Overdosed and Contaminated: A Critical Examination of The FDA and Drug Industry's Role in Drug Safety in the Context of the Heparin Catastrophe Caidin E. Fleming* L Introduction At some point in your life, a medical mistake will affect you. More people die from medical errors than in car accidents or from breast cancer.' In fact, just under 100,000 people die every year from medical errors.2 These numbers are the equivalent of a jumbo jet crashing every day. In light of these statistics, the question arises: how many of these errors are preventable? In November 2007, a medical error involving the drug Heparin received national attention. Twins Thomas Boone and Zoe Grace were born premature, but seemingly healthy.' Eleven * Candidate forJuris Doctorate, 2010. I would like to acknowledge the members of the Quinnipiac Health Law Journal for their editing support and insightful comments. I would also like to thank my family, in particular, Chris Berich, for his love and support throughout the writing of this Note. Finally, this Note is dedicated in loving memory to my grandmother, Roberta A. O'Dea, whose passing took place prior to the written completion of this note. May she rest in peace knowing that the Wyeth decision will enable us to continue her struggle against the drug manufacturer that harmed her in the final years of her life. IOprah: Medical Mistakes (ABC television broadcast Mar. 10, 2009) [hereinafter Oprah] (notes on file with the author); see also COMMITTEE ON QUALITY OF HEALTH CARE IN AMERICA, INSTITUTE OF MEDICINE, To ERR IS HUMAN: BUILDING A SAFER HEALTH SYSTEM 1 (Linda T. Kohn et al. eds., 2000) [hereinafter To ERR ISHUMAN] (suggesting that the number of people who die each year as a result of in hospital medical errors exceeds the number of deaths from auto accidents, breast cancer, or AIDS). 2 Oprah, supra note 1. Many studies indicate high rates of adverse events. See Troyen A. Brennan et al., Incidence of Adverse Events and Negligence in HospitalizedPatients: Results of the HarvardMedical Practice Study 1, 324 NEw ENG. J. MED. 370, 370 (1991) (showing that adverse events occurred in 3.7 percent of hospitalizations); see also To ERR IS HUMAN, supra note 1, at 29-31 (studying healthcare accidents in Utah and Colorado and finding that adverse events occurred in 2.9 percent of hospitalizations). In the Harvard study as much as 13.6 percent of events led to death while 6.6 percent of the events led to death in the Utah-Colorado study. To ERR IS HUMAN, supra note 1, at 30. With a total of 33.6 million hospital admissions in the United States in 1997, these studies suggested that between 44,000 and 98,000 people die each year as a result of inhospital medical errors. Id. at 1. 3 Should the fDA Drug and Medical Device Regulation Bar State Liability Claims?:Hearing Before the H. Comm. On Oversight and Government Reform, 110th Cong. 1 (2008) (state- QUINNIPIAC HEALTH LAW [Vol. 13:117 days after their birth, the newborns developed skin irritations, so their parents, actor Dennis Quaid and wife Kimberly, took them to the doctor.4 The doctor sent the Quaids to Cedars-Sinai Medical Center in Los Angeles, California for a more thorough examination, and there the babies were diagnosed with a staph infection. 5 Treatment required the babies to be on a constant intravenous (IV) drip of antibiotics. 6 After the first dose of antibiotics, Thomas Boone and Zoe Grace had their lVs flushed with a blood thinner, so they could begin the next dose of antibiotics.' As their parents looked on, the tiny newborns were administered a potentially lethal dose of Heparin, approximately one thousand times the recommended dosage.8 Within eight hours, they were again given the same lethal dosage of Heparin. 9 At this time, it was clear something was wrong. Quaid stated that the babies "were [ ] bleeding profusely and severely bruised from internal bleeding."1 Quaid further stated that "doctors tried to clamp shut a bleeding wound in the remnants of TBoone's umbilical cord, [and] blood spurted six feet across the room and splattered on the wall."" Hospital staff explained to the Quaids that the babies were inadvertently given a higher concentrated dosage of the medicine because of the similarity between the labels of two different concentrations of Heparin.1 2 Fortunately for the Quaid family, the overdose of Heparin did not prove fatal; today, Thomas Boone and Zoe Grace are healthy babies.' 3 Despite the heavy media coverage of the overdose incident, the Quaid family was not the first family to be harmed by the ment of Dennis Quaid and Kimberly Quaid), available at http://www.gminjurylaw.com/ Quaid-Testimony.pdf [hereinafter Statement of Dennis Quaid]. 4 Id. 5 Id. 6 Id. 7 Id. at 2. 8 Statement of Dennis Quaid, supra note 3, at 2. 9 Id. 10 Id. at 3. 11 Id. 12 Id. After interviewing doctors and nurses the Quaids found out that the labels on the bottle of 10-units of Hep-Lock and the 10,000-unit bottle of Heparin, "were deadly similar in labeling and size;" "[t]he 10,000-unit label is dark blue, and the 10unit bottle is light blue." Id. 13 See, e.g., Dennis Quaid is a CalmerDad, CELEBToTs, Jul. 27, 2009, http://www. celebtots.com/2009/07/27/dennis-quaid-is-a-calmer-dad/. 2009] OVERDOSED AND CONTAMINATED 119 similarity between the labels of the different vials of Heparin. In Indiana, six children were administered multiple adult doses of the drug; three children survived but three others did not. 4 In Texas, medical providers gave overdoses of Heparin to fourteen newborns in the last year. 5 The difficulty distinguishing between the labels for the adult and child doses of Heparin was not the only issue with the drug. About a month after the Quaid children were overdosed, on December 19, 2007, Bonnie Hubley passed away with her family and husband of forty-eight years at her side. 6 Three days earlier, the Ohio Hospital administered Heparin to Bonnie during a hemodialysis session.1 7 She suffered from a genetic disease known as polycystic kidney disease (PKD) whereby cysts grow in the kidneys; if they grow too numerous or too large in size, the kidneys become damaged." Bonnie received a kidney transplant in 1995, but in 2007, her body began to reject the kidney, and she required hemodialysis to treat her condition." While on dialysis in December of 2007, Bonnie began to experience severe diarrhea, vomiting and rapid heartbeat.2 0 During and after her last dialysis session, Bonnie experienced chest and abdomen pain, a drop in her blood pressure, and difficulty breathing. 2' Bonnie was put on a breathing tube, but her condition declined dramatically. 22 Her family was faced with the unthinkable task of following her physician's recommendation to 14 14 Preemies Given Blood Thinner Overdose: Babies At Texas Hospital Given Too Much Heparin; Mistake Probed, Children Being Monitored, CBS NEWS, Jul. 8, 2008, http://www.cbsnews.com/stories/2008/07/08/health/main4240519.shtml?source=rel ated-story [hereinafter 14 Preemies]; Steve Kroft, Dennis Quaid Recounts Twins' Drug Ordeal: Actor Tells 60 Minutes' Steve Kroft Medical Errors Kill Thousands, 60 MINUTES, Mar. 16, 2008, http://www.cbsnews.com/stories/2008/03/13/60minutes/main393641 2 page2.shtml?tag=contentMain;contentBody. 15 14 Preemies, supra note 14. 16 The Heparin Disaster: Chinese Counterfeits and American Failures. HearingBefore the Subcomm. on Oversight and Investigations of the H. Comm. on Energy and Commerce, I10th Cong. 2 (2008) (statement of Leroy Hubley), available at http://energycommerce. house.gov/images/stories/Documents/Hearings/PDF/I 10-oi-hrg.042908.LeroyHuble y-testimony.pdf [hereinafter Statement of Leroy Hubley]. 17 Id. at 1-2; See also Bill Powell, Heparin'sDeadly Side Effects, TIME, Nov. 13, 2008, http://www.time.com/time/magazine/article/0,9171,1858870-1,00.html [hereinafter Heparin'sDeadly Side Effects]. 18 Statement of Leroy Hubley, supra note 16, at 1. 19 Id. 20 Id.; see also Heparin'sDeadly Side Effects, supra note 17. 21 Statement of Leroy Hubley, supra note 16, at 1-2. 22 Id. QUINNIPIAC HEALTH LAW [Vol. 13:117 end her suffering by removing her breathing tube.2 3 Bonnie's death was only the beginning of the suffering for the Hubley family. A month later, on January 15, 2008, Bonnie's son Randy passed away after being administered Heparin.2 4 Randy also had PKD and required hemodialysis sessions. 2 1 With the help of his wife Colleen, a registered nurse, Randy was able to undergo hemodialysis sessions in the comfort of his own home; however, after a surgery, Randy needed to start 'in center dialysis' at the same facility where his mother was treated.2 6 When he arrived home from dialysis on Friday, January 11, 2008, he began experiencing symptoms such as low blood pressure and severe diarrhea, which lasted throughout the weekend.2 7 On Monday, Randy awoke during the night, grabbed his chest and ultimately collapsed. 21 Colleen administered CPR to Randy, but to no avail. 29 In her testimony before the House Subcommittee on Oversight and Investigations, Colleen stated: "As a nurse, I thought I would be there to save my husband from any [medical] errors, but I guess I was naive. I never thought that the lifesaving medication we were relying on might be contaminated."3 These Heparin-related tragedies were accompanied by some remedial efforts, and in the case of the Heparin label mix-up, a failed preventative effort by Baxter Healthcare Corporation (Baxter). In February 2007, eight months before the Quaid incident, Baxter issued a warning letter urging medical professionals to carefully read Heparin drug labels and alerting hospitals about the potential for fatal mix-ups.3 1 After a number of new23 Id. at 2. 24 The Heparin Disaster: Chinese Countefeits and American Failures. Hearing Before the Subcomm. on Oversight and Investigations of the H. Comm. on Energy and Commerce, 1I0th Cong. 2 (2008) (statement of Colleen Hubley), available at http://energycommerce. house.gov/images/stories/Documents/Hearings/PDF/1 10-oi-hrg.042908.ColleenHub ley-testimony.pdf [hereinafter Statement of Colleen Hubley]; See also Heparin's Deadly Side Effects, supra note 17. 25 Statement of Leroy Hubley, supra note 16, at 2. 26 Statement of Colleen Hubley, supra note 24 at 1-2. 27 28 29 30 31 Id. at 2. Id. Id. Id. at 3. See generally BAXTER, IMPORTANT MEDICATION SAFEY ALERT: BAXTER HEPARIN SO- DIUM INJECTION 10,000 UNITS/ML AND HEP-LOCK U/P 10 UNITS/ML (2007), http:// www.fda.gov/downloads/Safety/MedWatch/SafetyInformation/SafetyAlertsforHuman MedicalProducts/UCM154539.pdf; see also Statement of Dennis Quaid, supra note 3, at 4. 2009] OVERDOSED AND CONTAMINATED born overdoses, Baxter also redesigned the drug labels to make it easier to distinguish between adult Heparin drug vials and child Heparin drug vials by enlarging the font and changing the color of the label.3 2 However, Baxter did not recall the vials of Heparin that were still on the market or those already stocked in hospitals ready for use; if it had, Baxter could have prevented the misfortune that befell the Quaid family nine months after the corporation's initial warning.3 3 In the wake of the Hubley family tragedy, in January 2008, Baxter announced a voluntary recall of Heparin and stopped manufacturing the drug.3 4 Baxter and United States Food and Drug Administration (FDA) officials launched an investigation into the potential contamination of the drug, ultimately finding one: oversulfated chondroitin sulfate. 5 The investigation revealed that the site of contamination was the Scientific Protein Laboratories (SPL) facility in China, 36 which Baxter inspected five months prior to this discovery and found adequate. The FDA had not inspected the facility,3 8 even though FDA officials later admitted that their failure to conduct an inspection was a mistake.3 9 The investigation concluded that the contaminant was introduced during the raw material state in "a deliberate scheme to adulterate a life-saving medication."40 32 Statement of Dennis Quaid, supra note 3, at 4. 33 Id. 34 Baxter Healthcare, Heparin Sodium Injection: 2008 Heparin Information, http:// www.baxter.com/products/biopharmaceuticals/heparin_2008.html (last visited Dec. 13, 2009) [hereinafter Heparin Sodium Injection]. 35 Id.; see also The HeparinDisaster: Chinese Counterfeits and American Failures. Hearing Before the Subcomm. on Oversight and Investigationsof the H. Comm. on Energy and Commerce, 110th Cong. 2 (2008) (statement of Janet Woodcock, M.D.), available at http:// energycommerce.house.gov/images/stories/Documents/Hearings/PDF/110-oi-hrg.04 2908.Woodcock-Testimony.pdf [hereinafter Statement of Janet Woodcock]; see generally Takashi Kei Kishimoto et. al., ContaminatedHeparin Associated with Adverse Clinical Events and Activation of the Contact System, 358 NEw ENG. J. MED. 2457 (2008). 36 Families Tell U.S. Lawmakers of Heparin Deaths, REUTERS, Apr. 29, 2008, http:// www.reuters.com/article/idUSN29333077 [hereinafter Families Tell U.S. Lawmakers]. SPL has two facilities: one in Wisconsin and another in China. Heparin Sodium Injection, supra note 34. 37 Families Tell U.S. Lawmakers, supra note 36. 38 Id. 39 Gardiner Harris, Heparin Contamination May Have Been Deliberate, FD.A. Says, N.Y. TIMES, Apr. 30, 2008, available at http://www.nytimes.com/2008/04/30/health/ policy/30heparin.html?em&ex=1209700800&en=2c7flb380ee3057e&ei=5087%OA [hereinafter Harris]. 40 Heparin Sodium Injection, supra note 34. 122 QUINNIPIAC HEALTH LAW [Vol. 13:117 As a result of the Heparin catastrophe, families such as the Quaids and the Hubleys must fight for compensation from drug manufacturers so they can pick up the pieces of their lives and work to prevent such tragedies in the future. Unfortunately, many victims seeking a remedy have found it extremely difficult to do so. The FDA, with the support of drug manufacturers, contends that state common law tort claims, such as failure to warn of the risks associated with a drug, are preempted when the FDA approved the drug at issue. 4 ' Under this theory of liability, victims like the Quaids and the Hubleys are unable to sue Baxter because the FDA approved Heparin. Drug manufacturers called into court have asserted the preemption defense and the lawsuits against them have been dismissed.4 2 This note addresses two distinct issues that have arisen from the Heparin controversy: the drug labeling dilemma and the FDA's regulatory authority to oversee foreign drug manufacturers. This note first argues that the United States Supreme Court correctly decided Wyeth v. Levine by holding that drug labeling regulations promulgated by the FDA do not preempt state tort law claims because state tort law claims supplement the federal regulations and provide appropriate avenues, if not the only avenues, for injured parties to seek redress. Secondly, this note argues that the FDA is ill-equipped to enforce regulations already in place that are necessary to protect consumers. Part II of this note provides background information on the key players in the Heparin controversy: the FDA, Heparin and Baxter Healthcare Corporation. Part III addresses the drug la41 See Requirements on Content and Format of Labeling for Human Prescription Drug and Biological Products, 71 Fed. Reg. 3922, 3934 Uan. 24, 2006) (to be codified at 21 C.F.R_ pts. 201, 314, 601) [hereinafter Physician's Labeling Rule] (noting the Department ofJustice "ha[d] filed a number of amicus briefs" on the FDA's behalf). These briefs suggested that FDA approval of labeling preempts conflicting or contrary state law. Id. 42 See Statement of Dennis Quaid, supra note 3, at 6 (stating that Baxter moved to dismiss the Quaid's lawsuit on the basis of preemption); see also Morris v. Wyeth, Inc., 582 F. Supp. 2d 861 (W.D. Ky. 2008) (holding that drug consumer's state law claim against drug manufacturer was preempted); see also Demahy v. Wyeth, Inc., 586 F. Supp. 2d 642 (E.D. La. 2008) (drug manufacturer moved to dismiss consumer's state failure to warn claim, asserting preemption as a defense); see also Knipe v. SmithKline Beecham, 583 F. Supp. 2d 553 (E.D. Pa. 2008) (drug manufacturer asserted preemption defense after survivors of patient brought state failure to warn claim); Colacicco v. Apotex, Inc., 521 F.3d 253 (3d Cir. 2008) (affirming dismissal of the consumers' state failure to warn claims on the basis of preemption). 2009] OVERDOSED AND CONTAMINATED beling conundrum, in particular, the FDA's oversight of drug labeling, the doctrine of federal preemption, the United States Supreme Court's decision in Wyeth v. Levine and the post-Wyeth federal drug labeling regime. Part III also provides general recommendations for interested parties as to how to prevent future medical errors involving inadequate drug labeling. Part IV examines the FDA's regulatory power abroad, and provides an analysis of the FDA's ability to address foreign drug manufacturing issues in the context of the Heparin contamination. Part IV also provides general recommendations to prevent similar drug manufacturing errors and to improve post market drug safety. II. Background A. The Food, Drug and Cosmetic Act and the Food and Drug Administration i. Establishing the FDA Congress enacted the Federal Food, Drug, and Cosmetic Act (FDCA)4" in 1938 "for the purposes of safeguarding the public health, [and] preventing deceit upon the purchasing public."4 4 The FDCA delegated authority to the FDA to regulate the safety of food, drugs and cosmetics.4" The FDA is one of the oldest consumer regulatory agencies in the government. It is organized as part of the United States Department of Health and Human Services and consists of nine centers or offices.46 It is a scientific, regulatory and public health agency that oversees many things, including most food products (excluding meat and poultry), human and animal drugs, biological products, medical devices; radiation-emitting consumer products, cosmetics, and animal feed.4 7 The FDA also "monitors the manufacture, import, transport, storage, and sale of about" one trillion dollars of products; the annual cost to tax43 Federal Food, Drug and Cosmetics Act of 1938, 52 Stat. 1040, 1052 (1938) (codified as amended by 21 U.S.C. §§ 301-392 (2009)) [hereinafter FDCA of 1938]. 44 H.R. REP. No. 75-2139, at 3 (1938). 45 21 U.S.C. § 393 (2008). 46 U.S. Food and Drug Admin., Centers & Offices, http://www.fda.gov/AboutFDA/ CentersOffices/default.htm (last visited Nov. 15, 2008). 47 Id.; see also John P. Swan, Ph.D., U.S. Food and Drug Admin., FDA's Origin, http://www.fda.gov/AboutFDA/WhatWeDo/History/Origin/ucm124403.htm (last visited Nov. 27, 2009) [hereinafter FDA's Origin]. 124 QUINNIPIAC HEALTH LAW [Vol. 13:117 payers is approximately three dollars per person.4 8 The FDCA imposed new regulations on cosmetics and medical devices, and "it required that drugs be labeled with adequate directions for safe use."4 9 A fundamental provision of the FDCA prohibits misbranding or adulteration of drugs, and the introduction, delivery for introduction, sale or receipt of any drug into interstate commerce that is adulterated or misbranded.5 ° The Act requires drug manufacturers to submit to federal safety review before marketing new drugs. 5' The pre-market approval process is rigorous; "[a] manufacturer must submit what is typically a multivolume application. '5 2 For example, a drug manufacturer is required to file a new drug application prior to the drug's approval, which includes "as a part of the application. . . full reports of investigations which have been made to show whether or not such drug is safe for use and whether such drug is effective in use. '53 The Secretary can deny the application on a finding that "the investigations... do not include adequate tests by all methods reasonably applicable to show whether or not such drug is safe for use under the conditions prescribed, recommended, or suggested in the proposed labeling thereof.... FDA scientists evaluate applications for, among other things, new drugs, biologics and complex medical devices.55 Within the FDA, the Center for Drug Evaluation and Research (CDER) evaluates drugs before they can be marketed, verifying that the drugs have effective labeled instructions and provide benefits that outweigh risks.5 6 When Heparin was approved in 1939, the FDCA prohibited selling a new drug, unless an application was filed and put into 48 Id. 49 U.S. Food and Drug Admin., FDA History - Part II:The 1938 Food, Drug, and Cosmetic Act, http://www.fda.gov/AboutFDA/WhatWeDo/History/Origin/ucm54826. htm (last visited Nov. 27. 2009) [hereinafter FDA History - Part 1I]. 50 21 U.S.C. §§ 331(a)-(c) (2008). 51 FDA History - Part II, supra note 49; see also 21 U.S.C. § 355 (b) (2009). 52 Riegel v. Medtronic, Inc,, 128 S. Ct. 999, 1004 (2008). 53 21 U.S.C. § 355(b) (2009). 54 21 U.S.C. § 355(d). 55 FDA's Origin, supra note 47. 56 U.S. Food and Drug Admin., CDER"The Consumer Watchdog for Safe and Effective Drugs, http://www.fda.gov/Drugs/ResourcesForYou/Consumers/ucml43462.htm (last visited Dec. 13, 2009). OVERDOSED AND CONTAMINATED 2009] effect. 7 Applicants had to submit reports of many things, including investigations and other materials "to show whether or not such drug [was] safe for use, '"" and they had to provide "specimens of the labeling proposed to be used for such drug."5 9 If the FDA failed to act, the application became effective sixty days after filing.6" The FDCA provided for judicial review of "an order of the Secretary refusing to permit the [drug] application to become effective or suspending the effectiveness of the application" under section 505, but it did not permit judicial review of an effective drug application. 6 ' In fact, "Congress has never authorized judicial review of FDA approval of a new-drug application."6 2 ii. The Ever Expanding and ContractingPower of the FDA Over time, Congress has both contracted and expanded the FDA's power through the passage of various amendments to the FDCA. For example, when Congress passed the Drug Amendments of 1962, it expanded FDA power by requiring that "new drugs meet an additional test of 'effectiveness' in addition to the existing test of 'safety,"'63 and by requiring the FDA to approve new drug applications, doing away with the previous procedure whereby a new drug could become affective if the FDA failed to act for 60 days.6 4 However, Congress limited FDA power by including a savings clause in the 1962 Amendments that stated, "Nothing in the amendments made by this Act to the [FDCA] shall be construed as invalidating any provision of State law which would be valid in the absence of such amendments unless there is a direct and positive conflict between such amendments 57 FDCA of 1938, supra note 43, § 355(a). Section 505(a) of the FDCA, provides that "[n]o person shall introduce or deliver for introduction into interstate commerce any new drug, unless an approval of an application filed [with the Food and Drug Administration] . . . is effective with respect to such drug." Id. § 355(a). 58 Id. § 355 (b) (1) (A). 59 Id. §§ 355(b)(1)(F), (d)(6). 60 Id. § 355(c). 61 Id. § 355(h). 62 Brief for Appellee-Respondent at 5, Wyeth v. Levine, 944 A.2d 179 (Vt. Nov. 3, 2008), available at http://www.abanet.org/publiced/preview/briefs/pdfs/07-08/061249-Respondent.pdf [hereinafter Brief for Appellee]. 63 Id. at 5-6; See alsoDrug Amendments of 1962, Pub. L. No. 87-781, §102(a) (2), 76 Stat. 780 (1962) [hereinafter Drug Amendments of 1962]. 64 See Brief for Appellee, supra note 62, at 5-6; see also Drug Amendments of 1962, supra note 63, §§ 102(d), 104. 126 QUINNIPIAC HEALTH LAW [Vol. 13:117 and such provision of State law."6 5 Generally, the FDA's power is limited in the drug labeling industry. Once a drug is approved, the FDA lacks the authority to compel manufacturers to make labeling changes.6 6 Under the FDCA, drug manufacturers are encouraged to update their drug labels,6 7 and under the 'changes being effected' (CBE) regulation, 68 drug manufacturers can make changes to a label, without prior FDA approval, "[t]o add or strengthen a contraindication, warning, precaution, or adverse reaction,"69 or " [t] o add or strengthen an instruction about dosage and administration that is intended to increase the safe use of the drug product. ' 7° Such changes to a drug's label can be implemented immediately upon the FDA's mere receipt of the supplemental application 7 ' rather than after a thirty-day waiting period. 72 The FDA has required manufacturers to revise drug labeling "to include a warning as soon as there is reasonable evidence of an association of a serious hazard with a drug; a causal relationship need not have been proved. ' 7' The CBE regulation is in keeping with a "central premise of federal drug regulation" that drug manufacturers traditionally bear ultimate responsibility for the content of drug labels." In a significant addition to FDA authority, former President George W. Bush signed the Food and Drug Administration 65 Brief for Appellee, supra note 62, at 6; see also Drug Amendments of 1962, supra note 63, § 202. 66 Brief for Appellee supra note 62, at 8 (citing FDA's DrugApproval Process: Up to the Challenge?: HearingBefore the Subcomm. On Health Education, Labor and Pensions, 109th Cong. 5 (2005) (testimony of Sandra Kweder, M.D., Deputy Dir., Off. of New Drugs, U.S. Food and Drug Admin.), available at http://help.senate.gov/Hearings/2005_ 03_01/kweder.pdf ("FDA may ask the manufacturer to revise the labeling to add information on adverse reactions not previously listed.") 67 See Brief for Appellee, supra note 62, at 7; see also Werner v. Upjohn, Co., Inc., 628 F.2d 848, 860 (4th Cir. 1980) ("FDA's regulations and policies encourage early unilateral action by the drug companies to improve their warnings"). 68 See Brief for Appellee, supra note 62, at 7; see also Wyeth v. Levine, 129 S. Ct. 1187, 1196 (2009). Congress, in 2007, for the first time granted the FDA authority to require certain post-market drug labeling changes. Wyeth, 129 S. Ct. at 1196. Generally, a drug manufacturer may only make changes to a drug's label after FDA approval, but there is a regulation that permits them to do so before it. Id. 69 21 C.F.R. § 314.70(c)(6)(iii)(A) (2009). See also Wyeth, 129 S. Ct. at 1196. 70 21 C.F.R. § 314.70(c)(6)(iii) (C) (2009). See also Wyeth, 129 S. Ct. at 1196. 71 21 C.F.R. § 314.70(c) (6) (2009). 72 21 C.F.R. § 314.70(c) (4) (2009); see also 21 C.F.R. § 314.70(c) (6) (2009). 73 21 C.F.R. § 201.80(e) (2009). 74 Wyeth, 129 S. Ct. at 1197-98. OVERDOSED AND CONTAMINATED 2009] 127 Amendments Act of 2007 (FDAAA) into law on September 27, 2007. 7 ' The Act provides the FDA with authority and resources to oversee pre-market and post-market drug safety. 76 Notably, the Act provides the FDA with new, albeit limited, authority to require certain drug safety labeling changes. However, the FDA must first attempt to negotiate with the drug manufacturer before it can order changes to be made to a drug label. 77 The Act also includes a provision that allows the FDA to collect fees from drug companies to help fund the review of new drugs. 78 The Act further allows for shorter review times of new drug applications while maintaining the quality of the reviews. 7' Finally, the Act provides the FDA with some authority to require drug manufacturers to participate in post-market drug safety studies.8 " iii. GlobalizationAct of 2009 Another law that would expand FDA authority is the proposed Globalization Act of 2009.1 The Globalization Act out75 U.S. Food and Drug Admin., Food and Drug Administration Amendments Act (1DAAA) of 2007, http://www.fda.gov/Regulatorylnformation/Legislation/FederalFoo dDrugandCosmeticActFDCAct/SignificantAmendmentstotheFDCAct/FoodandDrugAd ministrationAmendmentsActof2007/default.htm (last visited Nov. 10, 2009). 76 U.S. Food and Drug Admin., FDAAA Implementation: Highlights One Year after Enactment, http://www.fda.gov/Regulatorylnformation/Legislation/FederalFoodDrugan dCosmeicActFDCAct/SignificantAmendmentstotheFDCAct/FoodandDrugAdministra tionAmendmentsActof2007/ucm083161.htm (last visited Dec. 13, 2009). 77 U.S. Food and Drug Admin. Amendments Act of 2007, Pub. L. No. 110-85, 121 Stat. 823, 841 (2007) (requiring the Secretary to "hold discussions"); See also INST. OF MED. COMM. ON ASSESSMENT OF U.S. DRUG SAFETY Sys., BD. ON Pop. HEALTH & PUB. HEALTH PRAc., THE FUTURE OF DRUG SAFETY: PROMOTING AND PROTECTING THE HEALTH OF THE PUBLIC 157 (Alina Baciu et al. eds., 2007) [hereinafter FUTURE OF DRUG SAFETY] ("Currently, most actions involve softer remedies negotiated with a drug sponsor; FDA cannot unilaterally compel label changes, addition of boxed warnings, or fulfillment of postmarketing study commitments. Nor can it unilaterally restrict marketing, change the content of a package insert (including Medication Guides), or change the content of other documents intended for the public."). 78 U.S. Food and Drug Admin., Renewed Legislation Improves Safety of FDA-Regulated Products, http://www.fda.gov/ForConsumers/ConsumerUpdates/ucm61229.htm (last visited Nov. 10, 2009). 79 Id. 80 FDA's Role in Identifying and Communicating Drug Safety Issues: HearingBefore the H. Comm. On Veteran's Affairs, 110th Cong. (statement of Paul Seligman, M.D., M.P.H., Assoc. Dir. of Safety Policy and Commc'n, CDER, FDA), available at http://veterans. house.gov/hearings/Testimony.aspx?TID=45155&Newsid=270&Name=%2OPaul%20% 20Seligman,%20M.D.,%20M.P.H [hereinafter Statement of Paul Seligman]. 81 See generally Discussion Draft of the 'Food and Drug Administration Globalization Act' Legislation: Drug Safety: Hearing Before the Subcomm. On Health of the H. Comm. On Energy and Commerce, 110th Cong. (2008), available at http://www.govtrack.us/congress/bill text.xpd?bill=H 111-759 [hereinafter Globalization Act]. See infta Part IV. QUINNIPIAC HEALTH LAW [Vol. 13:117 lines proposed amendments to the FDCA, such as authorization for the imposition of a registration fee on drug manufacturers who are already required to register each year with the FDA. 2 The Act proposes to utilize the collected registration fees for the purpose of funding increased inspections of drug manufacturing facilities.8 3 The Globalization Act will also require all drug manufacturing facilities to be inspected before a drug manufactured in the facility is introduced into interstate commerce.8 4 The Act authorizes a civil penalty of up to $100,000 for each violation of 85 the Act. If it passes, the Globalization Act is likely to increase FDA initiatives overseas. Currently, the Office of International Programs coordinates the FDA's international activities." The FDA is responsible for monitoring products within its jurisdiction that are imported to the United States. 8 7 To facilitate the process, the FDA requires foreign drug manufacturers to register with the FDA and provide the name and address of its United States agent.8 8 However, the FDA lacks the resources to inspect imports arriving from over one hundred and fifty countries.8 9 To compensate for this lack, the FDA, among other things, imposes high public health standards that imports must meet,9" and inspects hundreds of foreign facilities each year.9 1 In conjunction 82 Id. § 736C(a). 83 Id. 84 Id. § 202(a) (2) (A). 85 Id. § 211(a) (2). 86 U.S. Food and Drug Admin., Office of International Programs, http://www. fda.gov/AboutFDA/CentersOffices/OC/OfficeoflnternationalPrograms/ucm 119564. htm (last visited Nov. 10, 2009). 87 Drug Safety: Preliminary Findings Suggest Weakness in FDA's Programfor Inspecting ForeignDrug Manufacturers: HearingBefore the Subcomm. On Oversight and Investigations of H. Comm. On Energy and Commerce, 109th Cong. 4 (2007) (testimony of Marci Crosse, Dir., Health Care, U.S. Gov't Accountability Off.), available at http://www.gao.gov/ new.items/d08224t.pdf [hereinafter Statement of Marcia Crosse 1] ("FDA is responsible for overseeing the safety and effectiveness of human drugs that are marketed in the United States, whether they are manufactured in foreign or domestic establishments."). 88 21 C.F.R. § 207.40(c); see also 21 U.S.C. § 360(h) (i) (2009). 89 Kristen E. Schleiter, Court Support for FDA Regulation of Drug Importation, 11(7) Am. Med. Assoc. J. Ethics 521, 523 (2009) ("The United States imports products from more than 150 countries, with India and China accounting for more than half of these imports."). 90 Id. at 522 ("The FDA inspects foreign or domestic manufacturing facilities to ensure they meet the same manufacturing standards for quality, purity, potency, safety, and efficacy required of domestic establishments."). 91 Discussion Draft of the Tood and Drug Administration Globalization Act' Legislation: DrugSafety: HearingBefore the Subcomm. On Health of the H. Comm. On Energy and Commerce, OVERDOSED AND CONTAMINATED 2009] with its foreign inspections, the FDA educates regulatory counterparts in other countries on United States public health standards, and on how to comply with the FDA's Good Manufacturing Practices.9 2 The FDA has also been an advocate for raising international health safety standards and for harmonizing the standards amongst different countries.9 3 Thus, by providing for increased resources for inspection of drug manufacturing facilities that import products to the United States, the Globalization Act would assist the FDA with its current initiatives and in its role of protecting the public health. iv. Changes in the FDA's Landscape In the last twenty years, political pressure, consumer activism, and industry involvement have incited rapid changes in the nature of the FDA's work.9 4 For example, "patient advocacy groups ... played a role in the agency's development of accelerated techniques for drug approval." 5 Also, a law was passed which requires the "industry to reimburse the FDA for review of drugs and biologics to speed up the agency's evaluations. '"" Despite these changes, the overall expansion of the agency's regulatory authority has left the agency strained and unable to adequately fulfill its stated purpose. These strains have manifested into infrequent drug label updates and inadequate (or sometimes, non-existent) drug manufacturing facility inspections. As a result, the FDA has left the public exposed to new dangers. However, patients injured by dangerous drugs have successfully brought state law failure-towarn claims against drug manufacturers. 7 Aware of those state 110th Cong. (2008) (statement of Andrew C. von Eschenbach, M.D., Comm'r of Food and Drugs, U.S. Dep't of Health and Hum. Res.), available at http://www.fda.gov/ NewsEvents/Testimony/ucm109676.htm [hereinafter Statement of Andrew von Eschenbach]. 92 U.S. Food and Drug Admin., Overview: Office of InternationalPrograms, http:// www.fda.gov/AboutFDA/CentersOffices/OC/OfficeoflnternationalPrograms/ucm 116 397.htm [hereinafter Overview: Office of InternationalPrograms]. " Id. 94 U.S. Food and Drug Admin., FDA History - Part V Trends in the Last QuarterCentury, http://www.fda.gov/AboutFDA/WhatWeDo/History/Origin/ucm125632.htm (last visited Dec. 13, 2009). 95 Id. 96 Id 97 See, e.g., Levine v. Wyeth, 183 Vt. 76 (2006); Demahy v. Wyeth, Inc., 586 F. Supp. 2d 642 (E.D. La. 2008); Brochu v. Ortho Pharm. Corp., 642 F.2d 652 (lst Cir. 1981). QUINNIPIAC HEALTH LAW [Vol. 13:117 law remedies, Congress has not included an express preemption provision for prescription drugs in various amendments to the FDCA despite having done so for medical devices.9" The FDCA, as originally drafted, "included a federal private right of action for injured consumers."9 However, witnesses testified that the provision was unnecessary because state law remedies adequately protected consumers injured by dangerous drugs; thus, the provision was omitted from the Act.'0 0 Until recently, the FDA viewed such state law claims as complementing federal regulation. 101 B. Heparin Heparin, an anti-coagulant or blood thinner that helps prevent the formation of blood clots in the veins, arteries, lungs or heart,' 0 2 was discovered in 1916 and was approved by the FDA in 1939.03 The drug is used to prevent blood clotting during open-heart surgery, during dialysis 0 4 and in patients who are confined to bed.' 5 Heparin is also often considered the drug of choice for anti-coagulation in pregnancy.' 016 It is available by prescription only.'0 7 Heparin is usually made from pig intestine enzymes, 10 8 and consists of a long series of complex sugar molecules.' 0 9 There are generally two types of Heparin: unfractionated Heparin and low molecular weight Heparin." ° Unfractionated Heparin is composed of many different sizes of sugar compounds.1 1 ' The 98 Wyeth, 129 S. Ct. at 1200. 99 Brief for Appellee supra note 62, at 4. 100 Id. 101 Id. at 1. 102 Heparin Injection, DRUG DIGEST, May 1, 2009, http://www.drugdigest.org/wps/ portal/ddigest (search for "heparin injection") [hereinafter Heparin Injection]. 103 INDIANA MEDICAID THERAPEUTICS COMMIrrEE, THERAPEUTICS CLASS REVIEW 1 (2008), http://www.indianapbm.com/Doc%2021/Hematologic%20Agents /Heparin%20and%2ORelatedES%2003-08.pdf [hereinafter HEPARIN THERAPEUTICS]. SUMMARY 104 Id. 105 HeparinInjection, supra note 102. 106 HEPARIN THERAPEUTICS, supra note 103. HeparinInjection, supra note 102. 108 Scientists Unravel Heparin Death Mystery, SCIENCE DAILY, Apr. 24, 2008, http:// www.sciencedaily.com/releases/2008/04/080423171529.htm. 109 Id.; see also What is Heparin?, http://www.anticoagulation-advisor.com/ckshop. php?category=7 (last visited Oct. 18, 2008) [hereinafter What is Heparinf]. 110 What is Heparin?, supra note 109. 111 Id. See also David N. Leff, Heparins Oddest Ball Molecular Sequence Yields to MIT 107 OVERDOSED AND CONTAMINATED 2009] dosage for this type of Heparin depends on results from a blood clotting test, so frequent blood clotting tests are necessary to administer the drug appropriately.' 2 In contrast, low molecular weight Heparin contains only one small size sugar compound and the dosage depends on the patient's weight."' Both types of Heparin are usually administered intravenously through an IV bag, or subcutaneously, under the skin like an insulin shot." 4 The drug takes effect very quickly in patients; for example, "peak plasma levels of heparin are achieved 2 to 4 hours following subcutaneous administration.""' 5 Heparin can lead to excessive bleeding, especially in patients who have recently undergone surgery. 1 6 Heparin may also cause back pain, burning or itching of the feet, allergic reactions such as hives and swelling of the face, feeling faint, coughing up blood, breathing problems, stomach pain, nausea, vomiting and unusually low blood pressure.' 17 C. Baxter Healthcare Corporation Baxter Healthcare Corporation has a longstanding history of service to the healthcare industry; it was founded in the 1930s "as the first manufacturer of commercially prepared intravenous  solutions.""' 8 Currently, "Baxter manufactures products in 26 countries and sells them in more than 100 countries."119 Sixty percent of Baxter's sales come from outside the United States and, in 2008, its worldwide sales totaled $12.3 billion. 2 0 To facilitate this magnitude of sales, Baxter has facilities located all over Biotech Analytical Tool Formula, 11 BIOWORLD TODAY 1, 5 (2000), available at http:// web.mit.edu/tox/sasisekharan/downloads/bioworld.pdf (stating that if you imagine putting heparin into a food blender, you would get sugar molecules) [hereinafter BioWORLD]. 112 What isHeparin, supra note 109. 113 Id.; See also BioWORLD, supra note 111, at 5. 114 Id. 1 (2008), http://www.baxter.com/products/biopharmaceuticals/downloads/Heparinlmp_Safe tyInformationHealthCareProf.pdf. 116 See BIOWORLD, supra note 111, at 5 (stating that bleeding is a risk associated with Heparin). 117 Heparin Injection, supra note 102. 118 Baxter Healthcare Corp., History, http://www.baxter.com/about-baxter/com pany-profile/sub/history.html (last visited Nov. 20, 2009). 119 Baxter Healthcare Corp., Company Profile, http://sustainability.baxter.com/ company-profile/index.html#worldwide (last visited Nov. 20, 2009). 1 15 BAXTER HEALTHCARE CORP., IMPORTANT HEPARIN SAFETY INFORMATION 120 Id. 132 QUINNIPIAC HEALTH LAW [Vol. 13:117 the world and in the United States, including Arkansas, California, Florida, Illinois, Indiana, Maryland, Mississippi, New Jersey, and North Carolina. 12 1 Baxter's headquarters is located about 22 twenty miles north of Chicago, Illinois.' For over thirty years, "Baxter, and its predecessor company ESI Lederle (Wyeth), has been manufacturing heparin in a vial form. 1 23 Together they supply fifty percent of the United States market for Heparin.1 24 A factory owned by SPL in Chagzhou, China produces the active ingredient for the drug, which is derived from a pig intestine enzyme.' 2 5 Baxter then "processes, sterilizes and packages the finished product for distribution" in the United States.1 2 6 Since Heparin was approved, Baxter is responsible for investigating and reporting to the FDA any adverse drug event information associated with the drug that it receives and periodically submitting any new or follow-up information to the FDA that may call into question the FDA's previous conclu127 sions about the safety, effectiveness, or labeling of the drug. The Drug Labeling Dilemma Drug labeling is "[t] he centerpiece of risk management."128 The contents of drug labels have increased over the years, and now include the container label, package insert, consumer medication information, a medication guide, a Highlights section and patient counseling information.1 29 In 2006, the FDA promulgated the Physician's Labeling Rule, which was aimed at simplifying prescription drug labeling for medical practitioners." 0 The III. 121 Baxter Healthcare Corp., Global Presence, http://www.baxter.com/about-bax ter/company-profile/sub/globalpresence.html (last visited Nov. 15, 2008). 122 Id. 123 Testimony Of Baxter Int. CEO Before Subcommittee On Oversight And Investigations Committee On Energy And Commerce U.S. House Of Representatives, MEDICAL NEws TODAY, Apr. 29, 2008, http://www.medicalnewstoday.com/articles/ 105761.php [hereinafter Testimony of Baxter CEO]. 124 Heparin Sodium Injection, supra note 34. 125 Heparin Chinese Supplier Was Never Checked by Chinese Drug Regulators, MEDICAL NEWS TODAY, Feb. 16, 2008, http://www.medicalnewstoday.com/articles/97598.php [hereinafter Chinese SupplierNever Checked]. 126 Id. 127 See 21 C.F.R. § 314.80(b) (2009). 128 Physician's Labeling Rule, supra note 41, at 3934. 129 IMPROVING PRESCRIPTION DRUG CONTAINER LABELING IN THE UNITED STATES: A HEALTH LITERACY AND MEDICATION SAFETY INITIATIVE 24-25 (2007), http://foundation. acponline.org/files/medlabel/acpfwhitepaper.pdf [hereinafter INIPROVING LABELING]. 13O See Physician's Labeling Rule, supra note 41, at 3923. OVERDOSED AND CONTAMINATED 2009] 133 FDA set specific requirements for what information must appear on a prescription drug container label: the drug name, pharmacy name and address, serial number of the prescription, prescribing physician's name, patient name, and instructions for use. 1 3 ' Oversight of drug labeling has always been a focus of the FDA, and in 2006, the FDA attempted to adopt a policy of exclusive oversight of drug labeling through the doctrine of federal 32 preemption. A. Federal Law Preemption i. Generally The United States Constitution establishes the three branches of the government and lists their respective duties and powers. The power of the Federal government consists of only those powers enumerated in the text of the Constitution. The Tenth Amendment to the Constitution reserves to the States the powers not expressly granted to the federal government. 133 As a result, '[t]he powers delegated . . . to the federal government, are few and defined' and '[t]hose which are to remain in the state governments, are numerous and indefinite. ' 1 34 The Supreme Court ruled The Framers adopted this "'constitutionally mandated balance of power,"' to "reduce the risk of tyranny and abuse from either front," because a "federalist structure ofjoint sovereigns preserves to the people numerous advantages," such as "a decentralized government that will be more sensitive to the diverse needs of a heterogeneous society". [and] provide[ ] "a double security to the rights of the people". 135 However, when Congress chooses to exercise its power and create a federal law, the federal law may supersede a contrary state law by operation of the supremacy clause. The supremacy clause of the Constitution provides that federal law is "the supreme Law 131 IMPROVING LABELING, supra note 129, at 25. 132 See Physician's Labeling Rule, supra note 41, at 3934. 133 U.S. CONST. amend. X. 134 Wyeth, 129 S. Ct. at 1206 (Thomas, J., concurring) (citations omitted). 135 Id. at 1205 (citations omitted). 134 QUINNIPIAC HEALTH LAW [Vol. 13:117 of the Land."' 3 6 Thus, when a federal law and a state law conflict, federal law will preempt the state law. A federal law can preempt a state law in three ways: by express statement (express preemption), by implied occupation of the regulatory field (field preemption), or by implied preclusion of conflicting state regulations (conflict preemption). 3 7 In the case of express preemption, the only issue to consider "is 13 whether the state statute falls within the area preempted."" More complex issues arise when the federal statute is unclear about its intended impact on state laws. When the law is ambiguous, it is often necessary to examine Congressional intent and the legislative history of the federal law in order to determine if Congress intended the law to have preemptive effect. Ordinary principles of field preemption establish that a federal law will preempt state law if the "scheme of federal regulation is 'so pervasive as to make reasonable the inference that Congress left no room for the States to supplement it.I" 39 Ordinary principles of conflict preemption establish that a federal law preempts a state law if "the state requirement actually conflicts with the federal requirement - either because compliance with both laws is impossible ...or because the state law 'stands as an obstacle to the accomplishment and execution of the full purposes and objectives of Congress."" 4 Furthermore, "a federal agency acting within the scope of its congressionally delegated authority" may pass regulations that preempt state regulations.14 ' ii. Reading Preemptive Intent into the Preamble As one reporter succinctly stated, "The issue is increasingly whether [agencies, and consequently, drug manufacturers] can use broad preemption language in regulatory preambles to get" lawsuits dismissed. 142 Arguably, one can view the preamble as 136 U.S. CONST. art. VI, cl. 2. 137 GERALD GUNTHER & KATHLEEN M. SULLIVAN, CONSTITUTIONAL LAW 234-35 (16th ed. 2007). 138 Id. at 234. 139 Medtronic, Inc. v. Lohr, 116 S. Ct. 2240, 2261 (1996) (Breyer, J., concurring) (citation omitted). 140 Id. at 2261 (citations omitted). 141 City of New York v. F.C.C., 108 S. Ct. 1637, 1642 (1988). 142 Pete Yost, Bush Administration Rules Limit Lawsuits, USA TODAY, May 13, 2008, http://www.usatoday.com/money/economy/2008-05-13-536172364_x.htm. 20091 OVERDOSED AND CONTAMINATED "the agencies' interpretation of whether the federal regulatory law permits preemption of lawsuits."143 The FDA's Physician's Labeling Rule was accompanied by a preamble containing broad preemptive language, suggesting that if the FDA approved a prescription drug, then state tort law claims are preempted. 144 The "FDA believes that under existing preemption principles, FDA approval of labeling under the act, whether it be in the old or new format, preempts conflicting or contrary State law."14' 5 In particular, the FDA contemplated that at least the following claims would be preempted: (1) (2) claims that a drug manufacturer breached an obligation to warn by failing to include a statement in labeling or advertising the substance of which the FDA has prohibited in labeling or advertising; claims that a drug manufacturer breached an obligation to warn by failing to include a statement in labeling or advertising the substance of which has been proposed by the FDA for inclusion in the labeling or advertising, if such statement was not required by the FDA at the time the plaintiff claims the sponsor had an obligation to warn; (3) (4) claims that a drug manufacturer breached an obligation to warn by failing to include in the "Highlights" section of the drug label, or otherwise emphasize, any information the substance of which is included in the label; and claims that a drug manufacturer breached an obligation to warn by failing to include contraindications or warnings that are not supported by evidence satisfying FDA standards. 146 In an attempt to justify its position on preemption, the FDA asserted in the preamble that it "is the expert federal public health agency charged by Congress with ensuring that drugs are safe and effective, and that their labeling adequately informs users of the risks and benefits" associated with the product.14 7 A recent 2008 regulation reaffirmed the FDA's position on 143 Id. 144 Physician's Labeling Rule, supra note 41, at 3933-34. 145 146 147 Id. at 3934. Id. at 3934-35. Id. at 3934. 136 QUINNIPIAC HEALTH LAW [Vol. 13:117 preemption that it asserted in the Physician's Labeling Rule.' 4 ' Specifically, the FDA stated in the regulatory preamble that it "does not believe that the absence of an express preemption provision with respect to drugs affects the application of the doctrine of implied preemption."' 4 9 On May 14, 2008, Randall W. Lutter, Deputy Commissioner for Policy of the FDA testified before the House Committee on Oversight and Government Reform about challenges to FDA determinations. Lutter stated that in order to "protect the public health... state law claims are preempted if they challenge a design or labeling that FDA approved.' 150 Lutter generally believed that state courts should not second guess the FDA's decisions "about the safety, efficacy, and labeling of medical products." 15 1 Lutter further testified, [The] FDA is concerned that state product liability lawsuits that challenge [the] FDA's careful determination of safety, efficacy and appropriate labeling can have detrimental effects to public health in a number of ways, including limiting patient and doctor choices and decreased patient access to beneficial products, and increased confusion over warnings or statements that can deter the use of [the most] beneficial 152 medical products. Thus, through Lutter's testimony, the FDA clearly delineated its attitudes about preemption. B. Preemption and State Tort Claims The United States Supreme Court articulated a two-part standard in Chevron, U.S.A., Inc. v. NR.D.C.1 53 - known as the "Chevron deference" standard - in order to determine the level 148 See generally Supplemental Applications Proposing Labeling Changes for Approved Drugs, Biologics, and Medical Devices, 73 Fed. Reg. 49603-01 (Aug. 22, 2008) (to be codified at C.F.R. pts. 314, 601, and 814). 149 Id. at 49605. 150 Should FDA Drug and Medical Device Regulation BarState Liability Claims?: Before the H. Comm. on Oversight and Govt. Reform, 110th Cong. (2008) (statement of Randall W. Lutter, Deputy Comm'r for Policy, Assoc. Comm'r for Policy and Planning for the U.S. Food and Drug Admin.), available at http://www.hhs.gov/asl/testify/2008/05/t20 080514b.html. 151 152 Id. Id. 153 See generally Chevron, U.S.A., Inc. v. N.R.D.C., 104 S. Ct. 2778 (1984). OVERDOSED AND CONTAMINATED 2009] of deference given to an agency's interpretation of its own laws. For example, the Chevron standard is applicable to determine the deference due to the FDA's statement about preemption in the preamble of the Physician's Labeling Rule. Accordingly, a Court must first "question whether Congress has directly spoken to the precise question at issue."' 5 4 If the intent of Congress is clear, then the agency and the Court are obliged to give effect to the unambiguous intent of Congress.15 5 If, however, the intent of Congress is ambiguous, then the Court must decide "whether the agency's answer is based on a permissible construction of the 156 statute." The United States Supreme Court has used Chevron deference to preempt state tort claims. For example, in Geier v. American Honda Motor Co. the Supreme Court granted Chevron deference to a rule promulgated by the Department of Transportation (DOT) .157 The DOT rule provided for a phase-in of a mix of passive restraints instead of requiring air bags in all cars.15 ' The plaintiff, Geier, drove her Honda into a tree, and although she was wearing her seatbelt, she suffered serious injuries.159 As a result, she filed suit against Honda, alleging that it had "designed its car negligently and defectively because it lacked a driver's side airbag." 16' The Court determined that Geier's claim, based on the car manufacturer's state duty to install air bags, was an obstacle to achieving "the variety and mix of devices that the federal regulation sought.1 6 1 Ultimately, the Supreme Court held that state tort claims premised on Honda's failure to install air bags conflicted with a federal regulation that did not require air bags, and therefore, state tort claims were preempted. 162 The FDA has achieved mixed success in its attempt to preempt state tort law claims based on defective drugs and medical devices. In Wysocki v. Reed, the plaintiffs husband suffered se154 Id. at 2781. 155 Id. 156 157 158 159 Id. at 2782. See generally Geier v. Am. Honda Motor Co., 120 S. Ct. 1913 (2000). Id. at 1924. Id. at 1917. 160 Id. 161 Id. at 1925. 120 S. Ct. at 881. 162 Geier, QUINNIPIAC HEALTH LAW [Vol. 13:117 vere injuries as a result of an adverse reaction to Heparin, which he received as treatment for phlebitis.16 Mr. Wysocki's right leg was amputated below the knee, his right arm was paralyzed and he experienced mental deterioration, loss of speech, memory and self-control.1 6 4 The Heparin was manufactured by either Upjohn Company or Wyeth Laboratories. 1 65 The Court, in determining whether the plaintiff could proceed with a legal malpractice claim against the attorneys who represented her in the underlying products liability action, found that both Upjohn and Wyeth were negligent toward Mr. Wysocki and could consequently be held liable. 1 66 The state tort claims were allowed. Similarly, in Medtronic, Inc. v. Lohr, the Supreme Court held that the Medical Device Amendments of 1976 (MDA) "does not preempt state or local requirements that are equal to, or substantially identical to, requirements imposed under federal law.' 6 7 In this case, Lohr depended on a pacemaker to keep her heart functioning properly. 16 In 1987, Lohr received a pacemaker from Medtronic; when it failed on December 30, 1990 Lohr was rushed into emergency surgery.' 6 9 She filed suit as a result. The MDA, which established federal oversight of medical devices, also contained an express preemption clause whereby the MDA preempted state law tort claims against medical device manufacturers if the FDA approved the device. 170 However, the Court in Lohr narrowed the scope of the provision, finding the provisions of the pre-emptive MDA ambiguous. 171 In its reasoning, the Court applied two presumptions: first, the police powers of the states are not to be superseded by federal law "unless that was the clear and manifest purpose of Congress"; and second, "'[t]he purpose of Congress is the ultimate touchstone' in every 163 Wysocki v. Reed, 222 Il. App. 3d 268, 270 (1991) (stating that "Wysocki allegedly suffered a severe adverse reaction to the heparin," which led to his total disability, which in turn led to his death). 164 Id. 165 Id. 166 Id. at 279. 167 See generally Medtronic, 116 S. Ct. at 2240. 168 Id. at 2248. 169 Id. 170 Medical Device Amendments of 1976, §521, 90 Stat. 574 (codified as amended by 21 U.S.C. 360k (a) (2009)). 171 Medtronic, 116 S. Ct. at 2252. 2009] OVERDOSED AND CONTAMINATED preemption case. 1 72 The Court determined that it was "difficult to believe that Congress would, without comment, remove all means of judicial recourse for those injured by illegal conduct" in relation to medical devices.1 7 3 The Court went on to state that the MDA's legislative history does not contain any evidence of "fear that product liability actions would hamper the develop'' ment of medical devices.""4 Thus, Lohr's claim was successful. In contrast, in Riegel v. Medtronic, Inc., the Supreme Court held that the patient's state law claims of negligence, strict liability and implied warranty against the manufacturer of a medical device were preempted. 7 5 In 1996, Charles Riegel suffered a myocardial infarction and subsequently underwent coronary angioplasty. 1 76 Riegel's doctor inserted a catheter, the medical device at issue, into Riegel's coronary artery in an attempt to dilate the artery. 7 7 The label for the catheter warned that it "should not be inflated beyond its rated burst pressure."' However, Riegel's doctor ignored the warning and the catheter ruptured.179 Riegel developed a blockage in his heart, "was placed on life support, and underwent emergency coronary bypass surgery." ' Riegel alleged that Medtronic's catheter was designed, labeled, and manufactured in violation of New York common 8 law.' ' The Riegel Court stated that general tort duties of care 'directly regulate' the medical device, including its design.1 82 However, the Court recognized the argument that "[s]tate requirements are pre-empted under the MDA only to the extent that they are 'different from, or in addition to' the requirements imposed by federal law."'8 3 Thus, as in Lohr, the Court upheld the determination that federal law would not "prevent a State 172 Id. at 2250 (citations omitted). 173 Id. at 2251. 174 Id. 175 See Riegel, 128 S. Ct. at 1009. 176 Id. at 1005. 177 Id. 178 Id. 179 Id. 180 Riegel, 128 S. Ct. at 1005. 181 Id. at 1005. 182 Id. at 1010. 183 Id. at 1011 (citing Medical Device Amendments of 1976 (MDA), § 360k(a) (1)). 21 U.S.C. QUINNIPIAC HEALTH LAW [Vol. 13:117 from providing a damages remedy for claims premised on a violation of FDA regulations."' 4 However, the doctrine of preemption as it applies to medical devices and the MDA is decidedly different from the doctrine's application to drug labeling. As previously mentioned, the MDA contains an express preemption clause, but there is no similar provision related to drug labeling. State courts traditionally litigated claims based on inadequate drug labeling, but increasingly, state courts have been reluctant to allow the claims because of the FDA's statement in the preamble to the Physician's Labeling Rule and the Supreme Court's decision in Reigel. C. Wyeth v. Levine: The Supreme Court Weighs In i. Overview of the Arguments On March 4, 2009, the United States Supreme Court decided Wyeth v. Levine. i" 5 The Wyeth Court affirmed the Supreme Court of Vermont's decision, ultimately holding that state law failure-to-warn claims are not preempted by FDA drug labeling regulations. 8 6 Levine, a professional musician, 18 7 was suffering from a severe migraine. To treat her symptoms, she was injected with Demerol for her pain and Phenergan, a drug manufactured by Wyeth to treat nausea.' 8 8 Phenergan is administered in two ways: "intramuscularly or. . . intravenously through either the 'IVpush' method. . . or the 'IV-drip' method."' 9 However, "[t]he drug is corrosive and causes irreversible gangrene if it enters a patient's artery."' 90 Levine's first injection of Phenergan was administered intramuscularly, but Levine's symptoms were not relieved, so she returned to her local clinic later in the day for additional treatment.' The second injection of the drug entered Levine's 184 Id. 185 WAlyeth v. Levine, 129 S. Ct. 1187, 1196 (2009); see also Levine v. Wyeth, 944 A.2d 179, 193-94 (Vt. 2006). 186 Levine, 944 A.2d at 193-94. 187 Wyeth, 129 S. Ct. at 1189. 188 Id. at 1191. 189 Id. 190 Id. 191 Id. 20091 OVERDOSED AND CONTAMINATED artery, and a gangrene infection formed. As a result, Levine's 1 92 right hand, and eventually her entire forearm, was amputated. Afterward, Levine initiated a state tort law action against Wyeth, alleging that Wyeth was negligent because "[Phenergan's] labeling was defective [as] it failed to instruct clinicians to use the IVdrip method of intravenous administration instead of the higher risk IV-push method."1 93 Furthermore, "she alleged that Phenergan is not reasonably safe for intravenous administration because the foreseeable risks of gangrene and loss of limb are great 194 in relation to the drug's therapeutic benefits." In its defense, Wyeth argued that Levine's failure-to-warn claims were preempted by federal law because "there was an 'actual conflict between a specific FDA order,' and Levine's failureto-warn action," ' 95 and because the FDA approved Wyeth's label. The FDA first approved Phenergan in 1955.196 In 1987, "the FDA suggested different warnings about the risk of arterial exposure" to Wyeth, and Wyeth submitted proposed revisions to Phenergan's label in 1988.117 The FDA finally approved the label in 1998 and instructed that the "final printed label 'must be identical' to the approved package insert." 9 ' ii. The Lower Court Decisions The trial court evaluated the "correspondence between Wyeth and the FDA [regarding] Phenergan's labeling and found no evidence that Wyeth had 'earnestly attempted' to strengthen the intra-arterial injection warning or that the FDA had 'specifically disallowed"' a stronger warning.' 9 9 The jury was instructed that Wyeth's compliance with the FDA requirements did not establish that the warnings on Phenergan's label were adequate: a drug manufacturer is permitted under the FDA regulations to change a drug label to add to or strengthen a warning without prior FDA approval so long as it submits the revised warning for 192 Wyeth, 129 S. Ct. at 1191. 193 Id. at 1191-92. 194 Id. at 1192 (citation omitted). 195 Id. (citation omitted). 196 Id. at 1192. 197 Wyeth, 129 S. Ct. at 1192. 198 Id. (citation omitted). 199 Id. (citation omitted). QUINNIPIAC HEALTH LAW 142 [Vol. 13:117 FDA review and approval. 2 "° The jury ultimately found that Wyeth was negligent and that "Phenergan was a defective product as a result of inadequate warnings and instructions"; the jury awarded Levine $7.4 million in damages. 0 1 The Vermont Supreme Court affirmed.20 2 The Court recognized that the FDA's Physician Labeling Rule contained a preamble with preemptive language; however, the Court concluded that the agency's assertion did not deserve deference. 20 3 The Court determined that FDA labeling requirements "create a floor, not a ceiling, for state regulation. "204 The Court found that a manufacturer's duty to warn "does not create a conflict with federal requirements because the FDA and the state share the purpose of encouraging pharmaceutical companies to alter their drug labels when they are inadequate. ' 20 5 The Court further determined that Levine's claims did not interfere with Congress' objectives because, in the Court's view, "Congress intended that the FDCA would leave state law in place except where it created a 'direct and positive conflict' between state and federal law." iii. 206 The United States Supreme Court Decision Wyeth made two preemption arguments to the United States Supreme Court: first, that it was impossible to comply with state law without violating federal law and second, that "recognition of Levine's state tort action create[d] an unacceptable 'obstacle to the accomplishment and execution of the full purposes and objectives of Congress,' because it substitutes a lay jury's decision about drug labeling for the expert judgment of the 20 7 FDA." To guide its analysis, the Court identified two factual propositions decided during the trial court proceedings. First, "the trial court proceedings established that Levine's injury would not have occurred if Phenergan's label had included an ade200 201 202 203 204 205 206 207 Id. at 1192-93. Id. at 1193. Wyeth, 129 S. Ct. at 1193. Levine, 944 A.2d at 193. Id at 184. Id. at 188. Id. at 190. Wyeth, 129 S. Ct. at 1193-94 (citation omitted). 2009] OVERDOSED AND CONTAMINATED quate warning about the risks of the IV-push method of administering the drug. ' 2°8 Second, the trial court proceedings established that the "critical defect in Phenergan's label was the lack of an adequate warning about the risks of IV-push administration. 2 0 In order to determine whether Levine's claim - that Phenergan's label was inadequate - was preempted by federal law, the Court identified "two cornerstones of [its] pre-emption jurisprudence": First, "the purpose of Congress is the ultimate touchstone in every pre-emption case." Second, "[i]n all pre-emption cases, and particularly in those in which Congress has 'legislated... in a field which the States have traditionally occupied,' . . . we 'start with the assumption that the historic police powers of the States were not to be superseded by the Federal Act unless that was the clear and manifest purpose of Congress.' "210 To determine the "purpose of Congress," the Court examined the history of federal regulation of drugs.2 m When the FDCA was first enacted, it provided for pre-market approval of drugs, whereby a drug could not be distributed until it was determined by the FDA to be safe for use.21 2 Congress then enacted the Drug Amendments of 1962; consequently, drug manufacturers were required to prove not only that the drug was safe for use, but that it was safe for use "under the conditions prescribed, recommended, or suggested in the proposed labeling. 21 3 Furthermore, the drug manufacturer had to "prove the drug's effectiveness by introducing 'substantial evidence that the drug will have the effect it purports or is represented to have under the conditions of use prescribed, recommended, or suggested in the proposed labeling."' 214 The Drug Amendments also "added a saving clause, indicating that a provision of state law would only be invalidated" if it created a "'direct and positive conflict' Id. at 1194. Id. 210 Id. at 1194-95 (citations omitted). 211 Id. at 1195. 212 Wyeth, 129 S. Ct. at 1195. 213 Id. (citing Drug Amendments of 1962, 21 U.S.C. §§ 102(d), 104(b)) (internal citations omitted). 214 Id. (citations omitted). 208 209 144 QUINNIPIAC HEALTH LAW [Vol. 13:117 with the FDCA. 2 15 The Court noted that state tort law claims 'continued unabated despite . . .FDA regulation' and that Congress, despite enacting an express preemption provision with regard to medical devices, never enacted a similar provision with respect to prescription drugs.2 6 When Congress again amended the FDCA in 2007, it did not enact a provision mandating FDA pre-approval for all drug label changes; rather, it kept the ultimate responsibility for drug label changes with the drug manufacturer.2 1 7 The Court believed it is "a central premise of federal drug regulation that the manufacturer bears responsibility for the content of its 218 label at all times. The Court then rejected Wyeth's claims. First, the Court found it was not impossible for Wyeth to comply with both state and federal law. 21 ' The Court recognized that generally, a manufacturer is only permitted to change a drug label after FDA approval of a supplemental drug application. 220 However, the Court emphasized that an FDA regulation permits a manufacturer to change "a label to 'add or strengthen a contraindication, warning, precaution, or adverse reaction' or to 'add or strengthen an instruction about dosage and administration that is intended to increase the safe use of the drug"' without prior FDA approval, so long as the drug manufacturer submits a supplemental drug application. 221 Thus, the Court rejected Wyeth's claims that it would have been in violation of federal law if it unilaterally changed Phenergan's label, especially given the absence of any evidence that the FDA would have rejected Wyeth's proposed changes to the drug label.2 2 2 Wyeth failed to prove the elements of its "impossibility pre-emption" defense.2 23 Second, the Court failed to find that recognition of Levine's state tort action thwarted "the full purposes and objectives of Congress" by substituting the expert judgment of the FDA for 215 Id. at 1196 (citation omitted). 216 Id. (citation omitted). 217 Wyeth, 129 S. Ct. at 1196. 218 Id. at 1197-98. 219 Id. at 1199. 220 ld. at 1196. 221 Id. at 1196; see also 21 C.F.R. §§ 314.70(c)(6)(iii)(A), (c) (6)(iii)(C). 222 Wyeth, 129 S. Ct. at 1197. 223 Id. at 1199. 2009] OVERDOSED AND CONTAMINATED that of a lay jury. 224 The Court found Wyeth's argument relied on an "overbroad view of an agency's power to pre-empt state law," and contradicted all the evidence of Congress' purposes.2 2 5 The Court acknowledged that Congress decided not to provide a federal remedy in light of the adequacy of "state rights of action,"22 6 but could only speculate whether or not Congress "recognized that state-law remedies [enhance] consumer protection by motivating manufacturers to produce safe and effective drugs and to give adequate warnings. '227 Ultimately, Congress' failure to enact an express preemption provision and its awareness of state tort litigation was "powerful evidence that Congress did not intend FDA oversight to be the exclusive means of ensuring drug 228 safety and effectiveness." Third, the Court determined that the FDA's preamble to the Physician's Labeling Rule did not merit deference because it was a mere assertion, not a regulation with the force of law, and 2 29 Congress had not authorized the FDA to preempt state law. The Court stated, "[t] he weight we accord the agency's explanation of state law's impact on the federal scheme depends on its thoroughness, consistency, and persuasiveness. ' 23 ° The Court found the FDA's preamble did not meet this standard because it was rendered inherently suspect due to the agency's procedural failure to offer "[s] tates or other interested parties notice or opportunity for comment" on the preemption of state tort law. 23 ' Additionally, the Court found the agency's position in the preamble was a reversal of its longstanding policy to use its "limited resources to monitor the 11,000 drugs on the market," and allow 224 Id. at 1193. 225 Id. at 1199. 226 Id. (citation omitted). 227 Wyeth, 129 S. Ct. at 1199-1200. 228 Id. at 1200. at 1201. 230 Id. at 1201 (citation omitted). 229 Id. 231 Id. The decisions reads: When the FDA issued its notice of proposed rulemaking in December 2000, it explained that the rule would "not contain policies that have federalism implications or that preempt State law." In 2006, the agency finalized the rule and, without offering States or other interested parties notice or opportunity for comment, articulated a sweeping position on the FDCA's preemptive effect in the regulatory preamble. The agency's views on state law are inherently suspect in light of this procedural failure. Id. (citations omitted). QUINNIPIAC HEALTH LAW [Vol. 13:117 state law to complement FDA regulations by offering a layer of consumer protection.2 3 2 Generally, "manufacturers [that] have superior access to information about their drugs, especially in the postmarketing phase" can better benefit from increased involvement in state tort suits,23 3 which often "uncover unknown drug hazards and provide incentives for drug manufacturers to disclose safety risks promptly."2 3' 4 The FDA can better benefit by allocating its resources to other areas. The FDA seemed to reject this longstanding acceptance regarding the high value of state tort suits. Justice Breyer and Justice Thomas concurred; however, Justice Thomas disagreed with the majority's endorsement of implied preemption.2 3 5 He argued the supremacy clause will give supreme status to only those laws which are made "in pursuance of the Constitution. 2 3 6 In other words, a law is made in pursuance of the Constitution when it is within Congress's power to enact and the law is enacted through the constitutionally required procedures. 2 7 Thus, Justice Thomas argued that the Court strayed too far from traditional principles of preemption by expanding federal statutes beyond their text through the doctrine of implied preemption.23 8 In particular, he criticized the majority's discussion of the "purposes and objectives of Congress." 23 9 Instead, Justice Thomas argued " [p]re-emption must turn on whether state law conflicts with the text of the relevant federal statute or with the federal regulations authorized by that text."24 0 He argued, under this standard, it was not impossible for Wyeth to comply with both state and federal law because the 2 41 texts do not conflict. Chief Justice Roberts and Justice Scalia joined Justice Alito in the dissent. The dissent argued that the FDA's authority to determine adequate labeling for a drug has been usurped by lay 232 Wyeth, 129 S. Ct. at 1201-02. 233 Id. at 1202 (citation omitted). 234 Id. 235 Id. at 1205 (Thomas, J., concurring). 236 Id. at 1206. 237 Wyeth, 129 S. Ct. at 1206. 238 Id. 239 Id. 240 Id. 241 Id. at at at at 1205. 1205-07. 1208. 1209. OVERDOSED AND CONTAMINATED 20091 juries, and that the majority reached a conclusion that circumvented the FDA's expert policy judgments. 242 The dissent, like the majority and in contrast to Justice Thomas, endorsed implied preemption, and suggested "it is irrelevant in conflict preemption cases whether Congress 'enacted an express pre-emption provision.' ,,243 The dissent analogized the case to Geier, and would give deference to the FDA's intent to preempt state tort law as expressed in the preamble to the Physician's Labeling Rule because the preamble was published in the Federal Register like any other law.244 The dissent further commented that 'juries are ill-equipped to perform the FDA's cost-benefit-balancing function" because 'juries tend to focus on the risk of a particular product's design or warning label that arguably contributed to a particular plaintiff's injury, not on the overall benefits of that design or label. '245 Also, the dissent argued, "the FDA conveys its warnings with one voice, rather than whipsawing the medical community with 50 (or more) potentially conflicting 246 ones." Analysis of the Wyeth Decision and the Drug Labeling Regime D. i. Preserving a Necessary Cause of Action Actor Dennis Quaid expressed the sentiment of many drug consumers when he said, "[i]f all lawsuits were to be pre-empted ... then 'it will basically make us uninformed and uncompensated lab rats.' ,247 Thus, the United States Supreme Court correctly decided Wyeth by holding that drug labeling regulations promulgated by the FDA do not preempt state tort law claims The Wyeth decision preserves the states historical role regarding domestic products. States have traditionally exercised principal control over domestically produced and distributed drugs, and although the FDCA allocated some authority to the 242 See generally Wyeth, 129 S. Ct. at 1229-30 (Alito, J., dissenting). 243 Wyeth, 129 S. Ct. at 1220. 244 Id. at 1228. 245 Id. at 1229-30. 246 Id. at 1230. 247 Dennis Quaid Tells Lawmakers How Drug Mix Up Nearly Killed His Newborn Twins, MEDICAL NEWS TODAY, May 14, 2008, http://www.medicalnewstoday.com/articles/ 107486.php. QUINNIPIAC HEALTH LAW [Vol. 13:117 federal government to regulate drugs, it also preserved state law's ability to do the same, absent a direct and positive conflict between state law and federal regulations. 248 The Wyeth Court was persuaded by Congress' inaction or silence with respect to whether the FDA's drug labeling regime preempts state tort law, particularly in light of Congress' awareness of state tort litigation and the enactment of a preemption provision with respect to medical devices.24 9 Furthermore, the Wyeth decision fully exalts the importance of state tort law claims. State tort law claims supplement federal regulations and provide appropriate avenues, if not the only avenues, for injured parties, like the Quaids and the Hubleys, to seek redress. Consequently, state tort suits provide an important function for consumers, and the FDA, by exposing post-market drug safety issues. In the Court's words, "State tort suits uncover unknown drug hazards and provide incentives for drug manufacturers to [promptly] disclose safety risks."2 5 ° Although some consumer advocates argue "that state tort law can sometimes raise prices to the point where those who are sick are unable to obtain the drugs they need, ' 25' a drug that is inadequately labeled can deprive a person of the benefit they seek, and may cause more harm than good. State lawsuits "also serve a distinct compensatory function that may motivate injured persons to come forward with information. "252 The dissent correctly noted that "state tort suits can peacefully coexist with the FDA's labeling regime, and they have done so for decades. '25 3 In addition, the FDA is ill-equipped to exercise exclusive oversight of drug labeling due primarily to a lack of resources.25 4 ii. The FDA's Troubling View of Preemption Despite the positive results of the Wyeth decision, we are still left with a disturbing belief that the FDA does not fully grasp the inherent issues with the drug labeling regime. The FDA's posi248 See supra Part 11A; see also Brief for Appellee, supra note 62, at 6; see also Drug Amendments of 1962, supra note 62, §202; see also EDA Origin, supra note 47. 249 Wyeth, 129 S. Ct. at 1200 (majority opinion). 250 Id. at 1202. 251 Id. at 1204 (Breyer,J., concurring). 252 Id. at 1202 (majority opinion). 253 Id. at 1231 (Alito,J., dissenting). 254 Wyeth, 129 S. Ct. at 1202-03 (majority opinion). OVERDOSED AND CONTAMINATED 2009] tion on preemption is troubling in several respects, and reveals flaws in the Agency's attitude and understanding of the drug labeling regime. First, if Wyeth were decided differently, drug manufacturers would be able to assert preemption as a defense to liability if their drug was approved by the FDA; this would effectively immunize drug manufacturers from accountability for their products. However, the Wyeth court emphasized that it is a "central premise of federal drug regulation that the manufacturer bears responsibility for the content of its label at all times. 25 5 The FDA would portray its approval of a drug as a warranty that the drug is safe and effective; yet, "FDA approval does not represent a lifetime guarantee of safety and efficacy, and what is newest is not always the best."2 56 The FDA has been under considerable pressure to get potentially life-saving drugs onto the market, and as a result, safety has been compromised for speed during the drug approval process.2 5 7 Wyeth argued that the FDA "must be presumed to have performed a precise balancing of risks and benefits" associated with a drug before it is approved as safe and effective for its intended use.25 8 Indeed, the FDA has stated that state failure-to-warn claims "threaten FDA's statutorily prescribed role as the expert federal agency responsible for evaluating and regulating drugs."2 59 Yet, the FDA and drug manufacturers such as Wyeth ignore the fact that the FDA did not always have to approve drugs before they entered the market. 26 ° Prior to 1962, when many drugs such as Heparin entered the market, a drug could be approved upon FDA inaction after a period of sixty days. 2 6 ' Furthermore, Congress has never authorized judicial review of a new drug approval.2 6 2 Consequently, an interested party with knowledge relevant to the safety or efficacy of a drug cannot challenge the approval of the drug or bring to light the FDA's 255 Id. at 1197-98. 256 FUTURE OF DRUG SAFETY, supra note 77, at 2. 257 Id. at 154. 258 Wyeth, 129 S. Ct. at 1200. 259 Id. (citation omitted). 260 See FDCA of 1938, supra note 43, at § 355(h) (permitting an application for a new drug to become effective after 60 days, despite FDA inaction). 261 Brief for Appellee, supra note 62, at 5. 262 Id. 150 QUINNIPIAC HEALTH LAW [Vol. 13:117 possible failure to consider certain information; such drug safety issues will only become apparent when a consumer is injured, and the adverse event is reported. Thus, the FDA cannot be presumed to have performed a precise balance of the risks and benefits of a drug because of the external pressure on the agency to get drugs onto the market, and the fact that many drugs, including Heparin, could be approved to enter the market by agency inaction. Thus, if information regarding the safety or efficacy of a drug slips through cracks during the approval process, state tort lawsuits can, and do, serve the purpose of bringing this information to light. iii. The FDA's Capacity to Carry Out Its Responsibilities Formally approved or not, however, the FDA is responsible for a drug over its lifecycle, "from drug discovery to the end of its useful life." 26 3 But, "[t] he FDA's ability to form judgments about the safety and efficacy of drugs depends upon the submission of data, usually from drug company sponsors, rather than on the use of data developed independently or on its own initiative. '' 264 As the Wyeth Court noted, "[drug] manufacturers have superior access to information about their drugs, especially in the postmarketing phase." 26 5 Consequently, the FDA cannot, by itself, oversee post-market drug safety issues and at the same time, remove incentives for drug manufacturers to notify the public of drug safety risks.2 66 In fact, the FDA has "few tools... for addressing postmarketing safety issues. ' 2 6 7 After a drug is approved, the FDA's regulatory and enforcement options have been limited, often to doing nothing or to participating in the voluntary withdrawal of the drug from the market. 26 8 The FDA's primary tool is withdrawal of the drug from the market, but where a drug has substantial life-saving benefits, the threat of withdrawal often rings hollow. 26 9 Another tool for the FDA in the promotion of post263 FUTURE OF DRUG SAFETY, supra note 264 Id. at 152. 265 Wyeth, 129 S. Ct. at 1202. 266 77, at 1. See id. 267 FUTURE OF DRUG SAFETY, supra note 268 Id. at 155. 269 Id.; see also Drug Safety: FDA Needs to 77, at 153. FurtherAddress Shortcomings in Its Postmarket Decision-makingProcess Hearingbefore the Subcomm. On Oversight and Investigations of the H. OVERDOSED AND CONTAMINATED 2009] market drug safety is to require post-marketing studies, which, until recently, was controversial.2 7 ° Under the FDAAA, the FDA can now require sponsors to make certain drug labeling changes and to conduct post-marketing studies instead of relying on voluntary compliance. 7 1 Nonetheless, the "FDA has limited resources to monitor the 11,000 drugs on the market. ' 27 2 The FDA has only nine thousand employees nationwide.2 7 3 The "FDA's Office of New Drugs, which reviews new drug applications, employs over 1,000 physicians and scientists to review" new drug applications "and to supervise post-marketing studies."2 7 4 In contrast, the FDA's Office of Drug Safety, which monitors adverse event reporting, has only about one hundred employees.2 75 Additionally, a March 2006 report conducted by the Government Accountability Office (GAO) indicated that there is a lack of communication between the two offices of the CDER, which hinders the FDA's decision making process with regard to post-market drug safety. 27 6 The GAO found that the "FDA lacked a clear and effective process for making decisions about, and providing management oversight of, postmarket drug safety issues. 27 7 Furthermore, the GAO found that "there was a lack of clarity about how decisions were made and about organizational roles, insufficient oversight by management, and data constraints. '"278 The GAO also observed that "there was a lack of criComm. On Energy and Commerce, 110th Cong. 5 (2007) (statement of Marcia Crosse, Dir., Health Care, U.S. Gov't Accountability Off.), available at http://archives.energycom merce.house.gov/cmtemtgs/110-he-hrg.050907.Crosse-testimony.pdf [hereinafter Statement of Marcia Crosse on Post-market Drug Safety]. 270 See FUTURE OF DRUG SAFETY, supra note 77, at 155; see also Statement of Marcia Crosse on Post-market Drug Safety, supra note 269, at 9 (stating that the "FDA does not have broad authority to require that a drug sponsor conduct an observational study or clinical trial for the purpose of investigating a specific postmarket safety concern."). 271 Statement of Paul Seligman, supra note 80. 272 Wyeth, 129 S. Ct. at 1202. 273 CHRISTINE HUMPHREY, AN ANALYSIS OF HEPARIN, ACCOUNTABILITY AND PRE-EMPTION: WHERE ARE WE Now? PART pdf [hereinafter 274 Id. II 3 (2008), http://fuerstlaw.com/files/heparinpt2. HUMPHREY]. Id. Statement of Marcia Crosse on Post-market Drug Safety, supra note 269, at 2; see also FUTURE OF DRUG SAFETY, supra note 77, at 6 (stating that the Office Drug Safety is now the Office of Surveillance and Epidemiology). 277 Statement of Marcia Crosse on Post-market Drug Safety, supra note 269, at 2. 278 Id. 275 276 QUINNIPIAC HEALTH LAW [Vol. 13:117 teria for determining what safety actions to take and when to take them, which likely contributed to disagreements over deci2 79 sions about postmarket drug safety." Thus, the court in Wyeth correctly denied deference to the FDA's position on preemption, expressed in the preamble to the 2006 Physician's Labeling Rule, finding it "inherently suspect." The Court noted that the FDA's position was a "dramatic" reversal of its long-standing position that "state law offers an additional, and important, layer of consumer protection that complements FDA regulation. ' 2 0 The Court also noted that the "FDA traditionally regarded state law as a complementary form of drug regulation. '28 1 Thus, the FDA's position on preemption is without merit, and reveals a misunderstanding by the Agency of its capacity to address post-market drug safety issues. iv. The FDA's Credibility: Too Little, Too Late Besides its troubling, inconsistent view of state law causes of action, "there is a perception of crisis that has compromised the credibility of FDA." 282 In turn, the "FDA's credibility is intertwined with that of the [pharmaceutical] industry."2 3 In the case of Heparin, Baxter was in a position to assist the FDA, and the public, in post-market drug safety review, which arguably the corporation failed to do. As previously mentioned, Baxter, as the drug manufacturer, has primary responsibility for its drug labels, 2 4 and under FDA regulations, Baxter was permitted to change the content or color of its Heparin drug label without prior FDA approval. 2 5 Baxter's failure to sufficiently diffuse the labeling problem tainted the FDA's credibility. For example, in May 2005, a report was sent to United States Pharmacopeia's Medication Errors Reporting Program, regarding confusion with the label on one of Baxter's Heparin sodium 286 IV bags pictured below. 279 Id. 280 Wyeth, 129 S. Ct. at 1202. 281 Id. 282 FUTURE OF DRUG SAFETY, supra note 77, at 4 (citations omitted). 283 Id. at 5. 284 Wyeth, 129 S. Ct. at 1202. 285 See generally 21 C.F.R. § 314.70(c)(6) (2009); see also Wyeth, 129 S. Ct. at 1196. 2386 Practitioners'ReportingNews: Total Bag/Vial Content Confusion, US PHARMACOPEIA, OVERDOSED AND CONTAMINATED 2009] 153 Generally, the label's coloring and layout emphasizes the red box and "attention is drawn to the red box and not the total volume contained in the bag. '28 7 As a result of this packaging, patients were administered the wrong concentrated dose of Heparin. 28 8 The facility that used these bags "recommended to Baxter that they change their labeling to include the volume of the bag in the same color and in the same location as the total num28 ber of heparin units." 9 A year later, "some patient safety advocates  called on Baxter Healthcare to change the labeling on heparin products so that there is a greater distinction between adult and pediatric doses. '29" However, the changes were not made or did not reach all Heparin bags. An investigation found that errors made by pharmacy and nursing staff caused the wrong concentration of heparin to be used... [when] [a] pharmacy technician... mistakenly retrieved a higher concentration of May 31, 2005, http://www.usp.org/hqi/practitionerPrograms/newsletters/practitioner ReportingNews/prn252005-05-31.html. 287 Id. 288 Id. 289 Id. Anthony Vecchione, Heparin Overdoses Bring Changes, DRUG Topics, Oct. 26, 2006, http://drugtopics.modernmedicine.com/drugtopics/article/articleDetail.jsp?id= 379887 [hereinafter Vecchione]. 290 154 QUINNIPIAC HEALTH LAW [Vol. 13:117 heparin (10,000 units per milliliter) instead of the lower-concentration heparin (10 units per milliliter) . . .[and] the higher concentration heparin was delivered to the satellite pharmacy that serves the pediatrics unit. A second pharmacy technician, working in the satellite pharmacy, did not verify the concentration of the delivery from the main pharmacy ...291 In November 2007, the Quaid twins were given an overdose of Heparin, primarily due to the similarity in the labels between the adult vials and pediatric vials.2 9 2 In his testimony before Con- gress, Quaid stated that the bottles of Heparin "were deadly similar in labeling and size. The 10,000-unit label is dark blue, and the 10-unit bottle is light blue. '293 Furthermore, "if the bottles are rotated slightly, as they often are when stored, they are virtu29 4 ally indistinguishable." A month later, in December 2007, Baxter introduced a new drug safety initiative to reduce medication errors by creating enhanced packaging of its drugs. Heparin was the first drug to receive the new enhanced label. 29 5 The label features a twenty percent increase in font size, a unique color combination, and a 296 red tear-off label. However, Baxter's actions may be too little too late. And where was the FDA during this three-year period? More information is needed about the correspondence between Baxter and the FDA regarding Heparin's drug labels to provide a better evaluation of a claim against Baxter. If the FDA and Baxter had entered into discussions regarding changes to Heparin's label, and the FDA prohibited Baxter from making a certain change to the label, such as changing the color, this fact may impact Baxter's liability under state law. 2 9 7 Nonetheless, plaintiffs lawyers 291 InvestigationReveals How Hospital Gave Dennis Quaid's Babies an Overdose, THE INSIDER, Dec. 5, 2007, http://www.theinsider.com/news/508304_Investigation Reveals_ How HospitalGaveDennis Quaids_Babies anOverdose. 292 Statement of Dennis Quaid, supra note 3, at 3. 293 Id. 294 Id. Id. 296 Baxter Healthcare Corp., Baxter Introduces New Drug Safety Packagingfor High Alert Medications: Enhanced Labels the First of Several Initiatives Aimed at Medication Error Reduction, http://araplus.com/aboutIbaxter/news_room/news-releases/2007/12-03-07drug-safety.html (last visited Jan. 13, 2009). 297 See Wyeth, 129 S.Ct. at 1198 (stating that "absent clear evidence that the FDA 295 OVERDOSED AND CONTAMINATED 2009] would be remiss not to comprehend the significance of the decision in Wyeth v. Levine. E. Recommendations for the Improvement of Drug Labeling Safety Issues In the wake of the United States Supreme Court's decision in Wyeth, consumers harmed by drug products with inadequate labeling will be able to bring their claims in state court. As previously discussed, these lawsuits will serve the important function of exposing drug safety issues caused, for example, by a drug's inadequate label. However, in order to prevent the tragedies that befell the Quaid family, and in order to assist the FDA in the oversight of drug labeling, significant changes must be made to the current drug labeling regime. Below, are a few recommendations to consider. i. Drug manufacturers must be vigilant in their duty to update drug labels when new information, such as adverse events or other safety risks, becomes available. As previously discussed, Baxter was aware of potential issues with its Heparin drug labels as early as 2005 but it failed to make any labeling change until 2007. If Baxter had been vigilant in its duty, Thomas Boone and Zoe Grace would likely not have been overdosed. ii. Hospitals should review their proceduresfor administering medicine and implement changes as necessary. When three premature infants died as a result of fatal doses of Heparin at Methodist Hospital in Indianapolis, 298 the hospital implemented a "series of drastic changes" to prevent the incident from happening again, including (1) initiating "a double check for all drugs pulled from inventory"; (2) having one person "pull the drugs from inventory and another... read the drug label and put the drug into the dispensing cabinet"; (3) eliminating all 10,000-unit Heparin from the hospital and no longer keeping it in inventory; and (4) having "a minimum of two would not have approved a change to Phenergan's label, we will not conclude that it was impossible for Wyeth to comply with both federal and state requirements"). 298 Vecchione, supra note 290. QUINNIPIAC HEALTH LAW 156 [Vol. 13:117 nurses validate all Heparin doses" administered in the "neonatal and pediatric intensive care units."299 Likewise, Cedars-Sinai Hospital (Los Angeles, California), where the Quaid twins were given an overdose of Heparin, instituted several changes. Cedars-Sinai discontinued use of Heparin to flush catheters in the pediatric unit; instead, it uses saline solution. 3 0" The hospital also revised its "internal training [program] on the use of 'high alert' medications. 3 1 1 These kinds of responses to adverse events need to be happening in all hospitals. iii. Implementing the use of bar-code technology in hospitals should be a nationalpriority. Some believe that "[t]he absence of bar-code technology and a double-check system contributed to the fatal doses [of Heparin]."3°2 Bar code technology involves affixing a bar code to each dose of medication.30 3 The bar code on the medication is scanned before the medication is given to the patient as an additional step to make sure that the patient is receiving the correct medication.30 4 Patients have a bar-coded wrist band which a doctor or nurse scans before administering the drug to the patient to make sure that the medication is approved for the particular patient.3 0 5 Some bar code scanners use a red light or green light to indicate whether, upon scanning, the medication is ap36 proved for the particular patient. Michael Cohen, M.S., President of the Institute for Safe Medication Practices, said, "[I]f a hospital isn't looking into adopting bar-code technology, it is making a terrible mistake.... 299 Id. 300 Howard Breuer, HospitalAnnounces Changes in the Wake of Quaid Mishap, PEOPLE, Dec. 5, 2007, http://www.people.com/people/article/O,,20164320,0O.html. 301 Id. 302 Vecchione, supra note 290. 303 Bar Code Technology in HospitalPharmacy Cuts Errors, HARVARDSCIENCE, Sept. 18, 2006, http://www.harvardscience.harvard.edu/medicine-health/articles/bar-code-tech nology-hospital-pharmacy-cuts-errors. 304 See id.; Bar Code Label Requirement for Human Drug Products and Blood, 68 Fed. Reg. 12500, 12502 (Mar. 14, 2003) (codified at 21 C.F.R. pts. 201, 606, and 610) [hereinafter FDA Bar Code Requirement]. 305 FDA Bar Code Requirement, supra note 304, at 12502. 306 See Oprah, supra note 1. 2009] OVERDOSED AND CONTAMINATED It should become a requirement."3 °7 In fact, the FDA promulgated a rule in 2003 mandating drug manufacturers to include bar codes on prescription medications. °8 However, in promulgating the rule the FDA realized that [T]he bar codes' ability to prevent medication errors depends on many external factors... such as the availability of bar code scanners, computer software that can process the bar code information and compare it against patient information, training health care professionals to use scanning equipment, and the willingness of hospitals to invest in bar code 30 9 scanning equipment. Unfortunately, bar code scanners are expensive; they cost over one thousand dollars.3 10 Whether or not cost is a deterrent, a 2006 study showed that only 9.4 percent of hospitals use bar code technology for medication administration.3 ' Yet, bar-code technology is becoming prevalent in other areas of our lives; for example, local grocery stores are now equipped with bar code scanners. The use of bar-code technology improves ones experience with buying, categorizing or using products and should be implemented where we can benefit in life-altering ways, not just for shopping convenience. In light of the Quaids' overdose, Cedars-Sinai Hospital implemented bar-code technology. 31 2 Other hospitals should not wait for a similar tragedy before following Cedars-Sinai's example. 307 Vecchione, supra note 290 (internal citations omitted). 308 See FDA Bar Code Requirement, supra note 304, at 12502. 309 310 Id. at 12512. Bar Coding Helps Hospitals Reduce MedicationErrors: TrackingErrorReduction Proves Challenging, but Users are Pleased, http://findarticles.com/p/articles/mi-mONUZ/is_5_ 12/ai_n13759942/?tag=content;colI (last visited Dec. 3, 2009). 311 Debbie Murphy, Barcode Basics: Why Printing,Symbology, and Media Choices Matter, PATIENT SAFETY & QUALITY HEALTHCARE, Jul./Aug. 2007, http://www.psqh.com/julaug 07/barcode.html. 312 Elizabeth Fry, Dr. Oz and Dennis Quaid with Medical Mistakes - Show Recap, ABOUT.COM, http://oprah.about.com/od/oprahshowrecaps/p/medicalmistakes.htm. QUINNIPIAC HEALTH LAW zv. [Vol. 13:117 The FDA should receive increasedfunding and resources to enhance the effectiveness of its Adverse Event Reporting System and health professionals should be obligated to report adverse drug events to the FDA. Reports of adverse events submitted to the FDA are stored in the agency's Adverse Event Reporting System (AERS). 3" 3 Quarter Watch, a pilot program developed by the Institute for Safe Medication Practices "to improve patient safety through regular monitoring of all adverse drug events reported to the FDA. ' 314 This program found that "[a] record number of deaths and serious injuries associated with drug therapy were reported to the" FDA "in the first quarter of 2008. "315 Heparin ranked 16 second on the list of drugs with most reported serious injuries, with 779 cases reported to the FDA in the first quarter of 2008, 3 17 including 102 deaths. The chart below shows the number of deaths reported to the FDA from January 1, 2007 to May 31, 2008; these are deaths occurring after the patient was administered Heparin.3" 8 The middle column shows the number of deaths regardless of cause. The third column shows the number deaths where allergic reactions were reported. From January 1, 2007 to May 31, 2008, Heparin was linked to 246 deaths.3 1 9 313 THE INSTITUTE FOR SAFE MEDICATION PRACTICES, QUARTER WATCH: 2008 QuAR- TER 1 6 (2008), http://www.ismp.org/QuarterAlVatch/20O8Q1.pdf [hereinafter QuARTER WATCH]. 314 315 316 317 Id. at 1. Id Id. Id. at 3. 318 PDA: Information on Adverse Events Reports and Heplarin, Nov. 18, 2008, http:// blog.heparin-law.com/2008/11/fda-information-on-adverse-event.html. 319 Id. 20091 159 OVERDOSED AND CONTAMINATED Number of Deaths of Patients Receiving Heparin Reported to FDA, January 1, 2007 through May 31, 2008 Month the Medical Event(s) Occurred Number of Reported Deaths* Reported Deaths with One or More Allergic/Hypotensive Symptom(s) Jan-07 6 3 Feb-07 2 1 Mar-07 5 2 Apr-07 7 4 May-07 3 1 Jun-07 5 2 Jul-07 6 3 Aug-07 4 4 Sep-07 3 2 Oct-07 10 5 Nov-07 12 11 Dec-07 34 23 Jan-08 50 32 Feb-08 49 29 Mar-08 14 10 Apr-08 7 4 May-08 5 3 Unknown date 24 10 Total 246 149 *The reports in this table concern heparin produced by any 320 manufacturer. Studies indicate that no more than ten percent and possibly as little as one to two percent of adverse events are reported to the FDA. 32 1 For consumers and health professionals, submission of reports is voluntary,3 22 and consequently, these numbers may be understated. Drug manufacturers must investigate serious adverse drug reactions they become aware of, "[b]ut a company 320 Id. 321 QUARTER WATCH, 322 Id. at 1. supra note 313, at 7. QUINNIPIAC HEALTH LAW 160 [Vol. 13:117 does not have to act unless informed of a potential adverse event 323 by an employee, consumer or health professional. Additionally, the Institute for Safe Medication Practices "detected a significant technical error" in the way adverse event reports "were being coded by the FDA."3 24 Thus, the FDA needs additional funding and resources to correct problems in its infrastructure to ensure accuracy of its data, and in turn, knowledge of the potential drug safety issues. v. A national method for determining the number of people seriously injured or killed by prescriptiondrugs is necessary in order to accurately quantify the problem and to track progress in measures designed to address the problem. The true number of "individuals seriously injured or killed by prescription drugs is unknown" because the data is "not calculated by a recognized statistical method."3 2' 5 Because of the problems with collecting data in this field, many statisticians have to estimate the numbers. One study, which aggregated information from "hospital admission studies collected over many decades calculated that 100,000 persons die annually from the complications of prescription drugs and 1 million or more may be hospitalized." 2 6 To put this data in context, "44,572 persons died in 2006 in motor vehicle accidents, 18,029 from homicide and 560,102 from all forms of cancer.31 27 The Institute for Safe Medication Practices concluded that the data from studies indicated "the need for additional progress to better manage the 3 28 risks [of prescription drugs] to patients. IV. FDA Regulation of Foreign Drug Manufacturers In addition to issues raised by the drug labeling dilemma and federal preemption analysis, victims of contaminated Heparin, such as the Hubleys, face more hurdles in their attempt to 323 Id. 324 Id. 325 at 6. at 3. Id. at 6. 326 QUARTER WATCH, supra note 327 328 Id. Id. at 4. 313, at 6. OVERDOSED AND CONTAMINATED 2009] find an adequate remedy against drug manufacturers in the United States and abroad. A. 29 The FDA's InternationalRole and the Globalization Act& It is generally accepted that "most Active Pharmaceutical Ingredients (APIs) are made by foreign manufacturers. '330 Yet, the FDA has limited ability to oversee foreign drug manufacturers.13 ' The FDCA requires foreign drug manufacturers exporting drugs to the United States to register with the FDA. 332 The FDA also requires foreign drug manufacturers to comply with the current Good Manufacturing Practice (cGMP) requirements. 33 The FDA educates regulatory counterparts in other countries about United States public health standards, and on how to comply with cGMP. 33 4 The FDA has also been an advocate for raising international health safety standards and for harmonizing the standards amongst different countries.3 3 5 The FDA is further responsible for monitoring products 3 within its jurisdiction that are imported to the United States. 1 The United States Customs and Border Protection notifies the FDA when one of the products it regulates, such as a drug, is offered for import. 33 7 The FDA screens drug products entering the United States to determine whether the FDA has approved the product, and "whether the manufacturing plant is registered and the drug is listed. '33 ' The FDA can issue Import Alerts, to See supra, Part II.A.iii. FDA's Foreign Inspection Program: Hearing Before the Subcomm. On Oversight and Investigations of the H. Comm. On Energy and Commerce, I10th Cong. 3 (2007) (statement of Carl Nielsen, Former Dir. of ORA's Div. of Imp. Operations and Policy, U.S. Food and Drug Admin.), available at http://archives.energycommerce.house.gov/cmte mtgs/ 110-oi-hrg.110107.Nielsen-Testimony.pdf [hereinafter Statement of Carl Nielsen]. 329 330 331 See id. at 2. 332 21 U.S.C § 360(h)(i) (2009); see also 21 C.F.R. § 207.40(c) (2009). 333 Statement of Andrew von Eschenbach, supra note 91. 334 Overview: Office of InternationalPrograms, supra note 92. 335 Id. 336 Drug Safety: PreliminaryFindings Suggest Weakness in FDA's Programfor Inspecting Foreign Drug Manufacturers:Hearing Before the Subcomm. On Oversight and Investigations of H. Comm. On Energy and Commerce, 109th Cong. 4 (2007) (testimony of Marci Crosse, Dir., Health Care, U.S. Gov't Accountability Off.), available at http://www.gao.gov/ new.items/d08224t.pdf (FDA "is responsible for overseeing the safety and effectiveness of human drugs that are marketed in the U.S., whether they are manufactured in foreign or domestic establishments.") 337 Statement of Andrew von Eschenbach, supra note 91. 338 Id. QUINNIPIAC HEALTH LAW [Vol. 13:117 get "field personnel to pay special attention to 3a39particular product, manufacturer, shipper and/or importer." While the FDA is able to inspect foreign facilities,34 ° the process for doing so is challenging.3 4 ' In some countries, the FDA must receive authorization from the government before entering and inspecting facilities. 4 2 In addition, foreign inspections are costly. 34 3 If passed, the Globalization Act would increase FDA initiatives overseas by requiring the inspection of all drug manufacturing facilities that plan to trade interstate, 34 4 and authoring the imposition of register fees on manufacturers to fund the inspections.34 5 The Globalization Act would also require all drug manufacturing facilities to be inspected before a drug manufactured in the facility is introduced into interstate commerce. The Act would further require country-of-origin labeling,3 4 6 and that facilities develop risk management plans.3 4 7 The FDA would have to oversee and monitor these new initiatives. B. Chinese State Food and DrugAdministration The Chinese State Food and Drug Administration (SFDA) is the FDA's regulatory counterpart in China. In 2001, a revised version of China's 1984 Drug Administration Law3 48 came into effect and vested the SFDA with licensing authority. 34 9 The licensing scheme is complex; it consists of many different levels but it is a necessary prerequisite that a pharmaceutical product manufacturer obtain a manufacturer's license from the SFDA, indicating that its facilities are appropriate for the manufacture 339 Id. 340 Statement of Andrew von Eschenbach, supra note 91. 341 Id. Id. Id. 344 Globalization Act, supra note 81, § 202(a) (2) (A). 345 Id. § 736C. 346 Id. § 206. 347 Id. § 204(b). 348 The Drug Administration Law of the People's Republic of China, enacted in 1984, was "the country's first comprehensive legislation regulating the research, production, and distribution of drugs ... " Qing Zhang, The Chinese Regulatoiy Licensing Regime for PharmaceuticalProducts:A Law and Economics Analysis, 15 MICH. TELECOMM. & TECH. L. Rv. 417, 420 (2009). 349 Qing Zhang, The Chinese Regulatory Licensing Regime for PharmaceuticalProducts: A Law and Economics Analysis, 15 MICH. TELECOMM. & TECH. L. Rv. 417, 421 (2009). 342 343 2009] OVERDOSED AND CONTAMINATED of the product and that quality control arrangements are in place.35 ° Manufacturers are also required to obtain a "Product Permit Number from the SFDA" before "manufactur[ing] a new 351 drug or other drugs regulated by national standards. Yet, the regulatory infrastructure in China is still in its infancy; the Chinese government has been working on revising its cGMP for drugs, while drug manufacturers comply with cGMP's inconsistently.3 52 The United States Commissioner of Food and Drugs stated that the FDA has "limited knowledge of the quality of ingredients and products manufactured in China as this fast growing source is just beginning to put in place a national regulatory infrastructure."3 5' 3 In addition, he stated that from 2003 to 2007 "the number of FDA-registered drug manufacturers in China has at least doubled."'3 54 Around seventy-five to eighty percent of all API's used by United States drug manufacturers are imported from India and China.3 5 5 China is the world's largest producer of the active ingredient in Heparin.35 6 Chinese manufacturers of APIs, who export to the United States, are required to register with Chinese drug regulators. 5 7 However, "[m] ost of the shops that produce the crude Heparin are not licensed or regulated by the [Chinese] Food and Drug Administration"; 358 many times the pig intestines for Heparin are collected and "dried in homes and small factories." 5 9 Thus, "[t]he Chinese government considers [Heparin producers] chemical companies, not drug makers, and therefore not subject to meeting the standards for making drugs 360 in China. Id. Id. 352 Statement of Andrew von Eschenbach, supra note 91. 353 Id. 354 Id. 355 Kristy Barnes, China's API Manufacturers Facing Further Crackdowns, INPHARMATECHNOLOGIST.COM, Dec. 13, 2007, http://www.in-pharmatechnologist.com/ Materials-Formulation/China-s-API-manufacturers-facing-further-crackdowns [hereinafter Barnes.] 356 China Gets Serious about Heparin Contamination, MEDHFADLINES.COM, Mar. 22, 2008, http://medheadlines.com/2008/03/22/china-gets-serious-about-Heparin-conta mination/ [hereinafter China and Heparin Contamination]. 357 Barnes, supra note 355. 358 China and Heparin Contamination, supra note 356. 359 Id.; see also Harris, supra note 39. 360 China and Heparin Contamination, supra note 356. 350 351 164 QUINNIPIAC HEALTH LAW [Vol. 13:117 Furthermore, in China, it is not mandatory to inspect plants that manufacture drugs for export.3 6 Arguably, the SFDA is willing to work with foreign countries "to monitor drug-ingredient production. ' 362 However, the SFDA believes "that based on international practice, 'safeguarding the legality, quality and safety of active pharmaceutical ingredients' is the responsibility of the importing countries. "363 C. Contaminated Heparin Baxter identified the Heparin contaminant as oversulfated chondroitin sulfate, a Heparin-like product derived from animal cartilage that is a derivative of a chemical compound normally sold as a dietary supplement.3 6 4 The contaminant reacts like Heparin, and consequently, it was not detected through traditional tests.3 "6 5 The FDA had to develop a new test, using state-of36 6 the-art technologies in order to isolate the contaminant. When using this new test, Baxter located the site of the contamination - the SPL facility in Changzhou, China.36 7 Recent allegations suggest that contamination of Heparin may have been deliberate. 8 First, the cost of the contaminant used in the drug was markedly less than Heparin. The sulfate cost only twenty dollars per kilogram compared to a cost of $2,000 dollars per kilogram for Heparin.3 69 Second, the means of acquiring the Heparin ingredients was completely unregulated and easy to infect with other ingredients. The Changzhou SPL facility bought "its raw ingredients from a system of consolidators who [bought] the ingredients from thousands of small, unregulated, producers. "370 361 362 Shows, Chinese Supplier Never Checked, supra note 125. Global Supply Chain: Monitoring Quality in China is Not Easy, as Heparin Problem SUPPLY CHAIN DIGEST, Mar. 18, 2008, http://www.scdigest.com/assets/On- Target/08-03-1 8-4.php?cid= 1558&ctype=content. 363 Id. 364 Statement of Janet Woodcock, supra note 35, at 3. 365 Id. 366 Id. 367 Id. 368 Harris, supra note 39. 369 The Heparin Disaster: Chinese Counterfeits and American Failures- Hearing Before the Subcomm. On Oversight and Investigations of the H. Comm. On Energy and Commerce, ll0th Cong. 3 (2008) (staff testimony), available at http://archives.energycommerce.govcmte.mtgs/110-oi-hrg.042908.Nelson-Testimony.pdf [hereinafter Staff Testimony]. 370 China and Heparin Contamination, supra note 356. OVERDOSED AND CONTAMINATED 2009] The FDA approved Baxter's application to change its Heparin manufacturing facility to the one in China, but did not inspect the facility. 371 However, Bob Parkinson, CEO of Baxter, testified before Congress, "[W]e don't rely on FDA inspections to ensure the quality of our product - that's our job. '3 72 Baxter inspected the Chinese facility five months prior to the discovery of the contamination and found that conditions were adequate. 373 The results of Baxter's inspection of the China plant differed significantly from the FDA's when FDA officials eventually toured the Changzhou factory. 374 FDA officials "described find- ings that indicated flaws in record-keeping and a lack of evidence that appropriate steps were being taken to effectively rid crude heparin of possible contaminants."3 7' 5 When the FDA released its inspection report, it stated, "Changzhou SPL's processes for the 'repeated and efficient removal of impurities' have 'not been evaluated' to determine their effectiveness. "376 Furthermore, the report stated, "'manufacturing instructions' followed at the plant were 'incomplete.' 377 D. Using the Heparin Case to Analyze the FDA's Competence The contamination of Heparin shows weaknesses on the part of drug manufacturers (Baxter in particular), Chinese drug regulators, and the FDA to adequately address international drug safety issues. After a series of Congressional hearings on the FDA's ability to oversee foreign drug manufacturers and protect the public, Congressional staff found that "corporate due diligence cannot be relied upon. '3 78 Yet, United States manufacturers have a responsibility to ensure the safety of foreign ingredients that are used to manufacture their finished drug Families Tell U.S. Lawmakers, supra note 36; see also Harris, supra note 39. Testimony of Baxter CEO, supra note 123. 373 Families Tell U.S. Lawmakers, supra note 36. 374 Staff Testimony, supra note 369, at 8. 375 Global Supply Chain: Monitoring Quality in China is Not Easy, as Heparin Problem 371 372 Shows, SUPPLY CHAIN DIGEST, Mar. 18, 2008, http://www.scdigest.com/assets/On- Target/08-03-18-4.php?cid=1558&ctype=content. 376 Id. 377 Id. 378 Staff Testimony, supra note 369, at 7. 166 QUINNIPIAC HEALTH LAW [Vol. 13:117 products.3 79 Baxter performed an inspection of the Chinese facility in September of 2007 and found conditions adequate. Yet, when the FDA performed an inspection soon after, the FDA found quite the opposite. Congressional staff testified that either "Baxter's auditors were less then competent or the facility fell radically out-of-compliance in the few months that elapsed 38 0 between the two inspections. Chinese drug regulators did not certify the Chinese facility that manufactured active ingredients for Baxter's Heparin to make pharmaceutical products, and because the facility was not certified, Chinese drug regulators did not inspect it.381 Furthermore, the FDA stated that "due to confusion over similar-sounding names," the Chinese facility that supplied Baxter's Heparin was mistaken for a previously inspected facility;3 8 2 thus, the reason why the FDA did not inspect the facility before approving Baxter's application to use it as its new Heparin facility. Even if the FDA knew the right name of the facility, there is no guarantee that the facility would have been inspected prior to the importation of Heparin into the United States as the FDA lacks the necessary resources to oversee and inspect all registered foreign manufacturers; the FDA is struggling just to fulfill its domestic initiatives. Former Director of the Office of Regulatory Affair's Division of Import Operations and Policy, Carl Nielsen, stated before Congress, "[T]he current paradigm [for regulation of the foreign drug industry] is grossly inadequate... and is incapable of determining or verifying the safety and efficacy of most imported drug products." '8 3 Nielsen further stated, "Product liability is protecting us more than the FDA's oversight of the international supply of pharmaceu3 84 ticals." Nielsen argues that the current FDA organizational structure largely ignores the foreign industry.' Nielsen estimates, 379 Statement of Andrew von Eschenbach, supra note 91. 380 Staff Testimony, supra note 369, at 9. 381 LegislatorsReview FDA Inspection Policy After Heparin Adverse Reactions, B-NET.COM, Feb. 26, 2008, http://findarticles.com/p/articles/mi_6905/is_/ai_n28539377 [hereinafter Legislators Review FDA Inspection Policy]. 382 Id. 383 Statement of Carl Nielsen, supra note 330, at 2. 384 Id. at 2. 385 Id. at 7. 2009] OVERDOSED AND CONTAMINATED " IT] he inventory of foreign manufacturers of [prescription] finished drugs and API's... range from approximately 3,000 to 6,000 firms. '3 86 With more drug manufacturing occurring offshore, Nielsen laments that the FDA, unfortunately, "has not redeployed, and will not re-deploy significant resources away from the domestic industry to the international arena commensurate with the industry trend," despite external pressure on the agency to do so. 3 8 71 The FDA inspects almost all domestic facilities regu38 9 If larly, 8 but only a few hundred foreign facilities each year. the FDA continues to inspect the foreign drug prescription industry at the rate of two- to three-hundred firms per year, then the manufacturers of [prescription API's] and finished drugs would be competed on an inspection cycle up to 30 years.... Such a cycle would mean a 2-3 day inspection once every 30 years in the worst case to make sure drugs are made in a manner to ensure safety and efficacy. The best case scenario may be approximately a 10 year inspection cycle.... The FDA needs "$250 million per year to inspect every foreign drug manufacturer every other year; "s31 yet, in 2008, the FDA allocated only about eleven million dollars to fund foreign drug manufacturing facility inspections. 9 2 The Government Accountability Office (GAO) audit reported that "China, which has the largest number of drug manufacturers eligible for FDA inspection (714), [was] earmarked for only 13 regulatory visits by the FDA" in 2008, which translates to an examination of "less than 2 per cent of the country's drug exporters. If the Globalization Act is passed, the FDA will have more resources and authority to conduct inspections abroad. Under the Act, fees allocated to foreign drug manufacturers importing 386 387 388 389 Id. at 12. Id. at 6-7. Id. at 6. See generally 21 U.S.C § 374 (2009). Statement of Andrew von Eschenbach, supra note 91. 390 Statement of Carl Nielsen, supra note 330, at 12. 391 HUMPHREY, supra note 273, at 1. 392 Drug Safety: PreliminaryFindingsSuggest Recent J'DA InitiativesHave Potential, but Do Not Fully Address Weaknesses in Its Foreign Drug Inspection Program:Hearing Before the Subcomm. on Oversight and Investigationsof the H. Comm. on Energy and Commerce, 110th Cong. (2008) (statement of Marcia Crosse, Dir., Health Care, U.S. Gov't Accountability Off.), available at http://www.mindfully.org/Health/2008/FDA-Heparin-Chinese22apr8. htm [hereinafter Statement of Marcia Crosse 2]. 393 Barnes, supra note 355. 168 QUINNIPIAC HEALTH LAW [Vol. 13:117 drugs into the United States will fund the necessary inspections.3 9 4 Arguably, if foreign drug manufacturing establishments are inspected more often, this in turn will lead to safer drugs being imported to the United States. However, until the FDA receives more funding to conduct inspections, it should come up with a systematic plan to prioritize which facilities to inspect. Currently, "there is no systematic rationale for choosing which sites to inspect and which to ignore prior to approval by CDER 31' 9 5 of a foreign inspection application. Some argue that the criteria "for prioritizing pre-approval inspections would be geography, complexity of the manufacturing process, and sensitivity of the final drug product."39 6 For example, Congressional staff suggest that Baxter's request to change the manufacturing site of its Heparin from Wisconsin to China "should rank in the highest priority of risks. 39 7 Congressional staff point out that the manufacturing process for Heparin is very complex, in part because the drug's ingredients are extracted from a biological source, and consequently, "manufacturing complexity should have triggered an inspection by FDA before the product was approved for export." ' Also, the staff explains that "heparin is a sterile drug administered to very sick patients ... [b]ecause patients who receive heparin are particularly vulnerable physically, the margin for error in production is virtually zero. 39 9 While following these criteria leads to logical results, the FDA has not used such criteria when prioritizing its site inspections. In addition to a lack of resources and clear criteria for prioritizing which foreign facilities to inspect, the FDA faces diplomatic hurdles in its attempt to oversee foreign drug manufacturing. Congressional investigators claim that Chinese authorities were resistant to inspection of the facilities once contamination was suspected because "Chinese officials have disputed . . . that the contaminant caused death and injury," and have asserted that "if the F.D.A. insists on inspecting Chinese" 395 396 See Globalization Act, supra note 81, § 736C. Staff Testimony, supra note 369, at 6. Id. 397 398 Id. Id. 394 399 Id. at 6-7. 2009] OVERDOSED AND CONTAMINATED facilities, then the Chinese will insist "on the right to inspect American drug plants."4 ° Nevertheless, the FDA was able to negotiate an agreement with China to facilitate inspection of facilities.4"' In December 2007, the Secretary for the Department of Health and Human Services, Michael Leavitt, 40 2 announced the signing of a Memorandum of Agreement (MOA) between the United States and China to improve the safety of drugs and medical devices.40 3 The MOA, among other things, covers registration of facilities with Chinese authorities, information sharing regarding inspectional failures, and under the agreement, "the Chinese will facilitate and expedite inspections by FDA investigators of Chinese drug plants."40 4 However, the agreement only addresses "a fraction of the APIs being imported by China to the US."40 5 In the aftermath of the Heparin contamination, China's SFDA "has implemented a new [regulatory plan] that requires drug manufacturers to recall unsafe drugs voluntarily as soon as they become aware of a problem, in order to minimise their exposure to the supply chain."40 6 More specifically, Under the new recall system, [(1)] pharmaceuticals that are classed as being harmful or potentially fatal which must be recalled within 24 hours of the discovery of a safety issue; [(2)] drugs that may cause temporary or reversible health problems must be recalled within two days; and [(3)] medicines that need to be recalled for non-safety related issues will be required to be removed from circulation within three days.40 7 These rules will "apply to both domestic and foreign manufacturers importing drug products to China."408 In addition, China's SFDA "has issued a directive to the makers of heparin ...to purchase supplies from only registered 400 401 402 403 Harris, supra note 39; see also Statement of Marcia Crosse 2, supra note 392. Statement of Janet Woodcock, supra note 35, at 14. Id. Id. 405 Id. Barnes, supra note 355. 406 407 408 Id. Id. Id. 404 170 QUINNIPIAC HEALTH LAW [Vol. 13:117 suppliers and to strengthen quality control standards."4 9 The agency's directive "calls for the development of a system capable of tracking the raw ingredients from the initial workshop all the way up the supply line to the factory," and is supported by "a similar announcement from the Chinese Ministry of 41 Commerce."" In sum, the Institute for Safe Medication Practices found that, in the case of Heparin, "[t] he scale of injury - hundreds of deaths or serious injuries in a short period - underlines the importance of strengthening oversight of drug manufacture abroad."4 1 ' Increasing the FDA's oversight will help ensure drug safety and may prevent future drug contamination. In addition, the FDA needs to increase the frequency of foreign inspections to ensure safer drugs. To accomplish these goals Congress should enact the Globalization Act of 2009, the FDA should reallocate resources to the foreign sector, and the FDA should continue to facilitate agreements with other countries to promote drug safety. E. Recommendations In order to ensure the safety and effectiveness of drugs manufactured abroad, the following recommendations should be implemented. i. Congress should enact the FDA GlobalizationAct. The Globalization Act, would provide for mandatory inspections of drug facilities.4 1 2 Currently, it is only an agency policy to inspect foreign facilities prior to the approval of a new drug.41 3 Furthermore, the Act would provide the FDA with more monetary resources to conduct the inspections. Thus, the Globalization Act will increase the safety and efficacy of drugs imported into the United States by ensuring that facilities manufacturing the drugs for import into the United States are inspected. 409 China and Heparin Contamination,supra note 356. 410 Id. 411 QUARTER WATCH, supra note 313, at 4. 412 See GlobalizationAct, supra note 81, § 202. 413 Legislators Review FDA Inspection Policy, supra note 381. OVERDOSED AND CONTAMINATED 2009] In addition, the Globalization Act, as currently drafted, contains a provision for country of origin labeling. Such a requirement would increase transparency in the pharmaceutical supply chain and lead to more informed decisions by consumers about the drugs they take. For example, if doctors and patients were aware that Baxter's Heparin API was manufactured in China, and also that the FDA conducts very few inspections of facilities in China, an informed consumer may choose to take a different anticoagulant manufactured in the United States where inspections occur more frequently. In the case of Bonnie and Randy Hubley, this information could have saved their lives. ii. Drug manufacturersshould implement a supply chain threat evaluation system and the FDA should require foreign drug manufacturers to keep detailed records of drug ingredients as they move through the supply chain. The contamination of Heparin was accomplished with a nearly undetectable drug. Drug manufacturers must be aware of the potential supply chain threats and be prepared to address them. In addition, the FDA should require foreign drug manufacturers to keep detailed records of drug ingredients as they move through the supply chain in order to better evaluate and isolate supply chain threats. Ii. If the FDA cannot fulfill its stated obligations with respect to foreign drug manufacturing oversight, it should adopt a policy to encourage drug manufacturers to manufacture drugs domestically instead of abroad. The social and financial costs of foreign inspections are high. Providing an incentive program for drug manufacturers to increase domestic production of drugs would likely increase inspections of domestic facilities and be more cost efficient. It is more costly for the FDA to conduct inspections of foreign facilities. Plus, it strains foreign relationship for the FDA to be dependent on foreign governments' permission to enter the country for the purpose of conducting an inspection. This recommendation, however, would likely be met with resistance QUINNIPIAC HEALTH LAW [Vol. 13:117 from drug manufacturers who continue to out-source production of drug ingredients because they are cheaper abroad than in the United States. However, it still may be in the public interest to domestically manufacture drugs, as the FDA has clearjurisdiction to regulate domestic drug manufacturers and consequently, it can more effectively monitor production and ensure the protection of the nation's health. V. Conclusion Although medical errors kill thousands of people each year, they do not have to. The Heparin case study illustrates the tragic costs of a preventable medical mistake. If the Heparin labels on the vials of the adult doses were more distinguishable from the pediatric doses, the Quaid twins may not have received lifethreatening overdoses of the drug. Drug manufacturers bear the ultimate responsibility for the labels on their products and it is a matter of public health to ensure drugs are adequately labeled for their proscribed use and distinguishable from different concentrations of the same drug. The United States Supreme Court affirmed this duty on the part of drug manufacturers and correctly decided against preemption of state tort lawsuits, thereby preserving the ability of consumers, such as the Quaids, to seek redress for the harm done to them. In addition, drug manufacturers retain ultimate responsibility for their finished drug product, even if the active ingredients are manufactured abroad. Drug manufacturers must take care to evaluate risks in the supply chain, and preserve its integrity to prevent contamination of drugs like Heparin. If Baxter had exercised more diligence, it would have discovered that the facility in China had not been inspected by Chinese drug regulators. Baxter was already aware that the FDA had not inspected the facility.4 14 These risk factors should have militated against Baxter's use of the particular supplier of Heparin's active ingredient. If Baxter had been more assiduous, Bonnie and Randy Hubley may be alive today. Finally, the Heparin case demonstrates the need for FDA reform. The FDA is not adequately equipped to handle over414 Staff Testimony, supra note 369, at 8. 2009] OVERDOSED AND CONTAMINATED 173 sight of the drugs on the market and it needs increased resources to monitor post-market drug safety and exercise oversight of foreign drug manufacturers. If we use the Heparin case study as a platform for reform, we can start to make critical changes to the FDA and the drug industry overall. In doing so, the Heparin-related deaths will no longer be just unfortunate results of preventable medical mistakes. The Heparin tragedies will be the first step of a necessary, long-awaited-for revolution aimed at setting higher standards for drug manufacturing and administration. We do an injustice to families like the Hubleys and the Quaids if we ignore this call for change.
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