Some background: Antibiotics used on farm animals account for more than 80% of all antibiotics sold in the U.S., and most of them are not used to treat sick cows, chickens, and pigs, but because these animals get bigger when these drugs are put into their feed and water.
Unfortunately, continual low-dose use of antibiotics also has the effect of creating drug-resistant bacteria. That’s not good for the animals or humans, which is why there has been increasing pressure on regulators to limit non-medical use of important antibiotics on farm animals.
In 2013, after decades of inaction on the issue, the FDA issued voluntary guidelines for drug makers, asking them to stop selling medically important antibiotics for non-medical applications.
And yet Novartis Animal Health (which is now owned by Eli Lilly) continued to market the growth-promotion aspects of its swine antibiotic product Denagard with an entire section of the drug’s website dedicated to the topic, touting weight gains for pigs that consumed the drug and how the antibiotic “provided a 4:1 return on investment.”
The FDA’s initial response to complaints from advocacy group Keep Antibiotics Working about Denagard’s marketing was lackluster to say the least. At the time, the agency said, “We understand your concern and… we intend to look for ways to reinforce the importance of the principles of judicious and appropriate use, including engaging animal drug manufacturers on the appropriate use of promotional materials.”
Meanwhile, Novartis defended its marketing and argued that — in spite of evidence to the contrary — it was not pushing an off-label use of Denagard.
But in a warning letter sent earlier this month from the FDA’s Center for Veterinary Medicine to Novartis Animal Health, the agency disagreed with the drug company.
Citing the Denagard website’s growth-promotion section, the letter contends that the company is marketing the drug for “new uses for which it lacks approval, conditional approval or an index listing, and for which its labeling does not provide adequate directions for use.”
According to the Food, Drug and Cosmetic Act, Denagard would thus be considered unsafe, adulterated, and misbranded.
The letter takes issue with statements about Denagard, like, “Success starts in the nursery with Denagard,” and various statistics given about things like the ratio of weight gain to feed.
Also of concern to the FDA was that some the studies cited in the Novartis marketing materials were designed specifically to demonstrate the economic benefits from increased weight gain and more efficient use of animal feed, of using Denagard.
“Variables related to clinical disease were not measured with the exception of mortality, which was not found to be statistically different between the control and treated groups,” writes the FDA. “In fact, the authors of one article reported ‘No significant health issues were observed,’ and ‘Overall mortality was relatively low for both treatment groups.’ Therefore, the supporting studies cited in the materials do not support the claims that the weight gain and feed efficiency improvements described in these studies resulted from Denagard plus CTC being effective for its approved indications.”
Another concern raised in the letter was the description of Denagard as a “broad-spectrum” drug for enteric and respiratory diseases in pigs, even though the antibiotic is only approved for the treatment of one respiratory ailment caused by one type of bacteria. Its use in enteric disease treatment is also limited.
“Use of the term ‘broad spectrum control’ implies that this product could be used for control of a wider range of disease organisms than the four pathogens included in the product approval,” states the FDA letter. “The approved indications are limited and very specific. Therefore the claim of broad spectrum control of enteric and respiratory disease in nursery pigs seen in these materials broadens the indication and is a new intended use.”
The FDA has called on the Denagard makers to “immediately cease misbranding Denagard plus CTC and cease introducing the adulterated and misbranded drug into interstate commerce.”
The letter also clarifies that the violations listed in the warning are not exhaustive and that Novartis Animal Health is now responsible for re-vetting all its materials to make sure they are compliant.
“Failure to correct the violations discussed above may result in enforcement action by FDA without further notice, including seizure and injunction,” reads the warning.
NAH has 15 days to respond to the warning.