The Food and Drug Administration (FDA) is implementing a voluntary strategy to promote the judicious (appropriate) use in food-producing animals of antibiotics that are important in treating humans. The goal of the strategy is to protect public health and help curb the development of resistant drugs and in turn help to reduce the number of infections in humans that are difficult to treat because existing antibiotics have become ineffective. A public meeting was held at Western Kentucky University on April 9, 2013 to “provide an opportunity for public dialogue and feedback on challenges faced by the animal agriculture industry and practicing veterinarians as FDA implements its initiative for the judicious use of medically important antimicrobials in medicated feed or drinking water of food-producing animals.” This meeting was offered because FDA is seeking input as it moves ahead with its strategy to promote the judicious use in food-producing animals of antibiotics that are important in treating humans. This three-pronged approach includes:
• Issuing a guidance for industry (Guidance #209), entitled “Judicious Use of Medically Important Antimicrobials in Food Producing Animals,” which establishes a framework for phasing out production uses (growth promotion and feed efficiency) of antimicrobials important in treating humans, and phasing in veterinary oversight of the remaining therapeutic uses of such drugs. This GFI was finalized on April 11, 2012 and can be found at: http://www.fda.gov/downloads/AnimalVeterinary/GuidanceComplianceEnforcem...
• Issuing a draft guidance (Guidance #213) that will help drug companies voluntarily revise product labels to remove production uses (feed efficiency and growth promotion) and add instead disease prevention, control, and treatment uses. This guidance document also advises companies on how to voluntarily change the marketing status of these medically important antimicrobials to include veterinary oversight or supervision.
• Providing draft text for a proposed regulation intended to improve the efficiency and practicality of existing Veterinary Feed Directive (VFD) requirements. VFD drugs are drugs intended for use in or on animal feed which are limited to use under the professional supervision of a licensed veterinarian. Which drugs currently used in food animals are the focus of FDA’s strategy? The voluntary strategy is primarily focused on medically important antimicrobial drugs that:
• Were approved prior to the issuance of Guidance 152, Evaluating the Safety of Antimicrobial New Animal Drugs with Regard to Their Microbiological Effects on Bacteria of Human Health Concern, which was published in October 2003.
• Are used in food-producing animals to increase feed efficiency and promote growth;
• Are available over-the-counter (OTC), and therefore, can be given without a veterinarian’s involvement; and
• Are given continuously through the feed or water to entire herds or flocks of animals.
A list of antimicrobial drugs FDA considers medically-important are listed in Appendix A of Guidance for Industry #152. Interestingly, we have several growth promotion products in the cattle industry that are not listed in Appendix A. Bacitracin, bambermycins (Gainpro®), laidlomycin (Cattlyst®), and ionophores (such as Rumensin®) are not affected by this GFI.
What is “Judicious Use”? “Judicious use” is using a drug appropriately and only when necessary. The development of resistance to medically important drugs, and the resulting loss of their effectiveness, poses a serious public health threat. Misuse and overuse of antimicrobial drugs creates selective pressure that allows resistant bacteria (the “bad bugs”) to increase in numbers faster than susceptible bacteria and can transfer through the food chain to humans, increasing the opportunity for individuals to become infected by resistant bacteria. This could potentially result in treatment failure or a prolonged course of disease in a human patient because the antibiotics routinely used for that condition were not effective (for example: methicillin-resistant Staph. aureus or MRSA). Because antibiotic overuse contributes to the formation of drug resistant organisms, these important drugs must be used carefully in both animal and human medicine to slow the development of resistance.
The Judicious Use Guidance (GFI #209) provides two recommended principles regarding the appropriate use of drugs: (1) Limit medically important antimicrobial drugs to uses in animals that are considered necessary for assuring animal health, and (2) Limit medically important antimicrobial drugs to uses in animals that include veterinary oversight or consultation. Regarding Principle 1, FDA considers uses that are associated with the treatment, control, and prevention of specific diseases to be necessary for assuring the health of food-producing animals. In contrast, “production uses” are not directed at any specifically identified disease, but rather are used for enhancing the production of animal-derived products. FDA believes that production use indications such as “increased rate of weight gain” or “improved feed efficiency” are no longer appropriate for medically important antimicrobial drugs. Because drugs given in feed or water are often administered to entire herds or flocks of food-producing animals for production purposes, this poses a higher risk to public health than the administration of these drugs to individual animals or targeted groups of animals to prevent, control, or treat specific diseases. For that reason, this guidance is focused on antibiotics that are approved for use in the feed or water of food-producing animals.
Why is veterinary oversight necessary? Prior to 1993, most drugs given in feed and water were approved for over-the-counter use in food-producing animals. At that time, the methods used by FDA to assess food safety aspects of new animal drug applications were not as rigorous as those used today, in part because less scientific data was available about the public health ramifications of antimicrobial resistance. However, as time passed and data has accumulated, all antimicrobial new animal drugs for use in food-producing animals approved by the FDA Center for Veterinary Medicine (CVM) since 1993 have been labeled with prescription (Rx) or VFD marketing status, with the exception of generic copies of existing over-the-counter (OTC) products. This shift to requiring veterinary oversight was viewed as an important step to slow the food safety risks potentially caused by the use of new animal drugs, particularly for those drugs considered to be medically important. Based on the available scientific evidence, FDA believes that the judicious use of medically important antimicrobial drugs intended for use in food-producing animals should involve the scientific and clinical training of a licensed veterinarian. This is because judicious use involves accurately identifying bacterial disease that is present or likely to be present and selecting the suitable antimicrobial drug. Veterinarians are uniquely qualified to determine which specific disease-causing organisms are likely to be present and to determine appropriately timed administration of medication relative to the disease. The decision to use a specific approved drug or combination drug is based on factors such as the mode of antibacterial action, drug distribution in specific tissues, and the duration of effective drug levels at the site of infection. In the case of prevention, judicious use includes the ability to consider all relevant factors in order to determine the risk of developing a specific bacterial disease.
Timeline for Implementation? Once the final version of Guidance #213 is finalized, FDA intends to monitor the progress of its strategy for the voluntary adoption of the changes outlined, including the progress of measures intended to make an orderly and relatively smooth transition. This final guidance simply represents the FDA’s “current thinking” regarding antimicrobial drugs and contains “nonbinding recommendations” so adoption of these practices by drug companies is considered voluntary. After 3 years, FDA will evaluate the rate of voluntary adoption of the proposed changes across affected products. The agency will then consider further action as warranted in accordance with existing provisions of the Food, Drug, and Cosmetic (FD&C) Act for addressing matters related to the safety of approved new animal drugs.
Developing strategies for reducing antimicrobial resistance is critically important for protecting both public and animal health. Collaboration involving the public, the public health, animal health, and animal agriculture communities is needed to assure that the public health is protected while also assuring that such strategies are feasible and that the health needs of animals are addressed. It is critically important to remember the benefits of using antibiotics in food animal production and the adverse effects that would result from their removal. FDA recognizes that it is important to work with the veterinary and animal producer communities to ensure that their concerns are taken into consideration as these changes are implemented. FDA is very interested in receiving comments on the practical implications of these changes for animal producers, particularly those with smaller operations in remote locations. The agency is also interested in receiving input on how impacts or disruptions to animal producers could be minimized and the economic effects that may result from the adoption of the practices set out in this Guidance. Submit comments on the draft guidance (GFI #213) by the date provided in the Federal Register notice announcing the availability of the draft guidance. Submit written comments to the Division of Dockets Management (HFA-305), Food and Drug Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852. Submit electronic comments to http://www.regulations.gov. You should identify all comments with the docket number listed in the notice of availability that publishes in the Federal Register. For further information regarding this document, contact William T. Flynn, Center for Veterinary Medicine (HFV-1), Food and Drug Administration, 7519 Standish Place, Rockville, MD 20855, 240-276-9084. E-mail: email@example.com.
Additional copies of this guidance document may be requested from the Communications Staff (HFV-12), Center for Veterinary Medicine, Food and Drug Administration, 7519 Standish Place, Rockville, MD 20855, and may be viewed on the Internet at either http://www.fda.gov/AnimalVeterinary/GuidanceComplianceEnforcement/Guidan... or http://www.regulations.gov.
Source: Dr. Michelle Arnold, Large Ruminant Extension Veterinarian, University of Kentucky