The Food and Drug Administration (FDA) has released new guidance for veterinary drug makers to define how long medically important antibiotics should be used in livestock.
The document, published February 12 by the FDA’s Center for Veterinary Medicine (CVM), provides recommendations to animal drug sponsors on how to add duration limits to medically important antibiotics used in food-producing animals for indications (ie, approved treatment uses) that currently have no set limits. Nearly 30% of all medically important antibiotics used in cows, pigs, and poultry on US farms have at least one indication without a defined duration of use, meaning farmers can use those antibiotics in animal feed for extended periods of time.
Guidance for Industry (GFI) #273 says labeling for those products “should be revised to include appropriate criteria regarding when to begin and end feeding of the antimicrobial drug.” The revisions should include an approximate duration range that veterinarians should consider when treating an animal, as well as a maximum duration limit that should not be exceeded.
The guidance, which is nonbinding, also suggests sponsors avoid instructions like “feed until market weight” to define the duration of use.
“This guidance provides specific recommendations on how sponsors may facilitate changes to the approved conditions of use of affected products in support of ongoing efforts to mitigate the development of antimicrobial resistance,” the FDA said.
The FDA frames the document as part of its ongoing efforts to promote judicious use of medically important antibiotics, which are also used to treat human infections, in food-producing animals. More than two-thirds of all medically important antibiotics globally are sold to treat, control, and prevent bacterial infections in livestock and poultry.
While antibiotics are necessary for treating farm animals with bacterial infections, antibiotic stewardship advocates have long warned overuse and misuse of antibiotics in food-animal production threatens both animal and human health by promoting the emergence and spread of antimicrobial resistance (AMR), which reduces antibiotic effectiveness. AMR is estimated to cause more than 1.2 million deaths annually.
Previous guidance issued by the FDA limited medically important antibiotic use on farms to disease treatment, control, and prevention and required a prescription and veterinary oversight for all antibiotic use. Prior to these changes, which were implemented in 2017, US farmers could use medically important antibiotics for growth promotion and could buy them over the counter.
In 2018, CVM called for all antibiotics used in the feed and drinking water of food -producing animals to have “an appropriately targeted duration of use” in its five-year action plan for supporting antimicrobial stewardship in veterinary settings.
Guidance doesn’t consider impact on human health
But critics say the guidance falls short of what is needed to adequately address the rise and spread of AMR.
The problem, according to Steven Roach of the Food Animal Concerns Trust (FACT), is that the guidance directs drug makers to set antibiotic durations based solely on the health needs of the animal, and does not include mitigation of AMR, or potential impact on human health, as considerations for veterinary decision-making. He said GFI #273 won’t really do anything to reduce food-animals’ exposure to antibiotics, which is what drives AMR.
“It’s unlikely to have very much impact on how much antibiotics are being used,” Roach told CIDRAP News. “And therefore, it’s very unlikely to have any impact on resistance.”
FACT was among a coalition of groups that submitted comments to the FDA when the GFI #273 was in draft form. Among their requests was that the FDA set a default maximum duration of 21 days for all covered antibiotics and require drug makers to provide microbial safety and efficacy data if they seek longer maximum durations. They also urged the FDA to ask sponsors to provide a definite, time-bound duration of use for each indication on a drug’s label, in addition to the 21-day maximum duration.
“The FDA should ask for sponsors to make changes consistent with science and its own public health mission, and at least seek voluntary changes that will more fully meet the FDA’s stated goals,” the members of Keep Antibiotics Working wrote. “It can do this by setting a default baseline 21-day maximum duration and by asking sponsors to make other changes that mitigate the development of antibiotic resistance.”
An indication that currently has no defined duration limits is liver abscess in cattle, which is treated with tylosin, a broad-spectrum macrolide antibiotic related to azithromycin. Tylosin is approved in cattle for “continuous use” to reduce incidence of the condition. Although it’s only used in veterinary medicine, there is concern that use of tylosin for as long as 100 days in cattle can select for bacteria that are resistant to all macrolides, including those that are used to treat infections in people.
It’s unlikely to have very much impact on how much antibiotics are being used....And therefore, it’s very unlikely to have any impact on resistance.
Roach noted that in the 1970s, drug makers seeking to use medically important antibiotics in feed for more than 14 days had to submit data from studies showing it would not lead to resistance, while guidance issued by the FDA in 2003 recommended against using antibiotics for more than 21 days when there is a high or medium risk of resistance.
“In this case, it’s whatever is needed for the animal’s health will be the determiner of the duration limit, and that’s really problematic,” he said.
Gail Hansen, DVM, MPH, a public health and veterinary consultant, noted the guidance is voluntary and gives drug makers three years to add “weak language” to their product labels. It also still allows sponsors to label and market antibiotics for disease prevention, a use that many stewardship advocates argue is inappropriate.
“The plus side is that it seems to give wiggle room or potentially allow for veterinarians to have a farm/ranch stop a drug early if it isn’t working,” Hansen said in an email.
Although he’s disappointed in the new guidance, Roach said FDA commissioner Martin Makary’s past support for limiting routine use of antibiotics in meat production gives him some hope that the agency will do more to address the issue.
“He clearly understands the issue, so our hope is that, if he pays attention to it, then maybe he’ll drive some change,” Roach said.
