Unintended Drug Residues of Approved Veterinary Products in Human Food

Veterinary drug carryover or contamination in animal feed, meat, milk, cheese, fish and eggs has known negative health effects, and potentially impacts global trade. Risk assessment and management are essential to eliminate these contaminant causes.

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Learn more in Scott Haskell's online course “Animal Health, World Trade, and Food Safety” (this fall semester 2021), or in IFLR's courses "Codex Alimentarius - The World Food Code" (this spring semester 2022), or "International Food Laws and Regulations" (offered each fall and spring semester).

Food safety has become a challenge during this time of the pandemic and the rules associated with the Food Safety Modernization Act (FSMA). One recent area of global food safety concern is veterinary drug residues and carryover into human food.

Carryover or contamination by veterinary drugs in animal feed, meat, milk, cheese, fish and eggs can be a significant human and animal health hazard. Carryover can occur during the use of drugs in an unprescribed manner, within the incorporation of animal feed processing and handling, the feeding/use of inappropriate drug dose/treatment regimens, inappropriate drug withhold clearance times, and unapproved pharmaceutical use in agricultural production animals.

Carryover of veterinary drugs and pharmaceutical residues is unacceptable and can cause negative health effects in humans and animals. Drug residues and carryover, if not properly managed, can lead to negative trade issues, human and animal health sensitivities and antibiotic microbial resistance (AMR) development. Veterinary drug residues in food can render products unsafe for human consumption. These residues can pose legal, regulatory, ethical and global trade issues with many governments implementing their own non-enforceable non-transparent non-established legal non-science-based residue limits for food.

An informed attempt towards the international legal barriers for veterinary drug use and barriers to trade needs to be devised. Although national and global law currently emphasizes the legal approaches to infectious diseases, the global laws surrounding emerging toxicity, veterinary drug use, AMR and human health issues reflects a future role for international food law.

Upon the request of the Codex Alimentarius Committee on Residues of Veterinary Drugs in Foods (CCRVDF), the world Health Organization (WHO) and the Food and Agriculture Organization of the United Nations (FAO) convened an Expert Meeting in 2017 tasked with the review of veterinary drug carryover causes in at-risk animal feed and the subsequent transfer from feed to animals to human food.

How do we deal with these food safety issues? Human food safety risks are important especially if veterinary drug residues are present in human food and animal feed. This is especially true if these residues exceed the Health Based Guidance Values (HBGV). These contamination levels have been determined by Codex within the context of acceptable daily intake (ADI) levels and/or an acute reference dose (ARfD) (WHO/FAO JECFA). Routes of drug administration, product dose, prescribed lack of appropriate post treatment withhold times, type of medication, source and drug concentrations are hazards associated with veterinary drug carryover in animal feed and human food products. Additionally, antibiotic microbial resistance (AMR) is of increasing importance with the use of antimicrobials in animals worldwide. Pharmacokinetics of these agents (e.g., metabolism, elimination, absorption, distribution) is important in understanding food residue and carryover levels in food.

Historically, there is a much greater risk of residue transfer in milk, cheese, and eggs than in meat. It should be emphasized that many nations do an outstanding job evaluating feeds and human food for veterinary drug residues/carryover.

What drugs and pharmaceuticals are commonly utilized in veterinary medicine that may affect you as a global consumer? The classes of veterinary drugs and pharmaceuticals which are most commonly incorporated into animal feed can be broken down into three primary groups: antimicrobials/antibiotics, coccidiostats and growth promotants (β-adrenergic agonists). Due to global concerns over AMR, the common utilization of antimicrobials as a growth promotant has been greatly reduced, but not eliminated.

Approved drug classes for the use in animal agriculture and animal feeds varies greatly between nations; these differences can lead to disputed trade differences when residues occur. The most common classes of antimicrobial agents utilized in veterinary medicine include sulfonamides, tetracyclines, and macrolides. Sulfonamides may also be cojoined with the antibiotic trimethoprim. Additionally, antimicrobials such as β-lactam antibiotics, glycopeptides, aminoglycosides, lincosamides, and pleuromutilin are also utilized in animals within many nations and with differing species and methods/dosage of treatment. Veterinary carryover and tissue residue is a significant global issue especially with penicillin, tetracyclines, and sulfonamides. Aquaculture is associated with an important issue with the physical characteristics of veterinary drug products especially with sulfonamides incorporated into the feed. Shellfish and fish have an increased potential for veterinary carryover and subsequent tissue drug residues due to many drugs being metabolically temperature dependent. Water temperature significantly impacts drug metabolism allowing for the development of carryover.  

Coccidiosis is a global disease common where large numbers of animals are kept generally in confinement rearing. It is a contagious disease caused by single-celled parasites which are easily transferred within feces. Coccidiosis affects the husbandry, productivity and health of many species especially poultry, goats and rabbits. Coccidiostats differ substantially from many antimicrobials as they generally are required continuously throughout the life span of the production animal. This continuous treatment régime is required due to the ongoing transfer of infection and reinfection of animals consistent with increased stocking densities (e.g., animal intensified husbandry). Though the overall health risk to human and other animal species appears scientifically negligible, frequent product carryover is a regulatory/trade concern for many nations. Coccidiostats are generally not antibiotics so their use may fit into the ‘antibiotic free’ labeling category when used. Carryover can remain high in many traded species causing frequent product embargos.

What about the new issues surrounding multi-drug resistant bacteria in our hospitals, farms and food supply? AMR is a growing concern globally. The use/quality of antibiotics and antimicrobials in animals/humans is not highly regulated in many nations and there are risks involved in the development of microbial resistance both from human as well as animal dosing. Recent research has concluded that exposing animals to antimicrobials/antibiotics results in higher resistance rates to those antimicrobials than exposing animals to no (or a lower dose of) antimicrobials (Scott, 2018). An essential problem with the transfer of genes for resistance is that drug resistant bacteria can spread genetic material to humans through direct contact with commensal resistant bacteria, food, on farm facilities and contaminated animals and products. Concentrated feeding operations (CAFOs) that produce large numbers of animals as well as modern commercial slaughter facilities (farm to fork) can increase the risk of bacterial contamination, especially bacterial species of Salmonella, E. coli, Staphylococcus, Campylobacter, and Listeria, leading to foodborne illness transmission and the potential for AMR spread.

Finally, what about the trade aspects of safe food? Global trade and legal issues from carryover and drug residues in food, feed and food products can be quite a regulatory burden. Regulatory provisions vary substantially on a national basis and detectable levels of carryover in countries with a ‘zero’ tolerance for residues can block trade completely. Commonly, regulatory concerns over drug residues in meat, milk, cheese, fish and poultry may be used as trade barriers. Legal liberalization and standards development emphasizing transparency has been promoted by the Codex Alimentarius Commission (CAC). Maximum Residue Levels (MRLs) of veterinary drugs can vary by country and trading partners.  MRLs are the maximum acceptable levels of pesticides and/or veterinary drugs in food and agricultural products set by Codex and the USDA. A lack of international harmonization of MRLs can result in overt barriers to trade. The World Trade Organization (WTO) as well as the CAC works with global nations and trading partners to harmonize their sanitary and phytosanitary measures. The development of transparent international standards concerning drug residues is the overarching goal of these organizations to insure free trade. The Agreement on Sanitary and Phytosanitary Measures of the WTO allows nations to set higher residue levels that reflect current science-based global health standards. However, these measures must be based on consistent sound science from the WHO and the FAO. Trade issues based on MRL differences are common and can impede trade. The Codex Alimentarius Commission has established professionally transparent Risk Management Recommendations for the global use of veterinary drugs. (JECFA WHO/FAO). https://www.who.int/foodsafety/chem/jecfa/Guidance-document-ARfD-2017.pdf?ua=1

So, what can we do to help with these legal and trade issues associated with food carryover of veterinary drugs? Effective public health strategies and laws are essential to manage these issues and need to be informed by both legal as well as scientific analysis. Legal issues can arise from international attempts to regulate food safety and actually underscores the need for a joint effort between public health and international law. Most U.S. public health law is at the state and local level. State laws concerning public health may need to be reevaluated in the context of emerging toxicity and disease control as well as food safety issues like AMR. The emerging issues concerning AMR, food trade barriers, and acceptable veterinary drug residue levels places the importance on sound scientific analysis, as well as international and federal law. Policymakers now must grapple with a substantially different set of government issues, economic barriers, scientific understanding, political inclusion, and largely sensitive trade interests.

Understanding the importance and influence of the intergovernmental Codex standards is essential to our national food safety success. Our national and international food producing industries are already involved with these legal issues and should always be included at the domestic and global negotiating tables. Consumers are becoming increasingly informed about AMR and the veterinary drugs that may enter the food chain through the use of antibiotics in animal feed and food production. Trade-related insight in the use and direct access of antimicrobial agents needs to be understood by the government, producers, industry, legal experts and trading partners.

It should be accepted that trading interests and negotiations are guarded by global governments and as always, they will protect their national best interests. To help facilitate these food safety carryover issues, Codex negotiations need to be of increased discussion by everyone within the international food producing microcosm.

Disclaimer

References

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https://www.who.int/foodsafety/chem/jecfa/Guidance-document-ARfD-2017.pdf?ua=1

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