The United Kingdom (UK) is determined to sustain its efforts to combat resistance, taking local, national and global 'One-Health' approaches across humans, animals, the environment and food, in line with global ambitions and in collaboration with other nations, partners and the international community.

Globally, unchecked antimicrobial resistance also threatens many of the Sustainable Development Goals (Figure 1). The World Bank estimates that an additional 28 million people could be forced into extreme poverty by 2050, through shortfalls in economic output, unless resistance is contained

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our 2019–2024 plan uses the United Nation's Ad-hoc Interagency Coordination Group Framework for Action to set out our commitments). | In the UK, we will contribute to the global effort through:

• A lower burden of infection, better
• Optimal use of antimicrobials
• New diagnostics, therapies, vaccines and interventions | | | Our approach needs to prioritise actions that offer value for money and a real opportunity to make a difference (figure 5). We must align with other relevant national and international initiatives, including the Sustainable Development Goals, the Global Health Security Agenda, Codex Alimentarius and the Global AMR Research and Development Hub, among others

Our approach must also be rooted in robust multi-sectoral data and evidence gathered from human and animal health, agriculture, environment, food and water. This includes ensuring that we can learn from regular self-assessment and independent monitoring as well as from good practice in managing resistance at home and abroad. We will benchmark with the best countries in the world where comparable data are available.

Over the next 20 years, we will build on these foundations through a series of five-year UK national action plans that will each consider past and then present contexts to prioritise actions and direct resources based on the latest information about what the biggest risks are and which interventions are most effective in addressing them. | | | | | Tackling antimicrobial resistance 2019–2024: The UK’s five-year national action plan: https://www.gov.uk/government/publications/uk-5-year-action-plan-for-antimicrobial-resistance-2019-to-2024 | This 5-year national action plan supports the UK 20-year vision for antimicrobial resistance.

Our vision for AMR in 2040 recognises that a global problem as significant and complex as antimicrobial resistance will not be addressed in a single five-year plan. The national action plan, published alongside the vision, aims to build on our achievements so far.

The plan is structured using the United Nation’s Ad-hoc Interagency Framework for Action on AMR and sets out the need for action in 15 areas, together with what we are doing domestically and how we are supporting global action in each area.

Developed in consultation with a broad range of stakeholders across different sectors, it builds on the achievements of our last strategy (2013–2018), and is aligned with global plans and frameworks for action.

Publication of the next 5-year AMR National Action Plan in 2024 | It focuses on three key ways of tackling AMR: • reducing need for, and unintentional exposure to, antimicrobials; • optimising use of antimicrobials; and • investing in innovation, supply and access.

The plan also sets out four measures of success to ensure progress towards our 20-year vision. These include, among others, targets to: • halve healthcare associated Gram-negative blood stream infections; • reduce the number of specific drug-resistant infections in people by 10% by 2025; • reduce UK antimicrobial use in humans by 15% by 2024; • reduce UK antibiotic use in food-producing animals by 25% between 2016 and 2020 and define new objectives by 2021 for 2025; and • be able to report on the percentage of prescriptions supported by a diagnostic test or decision support tool by 2024.

<I like that they have measurable targets, this fits well for both the linear model and an entrepreneurial state approach> | | | We are leading the way in testing solutions that will address our global failure to incentivise the development of new antimicrobials and alternative treatments. We will test a new model that will de-link the payments made to companies from the volumes of antibiotics sold, basing the payment on a NICE led assessment of the value of the medicines and supporting good stewardship.

Promoting access and responsible use > The Fleming Fund Improving detection and surveillance > The Fleming fund

Incentivising R&D > UK Global AMR Innovation Fund (GAMRIF)

Developing new treatments >

| | | | | Tackling antimicrobial resistance 2019–2024: The UK’s five-year national action plan (ACTUAL INIATIVES THAT HAVE INFORMED POLICIES)

Investing in innovation, supply and access to tackle AMR | Investing in research is critical: not only for new product development but also to support predictive modelling, interdisciplinary analyses and intervention research that can help inform effective AMR interventions and strategies.

Despite high levels of coordination, collaboration and investment in basic research for AMR, gaps remain. We still do not know much about AMR in the environment; innovation in IPC is low, as is research to improve protein yield in food production; and drug pipelines remain weak. There is also a pressing need for interdisciplinary research to better prioritise and understand which AMR interventions work for which populations, where and when.

| 1.Provide strategic leadership in AMR research: Since 2014 the UK Government has invested more than £360 million in research and development on AMR, coordinated through the AMR Funders' Forum. This includes £117 million interdisciplinary AMR research and infrastructure. It also includes the £50 million GAMRIF fund, which runs until 2021, and funds various projects to support innovation in product development, £55 million of capital funding, and the £85 million UKRI initiative, which has built a portfolio of national and international interdisciplinary research projects.

To provide strategic leadership in AMR research, the UK will: Continue to influence global research strategies on AMR-related topics through JPIAMR and the Global AMR R&D Hub, ensuring the alignment of UK-funded research, and emphasising the need for research to be useful for front-line teams.

2. Strengthen insight and capacity for doing highquality research: The discovery and development of new health products and technologies requires time and expertise. We need to continue our efforts to provide the right incentives, and promote industry investment, to further strengthen the UK’s capacity for the task.

At the same time, we need to boost our scientific skills in related fields and disciplines and improve our ability to identify, prioritise and embed effective and sustainable interventions that produce change at scale.

3. Development of new therapeutics: The UK cannot solve such market failures alone, but we can catalyse efforts to address the problems at an international level and work to change the incentives to improve the rewards for investment within our domestic market

Pay OR play > It also includes exploring new approaches, such as de-linking the price paid for antimicrobials from the volumes sold (see Section 4.3 below), or adopting a ‘pay or play’ approach (see ‘Pay or play’).

| Strengthen insight and capacity for doing highquality research: The discovery and development of new health products and technologies requires time and expertise. We need to continue our efforts to provide the right incentives, and promote industry investment, to further strengthen the UK’s capacity for the task.

• Continue to develop the scientific capacity needed to support and deliver ongoing high-quality research in infectious disease, prevention and microbiology-related disciplines. • Develop multidisciplinary networks to better undertake predictive analysis and inform interventions across all sectors

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Development of new therapeutics: Antimicrobial pipelines are slow. The UK cannot solve such market failures alone, but we can catalyse efforts to address the problems at an international level and work to change the incentives to improve the rewards for investment within our domestic market.

 Work with international partners to agree a coordinated global system for incentivising new therapeutics.  Establish collaboratives that link UK researchers and industry to make best use of data, information and skills.  Support successful and emerging Product Development Partnerships for priority therapeutics.  Invest in research in academia and businesses, including SMEs, through UKRI and other funding agencies.  Continue to support the AMR Benchmark to stimulate improved accountability and positive competition in industry

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Incentivise R&D for new diagnostics: Designing incentives for new diagnostic development faces similar challenges to incentivising new therapeutics. For example, existing diagnostic methods such as plate culture are generally cheap so companies are reluctant to invest in developing new ones.

These market failures need to be addressed and coupled with other activities to ensure we cover the full range of research required to deliver the type of rapid point of care testing that can make a real difference to clinical practice. The longitude prize was launched in 2014 to incentivise the development of novel approaches (figure 16).

• Introduce incentives to develop and evaluate rapid diagnostics

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Development of, and access to, vaccines: At global level, the UK supports initiatives such as Gavi, the Vaccine Alliance and the Global Vaccine Action Plan to improve equitable access to vaccines for people, and GALVmed for animals, especially in LMICs.

For example, UK Aid is the largest donor to Gavi, investing £1.44 billion in the alliance from 2016 to 2020. UK Aid also supports initiatives to ensure that all LMICs have introduced one or more new or underused vaccines by 2020

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• 5 year action plan within the context of 20 year vision • Key ambitions**

• three key ways to tackle AMR
• Narrative on innovation specifically • Two key actions (the GAMRIF fund and the NICE-NHS England pilot project)*

GAMRIF FUND (PUSH INCENTIVE) Global Antimicrobial Resistance Innovation Fund (GAMRIF): supports early-stage innovative research in underfunded areas of antimicrobial resistance (AMR) research and development for the benefit of people in low and middle income countries (LMICs).

By: • establish international research partnerships and support research competitions that fund innovation and development of new technologies to tackle AMR • leverage investment from other partners and donors to support sustainable financing for AMR • establish global research partnerships using a ‘One Health’ approach • fund projects that will develop solutions specifically for LMICs

NICE-NHS England pilot project (PULL INCENTIVE to market shape) The UK Government’s national action plan for AMR includes the commitment to test solutions that address this issue, by evaluating and paying for selected antimicrobial products in a different way from other medicines.

To meet this commitment, NICE and NHS England ran a pilot project. This project tested an innovative approach that pays companies a fixed annual fee for antimicrobials, based primarily on a health technology assessment of their value to the NHS, instead of the volumes used.

| >>> WHO REPORT ON PILOT PROJECT:

July 2022: Following implementation of a pilot subscription model, the UK became the first country in the world to pay drug companies (Pfizer, US; Shionogi, Japan) a fixed fee per year (GBP 10 million per year for 3-10 years) for supplying antibiotics (ceftazidime with avibactam and cefiderocol). This is the first implementation of a fully delinked pull incentive globally. Payments for the new antibiotics are not linked to the volume of sales but are based on the added value to the health and social care system. The subscription model provides a known yearly revenue for the developer of the drug to ensure access, regardless of amounts used. The National Institute for Health and Care (NICE) used a Quality-of-Life Years (QALY) - based assessment valuing each drug at GBP 11-19 million per year. The level of revenue provided not only guarantees access but is aimed to render the R&D of new antibacterials a more attractive proposition, encouraging innovation in the sector. It is currently too soon to evaluate whether this model has stimulated R&D and innovation in the sector. | | | | The Fleming Fund | The Fleming Fund is a £265m UK Aid programme established to help low and middle income countries tackle AMR focusing particularly on surveillance.

• The fund finances activities to collect and share data
• The fund supports countries to develop a National Action Plan (NAP) for AMR and to roll out protocools and tools needed to survey antimicrobial use and resistance
• The fund helps periphery countries build sustainable One-Health surveillance systems
• The fund builds the capacity of AMR leaders through a range of fellowships that offer mentorship, secondments, training and networking opportunities for individuals in both scientific and policy fields | | | | Through initiatives like the Fleming Fund, the UK supports LMICs to collect and share globally high-quality surveillance data on AMR as well as antimicrobial use and quality for human and animal health | | | | | The Global AMR Innovation Fund: https://www.gov.uk/government/groups/the-global-amr-innovation-fund

Global Antimicrobial Resistance Innovation Fund (GAMRIF) Annual Review 2021/22

THE PROJECTS > https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/886146/projects-funded-by-GAMRIF.pdf | GAMRIF is a UK aid fund that supports research and development around the world to reduce the threat of antimicrobial resistance in low and middle income countries.

GAMRIF takes a ‘One Health’ approach, which means that the fund invests in potential solutions to reduce the threat of AMR in humans, animals, fish and the environment. This approach supports several different types of health products to address a range of antimicrobial threats to human health.

GAMRIF invests in underfunded and neglected areas of early-stage, innovative research and development (R&D) that address antimicrobial resistance (AMR) for the benefit of people in low- and middle-income countries (LMICs) | | GAMRIF's portfolio has continued to grow, contributing to an improved supply of promising appropriate and affordable products and tools for combatting AMR in LMICs (Outcome 2). As of 31 March 2022, GAMRIF has funded 82 projects in total across the One Health spectrum. This is through a combination of new projects with existing partners, such as 10 new projects through BactiVac (WP7), and 2 additional WPs (ICARS (WP8) and CHAI (WP9)). Many of these projects have progressed up the technology readiness levels (TRL (Annex 2)) towards real-world testing. The new ICARS project involved real-world testing and 3 projects through FIND progressed to phase I, II and IV clinical trials respectively, demonstrating Output 3.1. Funded through CARB-X, GSK Bio's iNTS-TCV, a paediatric vaccine, received a safe-to-proceed letter from the Belgian regulators to commence a firstin-human program. The initial study will evaluate safety and immunogenicity in healthy adults in Belgium, followed by a similar study in Malawi. | Through this additional funding, GAMRIF supported the development of new treatments for drug-resistant infections, including the new, first-in-class antibiotic (in over 30 years) Zoliflodacin which is in Phase III clinical trials. • Downstream partner projects producing 162 knowledge transfer outputs (KTOs); increasing awareness of AMR and raising the profile of GAMRIF research | we are supporting: • the Combating Antibiotic Resistant Bacteria Biopharmaceutical Accelerator, a nonprofit international partnership supporting research on the most dangerous drugresistant bacteria; • in-country research to tackle AMR in agriculture and the impact on the environment (for example, in Argentina); • the work of the Foundation for Innovative New Diagnostics (FIND) to enhance the impact of diagnostic tools, in particular the connectivity of point-of-care diagnostics for AMR surveillance; and • the development of a new antibiotic for drug-resistant gonorrhoea through the Global Antibiotic Research and Development Partnership (GARDP).

We also promote EU and international AMR research collaborations through other initiatives including UK Research and Innovation (UKRI) AMR initiative which has committed £41million from 2014-2018, to support projects in partnership with members of the Joint Programming Initiative on AMR (JPIAMR) and through partnerships with low- and middle-income countries (see box "SNAP-AMR") and the recently launched Global AMR R&D Collaboration Hub, which is coordinated by Germany | | | | | Addendum to the UK 5-year action plan for antimicrobial resistance 2019 to 2024: https://www.gov.uk/government/publications/addendum-to-the-uk-5-year-action-plan-for-antimicrobial-resistance-2019-to-2024 | | | | | | | | | | AMR Framework for Action Supported by the IACG: https://cdn.who.int/media/docs/default-source/antimicrobial-resistance/amr-gcp-tjs/iacg/other-documents/20170818-amr-ffa-v01.pdf?sfvrsn=796a325e_6 | A comprehensive structure to address AMR grouped into 14 content areas > Six levers to implement the 14 overall content areas > Three overall enablers that underpin the successful application of levers across the 14 content areas > Actions in the 14 content areas will directly impact several SDGs | | | | | | | |