1
Importance of Veterinary Drug Residues

Ronald E. Baynes1 and Jim E. Riviere2

1 Department of Population Health and Pathobiology, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, USA

2 Department of Anatomy and Physiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS, USA

1.1 Introduction

Food animal production over the last 50–60 years has significantly increased with the implementation of modern genetics, breeding, husbandry, and nutrition. During this same time period, livestock producers have relied on the use of veterinary drugs as one of several strategies to ensure economic viability of the industry. This need for increased use of veterinary drugs, and especially antimicrobial drugs, has been linked to changes in standard livestock practices where the objective is to increase feed and space efficiency and to a need to generate greater quantities of meat, milk, and egg products in an ever increasing competitive global market. While the consumer appreciates the need to increase livestock production and generate reliable and affordable animal-derived products, this is tempered by the consumers’ requirement that the food items be “free” of drugs or chemicals introduced in the production system. The wide availability of related information via the Internet has exposed the consumer to useful facts but all too often to controversial statements and hypotheses with very little factual support from the scientific literature regarding the prevalence of drug residues in our food, how veterinary drugs are used, and what safeguards are implemented to reduce these residues. This introductory chapter will briefly review the role of drugs in modern livestock production, quality assurance programs, adverse human health effects of drug residues, and economic impact of these residues to the livestock industry.

1.2 Veterinary Drug Use in Livestock

Modern livestock production can be described as involving intensive animal production practices that often use veterinary drugs at subtherapeutic level in feed and water in order to improve feed efficiency for growth and production and maintain animal health. In such close animal–animal contact practices, prevention of disease is more important than treating for disease that would require therapeutic levels (higher doses) of the drug. The United States defines subtherapeutic use of an antimicrobial as a feed additive less than 200 g of drug per ton of feed.

Subtherapeutic drug use may take the form of (i) antimicrobials delivered to the animal as a feed or water additive and (ii) hormones delivered via ear implants or feed additives.

The antimicrobials approved in the United States and EU to be used in this legal manner often belong to the tetracycline, sulfonamide, or macrolide class of antimicrobials. Several EU countries and others banned or limited the use of these drugs as growth promoters as there are concerns that their use promotes the emergence of antimicrobial resistance. This cause-and-effect relationship is continually being debated across various jurisdictions; although epidemiological evidence continues to accumulate, definitive conclusions from rigorous research in livestock production systems has not been forthcoming. This issue will be further explored in this and other chapters of this book.

The use of hormone growth promoters in livestock has also been a controversial debate as various regulatory authorities in different jurisdictions regulate these drugs in a different manner. The U.S. FDA has approved the legal use of 17β-estradiol, testosterone, progesterone, trenbolone, and zeranol as solid ear implants and melengestrol acetate (feedlot heifers) and ractopamine (swine) as feed additives. Compared to the United States, the EU in 1988 issued a total ban of all hormonal active growth promoters in livestock production. Prior to 1988, in the Netherlands (1961) and Belgium (1962–1969), there was a total ban on anabolic agents for growth promotion purposes in slaughter animals in order to protect consumers and for the benefit of international trade (Stephany, 2010). It should be noted that the United States challenged the EU’s ban, and in 1998, the WTO found that the EU’s ban was not supported by science and inconsistent with WTO obligations (USTR, 2009).

Therapeutic drug use in veterinary livestock involves administration of veterinary drugs according to label to treat an individual animal or herd or flock of animals by various approved routes of administration. The use of water additives is recognized in all countries as a form of therapeutic drug use and not subtherapeutic drug use or for growth promotion purposes. It has however been our experience (Mason et al., 2012) that treatment of large herds via water medication does not always result in each animal in the herd receiving therapeutic drug levels. This has often been associated with competition between animals in the herd and/or malfunctioning medicators. The approved use of the many therapeutic drugs will be outlined in the species-specific chapters of this book.

The passage of the Animal Medicinal Drug Use Clarification Act (AMDUCA) 1994 in the United States allows food animal veterinarians to administer drugs in an extralabel manner within certain guidelines as outlined in the following text. Veterinarians often have to resort to using these drugs in an extralabel manner for a number of reasons. New generics of old drugs are approved based on bioequivalence to pioneer formulation, which allows the same dosage and milk discard/meat withdrawal times. The problem with this approach is that new bacteria being treated have much higher MICs than bacteria and microorganism many years ago, and thus, higher dose must now be used. Veterinarians often consult with FARAD to find out new withdrawal times, and this is described in more detail in Chapter 14. The scientific issue is that most antimicrobials used in dairy practice today are old drugs (or generic copies of old drugs) that are now not effective unless given at higher doses, necessitating extended milk discard times. Risk of exposure to low-level residues of most other drugs out there is “theoretical,” but low label dosages of antimicrobials, used to insure adequate withdrawal times, will promote resistance, which is the major public health issue. There are more modern approaches that would allow dosage adjustments with new withdrawal times, but we are stuck in the science of the 1970s. Legal precedence and business issues tend to hand tie the FDA (in approving all generics just like the first one that was approved even if science has advanced in 30 years). Production use of antibiotics as growth promoters may very well be banned, and therapeutic use at higher doses by licensed vets maintained.

Phytoceuticals are increasingly being used on organic farms with varying degrees of success. These drugs are not regulated by the FDA-CVM as they are often described as “generally recognized as safe” (GRAS). There are however several guidance documents and requirements that organic livestock farms are required to follow and are discussed elsewhere in this book.

1.3 Quality Assurance Programs

Consumers are very aware of drug and chemical use in the livestock industry, and oftentimes, there is general misinformation about how these drugs are used in the industry. The infrequent catastrophic drug residue violations are often a direct result of careless farm management. The subsequent economic cost to the livestock industry is not ignored by the many stakeholders involved in livestock production and distribution and sales of meat, milk, fish, and egg products. This will be discussed in more detail in a later section of this chapter.

In lieu of these scenarios, the livestock industry has been aggressively policing itself to make sure that producers are educated and trained to prevent drug residue violations on their farms. Many if not most livestock producers follow and adhere to their respective quality assurance programs for their commodity group that attempt to minimize drug residue violations and promote judicious use of veterinary drugs. A summary of the steps producers are encouraged to follow whether it is the beef, dairy, pig, goat, or poultry industry is as follows:

1. Improve husbandry practices by maintaining appropriate husbandry, hygiene, examinations, and vaccinations.
2. Consult with a veterinarian prior to use of drugs or medicated feed or water as therapeutic alternatives may be more appropriate.
3. Use drug according to veterinary label and only resort to using veterinary drugs as a last resort. This is especially important for antimicrobial drug use.
4. Antimicrobial drug use is inappropriate for viral infections without bacterial complication.
5. Optimize antimicrobial drug regimen using current pharmacological information and principles.
6. Mitigate veterinary drug spillage into the environment.
7. Keep good records of drug use on each farm.
8. Extralabel drug use in the United States must follow the FDA regulations: prescriptions, including extralabel use of medications must meet the AMDUCA amendments to the Food, Drug, and Cosmetic Act and its regulations. This includes having a valid veterinary–client relationship.

The passage of the AMDUCA in the United States in 1994 allows food animal veterinarians in the United States to administer drugs in an extralabel manner within certain guidelines. Several...