New FDA regulations will phase out use of growth promotion indications in medically important antibiotics.

MANHATTAN, Kan. — The U.S. Food and Drug Administration (FDA) has announced that revised labels established according to Guidance Documents #209 and #213 will go into effect in December 2016.  There will also be new regulations regarding how veterinarians will authorize the use of medically important antibiotics in the feed of food animals.

Michael Apley, DVM and professor of Production Medicine and Clinical Pharmacology with Kansas State University’s College of Veterinary Medicine, explained some of the changes producers and veterinarians can expect to see as a result of the new regulations at K-State’s Beef Stocker Field Day on Sept. 25, 2014.

In 2012, the FDA finalized Guidance #209, which requests companies to phase out growth promotion indications for medically important antibiotics used in food-producing animals as well as changing the remaining antibiotic label approvals for feed and water uses of antibiotics in food animals to Veterinary Feed Directive (VFD) or prescription status, respectively.  Guidance #213 contains the procedures for companies to make these changes.

This request affects 26 companies holding 283 different product labels.  As of today, all 26 companies have agreed to cooperate and withdraw labels, or portions of labels, with growth promotion claims, as well as changing the remaining uses to VFD or prescription status.

Apley said one of the biggest questions posed by producers and veterinarians is what antibiotics will be affected. He noted that the ionophores, feed additives used in cattle diets to increase feed efficiency and body weight gain, will not be affected by the new regulations. Products including Rumensin, Bovatec and Gainpro are not involved because they are not listed as medically important to human therapy.

The new regulations have producers, licensed feed mill operators and veterinarians wondering, “Who’s paying for this?” Apley said VFD regulations would require more effort from the producer and time from the veterinarian to write the mandatory VFDs.

“By law, the veterinarian is going to be required to have knowledge of the producer’s operation to write the VFD,” he explained. “There are a lot of questions, and the licensed feed mills and feed distributors are going to have a heck of a lot of VFDs coming through to make this work.”

Looking ahead in contemporary management of growing cattle, Apley said the new VFD regulations will dramatically change the antibiotic administration process.

“I think one of the things that resonated with the stockers is the use of tetracycline in feed,” Apley said. “If they’re using the therapeutic regimen of one gram of oxytetracycline or chlortetracycline per 100 pounds per day for calves, administered in the feed, the only way they can use that is with a veterinary feed directive.”

Changes for producers
The most significant changes will come with producers’ inability to walk in, request a product and buy it, Apley said.

“Any water use is prescription now,” he said. “The cattle feeder that uses tylosin, that’s going to need to be authorized by the veterinarian for that use, strictly by the label.  But, is has always been illegal to use a drug in feed other than allowed by the label.”

While the final form of the Veterinary Feed Directive regulation is still in the works, Apley said it is clear that veterinarians will have to authorize all uses of medically important antibiotics in the feed or water of food animals.

“If there’s a Veterinary Feed Directive drug that’s used concurrently with one that’s not a VFD drug, the VFD still has to authorize the use of both drugs together,” Apley said. “For example, tylosin will be a VFD drug and monensin will not, but the veterinarian will be required to authorize the use of both in combination.”

The final form of the Veterinary Feed Directive is still in the works, but organizations like the American Veterinary Medical Association (AVMA) and American Association of Bovine Practitioners (AABP) have groups assigned to address members concerns and to have a dialogue with the FDA Center for Veterinary Medicine, Apley said. The FDA has held listening sessions across the country for people to give input.

One of the greatest concerns for the new veterinary feed directive is how they will be standardized, Apley said.

“These could be effective for up to six months, but are we going to have some that are three months, four and five months?” he asked. “You would end up with this rolling cascade of renewal requirements. We’re asking that they standardize these as much as possible for producers and veterinarians.”

Producers should look to their extension service, local veterinarian and new sources for information going into 2016, when the final version begins to emerge, Apley said.

Metrics needed to measure success

“Part of the success metrics, or a way to evaluate the intended effect of Guidance #209 is to ask, “Did antibiotic use in food animals in the United States decrease?” We’ve got a rather crude measure of actual uses now in sales reporting data, and I think they’re wanting to have more,” he said.

Apley said it is unlikely to see a dramatic decrease in antibiotic use because of the way the new regulations are structured.

“The next area of concern is the routine or constant use of in-feed antimicrobials to control a condition, such as liver abscesses,” he said. “They’re very effective, but the issue that gets pushed back at us is that we use those because of the nature of the production system. Unfortunately, the actual science of whether or not we could have any adverse effect on human therapeutics from these kind of uses ends up being only a dash of flavor in policy soup.”

Apley said the greatest catastrophe the industry faces now is the precedent for evidence that growth promotion uses are any different from other uses as to the potential to select for resistant organisms.  Hopefully, this is not the precedent for the evidence that may be required to separate off prevention and control uses from uses for therapy of diseased animals in the future.

“That gets people up in a mood to fight, but that’s the fact,” Apley said. “They really didn’t provide any data to say growth promotion is any different. That was just a line to decrease antibiotic use.”

“We’ve got to work hard as an agricultural industry to make sure that a different level of evidence is applied to evaluate prevention and control uses than was used for growth promotion uses,” he said.

Antibiotic development has run into roadblocks at every corner of the animal agriculture industry, but it’s also sparked controversy in the human health sector. Apley said the chance of animal agricultural acquiring a new set of antibiotics is unlikely.

“The last time we got a new and novel group of antibiotics approved for human and veterinary use that we use today in animal agriculture was 1978,” Apley said. “Everything we’ve had since then has been some kind of molecular modification of these existing groups.”

Apley said a new drug with slightly different properties may be released here and there, but the last two new groups of antibiotics released were for human medicine in 2000 and 2003. There is one other new antibiotic group on the horizon for human medicine.

While the absence of new antibiotics for use in animal agriculture may pose some hindrance to the industry, Apley said there are some advantages to this lack of development.

“They’re looking at new ways to address infectious disease, such as addressing the virulence of the organism – it’s ability to cause disease – rather than just outright killing it,” Apley said. “There are ways of working with the immune system and there are ways of suppressing disease. We’re just on the forefront of our genetic analysis and discovering really new and interesting things about the host-pathogen interaction.”

Apley said he and colleague Bob Larson, professor of production medicine, DVM and the Edgar E. and M. Elizabeth Coleman Chair Food Animal Production Medicine executive director, who specializes in epidemiology in K-State’s College of Veterinary Medicine, recently reviewed a paper from 1971 explaining that many advancements in control of diseases like cholera and tuberculosis came long before antibiotic intervention.

“Antibiotics took the last little bit of the disease challenge off,” Apley said. “But, the initial huge decrease in the curve was from epidemiology and applying things like basic sanitation and procedures to reduce the risk of spread. All is not lost, but we need to make sure tools are not taken from us unless there is a scientifically sound reason to do so.”

If there is a silver lining to the new FDA guidelines for food-grade antibiotic usage in animals raised for food production, Apley said it will likely be in the form of increased relationships between producers and veterinarians.

“If this fosters more interaction between producers and veterinarians, and enables veterinarians getting to know more about producers’ operations, I think that’s good for the industry,” Apley said.