Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Antibiotic development — economic, regulatory and societal challenges

Antibiotic resistance is undoubtedly one of the greatest challenges to global health, and the emergence of resistance has outpaced the development of new antibiotics. However, investments by the pharmaceutical industry and biotechnology companies for research into and development of new antibiotics are diminishing. The public health implications of a drying antibiotic pipeline are recognized by policymakers, regulators and many companies. In this Viewpoint article, seven experts discuss the challenges that are contributing to the decline in antibiotic drug discovery and development, and the national and international initiatives aimed at incentivizing research and the development of new antibiotics to improve the economic feasibility of antibiotic development.

The contributors

Christine Årdal co-leads research and innovation in the European Union Joint Action on Antimicrobial Resistance and Healthcare-Associated Infections. Previously she was the co-lead on incentives to stimulate antibacterial innovation for the European Union’s DRIVE-AB project. She is a senior adviser at the Norwegian Institute of Public Health, where her research and policy work focuses on medicine innovation, access and stewardship.

Manica Balasegaram trained as a medical doctor at the University of Nottingham, United Kingdom, and from 2001 onwards worked as a doctor and researcher in several countries in sub-Saharan Africa and southern Asia with Médecins Sans Frontières. In 2007, he joined the Drugs for Neglected Diseases initiative as Head of the Leishmaniasis Clinical Program before returning to Médecins Sans Frontières as Executive Director of the Access Campaign. He joined the Global Antibiotic Research and Development Partnership in June 2016, and is a board member of the Medicines Patent Pool as well as FIND’s Scientific Advisory Committee. He is also the executive director of GARDP.

Ramanan Laxminarayan is the founder and Director of the Center for Disease Dynamics, Economics & Policy in Washington, DC, United States, and a senior research scholar at Princeton University. He is a voting member of the US Presidential Advisory Council on Combating Antibiotic-Resistant Bacteria.

David McAdams is a game theorist and professor of economics in the Fuqua School of Business and Economics Department at Duke University, United States. His current research focuses on the economic epidemiology of information, with applications from antibiotic resistance to ‘fake news’.

Kevin Outterson is a professor of law and N. Neal Pike Scholar in Health and Disability Law at Boston University, United States, and Executive Director of CARB-X. He has grappled for a dozen years with issues peculiar to antibiotic research and development, especially relating to intellectual property, reimbursement and business models. He now leads the world’s largest push incentive for antibacterial research and development, CARB-X, with a 5-year budget exceeding US$500 million. The views expressed herein are personal, and do not necessarily represent the views of CARB-X or any CARB-X funder.

John H. Rex is a physician and drug developer with more than 30 years of development and policy experience focused on antimicrobial agents. He is currently Chief Medical Officer of F2G Ltd (an antifungal biotechnology company), an expert-in-residence for the Wellcome Trust and an operating partner with a venture capital group (Advent Life Sciences) and was (2015–2019) a voting member of the US Presidential Advisory Council on Combating Antibiotic-Resistant Bacteria. He blogs regularly at http://amr.solutions/blog.html.

Nithima Sumpradit is a pharmacist and lead coordinator for development and implementation of Thailand’s National Strategic Plan on Antimicrobial Resistance 2017–2021. She is also a programme manager of the Royal Thai Government–WHO Country Cooperation Strategy Programme on Antimicrobial Resistance.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

References

  1. 1.

    Payne, D. J., Gwynn, M. N., Holmes, D. J. & Pompliano, D. L. Drugs for bad bugs: confronting the challenges of antibacterial discovery. Nat. Rev. Drug Discov. 6, 29 (2007).

    CAS  Article  Google Scholar 

  2. 2.

    Sertkaya, A. et al. Analytical framework for examining the value of antibacterial products. Submitted to the US Department of Health and Human Services https://aspe.hhs.gov/report/analytical-framework-examining-value-antibacterial-products (2014).

  3. 3.

    Årdal, C. et al. Insights into early stage of antibiotic development in small-and medium-sized enterprises: a survey of targets, costs, and durations. J. Pharm. Policy Pract. 11, 8 (2018).

    Article  Google Scholar 

  4. 4.

    World Health Organization. WHO report on surveillance of antibiotic consumption: 2016-2018 early implementation. https://www.who.int/medicines/areas/rational_use/oms-amr-amc-report-2016-2018/en/ (2018).

  5. 5.

    Holmes, A. H. et al. Understanding the mechanisms and drivers of antimicrobial resistance. Lancet 387, 176–187 (2016).

    CAS  Article  Google Scholar 

  6. 6.

    Pew Charitable Trusts. Antibiotics Currently in Global Clinical Development https://www.pewtrusts.org/en/research-and-analysis/data-visualizations/2014/antibiotics-currently-in-clinical-development (2019).

  7. 7.

    Mullard, A. Achaogen bankruptcy highlights antibacterial development woes. Nat. Rev. Drug Discov. 18, 411 (2019).

    PubMed  Google Scholar 

  8. 8.

    World Health Organization. Global priority list of antibiotic-resistant bacteria to guide research, discovery, and development of new antibiotics. https://www.who.int/medicines/publications/global-priority-list-antibiotic-resistant-bacteria/en/ (2017).

  9. 9.

    Rex, J. H. Scary, Scarier, Scariest: Achaogen, http://amr.solutions/blog/scary-scarier-scariest-achaogen-ft-editorial-cbs-60-minutes-on-amr (2019).

  10. 10.

    The Pew Trust. The critical need for new antibiotics. https://www.pewtrusts.org/en/research-and-analysis/data-visualizations/2016/the-critical-need-for-newantibiotics. (2019)

  11. 11.

    Årdal, C. et al. DRIVE-AB - Revitalizing the antibiotic pipeline: Stimulating innovation while driving sustainable use and global access. http://drive-ab.eu/wp-content/uploads/2018/01/CHHJ5467-Drive-AB-Main-Report-180319-WEB.pdf (2018).

  12. 12.

    AMR Review. Tackling drug-resistant infections globally: Final report and recommendations. The Review on Antimicrobial Resistance, London. https://amr-review.org/Publications.html (2018)

  13. 13.

    Daniel, G. et al. Value-Based Strategies for Encouraging New Development of Antimicrobial Drugs. https://healthpolicy.duke.edu/sites/default/files/atoms/files/value-based_strategies_for_encouraging_new_development_of_antimicrobial_drugs.pdf (2017).

  14. 14.

    The Boston Consulting Group. Breaking through the Wall: A Call for Concerted Action on Antibiotics Research and Development. https://www.bundesgesundheitsministerium.de/fileadmin/Dateien/5_Publikationen/Gesundheit/Berichte/GUARD_Follow_Up_Report_Full_Report_final.pdf (2017).

  15. 15.

    CARB-X. Portfolio Companies: Supporting great science from around the world, https://carb-x.org/portfolio/gallery/ (2019).

  16. 16.

    Emanuel, E. Big Pharma’s Go-To Defense of Soaring Drug Prices Doesn’t Add Up. The Atlantic https://www.theatlantic.com/health/archive/2019/03/drug-prices-high-cost-research-and-development/585253/ (2019).

  17. 17.

    Verma, S. Aligning Payment And Prevention To Drive Antibiotic Innovation For Medicare Beneficiaries, https://www.healthaffairs.org/do/10.1377/hblog20190802.505113/full/ (2019).

  18. 18.

    Public Health Agency of Sweden. Folkhälsomyndigheten utvärderar ny ersättningsmodell för viktiga antibiotika, https://www.folkhalsomyndigheten.se/nyheter-och-press/nyhetsarkiv/2019/juni/folkhalsomyndigheten-utvarderar-ny-ersattningsmodell-for-viktiga-antibiotika/ (2019).

  19. 19.

    Department of Health and Social Care and The Rt Hon Matt Hancock MP. Antimicrobial resistance needs an urgent global response, https://www.gov.uk/government/speeches/antimicrobial-resistance-needs-an-urgent-global-response (2019).

  20. 20.

    The AMR Industry Alliance. Tracking progress to address AMR. https://www.amrindustryalliance.org/wp-content/uploads/2018/01/AMR_Industry_Alliance_Progress_Report_January2018.pdf (2018).

  21. 21.

    McAdams, D., Waldetoft, K. W., Tedijanto, C., Lipsitch, M. & Brown, S. P. Resistance diagnostics as a public health tool to combat antibiotic resistance: A model-based evaluation. PLOS Biol. 17, e3000250 (2019).

    CAS  Article  Google Scholar 

  22. 22.

    McAdams, D. Game-Changer: Game Theory and the Art of Transforming Strategic Situations (WW Norton & Company, 2014).

  23. 23.

    Woodworth, K. R. et al. Vital signs: containment of novel multidrug-resistant organisms and resistance mechanisms—United States, 2006–2017. Morb. Mortal. Wkly Rep. 67, 396 (2018).

    Article  Google Scholar 

  24. 24.

    Melander, E., Hansson, H.-B., Mölstad, S., Persson, K. & Ringberg, H. Limited spread of penicillin-nonsusceptible pneumococci, Skåne County, Sweden. Emerg. Infect. Dis. 10, 1082 (2004).

    Article  Google Scholar 

  25. 25.

    Unitaid. Unitaid’s investment in tuberculosis hits record levels with new grant for diagnostic technologies, https://unitaid.org/news-blog/unitaids-investment-in-tuberculosis-hits-record-levels-with-new-grant-for-diagnostic-technologies/#en (2019).

  26. 26.

    Stein, R. Scientists modify viruses with CRISPR to create new weapon against superbugs. NPR.org. https://www.npr.org/sections/health-shots/2019/05/22/723582726/scientists-modify-viruses-with-crispr-to-create-new-weapon-against-superbugs (2019).

  27. 27.

    Theuretzbacher, U. & Piddock, L. J. Non-traditional antibacterial therapeutic options and challenges. Cell Host Microb. 26, 61–72 (2019).

    CAS  Article  Google Scholar 

  28. 28.

    World Health Assembly. In the face of slow progress, WHO offers a new tool and sets a target to accelerate action against antimicrobial resistance. https://www.who.int/news-room/detail/18-06-2019-in-the-face-of-slow-progress-who-offers-a-new-tool-and-sets-a-target-to-accelerate-action-against-antimicrobial-resistance. (2019)

  29. 29.

    Hsia, Y. et al. Consumption of oral antibiotic formulations for young children according to the WHO Access, Watch, Reserve (AWaRe) antibiotic groups: an analysis of sales data from 70 middle-income and high-income countries. Lancet Infect. Dis. 19, 67–75 (2018).

    Article  Google Scholar 

Download references

Author information

Affiliations

Authors

Corresponding authors

Correspondence to Christine Årdal, Manica Balasegaram, Ramanan Laxminarayan, David McAdams, Kevin Outterson, John H. Rex or Nithima Sumpradit.

Ethics declarations

Competing interests

R.L. is a voting member of the US Presidential Advisory Council for Combating Antibiotic-Resistant Bacteria and Board Chair of the Global Antibiotic Research and Development Partnership, which works to bring new antibiotics to market. J.H.R. is Chief Medical Officer and a director of F2G Ltd, a non-executive director of and a consultant for Adenium Biotech ApS, an operating partner of and a consultant for Advent Life Sciences and an expert-in-residence for the Wellcome Trust. He sits on the scientific advisory boards of Macrolide Pharmaceuticals, Bugworks Research Inc., Basilea Pharmaceutica, Forge Therapeutics Inc., Novo Holdings and Roche Pharma Research & Early Development. He is a shareholder in AstraZeneca Pharmaceuticals, F2G Ltd, Adenium Biotech ApS, Advent Life Sciences, Macrolide Pharmaceuticals and Bugworks Research Inc. He has received consulting fees from Phico Therapeutics, ABAC Therapeutics, Polyphor Ltd, Heptares Therapeutics Ltd, Gangagen Ltd, Meiji Seika Pharma, Basilea Pharmaceutica International Ltd, Allecra Therapeutics GmbH, Forge Therapeutics Inc., SinSa Labs, AtoxBio, Peptilogics, F. Hoffmann-LaRoche Ltd, Novo Holdings, Innocoll, Vedanta, Progenity, Nosopharm SA, Roivant Sciences and Shionogi Inc. C.Å., M.B., D.M., K.O. and N.S. do not declare competing interests.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Related links

AMR Industry Alliance: https://www.amrindustryalliance.org

Announcement: https://www.federalregister.gov/documents/2019/08/16/2019-16762/medicare-program-hospital-inpatientprospective-payment-systems-for-acute-care-hospitals-and-the

AWaRe: https://adoptaware.org

AWaRe tool: https://aware.essentialmeds.org/groups

Bill & Melinda Gates Foundation: https://www.gatesfoundation.org

Biomedical Advanced Research and Development Authority (BARDA): https://www.phe.gov/about/barda/Pages/default.aspx

Combating Antibiotic Resistant Bacteria Biopharmaceutical Accelerator (CARB-X): https://carb-x.org

DRIVE-AB: http://drive-ab.eu

European Gram Negative AntiBacterial Engine (ENABLE): http://nd4bb-enable.eu

Gavi Alliance: https://www.gavi.org

Global Antibiotic Research and Development Partnership (GARDP): https://www.gardp.org

Global Action Plan on Antimicrobial Resistance: https://www.who.int/antimicrobial-resistance/global-action-plan/en/

Innovative Medicines Initiative: https://www.imi.europa.eu

Innovative Medicines Initiative New Drugs for Bad Bugs (IMI ND4BB): https://www.imi.europa.eu/projects-results/project-factsheets/nd4bb

Joint Programming Initiative on Antimicrobial Resistance (JPIAMR): https://www.jpiamr.eu

Medical Research Council: https://mrc.ukri.org

National Institute of Allergy and Infectious Diseases (NIAID): https://www.niaid.nih.gov

Novo Nordisk Foundation: https://www.novonordisk.com/about-novo-nordisk/corporate-governance/foundation.html

REPAIR Impact Fund: https://www.repair-impact-fund.com

Unitaid: https://unitaid.org/#en

Wellcome Trust: https://wellcome.ac.uk

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Årdal, C., Balasegaram, M., Laxminarayan, R. et al. Antibiotic development — economic, regulatory and societal challenges. Nat Rev Microbiol 18, 267–274 (2020). https://doi.org/10.1038/s41579-019-0293-3

Download citation

Further reading

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing