EU’s New Health Threats Body Could Speed Arrival Of New Antibiotics
‘Pull’ Incentives Will Be Vital In Spurring Drug Development
Executive Summary
Europe is preparing a “preparatory action” to review existing measures for tackling antimicrobial resistance, identify the gaps, and to determine what products will be needed in future.
The planned Health Emergency Response Authority (HERA) offers the EU the chance to act as a “pipeline coordinator” in bringing promising new classes of antibiotics to the market and to help avoid critical product shortages in future health crises, according to a policy paper by Norwegian and French researchers.
But other interventions will also be needed to simulate innovation and secure access to new antibiotics, including “pull” mechanisms and more transparent procurement systems, say the authors of the paper, who work at Norway’s Institute of Public Health and France’s University of Limoges.
The European Commission decided to set up HERA when the coronavirus pandemic revealed vulnerabilities in the EU’s health preparedness and crisis response and in global supply chains, as well as insufficient oversight of manufacturing capacities and research priorities.
Seen as an equivalent to the US Biomedical Advanced Research and Development Authority (BARDA), HERA would aim to support the development, manufacturing and deployment of medical countermeasures in the event of future health crises. According to the commission, it will have “flexible and resourced financing and procurement capacities.”
A consultation on HERA was held from 31 March to 12 May, and the commission expects to adopt a regulation setting out the remit of the new body in the third quarter of this year.
AMR Capabilities
While the idea of HERA was predominantly spurred by COVID-19, it is also expected to be of benefit in the context of other health threats such as antimicrobial resistance (AMR).
The policy paper notes that a steady supply of new antibiotics for unmet public health needs is required, but companies are often not incentivized to carry out the necessary research, so countries will need to continue to provide R&D grants.
“Small innovators struggle to cover their operational costs," says the paper. "Three small companies with marketed antibiotics have gone bankrupt in the past two years. Large pharmaceutical companies have largely abandoned the development of new antibiotics.”
However, this could change with the advent of the new EU support mechanism. “With the advent of the Health Emergency Response Authority (HERA), the EU has an opportunity to act as a pipeline coordinator, shaping and bringing promising new classes to market,” the researchers say.
Public funding “ensures that critically needed antibiotics are financed, as opposed to those most likely to be profitable. Public funding may also improve the quality of the clinical evidence, so that physicians have a better understanding of how to use new antibiotics when approved.”
The paper notes that the EU has supported the development of clinical trial networks that can improve evidence generation and suggest that “HERA may also act to ensure a minimum level of regional production competencies that may be used for critical shortages.”
The paper emerged from work by the publicly funded EU Joint Action on Antimicrobial Resistance and Healthcare-Associated Infections (EU-JAMRAI), a project that ran from 2017 to 28 February this year in an effort to build a European program and policies to fight AMR. It was presented at a joint meeting of EU directors for pharmaceutical policy and the EU’s Pharmaceutical Committee on 8-9 July, and published alongside other presentations from that meeting on 2 August.
HERA Preparatory Actions
While HERA is being established, the EU has launched the “HERA Incubator” which is working with researchers, biotech companies and public authorities to allow the rapid detection of new SARS-CoV-2 variants, the production of modified COVID-19 vaccines, the fast-tracking of vaccine regulatory approval processes, and the upscaling of vaccine production and delivery. (Also see "Stung By COVID Critics, EU Looks To BARDA-Style Agency To Act Faster On Variants" - Pink Sheet, 18 Feb, 2021.)
Other than COVID-19, HERA “preparatory actions” are under way in a number of areas including AMR – which the EU estimates causes at least 33,000 deaths a year with additional healthcare costs of at least €1.5bn ($1.76bn) – and emerging biological threats.
Wolfgang Philipp of the commission’s health directorate (DG SANTE) told the July meeting that the preparatory action on AMR would include a technological review of the latest medical countermeasures as well as a gap analysis and needs assessment in the EU member states.
It would also involve a feasibility study to establish the medical countermeasures that are most needed to tackle AMR, Philipp said. Work on these two initiatives would begin this year and be completed in 2022.
As part of the preparatory action program, a tender was published last month for proposals on a methodology that HERA could use in intelligence gathering and anticipatory threat assessment once it has been set up. The deadline for proposals is 6 September 2021.
Pull Incentives
Alongside the HERA actions, other mechanisms will be needed to stimulate the development of new antibiotics, with the implementation of “pull” mechanisms being one of the most urgent, according to the researchers’ policy paper.
“EU-JAMRAI found that many European countries support the implementation of pull incentives for essential antibiotics (old and new) but are uncertain how to proceed and would prefer multinational collaboration,” they say. “The EU has committed to trial a pull incentive in 2021. EU-JAMRAI recommends a revenue guarantee.”
Under such an incentive, newly approved antibiotics would be recommended by the European Medicines Agency based on their ability to meet a public health need as assessed by the World Health Organization and national governments through health technology assessments. Existing antibiotics would be nominated by European countries that are concerned with vulnerable supply.
The commission would assess countries’ willingness to take part in the revenue guarantee for each eligible antibiotic, and a minimum number of countries would need to express interest for the antibiotic to be included in the tender, according to the researchers. “National financial responsibility for the guarantee would be apportioned and agreed.”
The commission would then carry out a tender for all the identified products, with companies marketing them having to commit to “access and stewardship stipulations for all participating countries.” Ideally, for older antibiotics multiple companies would be selected. “The revenue guarantee would be adjusted based upon the countries served.”
Countries taking part “would continue to price, procure, and reimburse the antibiotics as per normal national practices,” the researchers suggest. Companies would meet the access requirements in line with the revenue guarantees, which would ideally last for three to five years.
Each year, companies would report their total unit sales for each participating country to the commission, and national governments would validate these figures. “Each country would then pay the difference between its apportioned guarantee amount and actual sales to the company. If actual sales exceeded the guarantee amount, no further action would be taken.”
Piloting innovative approaches to EU R&D into antibiotics and preparing for “pull incentives” are part of the commission's Pharmaceutical Strategy, which was announced at the end of 2020, while the Horizon Europe Work Program for 2021-2022 includes the “design of a feasible option for a pull incentive that combines EU support for late-stage development of antimicrobials with procurement by member states and associated countries.”
Procurement Issues
The policy paper also stresses the importance of transparent and effective procurement procedures for antibiotics.
Many European countries award contracts to a single provider for the national supply of a medicine based solely on price. This pushes antibiotic prices as low as possible and incentivizes companies to consolidate to achieve even greater economies of scale, the researchers say. When a sole provider has production problems, this may result in a regional or global shortage, "potentially costing healthcare systems millions trying to alleviate the situation."
Some European countries have started awarding contracts to multiple providers. "However, to actually strengthen a diverse supply base, more countries must join them, resulting in stronger global supply chains for the benefit of all countries,” they suggest.