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vaccines production have remained almost unchanged since the 1960s, are expensive and time-consuming, and would constitute a serious bottleneck in the event of a pandemic. For other respiratory pathogens, very little progress has been made in developing medical countermeasures. • Research infrastructure and level/predictability of funding are weak. Overall funding remains too low, with sustained investment hampered by the high costs of R&D and high probability of failure. The bulk of R&D funding and activities, including research on neglected tropical diseases, remains in high-income countries. While these investments are laudable, research agendas in these countries may not always reflect low-income country needs (e.g. development of Ebola countermeasures in developed countries used for biodefence). • More resources have gone into vaccines, basic research and therapeutics than into diagnostic advances. Attention to diagnostics is important not just for treatment of individuals, but also to assess efficacy of vaccines and treatments and to gauge the speed and breadth of disease spread. • Social science research is poorly integrated into national and international research portfolios, and not applied to preparedness. 19 Research and development, key to developing medical countermeasures and effective preparedness, have major systemic problems PROGRESS, CHALLENGES, ACTIONS: PREPARING FOR THE WORST Progress indicator(s) by September 2020 • Donors and countries commit and identify timelines for: financing and development of a universal influenza vaccine, broad-spectrum antivirals and targeted therapeutics. WHO and its Member States develop options for standard procedures and timelines for sharing of sequence data, specimens and medical countermeasures for pathogens other than influenza. • Donors, countries and multilateral institutions develop a multiyear plan and approach for strengthening R&D research capacity, in advance of and during an epidemic. • WHO, the United Nations Children’s Fund, the International Federation of Red Cross and Red Crescent Societies, academic and other partners identify strategies for increasing capacity and integration of social science approaches and researchers across the entire preparedness/response continuum. Required actions Ultimate objectives: The tools and systems needed to respond effectively to a fast-moving and lethal respiratory pathogen are in place: A universal influenza vaccine is effective and routinely used to protect the global population; new therapeutics and broad-spectrum antivirals are widely available to treat and reduce mortality from a range of viruses; novel pathogens are routinely identified and sequenced, and the sequences are shared on a globally accessible website. Distributed manufacturing of vaccines (including nucleic acid types) begins within days of obtaining the new sequences and effective vaccines are pre-tested and approved for use within weeks. Countries, donors and multilateral institutions must be prepared for the worst 20 A rapidly spreading pandemic due to a lethal respiratory pathogen (whether naturally emergent or accidentally or deliberately released) poses additional preparedness requirements. Donors and multilateral institutions must ensure adequate investment in development of innovative vaccine and therapeutics, surge manufacturing capacity, broadspectrum antivirals and appropriate non-pharmaceutical interventions. All countries must develop a system for immediately sharing sequences of any new pathogen for public health purposes, along with the means to share limited medical countermeasures across countries. PROGRESS, CHALLENGES, ACTIONS: PREPARING FOR THE WORST Even the most conservative models suggest that pandemic risks are on par with other high-profile economic threats, including climate change (0.2-2.0% of global GDP, according to the Intergovernmental Panel on Climate Change 2014) or natural disasters (0.3-0.5% of global GDP and 65,000 deaths per year) (42). The International Monetary Fund’s threshold for a major economic disaster is 0.5% of GDP loss (43). Despite the high cost-benefit ratio of emergency