11–12 June 2019 | Geneva, Switzerland
BETTER GLOBAL TOOLS FOR INFLUENZA
Technical consultation on product research & innovation for influenza prevention, control & treatment
Prevent. Control. Prepare.
11–12 June 2019 | Geneva, Switzerland
BETTER GLOBAL TOOLS FOR INFLUENZA
Technical consultation on product research & innovation for influenza prevention, control & treatment WHO/WHE/IHM/IPR/2019.1
© World Health Organization 2019
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This publication contains the report of the June 2019 Technical Consultation on Product Research and Innovation for Influenza Prevention, Control and Treatment and does not necessarily represent the decisions or policies of WHO.
Written by Sian Lewis Design & layout by Vivian Lee CONTENTS Executive summary 4
PART I Introduction 5 Setting the scene WHO framework 6
PART II Innovating for influenza 7 The role of innovation Understanding virus characteristics and host factors 9 Building on lessons learnt 10
PART III Landscape overview 12 Towards better tools Diagnostics 13 Vaccines 14 Therapeutics 17
PART IV Scenario planning 21 Action planning Recommendations for action 22 Next steps 25
Annex I: Meeting agenda 26 Annex II: List of participants 28 Annex III: Individual suggestions 32 NOTE TO READER This report aims to capture key messages that emerged from the presentations and discussions rather than trying to provide a strictly chronological account of the meeting. The priorities for innovation and recommendations for action include suggestions made by all meeting participants (across all sessions), and do not necessarily imply consensus. Some priorities for innovation are repeated to reflect their emphasis by participants in different sessions and contexts.
The presentations and background reading for the meeting are available at: https://www.who.int/influenza/global_influenza_ strategy_2019_2030/en/. Technical consultation on product research and innovation for influenza prevention, control and treatment | BETTER GLOBAL TOOLS FOR INFLUENZA | 1
ACRONYMS AND ABBREVIATIONS
AMR antimicrobial resistance BARDA Biomedical Advanced Research and Development Authority CDC Centers for Disease Control CVV candidate vaccine virus DIA digital immunoassay FAO Food and Agriculture Organization of the United Nations FDA Food and Drug Administration GAP Global Action Plan for Influenza Vaccines GISRS Global Influenza Surveillance and Response System HA hemagglutinin HICs high-income countries IHR International Health Regulations (2005) LAIV live attenuated influenza vaccine LMICs low- and middle-income countries mAbs monoclonal antibodies NAAT nucleic acid amplification test NAI neuraminidase inhibitor NPI nonpharmaceutical intervention PAI polymerase inhibitor PCR polymerase chain reaction PIP Pandemic Influenza Preparedness R&D research and development RIDT rapid influenza diagnostic test RCT randomized control trial SDG Sustainable Development Goal WHE WHO Health Emergencies Programme WHO World Health Organization 2 | BETTER GLOBAL TOOLS FOR INFLUENZA | Technical consultation on product research and innovation for influenza prevention, control and treatment
EXECUTIVE SUMMARY
The 2019–2030 Global Influenza Strategy aims to protect all people Table 1. Sumtmary recommendations for delivering better global tools and communities from the threat of influenza by delivering better global to tackle influenza tools and stronger country capacities for tackling the virus and disease. Boost public understanding, confidence & uptake As a first step towards implementing the strategy, WHO convened • Find new ways to engage & inform the public a meeting of experts in June 2019 to explore the challenges and • Target messaging to key groups opportunities in research and innovation for developing new and improved products to prevent, treat, and potentially control influenza. Build political will • Turn global strategy into call for action • Make an effective case for investment Meeting participants reviewed the latest trends and current product • Leverage burden of disease studies pipelines in diagnostics, vaccines, and therapeutics. For each type of product, they identified knowledge gaps and barriers to development Secure funds and direct investors and utilization and put forward a selection of priorities for innovation. • Fundraise beyond the private sector These ranged from broad goals, for example to improve the way we • Coordinate donors • Direct investors towards high impact action collect and share data, to very specific suggestions such as conducting fixed and focused studies to better understand influenza transmission Work together to align efforts patterns in hospitals. • Build partnerships across research & clinical practice • Improve infrastructure for alignment & Key recommendations are highlighted throughout this report and collaboration summarized in Table 1. A common theme across product types was the • Harness new applications & methods for data need to focus on making tools as relevant and effective as possible. sharing This is not necessarily about only creating new tools or technologies, • Adopt a holistic view of production although participants agreed that developing a universal vaccine Strengthen the evidence base would be a significant leap forward. Rather, it is also about improving • Improve understanding of the virus and increasing the utilization of the currently available products and • Leverage existing or establish new clinical technologies through incremental innovations. networks • Harness existing evidence • Harmonize clinical trial methods Several speakers suggested that small technological innovations could make a big difference to efficiency and effectiveness, for example Support early detection & rapid data sharing by expanding breadth of protection for seasonal influenza vaccines. • Develop deployable diagnostics Incorporating public health outcomes in clinical trials or redesigning • Strengthen global surveillance clinical trials to focus on public health outcomes would help make Improve vaccine production efficiencies influenza products more relevant to health ministers and key decision • Speed up vaccine production makers. And tailoring existing diagnostics, vaccines, and therapeutics to • Streamline manufacturing processes resource-limited contexts would make them more appealing, relevant, Establish clear regulatory pathways and accessible to the low- and middle-income countries (LMICs) that • Develop pandemic plans are often most heavily impacted by epidemic and pandemic influenza • Build partnerships with manufacturers viruses, in addition to zoonotic events. • Gather more data on safety & efficacy LMIC • Clarify approval pathways for emerging products LMIC Following the June 2019 meeting, the WHO Secretariat will review LMIC Make influenza products sustainable all suggestions made and prioritize activities to implement the Global • Ensure guidance accompanies new products Influenza Strategy and accelerate the development of new and • Secure demand for new products LMIC improved vaccines, antivirals and treatments. • Drive improvements of existing products
Focus on LMIC needs LMIC • Promote tools for resource-limited settings LMIC LMIC • Tailor studies to LMIC contexts LMIC • Build capacity for seasonal influenza • Strengthen LMIC manufacturing base • Secure supply chains Technical consultation on product research and innovation for influenza prevention, control and treatment | BETTER GLOBAL TOOLS FOR INFLUENZA | 3
PART I. SETTING THE SCENE
Introduction
Influenza affects all countries, communities, and individuals. Seasonal influenza viruses will continue to circulate, and influenza viruses with pandemic potential will continue to emerge. In March 2019, building “We are looking at how to on its 70 years of global health leadership and experience in the field, infuse innovation into all WHO launched the Global Influenza Strategy for 2019–2030, aimed at aspects of influenza detection, protecting people in all countries from the threat of influenza. prevention and control.” The strategy provides a common framework for WHO, countries, and partners to jointly enhance global and national pandemic preparedness, combat the ongoing threat of zoonotic influenza, and improve seasonal In June 2019, WHO convened a meeting of experts to shape action influenza prevention and control. With strong links to major existing towards the first of these high-level outcomes by exploring the global health strategies and programmes (including the Thirteenth opportunities and challenges in research and innovation for new and WHO General Programme of Work, the International Health Regulations improved products to treat, control, and prevent influenza. This ‘better (2005) and the Public Health Research Agenda for Influenza), the new global tools meeting’, which had more than 85 participants, had three strategy is designed around two high-level outcomes (see Figure 1): key objectives:
1. Better global tools. A focused, consensus-driven plan leads to • Review trends and product landscapes and pipelines for influenza greater research, innovation, and availability of improved tools to prevention, control and treatment. prevent, detect, control, and treat influenza. • Identify synergies among existing global initiatives and funders. 2. Stronger country capacities. Every country has a prioritized influenza programme that is evidence-based; optimized to fit their needs; • Discuss actions for WHO and partners to accelerate research and and contributes to national and global preparedness, response and innovation for better global tools. health security.
Figure 1. Global Influenza Strategy 2019–2030 OBJECTIVES OUTCOMES GOALS
Reduce burden of seasonal Reseach Better global tools influenza & innovation • Improved, novel and universal vaccines • More effective treatments • Better understanding of virus & host response Surveillance, monitoring & • Better detection methods data utilzation • Optimized use of current tools Minimal risk of zoonotic Seasonal prevention & influenza control policies Stronger country capacities & programmes • Integrated capacity building • Seasonal influenza prevention programmes Pandemic • Early detection capacity preparedness Mitigated impact of & response • Up-to-date preparedness plans pandemic influenza 4 | BETTER GLOBAL TOOLS FOR INFLUENZA | Technical consultation on product research and innovation for influenza prevention, control and treatment
The WHO Framework Public health research agenda for influenza The new Global Influenza Strategy builds on WHO’s existing influenza initiatives and the significant achievements and advancements these Any suggestions for promoting research and innovation under the have made since the last global strategy was published in 2002. These Global Influenza Strategy should build on and focus those already include, for example, enhanced surveillance built through the Global outlined in the WHO Public Health Research Agenda for Influenza, which Influenza Surveillance and Response System (GISRS), broader virus and serves to guide research so that knowledge gained improves public benefit sharing achieved through the Pandemic Influenza Preparedness health decision-making in the prevention, control, and preparedness (PIP) Framework, and expanded access to vaccines through the Global for influenza. Action Plan for Influenza Vaccines (GAP).1 Last updated in 2017, the Public Health Research Agenda for Influenza The focus of the better global tools meeting was the strategy’s first promotes research in priority areas across five streams of work: objective to promote research and innovation, which includes three reducing risk, limiting spread, minimizing impact, optimizing treatment, specific priorities: and promoting tools. Participants at the better global tools meeting received a summary of the latest recommendations on two of these: a. promote research and innovation for improved and novel diagnostics, minimizing impact and optimizing treatment (see Table 2). vaccines and treatments; b. promote operational research for influenza prevention, control and Table 2. Relevant research recommendations (in brief) to emerge from programme delivery; and the Public Health Research Agenda for Influenza c. promote research to better understand the virus characteristics and host factors that drive impact. WORK STREAM RESEARCH RECOMMENDATIONS
In considering how to achieve each of these, participants at the meeting Minimizing impact • Improve vaccine strain selection • Enhance clinical applications of existing were asked to adhere to the five guiding principles of the new strategy: vaccines enable country ownership, strengthen existing influenza programmes • Improve vaccine production processes and initiatives, secure continued implementation of the PIP Framework, • Optimize and standardize animal models expand multisectoral partnerships, and ensure value for money. • Develop new vaccines, platforms, and formulations • Identify correlates of protection for different vaccines • Develop innovative clinical trial methods “When the next pandemic virus hits, will we have Optimizing • Develop rapid, sensitive and affordable treatment point-of-care diagnostic tests predicted the strain at hand? • Develop improved point-of-care tools for prognosis and clinical management Will we have treatments that • Optimize use of current antivirals work? Will we be able to • Optimize the effectiveness of current and novel antivirals quickly get vaccines to those • Develop new and effective treatment strategies who need them most?” • Optimize management of patients with severe influenza disease
1 For a full list of achievements in influenza prevention, control and preparedness since 2002, see Annex 1 of the Global Influenza Strategy 2019–2030 www.who.int/influenza/global_( influenza_strategy_2019_2030). empowers thepatienttoseekearlytreatmentandreducetransmission. the housecanchangedynamicofcareforinfluenzapatients. This can detectinfluenzaearlyandensurethepatientneverneedstoleave particular, developingandincorporatinghome-baseddiagnosticsthat that can save lives and reduce transmission risk.intervention In and easytouse. point-of-caretestingsothatitisreadilyaccessibleImprove Priorities forinnovation 4. 3. 2. 1. ingredients forsuccess: Research and Development Authority (BARDA) highlighted four critical and treatment, DrRobertJohnsonfromtheUSBiomedical Advanced In discussingtheroleofinnovationininfluenzaprevention, control, Innovating forinfluenza Figure 2. 2 THE ROLE OFINNOVATION PART II. Data publishedbyUSCDC ( Percent effective effectiveness, andbetteruseofthecurrentinfluenzavaccines. make abigdifferencetopotentiallyimprovingthetimelyavailability, process offersanopportunityforinnovation, andsmallgainscan public health. Forexample, stepinthevaccineproduction every maintaining resources to continue research and development (R&D). ways tosustaincapabilitiesaftersuccessfuldevelopment, whilealso term sustainmentoftheoveralleffort, includingforexample, finding you defineit. single actionbutbyarangeofactivities. nrmna improvements. Incremental A long-termoutlook. An openmindset. A continuumofinnovation.
Technical consultationonproductresearchandinnovationforinfluenzaprevention, controlandtreatment SeasonalinfluenzavaccineeffectivenessascalculatedbyUSCDC 10% Early identificationofinfectionenablesearlier https://www.cdc.gov/flu/vaccines-work/past-seasons-estimates.html 21% This isacornerstoneofinnovation, however Innovationrequiresthinkingaboutthelong- 52% Small, well-timed steps also advance Innovationisrarelydefinedbya 37% 41% 56% ) andsharedatthebetter toolsmeetingbyspeakersfromtheJohnsHopkins CenterforHealthSecurity. 60% Flu season who areathigh-riskforinfluenzacomplications. of communicating/messagingthistothepublic, particularlytopersons that resultsinhospitalizationandwecollectivelyneedtodoabetterjob Additionally, there arebenefitstoreducingtheriskofsevereinfluenza may allcontributetoimprovementsinourexistinginfluenzavaccines. Innovation incurrentvaccineformulation, dosingandcomposition the lastdecadesodecreasemaybeanartifactofmethodology. the methodsforassessingvaccineeffectivenesshavechangedwithin hospitalized patients)formorethanadecade(seeFigure2). Notethat of medically-attendedinfluenzainoutpatientsbutnotthat more than60%effectiveness(whichreferstotheprevention Prevention (CDC)showthatvaccineshavegenerallynotachieved effectiveness conductedbytheUSCentersforDiseaseControland that arecurrentlyavailable;studiesofseasonalinfluenzavaccine may stillbemanyyearsaway. Itisalsoaboutimprovingthevaccines towards auniversalvaccine, eventhoughinpracticesuchavaccine Increase effectivenessofvaccines. where applicable. longer-lasting formulationsmayenablemorecost-effectivestockpiling, established productionprocesses. At thesametime, researchinto to haveanimplementationplanintroduceimprovementsinto including securingthe supply chain of rawmaterials. It is alsocritical steptospeeduptheprocess,and innovationarerequiredatevery months togetapandemicvaccinethepeoplethatneedit. Research productionefficiencies.Improve 2