The Fight Against Antimicrobial Resistance:
International Regulatory Convergence

Sandra Blumenrath
DIA Science Writer

ntimicrobial resistance (AMR) has become a serious global health concern. It is estimated that worldwide, between 2015 and 2050, roughly 10 million people will have died of infections caused by resistant bacteria. In addition to the health threat, the direct and indirect economic damage from AMR could amount to an annual loss in global GDP similar to the loss during the 2008 global financial crisis, according to the 2017 World Bank Report.

The “International Regulatory Convergence” DIAmond session brought together representatives from the European Medicines Agency (EMA), the US Food and Drug Administration (FDA), the Japanese Pharmaceuticals and Medical Devices Agency (PMDA), and Health Canada to discuss how regulatory agencies seek to set strategic goals and priorities for various collaborative regulatory initiatives addressing AMR. Each panel member outlined important initiatives that are on their agency’s agenda for the next two years as well as efforts to seek collaborations at an international level.

Key Takeaways

• Regulatory agencies can and should play a primary role in increasing AMR awareness and in promoting surveillance, coordination, and cooperation across geographies.
• All four regulatory agencies coordinate their research activities through various international initiatives, including efforts such as the Trans-Atlantic Task Force on Antimicrobial Resistance (TATFAR), tripartite EMA-FDA-PDMA meetings, bilateral EMA-FDA initiatives as well as cooperations with WHO (including PAHO), OIE, and Codex Alimentarius.
• Each country is also engaged in various regional initiatives that are focused on supporting R&D and streamlining the development of new antibacterial agents as well as their prudent use.
• The panel suggested “Push” and “Pull” incentives as a potential new business model to incentivize pharmaceutical industries to invest in the development of new antimicrobial agents.

As more and more bacteria become resistant to currently available antibiotics, international regulatory agencies are committed to tackling the issue on all fronts and seeking new approaches, including helping to ensure good antimicrobial stewardship and the use of appropriate clinical scenarios.

Global Coordination of Research Activities

Panelists agreed that AMR is a complex public health challenge that requires coordinated and sustained global action and a “One Health” approach that looks at both the human and the animal sectors. Each agency or region represented on the panel has done its share to address the AMR problem both regionally and internationally. The incentives of the agencies represented at this session follow a four-pillar action plan that addresses surveillance, infection prevention, stewardship, and research and innovation – all of which have both a domestic and an international angle.

The Trans-Atlantic Task Force on Antimicrobial Resistance (TATFAR):
TATFAR is a transatlantic taskforce that addresses three urgent actions to slow AMR globally: (1) the appropriate use of antimicrobial drugs in medical and veterinary communities, (2) the prevention drug-resistant infections, and (3) strategies for supporting the pipeline of new antimicrobial drugs.

TATFAR is a valuable and vibrant forum to capitalize on partnerships that implement strategies to reduce the public health threat of AMR. Originally established in 2009 as a partnership between the U.S. and the European Union (EU), TATFAR expanded in 2015 to include Canada and Norway.

Tripartite EMA-FDA-PDMA meetings:
As part of ongoing international harmonization efforts, the tripartite meetings held between the EMA, FDA, and PMDA discuss convergent regulatory approaches for the evaluation of antibacterial agents as well as other strategies required to encourage and accelerate the development of new antibacterial drugs to address unmet medical needs.

Bilateral EMA-FDA initiatives:
Bilaterally, EMA and FDA have a robust dialogue, identifying and reviewing progress on joint action items, exchanging new information about regulatory approaches, and identifying areas for further work.

WHO Action Plan:
The 2015 action plan on AMR was developed by WHO in collaboration with the Food and Agriculture Organization of the United Nations (FAO) and the World Organisation for Animal Health (OIE), to assist countries in refining and implementing national action plans in line with the objectives of the global action plan.

Left to right: Tatsuya Kondo, Donald Prater, Guido Rasi, Agnès Saint-Raymond (Moderator), Pierre Sabourin, Ivo Claassen.

To raise awareness worldwide, Canada is seeking to improve the quality and scope of surveillance data collected from both hospital and community settings to be able to transfer these data to WHO’s global surveillance system by 2019.

The Need for a New Business Model

To ensure a sustainable pipeline of antimicrobials, new financial incentives are needed to reward innovation. New antibiotics are not profitable, and R&D in this area is scientifically challenging, yielding only low success rates.

As a new business model the panel suggested “Push” or “Pull” incentives. “Push” incentives would support discovery and early phases of development, for example in the form of research grants. Current incentives include the Joint Program Initiative on AMR (JPIAMR) supported by 27 countries, EC grants, and the public-private partnership Combating Resistant Bacteria (CARB-X).

“Pull” incentives, on the other hand, delink payment from prescribing volume, which in turn encourages good stewardship (i.e. prudent use of antimicrobials) in the market, on both the human and the veterinary side. In a fully delinked market, an entry reward system should be considered, such as entry rewards without sales-based income or market-priced entry rewards with some sales-based income. Several initiatives in the EU and US, including TATFAR, are currently discussing these approaches.