The U.S. Food and Drug Administration’s five-year plan to foster antimicrobial stewardship in animal agriculture and veterinary settings builds on the agency’s previous work and requires timely implementation. The plan, unveiled by Commissioner Scott Gottlieb on Sept. 14, outlines key objectives that are critically important to ensuring the judicious use of antibiotics in food animals.
The Pew Charitable Trusts has reviewed FDA’s plan and is encouraged by its scope and focus. However, given the urgency of the antibiotic resistance threat, the agency should accelerate the timelines to ensure that these important changes are made expeditiously. FDA also should publish more detailed, milestone-based roadmaps outlining how each objective will be achieved and commit to providing the public with regular progress reports.
Among the most noteworthy elements of the plan are provisions to ensure appropriate veterinary oversight for all medically important antibiotics, define appropriate durations for their use, and improve collection of critical data.
Ensuring veterinary oversight of all medically important antimicrobials
To ensure judicious use, all medically important antimicrobials administered to food-producing animals via feed or water were brought under veterinary oversight at the start of 2017 through agency Guidance for Industry 209 and 213. But medically important antimicrobials administered through other means—such as injection—can still be purchased over the counter without a prescription and without veterinary oversight. These include several antibiotics considered critical for human health by the World Health Organization (WHO) and whose use should be carefully managed.
As part of the five-year plan, FDA committed to ensuring appropriate veterinary oversight of all medically important antibiotics. Along the same lines, when Congress in 2018 reauthorized the Animal Drug User Fee Act, lawmakers required the agency to provide a report by Sept. 30, 2019, outlining more precisely how it will bring these remaining products under veterinary oversight. FDA should set an ambitious timeline to meet this critical objective, given the growing threat posed by the emergence of resistance to last-resort antibiotics.
For more details, see action items 1.1.3 and 1.1.4 in the plan. The deadline for initial action is 2021.
Establishing defined durations of use
Duration limits, or durations of use, specify the appropriate length of time that a drug should be used to address a given condition. Stewardship requires establishing science-based limits, which are already a central part of FDA’s animal drug approval process. However, many antibiotics for animals were approved before these requirements were in place.
As a result, about 1 in 3 medically important antibiotics can legally be given for very long or undefined durations of use, according to a Pew analysis. To address this long-identified problem, FDA opened a docket in 2016 seeking public input. The agency received more than 250 comments from a wide cross-section of animal agriculture and public health representatives.
For many drugs, scientifically based duration limits can be set using data for similar antibiotics that have defined durations of use, contain have the same ingredients, and are approved for the same or similar indications in the same or related species. Although differences would need to be considered—in product formulation, for example—using data from comparable drugs could expedite efforts to meet this goal. It also would minimize the regulatory burden on drug companies and ensure that animal producers and veterinarians maintain access to these vital drugs. Given how long FDA has recognized duration limits as a problem, the agency should accelerate current timelines, publish a milestone-based roadmap outlining how each objective will be achieved, and commit to providing the public with regular progress reports.
Pew’s analysis revealed other ways in which antibiotic labels do not meet FDA’s judicious use guidelines. For example, some labels allow antibiotics to be used for injudicious reasons—such as “maintaining weight gains during times of stress”—or tie duration of use to subjective or poorly defined external factors. FDA has publicly signaled plans to address these problematic uses.
For more details, see action items 1.1.1, 1.1.2 and 1.1.6 in the plan. The deadline for initial action is 2023.
Improving collection of antibiotic use data and disease surveillance
One of the three main goals in the FDA plan is “enhancing monitoring of antimicrobial resistance and antimicrobial drug use in animals,” emphasizing the importance of such data. Understanding how antibiotics are used on the farm, and for what purposes, is vitally important to assessing stewardship practices and evaluating the impact of policies to reduce unnecessary use of antibiotics.
In the plan, FDA commits to improving antibiotic use information, including development of a functional and efficient animal antimicrobial use data collection system. As part of that effort, FDA is working to enhance the National Antimicrobial Resistance Monitoring System, which provides vital insights into the emergence of antibiotic-resistant bacteria and tracks them in people, food animals, and retail meat. These improvements are consistent with previous recommendations from FDA’s Science Board and will allow FDA to capture more actionable data. They also will provide scientists and regulators with better information on how antimicrobial resistance arises and spreads.
For more details see action items 3.1.1, 3.1.3, 3.2.1, 3.2.2, and 3.3.2 in the plan. The deadline for initial action is 2023.
Update the list of medically important antibiotics
FDA’s Guidance for Industry (GFI) 152 outlines a recommended approach for assessing any public health risk related to antibiotic resistance posed by new antimicrobial drugs. Drugs considered medically important by FDA, and affected by GFIs 209 and 213, are listed in Appendix A of GFI 152. The list should be re-evaluated regularly to incorporate new data and account for changing antibiotic use practices.
The agency plans to revisit Appendix A, which was drafted in 2003 and has not been updated. WHO, by contrast, published a similar ranking of antibiotics in 2005 and has revised it five times. FDA’s list is largely consistent with WHO’s, but the agency does not consider some drugs, such as colistin and bacitracin, to be medically important, while WHO considers them critically important or important to human medicine.
Recent research, such as the discovery of the plasmid-mediated mcr-1 gene—which makes bacteria resistant to the last-resort antibiotic colistin—re-enforces the importance of regular updates to the list. Rigorous, science-based revisions underpin effective stewardship policies and ensure that FDA’s actions align with public health goals.
For more details, see action item 1.3.1. The deadline for initial action is 2021.
Other important agency actions
FDA also has committed to finalize a method for calculating animal biomass by 2021 as part of ongoing efforts to enhance the quality of antibiotic consumption data for food-producing animals. This will improve understanding of trends in consumption of antibiotics sold for and used in animals.
The plan also includes objectives to improve antimicrobial stewardship in companion animals such as cats and dogs and expand surveillance systems to capture relevant resistance data. Another provision seeks to foster international collaboration to promote stewardship in other countries and cooperation with international counterparts to identify ways to promote development of alternatives to antimicrobials.
As a whole, the plan can advance antimicrobial stewardship, combat antibiotic resistance, and help ensure that medically important antimicrobials remain effective. FDA should publish specific, concrete timelines with additional detail on how it will achieve the objectives and actions in its plan. Pew will continue to work with the agency and other stakeholders to advance the fight against antibiotic-resistant bacteria and better protect human and animal health.
Karin Hoelzer works on The Pew Charitable Trusts’ safe food and antibiotic resistance projects and is a veterinarian by training. Daniel Feingold works on Pew’s antibiotic resistance project.