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Timeline of FDA Action on Antimicrobial Resistance

Timeline of FDA Action on Antimicrobial Resistance

  • 1980’s - All new medically important antibiotics have been approved with veterinary oversight.
  • 1993 to present - New applications for medically important antimicrobials used in food-producing animals have only been approved as VFD or prescription products. Both marketing status designations require a veterinarian to be involved in decisions about when and how to use these products in animals.
  • 1996 - Together with two other federal partners (USDA and CDC), CVM established the National Antimicrobial Resistance Monitoring System (NARMS) program. Since 1996, the program has undergone several enhancements. For example, NARMS revised its animal sampling structure in 2013 to obtain more representative animal data on all four target organisms under surveillance (Salmonella, Campylobacter, Escherichia coli, and Enterococcus).
  • 1997 - Prohibited extralabel use of fluoroquinolones and glycopeptides (FR Doc No: 97-13677). Note: While other countries approved the glycopeptide, avoparcin, for use in food-producing animals, this class was never approved or marketed for such uses in the U.S.
  • 2003 - FDA established industry guidance for assessing antimicrobial resistance risks as part of the drug approval process (Guidance for Industry #152, FR Doc No: 03-27113). This guidance also established a qualitative risk assessment approach for evaluating the microbial food safety of antimicrobial new animal drugs as part of the new animal drug approval process.
  • 2005 - Withdrew of approval of fluoroquinolones for use in poultry (FR Doc No: 05-15223 [Final Rule], Docket ID: FDA-2000-N-0109). Note: fluoroquinolones are still used in some other countries for poultry; see Withdrawal of Enrofloxacin for Poultry for more information.
  • 2005 - FDA incorporated a step-wise approach into the pre-approval process to evaluate the effect of antimicrobial residues on human intestinal flora into the pre-approval safety assessment of agents for food-producing animals; one of the end points of concern is the increase of antimicrobial resistant bacteria. (Guidance for Industry #159, Docket ID: FDA-2003-D-0433).
  • 2010 - Initiated judicious use effort with issuance of draft Guidance #209 (Docket ID: FDA-2010-D-0094).
  • 2010 – Published the first annual summary report of antimicrobials sold or distributed for use in food-producing animals in accordance with section 105 of the Animal Drug User Fee Amendments of 2008 (ADUFA Reports).
  • 2012 - Prohibited certain extralabel uses of cephalosporins (FR Doc No: 2012-35 [Final Rule]; Docket ID: FDA-2008-N-0326). Note: 4th generation cephalosporins have never been approved for use in food-producing animals in the U.S.
  • 2012 - Published final Guidance for Industry #209, which established a framework for ending production uses (e.g., increased rate of weight gain and improved feed efficiency) of medically important antimicrobials and brought the remaining therapeutic uses of such drugs in food-producing animals under veterinary oversight.
  • 2012 - Published draft Guidance #213 (Docket ID: FDA-2011-D-0889), in which CVM provided more detailed guidance to sponsors regarding how to align their antimicrobial drug products with GFI #209 recommendations. More specifically, the guidance defined which drug products are affected and established a three-year implementation timeline.
  • 2012 - Published draft Veterinary Feed Directive (VFD) proposed rule (Docket ID: FDA-2010-N-0155).
  • 2012 & 2013 Solicited public input on data collection and reporting related to antimicrobial use in food-producing animals. In response to the comments received on reporting, FDA proposed additional tables to enhance annual summary reports of antimicrobials sold for use in food-producing animals (Docket ID: FDA-2012-N-0447).
  • 2013 - Published final Guidance for Industry #213 and proposed VFD rule (Docket ID: FDA-2010-N-0155).
  • 2013 - FDA revised its animal sampling structure in NARMS to get more representative animal data on all four target organisms under surveillance.
  • 2014 - First publication of annual summary report of antimicrobials sold for use in food-producing animals in expanded format (ADUFA Reports).
  • 2014 - NARMS implements whole genome sequencing and uploading of the information to the public database at NCBI.
  • 2015 - FDA issued the Veterinary Feed Directive (VFD) final rule, which governs how veterinarians authorize the use of VFD-designated animal drugs in feed. The revised regulation improves the efficiency of the VFD process, a critical step to facilitate implementation of GFI #213 to transition the marketing status of antimicrobial drug products from OTC use to VFD use under the direction of a licensed veterinarian (veterinary oversight).
  • 2015 - Concurrent with the publication of the final rule updating the VFD regulation in June 2015, CVM developed a VFD inspection framework to assist field personnel as they conduct inspections of the various parties involved in the VFD process (veterinarians, distributors, and animal producers). This inspection framework looks at VFD orders, requirements for the parties involved, and recordkeeping. Our intent is to phase in compliance activities related to the VFD rule over time, with the initial phases devoted heavily to educating feed mills, retailers, veterinarians, and animal producers about VFD requirements. 
  • 2016 - Announced a funding opportunity for antimicrobial use and resistance data collection. These collection efforts are intended to provide part of the baseline information on antimicrobial use practices in the four major food-producing animal groups (cattle, swine, chickens, and turkeys), a critical element in measuring overall impact of the agency’s judicious use strategy. We also expect the data collection efforts to provide important information on methodologies to help optimize long-term strategies for collecting and reporting such data.
  • 2016 - Approved the first alternative to an antimicrobial drug, Imrestor. Imrestor was also the first animal drug for use in food-producing animals simultaneously reviewed and approved in both the United States and Canada.
  • 2016 - Sought public input on establishing appropriately targeted durations of therapeutic use of medically important antimicrobial drugs in food-producing animals. 
  • 2016 - Issued a final rule revising the annual reporting requirements for drug sponsors of antimicrobials sold or distributed for use in food-producing animals. The additional data CVM will gather as a result of this rulemaking will improve our understanding of how antimicrobials are sold or distributed for use in the four major food-producing species and help further target efforts to ensure judicious use of medically important antimicrobials. 
  • 2016 – FDA, in collaboration with USDA, initiated planning activities and surveys of laboratory network partners to begin projects to fulfill the presidential CARB goals which named Vet-LIRN and NAHLN networks to conduct AMR testing of select animal pathogens and expand sequencing capabilities of network laboratories.
  • 2017 - Completed implementation of GFI #213. This process transitioned medically important antimicrobial drugs used in the feed or drinking water of food-producing animals from over-the-counter status to VFD or prescription status requiring veterinary oversight and eliminated production uses (e.g., growth promotion). This represents a significant change to how antimicrobials had been used for decades in food animals.

    Of the 292 new animal drug applications initially affected by GFI #213:
    • 84 were completely withdrawn

    Of the 208 remaining applications:
    • 93 applications for oral dosage form products intended for use in water were converted from over-the-counter to prescription status
    • 115 applications for products intended for use in feed were converted from over-the-counter to veterinary feed directive status
    • Production (e.g., growth promotion) indications were withdrawn from all (31) applications that included such indications for use
  • 2017 - Published a paper proposing the use of a biomass denominator to adjust annual data on the amount of antimicrobials sold or distributed for use in food-producing animals in the United States. This adjusted estimate will provide insight into broad shifts in the amount of antimicrobials sold for use in food-producing animals and give the agency a more nuanced view of why sales increase or decrease over time in a manner that is specific to U.S. animal production. Such analysis will also support our ongoing efforts to encourage the judicious use of antimicrobials in food-producing animals to help ensure the continued availability of safe and effective antimicrobials for animals and humans.
  • 2017 - Along with its NARMS partners CDC and USDA’s Food Safety and Inspection Service, released a new format for the 2015 NARMS Integrated Report. The annual report highlights antimicrobial resistance patterns in bacteria isolated from humans (by CDC), raw retail meats (by FDA), and animals at slaughter (by USDA). The report also provides information derived from whole genome sequence data about resistance genes for all Salmonella and some Campylobacter isolates. The report includes NARMS Now, a set of interactive data tools that allow users to explore the dynamics of antibiotic resistance and the genes involved. While overall resistance remains low for most human infections and there have been measurable improvements in resistance levels in some important areas, NARMS is closely monitoring a few areas of concern.
  • 2017 - Launched Resistome Tracker, an interactive research and data visualization tool for antibiotic resistance genes.
  • 2017 - CVM’s Vet-LIRN network conducted a Pilot AMR-CARB project which consisted of 20 Source laboratories which isolated 3 prioritized pathogens and conduct AMR testing monthly. Approximately 1500 isolates were tested.  Vet-LIRN provided sequencers, training and project funds to 4 WGS laboratories who sequenced approximately 150 isolates collected by the Source laboratories.  Data was transferred to CFSAN GenomeTrakr for quality control evaluation and uploading to NCBI, a public database.
  • 2017 - A subcommittee of the FDA Science Board reviewed the NARMS program and made recommendations to adopt a One Health framework for surveillance.
  • 2018 - CVM released a Five-Year Plan for Supporting Antimicrobial Stewardship in Veterinary Settings. This plan builds upon the important steps CVM has taken to eliminate production uses of medically important antimicrobials (i.e., antimicrobials important for treating human disease) and to bring all remaining therapeutic uses of these drugs under the oversight of licensed veterinarians. It also supports the judicious use of antimicrobials in food-producing animals and is driven by the concept that medically important antimicrobial drugs should only be used in animals when necessary for the treatment, control or prevention of specific diseases
  • 2018 - CVM’s Vet-LIRN network continued its Pilot AMR CARB project of 20 Source laboratories which isolated 3 prioritized pathogens (Salmonella and Staphylococcus pseudointermedius and conducted AMR testing monthly. Over 2500 isolates were tested.  Vet-LIRN provided sequencers, training and project funds to 4 WGS laboratories who sequenced Over 800 of the isolates collected by the Source laboratories.  Data was made publicly available by uploading to NCBI, via CFSAN’s GenomeTrakr.
  • 2019 – CVM issued Revised Question & Answer Draft Guidance on Veterinary Feed Directive Regulation to aid industry in complying with the requirements of the Veterinary Feed Directive (VFD) final rule published in June 2015, and serves as a Small Entity Compliance Guide.
  • 2019 – CVM announced a funding opportunity 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. The agency also posted a list of the affected products.
  • 2019 - CVM’s Vet-LIRN network began its AMR Monitoring Program based on the previous 2-year Pilot Projects.  The Program expanded the number of participating laboratories from 20 to 25 Source AMR testing laboratories and to 5 (from 4) WGS sequencing Laboratories.  Testing was expanded from 3 prioritized pathogens to 4. Approximately 3000 isolates will be tested and 1000 of those will be sequenced.  Data will continue to be made publicly available by uploading to NCBI, via CFSAN’s GenomeTrakr.  Vet-LIRN will also be setting up a Vet-LIRN Antimicrobial Working Group to develop stewardship response recommendations for network laboratories that find bacterial pathogens that are highly resistant.