Oral argument: Mar. 30, 2011
Appealed from: United States Court of Appeals for the Eighth Circuit (Nov. 27, 2009); United States Court of Appeals for the Fifth Circuit (Jan. 8, 2010)
DRUGS, FAILURE-TO-WARN, FOOD, DRUG, AND COSMETIC ACT, FEDERAL PREEMPTION, HATCH-WAXMAN ACT
Doctors prescribed both Gladys Mensing and Julie Demahy the drug Reglan. They each had their prescriptions filled with the generic equivalent of the name brand drug. After long-term use of this generic drug, Mensing and Demahy developed severe neurologic disorders. The women separately sued Pliva and Actavis, the generic drug manufacturers, making state law failure-to-warn claims, alleging that the drug’s warning label failed to adequately warn them of the risks. Pliva and Actavis argue that the federal Food, Drug, and Cosmetic Act, along with Food and Drug Administration regulations that govern the entire drug approval and labeling process, preempt Mensing and Demahy’s state law claims because it was impossible for Pliva and Actavis to comply with both federal and state law. The companies argue that they could not provide additional warnings beyond what the brand manufacturer provided on its label. In deciding this case, the Supreme Court will ultimately have to weigh the costs born by generic drug manufacturers and the public against the benefits of incentivizing manufacturers to create safer drugs with more complete warnings.
Pliva, Inc. v. Mensing
The Drug Price Competition and Patent Term Restoration Act (the "Hatch-Waxman Amendments"), which amended the federal Food, Drug, and Cosmetic Act ("FDCA") allow for the approval of low-cost generic versions of previously approved drug products through an abbreviated application process.
The question presented is:
Whether the Eighth Circuit abrogated the Hatch-Waxman Amendments by allowing state tort liability for failure to warn in direct contravention of the Act's requirement that a generic drug's labeling be the same as the FDA-approved labeling for the listed (or branded) drug.
Actavis Elizabeth, LLC v. Mensing
The Drug Price Competition and Patent Term Restoration Act (the "Hatch-Waxman Amendments" to the Food, Drug and Cosmetic Act (FDCA)) and its implementing regulations require a generic drug manufacturer to maintain the labeling for a generic the "same as" the labeling for the "brand" or "listed" drug that is its bioequivalent. See 21 U.S.C. 9 §355(j)(2)(A)(iv-v); 21 C.F.R. § 314.94(a)(8).
The question presented is whether the Eighth Circuit Court of Appeals misinterpreted that requirement and the doctrine of conflict preemption when it concluded that generic drug manufacturers could be held liable under state law for failing to strengthen the warnings in the labeling for the generic drug.
Actavis, Inc. v. Demahy
Are the states preempted under the Supremacy Clause of the Constitution from requiring additional safety information on a generic product label where the brand has not changed its label?
1. Can a generic drug manufacturer be liable for a state-law failure-to-warn claim even though, in compliance with the federal Food, Drug, and Cosmetic Act, its label is the same as that of its name brand equivalent?
2. Does the Food, Drug, and Cosmetic Act, along with the regulations promulgated by the Food and Drug Administration, preempt any state-law failure-to-warn claim where a generic label does not include safety information above and beyond that of the brand label?
Before marketing a new drug, a manufacturer must submit a new drug application to the Food and Drug Administration (“FDA”). See Mensing v. Wyeth, Inc., 588 F.3d 603, 605 (8th Cir. 2009). This application includes the results from clinical trials and a mock label displaying the drug’s use, warnings, and possible negative effects. See id. at 605–06. In 1984, Congress amended the Food, Drug, and Cosmetic Act (“FDCA”) to include the Abbreviated New Drug Application which, after the expiration of the name brand drug’s patent, allows generic drugs to expediently reach the market at a lower price. See id. at 606. This is possible because these amendments, called the Hatch-Waxman Amendments, exempt generic drug manufacturers from conducting costly clinical trials. See id. Instead, generic drug manufacturers must show that the generic drug’s composition and label are the “same as” that of the name brand drug. See id.
In 1980, the FDA approved the marketing of a drug called Reglan. See id. Five years later, the FDA approved the sale of metoclopramide, the generic version of Reglan. See id. For all relevant purposes, the metoclopramide label has been the same as Reglan’s label. See id. Further, neither drug changed its label warning regarding the risks of tardive dyskinesia, a neurological movement disorder, from the initial approval of the generic drug until 2007. See id.
In 2001, Gladys Mensing was prescribed Reglan to treat her diabetic gastroparesis. See Mensing, 588 F.3d at 605. Her prescription was filled with metoclopramide, Reglan’s generic equivalent. See id. Mensing took metoclopramide for four years before developing tardive dyskinesia. See id. at 604–05. Mensing sued the manufacturers of metoclopramide, including Actavis Elizabeth and Pliva, alleging that the manufacturers failed to adequately warn her of the long-term usage risks in violation of state tort law. See id. at 605. Actavis Elizabeth and Pliva moved to dismiss the case. See id. Despite never having ingested the brand name drug, Mensing also sued the manufacturers of Reglan, who moved for summary judgment. See id. The United States District Court of the District of Minnesota held that the FDCA’s requirement that generic labels match their name brand counterparts preempted Mensing’s failure-to-warn claim because the claim would require the generic label to differ from the name brand label. See id. The district court granted the Reglan manufacturers summary judgment as Mensing never took their drug. See id. On appeal, the United States Court of Appeals for the Eighth Circuit upheld the district court’s decision as to the brand name manufacturer. See id. at 603. However, the appeals court reversed the dismissal of the claims against the generic producers, stating that, despite the language of the FDCA, Mensing had viable failure-to-warn claims against Actavis Elizabeth and Pliva. See id. at 614.
Julie Demahy was prescribed Reglan to treat her gastroesophageal reflux. See Demahy v. Actavis, Inc., 593 F.3d 428, 430 (5th Cir. 2010). Demahy’s prescription was also filled with metoclopramide, the generic version of Reglan. See id. Demahy took metoclopramide for four years before developing tardive dyskinesia, which she attributes to her long-term use of the drug. See id. Demahy sued Actavis, Inc., the generic drug manufacturer, alleging that Actavis violated state tort law by failing to warn her of the long-term dangers associated with metoclopramide. See id. Actavis moved to dismiss Demahy’s claims, alleging that these state law duties were preempted due to their conflict with the federal law governing generic drug labeling. See id. The United States District Court for the Eastern District of Louisiana denied Actavis’ motion to dismiss and held that Demahy’s failure-to-warn claims were not preempted. See id. On appeal, the United States Court of Appeals for the Fifth Circuit upheld the district court’s decision, concluding that Demahy’s claim is not preempted because the state-imposed duties to warn did not conflict with the federal law. See id.
The Supreme Court granted certiorari, consolidating the two Mensing claims with the Demahy case, to determine if federal law preempts state law from requiring that a generic drug label include additional safety information not found on the label of its name brand counterpart. See Actavis Elizabeth, LLC v. Mensing, 131 S. Ct. 817 (2010); Pliva, Inc. v. Mensing, 131 S. Ct. 817 (2010); Actavis, Inc. v. Demahy, 131 S. Ct. 817 (2010).
In 1984, Congress amended the Food, Drug, and Cosmetic Act (“FDCA”) to implement the Abbreviated New Drug Application (“ANDA”) for generic drug approval by the Food and Drug Administration (“FDA”). See Demahy v. Actavis, Inc., 593 F.3d 428, 432 (5th Cir. 2010). The ANDA requires a generic drug to be the “same as” its FDA-approved name brand equivalent, thereby exempting generic manufacturers from conducting costly clinical trials. See id. In adopting this application process, Congress sought to balance competition and costs against the need for research. See id. Petitioners Actavis, Inc. and Actavis Elizabeth (collectively “Actavis”) and Pliva, along with their amici curiae, contend that the FDA has monitoring procedures to ensure generic drugs display adequate warning labels, and that allowing state-law failure-to-warn claims will unnecessarily raise generic drug costs. See, e.g., Brief of Amici Curiae Morton Grove Pharmaceuticals, Inc. and Impax Laboratories, Inc. (“Morton”) in Support of Petitioners at 28, 32–34. In contrast, Respondents Gladys Mensing and Julie Demahy (collectively “Mensing”) allege that failing to hold generic drug manufacturers liable under state tort law actually discourages manufacturers from creating safe generic drugs, increases health care costs, and creates uncertainty in the safety of generic drugs. See Brief for Respondents, Gladys Mensing and Julie Demahy at 49–51.
What Will be the Impact on the FDA and Generic Drug Manufacturers?
The Generic Pharmaceutical Association (“GPhA”) contends that requiring individual generic drug manufacturers to alter their labels pursuant to state-law tort claims will be counterproductive to the FDA’s mission of streaming safe, affordable generic drugs into the market. See Brief of Amicus Curiae Generic Pharmaceutical Association in Support of Petitioners at 20. Instead of receiving the relevant reports of drug incidents from generic drug manufacturers, as is the current FDA practice, the GPhA argues that the FDA would instead be flooded with irrelevant drug information from manufacturers seeking to limit their state-law liability. See id. at 30. Furthermore, Morton Grove Pharmaceuticals (“Morton”), a generic drug manufacturer, asserts that because generic drugs are interstate products, their warnings will no longer be uniformly controlled by the FDA but instead will be governed by the “most warning-happy [s]tate.” See Brief of Morton at 25. Actavis contends that an additional burden will be thrust upon generic drug manufacturers because these manufacturers may now be sued without proof that they had any knowledge of safety risks unknown to the FDA. See Brief for Petitioners Actavis at 31.
Mensing argues that state tort law will complement the FDA legislation. See Brief for Respondents at 48–49. The FDA has limited resources, yet is responsible for monitoring more than 10,000 drugs on the market. See id. at 48. Allowing state-law failure-to-warn claims, Mensing states, will assist the FDA in its regulation by providing additional protections for consumers and additional encouragement for manufacturers to create the safest drugs with the most informative warning labels. See id. at 48–49. The United States, writing as amicus curiae, contends that if the Supreme Court rules that these state tort claims are preempted by federal law, it will diminish the incentive for generic drug manufacturers to provide the most current safety information to the FDA. See Brief of Amicus Curiae United States in Support of Respondents at 28–29. This is problematic, Mensing argues, because many drug risks are unknown when the generic drug is initially approved for sale. See Brief for Respondents at 50.
What Will be the Costs to the Public?
Morton contends that allowing state tort claims in this area will negatively impact the public. See Brief of Morton at 30–31. Morton argues that the FDA’s goals will be thwarted because generic drug prices will increase if these manufacturers are required to assume the burden of warning changes. See id. at 28. The GPhA asserts that even requiring generic drug manufacturers to survey scientific literature, as seemingly suggested by Mensing, can increase costs for consumers. See Brief of Generic Pharmaceutical Association at 18–19. According to Morton, consumers may face these costs in several ways, including: increased generic drug prices, decreased competition, and fewer options as manufacturers buckle under this new burden. See Brief of Morton at 30–31. Another concern, Pliva contends, is that state tort claims may alter just one manufacturer’s label, thereby allowing different manufacturers to have varying warning labels for the same drug. See Brief for Petitioners Pliva at 35.
Mensing argues that if the Court finds federal law preempts these state tort claims, the public will suffer the consequences. See Brief for Respondents at 49–51. Several states writing as amici curiae contend that when generic drug manufacturers are not liable for injuries caused by their failure to warn, the health care system and, consequently, patients bear the cost. See Brief of Amici Curiae Minnesota, Louisiana, et al. in Support of Respondents at 26–27. The American Medical Association further argues that doctors will be less willing to prescribe generic drugs, in place of their more expensive name brand counterparts, if generic drug manufacturers are not required to update their own labels. See Brief of Amici Curiae American Medical Association, et al. in Support of Respondents at 28–30. Finally, Mensing also asserts that there will not be a significant price increase for generic drugs if state tort claims are not preempted. See Brief for Respondents at 49.
The Federal Food, Drug, and Cosmetic Act of 1938 (“FDCA”) gives the Food and Drug Administration (“FDA”) oversight and approval authority for the safety of all new drugs. See Mensing v. Wyeth, Inc., 588 F.3d 603, 605 (8th Cir. 2009). In 1984, Congress amended the FDCA with the Drug Price Competition and Patent Restoration Act (popularly known as the “Hatch-Waxman Amendments”) and set up a streamlined Abbreviated New Drug Application (“ANDA”) for manufacturers to obtain approval for generic versions of branded drugs. See id. at 606. The FDA approves these generic versions only when the labeling of the generic drug is “the same” as the labeling for the branded drug. See 21 U.S.C. § 355(j)(2)(A)(v); Demahy v. Actavis, Inc., 593 F.3d 428, 432 (5th Cir. 2010).
Respondents Gladys Mensing and Julie Demahy (collectively “Mensing”), alleging injuries from generic versions of branded drugs, made successful claims against generic drug manufacturers under failure-to-warn state tort laws. See Mensing, 588 F.3d at 614; Demahy, 593 F.3d at 449. Such claims are valid only if federal law does not preempt them. Under the Supremacy Clause of the Constitution, however, a state law is preempted if Congress expressly provides for it, or if it is impossible to comply with both the state and the federal laws. See U.S. Const. art. VI. § 2.
May Generic Drug Labels Ever Deviate from Branded Drug Labels?
Petitioner Pliva, Inc., a generic drug manufacturer, argues that the Hatch-Waxman Amendments require the labels of a generic drug to be “the same” as those on the branded drug. See Brief for Petitioners, Pliva, Inc. et al. at 32–36. That is, while the FDA allows label variations as to manufacturer name and expiration date, Pliva argues that it does not permit any deviation for the warnings on the label. See 21 C.F.R. § 314.94(a)(8)(iv); Brief for Petitioners Pliva at 13, 32–33. Moreover, Pliva asserts, the FDA specifically rejected such a permissive warning-deviation proposal during the rulemaking notice-and-comment period on both statutory and public policy grounds. Brief for Petitioners Pliva at 13. Petitioners Actavis Elizabeth and Actavis, Inc. (collectively “Actavis”) agree and assert that “[t]his consistent labeling requirement applies at all times,” even after a generic drug enters the market. See Brief for Petitioners Actavis at 21. If the branded manufacturer changes its label, the generic manufacturer must also change its label, and the FDA may remove the generic drug from the market if it fails to make the alteration. Id. at 21–22; 21 C.F.R. §§ 314.70 & 314.150(b)(10). Though a generic manufacturer must make the labeling change through the “changes being effected” (“CBE”) process—that is, make the changes while FDA approval is pending—Actavis and Pliva maintain that the CBE process does not allow generic manufacturers to make unilateral label changes. See Brief for Petitioners Actavis at 19, 23–24; Brief for Petitioners Pliva at 17, 36–42. Only branded manufacturers with access to detailed clinical trials and in receipt of adverse reaction reports, Pliva and Actavis argue, have FDCA and FDA authority to make unilateral changes to the warning label. See Brief for Petitioners Actavis at 16, 20 n.13; Brief for Petitioners Pliva at 17, 38, 51.
In contrast, Respondents Mensing assert that FDA regulations promulgated under the Hatch-Waxman Amendments make it clear that generic labels need to be “generally the same” as a branded drug only at the time of approval. See Brief for Respondents, Gladys Mensing and Julie Demahy at 12; 21 C.F.R. § 314.94(a)(8)(iv). Even so, Mensing argues, this “sameness” requirement does not exempt a generic manufacturer from the FDCA requirement that its label bear “adequate warnings.” See Brief for Respondents at 12; 21 U.S.C. § 352(f)(2). Accordingly, a generic manufacturer has a duty to notify the FDA and to change its label—through, for example, the CBE process—if at any time it has “reasonable evidence” of a need for stronger warnings, even if the brand manufacturer has not changed its label. See Brief for Respondents at 29, 49; 21 C.F.R. § 201.57(e). In contrast to generic manufacturers’ claims that they do not have sufficient clinical information to alter labels, Mensing claims that adverse event reports and various published literature provide the “reasonable evidence” required by the FDA to mandate a label change. See Brief for Respondents at 49. Moreover, the FDA has made it clear, Mensing argues, that it will not punish a generic manufacturer for making a unilateral label change that is in the interest of public safety. See id. at 16–17, 33–34.
Preemption: Did Congress Intend for the Hatch-Waxman Amendments to Preempt State Law?
Actavis argues that, when read together, the FDCA and the FDA’s implementing regulations about generic labels clearly preempt any state law failure-to-warn claims against generic manufacturers. See Brief for Petitioners Actavis at 5, 18–26. The Hatch-Waxman Amendments, Actavis asserts, demonstrate Congress’s intention that generic drug manufacturers “rely on the safety and effectiveness information that the brand submitted” in its approval application, not being subject to any additional duties under state tort laws. Id. at 5, 18–26. Similarly, Pliva argues that Congress intended the Hatch-Waxman Amendments to preempt state law because the alternative is unreasonable: Congress could not have intended that the streamlined ANDA process, in which generic manufacturers need not conduct clinical trials or otherwise develop “comprehensive data” that would enable them to knowledgeably alter labels, open generic manufacturers to liability under state law. See Brief for Petitioners Pliva at 38–39.
In contrast, Mensing argues that had Congress wished to exempt generic drug manufacturers from state tort liability, it could have included an express preemption clause in the Hatch-Waxman Amendments. See Brief for Respondents at 25. When it enacted the Hatch-Waxman Amendments, Mensing asserts, Congress certainly knew of state tort litigation in this arena and could have given the FDA sole authority over drug safety issues had it thought that was appropriate. See id. The alternative, Mensing argues, is unfair: since federal law provides no remedy to persons injured by generic drugs, Congress would not have preempted state law, which has “long regulated public health and safety” through the tort system, without expressly so providing. See id. at 26–27.
Preemption: Is it Possible for Generic Drug Manufacturers to Comply with Both State and Federal Drug Label Warning Laws?
Pliva and Actavis argue that state failure-to-warn laws are preempted in the generic drug labeling arena because it is impossible for a manufacturer to comply with both state and federal laws. See Brief for Petitioners Pliva at 43; Brief for Petitioners Actavis at 18–21. Because Mensing’s state law claims seek to punish petitioners for failing to do what federal law forbids, Pliva claims, such claims are squarely preempted. Brief for Petitioners Pliva at 43. Generic drug manufacturers, Pliva argues, are in an entirely different situation than the brand manufacturer in Wyeth v. Levine; in this case the Supreme Court held that the FDCA did not preempt state law claims because a brand “manufacturer bears responsibility for the content of its label at all times.” 129 S. Ct. 1187, 1197–98 (2009); Brief for Petitioners Pliva at 51. Unlike brand manufacturers, Pliva and Actavis assert, which may unilaterally alter their labels through CBE or other processes, generic manufacturers are limited by the FDCA and FDA requirements to keeping their labels “the same” as those of the brand. See Brief for Petitioners Pliva at 36–42; Brief for Petitioners Actavis at 19, 23–24. While neither the FDCA nor the FDA regulations forbid a generic manufacturer from “suggesting” to the FDA that a label should change, Pliva argues, state law cannot hold a generic manufacturer liable for failing to make such suggestions to a federal agency, not least because such claims would “usurp” the FDA’s congressionally-delegated authority. See Brief for Petitioners Pliva at 47–49. Accordingly, Pliva and Actavis argue, generic manufacturers cannot comply with state laws in this arena, so those laws are preempted. See Brief for Petitioners Pliva at 43; Brief for Petitioners Actavis at 21–24.
Mensing, in contrast, argues that it was possible for Pliva and Actavis to comply with both state and federal law, so the FDCA and FDA regulations do not preempt state failure-to-warn claims. See Brief for Respondents at 27–28. Like brand manufacturers subject to state law claims under Wyeth, Mensing asserts, generic manufacturers have a variety of means at their disposal to notify the FDA of needed label changes and to make those label changes themselves, independent of anything the brand manufacturer does. See id. at 28–30, 45; 21 C.F.R. § 201.57(e). Providing an adequate warning label is both the brand and generic drug manufacturer’s duty, Mensing insists, and because the FDCA and FDA do not prohibit the generic manufacturer from using various methods—such as requesting that the FDA approve a stronger label or sending a letter directly to health care providers—generic manufacturers can be held liable under state law for failing to adequately warn an injured user. See Brief for Respondents at 28–37; 21 U.S.C. § 352(f)(2). Moreover, Mensing claims, the “FDA would have treated such a request promptly and seriously.” See Brief for Respondents at 30.
This case will resolve whether a generic drug manufacturer who has complied with federal requirements that its label parallel that of the brand drug can still be liable under a state failure-to-warn claim on the ground that its label was inadequate. Respondents Mensing and Demahy argue that Petitioners Pliva and Actavis were required to offer additional warnings on its labels because Congress clearly did not intend for the Hatch-Waxman Amendments to the Food, Drug, and Cosmetic Act to preempt state law. Pliva and Actavis argue, in contrast, that the FDA’s regulations overseeing the entire drug approval and labeling process preempt Mensing and Demahy’s state law claims because it was legally impossible for Pliva and Actavis to comply with both federal and state law. The Supreme Court’s decision will clarify federal preemption doctrine and the scope of generic drug manufacturers’ responsibilities to the persons prescribed their drugs.
Edited by: Sarah Chon
· LII: Food and Drug Law