Proceedings: DIA 2018 Global Annual Meeting

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.

DIAmond Session Panelists
Ivo Claassen, Head of Veterinary Medicines Division, European Medicines Agency (EMA)

Tatsuya Kondo, Chief Executive, Pharmaceuticals and Medical Devices Agency (PMDA)

Guido Rasi, Executive Director, European Medicines Agency (EMA)

Donald Prater, DVM, Assistant Commissioner for Food Safety Integration, OC, FDA

Pierre Sabourin, Assistant Deputy Minister, Health Products and Food Branch, Health Canada

Agnès Saint-Raymond (Moderator), Head of International Affairs, Head of Portfolio Board, European Medicines Agency (EMA)

Examples of Regional Initiatives

Europe: The need to reduce unnecessary use of antimicrobials in all areas as part of a “One Health” approach is a well-defined objective in the EU, with many countries setting specific targets for antimicrobial use reduction. Regulatory guidances have been developed to support R&D in humans and streamline the development of new antibacterial agents targeting infections caused by resistant bacteria.

In addition to coordinating activities with the EU Innovative Medicines Initiative (IMI), EMA collaborates regionally with the European Commission (EC) and sister agencies of EMA, like ECDC, and the European Food and Safety Authority (EFSA).

US: Since 2012, the FDA has been implementing a program called Generating New Antibiotic Incentives Now (GAIN Act) designed to help the development of antibacterial and antifungal drugs. As of Feb 2018, 147 Qualified Infectious Disease (QID) product designations, which reduce review times by roughly four months, were granted under the GAIN Act, and 12 QID designated antibacterial drugs have been approved so far.

To spur the development of new antimicrobial drugs intended for limited patient populations, the FDA recently announced a draft guidance for the Limited Population Pathway established under the 21st Century Cures Act. It includes recommendations for demonstrating the safety and effectiveness of antimicrobial drugs.

Tatsuya Kondo, PMDA

Japan: PMDA cooperates with academia to implement their AMR action plan and overcome existing problems. To support the appropriate use of antimicrobial agents beyond its borders, PMDA collaborates with other Asian countries on labeling changes and shares their experience with challenges and risk management plans via training seminars and staff dispatches. PMDA is also seeking to enhance public engagement to promote these activities and raise awareness.

Canada: Guidelines for healthcare professionals developed by the Public Health Agency of Canada as well as regular public awareness campaigns help raise awareness on the human side of antimicrobial use. Health Canada also requires AMR stewardship statements on all labels and the removal of all growth promotion claims on all antibiotics for animal use, which will be put on a prescription list by the end of the year. On the innovation side, Health Canada is considering foreign reviews to accelerate the approval of new antimicrobials.

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.