MMiinnnneessoottaa JJoouurrnnaall ooff LLaaww,, SScciieennccee && TTeecchhnnoollooggyy Volume 15 Issue 1 Article 25 2014 SSlloowwiinngg AAnnttiibbiioottiicc RReessiissttaannccee bbyy DDeeccrreeaassiinngg AAnnttiibbiioottiicc UUssee iinn AAnniimmaallss Jennifer Nomura Follow this and additional works at: https://scholarship.law.umn.edu/mjlst RReeccoommmmeennddeedd CCiittaattiioonn Jennifer Nomura, Slowing Antibiotic Resistance by Decreasing Antibiotic Use in Animals, 15 MINN. J.L. SCI. & TECH. 585 (2014). Available at: https://scholarship.law.umn.edu/mjlst/vol15/iss1/25 The Minnesota Journal of Law, Science & Technology is published by the University of Minnesota Libraries Publishing. Note Slowing Antibiotic Resistance by Decreasing Antibiotic Use in Animals Jennifer Nomura* While antibiotics were originally developed for human use, veterinarians eventually began using them in animals, hoping the drugs would perform in animals the same way they did in humans.1 Approximately sixty percent of the diseases that humans get originate from animals,2 so veterinarians hoped that by giving animals antibiotics, the spread of disease would lessen.3 Today, antibiotics are mainly used in farm animals for both health reasons and animal growth purposes.4 Antibiotics © 2014 Jennifer Nomura * JD Candidate, 2014, University of Minnesota Law School. The author would like to thank Professor Ralph Hall for all of his helpful input and feedback. The author thanks the editors and staff of MJLST for all of their hard work. The author also thanks family and friends for their support, specifically Joe Brown for all of his patience and encouragement. 1. See, e.g., Barbara O’Brien, Animal Welfare Reform and the Magic Bullet: The Use and Abuse of Subtherapeutic Doses of Antibiotics in Livestock, 67 U. COLO. L. REV. 407, 422 (1996) (noting that use of antibiotics in animals “began after veterinarians experimented with administering antibiotics to sick animals to determine if the miracle drugs that save so many human lives could also help livestock”). 2. COLO. DEP’T OF AGRIC., ZOONOTIC DISEASE ADDENDUM 1 (2011), available at http://www.colorado.gov/cs/Satellite?blobcol=urldata&blobheader= application%2Fpdf&blobkey=id&blobtable=MungoBlobs&blobwhere=1251690 810562&ssbinary=true. 3. See Animal Antibiotics and Food Safety: What You Should Know, FOOD INSIGHT (July 18, 2012), http://www.foodinsight.org/Resources/ Detail.aspx?topic=Animal_Antibiotics_and_Food_Safety_What_you_Should_K now; see also Browse by Disease, CENTERS FOR DISEASE CONTROL & PREVENTION, http://www.cdc.gov/healthypets/browse_by_diseases.htm (last updated Sept. 28, 2012) (listing the diseases that are known to pass from animals to humans). 4. See, e.g., KENNETH H. MATHEWS, JR., U.S. DEP’T OF AGRIC., ANTIMICROBIAL DRUG USE AND VETERINARY COSTS IN U.S. LIVESTOCK PRODUCTION 3 (2001), available at http://www.ers.usda.gov/media/480677/ aib766_1_.pdf; Herbert S. Goldberg, Veterinary Medical and Nonmedical Uses 585 586 MINN. J. L. SCI. & TECH. [Vol. 15:1 are typically given to animals either through their feed5 or water supply.6 The use of antibiotics in farm animals occurs most often in pork and poultry.7 Because farmers have been feeding antibiotics to animals for so many years, animals are becoming resistant to the effects of these drugs.8 Farmers want to continue to profit from the effects of antibiotics and have increased the amount of antibiotics given to animals to counter the effect of resistance.9 Today, animal consumption of antibiotics accounts for almost half of total antibiotic use in the United States.10 of Antibiotics, 22 FOOD DRUG COSM. L.J. 33, 34 (1967) (listing some of the benefits of antibiotics being used in animals, which includes animal survival and growth rate); Vanessa K.S. Briceño, Note, Superbug Me: The FDA’s Role in the Fight Against Antibiotic Resistance, 9 N.Y.U. J. LEGIS. & PUB. POL’Y 521, 523 (2005) (discussing how antibiotics are used in animals to promote growth and prevent disease); Steve Mirsky, Animal Production Practices Create Antibiotic Resistance, SCI. AM. (Oct. 20, 2011), http://www.scientificamerican.com/podcast/episode.cfm?id=animal-production- practices-create-11-10-20; Is Your Meat Safe? Antibiotic Debate Overview, PBS, http://www.pbs.org/wgbh/pages/frontline/shows/meat/safe/overview.html (last visited Sept. 5, 2013); see also Goldberg, supra, at 34 (discussing how antibiotics are helpful for weak and runt animals); O’Brien, supra note 1, at 422 (discussing how antibiotics are mainly used to promote an animal’s growth rate). 5. See, e.g., Ariele Lessing, Killing Us Softly: How Sub-therapeutic Dosing of Livestock Causes Drug-Resistant Bacteria in Humans, 37 B.C. ENVTL. AFF. L. REV. 463, 470 (2010) (“[A]ntibiotics are administered preemptively to all confined animals in drug-laced feed . . . .”); O’Brien, supra note 1, at 422 (discussing how farmers feed their animals antibiotic-laced feed). 6. Robyn L. Goforth & Carol R. Goforth, Appropriate Regulation of Antibiotics in Livestock Feed, 28 B.C. ENVTL. AFF. L. REV. 39, 50 (2000). 7. Terence J. Centner, Regulating the Use of Non-Therapeutic Antibiotics in Food Animals, 21 GEO. INT’L ENVTL. L. REV. 1, 19 (2008) (“In the United States, the greatest quantities of non-therapeutic antibiotics are used for swine and poultry production.”). 8. See O’Brien, supra note 1, at 423; cf. Goforth & Goforth, supra note 6, at 51 (“[T]here is a general consensus among scientists that subtherapeutic doses of antibiotics used in animal feed favors the selection of antibiotic- resistant bacteria.”). 9. See, e.g., Goforth & Goforth, supra note 6, at 46–47; O’Brien, supra note 1, at 423 (“Over time, farmers have had to increase gradually the amounts of antibiotics fed to the animals to maintain the same rate of growth per pound of laced feed.”). 10. See Lessing, supra note 5, at 469 (estimating seventy percent of all antibiotics in the United States are used in animals); Briceño, supra note 4, at 524 (estimating that the antibiotic use in animals accounts for thirty-five to eighty-five percent of all antibiotic use); Edwin Dobb, Growing Resistance, MOTHER JONES, http://www.motherjones.com/politics/2000/11/growing- 2014] SLOWING ANTIBIOTIC RESISTANCE 587 Antibiotic resistance in humans is a major health concern.11 Antibiotic resistant bacteria can pass from animals to humans.12 As humans become resistant to antibiotics, health care for treatable diseases becomes more costly.13 Antibiotic resistance can lead to hospitalization, longer-term care, and potentially even death.14 However, the cause of antibiotic resistance in humans is difficult to determine.15 Some studies have found a causal link between antibiotic use in animals and antibiotic resistance in humans.16 However, antibiotics are given to animals in such low doses that antibiotic resistance may be the consequence of over-use of antibiotics among humans.17 While there is some evidence of a linkage between resistance (last visited Sept. 5, 2013) (estimating approximately forty percent of all antibiotics are used in animals). 11. See, e.g., Lessing, supra note 5, at 476; Briceño, supra note 4, at 521. 12. See Centner, supra note 7, at 26–27 (“Resistant bacteria in animals are passed to humans through the consumption of contaminated meat, [and] the handling of food products . . . .”); Lessing, supra note 5, at 474 (“There are three main ways in which antibiotic use—and therefore antibiotic resistance— in animals is transferred to humans: via food, via human contact with livestock, and via the environment.”); O’Brien, supra note 1, at 426 (“[C]onsumers pick . . . up [resistant strains of bacteria] by eating contaminated foods.”). 13. Centner, supra note 7, at 13; Richard S. Saver, In Tepid Defense of Population Health: Physicians and Antibiotic Resistance, 34 AM. J.L. & MED. 431, 441 (2008); Antibiotic/Antimicrobial Resistance, CENTERS FOR DISEASE CONTROL & PREVENTION, http://www.cdc.gov/drugresistance/index.html (last updated Sept. 19, 2012); see Goforth & Goforth, supra note 6, at 67. 14. See Centner, supra note 7, at 13 (discussing how antibiotic resistance has led to more human suffering and death); Saver, supra note 13, at 441 (discussing how antibiotic resistance has a mortality risk, along with longer hospital stays, more follow-up care, and a greater risk of complications); Briceño, supra note 4, at 521 (discussing how antibiotic resistance can lead to hospitalization and severe side effects). 15. See, e.g., Robert R. Nelson, Antibiotics in Animal Feeds: Short-Term Economics v. Long-Term Health, 31 S.D. L. REV. 416, 421 (1986) (discussing the difficulty in determining where someone’s antibiotic resistance came from); Goforth & Goforth, supra note 6, at 51 (questioning whether antibiotic use in farm animals has actually contributed to the growing amount of antibiotic resistant bacteria). 16. See Goforth & Goforth, supra note 6, at 48–49, 53; Briceño, supra note 4, at 525. 17. See O’Brien, supra note 1, at 424 (discussing how human overuse of antibiotics likely contributes to antibiotic resistance). 588 MINN. J. L. SCI. & TECH. [Vol. 15:1 antibiotic use in animals and antibiotic resistance in humans, no direct connection has been established.18 Three governmental agencies, the U.S. Food and Drug Administration (FDA), the Centers for Disease Control and Prevention (CDC), and the U.S. Department of Agriculture (USDA), all play a role in the regulation of antibiotics—in both animals and people.19 Each of these agencies has an interest in regulations developed to control and slow the spread of antibiotic resistance.20 These agencies have formed the National Antimicrobial Resistance Monitoring System (NARMS), to monitor the spread of antibiotic resistance among people.21 The FDA is the agency with primary rulemaking authority for regulating antibiotic use in animals.22 So far, the FDA has not banned many classes of antibiotics from animal use.23 Because the FDA has taken little action, there is limited case law governing the use of antibiotics in animals.24 The FDA has issued a guidance document discussing the recommended proper use of antibiotics in animals.25 This guidance document provides a framework to eliminate the unnecessary and inappropriate use of antibiotics in food-producing animals.26 18. See Lessing, supra note 4, at 474 (discussing how there is circumstantial evidence linking antibiotic use in animals to the increase in antibiotic resistance in people); see also Goforth & Goforth, supra note 6, at 64 (discussing how there is an “ideal situation” created by the high amount of antibiotics used in animal feed for the growth of antibiotic-resistant bacteria). 19. See Nancy E. Halpern, Antibiotics in Food Animals: The Convergence of Animal and Public Health, Science, Policy, Politics and the Law, 14 DRAKE J. AGRIC. L. 401, 423 (2009) (discussing the roles of the FDA, CDC, and USDA in the regulation of antibiotic use). 20. See id. 21. See, e.g., FDA Announces Availability of the NARMS Strategic Plan 2012–2016, FOOD & DRUG ADMIN. (May 25, 2012), http://www.fda.gov/ AnimalVeterinary/NewsEvents/CVMUpdates/ucm305710.htm. 22. See, e.g., Halpern, supra note 19, at 423; Briceño, supra note 4, at 530. 23. See Cephalosporin Order of Prohibition Questions and Answers, FDA, http://www.fda.gov/AnimalVeterinary/NewsEvents/CVMUpdates/ucm054434. htm (last updated July 22, 2013). 24. See infra Part I.A.2. 25. CTR. FOR VETERINARY MED., FDA, GUIDANCE FOR INDUSTRY #209: THE JUDICIOUS USE OF MEDICALLY IMPORTANT ANTIMICROBIAL DRUGS IN FOOD-PRODUCING ANIMALS 4 (2012) [hereinafter GUIDANCE #209], available at http://www.fda.gov/downloads/AnimalVeterinary/ GuidanceComplianceEnforcement/GuidanceforIndustry/UCM216216.pdf. 26. Id. (describing how the guidance document provides strategies promulgated by the FDA to limit the amount of use of antibiotics that are important to human health). 2014] SLOWING ANTIBIOTIC RESISTANCE 589 Conflicts could develop between the governmental agencies, since they all have an interest in how antibiotic use in animals is regulated.27 Once one main governmental authority is designated by Congress to have complete regulatory control, the question becomes: what actions should that agency take? There is pressure from some consumers to increase regulations,28 while the farming industry wants the current regulations to remain.29 This Note makes recommendations for which government agency should be in complete control over the issue of antibiotic use in animals and what action that agency should take. Part I will describe the current regulation of antibiotic use in animals. Part II will analyze which government agency is best suited to have primary rulemaking authority and weigh the options for what steps should be taken next. Finally, this Note will conclude that the FDA is the agency that should be given primary regulatory control, and it should begin banning the use of antibiotics in animals. I. BACKGROUND: ANTIBIOTICS, ANTIBIOTIC RESISTANCE, CURRENT REGULATIONS, AND REGULATORY BODIES Antibiotics are a type of drug used to treat bacterial infections.30 Antibiotics are not effective against viral infections such as influenza, most ear infections, and the common cold.31 Antibiotics operate by killing off the bacteria in the human 27. See, e.g., Centner, supra note 7, at 17 (discussing how there are problems with coordination because there are three agencies involved in the regulation of antibiotic use in animals). 28. See id. at 23 (discussing how some consumers are willing to pay a higher price for “antibiotic-free meat products”). 29. See id. at 24 (discussing how the farming industry wants to maintain its current production and management practices based on “economic, business, and social interests,” which it would not be able to do if antibiotic use in animals was banned). 30. E.g., U.S. Nat’l Library of Med. & Nat’l Insts. of Health, Antibiotics, MEDLINE PLUS, http://www.nlm.nih.gov/medlineplus/antibiotics.html (last updated Aug. 16, 2013) [hereinafter Antibiotics]; Get Smart: Know When Antibiotics Work, Fast Facts, CENTERS FOR DISEASE CONTROL & PREVENTION, http://www.cdc.gov/getsmart/antibiotic-use/fast-facts.html (last updated Jan. 21, 2011) [hereinafter Fast Facts]. 31. E.g., Mayo Clinic Staff, Antibiotics: Misuse Puts You and Others at Risk, MAYO CLINIC (Feb. 4, 2012), http://www.mayoclinic.com/health/ antibiotics/FL00075. 590 MINN. J. L. SCI. & TECH. [Vol. 15:1 body or by preventing the bacteria from multiplying.32 A problem arises when the bacteria within the body develop a mutation thereby making the antibiotic ineffective in killing off the bacteria.33 This mutation, commonly called antibiotic resistance, can develop from a variety of sources, such as overuse34 and inappropriate use.35 Inappropriate use occurs when an antibiotic is used to treat a disease that it was not intended to treat.36 One study has shown that pediatricians are more likely to prescribe an antibiotic when they perceive that the parent wants them to prescribe it, even if the antibiotic will likely be ineffective in treating the disease.37 Inappropriate use can also occur when a patient does not follow the prescribed instructions, such as not taking the antibiotic for the entire length of prescribed time.38 Overuse of antibiotics is also a leading cause of antibiotic 32. See Antibiotics, supra note 30. 33. About Antimicrobial Resistance: A Brief Overview, CENTERS FOR DISEASE CONTROL & PREVENTION, http://www.cdc.gov/drugresistance/ about.html (last updated July 2, 2012) (“[T]he infectious organisms that antibiotics are designed to kill have adapted to them, making the drugs less effective.”). 34. See Mikaela Conley, Overuse of Antibiotics May Cause Long-Term Harm, ABC NEWS (Aug. 25, 2011), http://abcnews.go.com/Health/antibiotics- bad-good-bacteria/story?id=14374547#.UKpD2YZtCSo (discussing how the overuse of antibiotics adds to the increase of human disease). 35. See Antimicrobial Resistance, WORLD HEALTH ORG. (2011), available at http://www.richmondinstitute.com/wp-content/uploads/2012/05/WHO-Fact- Sheet-on-Antimicrobial-Resistance-2011.pdf (“Inappropriate and irrational use of antimicrobial medicines provides favourable [sic] conditions for resistant microorganisms to emerge, spread and persist.”); Fast Facts, supra note 30 (“Misuse of antibiotics jeopardizes the usefulness of essential drugs.”). 36. See Antimicrobial Resistance, supra note 35 (discussing some of the underlying factors that lead to antibiotic resistance, which include “inappropriate and irrational use of medicines”). 37. Fast Facts, supra note 30 (“For pediatric care, a study showed that doctors prescribe antibiotics 62% of the time if they perceive parents expect them and 7% of the time if they feel parents do not expect them.”). 38. Mayo Clinic Staff, supra note 31 (“Not taking antibiotics exactly as prescribed also leads to problems. For example, if you take an antibiotic for only a few days—instead of the full course—the antibiotic may wipe out some, but not all, of the bacteria.”). 2014] SLOWING ANTIBIOTIC RESISTANCE 591 resistance.39 Overuse of antibiotics can occur in animals, which can lead to antibiotic resistance in humans.40 Antibiotic resistance is considered one of the world’s most concerning health issues.41 Some scientists argue that antibiotic resistance could put the world back to a pre- antibiotic time.42 Bacterial infections that are now resistant to antibiotics are more difficult to treat.43 When bacteria are resistant to the antibiotic developed to treat a condition, a second- or even third-choice drug will be used.44 These second- or third-option drugs are usually not as effective at treating the infection.45 As a result, patients can be hospitalized and have to undergo prolonged treatment.46 In some cases, antibiotic resistance can lead to patient death.47 A. CURRENT FDA REGULATIONS FOR ANTIBIOTIC USE IN ANIMALS Antibiotics used in animals are regulated when these drugs first come into the market under the rules regulating “new animal drugs.”48 Before a new animal drug can be used, a 39. See Mission Critical: Preventing Antibiotic Resistance, CENTERS FOR DISEASE CONTROL & PREVENTION, http://www.cdc.gov/features/ antibioticresistance/ (last updated Nov. 7, 2012). 40. Cf. O’Brien, supra note 1, at 424 (“Human overuse [of antibiotics] certainly contributes to this problem, but the volume of antibiotics administered to animals vastly exceeds the amount taken by humans.”). 41. E.g., Fast Facts, supra note 30 (“Antibiotic resistance has been called one of the world’s most pressing public health problems.”). 42. Cf. Antimicrobial Resistance, supra note 35 (“The achievements of modern medicine are put at risk by [antibiotic resistance].”). 43. See About Antimicrobial Resistance: A Brief Overview, supra note 33 (discussing how alternative treatments can be less effective). 44. See Antimicrobial Resistance, supra note 35 (“When infections become resistant to first-line medicines, more expensive therapies must be used.”). 45. E.g., About Antimicrobial Resistance: A Brief Overview, supra note 33 (“When the drug of choice for treating [the patient’s] infection doesn’t work, they require treatment with second- or third-choice drugs that may be less effective, more toxic, and more expensive.”). 46. See Mayo Clinic Staff, supra note 31 (noting that antibiotic resistance can lead to “more doctor visits or extended hospital stays”). 47. E.g., Antimicrobial Resistance, supra note 35 (discussing how antibiotic resistance increases the risk of death); About Antimicrobial Resistance: A Brief Overview, supra note 33 (stating that a patient “may be more likely to die as a result of the infection”). 48. 21 U.S.C. § 321(v) (2012) (“The term ‘new animal drug’ means any drug intended for use for animals other than man, including any drug intended for use in animal feed . . . .”). 592 MINN. J. L. SCI. & TECH. [Vol. 15:1 new drug application must be filed.49 The FDA is responsible for determining whether “the drug is safe and effective for its intended use and that any residue that may exist in animal- based food is safe with regard to human health.”50 Unless and until a new animal drug application is approved, the drug is deemed unsafe for use.51 In order to be approved, the drug must be shown to be safe, effective, a quality manufactured product, and must be properly labeled.52 If the drug is intended to be used in food-producing animals, the FDA may require the development of a method to measure high drug residues in the food-product consumed by humans.53 If the drug is approved, an allowable level for use in animal feed is established.54 This maximum level is intended to prevent drug residues from ending up in the edible food product.55 However, the FDA can only require a method to measure high levels of residues and a maximum level of residue if “there is a reasonable probability that a use of an animal drug . . . may present a risk to the public health . . . .”56 1. Withdrawal Procedure Once a drug is approved for animal use, it can be difficult for approval to be withdrawn.57 There is a specific procedure 49. 21 U.S.C. § 360b(a)(1) (2012). 50. Halpern, supra note 19, at 424. 51. 21 U.S.C. § 360b(a)(1) (“A new animal drug shall . . . be deemed unsafe for purposes . . . of this title . . . unless [approved] . . . .”); New Animal Drug Applications, FOOD & DRUG ADMIN., http://www.fda.gov/ AnimalVeterinary/DevelopmentApprovalProcess/NewAnimalDrugApplication s/default.htm (last updated Nov. 13, 2012) (discussing how a new animal drug may not be sold until its new animal drug application has been approved). 52. Office of New Animal Drug Evaluation, FOOD & DRUG ADMIN., http://www.fda.gov/AboutFDA/CentersOffices/OfficeofFoods/CVM/WhatWeDo/ ucm077923.htm (last updated Nov. 13, 2012) (listing and describing the four requirements a new animal drug must meet in order to be approved). 53. 21 U.S.C. § 360b(a)(4)(B)(ii). 54. Id. § 360b(a)(4)(B); Halpern, supra note 19, at 424; LaVerne C. Harold, What Level of Drugs Can Be Used in Feeds?, 16 FOOD DRUG COSM. L.J. 239, 242 (1961). 55. See, e.g., Halpern, supra note 19, at 424 (2009); LaVerne, supra note 54, at 242 (“The quantity and combination of drugs as permitted by the different paragraphs . . . of the antibiotic feed regulations must be kept at a level in a feed which will prevent drug residues in edible products.”). 56. 21 U.S.C. § 360b(a)(4)(B). 57. See Briceño, supra note 4, at 530 (“Courts have interpreted [withdrawal procedure from the FDCA] to mean that the FDA has the initial 2014] SLOWING ANTIBIOTIC RESISTANCE 593 that the FDA must follow in order to withdraw an animal drug from the market, which includes producing adequate evidence to show the potential dangers of the drug.58 Once the FDA has obtained evidence that an animal drug is unsafe, they must provide notice to the drug’s sponsor and allow the sponsor the opportunity for a hearing.59 After the hearing the animal drug may be withdrawn, but only if the FDA finds one of the statutory scenarios to be true.60 Because of the strict withdrawal procedure, the FDA has not withdrawn many antibiotics from use in animals.61 However, on July 28, 2005 the FDA withdrew its approval of Baytril® “because it was contributing to the increase of antibiotic-resistant bacterial infections in humans.”62 Baytril® was a drug that was being used in farm animals,63 and it had a similar chemical structure to a drug called Cipro.64 Cipro was used in humans to treat food-borne illnesses, including salmonella.65 The only other antibiotic to have its approval withdrawn is cephalosporin in early 2012.66 Cephalosporins are a class of antibiotics that are burden, and must show that there are ‘serious questions’ as to a drug’s safety.” (footnotes omitted)); GUIDANCE #209, supra note 25, at 18 (“Under [the withdrawal] provision, if FDA initiates a withdrawal action, it must produce evidence to show that there is a reasonable basis from which serious questions may be inferred about the ultimate safety of the drug and any substance that may be formed in or on food as a result of use of such drug under approved conditions.”). 58. Briceño, supra note 4, at 530 (discussing the FDA’s procedure for having a drug’s approval withdrawn). 59. 21 U.S.C. § 360b(e)(1). 60. See id. The statute lists possible scenarios where a new animal drug’s approval may be withdrawn. Id. This list includes: experimental data showing the drug is unsafe for the use it was approved for, new evidence not available at the time the application was submitted—examined together with the evidence available at the time of the application showing the drug is unsafe, or the application contained a false statement. Id. 61. The FDA has withdrawn approval of Baytril® and cephalosporins. Infra notes 62–68 and accompanying text. 62. Lessing, supra note 5, at 477. 63. See Briceño, supra note 4, at 524–25 (“[E]nrofloxacin . . . is the key ingredient in Baytril® and an antibiotic that combats the presence of E. coli and other bacteria found in poultry.”); Lessing, supra note 5, at 477 (discussing how Baytril® was being used in poultry). 64. Lessing, supra note 5, at 477. 65. Id. 66. See Cephalosporin Order, supra note 23.