FDA Must Ensure That All Animal Antibiotics Have Defined Durations of Use

Limits for drugs most important to livestock health should be a priority

Article April 1, 2019 By: Karin Hoelzer & Nora Wong Read time:

Projects: Antibiotic Resistance

Slowing the emergence of resistant bacteria requires appropriate use of antibiotics in all settings, including animal agriculture. However, many medically important antibiotics can still be legally given to animals in ways that do not meet the Food and Drug Administration’s definition of judicious use.

For example, many antibiotic labels allow for very long or undefined durations of use, meaning that they can be given to animals for weeks or months, or even indefinitely. Additionally, some duration limits are tied to subjective or poorly defined external factors, such as when the animal experiences “times of stress.” As FDA works to establish appropriate, science-based duration limits for all antibiotics as part of its five-year plan to improve antibiotic use in food animals, the agency must prioritize these efforts based on factors such as each drug’s importance to animal health. (See Table 1.)

What Are Duration Limits, and Why Are They Important?

Duration limits specify the appropriate length of time for which a drug should be used to achieve the desired effect. FDA’s current animal drug approval process requires the establishment of science-based duration limits, but the agency approved many animal antibiotics long before these requirements were in place.

FDA recognizes that “long-term or open-ended use of medically important antibiotics is a significant stewardship issue” and that labeling medically important antibiotics “for continuous or undefined durations of use is not consistent with judicious use.” Using the right antibiotic for the optimal amount of time is fundamental to antibiotic stewardship. It protects the health of food animals, slows the emergence of resistance, and maximizes the probability of achieving the desired clinical response.

Adding defined, science-based duration limits would be relatively easy and straightforward for many of the nearly 30 percent of animal antibiotics labels that lack them. For example, where data exist, drug sponsors could use information from comparable antibiotics already approved for identical or similar indications that have well-defined duration limits. Still, the collection of new data would be necessary for some antibiotics. And because generating new data is time- and resource-intensive, FDA must put the highest priority in this process on those drugs most critical to animal and public health.

FDA should develop a robust, transparent, and evidence-based process to decide the animal antibiotics on which to collect new data first, based on the following criteria:

Are new data really needed? Or are other relevant data sources available, such as in the scientific literature or in dossiers of approved drugs, that drug sponsors can use to establish scientifically valid duration limits without having to initiate new research?
What other antibiotics with defined durations of use are available to address the same diseases? Is the antibiotic that does not have a defined duration of use the only viable option to address a disease? What antibiotic or non-antibiotic options, such as vaccines or changes in management practices, could help address the disease? Table 1 summarizes these data.
How important are the diseases addressed by the antibiotic? Does the disease have a high impact on animal health, public health, or the U.S. agricultural economy?

For example, FDA would put the higher priority on collecting data for antibiotics with limited alternatives. Because the agency has approved several antibiotics that do have durations of use for treating pneumonia or bacterial enteritis in cattle and swine, collecting new data to establish such limits for other antibiotics to treat these diseases may be a lower priority. In contrast, there are few or no treatment options with duration limits in other diseases important to animal health, such as anaplasmosis in cattle or necrotic enteritis in chickens. Therefore, collecting new data to establish appropriate limits for these drugs may be a higher priority.

Having publicly recognized the lack of duration limits as a problem for several years, FDA must now establish a systematic, data-driven process for prioritizing which animal antibiotics need additional data most urgently. This would help ensure the efficiency and effectiveness of FDA actions on these issues and better protect animal and public health.

Karin Hoelzer, a veterinarian by training, leads The Pew Charitable Trusts’ work on antibiotic use in animal agriculture. Nora Wong works on Pew’s antibiotic resistance project.