FDA-TRACK: Progress on FDA’s Support of Antimicrobial Stewardship in Veterinary Settings
FDA's Center for Veterinary Medicine (CVM) regulates animal drugs, animal devices and animal food under the Federal Food, Drug and Cosmetic Act. CVM protects and promotes the health of humans and animals by ensuring the safety of the American food supply, the safety of animal food and devices, and the safety and effectiveness of animal drugs.
For more than 60 years, antimicrobial drugs have been widely used to effectively fight bacterial infections in humans and animals. When bacteria develop resistance to an antimicrobial drug, that drug may be less effective in fighting infections caused by those bacteria. Using antimicrobial drugs in humans and in animals can contribute to the emergence of antimicrobial resistance in bacteria, thereby reducing the effectiveness of antimicrobial drugs for treating human disease.
The U.S. Food and Drug Administration’s (FDA) Center for Veterinary Medicine (CVM) has developed a multi-pronged, multi-year strategy designed to slow the emergence of resistance arising from the use of antibiotics in animals, while continuing to ensure the availability of safe and effective antibiotics for use in animals and humans. Supporting Antimicrobial Stewardship in Veterinary Settings: Goals for FYs 2019 - 2023 serves as CVM’s action plan for guiding its activities over the next five years to combat antimicrobial resistance and help preserve the effectiveness of medically important antimicrobial drugs. The performance measures on this web page align with three overarching goals in CVM’s plan:
Goal 1: Align antimicrobial drug product use with the principles of antimicrobial stewardship
- Veterinary Oversight of Medically Important Antimicrobial Drugs
- Duration of Use of Medically Important Antimicrobial Drugs
- Enhancing Processes to Support New Product Development
Goal 2: Foster stewardship of antimicrobials in veterinary settings
Goal 3: Enhance monitoring of antimicrobial resistance and antimicrobial drug use in animals
Goal 1: Align antimicrobial drug product use with the principles of antimicrobial stewardship
Veterinary Oversight of Medically Important Antimicrobial Drugs
Judicious use of antimicrobials is an integral part of good veterinary practice. We believe judicious use includes using antimicrobials only when it is necessary and in a manner that strives to provide effective therapy while minimizing the selection of resistant microorganisms.
The principles of FDA’s judicious use policy include ensuring medically important antimicrobial drugs are used under the supervision of licensed veterinarians and limiting uses of medically important antimicrobial drugs in food-producing animals to those considered necessary for assuring animal health.
Accomplishments: Implementation of Guidance for Industry (GFI) #213, New Animal Drugs and New Animal Drug Combination Products Administered in or on Medicated Feed or Drinking Water of Food-Producing Animals, brought all 292 approved applications for medically important antimicrobials intended for use in the feed and drinking water of food-producing animals under veterinary oversight or voluntarily withdrew their approvals.
Based on the FDA 2022 Summary Report on Antimicrobials Sold or Distributed for Use in Food-Producing Animals, this represents approximately 99%, by weight, of all medically important antimicrobials sold/distributed for use in food-producing animals in the United States. The remaining 1%, by weight, of medically important antimicrobials includes products approved for routes of administration other than feed or drinking water.
Next Steps: To understand the impact of CVM’s actions, we aim to track label revisions for the medically important antimicrobial drugs that remain available over-the-counter as they transition to prescription marketing status.
Disposition of the remaining 1 approved application is CVM’s target for the new effort being captured under GFI #263, Recommendations for Drug Sponsors for Voluntarily Bringing under Veterinary Oversight All Medically Important Antimicrobial Drugs in Animals that Continue to be Available as Over-the-Counter Products. Of the 1 remaining approved applications available without a prescription or Veterinary Feed Directive (VFD) authorization, 1 are dosage forms other than feed or water administration (e.g., injectable, intramammary) marketed for food-producing animals, 0 are all dosage forms for companion animals, and 0 are all dosage forms for both food-producing and companion animals.
In GFI #263, CVM is providing affected sponsors with a process to change the marketing status of the remaining over-the-counter products. As industry completes this process, updated labels will reflect the transition to veterinary oversight (prescription status). Alternatively, there may be cases where a sponsor decides to withdraw a product’s approval.
Once GFI #263 is fully implemented, all medically important antimicrobials approved for use in animals (both food-producing and companion) will be under the oversight of a licensed veterinarian.
Duration of Use of Medically Important Antimicrobial Drugs
Another contributor to the development of antimicrobial resistance could be the administration of medically important antimicrobial drugs for undefined periods. The principles of antimicrobial stewardship, including judicious use, emphasize that medically important antimicrobial drugs should only be used to treat, control, or prevent a disease and be administered for an appropriately targeted period (that is, have a defined duration of use).
Our primary objective in defining durations of use is to update certain product dosage regimens to define when and for how long the drug may be used. Defining appropriately targeted durations of use for the approved applications that lack this information supports CVM’s ongoing efforts to slow the development of antimicrobial resistance.
Accomplishments: Since 2003, CVM has required all new unique indications for pioneer new animal drug approvals to include a defined duration of use. As a result, about 65% of all currently approved medically important antimicrobial drugs administered in the feed or water of food-producing animals already have a defined duration of use.
Next Steps: There are currently 97 approved animal drug applications that lack a defined duration of use. CVM will work over the next several years to establish targeted durations of use, so that veterinarians have clear labeling indications and instructions on how long to use a medically important antimicrobial drug.
In some cases, there may be significant scientific and technical challenges to establishing defined durations of use, such as the potential need to generate appropriate supporting data. CVM has issued a funding opportunity announcement and Request for Applications (RFA) for studies that can help target and define durations of use for certain medically important antimicrobial drugs approved for use in the feed of food-producing animals. We intend this funding to help generate publicly available data that sponsor(s) of affected approved animal drug applications can use to update product dosage regimens to better target when and for how long the drug may be used.
Additionally, in advance of developing a draft guidance, CVM will publish and seek public comment on a concept paper outlining a draft strategy for how sponsors could establish defined durations of use for impacted applications. Public comment will help FDA gain additional information about how label modifications may impact animal production and ensure that veterinarians are able to continue using these products for therapeutic purposes.
As with our approaches to bringing medically important antimicrobial drugs under the supervision of licensed veterinarians, CVM will work with industry to update product labeling to provide for appropriately defined durations of use. We expect implementation timelines to vary by application. In some cases, sufficient data already may be available to establish appropriately defined durations of use, but in other cases, new studies may be needed to generate these data.
Enhancing Processes to Support New Product Development
CVM is responsible for ensuring that animal drugs are safe and effective for their approved conditions of use. To accomplish this, CVM conducts an extensive premarket review of the safety and effectiveness data for each animal drug and monitors the safety and effectiveness of each drug after it is approved for marketing.
While medically important antimicrobials are valuable tools for addressing certain animal health needs, identifying alternatives for managing animal disease can reduce reliance on such drugs and help slow the development of resistance.
Accomplishments: Since implementing GFI #152, Evaluating the Safety of Antimicrobial New Animal Drugs with Regard to Their Microbiological Effects on Bacteria of Human Health Concern, in 2003, CVM has assessed antimicrobial resistance risk for all new medically important antimicrobial products intended for use in food-producing animals. As part of CVM’s premarket antimicrobial resistance risk assessment, FDA ranks antimicrobial drugs according to their importance to human medicine following criteria in Appendix A of GFI #152.
Next Steps: FDA needs to update this human medical importance ranking to reflect current science and medical practice. Having an up-to-date GFI #152 in place is vital to ensure that as part of the animal drug approval process there is an effective process for assessing antimicrobial resistance concerns. Therefore, as part of our actions, in October 2020, CVM published a concept paper on a potential revised process and criteria for ranking antimicrobial drugs based on their importance in human medicine. Following that posting, CVM held a public meeting to obtain early public input on the information. The deadline to receive comments on the concept paper was March 16, 2021.
In addition to updating Appendix A of GFI #152 for assessing new animal drug applications, CVM will seek opportunities to facilitate alternative product development and focus on innovative methods to assess alternatives to antimicrobial drugs. CVM also advocates for non-drug alternatives when appropriate, such as changes in husbandry, biosecurity, vaccination, and other factors. Consistent with its mission, CVM is interested in exploring how new technologies and novel animal drug products could be used to address animal health needs and reduce reliance on medically important antimicrobials.
Goal 2: Foster antimicrobial stewardship in veterinary settings
Education and Outreach
Over the past several years, as part of fostering antimicrobial stewardship in veterinary settings, CVM has maintained its focus on educating affected stakeholders and continues to respond to various questions and challenges related to implementing GFI #213, the VFD final rule, and CVM’s 5-year Plan for Supporting Antimicrobial Stewardship in Veterinary Settings.
Accomplishments: To implement GFI #213 to bring under veterinary oversight animal drugs administered in the feed or drinking water of food-producing animals, CVM participated in more than 200 stakeholder meetings and webinars to provide education and training around its antimicrobial resistance strategy, including the VFD final rule. Several knowledge gaps emerged during those engagements, which led CVM to create videos and brochures on the VFD final rule and the following question and answer documents:
- CVM Draft GFI #120 Veterinary Feed Directive Regulation Questions and Answers
- CVM GFI #233 Veterinary Feed Directive Common Format Questions and Answers
- Using Medically Important Antimicrobials in Bees – Questions and Answers
- Questions and Answers: FDA Approved Free-Choice Feeding Options for Anaplasmosis Control in Cattle
Enhancing the availability and accessibility of information has been a key driver to the education and outreach component of CVM’s antimicrobial resistance strategy. In July 2019, CVM added medicated feed resources to the Animal Drugs @ FDA website to enhance information accessibility. One resource, Blue Bird labels, are representative labels sponsors of Type A medicated articles produce to guide manufacturers of medicated animal feeds in preparing final printed labels for Type B and Type C medicated feeds. Sponsors submit a Blue Bird label as part of the new animal drug approval process. A Blue Bird label contains the drug's indications for use, active drug ingredient, mixing directions, and other information to ensure the medicated feed can be used in a safe and effective manner. For feeds containing antimicrobial drugs, having the Blue Bird labels easily accessible on the internet provides feed manufacturers, veterinarians, and animal producers with a reliable source for label information, which is vital for the judicious use of these drugs in animals. CVM also added lists of licensed medicated feed mills and VFD distributors to Animal Drugs @ FDA, making it easier for stakeholders to find a medicated feed manufacturer or distributor in their area and access needed antimicrobial drugs.
While CVM offers educational and information resources directly, these materials have an extended impact when stakeholders disseminate CVM guidance and other resources to their constituencies in whole or in part. CVM’s partners in antimicrobial stewardship education include veterinary medical associations, academic organizations, consumer advocates, international partners, and other associations.
Next Steps: Consistent with the approach CVM took to implement GFI #213 and the VFD final rule, once we finalize GFI #263 to bring remaining dosage forms of antimicrobial drugs under veterinary oversight, we plan to pursue outreach platforms, such as public meetings, webinars, fact sheets, and similar communications to provide additional education opportunities to impacted stakeholders. Education and outreach remain critical tools to gain the support of the animal production industry and provide stakeholders with the tools they need to successfully implement recommendations from GFI #263. CVM will continue to encourage interested stakeholders to use our guidance and information resources to extend the reach and impact of our outreach.
Veterinary Feed Directive Compliance
CVM conducts VFD inspections to verify that antimicrobials used in or on the feed of food-producing animals are being authorized appropriately according to the VFD final rule. These inspections also help to ensure that veterinarians, animal producers, and VFD medicated feed distributors (medicated feed mills and retailers of VFD medicated feed) have the information they need to comply with the VFD final rule.
Accomplishments: In June 2015 CVM finalized the VFD rule and shortly thereafter, in January 2017, we completed the process outlined in GFI #213 to voluntarily transition all medically important antimicrobial drugs used in or on animal feed from over-the-counter to VFD marketing status. This step was essential in providing veterinarians the authority to oversee using antimicrobials in the feed of food-producing animals.
CVM began conducting initial VFD inspections in fiscal years 2016 and 2017. These initial inspections focused heavily on educating animal producers, veterinarians, and VFD medicated feed distributors as part of the phased-in compliance strategy, “Education Before Regulation.” In fiscal year 2018, CVM began to transition beyond education toward an inspection approach focused on compliance with the VFD requirements and documenting violations when found. CVM has rarely issued an “official action indicated” or “voluntary action indicated” finding during a VFD inspection. In conjunction with FDA’s Office of Regulatory Affairs, CVM has found 95% of inspected stakeholders in compliance with the VFD rule. This overwhelming compliance rate indicates veterinarian involvement in the judicious use of VFD feeds and serves as a signal that education and outreach related to VFD have been a success.
Next Steps: Monitoring VFD compliance helps to promote judicious use of medically important antimicrobials administered in feed. VFD inspections and their findings have allowed FDA to respond to additional stakeholder questions about VFD implementation, gain understanding of industry practices related to the VFD final rule, and shape a broader inspection strategy to ensure ongoing compliance with the VFD regulation.
Goal 3: Enhance monitoring of antimicrobial resistance and antimicrobial drug use in animals
Antimicrobial Use in Animals
Antimicrobial use in humans, animals, and the environment is one driver of antimicrobial resistance development. Understanding antimicrobial use through a One Health lens—which recognizes that the health of people, animals, and the environment is intertwined—also helps scientists and public health professionals track zoonoses and reverse zoonoses, which are infectious diseases that can spread from animals to humans and from humans to animals, respectively.
Furthermore, gathering information on the way antimicrobials are used in animals is essential to measuring the impact of CVM’s judicious use strategy. As described in the Goal 1 performance measures, these data have supported efforts to assess changes in veterinary oversight. These data could help CVM evaluate antimicrobial stewardship efforts and guide their continued evolution and optimization. Additionally, these data could help CVM assess associations between antimicrobial use practices and resistance in foodborne and animal pathogens.
Antimicrobial use data are also important to provide context to other stakeholders, like animal producers and veterinarians, who may be implementing antimicrobial stewardship programs of their own. By making antimicrobial use data collection methodologies and analyses available to the public, CVM will offer resources for all stakeholders to investigate and work toward nationally representative ways to understand antimicrobial use in animals.
Accomplishments: In 2016, CVM began funding two cooperative agreements to support data collection for on-farm antimicrobial use in animal agriculture in the United States. One collects on-farm antimicrobial use data from the poultry and swine industries, while the other collects on-farm antimicrobial use data from the dairy and feedlot cattle industries. Subject to funding availability, CVM expects to continue these pilots through 2021 and, once complete, they will provide baseline information about on-farm antimicrobial use practices. Information obtained from actual on-farm antimicrobial use data helps CVM determine how and why antimicrobials are being used and where CVM could direct efforts to enhance antimicrobial stewardship. Data collected through the on-farm antimicrobial use cooperative agreement projects may also be used to develop long-term sustained platforms for antimicrobial use data collection.
While CVM’s focus has been primarily on collecting data for food-producing animals, it is also important to collect data on the use of antimicrobial drugs in companion animals to help understand whether these use practices contribute to the development of antimicrobial resistant bacteria in pet owners and their pets. In 2020, CVM announced a new funding opportunity to collect antimicrobial use data in companion animals, specifically dogs and cats.
Next Steps: CVM will use data collected from the food-producing animal and companion animal cooperative agreements to optimize data collection methodologies in individual animal sectors and devise long-term strategies to collect and report antimicrobial use data in animals.
CVM plans to publish a report of the information gathered through the cooperative agreements that characterize antimicrobial use practices in poultry, swine, dairy cattle, and beef cattle. This report will help shape our stakeholder engagement and guide us in developing a long-term strategy to implement functional and efficient systems to collect antimicrobial use data in food-producing animals.
Additionally, CVM will engage with stakeholders to develop and implement a strategy to promote the judicious use of medically important antimicrobials in companion animals. Information gathered from the companion animal cooperative agreements will help shape this strategy.
Antimicrobial Resistance in Animals
Public health authorities rely on national antimicrobial resistance data to determine the nature and magnitude of resistance in specific pathogens from different sources, document changes in resistance over time, understand the factors driving which bacteria evolve resistance, detect new and emerging resistance patterns and strain types, identify resistance in strains causing outbreaks and the source of the strains, assess the impact of interventions designed to stop or reverse resistance, and enhance international cooperation through timely data sharing.
The National Antimicrobial Resistance Monitoring System (NARMS) is a U.S. public health surveillance system under which the FDA, Centers for Disease and Control and Prevention (CDC), and U.S. Department of Agriculture (USDA) track antimicrobial resistance in foodborne and other intestinal bacteria. 1 The FDA component of NARMS purchases retail meat in grocery stores across the United States and isolates and analyzes bacteria from those samples to understand antimicrobial resistance. These data are important because research shows that, in developed countries like the United States, most consumer exposure to bacteria originating in food-producing animals occurs in retail settings (grocery or restaurant purchases) rather than by direct exposure to livestock.
The Veterinary Laboratory Investigation and Response Network (Vet-LIRN) is a program run by FDA's Center for Veterinary Medicine. Vet-LIRN consists of 47 state, local, and university veterinary diagnostic laboratories located throughout the United States and Canada. Since 2017, Vet-LIRN has applied the One Health paradigm to successfully track antimicrobial resistance in bacterial pathogens from animals, particularly companion animals that reside with humans.
CVM uses data collected by NARMS and Vet-LIRN in various ways, including to understand how antimicrobial resistance emerges, persists, and spreads. Together, NARMS and Vet-LIRN are the FDA programs that help CVM understand and interpret the drivers of antimicrobial resistance. They also support risk analysis of foodborne antimicrobial resistance hazards when CVM evaluates a new animal antimicrobial drug for safety, help CVM understand the nature and magnitude of antimicrobial resistance trends, and guide evidence-based action to limit or reverse worsening antibiotic resistance trends.
Accomplishments: Part of CVM’s efforts to enhance the collection and analysis of antimicrobial resistance data includes expanding the reach of NARMS and the contributions of Vet-LIRN. Since its founding in 2002, the FDA component of NARMS has collected and analyzed bacteria from samples of retail meat from grocery stores around the country to reflect prevalent American diets: beef, chicken, pork, and turkey. NARMS has steadily increased the number of isolates each year, from 3,030 total bacterial isolates from all products in the first year (2002) to a cumulative total of 84,129 in 2023 (latest data available), and growing. This library of bacterial isolates, individually analyzed to understand their antimicrobial susceptibility, allows CVM and other public health authorities to understand antimicrobial resistance through time. Resistance monitoring and analysis of the growing database helps document resistance levels in different reservoirs to establish baselines; describe the spread of resistant bacterial strains and resistance genes; identify trends through time and geography; and generate hypotheses about sources of reservoirs and resistant bacteria to understand attribution. These data help animal producers, public health officials, and FDA make decisions intended to contain antimicrobial resistance or limit its spread. For example, to preserve the effectiveness of antimicrobials for human medicine, CVM limited certain uses of cephalosporins and withdrew the approval of fluoroquinolones for use in poultry.
Likewise, from its original survey of ground beef, retail chicken, pork chops, and ground turkey beginning in 2002, NARMS expanded in 2020 to begin retail sampling of seafood (shrimp, salmon, tilapia) to capture even more data about how antimicrobial-resistant bacteria may be developing in additional food products where antimicrobial drugs are used.
In addition to sampling seafood products, NARMS expanded its bacteria sampling in 2020. Original analyses centered on Campylobacter, Escherichia coli, Enterococcus, and non-Typhi Salmonella in each meat product. Expansion plans include analysis for a broader range of intestinal organisms in retail meat samples as well as for Aeromonas and Vibrio in seafood samples.
Partnerships with laboratories across the country are vital to NARMS’ success. NARMS retail meat testing began in 2002 collaborating with one university laboratory and sampling in 5 states. In 2020, NARMS boasted coverage of 24 states via 23 partner laboratories from universities and state and local health departments that purchase retail meat samples and culture them for target bacteria. They submit these isolates to CVM, where CVM scientists confirm the isolates’ species and serotype, perform antimicrobial susceptibility testing, and conduct genetic analyses using whole genome sequencing.
The NARMS program now routinely performs whole genome sequencing on nearly all sampled isolates and deposits the results into a national pathogen tracking database at the National Institutes of Health, National Center for Biotechnology Information. This near real time data sharing represents the latest information on antimicrobial-resistant bacteria in meat and poultry and provides public health officials and industry with definitive information on the types of foodborne bacteria making people ill.
CVM’s other program involved in antimicrobial resistance efforts, Vet-LIRN, has historically engaged in diagnosis and laboratory analysis to respond to animal illnesses caused by animal feed, pet food, and animal drugs. In response to a 2015 presidential initiative, however, Vet-LIRN has leveraged its laboratory network capacity to contribute to antimicrobial resistance efforts in veterinary settings.
During 2017-2018, Vet-LIRN coordinated a two-year pilot project to evaluate the feasibility of using member veterinary diagnostic laboratories to track the antimicrobial resistance of select veterinary pathogens. Twenty Vet-LIRN partner laboratories collected samples of veterinary pathogens from dogs and conducted antimicrobial susceptibility testing for Escherichia coli and Staphylococcus pseudintermedius. They also collected samples of veterinary pathogens from other hosts, such as cattle and swine, and tested these and the dogs’ samples for Salmonella enterica. Four additional laboratories sequenced a subset of the isolates. By 2019, Vet-LIRN had converted its pilot to a permanent surveillance program, expanding participation to 35 partner laboratories. These laboratories collect samples and perform susceptibility testing, submitting a subset of isolates to 6 of the participating laboratories to perform whole genome sequencing. By the end of 2019, Vet-LIRN’s antimicrobial resistance surveillance program had collected and tested antimicrobial susceptibility for more than 6,000 isolates from clinically ill animals and sequenced more than 2,500 of them. Vet-LIRN makes its animal pathogen antimicrobial resistance data public as part of the annual NARMS Integrated Report. The evolution of this pilot to continuing program status adds Vet-LIRN state veterinary diagnostic laboratory capacity to the overall effort to track and understand antimicrobial resistance in animals, including companion animals.
Next Steps: Public health professionals have reached consensus on adopting an interdisciplinary One Health model of infectious disease monitoring and control. The One Health paradigm recognizes that human and animal health are linked to environmental health and to the need to understand the role of the environment in the spread of diseases. Best practices for One Health antimicrobial resistance surveillance encompass tracking resistance in animal pathogens and in the environment. Following recommendations of FDA's Science Board, the agency has been a leader in adopting the One Health interdisciplinary model for antimicrobial resistance surveillance. CVM is focusing its NARMS enhancements on monitoring resistance in bacteria causing infections in the animals humans consume, and FDA is working to expand the interagency NARMS program to reflect the goals of One Health. Furthermore, with state veterinary diagnostic laboratories, Vet-LIRN's large pilot studies have established methods and data processes to track resistance in bacteria infecting animals. CVM is using all these results to establish long-term, sustainable tracking of resistance in companion animals and food-producing animals. The goals for antimicrobial resistance monitoring by NARMS and Vet-LIRN over the next five years are summarized in the NARMS Strategic Plan: 2021-2025.
Note: The data provided on this website is produced on an ongoing basis for performance management purposes and is subject to change due to updates of preliminary estimates, corrections, or other reasons.
- 1CDC tracks changes in the antimicrobial susceptibility of certain intestinal bacterial found in ill people. USDA tracks antimicrobial susceptibility in food animals.