TOPRA 2025

Regulatory professionals are striving to meet these challenges and adapt against a backdrop of constant change. TOPRA acts as a conduit to help regulatory scientists to explore, consider, discuss and share potential solutions and best practices – always with the benefit of the patient in mind. Innovation and impact summits

Each year leading regulatory professionals and interested stakeholders gather together at the TOPRA Summit to focus on issues affecting regulatory science at a top level from a multidisciplinary perspective. Discussions are wide-ranging and the ideas are distilled into reflection papers that are then sharedmore widely. Topics debated include: challenges to the regulatory paradigm and increasing the sustainability of medicines development; the importance of regulatory convergence in improving access to healthcare; the impact of disruptive technologies, using digital technologies to validate and gather health data; and the collection and analysis of digital data in real time to support better regulatory decision-making. The establishment of an Innovation Advisory Group – tasked with horizon scanning for technological and procedural advances as potential short, medium and long-term disruptors of established regulatory practice – will enable us to remain abreast of

ARTIFICIAL INTELLIGENCE FEATURE

Forsome time now,bigpharma hasbeen

adeviceasa consistentlyperforming system, manyAI systemswithalgorithms thatevolve and sharpenon theirownarealready in development. The FDAhasclearedmedicaldevices that relyonAIalgorithms for themarket,but so far, theagencyhaspassedonlydeviceswith “lockedalgorithms”— those that remain the sameuntil theyareactivelyupdatedby the manufacturer. Withmany futureAIapplications, the

time togetprepared.As innovationprogresses, sowill thedemandson regulatoryaffairs,and particularly initially thosewithin themedical technology sector. AIwithinmedtech lifesciences AIhit theheadlines in theUK in summer2019 when itwasannounced that£250mwillbe spentonboosting the roleofAI in thenational health service (NHS). 2 UKHealthSecretaryMatt Hancockstated thatAIhadenormouspower to improve care, save livesandensuredoctors hadmore time to spendwithpatients.Emerging technologiesareplayingakey roleacross the value chain, fromdrugdiscovery through to patientcare.

preparing for the AI revolutionand manyareeither in collaborationwith, orhaveacquisition

FEATURE ARTIFICIAL INTELLIGENCE

Potential impactofAIon regulatory affairsmedical technology roles

of,emerging technologies

accuracyofoutput informationwillcontinually improveasusage increases.Thiswillproducea perpetuallydynamic systembydesign.Without anyprior technicalknowledge, itwillbehard fora regulator toassess the safetyandefficacy ofaproduct.Notonlywill regulatoryaffairs leadersneed tounderstand the concept fully, theywillneed tobeable toexplain itaccurately to the regulatorybodies.As such,an increasing levelof technological literacywillundoubtedly becomea core competency for regulatory affairsprofessionals in the future. However thatdoesnotmean regulatoryprofessionalswillhave

intervention.AI isanemerging technology that isbeingexplored inevery facetof pharma, fromdrugdevelopment todiagnosis

A rtificial intelligence (AI) is rapidly emergingwithin thepharmaceutical industryand is likely to transform themedicinal technology environment in the imminent future. Although suchadvancesarewidelywelcomed – since theywillultimately improvepatient outcomes– it isnotyetunderstoodhow they willaffect thevarious teamsacross thedrug pipeline, including regulatoryaffairs. It isclear thatadvances inAIwillbringnew challenges

andevenpatientcare.Theglobalmarket forhealthcareAI solutions isexpected to increase froma reportedUS$1bn in2017 to more than$34bnby2025. 1 Over thepast 12 months, thepacehasgatheredconsiderably, withvarious “fast-tracked” FDAapprovalsof AI-based technologies, further cross-industry collaborations,and raised interest from investors.New technologies,newpartnerships andnew ideasarebeing reported in the mediadailyand,although thesearewelcome developmentswith clearbenefits,what is lessunderstood ishowmachine learningand automationwillaffect traditional roleswithin pharmaand life sciences, including regulatory affairs. AI is thereforegeneratingbothexcitement andadegreeofuncertaintyacross the life sciences industry.Despitebeing yearsaway frommaking itsgreatest impacts,now is the

For some timenow,bigpharmahasbeen preparing for theAI revolutionandmany areeither in collaborationwith,orhave

Advances in artificial intelligencewillbringnew challengesanddemand new skillsets. In this article, insightsare shared from companiesand candidates in regulatory affairs,particularlywithin themedical technology sector

acquisitionof,emerging technologies.There areanumberofways inwhichAI isbeing–or willbe–usedand the scaleandbreadthof potentialapplications isastounding.There is scopeateach stageof thedrug lifecycle, from discovery through to researchandanalytics, and,most interestinglyofall, improved outcomes forpatients. Forexample,BioMind’s artificial intelligencemedical systemwas able tooutsmarthumanexperts inpredicting theexpansionofbrainhaematomas,making correctdiagnoses in87%of225 cases in

tobecomeexperts insoftware developmentandcybersecurity themselves.Thekey isa multidisciplinaryapproach thatbuilds relationshipswith peoplewhoareexpertsbut whomaynotbebestsuited to navigatingcomplex regulatory challenges,andpossessing sufficientknowledge to beable toask the right questionsandknowwhere

anddemandanew setof skills,butwhat is lessobvious isexactlyhow specific roleswill beaffected. In thisarticle, insightsare shared frombothhiring companiesandcandidates in regulatoryaffairs,particularlywithin themedical technology sector. The riseofAI Artificial intelligence (AI)within life sciences refers to the systemof interconnectedand automated technologieswhich can function autonomously,with littleornohuman

AKEELHUSSAIN , RegulatoryAffairsRecruiter, Talentmark,UK

about 15minutes,versus66%accuracy in30 minutesbya teamof 15doctors. 3 Currently,a wearabledevice thatusesmachine learning to remotely trackandanalysemultiplevital signs hasbeen clearedby theUSFDA,expanding the scopeofhomemonitoring systemswhich willhelp tokeepmore chronically illpatients outof thehospital.MayoClinicphysicians andengineersaredevelopingAI foravariety ofclinicaluses, suchas screeningpatients forearly signsofheartdiseaseandwarning peoplewithepilepsyaboutoncoming seizures. ElonMusk’sNeuralink 4 isdevelopingabrain implantwhich theyhopewill read thebrainsof paralysedpatients.Theoutcomesof theseand similardevelopmentscouldbe far-reachingand evenhelp todiagnosepatientswith “hidden” symptoms. Impacton regulatoryaffairs

theyneedspecialistassistance. Regulatoryprofessionalswill need toexpand theirnetworks to include technicalexperts inawide rangeoffields. Increasingly,muchof this expertisewillbe foundvia

Transparency iskey ina regulatoryenvironment duringassessment, yetmostAIapplicationsare a “blackbox”, lacking clarityandencompassing agamutofcomplexities.AIapplicationscan producevalidconclusions thatare counter- intuitive to thosewhichhuman teamsmay derive.Comparedwitha standardmedical device,whereby regulators reviewandclear

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FALKEHMANN , Chairof theEuropeanMedicinesAgency’s InnovationTaskForce (ITF) ,describeshis role, theachievementsandchallengesof the task force,andprovides tipsandadvice toorganisations

www.topra.org

www.topra.org I t is easy for us to focus on the immediate history of innovation in medicine. Indeed,wewouldguess that, ifasked todescribe thefirst truly novelapproach topatientcare,anyoneworking in regulatoryaffairs today would generally only think back around 30–40 years. However, innovation is a progressive path, and one which builds up as new technologies develop.Would James Blundell, who performed the first recorded human blood transfusion back in 1818, ever have imaginedwe would see a time ensure thatwekeeppacewith currentdevelopment,and ensure consistentcontactwith stakeholders throughmeetings, workshops,andcommentonupcomingguidance.Wehave to listen, takenoteof innovationandassess the impactof the challenges theymaypresent fordevelopersand theexisting regulatory system. It is the stakeholders (academia, researchand developmentcentres,andcompanies) thatbring innovation to theagency,andwe currentlydealwitharound80 requestsper year.The ITFhas toassesswhat’s importantand this involves both internalandexternaldialogue throughout itsnetwork, so weworkwith regulatoryagenciesacrossEuropeandwith the24 national innovationoffices to createa collaborativeenvironment thatenablesus to improve thedetection rate for innovation.At theendofNovember2019, theEMAheldaworkshopon the regulatory science strategy to2025 (seep15)andakeymessage thatemerged from thatmeetingwas thatweneed to facilitate innovation in theEUproactively, so thiswillbeakey focusover thenextfive years. Q: Howcan industrycontribute toknowledgesharingwith regard to innovation? A: Wemustnot forget that innovation isnot justan industry activity, theEMAalsohasastakeholderdivisionand liaiseswithpatientgroups,academicgroups,healthcare professionals, individualsandotherparties. I think thereare two recommendationsonknowledgesharing:firstly,weneed toencouragedevelopers tobringnoveldevelopments toEMA ora local innovationofficeassoonaspossibleand regardless ofdevelopmentstage.Secondly,weneed toencouragevarious stakeholders tocommentonEMAdocumentssuchasdraft guidanceandattendworkshops.TheEMAalso tries tocollect informationviabusinesspartnermeetings,andundertakeshorizon scanning to lookatwhatmightbe landingonourdoorstep in the nextfive to tenyears.We likedevelopers tobeproactive. In thepast two years, theEMAhasestablisheda research anddevelopment stakeholderplatformwhere itcollaborateson different topics, suchas theEUMedicalDeviceRegulation.This providesagoodopportunity toengagebut,again,weencourage early interactions.Weknow thatearlydialogue,especially through scientificadvice, increases the chancesofa successful marketingauthorisationapplication. Q: Howdoes the ITFensurediscussionson innovative medicinesand technologieswithstakeholdersareshared within thedifferentgroupsat theEMA togeneratenew guidelinesorcontribute to revisionsof the regulatory paradigm? A: Ibelievenetworkingandcollaborationareextremely important, in linewith theoldChineseproverb: “Ifyouwant to go fast,goalone; ifyouwant togo further,go together”.The ITF’smain task iscollaborationand the sharingof information within theagencyandwith the innovationnetwork.Wehave theCommittee forHumanMedicinalProducts (CHMP)monthly meetings inwhichwe shareall requests the ITFhas received andassesshowvaluable these requestsare,what impact they haveandhow canwebest facilitate this information.Once this hasbeen identified,we target specificcommitteesandworking parties thathave the tailoredexpertise tohelpwith requests to the ITF fromapplicants.We circulateallnew relevant topics to

the innovationnetwork for considerationandwill furtherengage with thenetworkviaactivities suchaswebinars,meetings,or workshops.Minutesofmeetingsarealways sharedwith the CHMP, theEMA’sother committees,workingparties,expertsand attendees. It is important to remember that fullconfidentiality is guaranteedduring thisprocess. Regardingnewguidelinesor reflectionpapers,we takea cautiousapproach,because it’s important thatnewguidelines arenot so restrictiveas toprevent innovation.Weask three questions:does somethingneed tobedone,how canwebestdo it,andwhatwill the impactbe?We then reachout to the relevant experts,assesscurrentguidelinesanddiscusswhether these need tobemodified. Ifweneed tomake changes,weuseour network,make recommendationsand runworkshops todiscuss upcoming changes.

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30 | REGULATORYRAPPORTEUR | Vol. 17,N03,March2020 Facilitating innovation in medicines

BY JOANBOREN , ConsultantEditor, RegulatoryRapporteur ,and JONATHANMONTAGUE ,RegulatoryAffairsAssociate,BoydConsultants Ltd,UK

Q: Couldyou tellour readersabitaboutyourbackground, whatattractedyou to the regulatoryarenaandhowyoucame join theEuropeanMedicinesAgency (EMA)? A: I’mamedicaldoctorby training,withaPhD inexperimental medicine.Before joiningEMA, I spenta coupleofyearsworking inhospitals, including in intensive careunits. Itbecameapparent during this time thatmyworkwashavingan impactononlya limitednumberofpatients.Then, followinga short stintat the WorldHealthOrganization inGeneva, IbecameawareofEMA in London.Theorganisation interestedmeas itoffered the opportunity towork inamulticulturalenvironmentandmakeuse ofmyexperience inmedicineand time spent treatingpatients. Iwas interested in the ideaofcontributing to researchand development through theagency,as I couldhavean impacton innovationand scientificgrowth.This isagreat job forahungry scientist,ashardlyaweekgoesbyatEMAwithoutadiscussion on cutting-edge science. A: Mymain role involvesmanaging the ITF’sactivities.This is amultidisciplinarygroup comprisedof representatives from throughout theagency, including legal,quality, regulatory, nonclinicalandclinicalexperts. Inmanaging the ITF, Iam the firstcontactpoint for companies. It’s important to remember that, inaddition to innovativemedicines, innovationalso applies to technologiesandmethodologiesused indrug development, sowehave to takeabroadapproach.Once we identify the relevanceandpotentialvalueofa requeston innovation,we involveourEU regulatorynetworkofexpertsand engage in furtherdialogue,organisinga face-to-facemeetingor teleconference tobrainstormon thedevelopmentandaddress issues.Wealso lookatmeetingminutesandanalyse trends to identifyareasof innovation thatare then carried forward into workshopsandother fora. I reallyenjoybeing involved innovel, excitingdevelopments,discussing cutting-edge sciencewith internationalexperts,andworking inamulticulturalenvironment inwhich I can interactwith innovatorsanddevelopersofnew productsand technologies. Q: Howdoes the InnovationTaskForce (ITF)stayaheadof cutting-edge technologiesandemerging techniques? A: The ITFaims tobe thefirstpointofcontact fornewproducts, innovativemethodologiesand technologies.Our role is to Q: Whatdoesyourcurrent role involve,andwhatareyour favouriteaspectsof this role?

Q: Does the ITFpropose theconductofworkshopsonkey topics forcross-discussionamong regulators,academiaand industry? A: Yes,absolutely.We recommendworkshopsbutwedon’t conduct themourselvesasabroadernetworkneeds tobe involved.Wehighlight trendsand these flow into thework programmesof the committeesandworkingparties.TheEMA workshops takeabout sixmonths toplan,andconducting them canbequite resource-intensive.Hence, the ITF is the initiating spark for furtherdiscussions,butwedon’tusually takean organising roleata later stage.Recentexamples include the EMA’sexpertmeetingongenome-editing technologies, the discussiononnanomedicines, (theEMA is thefirst regulatory agency toaddress this topic)and,more recently, theuseof digital toolsand technologies indrugdevelopment. A: Mybestadvice is tonothesitate to reachoutasearlyas possible.Weappreciateapplicantsmay think it’s “too soon” for interactionsbutwepreferearlyengagementanddiscussion,even witha telephone call.Weaim toofferan informal interaction so ITF interactions shouldbeviewedasa low-threshold,planning zone.Toooften,we’re consulted too late,whichmakes itmore difficult forus to influenceandadvise.Please reachoutearly for greater impactand input. groups,academicgroups, healthcareprofessionals, individualsandotherparties Wemustnot forget that innovation isnot justan industryactivity, theEMAalsohasastakeholder divisionand liaiseswithpatient

developments and anticipate likely impact. Regulatory science resources

Q: Whatadvicewouldyougive toorganisationsseeking input from the ITF? Innovation:newtechnologyplus anoldproblemandabig idea BY JOANBOREN , Director,RgulatoryAffairs ,AstraZeneca,UKand JULIEWARNER , VicePresident,RegulatoryAffairs ,AlanBoydConsultants Ltd,UK

EDITORIAL

COURTESYOF EMA

Regulatory science related articles have always featured regularly in our peer-reviewed journal, evenmore so recently reflecting the increasing pace of innovation within

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reduced.Wemust recognise thatmost true innovations have their origins in academia, a settingnot traditionally familiarwith regulatoryexpectations or requirements andusuallywithbudget limitations.Could thisbebecause that environment supports free thinkingwithout the constraints of industry timelines and commercial pressures? Thinking of Henry Ford’s quote (“If I had asked the public what they wanted, they would have said a faster horse”) reallydoesdrivehome themessage that it isagifted fewwhohave

when the natural properties of red blood cellswould result in theiruse asnoveldrug deliverysystems,or that theywouldevenbe artificially created, dried and administered topatients? The introduction of novel approaches to the treatment of human and veterinary disease is moving at a rate never seen before, largely owing to the fast-paced advancements in scientific knowledge and improvements in technologies that are used throughout the product development spectrum, from drug discovery to new methodologies toassess clinicalendpoints. Considering that thefirstexperimentalgene therapy was administered to humans just short of 30 years ago, significant progress has been made and the field continues to evolve at blistering speed. Of course,

sufficient numbers of ideas for some to fall by the wayside and the true diamonds – really innovative concepts – to emerge. However, this is definitely not without its challenges froma chemistry,manufacturing and controlsperspective, aswehear in this issue. Although such innovators often have the technical knowledge around a concept orproduct, theymaybesomewhatdetached from the regulatory reality– inotherwords, what are the next logical steps on the path todevelopmentandwhatevidenceneeds to be generatedorplansput inplace tomake thishappen,andwhatare thedependables?

regulatory affairs. Regulatory Rapporteur continues to be a valued resource across the wider regulatory community for addressing cutting edge topics. Focus articles include real world data/real world evidence (RWD/RWE) and the implications of big data; artificial intelligence (AI) and how it can be applied in regulatory data management; digital health (eHealth, mHealth); advancedmedicinal therapy products (ATMPs); and COVID-19 related content.

It is clear that close communication betweenacademia, industryanddevelopers is required. Speaking from an industry perspective, it is our responsibility, as regulators, to increase awareness, within academia and in sponsor organisations, of the need for and value of early regulatory interactions. This is a clear goal of the European Medicines Agency’s Innovation Task Force, as you will read in this issue, andwe clearly need to help overcome the reticence ofmany organisations to engage

regulation has had to keep pace with this rate of progress and, as a result, there is now a growing portfolio of regulations and guidance covering themore prevalent advanced therapies and medical device legislation,whichhas recentlybeenupdated in theEU. However, there remains a need for this portfolio to continue to expand to cover emerging science such as gene editing, microbiome applications or the potential roleofartificial intelligence indevelopment,

Innovation isa progressivepath,andone whichbuildsupasnew technologiesdevelop

earlywith regulators.Thisearlyengagement offers an opportunity to lead the field of novel therapies and the EMA’s Regulatory Science to2025strategyalso recognises the need for early engagement, as presented

asexistingguidelinesonly just touch the surfaceof thepotential challenges in these areas. So, in the absence of guidance, the question is how dowe lead thefield? Industryoftenapplauds itselfforworkingatthecuttingedgeof innovation. However,by the timewe regulatoryprofessionalsseea late-stageconceptor earlydevelopment stageproduct, the technology is already a few yearsold and the capacity tomould it to complywith regulatory requirementsmaybe

in thismonth’smeeting report. It also offers a transparent approach for all stakeholders and enables regulators to perform horizon scanning which, ultimately, speeds access both for patients to ground-breaking therapies and, fordevelopers, to the targetmarket (it isawin-winsituation). The clear theme emerging at the start of this new decade is thatwe all need tocommunicate,educate,andcollaborate, to innovate.The framework todo this isout there–weall justneed toembrace it.

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TOPRA 2025 – Aspire | Adapt | Achieve 15