July 12, 2012
Comments of the National Consumers League to the Food and Drug Administration
Comment on Draft Guidance for Industry #213: Docket No. FDA-2011-D-0889-0001
The National Consumers League (NCL), the nation’s oldest consumer advocacy organization, is pleased to have this opportunity to comment on draft Guidance for Industry (GFI) #213 (Docket No. FDA-2011-D-0889-0001). NCL is concerned that the voluntary framework established by GFI # 213 does not adequately address the growing concern of antimicrobial resistance, particularly resistance caused by the over-application in livestock. The U.S. Food and Drug Administration (FDA) has an important leadership role to play in halting the continued development of antibiotic resistance.
Antimicrobial resistance is not a new problem. For decades, scientists have warned that the overuse of antibiotics will lead bacteria to develop resistance to these life saving drugs. Inappropriate use of antimicrobials selects for the strongest strains of bacteria. The reality is that the continued development of resistance could leave us with an arsenal of once powerful drugs which are no longer effective. Resistant bacteria are a challenge to medical professionals, who are sometimes forced to substitute drugs which can be less effective or have more serious side effects.
Approximately 80% of the antibiotics used in the United States are administered to food producing animals. Antibiotics are administered to livestock for three main purposes. In the first instance, antimicrobials are given to a sick animal to treat a specific, present disease. Secondly, antibiotics are administered in food and water to whole herds and flocks of animals to prevent the occurrence of diseases, diseases that are increasingly likely to occur due to the crowded conditions common to much of modern agricultural production. Finally, antibiotics have been used since the 1940s to promote faster growth in livestock.
While the first use of antimicrobial drugs is widely accepted and supported by both the agricultural community and public health professionals, the second two uses are more controversial. When antibiotics are used for disease prevention and growth promotion, they are often administered for longer periods of time and at lower doses, two conditions which are known to help promote resistance.
Background on GFI #209 and #213
GFI #209, “The Judicious Use of Medically Important Antimicrobial Drugs in Food-Producing Animals,” states that “it is imperative that strategies for controlling antimicrobial resistance include a consideration of how microbial drugs are being used and measures to address those uses that are injudicious in nature.” GFI #209 proposes two guiding principles: that the use of antibiotics in animals should be limited to medically necessary circumstances and that use of medically important antibiotics should take place under the guidance of a veterinary professional.
The first principle articulated in GFI #209 is that “the use of medically important antimicrobial drugs in food-producing animals should be limited to those uses that are considered necessary for assuring animal health.” Under this principle, FDA addresses the question of whether prevention uses of antibiotics are necessary, saying “FDA believes that some indications for prevention use are necessary and judicious as long as such uses include professional veterinary involvement.”
The second principle enumerated in GFI #209 is that “the use of medically important antimicrobial drugs in food-producing animals should be limited to those uses that include veterinary oversight or consultation.” This guidance introduces a new paradigm that includes closer consultation with veterinary professionals.
GFI #213 provides the steps to achieve the implementation of GFI #209. GFI #213 reiterates that disease prevention uses of drugs are considered judicious if a veterinarian “determines that the use of antimicrobials is necessary to prevent the onset of diseases that are likely to occur.” The guidance emphasizes that FDA intends to work with the sponsors of impacted antibiotics, as well as the “end users of these products,” the veterinarians and animal producers, to voluntarily change the indications on animal drugs. This voluntary system, combined with increased oversight on the part of veterinarians, would result in the end of growth promotion uses of antimicrobials.
GFI #213 also lays out a timeline for implementation that it hopes will “minimize the impacts and provide for an orderly transition.” According to the draft guidance, a three year phase is proposed, during which time sponsors would adjust the labels on their products to eliminate growth promotion and provide for increased veterinary oversight.
Concerns with the Proposed Paradigm
NCL has several concerns with the draft GFI as it is written. First, NCL is troubled by the voluntary system which GFI #213 lays out for the reduction of production uses of antibiotics. We do not believe that voluntary systems provide regulatory incentives necessary to spur change in the industry. It is appropriate and necessary for FDA to step in and issue mandatory measures that would ensure antibiotics are no longer used for growth promotion.
Secondly, NCL is concerned that that this voluntary system of reduction, proposed by FDA, still allows for the use of antibiotics for disease prevention. The use of antimicrobials throughout a herd or flock to prevent disease is an important contributor to the development of antibiotic resistant pathogens. We are concerned that FDA, in its draft guidance, considers the use of antimicrobials for disease prevention as judicious use. Many preventive uses have no limit on duration and are given to all the animals on the farm. This is inconsistent with FDA’s guidance in both GFI #213 and the previously released GFI # 152.
Third, NCL is concerned that GFI #213 creates a method for determining the safety of antimicrobials that is weaker than the previous set of criteria established in GFI #152. We are concerned that these new guidelines will be used in lieu of the original guidance and will result in decreased levels of oversight. Furthermore, we are worried that the method proposed by GFI #213 does not include recommendations against using medically important antibiotics on all animals in a flock or herd. Additionally, there is no clear limitation on the duration of use, another important factor in the development of resistance.
Fourth, NCL is concerned that a voluntary approach which allows for the continued use of antibiotics for disease prevention will allow drug companies to circumvent the spirit of the guidance, which is intended to reduce the use of antibiotics. Specifically, we are concerned that while the proposed paradigm will lead drug companies to remove label indications for growth promotion, it may also incentivize drug companies to simply expand the parameters of disease prevention use.
Finally, NCL questions the very foundation of the draft guidance; that is, we question whether a system that is voluntary can be effective at reducing the use of antibiotics for growth promotion. NCL is troubled by the ability of drug sponsors to choose whether to participate and feel that a voluntary system may not provide the incentives necessary to ensure compliance.
Recent Court Decisions
Two recent decisions have been handed down by U.S. Magistrate Judge Theodore Katz, of the U.S. District Court, Southern District of New York. The first was a summary judgment issued on March 22, 2012. In 1977, in response to growing concern about the development of antimicrobial resistance, FDA announced its intent to withdraw the approval for subtherapeutic uses of penicillin and two types of tetracycline. After making this announcement, FDA failed to move forward with the appropriate hearings and did not remove approval for the drugs. In his ruling, Judge Katz stated that the FDA “must re-issue a notice of the proposed withdrawals (which may be updated) and provide an opportunity for a hearing. . .If, at a hearing, the drug sponsors fail to show that use of the drugs is safe, the Commissioner must issue a withdrawal order.”
In another decision, issued on June 1, 2012, Judge Katz declared that an FDA decision to deny two citizens petitions to end subtherapeutic use of antibiotics was “arbitrary and capricious.” He goes on to note that had FDA “addressed the Petitions in a timely fashion,” looking at them when they were initially filed, “withdrawal proceedings could have been commenced and completed by now.” Judge Katz concluded that “the adoption of voluntary measures does not excuse the Agency from its duty to review the Citizen Petitions on their merits.”
NCL is encouraged by these decisions, which reinforce the fact that FDA has long considered antimicrobial resistance a serious issue and must take action to put a halt to subtherapeutic uses. NCL urges the agency not to appeal these cases and to move forward with repealing the approval for penicillin and tetracyclines as ordered by Judge Katz. It is the agency’s duty to comply with the law’s mandate to protect public health from risky uses of antibiotics, such as growth promotion and prevention uses.
Given our concerns with the proposed system, which would focus on voluntary reductions in the use of antibiotics for growth promotion purposes, NCL has several recommendations.
- Because disease prevention uses of antibiotics create the same selective pressures as growth promotion, FDA should move forward with withdrawing approvals for the use of antimicrobials for prevention of diseases. This is necessary as drug companies are unlikely to make this move on their own.
- The new system that FDA has proposed relies on a voluntary scheme for eliminating the use of antimicrobials for growth promotion. Because some companies may choose not to participate, a voluntary system is not sufficient for reducing the use of antibiotics. We encourage FDA to use its regulatory authority to create a mandatory reduction plan that will ensure compliance and increased public health.
- The FDA should choose a measure of success that is meaningful to public health. Because of our concerns that drug sponsors may add indications to their drugs for prevention uses, merely looking at whether sponsors do away with growth promotion uses of antimicrobials is an insufficient measure of whether the program is succeeding. A more appropriate measure of success would be to look at whether or not the amount of antibiotics used has decreased.
- Transparency in the implementation of this new process is essential. FDA has proposed a three year implementation period. FDA should publish detailed quarterly reports on proposed and finalized voluntary changes. These reports should facilitate the independent verification of progress made towards implementation as well as an assessment of the public health implications of these changes.
While NCL applauds FDA for recognizing that there is an urgent need to reduce the use of antibiotics in food-producing animals, we have concerns about the new framework of reduction which the agency has proposed. NCL is pleased that the agency has decided to recommend the increased involvement of veterinarians in the application of antimicrobials. However, we are concerned that a voluntary approach to reduction of antimicrobial use will not provide strong enough incentives to ensure industry compliance.
FDA has recently been instructed in two court cases to continue forward with action to reduce the use of antibiotics in food-producing animals. NCL urges the agency not to appeal these court decisions and to use them as the basis for future reduction of antibiotics in livestock.
NCL appreciates having this opportunity to comment on FDA’s draft Guidance for Industry #213 and encourages the agency to reconsider its framework for ensuring that drugs critically important to human medicine are preserved.
 Nugent, Rachel, Emma Back, and Alexandra Beith. The Race Against Drug Resistance. Center for Global Development, 2010. https://www.cgdev.org/files/1424207_file_CGD_DRWG_FINAL.pdf.
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 United States of America. U.S. Department of Health and Human Services. Food and Drug Administration, Center for Veterinary Medicine. Guidance for Industry # 209, The Judicious Use of Medically Important Antimicrobial Drugs in Food-Producing Animals, 21.
 Guidance for Industry #209, 22.
  United States of America. U.S. Department of Health and Human Services. Food and Drug Administration, Center for Veterinary Medicine. Draft Guidance for Industry #213, New Animal Drugs and New Animal Drug Combination Products Administered in or on Medicated Feed or Drinking Water of Food-Producing Animals: Recommendations for Drug Sponsors for Voluntarily Aligning Product Use Conditions with GFI #209, 3.
 Draft Guidance for Industry #213, 4.
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 Natural Resources Defense Council, Inc. Et Al. (NRDC) v United States Food and Drug Administration, Et Al. U.S. District Court, Southern District of New York. 22 Mar. 2012.