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Developments in Regulating Antibiotic Use

FDA Releases Two Guidelines to Limit Use of Antibiotics in Meat Production

On Wednesday, December 11, 2013 the FDA released the final FDA Guidance for Industry #213 and draft Veterinary Feed Directive (VFD). This is the first time since 1977 the FDA has taken broad action against the use of antibiotics in livestock. Once fully implemented, these policies will eliminate the use of medically important antibiotics for growth promotion. Still, the Obama administration will need to eliminate the use of antibiotics for other sub-therapeutic purposes, such as the use of low-dose antibiotics in healthy animals to account for unsanitary conditions and overcrowding.
This is a step in the right direction that will help the US catch up with EU regulations on agriculture. APUA played a major role in promoting this policy change by documenting the science as evidence and publishing in journals such as Microbiology. Our comprehensive FAAIR (Facts About Antibiotics in Animals and their Impact on Resistance) reports, published in Clinical Infectious Diseases (CID) were used as evidence and expert opinion in testimony by advocacy groups. Although these guidelines are only voluntary, they still show progress toward our goal of eliminating sub-therapeutic antibiotic use in food production. See the New York Times coverage, with a quote from our president, Dr. Stuart Levy here.

FDA bans unapproved use of Cephalosporins

On January 4, 2012, FDA issed an order of prohibition on certain extralabel uses of cephalosporin drugs in cattle, swine, chickens, and turkeys, to become effective April 5, 2012. FDA took this action to preserve the efficacy of cephalosporin drugs for treating human disease, including pneumonia, septicemia, meningitis, and infections of the urinary tract, bones, and upper respiratory tract. Cephalosporins are used against life-threatening infections and are considered drugs of last resort for people with sever foodborne illness. They are also the only class of antibiotic that carry no warnings against use in children or immunocompromised patients. With the exception of cephapirin (an older antibiotic drug not believed to contribute significantly to antibiotic resistance), the prohibited uses of cephalosporins included: Use at unapproved doses, frequencies, durations, or routes of administration, Use in species or production classes outside the ones specifically designated on the label, and Use for disease prevention. 

Federal Court Rules FDA must ban use of penicillins and tetracyclines for growth promotion

In May 2011, a lawsuit was filed by the Natural Resources Defense Council (NRDC), Center for Science in the Public Interest (CSPI), Food Animal Concerns Trust (FACT), Public Citizen, and Union of Concerned Scientists (UCS) against the FDA for failing to ban the use of penicilins and tetracyclines in food animal growth promotion despite having formally recognized in 1977 that the use of penicillin and most tetracyclines is not shown to be safe and may pose a risk to human health.The March 2012, Federal Court ruling compels FDA to take action on its own safety findings by withdrawing approval for most non-therapeutic uses of penicillin and tetracyclines in animal feed, unless the industry can prove in public hearings that those drug uses are safe. FDA must schedule hearings to let drug manufacturers make their case, and if the drug manufacturers cannot prove that the use of antibiotics in animal feed is safe, FDA must withdraw approval for those drug uses. Further court proceedings will likely be required to establish a timeline for FDA to act, and FDA could appeal the decision.

Issuance of FDA Regulations

In April 2012, the FDA issued two long-awaited guidances for the regulation of antibiotic use in food animal production – final Guidance #209 and draft Guidance #213 and also announced proposed changes to the Veterinary Feed Directive Program.

Final Guidance #209: (“The Judicious Use of Medically Important Antimicrobial Drugs in Food-Producing Animals”) recommends that food animal producers voluntarily phase out the use of medically important drugs for growth promotion or feed efficiency. It also recommends phasing in, over a period of three years, veterinary oversight of all medically important drugs being used in therapeutic situations (which include disease treatment, control, and prevention). This is the first time that the FDA has officially designated growth promotion as an “injudicious use” of antibiotics.

Draft Guidance #213:  (“Recommendations for Drug Sponsors for Voluntarily Aligning Product Use Conditions with Guidance for Industry #209”) asks drug companies to comply with Guidance #209 by removing growth promotion from the lists of FDA-approved uses on their products’ labels. Within three months of issuance of the final Guidance #213, companies will have the option of applying to list therapeutic uses (including disease treatment, control, and prevention) on their products’ FDA labels instead. Three years from the date of publication of the final guidance, the FDA plans to evaluate how many companies have adopted Guidance #213, and how long it took them to do so, as they consider their next actions.

Veterinary Feed Directive; Draft Text for Proposed Regulation: The proposed changes to the Veterinary Feed Directive (VFD) program are designed to make it consistent with the above guidances and to transition certain new animal drug products containing medically important antimicrobial drugs from an over-the-counter (OTC) status to a status that requires veterinary oversight. The FDA is concerned by the ability of producers, particularly those with smaller operations in remote locations, to have adequate access to veterinary services. Therefore, as steps are taken to phase in the changes discussed in this document, FDA recognizes the need to concurrently engage key stakeholders on this broader issue. Therefore, FDA intends to work collaboratively with U. S. Department of Agriculture (USDA) to engage the veterinary community and other stakeholders to explore strategic approaches (e.g., new models, pilot programs) to address this issue.

Federal Court rules on another five classes of medically important antibiotics

The Federal Court directed FDA to reexamine its decision to deny two Citizen Petitions filed in 1999 and 2005, which asked the FDA to stop the unnecessary use of medically important antibiotics on livestock. The Petitions cover five classes of antibiotics in addition to the two—penicillin and tetracyclines—implicated in the March decision from the Court. The Court wrote:

“[T]he statutory scheme requires the Agency to ensure the safety and effectiveness of all drugs sold in interstate commerce, and, if an approved drug is not shown to be safe or effective, the Agency must begin withdrawal proceedings. The Agency has forsaken these obligations in the name of a proposed voluntary program, Guidance # 209, and acted contrary to the statutory language.
. . .
[FDA] must evaluate the safety risks of the petitioned drugs and either make the finding that the drugs are not shown to be safe or provide a reasoned explanation as to why the Agency is refusing to make such a finding.”

Federal Court Rules that FDA cannot delay banning the use of penicillins and tetracyclines for growth promotion

In a follow-up to the ruling from March, a Federal Court ruled in August that the Food and Drug Administration (FDA) cannot delay regulatory proceedings for penicillin and tetracyclines use in livestock.

The court action
1) ensures that action is not delayed further until after the resolution of an appeal by FDA of the court’s original decision to mandate these proceedings and  
2) imposes a deadline for the completion of the proceedings. FDA will have approximately five years to complete proceedings.

Developments in Collecting Data on Animal Use of Antibiotics

In August 2008, Congress passed the Animal Drug User Fee Amendments of 2008 requiring the animal drug manufacturers to report to the Food and Drug Administration (FDA) on the quantity of antimicrobial drugs sold or distributed annually for use in food animals. The data includes the dosage form, the target animal, and the approved indication for use (such as growth promotion or therapy).

However, FDA shares only a limited summary of these data with the public, but withholds almost all of what companies report. The Government Accountability Project (GAP) submitted a Freedom of Information Actrequest for this data to the FDA in February 2011. Upon denial, GAP appealed to the Public Health Service, which includes the FDA. Following a one-year delay, the appeal was denied in September 2012. A lawsuit has followed. 

In October 2012, Representative Waxman of California has proposed a bill called the “Delivering Antibiotic Transparency in Animals (DATA) Act.” It could provide the FDA with important information about the types, purposes, and quantities of antibiotics being fed to livestock. Information would be gathered from drug manufacturers as well as feed mills.

APUA's stance

In an April 2012 press release, APUA agrees that the FDA guidances may encourage leadership among large food animal producers to reduce inappropriate antibiotic use on farms, but cautions that “there is a need for strong monitoring of their implementation.” 

“FDA’s guidance documents, including this draft guidance, do not establish legally binding responsibilities. Instead, guidances describe the FDA’s current thinking on a topic and should be viewed only as recommendations… the use of the word ‘should’ in FDA’s guidances means that something is suggested or recommended, but not required.”

In May 2012, APUA convened a National Stakeholder Meeting in Washington, DC to discuss antibiotic use in food animals, including alternatives to antibiotic use and incentives to adopt them .

Other groups (including the National Resource Defense Council, the Center for Science in the Public InterestKeep Antibiotics Working, and the American Academy of Pediatrics) have taken similar or harsher stances on the FDA’s actions. Considering the sheer volume of antibiotic use in food animals (accounting for 80% of all antibiotics sold in the U.S.), it may be that voluntary compliance falls short of addressing the problem. According to these groups, overuse must be reduced through required cooperation from the entire industry and a clear plan for monitoring drug use to measure the guidances’ effectiveness.

As a comment to the Draft Guidance #213, APUA wrote an organizational letter to the FDA commissioner detailing our recommendations for the strengthening of this Guidance. In addition, APUA developed a leadership statement addressed to President Obama and FDA Commissioner Hamburg asking that the FDA and congress take action to reduce antimicrobial use in food production. APUA reached out to colleagues for support and this statement was signed by 21 leaders in science and medicine including 4 Nobel Laureates and 5 ASM Presidents.

APUA also signed on to a joint-letter to the FDA Commissioner Hamburg encouraging the FDA to include representatives from the public health community and consumer groups in the stakeholder dialogue over the proposed changes to the VFD. 

Why does this matter?

It is now known that constantly exposing food animals to sub-therapeutic doses of antibiotics (i.e. during growth promotion) is a potent selector for drug-resistant bacteria, which can then enter the food chain and infect humans. While final Guidance 209, draft Guidance 213, and the VFD may constitute the most sweeping action the FDA has taken to protect public health from antibiotic resistance, there are serious gaps in these measures that must be addressed.

Final Guidance 209 and draft Guidance 213 designate “growth promotion” as an injudicious use of antibiotics, but not “disease prevention” – the non-therapeutic use of antibiotics when a herd or flock is not actually sick. Many antibiotics are currently FDA-approved at the same dosages for both growth promotion and disease prevention, so in practice they are identical. If growth promotion is discouraged but disease prevention is not, producers can continue practicing inappropriate antibiotic use simply by calling it disease prevention.  This is also why it is important to collect data from feed mills and drug manufactorers with specifics on what the intended use (ex. "growth promotion", "disease prevention", etc.) and by the percentage of antimicrobials being sold over the counter, or by prescription or veterinary feed directive. Given the FDA guidances, there may soon be a decrease in sales for growth promotion but a corresponding increase in sales for disease prevention, that could mean the drug companies are just changing terminology. With no expanded requirements for reporting, no one outside of the FDA will be able to see this data.

The FDA needs to clearly define the differences between antibiotic use for treatment, for control, and for prevention, and state once and for all which uses are acceptable and which are not. If industrial farms can improve conditions and change animal husbandry practices without using antibiotics, the FDA should encourage that first. The FDA must also lay out a clear outline of how it intends to monitor the results of the voluntary guidances and measure their effectiveness.

What can I do to help?

Motivated citizens: address your comments to President Barack Obama and FDA Commissioner Margaret Hamburg via the “Take Action” link at The Pew Campaign on Human Health and Industrial Farming: Urge FDA to Strengthen Measures to End Overuse of Antibiotics on Industrial Farms.

A few months ago, with the help of responsible citizens like you, APUA and Pew mobilized over 32,400 signatures in support of the FDA’s ban on cephalosporin use in food animals.

Past work by APUA on the issue

Past work with The Pew Charitable Trusts