’sobjectives.

In addition, key performance indicators have beenestablishedtomeasureprogressrelatedtothestrategicfunctions,examplesofwhicharepresentedinTable4.

Aspartofthemonitoringandevaluationexercise,IVRwillperiodicallycarryoutariskmanagementanalysisto screen for threebroad risks: (i) thatoneormoremajorprojects fail; (ii) that IVRbecomes redundant;and(iii) that fundingbecomesinadequatetosustain

the programmeofwork. Regular portfolio reviews,discussionswithIVACandotherstakeholders,andafocusonstrategicfunctionsshouldassurethatIVRinvestsinareasofcomparativeadvantage.

Inaddition,IVRwillstrivetoraisethevisibilityonitsrole invaccineresearch,particularlyon thepositiveimpactitcanhaveonvaccinationpoliciesandvaccineavailabilityinresource-poorcountries.

IVRwillsolicitanexternalevaluationofitsworkatmid-termandattheendofthisStrategicPlan.

Strategic function Indicator Output2008–2009

Expected output 2010–2011

Research priorities Number of target product profiles developed through an IVR-managed process 1 1

Research standards Number of regulatory standards developed based on IVR-sponsored research 1 2

Capacity strengthening Number of developing country vaccine products licensed following technology transfer

facilitated by IVR2 3


Number of SAGE policy recommendations informed by IVR-supported research 4 4

Table 4. seleCTed key PeRfoRManCe IndICaToRs PeR sTRaTegIC funCTIon

27endnotes

endnoTes

1 Global Immunization Vision and Strategy 2006–2015.Geneva,WorldHealthOrganization/NewYork,NY,UnitedNationsChildren’sFund,2005(WHO/IVB/05.05),availableatwww.who.int/vaccines-documents/DocsPDF05/GIVS_Final_EN.pdf.

2 The global burden of disease: 2004 update (2008).Geneva,WorldHealthOrganization,2008.

3 InformationonWHO'sworkonhealth-relatedMillenniumDevelopmentGoalsisavailableatwww.who.int/topics/millennium_development_goals/en.

4 SeeWHOrecommendationsforroutineimmunization–summarytables,availableatwww.who.int/immunization/policy/immunization_tables/en/.

5 Neglected disease research & development: How much are we really spending?Sydney,TheGeorgeInstituteforInternationalHealth,2009,availableatwww.thegeorgeinstitute.org/shadomx/apps/fms/fmsdownload.cfm?file_uuid=409D1EFD-BF15-8C94-E71C-288DE35DD0B2&siteName=iih.

6 ResolutionEB124.R12,availableatwww.who.int/gb/ebwha/pdf_files/EB124/B124_R12-en.pdf.

7 ResolutionWHA61.21,availableatwww.who.int/gb/ebwha/pdf_files/A61/A61_R21-en.pdf.

8 Guidelines for the clinical evaluation of dengue vaccines in endemic areas.Geneva,WorldHealth

Organization,2008(WHO/IVB/08.12),availableatwww.who.int/entity/immunization/documents/WHO_IVB_08.12/en/index.html.

9 Mexico Statement on Health Research,MinisterialSummitonHealthResearch,MexicoCity,16–20November2004,availableatwww.who.int/entity/rpc/summit/agenda/Mexico_Statement-English.pdf.

10 Seehttp://andi.tropika.net/formoreinformationonthenetwork.

11 Bamako Call to Action on Research for Health,GlobalMinisterialForumonResearchforHealth,Bamako,17–19November2008,availableatwww.who.int/rpc/news/BAMAKOCALLTOACTIONFinalNov24.pdf.

12 International health regulations (2005). Second edition.Geneva,WorldHealthOrganization,2008,availableathttp://whqlibdoc.who.int/publications/2008/9789241580410_eng.pdf.

13 InformationontheGlobalOutbreakAlertandResponseNetworkcanbefoundatwww.who.int/csr/outbreaknetwork/en/.

14 Forstatistics,seeCurnsATetal.InfectiousdiseasehospitalizationsamongolderadultsintheUnitedStatesfrom1990through2002,Archives of Internal Medicine,2005,165(21):2514–2520,availableathttp://archinte.ama-assn.org/cgi/reprint/165/21/2514.

The InITIaTIve for vaccIne research

strategic plan 2010–2020

InITIaTIve for vaccIne researchDepartment of Immunization,

vaccines and BiologicalsWorld health organization1211 Geneva 27, switzerlande-mail: [email protected]/IvB/10.02

www.who.int/vaccine_research

Progress in public health depends on innovation. some of the greatest strides forward for health have followed the development and introduction of new medicines and vaccines.

Dr Margaret chan, Director-General of the World health organizationconference on Intellectual Property and Public Policy Issues,

Geneva, 14 July 2009

strategic plan 2010â€“2020 - - world health organization

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