As part of its overall responsibility for ensuring the safety of animal drugs, CVM continues to address public health safety concerns associated with antimicrobial drug use in animals and the related development of antimicrobial resistant bacteria. These efforts are focused on the use of antimicrobial drugs in food-producing animals and the impact of such use on antimicrobial resistance in food borne bacterial pathogens. During FY 2012, we took steps to develop strategies for addressing antimicrobial resistance concerns. This included steps taken to limit the use of antimicrobial drugs in food-producing animals, and to enhance the quality and accuracy of data on antimicrobial drug sales and distribution. We also continued to evolve our effort to monitor resistance among enteric bacteria in both animals and humans through the National Antimicrobial Resistance Monitoring System (NARMS).
CVM completed an assessment of our organizational capacity to manage the antimicrobial resistance issue, which resulted in recommendations for CVM’s senior leadership. This assessment is critically important for ensuring that CVM has sufficient scientific capacity to effectively manage this important public health issue.
Limiting the Use of Antimicrobial Drugs in Food-Producing Animals
Our overall strategy, for medically important antimicrobial drugs, is to phase out production uses and phase in greater veterinary oversight of therapeutic uses. We are promoting “judicious use” of therapeutic antimicrobials to help curb the emergence of resistance, through targeted drug use that reduces unnecessary or inappropriate use. Our focus is on a collaborative approach for making changes in the use of currently approved products.
We made significant progress in implementing these strategies during FY 2012. This included:
Judicious Use of Medically Important Antimicrobial Drugs in Food-producing Animals Final guidance was issued in April 2012. This document, Guidance for Industry # 209, recommends steps to phase out agricultural production use of medically important drugs, and to phase in greater veterinary oversight of therapeutic use of these drugs.
Draft guidance issued in April 2012 that will assist drug companies in voluntarily removing production uses of antibiotics from their FDA-approved labels. The Draft Guidance for Industry # 213, is entitled, “Revising Approved Conditions of Use for New Animal Drugs and New Animal Drug Combination Products Administered in or on Medicated Feed or Drinking Water of Food-Producing Animals to Align with GFI#209.” It provides guidance on adding, where appropriate, labeling for scientifically-supported disease prevention, control and treatment uses, and for changing the marketing status to include veterinary involvement.
Veterinary Feed Directive (VFD) draft proposed regulation. In April 2012, CVM published for public comment the Veterinary Feed Directive draft proposed regulation to streamline the process under which veterinarians authorize the use of certain animal drugs in feed. The proposed changes are needed to improve the efficiency of the current VFD regulation. In March 2010, FDA issued an advance notice of proposed rulemaking (ANPRM) to solicit comments from the public on potential changes to its current regulation relating to VFD drugs. FDA received numerous comments from the pharmaceutical industry and veterinary and animal feed industry groups; these comments confirmed that this is a very complex issue, and that developing a workable set of requirements for VFD drugs is a critical first step in moving toward increased veterinary supervision of feed use antimicrobial drugs. We published the proposed regulation following careful review of the comments, and discussions with stakeholder groups.
Prohibition of certain extra-label uses of cephalosporins. CVM published a final order prohibiting certain extra-label uses of cephalosporins in cattle, swine, chickens and turkeys. The purpose is to preserve the effectiveness of this medically important class of drugs for treating disease in humans. FDA originally issued an order in July 2008 to prohibit all extra-label uses of cephalosporins in food-producing animals to address public health concerns associated with emerging bacterial resistance to this critical class of antimicrobial drug. FDA withdrew the order to provide additional time to consider public comment. The effort to develop and publish the final order required a review of all public comments, an analysis of additional scientific information, and the development of necessary revisions to the original prohibition order.
Collecting and Reporting Data on Antimicrobial Drugs
Section 105 of the Animal Drug User Fee Amendments of 2008 requires antimicrobial drug sponsors to report the amount of antimicrobial active ingredient in their drugs that has been sold or distributed for use in food-producing animals. The Animal Drug User Fee Act also requires FDA to summarize the sales and distribution information received from drug sponsors each year, and to provide these summaries to the public.
The collection of data on antimicrobial drugs, such as the sales and distribution information, assists CVM in its evaluation of antimicrobial resistance trends. It also supports analysis of other issues that may arise relating to the safety and effectiveness of antimicrobial drugs approved for use in food-producing animals.
During the year we implemented enhancements to improve the quality and accuracy of data obtained on the active antimicrobial ingredients in animal drugs, strengthening FDA’s position on the judicious use of antibiotics and limiting production use of antibiotics. For example, we made enhancements to the relational database for receiving food-producing animal antimicrobial data. The relational database is written in Microsoft Access, a powerful tool that allows for easy entry, access, and reporting of antimicrobial distribution data. The new database has helped save time and resources, and has ensured accuracy and consistency of the reported data.
With a view toward making further improvements in the existing requirements related to the collection of antimicrobial drug sales/distribution data, we published an Advance Notice of Proposed Rulemaking July 27, 2012 to solicit comments from the public. We also sought input on alternative methods for monitoring antimicrobial use in food-producing animals. We need such information to support FDA’s strategy for promoting the judicious use of medically important antibiotics in food-producing animals.
Antibiotic Residues in Distillers Products
Distillers products are by-products of the rapidly emerging and expanding fuel ethanol industry that pose some unique and challenging science, policy, and food safety issues. In particular, there are concerns that use of antimicrobials during the ethanol fermentation process may result in antimicrobial residues in the distillers’ products that are subsequently fed to food-producing animals, risking the development of resistant organisms. During 2011 we began developing draft guidance for industry that outlines a clear and consistent policy for addressing food and feed safety concerns associated with the emerging and expanding use of distillers’ products as an animal feed ingredient. This draft guidance was under review as fiscal year 2012 closed. (Mycotoxins are also a safety concern with distillers products; see “Science at CVM” for a description of mycotoxin related research).
Using the National Antimicrobial Resistance Monitoring System to Obtain Critical Information
The National Antimicrobial Resistance Monitoring System (NARMS) is the only national program that monitors antibiotic resistance in food borne bacteria, including both pathogenic (Salmonella, Campylobacter) and commensal (E. coli, Enterococcus) organisms. NARMS is an inter-agency collaborative effort that compares strains from human clinical cases (Centers for Disease Control and Prevention), retail meats (FDA) and food-producing animals (USDA Agricultural Research Service). FDA established NARMS in 1996 as part of an overall strategy to assess the impact of antimicrobial use in food animals on public health.
NARMS is dedicated to protecting human and animal health through integrated monitoring of antimicrobial resistance among enteric bacteria. The NARMS program is critical to accomplishing the missions of the U.S. Department of Health and Human Services and FDA, and ultimately in protecting the health of Americans through safer food.
NARMS monitoring supplies FDA the critical data needed to inform and prioritize science based approaches to minimizing public health hazards resulting from antimicrobial use in food animals. NARMS data also are helpful in disease outbreak investigations, and can be used to evaluate treatment guidelines for food borne pathogens, thereby ensuring better health outcomes.
Because NARMS data have played key roles in recent regulatory activities, such as the 2012 cephalosporin extra-label use prohibition, there is a need to critically re-evaluate sampling approaches to assure that the data being generated can withstand scrutiny from both a scientific and regulatory perspective. CVM developed an interagency agreement with USDA Agriculture Research Service (ARS) to initiate five on-farm pilot studies aimed at estimating the prevalence of Salmonella and Campylobacter in dairy and beef cattle, chickens, turkeys, and swine. We established a new consortium of ARS research centers and select universities to collect samples, culture food borne bacteria, and ship isolates to CVM for testing. The pilot studies were completed in late 2012, and the results were being evaluated to design on-farm testing for 2013.
During the year, CVM developed another interagency agreement with the USDA Food Safety Inspection Service (FSIS) to initiate a randomized sampling plan in processing plants to collect cecal samples from beef and dairy cattle, turkeys, broilers, sows and market hogs. This new program will become the core of the animal monitoring component of NARMS, replacing the historic reliance on Hazard Analysis Critical Control Point (HACCP) compliance samples from FSIS.
This will enable NARMS to report data that are nationally representative of food animal production and is sustainable long-term. By gathering pre-processing cecal samples, NARMS will avoid possible cross-contamination of in-plant samples. The in-plant and on-farm sampling approaches are based on recommendations from the FDA Science Board and NARMS stakeholder meetings.
To increase sample size and national representativeness of retail meat monitoring, three state health departments (LA, MO, and WA) were added to the NARMS retail meat program during the year. Microbiologists from those three states participated in a two-day methods training course held at CVM in February 2012. All three state laboratories were to begin full time testing in January 2013.
The result of these efforts is new collaborative approaches for NARMS on-farm and retail sampling, which are statistically representative, scientifically sound and directly support FDA regulatory activities. NARMS continues to mature and improve over time and has evolved into a mission-critical tool for FDA.
Additional NARMS accomplishments this year include publication of the 2010 retail meat annual report (published in March, 2012) and the 2010 executive report (published in July, 2012). We also made a public release of the 2012-2016 NARMS strategic plan, which was revised this year based on input from a series of stakeholder meetings held in 2011.