With plans underway for a new “Independent Panel” on Antimicrobial Resistance, endorsed at September’s UN High-Level AMR Meeting, the new body must become a strong scientific authority. It should have the power to “challenge” the agencies that create it and address both human and animal health factors driving drug-resistant pathogens.

That was a key message from AMR experts in the lead up to the Fourth Ministerial Meeting on Antimicrobial Resistance, which begins Friday in Jeddah, Saudi Arabia. 

The Independent Panel “needs to be an inclusive process… listening to scientists… civil society, to industry and other actors. But you also need to make sure that that panel, even though hosted by a Quadripartite, can actually challenge the Quadripartite,” declared John Arne Røttingen, CEO of the UK-based Wellcome Trust, of the panel’s central importance to providing evidence on future AMR policies.

The ‘Quadripartite’ includes the World Health Organization, as well as the global environment, food and animal health agencies, which are now formally collaborating to confront the AMR threat.

Røttingen was among the more than two dozen experts convened for two high-level AMR sessions at Berlin’s World Health Summit in mid-October to discuss next steps for the battle against drug resistant pathogens in the lead-up to the Jeddah meeting.

“Declarations are long. It’s hard to identify the real material commitments that have been made,”  Røttingen said at a panel discussion on Milestones and Challenges in Tackling AMR, hosted by the German Ministry of Health.

“So it’s great that we come to Jeddah for the ministerial meeting,” he said. “That should be a start of both countries’ [and development agencies]  coming together as well as the multi stakeholder partnership platform coming together across sectors to make sure that we are keeping our commitments.”

On the research front, meanwhile, new “pull incentives” recently developed in the United Kingdom, Italy and Canada to foster a sustainable market for next generation antibiotics are welcome, but they are not enough, industry experts asserted. Many more nations need to adopt supply-side incentives to ensure that badly-needed new drug candidates actually come to market.

Jeddah should be the start of making good on the UN’s AMR Declaration

The health ministers’ confab in Saudi Arabia (15-16 November) is supposed to lay out next steps for delivering on promises made in the Declaration on Antimicrobial Resistance approved at the UN High Level  Meeting, 26 September in New York City.  

September’s declaration was a major milestone in the battle to bring a long-ignored AMR epidemic to the forefront of global health policy. AMR is associated, directly or indirectly, a “silent, slow-motion pandemic” that could kill some 39 million people by 2050.

The mandate to create an “independent panel for evidence for action against antimicrobial resistance in 2025” is embedded in a 15-page text, with 106 clauses. But it is widely perceived as a key next move to maintain strategic momentum on AMR threats. 

The science panel should “facilitate the generation and use of multisectoral, scientific evidence to support Member States in efforts to tackle antimicrobial resistance, making use of existing resources and avoiding duplication of on-going efforts, after an open and transparent consultation with all Member States on its composition, mandate, scope, and deliverables,” the AMR  declaration stated.  

Final HLM declaration omitted target for reducing animal antibiotic consumption 

The science panel is supposed to be created and administered by the Quadripartite of agencies whose role in managing the AMR crisis was also formalized by the declaration. Along with WHO, the four-member body includes the UN Food and Agriculture Organization (FAO), the UN Environment Programme (UNEP), and the World Animal Health Organization (WOAH), a non-UN member state body.

And that makes the panel’s mandate and composition a sensitive point, in light of the political pressures from big food and other interests that want to play down their role in fostering AMR risks, which some researchers say is the leading driver. 

Pressures from agri-businesses and meat producing nations  already led to the deletion of a target for reducing animal antibiotic use by 30% by 2030 from the final HLM declaration. Now, the question is whether scientists can come together to articulate the evidence and agree on science-based policy recommendations.

“Even though the declaration was positive, it also didn’t achieve agreement on things that I, from my professional background, …would say should have been agreed,” Røttingen observed. “And that speaks to the interests and the trade offs between different sectors… it speaks to agri-food businesses versus human health, and that’s why we believe a science panel is important.”

He said, “We have the target of inverting AMR-related mortality [by 10% by 2030], but we need even more targets and more ambitious targets, so we have a lot to do,” he said.  

“In the climate sector, we have the IPCC (Intergovernmental Panel on Climate Change),” Røttingen continued. “We know how … contested the climate space is, but still, we have a collective international evidence base… We need authoritative evidence with scientists working in the human sector and the animal sector that can come together to actually give us that evidence base and give guidance. “

For animal health, as well, the ultimate aim is to curb abuse not essential use 

Worldwide, the overuse of such antibiotics in livestock production is widely regarded among experts as a leading, if not the leading, driver of pathogen resistance.

But ultimately, the aim of new measures should be win-wins that ensure better access to vaccines and other measures to pre-empt antibiotic use and ensure animal health, panelists at the sessions also underlined.

 “You need to be able to communicate with the people who can change that [AMR trends],” said Dr. Arshnee Moodley, a Kenya-based lead of CGIAR, which works with farmers on animal health. “And for me, it’s the smallholder famer outside of Nairobi.  I need to be able to tell him or her why they shouldn’t use antibiotics,” she said.

“And that’s really critical because livestock is also part of the solution; it’s vital food for vulnerable groups,” she continued.

“I worked every summer in my grandfather’s farm with three milk houses, from the age of 13. So I know about animal health and the need for small farmers, even in high income countries, to keep their herds healthy,” Røttingen countered.  

“When I’m concerned about the agricultural sector, it’s not really about the misuse of antibiotics among small scale farmers … it is about big food on several continents and making sure that they are … transparent and they are willing to engage in proper animal welfare, because that’s the starting point for ensuring animal health.

Too often, measures related to vaccines and hygiene are bypassed, “by using antibiotics to treat herds that aren’t necessarily requisite,” he explained.

Worst of all, is the use of antimicrobials or antibiotics “as growth promotion that has nothing to do with animal health. It’s not healthy for those who eat those animals, and it’s not healthy for the animals.

“So … animal health is an important part, but I think the hardest question lies with the big food companies.”

For human health – more prevention and better regulation are essential too

Much as with animals, infection prevention, appropriate access to drugs and better regulation need to be the operative goals for humans as well, panelists at a second high-level session on AMR agreed.  

That includes clean water, sanitation and hygiene that many communities and health facilities still lack, as well as stronger laboratory networks, and quality control of antimicrobials in settings were fake and substandard formulas often circulate.  

“Unfortunately for countries like us, we face challenges, because in terms of manufacturing…  we have to get them [products] from outside. So in terms of the quality…. you cannot be 100% sure that what you’re getting really is the very, very good quality,” said Khumbize Kandodo Chiponda Minister of Health, Malawi, speaking at the panel hosted by the global non-profit antibiotic accelerator CARB-X and the International Federation of Pharmaceutical Manufacturers and Associations (IFPMA).

Changing community behaviours and patterns can be a major lift, in light of the ease with which people can get antibiotics through more informal channels as well as the expense people might face in seeing a healthcare professional – who will in turn face challenges determining if antibiotics are needed or not – without adequate diagnostics equipment.  

Access to antibiotics is improving – but Africa is also becoming an AMR hotspot

“Access to antibiotics [in LMICs] is improving and that is a good thing,” said Tamas Koncz, a vice-president of Pfizer’s operations in Germany. He pointed to data citing a 114% increase in antibiotic use in low- and middle-income countries between 2000-2015.  Pfizer’s 2022 Accord for a Healthier World,  which committed to providing all of its patented medicines and vaccines to 45 lower-income countries on a not-for-profit basis, has been one enabler of better access to common antimicrobials, he said. At the same time, weak enforcement of prescription drug rules, as well as a lack of health provider knowledge about which drugs to prescribe, are drivers of drug resistance.   

“If physicians are not using [the drugs] appropriately, then it’s going to lead to problems. So we need to fix the challenge of access. But I think what is even more important is the overall approach.”

Africa, where sales of antibiotics by unlicensed vendors is often widespread, is also becoming a major AMR hotspot, he pointed out – highlighting the challenges of balancing access with judicious use. 

The landmark 2022 Lancet study that found 1.27 million deaths globally in  2019 were directly attributable to drug-resistant bacterial infections, including 860,000 in Africa. That same year, Africa saw 640,000 deaths from HIV.  

“We know from the recent communication from the African CDC and others, that it’s becoming probably the one of the biggest, if not the biggest, healthcare burden, superseding now HIV AIDs, maybe even malaria and tuberculosis,” said Koncz.  

‘Pull’ incentives 

On the supply side of the equation, meanwhile, “more pull incentives” that can incentivize pharma developers of newer, pathogen-resistant antibiotics is a long-neglected topic now finally rising to the top of health ministers’ agendas.  

The challenge lies in the fact that new antibiotics capable of beating drug-resistant infections also need to used sparingly – to ensure that they, too, don’t fail prey to AMR. But that means companies that develop the drugs can’t count on revenues from blockbuster sales to pay back years of investment in clinical trials. 

“AMR innovation is in a broken business model right now, needing incentives.” said Florence Séjourné. She is the CEO of the Aurobac Therapeutics, a joint AMR R&D venture created by two leading European pharma firms as well as the founder of the BEAM Alliance association of AMR-focused biotechs.  

Products risk death in the pipeline 

While there are now 20 “highly innovative” antibiotics in the early stages of development globally, the number will have dwindled by 75% within eight years if the business model doesn’t change, warned Dr Kevin Outterson, head of CARB-X.  “Within four years, we’ll have less than 10 in clinical development globally. And four more years after that, we’ll have less than five.” 

The of human capital” he added as large companies shut down programmes, and research is concentrated in underfinanced biotech startups. 

“There is absolutely no interest in private investors in the antibacterial field, which is complex,” added Séjourné. Of the startups, 60% of the BEAM Alliance members have less than a year of cash to fund their activities; 40% are firms of less than 9 employees.  

“The world is relying on micro companies, companies with less than 10 employees…That’s a very fragile base,” for developing urgently needed new drugs, Outterson added. 

On the cusp of a solution? 

But, there are also some glimmers of hope on the horizon. 

The first was the launch of the United Kingdom’s new “subscription model” in May for antimicrobial drugs that need to be held in ‘reserve’ for drug resistant pathogens. This aims to guarantee innovators a return on new drugs, regardless of the quantities used, that can guarantee a market incentive for new drugs, even if they are carefully rationed. 

Séjourné praised the UK decision as “something to highlight has a good example for others to follow” – although she warned that until a larger number of countries get on board with such changes, “the broken business model will remain.” 

More recently, at the 10 October meeting of G7 health and finance ministers in Ancona, Italy’s  Minister of Health, Orazio Schillaci announced a series of new “pull incentives” aimed at stimulating R&D and ensuring biotech firms a payback on their investment. Canada is also piloting an incentive programme, while other European Union members, as well as Japan, are considering similar moves. 

In light of those new developments, CARB-X’s Outterson sounds a note of cautious optimism. 

“At the G7 meeting, I made the economic case for a small, reasonable investment and push and mostly pull incentives, together, yields an amazing return on investment, both on the health side as well as the economic side,” Outterson said. “It was a rare opportunity to be able to speak not just to the health people, but also the finance people,” he said, noting that the issues raised at the meeting appeared to resonate with both sectors. 

“And so we have a problem, and we know that it’s desperate, and companies are filled with innovation, but not enough capital to move things forward. But we really are on the cusp of the solution as well.”

“The UN meeting finished only a few weeks ago,” said IFPMA director David Reddy. “We’re moving towards the meeting in Saudi Arabia, which is the fourth AMR high level event.

“I think one thing that is really important is that we are getting a common understanding of where we need to go, and what the challenges are,” he added. “We do need to make progress on the business model. The UK, Japan have already made good moves towards pull incentives, and a pilot has been put in place by Canada. There are a lot of remaining challenges, but I think the key message coming out of this is there is a real thirst to maintain momentum as we head into the meeting in Saudi Arabia.” 

But “it’s not just about financing,” he added, “it’s also about people and competencies.” 

“Access but having a really firm understanding of community needs on the ground is essential, because without that, we won’t make progress in the fight against AMR and in bringing antibiotics to those who need them.” 

Image Credits: USAID Asia/Flickr, USAID Asia , Health Policy Watch , Van Boeckel, Pires et al, 2019, WHO, The Lancet, 2022, AMR Industry Alliance.