Strengthening regulatory science in academia: STARS, an EU initiative to bridge the translational gap

STARS consortium; Starokozhko, Viktoriia; Kallio, Marko; Kumlin Howell, Åsa; Mäkinen

Salmi, Anna; Andrew-Nielsen, Gunilla; Goldammer, M; Burggraf, Manja; Löbker, Wiebke;

Böhmer, Anne

Published in:

Drug Discovery Today

DOI:

10.1016/j.drudis.2020.10.017

IMPORTANT NOTE: You are advised to consult the publisher's version (publisher's PDF) if you wish to cite from

it. Please check the document version below.

Document Version

Publisher's PDF, also known as Version of record

Publication date:

2021

Link to publication in University of Groningen/UMCG research database

Citation for published version (APA):

STARS consortium, Starokozhko, V., Kallio, M., Kumlin Howell, Å., Mäkinen Salmi, A., Andrew-Nielsen, G.,

Goldammer, M., Burggraf, M., Löbker, W., Böhmer, A., Agricola, E., de Vries, C. S., Pasmooij, A. M. G., &

Mol, P. G. M. (2021). Strengthening regulatory science in academia: STARS, an EU initiative to bridge the

translational gap. Drug Discovery Today, 26(2), 283-288. https://doi.org/10.1016/j.drudis.2020.10.017

Copyright

Other than for strictly personal use, it is not permitted to download or to forward/distribute the text or part of it without the consent of the author(s) and/or copyright holder(s), unless the work is under an open content license (like Creative Commons).

Take-down policy

If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim.

Downloaded from the University of Groningen/UMCG research database (Pure): http://www.rug.nl/research/portal. For technical reasons the number of authors shown on this cover page is limited to 10 maximum.

feature

Strengthening

regulatory

science

in

academia:

STARS,

an

EU

initiative

to

bridge

the

translational

gap

ViktoriiaStarokozhko1,2_,MarkoKallio3_{,ÅsaKumlinHowell}4_{,AnnaMäkinenSalmi}4_,

Gunilla Andrew-Nielsen4, M. Goldammer5, Manja Burggraf6, Wiebke Löbker7, Anne Böhmer7, EleonoraAgricola8,CorinneS.deVries9,AnnaM.G.Pasmooij1andPeterG.M.Mol1,2

,p.mol@cbg-meb.nl,p.g.m.mol@umcg.nlonbehalfoftheSTARSconsortium

Abstract

Truly

disruptive

medicine

innovation

and

new

treatment

paradigms

tend

to

start

in

non-commercial

research

institutions.

However,

the

lack

of

mutual

understanding

between

medicine

developers

and

regulators

when

it

comes

to

medicine

development

significantly

delays

or

even

prevents

the

access

of

patients

to

these

innovations.

Here,

we

outline

what

regulatory-related

barriers

hamper

the

translational

development

of

novel

products

or

new

treatment

paradigms

initiated

in

academia,

and

propose

key

steps

towards

improved

regulatory

dialogue

among

academia,

funding

bodies

and

regulatory

authorities.

Moreover,

we

briefly

describe

how

the

STARS

(Strengthening

Training

of

Academia

in

Regulatory

Science)

project

aims

to

reach

out

to

medicine

innovators

in

academia

to

bridge

the

regulatory

knowledge

gap

and

enhance

this

dialogue

to

facilitate

the

implementation

of

academic

research

findings

in

clinical

practice.

Introduction

Trulydisruptivemedicineinnovationandnew treatmentparadigmstendtostartin non-com-mercialresearchinstitutions[1].Indeed,many importantadvancesinclinicalpractice,suchas precisionmedicine,biomarker-orientedresearch (includingbiomarkervalidation),immunotherapy oradvancedtherapeuticmedicinalproducts, havetheirrootsinacademia[2,3].Inparticular, academiahasakeyroleinfundamentalresearch ondrugdiscoveryanddevelopment[4].

Translatingresearchfindingsintomedicinal productsforclinicalpracticerequires

knowl-edge,skillsandfacilitiesthattypicallyresidein pharmaceuticalcompaniesandnotinpublic researchinstitutes.Suchcompanieshavethe resourcesto,forexample,developaproduct thatcomplieswithqualityandmanufacturing standards,compileadossierthatmeetsall requirementsforregulatoryacceptance,and upscalethemanufacturingprocess.Even thoughsomesuccessfulacademicprojectsfind theirwaytothepatientthroughcollaboration withindustry[1](Yegros,A.etal.‘Research trendsinbigpharma’:https://www.cwts.nl/

blog?article=n-r2s2b4&title=research-trends-in-big-pharma),thebulkofacademia-driven ther-apeuticsinnovationremainsintheearly devel-opmentphaseanddoesnotadvancefurther alongthetranslationalchain[2,5,6].Thisisa resultofvariousfactors.

First,thereisalackofmutualunderstanding betweenmedicinedevelopersandregulators whenitcomestomedicinedevelopmentin clinicalpractice,anditisimportantto under-standhowtonavigatethemedicineregulatory system[2,7–9].InEurope,thissystemincludes researchgovernance,regulatoryandlegislative requirementsatthelocal,regional,national

Features

PERSPECTIVE

(withinthe27memberstates)andEuropean levels.Developmentsinregulatoryscienceare helpingtoovercomesomeofthesefactors.

Second,otherfactorsplayarole,suchas reproducibilityandreliability,whichcanhamper therecognitionandutilizationofacademic re-searchfindings.Ininnovativebasicand non-clinicaldrugresearch,thereislessemphasison qualitycontrolandtheimplementationofbest practices(goodmanufacturingorgood labo-ratorypractices),whichcanresultinafailureto attractprivateinvestors,andleadtothe pre-maturediscontinuationofprojectsand unnec-essaryrepetitionofstudiesafterpharmaceutical companiesacquiretheproduct[8,10–12].

Otherareasofmedicinedevelopment,suchas drugrepurposing,wherebyapproveddrugsare usedfornewindications,arepredominantly carriedoutbyacademicresearcherswho,by beingindirectcontactwithpatients,areina goodpositiontospotnewpossibilitiesindrug use[13].Andeventhoughsuchresearchaids thedevelopmentofbestpracticeandtreatment guidelines,itrarelyleadstothelicenced indi-cationofaproduct.Thisis,however,oftendue todistinctlegalandcommercialissues[14,15]. Translationalgapbetweenacademic innovationsandpatienttreatment:anEU regulator’sperspective

Collectively,thereisoftenagapbetween aca-demicdrugR&Dandthetranslationofstudy

resultsintoclinicalpracticeandpatientcare[16]. ThisarticleintroducestheEU-fundedproject CoordinationandSupportActionon Strength-eningTrainingofAcademiainRegulatoryScience (CSASTARS,https://www.csa-stars.eu/),a collab-orationbetween18EuropeanNational Compe-tentAuthorities(NCAs),fourassociatecountries andtheEuropeanMedicinesAgency(EMA).The projectaimstoreachouttomedicineinnovators inacademiatobridgetheregulatoryknowledge gapandenhancethedialoguebetween acade-miaandregulatoryauthoritiesbymeansof,for example,scientificadvice,qualificationadvice andbidirectionalknowledgeexchange(Fig.1).

Aspartoftheproject,fouronline surveystudies arebeingperformedintheEU,whichhave re-ceivedresponsesfrom40fundingbodies,88 academicinstitutes,449academicresearchers and21regulatoryagencies.Onthebasisofthe resultsofthesestudies,aninventorywillbemade ofexistingsupportactivities,andpilotsupport activitieswillbeinitiatedtoclosethegapsin regulatoryknowledgeandsupport.Further,the STARSconsortiumenvisionsthedevelopmentof curriculafortrainingandeducationinregulatory knowledge,requirementsandaffairs.Buildinga harmonizedcurriculumwillhelptoensurethat relevantscientificprofessionsthroughoutEurope haveaccesstoregulatoryknowledge.Allofthese activitieswillbesupportedbythevarious com-municationanddisseminationstrategies orga-nizedbytheSTARSconsortium.

Communicationframeworkanditsgaps Althoughsomeunderstandingexistsbetween regulatorsandmedicineinnovatorsinacademia regardinghowtobringdisruptivemedicine innovationstothemarket,novelapproachesare neededtodealwithsomeofthechallengesin applyingthecurrentlegislativeframeworkto thetypeofmedicinesbeingdevelopedtoday. Withthisinmind,theSTARSconsortiumseeksto betterunderstandwhatregulatory-related bar-riershamperthetranslationaldevelopmentof novelproductsornewtreatmentparadigms initiatedinacademia.Oneaim,therefore,isto enhancecommunicationbetweendifferent stakeholders,usingamulti-prongedapproach.

Thecommunicationframeworkpresentedin

Fig.2outlinestheinformationflowbetween differentstakeholdersintheregulatorysystem. Regulatoryagenciesarekeyplayersthatactas licensingandsupervisoryauthoritiesatnational (NCAs)orEuropean(EMA)levels,andgenerate andconveyguidanceonhowtodesign suc-cessfuldrug-developmentprogrammesusing specificchannelstoreachthemainstakeholders inacademia:namely,universitymedicalcentres andhospitals.Otherkeystakeholdersinclude researchinstitutes,individualresearchers workingindrugR&D,andthepublicandprivate fundingbodiessupportingtheseresearch ac-tivities.

Theinformationprovidedbytheregulatory authoritiestoinnovatorsisbasedonyearsof

Drug Discovery Today

FIGURE1

MaingoalsoftheSTARSproject,inwhich18Europeannationalcompetentauthorities(NCAs),fourassociatecountriesandtheEuropeanMedicinesAgency (EMA)areinvolved.

284 www.drugdiscoverytoday.com

Features



experienceintheassessmentofclinicaland non-clinicalproductdevelopmentdossiersand productlifecycles,includingthe post-authori-sationphase.Regulatoryauthoritiesprovide informationaboutregulatorystrategies, requirementsandguidelinesthatcoverareasof pharmaceuticalandmedicalR&D(regulatory content),aswellasscientificsupporton manufacturing,formulations,protocol devel-opmentandclinical-trialdesign(scientific con-tent).Moreover,inputcanbeprovidedby relevantnationalandEuropeanpublic stake-holders,suchaspatientandhealth-care pro-fessionalrepresentatives,and

health-technologyassessmentbodies(clinicaland so-cietalcontent).

Regulatoryauthoritiesusevariouschannelsto reachdrugdevelopersandclinicalinvestigators. Webportalsdirectacademicresearchersand fundingbodiestokeydrug-development guidelines,whereasface-to-facemeetingsat nationalandEuropeanlevelslendthemselvesto theprovisionofmorespecificdialogue. Exam-plesofthelatterincludemeetingswiththe InnovationTaskForce(https://www.ema. europa.eu/en/human-regulatory/

research-development/innovation-medicines) asanearlyexchangeplatform;thequalification ofnovelmethodologies(https://www.ema. europa.eu/en/human-regulatory/research- development/scientific-advice-protocol-

assistance/qualification-novel-methodologies-medicine-development)toobtainregulatory opinionontheacceptabilityofnewconceptsin measuringtheeffectsofmedicines,suchas patient-reportedoutcomesorbiomarkersfor specificuses;scientificadviceregardingclinical developmentplans;andthePRIMEprocedure ( https://www.ema.europa.eu/en/human- regulatory/research-development/prime-priority-medicines)tostimulatethe develop-mentofdrugsthatcouldbepotentialgame changersinareasofunmetneed.Last, regula-toryauthoritiesarepresentatscientific confer-ences,andtheycanoffervarioussupport activitiessuchastrainingprogrammes, work-shopsandstakeholdermeetings.

Theaimofthisdialoguewithregulatory au-thoritiesistohelpensureahigh-qualityclinical developmentdossierandthusregulatory ac-ceptabilityofthedesignofnon-clinicaland clinicalstudieswhenstakeholdersapplyfor marketingauthorisation.Thisshouldincreasethe scientificandsocietaloutputofinvestedfunding, ultimatelyleadingtomoresuccessful drug-de-velopmentprogrammesthatresultinthe ap-provalandimplementationofacademicresearch findingsinclinicalpractice.Importantly,the communicationbetweenregulatoryauthorities andrecipientsisbidirectional;forexample, in-novativestudiesandfindingsmightstimulatethe modificationofregulatoryrequirements.

Onthebasisoftheliterature,thepreliminary resultsofthesurveystudiesandongoing

knowledge-sharingactivitiesintheSTARS project,wehaveidentifiedseveralgapsinthis regulatorycommunicationframework,the bridgingofwhichmighthelptoimprovethe publichealthimpactofacademicresearch.First ofall,academicresearchersarelessawarethan thepharmaceuticalindustryofthesupporttools providedatnationalandEuropeanlevelsby regulatoryauthorities.Thismightindicatethat themediachannelsandtoolscurrentlyusedby regulatoryauthoritiestoreachoutto

researchersareinadequate,oftenbeingtoo slowortoorigid(gapA,Fig.2).Also,thereislack ofawarenessandknowledgeofregulatory requirementsandtheirrelevancetotheworkof academicresearchersandfundingbodies(gap B,Fig.2).Academicresearchersmightperceive regulatorysupportasbeingsomething exclu-sivelyforindustryorfordrugdeveloperswho arealreadyinanadvancedphaseofdrug de-velopment.Thislackofattentiontoregulatory orethicalissues,however,mightlatermake regulatoryauthoritiesreluctanttoaccept find-ings[8,11]ormightbedetrimentalwhen attemptingtoattractinvestors.

Anotherimportantgapisthelimited collab-orationonregulatoryrequirementsand guide-linesbetweenacademicresearchersand regulatoryagencies,whichleadstothesebodies notbeingintunewithemergingresearch paradigms[2](gapC,Fig.2).Thislimited col-laborationis,forexample,reflectedbythefact

Regulators

Content

Media

Academia

Funding

bodies

Effect

Drug Discovery Today

FIGURE2

Informationflowandidentifiedgapsintheregulatorycommunicationframework.

Features

thatacademicgroups,incontrasttothe phar-maceuticalindustry,arenotdirectlyinvolvedin thedraftingofEuropean(EMA)andglobal regulatoryguidelines[i.e.,theInternational ConferenceonHarmonisationofTechnical RequirementsforRegistrationof Pharmaceuti-calsforHumanUse(ICH,https://www.ich.org/)]. Academicgroupscanoftenonlycontributetoa guidelinewhenitisopenforpublic consulta-tion.Also,regulatoryauthoritiesbenefitfrom collaborationwithacademiaandfundingbodies bylearningaboutinnovativedevelopmentsand methodologiescreatedbyacademicresearchers thatoftenrequireanindividuallytailored ap-proachandcertainflexibility(gapD,Fig.2). Changingthemindset

Stakeholders(academicresearchers,regulatory authoritiesandfundingbodies)needtochange theirmindsetandattitudestohelpensurethe maximumimpactofinnovative-medicine re-search.Theyneedtobecomeawareofthe currentgapinregulatoryknowledgeand im-plementappropriatesolutions.Keyaspectsare summarizedbelowandinTable1.

Open-minded

dialogue

Itisimportanttorealizethattheinformation flowpresentedinFig.2isbidirectional. Regu-latoryauthoritiesneedinputfromacademiato gainknowledgeoninnovativetechnologies (andtopotentiallyalignregulatoryacceptance withevolvingdevelopments),toaddressthe achievementsmadebyresearchersandtowork togetheronjointsolutions.Conversely, aca-demicgroupsandlearnedsocietiesneedto becomemoreinvolvedinpolicy-makingand guidelinedevelopment.Ingeneral,researchers andregulatorsshouldbeincommunication

fromthestartofaprojecttoensurethatlater developmentplansarefeasibleandtocreatea win-winsituationforallparties[17].

Althoughregulatoryrequirementsandrules servetoharmonizethedrug-development processandtoguaranteethequality,efficacy andsafetyofmedicinalproducts,a more-tai-loredapproachmightbeneededincertain settingstoaddressthedifferentneedsofthe variouspartiesinvolved.Agoodexampleofan adaptedandtime-savingapproachthat regu-latorscanapplyinexceptionalsituationsisthe currenteffortofNCAsandtheEMAinproviding advicetoacademiaandthepharmaceutical industryontheCOVID-19pandemic(Box1).

Closing

the

gap

between

research

and

regulation

Althoughthevalueofregulatorysciencecanbe especiallyrelevanttoappliedortranslational science,basicfundamentalresearchis increas-inglybeingaffectedbyhigherdemandsfor

transparencyandevidenceofscientificintegrity. Anearlyexchangeofinformationcanhelpto highlighttheregulatoryissuesthatarerelevant tothefurtherdevelopmentofaproduct.This mightresultinaslightshiftinresearchfocus, butatthesametimeitmightmaketheproject moreappealingtoventurecapitalists(funding) andindustry(collaboration),andbringthe productmoreswiftlytothepatient[9,18].Inany case,itiscrucialnottomisstherighttimeto startfocusingonthetranslationoftheproduct orfindingstoclinicalpractice.Itisimportantto realizethatgoodstudyresultsalonedonot implythatthefindingscanbeimplementedin health-carepractice[19].Additionalstepsare neededtoensurethatpatientsand/orthe publicbenefitfromthenewproductor tech-nology.

Trainingbasic,appliedandclinicalscientistsin regulatoryaffairsisimportant[18].Further,itis crucialtofosterandbuildupanetworkof trainedlocalrepresentativeunitsandsupport

-Activelyencouragedialoguebetweenacademicsandregulatorstohelpensuremaximumimpactoftheresearch -Interestinamore-definedpublicimpactoffundedresearchprojects

-Rewardprojectsthatareofhighpublicimpactindependentlyoftheirnovelty(i.e.,projectsthatinvolvepaediatric formulations,newdosingregimentsornewtreatmentcombinations)

Regulatoryagencies -Activedialogueversusone-waycommunication -Open-mindedcommunication

-Continuouslearningaboutupcominginnovativetherapiesthroughknowledgeexchangewithacademia(i.e.,invitedlectures andconferenceattendance)

-Timelyalignmentofregulatoryrequirementswithevolvingdevelopments -Involveacademiainguidelinedevelopment

BOX1

EU

regulators

and

scientific

advice

during

the

COVID-19

pandemic

Regulatorshavesteppeduptheireffortstoprovideadvicetoacademic-and industry-driveninitiativestostudymedicinalproductsthatmightbebeneficialtopatientsinfected withCOVID-19(seeEMAresponsetoCOVID-19:https://www.ema.europa.eu/en/

human-regulatory/overview/public-health-threats/coronavirus-disease-covid-19).

Regulatorshavesetupteamstorapidlyprovideclinicalinvestigatorswithpracticaladvice onhowbesttoorganizetheirstudies.Theemphasisisonexpeditedreview,withanopen viewtonoveldesigns,suchasfactorialdesignstudiesandsharingplacebocontrol.Intimes ofapandemic,itisclearthatregulatorsandresearchersshouldadapttotheclinical situation,butatthesametimetheyshouldsafeguardkeyresearchprinciplestoensurethat lessonsarelearnedandthattheevidencegeneratedisreliable.DerekAnguspublishedhis pleaof‘Optimisingthetrade-offbetweenlearninganddoinginapandemic’on30March 2020attheheightoftheCOVID-19crisis[25].TheSTARSprojectaimstostimulatetailored accesstoscientificadvicebothduringandafterthepandemic,withtheaimofaccelerating accesstotreatmentsthatmattertopatients.

286 www.drugdiscoverytoday.com

Features



officesinacademicclinicalresearchcentresnot onlytocreateawarenessoftheimportanceof regulatoryrequirementsatastafflevel,butalso tofunctionasapointofcontactforNCAsto communicatewithacademia.

Change

in

the

reward

system

in

academic

research

Tochangevaluesintheexistingsystem,itis importanttounderstandwhatmotivatesthe differentstakeholders.Despitesmallpositive changes,thereiscurrentlynotalwaysaclear incentiveforacademicappliedortranslational researcherstocomplywithregulatory require-ments.Althoughacademicresearchdoesstrive totargetpublicneedsandbenefitpatients,the academiccommunitystilloftenseespublishing inscientificjournalsorpresentingresultsat scientificmeetingsasthemainindicatorsof success[11].Thesystemshouldmovebeyond this,andshifttowardseffortstotranslate re-searchfindingstoclinicalpractice.

Fundingbodiescouldplayanimportantpart inpromotingregulatoryscienceinacademic researchbyadaptingtheirfundingpracticesand requirements.Currently,Europeanfunding bodiesseemtohaveadjustedtheirfunding strategiestoincludemoretranslationalprojects ofclearerbenefittosocietyandpatients[2](i.e., theSeventhFrameworkProgramofthe Euro-peanUnion,Horizon2020,continuingintothe plansforHorizonEurope).However,callsfor clearerbenefitsandthetailoringof corre-spondingtopicsarenotsufficientby them-selves.Thus,regulatoryandfundingbodies shouldscrutinizegrantproposalsintheareaof appliedandtranslationalresearchforthe adoptionofbestpractices(qualitycontroland goodlaboratory,manufacturingandclinical practices).Theyshouldalsorequestthat scien-tistsseekregulatorydialogueinadvanceof grantsubmissionandduringtheresearch project,therebyenhancingthechancethatthe projectwillbeasuccessandthefindingscanbe translatedintoclinicalpractice.

Itisalsoimportanttorecognizethatsome academia-drivenhealthresearchprojects,suchas thoseinvestigatingbetterdosingregimensand treatmentcombinationsorthosedeveloping paediatricformulations,mightseemtobe ‘un-attractive’fromaninnovationperspective,butare ofhighsocietalrelevance.Here,abetter under-standingoftheregulatoryframeworkmightbeof benefittoacademia:forexample,the paediatric-usemarketingauthorizationoffersa10-year pe-riodofdataandmarketprotectionforpaediatric formulationsthataredevelopedspecificallyfor children.Thisappliestopreviouslyauthorised

productsthatarenolongerprotectedbyapatent orsupplementaryprotectioncertificate(see ‘Rewardsandincentivesforpaediatricmedicines’, EMAwebsite:https://www.ema.europa.eu/en/ human-regulatory/research-development/ paediatric-medicines/rewards-incentives-paediatric-medicines).

STARS:

an

EU

way

to

tackle

old

problems?

Thegapbetween(academic)inventionsand productshasledtoanumberofinitiativesacross theglobetoaddressthischallenge.For exam-ple,intheEU,suchinitiativesincludethe In-novativeMedicinesInitiative(https://www.imi. europa.eu/),SafeandTimelyAccessto Medi-cinesforPatients(https://ec.europa.eu/health/ documents/pharmaceutical-committee/ stamp_en),DrugsforNeglectedDiseases Ini-tiative(https://www.dndi.org/),theEuropean ClinicalResearchInfrastructureNetwork(https:// www.ecrin.org/),theEuropeaninitiativeto boosttranslationalbiomedicalresearch[20],EU InnovationNetworkinitiatives,andvarious otherongoinginitiativesfromtheEMAand NCAs[21].Alloftheseinitiativesaimtoprovide essentialknowledgeandtoolsforbringingideas tothepatient.TheEMAalsoofferssomespecific instrumentstostimulateacademic develop-ments,suchasprovidinganearlierentrypoint intothePRIMEschemeforacademicresearch groupsorsmallandmedium-sizedenterprises (SMEs)byacceptingapplicationsbasedon promisingnon-clinicaldataandfirst-in-human tolerabilitydata[22],andtheEMAhas intro-ducedafeewaiverforacademiaforscientific advicefororphanmedicines.Suchinitiativesare notlimitedtotheEU:forexample,following publicationin2012ofthereporton‘Propelling InnovationinDrugDiscovery,Developmentand Evaluation’intheUnitedStates[23,24],several initiativeshavebeenlaunchedtoincreasethe returnsofbasicresearchandtoacceleratedrug discoveries(e.g.,theCriticalPathInitiative,

https://www.fda.gov/science-research/ science-and-research-special-topics/

critical-path-initiative;SPARKinitiative,https:// sparkmed.stanford.edu/;andScienceand TechnologyResearchInfrastructurefor Discov-ery,Experimentation,andSustainability Initia-tive,https://datascience.nih.gov/strides).

However,itisclearthatcurrenteffortsand existingexamplesofcooperationdonot suffi-cientlyaddresstheregulatorychallengesalong thetranslationalchain[17].TheEMA‘Regulatory Scienceto2025’strategicpaperstressesthe needforcollaborationbetweenacademiaand regulatoryauthoritiestoensureearly-career

trainingofresearchersinregulatoryscience,to addressnewtrendsindrugdevelopmentandto ensurethetranslationofacademicresearchinto newdrugproductsorregulatorytools[17]. Throughfurtherimplementationofregulatory scienceinacademicdrugresearch,theSTARS consortiumaimstohelpimprovetheefficiency ofdrug-developmentprocessesandprovide benefitstopatientsbystrengtheningthe dia-loguebetweenacademiaandregulatory au-thorities.

Giventheuniversalandmultifactorialnature ofthegapsinthecurrentinteractionbetween regulatoryauthoritiesandacademia,itisclear thataharmonizedapproachisneededto strengthenregulatoryscience,improvethe regulatoryenvironmentandincreasesupport forthisapproach.Consistingof18EUregulatory agencies,theSTARSnetworkisequippedto contributetotheharmonizationofregulatory supportataEuropeanlevel.Thiscoordinated approachwillassistinbringingacademia, fundingbodies,regulatoryauthoritiesandother stakeholdersclosertogether.Itwillpromotethe sounddevelopmentofnewproductsand shortenthetimebetweendevelopmentand approval.Theprojectisexpectedtostimulatea bidirectionalknowledgeexchangebetween academiaandregulatorsbypromotingscientific adviceofferedbyvariousNCAsandtheEMA;by developingacurriculumonregulatoryscience foracademics;bypromotingtheeducationof regulatorsbyacademicresearchersonmodern therapeuticdevelopments;andbyopeninga dialogueonregulatorypracticesandguidance thatarenotconducivetonewscientific devel-opments.

Importantly,theinformationandanalysis providedbySTARSwillformthebasisforother activitiesaimedatimprovingthemutual un-derstandingofregulatoryrequirementsand strengtheningacademicresearchinEurope.The goalisthatthiswillresultinamore-efficientand fasterdrug-developmentprocess,ahigher numberofsuccessfulprojectsandgreater sci-entificandpublicimpactofacademia-driven healthresearch,therebyacceleratingthe translationofresearchfindingsintoapproved drugsanddiagnosticsforthebenefitofpatients andhealthcareingeneral.

Acknowledgements

TheSTARSprojectisfundedbyHorizon2020 (grantagreement825881).OtherSTARS membersoftheWorkPackage5andSteering CommitteeincludeW.Ballensiefen,P. Schumann,T.Bodea,V.Imre,B.Pál-Szenthe,C. HernándesGarcía,B.Ziegele,E.Heinonen,P.Inki,

Features

effortsreceivingmorerecognitionwithdeclining industryefficiency? Expert Opin.DrugDiscov.14,605–607

2 deWilde,S.etal.(2016)Developmentofcelltherapy medicinalproductsbyacademicinstitutes.Drug Discov.Today21,1206–1212

3 Sampat,B.N.andLichtenberg,F.R.(2011)Whatarethe respectiverolesofthepublicandprivatesectorsin pharmaceuticalinnovation?HealthAff.30,332–339

4 Cleary,E.G.etal.(2020)GovernmentastheFirstInvestor inBiopharmaceuticalInnovation:EvidenceFromNew DrugApprovals2010–2019.InstituteforNewEconomic Thinking

5 Sanami,M.etal.(2017)Translatinghealthcare

innovationfromacademiatoindustry.Adv.Mech.Eng.

9.http://dx.doi.org/10.1177/1687814017694114

6 Cowling,B.S.andThielemans,L.(2019)Translational medicineinneuromusculardisorders:fromacademia toindustry.Dis.ModelMech.13 dmm041434

7 Gilliland,C.T.etal.(2016)Puttingtranslationalscience ontoaglobalstage.Nat.Rev.DrugDiscov.15,217–218

8 Parrish,M.C.etal.(2019)Survivinginthevalleyof death:opportunitiesandchallengesintranslating academicdrugdiscoveries.Annu.Rev.Pharmacol. Toxicol.59,405–421

9 Raths,S.etal.(2020)Mindthegap!Asurveyofthe challengesofbiomarkercommercializationDrug Discov.Today25,22–26

10Prinz,F.etal.(2011)Believeitornot:howmuchcanwe relyonpublisheddataonpotentialdrugtargets?Nat. Rev.DrugDiscov.10,712

11Higham,R.(2019)Imaginingthefutureofcell therapies:clinicaltrials,innovationandtheintersection

Discov.18,41–58

15Breckenridge,A.andJacob,R.(2019)Overcomingthe legalandregulatorybarrierstodrugrepurposing.Nat. Rev.DrugDiscov.18,1–2

16Clancy,C.M.etal.(2012)Fromresearchtohealthpolicy impact.HealthServ.Res.47,337–343

17EuropeanMedicinesAgency(2020)EMARegulatory Scienceto2025:StrategicReflection.European MedicinesAgency

18Mochly-Rosen,D.andGrimes,K.,eds(2014)APractical GuidetoDrugDevelopmentinAcademia,Springer InternationalPublishing

19Mohs,R.C.andGreig,N.H.(2017)Drugdiscoveryand development:roleofbasicbiologicalresearch. AlzheimersDement.11,651–657

20vanDongen,G.A.etal.(2013)EATRIS,aEuropean initiativetoboosttranslationalbiomedicalresearch. Am.J.Nucl.Med.Mol.Imaging3,166–174

21Ussi,A.andMigliaccio,G.(2016)TheEMAFramework ofCollaborationWithAcademicStakeholders.Mol. Ther.24,1883–1884

22Mullard,A.(2017)PRIMEtimeattheEMA.Nat.Rev.Drug Discov.16,226–228

23President’sCouncilofAdvisorsonScienceand Technology(2012)ReporttothePresidentonPropelling InnovationinDrugDiscovery,Development,and Evaluation.ExecutiveOfficeofthePresidentofthe UnitedStates

24Woodcock,J.(2013)ThePCASTReporton PharmaceuticalInnovation:ImplicationsfortheFDA. Clin.Pharmacol.Ther.94,297–300

ManjaBurggraf6 WiebkeLöbker7 AnneBöhmer7 EleonoraAgricola8 CorinneS.deVries9 AnnaM.G.Pasmooij1 PeterG.M.Mol1,2,*

onbehalfoftheSTARSconsortium1_Medicines EvaluationBoard,Utrecht,TheNetherlands 2

DepartmentofClinicalPharmacyand Pharma-cology,UniversityMedicalCenterGroningen, Uni-versityofGroningen,Groningen,TheNetherlands 3

FinnishMedicinesAgency,Helsinki,Finland 4

Swedish Medical Products Agency, Uppsala, Sweden

5

Division of Immunology, Paul EhrlichInstitute, Langen,Germany

6_{DivisionMajorPolicyIssues,Coordination,Paul} EhrlichInstitute,Langen,Germany

7

FederalInstituteforDrugsandMedicalDevices, Bonn,Germany

8

ItalianMedicinesAgency,Rome,Italy 9

European Medicines Agency, Amsterdam, The Netherlands *Correspondingauthor. 288 www.drugdiscoverytoday.com Features  PERSPECTIVE