Avoiding Unsafe Drug Residue in Human Food
One of FDA’s highest priorities is to ensure the safety of animal-derived foods for human consumption. As part of the approval process for a drug for a food-producing animal, the agency sets the drug’s tolerance. Selling animals for food with drug residues above the established tolerance is illegal and causes the food to be adulterated. FDA actively investigates the misuse of veterinary drugs in food animals, and violative tissue residues are a common trigger for follow-up investigations and the issuance of Warning Letters to all responsible parties in the animal production/marketing chain. Should continued violations occur, FDA can take enforcement actions such as injunctions, contempt of injunction, and prosecutions.
During FY 2011, the Division of Compliance’s Drug Residue Compliance Team completed reviews of 63 Warning Letters and 2 Untitled Letters; it finalized 2 injunction actions; and processed 5 contempt of injunction actions.
In addition, the Division’s Post-Market Approval Team completed reviews of 6 Warning Letters and 2 Untitled Letters; and it processed 1 contempt of injunction action.
For a number of years, a significant proportion of all violative tissue residues reported to CVM by the USDA have involved dairy animals. Although only 7.7 percent of the cattle slaughtered in the United States are adult dairy cows, these animals cause 67 percent of the tissue residue violations. Because of this high violation rate, FDA has focused attention on determining the causes of the violations and developing appropriate mitigation strategies. Drug residue violations in dairy cows often result from poor husbandry practices on the farm. Examples of such practices are failure to maintain adequate treatment records, failure to identify treated animals, failure to follow labeled withdrawal times, increasing the labeled dosage, increasing the length of treatment, administering the drug by an unapproved route of administration, and giving the drug in an unapproved species.
Any of these practices can lead to violative drug residues. CVM has provided information on the common causes of violative residues and shared prevention strategies at several official meetings held by the dairy industry, producers, veterinary practitioners, and state regulatory entities.
In July 2011, a U.S. District Court in Washington State found in favor of the U.S. government in a case involving the unlawful use of animal drugs in food-producing animals. The court agreed with the government that the defendants, a dairy farm and its owner, violated several provisions of the Federal Food, Drug, and Cosmetic Act.
Over a period of years, the USDA’s Food Safety and Inspection Service reported 13 illegal drug residues in the tissues of 9 culled dairy cows sold for beef by the dairy farm. The Food Safety Inspection Service sent the farm a residue violation letter, followed by several “repeat violator” letters.
The Food Safety Inspection Service reports of illegal tissue residues prompted FDA to inspect the dairy farm on three occasions. The inspections found that the farm had repeatedly used drugs in ways that caused illegal drug residues in animals sold for slaughter as food. The inspections also found that the farm had a history of incomplete recordkeeping.
Each inspection resulted in FDA issuing the dairy farm a Form FDA 483, which listed the observed violations of the Federal Food, Drug, and Cosmetic Act. The agency also issued the farm a Warning Letter, outlining the violations seen during the June 2004 inspection.
Based on the evidence from the FDA inspections, the district court permanently enjoined the dairy farm and its owner to prevent them from continuing to violate the Federal Food, Drug, and Cosmetic Act. The court noted that the defendants showed “a prolonged resistance” to complying with FDA regulations and “have not taken measures to achieve compliance,” despite receiving several notices from two Federal agencies.
Under the terms of the injunction, the dairy farm and its owner are not allowed to sell any animals for food until FDA is satisfied that they have adequate recordkeeping and other systems in place to prevent illegal tissue residues.
During FY 2011, the U.S. District Court for the Eastern District of California, Sacramento Division, entered a consent decree of permanent injunction against a veal calf dealer for selling for use as food veal calves that contained illegal drug residues in violation of Federal law.
The decree prevents the dealer from purchasing or selling any animals for use as food unless and until certain actions are taken to ensure that animals with illegal drug residues do not enter the food supply. The decree requires the dealer to keep written records to identify which animals have been medicated, and to segregate medicated and non-medicated animals. Previous FDA inspections of the operations found recurring violations of the Federal Food, Drug, and Cosmetic Act that the dealer failed to correct. Future violations of the decree may result in an order to cease selling animals for use as food and to take other corrective actions, including payment of fines for each day the dealer fails to comply, and for each animal sold in violation of the decree.
CVM’s Office of Surveillance and Compliance wanted to understand the factors that influence dairy farmers to make decisions that result in tissue residues. The Office of Surveillance and Compliance, in conjunction with the Office of the Commissioner, is conducting a mental modeling study to better understand dairy producer practices. The study will focus on analyzing current practices, knowledge, understanding, motivating factors, and information sources for dairy producers, and how best to reduce the occurrence of illegal residues of antimicrobial and non-steroidal anti-inflammatory drugs.
The preliminary research was completed during FY 2011. The Office of Surveillance and Compliance organized an expert panel workshop, which included veterinarians, producers, packers, and regulators, to provide input on factors that affect dairy producer decision making. The researchers have also conducted preliminary interviews of both tissue residue violators and non-violators. The results of the study will include recommendations for improving direct and indirect communications with dairy producers on how to avoid residues, with the goal of reducing the overall violative tissue residues.
In 1944, a drug called 3-Nitro (Roxarsone) became the first arsenic-containing new animal drug product approved by FDA. Its use, primarily in broiler chickens, continued for many years. Combined with other animal drugs, 3-Nitro has been used in the poultry industry to help control coccidiosis, a parasitic disease that affects the intestinal tracts of animals. It has also been used for weight gain, feed efficiency, and improved pigmentation.
Arsenic is in the environment as a naturally occurring substance or as a contaminant, and is found in water, air, soil, and food. Scientific reports published in recent years have indicated that organic arsenic, a less toxic form of arsenic and the form present in 3-Nitro, could transform into inorganic arsenic when fed to broilers. In response, scientists from CVM and the FDA Center for Food Safety and Applied Nutrition developed an analytical method capable of detecting very low levels of inorganic arsenic in edible tissue. Using the new method, Office of Research scientists found that the levels of inorganic arsenic in the livers of chickens treated with 3-Nitro were increased relative to levels in the livers of the untreated control chickens.
Provided with this information, the drug’s sponsor voluntarily suspended sale of 3-Nitro and devised an orderly process for removal of the product from the U.S. market. Allowing continued distribution for a short period provided time for animal producers to transition to other treatment strategies and helped ensure that animal health and welfare needs were met.
In addition, the sponsor is working with FDA to examine all relevant scientific data regarding the use of 3-Nitro in animals.
FDA has drafted a proposed rule providing procedures for the establishment, amendment, and revocation of import tolerances for unapproved new animal drugs. In establishing such tolerances, FDA will rely on data sufficient to demonstrate that a proposed tolerance is safe based on food safety criteria similar to those used to establish tolerances as part of the approval of new animal drug applications. The proposed rule, which was under review at the close of FY 2011, was authorized by the Animal Drug Availability Act of 1996.
During FY 2011, CVM’s Office of Research continued to make progress in its important work on developing innovative methods for detecting drug residue in edible food products. One example is the development and validation of a much more efficient and reliable liquid chromatography tandem mass spectrometry method for the determination and confirmation of the ceftiofur metabolite desfuroylceftiofur cysteine disulfide (DCCD) in bovine kidney. A second is the evaluation and validation of new methods for detecting multiple hormone residues. More details on these and other research efforts appear in the section of this report entitled, “Science at CVM"