– Dr. Michelle Arnold, UK Veterinary Diagnostic Laboratory
The Food and Drug Administration (FDA) is continuing to implement strategies to promote the *judicious or appropriate use of antibiotics considered important in human medicine when they are used in food-producing animals. FDA’s goal is to curb the development of antibiotic-resistant bacteria and in turn reduce the risk of human infections that are difficult to treat due to ineffective antibiotics. On June 11th of 2021, FDA finalized a Guidance for Industry (GFI) #263, which outlines the process for animal drug manufacturers to change all remaining antibiotic formulations used in animal health care from over-the-counter (OTC) to prescription status. Manufacturers will have two years from the date of issue to make this label change to their products. Basically, this means products commonly used by beef producers such as injectable penicillin and oxytetracycline (for example, LA-300) will no longer be available without a prescription as of June 2023.
The new GFI #263 is an extension of an earlier guidance published in 2013 designated GFI #213. As of January 2017, GFI #213 effectively moved all OTC antibiotics used in feed to Veterinary Feed Directive (VFD) status and those used in drinking water to prescription (Rx) status as well as eliminated production uses such as growth promotion. Of the 292 drugs affected by this government directive #213, 93 products used in drinking water were converted to prescription status; 115 products used in feed were converted from OTC to veterinary feed directive status; and 84 were removed from the market. Production indications were withdrawn from 31 product labels. With full implementation of GFI #213, approximately 96% of medically important antimicrobials used in animals are now under veterinary oversight. Once the recommendations in the new GFI #263 are fully implemented, all dosage forms of medically important antimicrobials approved for use in animals will only be available from, or under the supervision of, a licensed veterinarian, and only when necessary for the treatment, control or prevention of specific diseases. Producers will have to consult their veterinarian to obtain all antibiotics in any form (injectable, bolus, topical, intramammary) or for a prescription to purchase them from a distributor.
FDA’s new strategy with GFI #263 is primarily focused on “medically important antimicrobial drugs” that are available without a prescription and can be given without a veterinarian’s involvement. This includes, but is not limited to, beta-lactams (Penicillin G, Cephapirin), aminoglycosides (Gentamicin), lincosamides (Lincomycin), macrolides (Tylosin, Erythromycin), sulfonamides (Sulfadimethoxine, Sulfamethazine, Sulfachlorpyridazine) and tetracyclines (Oxytetracycline, Chlortetracycline). FDA first developed its list of antimicrobial drugs (antibiotics) considered “medically important” in Guidance #152, Evaluating the Safety of Antimicrobial New Animal Drugs with Regard to Their Microbiological Effects on Bacteria of Human Health Concern, published in October 2003. This list is available in Appendix A of GFI #152 and can be accessed at the following link: https://www.fda.gov/media/69949/download . Medical “importance” of a drug is based on its efficacy in human medicine and other factors including the usefulness of the drug in food-borne infections, the types of infections treated, the availability of alternative therapies, the uniqueness of the mechanism of action, and the ease with which resistance develops and is transferred between organisms. There are several growth promotion products in the cattle industry that are not listed in Appendix A. Bacitracin, bambermycins (Gainpro®), laidlomycin (Cattlyst®), and ionophores (such as monensin and lasalocid) are not affected by this GFI.
The FDA has made available a webpage entitled “GFI #263: Frequently Asked Questions (FAQs) for Farmers and Ranchers” available at https://www.fda.gov/animal-veterinary/judicious-use-antimicrobials/gfi-263-frequently-asked-questions-farmers-and-ranchers . One specific question of interest addressed on this website is “Will a veterinarian be required to physically examine each animal before writing a prescription?” The following answer is provided by FDA:
“Although specific requirements vary by state, veterinarians are generally not required to examine each individual animal for which a prescription is issued, as long as the veterinarian has established a valid veterinarian-client-patient relationship (VCPR) with the farmer or rancher that owns or cares for the animal(s) in need of treatment.”
Establishing a VCPR generally requires, among other things, that the veterinarian has become familiar with the management of the animals on a given farm or ranch by examining the animals and/or visiting the facility where the animals are managed. [See Box 1 for KY VCPR Requirements] Farmers and ranchers may want to consult with their veterinarian to have a plan in place prior to the transition period, including a plan for getting access to appropriate antimicrobial products to address animal health issues when a not veterinary visit is not feasible or not considered necessary by the veterinarian.”
During the two-year timeframe for implementation that began on June 11, 2021, FDA plans to work with affected stakeholders and state partners to answer questions about the voluntary transition process and provide assistance, hear feedback and answer questions about the guidance where possible. There are legitimate concerns regarding the increased cost of this legislation to beef producers and the lack of food animal veterinarians in many parts of the country. Similarly, veterinarians are concerned about the increased regulatory burden this move to prescription status will impose. The guidance document and a link for submission of comments can be found at https://www.fda.gov/regulatory-information/search-fda-guidance-documents/cvm-gfi-263-recommendations-sponsors-medically-important-antimicrobial-drugs-approved-use-animals. The FDA is reaching out to stakeholders for input and public comments. Comments on the proposal are due online via www.regulations.gov by December 24, 2021.
Comments may also be submitted by mail to:
Dockets Management Staff
HFA-305
Food and Drug Administration
5630 Fishers Lane, Room 1061
Rockville, MD 20852
Comments should reference docket number FDA-2019-D-3614.
*What is “Judicious Use”? “Judicious use”, according to FDA, 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 number faster than susceptible bacteria and is hypothesized to transfer through the food chain to humans, potentially increasing the opportunity for individuals to become infected by resistant bacteria. This scenario may 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.