Stopping Drug Resistance in Its Tracks: Ideas for the EU

Summary

• Antimicrobial resistance (AMR) is responsible for a large and growing burden of mortality, morbidity, and economic impacts. This is due to three underlying problems: lack of access to essential antimicrobials, insufficient stewardship of these drugs to prevent overuse and misuse, and a dearth of innovation to create new medicines and diagnostics. 
• The previous European Commission showed strong leadership on this issue. There is a window of opportunity to continue this momentum, especially following the UN General Assembly High-Level Meeting on AMR. 
• The EU should support the development of a sustainable access hub to ensure all countries can access a portfolio of essential antimicrobials and diagnostics. 
• The EU should implement a new model to drive innovation of novel antimicrobials. We propose a system whereby the EU would offer an incentive to reward innovation of an antibiotic meeting certain criteria. In return, companies must register and sell the antibiotic in all EU countries at an agreed, affordable price, and provide voluntary licenses to low- and middle-income countries to ensure sustainable access. 

Antimicrobial resistance (AMR) occurs when bacteria and other microorganisms develop the ability to survive in the presence of antimicrobial medicines that ordinarily kill them. While this is a natural process, it is being hastened by our overuse and misuse of antimicrobials—resulting in a serious problem whereby many medications are no longer effective. Estimates suggest that AMR is responsible for over 1.15 million deaths every year—mainly in low- and middle-income countries (LMICs), but also including about 58,000 in the European Union (EU). AMR also causes a substantial economic burden, in terms of both the increased health care costs associated with treating resistant infections and productivity losses. We have estimated that resistance causes excess health care costs of USD 66 billion globally and that USD 168 billion is spent treating patients with resistant infections. Within the EU, health systems spend EUR 15 billion each year treating resistant infections. Without concerted action, these numbers will only grow.  

Three main problem areas underlie the rise in AMR: a lack of reliable access to essential antimicrobials, insufficient stewardship of these drugs to prevent unnecessary use, and a dearth of innovation to create new drugs. A lack of access directly causes morbidity and mortality, as people are unable to access the treatments they require—it is estimated that more people die from a lack of access to antimicrobials than from resistance itself. But also, lack of access can indirectly lead to worsening resistance, as infections are left to spread unchecked, or inappropriate drugs are used. In some cases, lack of access to first-line drugs means that later-line drugs, which ideally would be kept in reserve, are used, thus allowing resistance to develop to these critical drugs. Lack of access to antimicrobials has long been an issue in developing countries with weaker health systems and in smaller EU countries with insufficient market size to be profitable, but recently we have seen more widespread access problems in the EU. For example, in 2022, many European countries faced acute shortages of the antibiotic medication, amoxicillin.  

Ensuring access to necessary medicines is crucial, but at the same time, protecting antimicrobials from unnecessary use is key to ensuring their lasting efficacy. This can be a difficult line for countries to tread, as stewardship measures such as limiting some antimicrobials to hospital-only use can have unacceptable consequences on access. Stewardship, therefore, should not be considered in isolation. 

Thirdly, current payment systems do not adequately reimburse developers of antimicrobials for their efforts, especially when new drugs are intentionally used only sparingly to preserve their efficacy. This means pharmaceutical companies are dropping out of the market and the pipeline of new drugs is worryingly dry: the World Health Organization (WHO) found that the pipeline is “insufficient” to tackle rising AMR. The EU is the second largest pharmaceutical market, and yet even here, companies are withdrawing due to difficulties generating sufficient profit for novel antimicrobials. Solving AMR will include developing new purchasing systems which adequately reward innovation, without incentivising companies to oversell their product to increase their profit. 

AMR is not a problem that can be solved at the individual country level but is inherently a global issue. Resistance can freely spread across borders—so all countries lose from inappropriate use in one country. Similarly, new innovations spread across borders—so all countries gain from the R&D investments of other countries. Unfortunately, this global nature means AMR, much like climate change, suffers from the collective action problem: while all countries would benefit from working together, each individual country has an incentive to “free ride” or rely on the efforts of others, resulting in insufficient or inefficient action. Therefore, international bodies have a crucial role to play in ensuring the necessary collaboration to tackle AMR. This was recognised in a 2023 resolution of the EU Parliament, which stated that “action at EU level to address AMR can deliver clear added value, since no single Member State alone can provide an adequate solution to this cross-border and global issue.” 

Why should the EU address AMR now?  

We applaud the work of the previous Commission in raising the profile of AMR and recognising the importance of coordinated action. In July 2022, the European Commission identified AMR as one of the three top priority health threats. It is imperative that the new Commission build on this work. The COVID-19 pandemic has demonstrated just how vital pandemic preparedness is, the importance of global access to medications for cross-border challenges, and the need for a strong, coordinated response to such threats.  

However, previous work has insufficiently targeted access concerns. In April 2023, the Commission adopted a proposal for new pharmaceutical legislation, which included a proposal for employing transferable exclusivity vouchers to incentivise the development of novel antimicrobials. In June 2023, the Council adopted a Recommendation on stepping up EU actions to combat AMR which mainly focused on stewardship. While five sections of this report (B to F) included detailed recommendations on the prudent use of antimicrobials, infection prevention and control, surveillance of resistance and consumption, and education, innovation and access were only briefly discussed in section G. Given the interlinkage of the three pillars of access, stewardship, and innovation, and the particular access challenges many countries are facing, it is important for the new European Commission to build on the previous work to develop a sustainable access plan which ensures that innovations reach the areas of need, and that stewardship is appropriately targeted. There is a unique window of opportunity to build on the declaration of the upcoming UN General Assembly High-Level Meeting on AMR. Without action, it is estimated that 38.5 people million will die from resistance between now and 2050, including 1.6 million in the EU. On the other hand, improving access to, and innovation of, health treatment could prevent more than 100 million deaths. This would add USD 960 billion to the world economy by 2050, including more than EUR 80 billion to the EU’s GDP. By 2050, it would also save health systems USD 97 billion and EUR 6 billion a year globally and in the EU, respectively, compared to current trends of drug resistance. 

What can the EU do about AMR?

Implement a sustainable access hub to ensure access to antibiotics 

The EU should use its collective power to support global access to necessary antimicrobials. This would immediately benefit LMICs where access is especially problematic, but also—in the long term—protect EU member states from dangerous rises in resistance. We propose that the EU should support the implementation of a sustainable access hub which would act as a backstop to ensure access to a suite of essential antimicrobials and diagnostics in places where the current market fails to do so. This hub would have six key functions: firstly, it would procure or support the procurement of key antimicrobials and diagnostics—assisting countries (and faith groups and private providers, which are responsible for a significant part of procurement in some LMICs) in determining and aggregating demand and establishing multi-year agreements with manufacturers. Secondly, it would reduce market entry barriers, including facilitating registration and simplifying distribution procedures. Thirdly, it would shape markets as a large procurer, procuring drugs in a way that recognises the value of a sustainable market and that values robust manufacturing, affordability, environmental standards, and quality assurance. Fourthly, it would track consumption and support countries in reporting this information, as well as working with countries to improve stewardship practices where high consumption rates are identified. Fifthly, it could stockpile antimicrobials in order to manage demand shocks and overcome stockouts. Finally, it would provide financial assistance and/or technical support for resource-constrained countries to implement stewardship and surveillance systems. 

Depending on need for different drugs and country preferences, the hub could act either as a single global entity, a set of regional initiatives, or both (for example, with a central hub responsible for low-volume drugs that are then sold to regional hubs). The hub should be housed at an existing institution and should be funded by country governments according to their ability to pay, supported by donors, and/or through subscription fees from users.  

Figure 1: Benefits of a sustainable access hub

Implement a subscription model to incentivise innovation 

The EU should adopt a new economic model to incentivise innovation of new antimicrobials. As the second largest pharmaceutical market, the EU is one of the few global markets large enough to solve the innovation problem. It should follow the example of several individual countries that have started to enact such models, demonstrating their feasibility. For instance, the UK is adopting a subscription model for purchasing antimicrobials where price is delinked from volume and Sweden has enacted a revenue guarantee model (although this model is more focused on access concerns). The model we propose for the EU is a modified version of the subscription model used in the UK and the model that has been introduced to the US Congress via the PASTEUR Act. For each new antibiotic developed that meets certain criteria, including suitability for LMIC use, the EU would offer a reward for innovation, paid out over 10 years. In return for accepting this payment, companies would be required to register and sell their antibiotics into every EU country at an agreed, affordable price and ensure the continual availability of the antibiotic. Companies would also commit to ensuring that the drugs are available in LMICs—a requirement that could be supported by the sustainable access hub described above. Companies would also be required to track use and protect the drug from overuse. 

Figure 2: Proposed subscription model to incentivise innovation, while ensuring sustainable access

Enacting this new economic model would generate a significant return-on-investment (ROI) for both the EU and the world. Assuming a global cost of USD 3.3 billion per drug, the global ROI for investing in innovative new antibiotics alongside the better treatment needed to ensure everyone has access would be 28:1, and there would be 10 million fewer fatalities by 2050. Assuming the G7 and EU all paid their ‘fair share’ towards new drugs (which would equate to an EU contribution of €1.4 billion per drug), the ROI for the EU by 2050 would be more than 50:1 and there would have been 300,000 fewer fatalities from resistance. In other words, EU health systems would save four times the cost per year by implementing the policy.  

The proposed new economic model is a far better way to incentivise antibiotic R&D than the Transferable Data Exclusivity Voucher (TDEV) proposed in the 2023 EU pharmaceutical legislation reform. The TDEV would grant developers of novel antimicrobials a voucher for an additional year of regulatory data protection which the developer could either use with one of their own products or sell to another company. However, 14 member states signed a non-paper opposing this method and there are several downsides to such a model: it is inefficient; it pushes costs onto the small subset of society who rely on the drugs which gain extended warranty; and, as it is proposed, it does not distinguish between the quality of antibiotics, nor does it delink price from volume. Importantly, the proposed model does not include any provisions to guarantee sustainable access in LMICs.  

Improve surveillance to support stewardship

We encourage the EU to continue to support surveillance efforts by improving links with the Global Antimicrobial Resistance and Use Surveillance System (GLASS) run by WHO. While the EU has set a strong example of conducting surveillance via the European Centre for Disease Prevention and Control, many EU countries do not report their surveillance data to GLASS. We encourage improved coordination across these bodies to enhance global collaboration to tackle AMR. 

Conclusion

AMR is a rising threat to global health and prosperity; tackling it will require coordinated global action. The EU is uniquely positioned to leverage its large pharmaceutical market and respected track record in this area to incentivise innovation, ensure stewardship, and guarantee access. Crucially, the EU should recognise the global nature of AMR and work to ensure sustainable global access to any products of EU innovation.