Mut. Pharm. Co. v. Bartlett

*475We must decide whether federal law pre-empts the New Hampshire design-defect claim under which respondent Karen Bartlett recovered damages from petitioner Mutual Pharmaceutical, the manufacturer of sulindac, a generic nonsteroidal anti-inflammatory drug (NSAID). New Hampshire law imposes a duty on manufacturers to ensure that the drugs they market are not unreasonably unsafe, and a drug's safety is evaluated by reference to both its chemical properties and the adequacy of its warnings. Because Mutual was unable to change sulindac's composition as a matter of both federal law and basic chemistry, New Hampshire's design-defect cause of action effectively required Mutual to change sulindac's labeling to provide stronger warnings. But, as this Court recognized just two Terms ago in PLIVA, Inc. v. Mensing, 564 U.S. ----, 131 S.Ct. 2567, 180 L.Ed.2d 580 (2011), federal law prohibits generic drug manufacturers from independently changing their drugs' labels. Accordingly, state law imposed a duty on Mutual not to comply with federal law. Under the Supremacy Clause, state laws that require a private party to violate federal law are pre-empted and, thus, are "without effect." Maryland v. Louisiana, 451 U.S. 725, 746, 101 S.Ct. 2114, 68 L.Ed.2d 576 (1981).

The Court of Appeals' solution-that Mutual should simply have pulled sulindac from the market in order to comply with both state and federal law-is no solution. Rather, adopting the Court of Appeals' stop-selling rationale would render impossibility pre-emption a dead letter and work a revolution in this Court's pre-emption case law.

*476Accordingly, we hold that state-law design-defect claims that turn on the adequacy of a drug's warnings are pre-empted by federal law under PLIVA . We thus reverse the decision of the Court of Appeals below.

I

Under the Federal Food, Drug, and Cosmetic Act (FDCA), ch. 675, 52 Stat. 1040, as amended, 21 U.S.C. § 301 et seq., drug manufacturers must gain approval from the United States Food and Drug Administration (FDA) before marketing any drug in interstate commerce. § 355(a). In the case of a new brand-name drug, FDA approval can be secured only by submitting a new-drug application (NDA). An NDA is a compilation of materials that must include "full reports of [all clinical]

*2471investigations," § 355(b)(1)(A), relevant nonclinical studies, and "any other data or information relevant to an evaluation of the safety and effectiveness of the drug product obtained or otherwise received by the applicant from any source," 21 C.F.R. §§ 314.50(d)(2) and (5)(iv) (2012). The NDA must also include "the labeling proposed to be used for such drug," 21 U.S.C. § 355(b)(1)(F) ; 21 C.F.R. § 314.50(c)(2)(i), and "a discussion of why the [drug's] benefits exceed the risks under the conditions stated in the labeling," 21 C.F.R. § 314.50(d)(5)(viii) ; § 314.50(c)(2)(ix). The FDA may approve an NDA only if it determines that the drug in question is "safe for use" under "the conditions of use prescribed, recommended, or suggested in the proposed labeling thereof." 21 U.S.C. § 355(d). In order for the FDA to consider a drug safe, the drug's "probable therapeutic benefits must outweigh its risk of harm." FDA v. Brown & Williamson Tobacco Corp., 529 U.S. 120, 140, 120 S.Ct. 1291, 146 L.Ed.2d 121 (2000).

The process of submitting an NDA is both onerous and lengthy. See Report to Congressional Requesters, Government Accountability Office, Nov. 2006, New Drug Development, 26 Biotechnology L. Rep. 82, 94 (2007) (A typical NDA spans thousands of pages and is based on clinical trials *477conducted over several years). In order to provide a swifter route for approval of generic drugs, Congress passed the Drug Price Competition and Patent Term Restoration Act of 1984, 98 Stat. 1585, popularly known as the "Hatch-Waxman Act." Under Hatch-Waxman, a generic drug may be approved without the same level of clinical testing required for approval of a new brand-name drug, provided the generic drug is identical to the already-approved brand-name drug in several key respects.

First, the proposed generic drug must be chemically equivalent to the approved brand-name drug: it must have the same "active ingredient" or "active ingredients," "route of administration," "dosage form," and "strength" as its brand-name counterpart. 21 U.S.C. §§ 355(j)(2)(A)(ii) and (iii). Second, a proposed generic must be "bioequivalent" to an approved brand-name drug. § 355(j)(2)(A)(iv). That is, it must have the same "rate and extent of absorption" as the brand-name drug. § 355(j)(8)(B). Third, the generic drug manufacturer must show that "the labeling proposed for the new drug is the same as the labeling approved for the [approved brand-name] drug." § 355(j)(2)(A)(v).

Once a drug-whether generic or brand-name-is approved, the manufacturer is prohibited from making any major changes to the "qualitative or quantitative formulation of the drug product, including active ingredients, or in the specifications provided in the approved application." 21 C.F.R. § 314.70(b)(2)(i). Generic manufacturers are also prohibited from making any unilateral changes to a drug's label. See §§ 314.94(a)(8)(iii), 314.150(b)(10) (approval for a generic drug may be withdrawn if the generic drug's label "is no longer consistent with that for [the brand-name] drug").

II

In 1978, the FDA approved a nonsteroidal anti-inflammatory pain reliever called "sulindac" under the brand name Clinoril. When Clinoril's patent expired, the FDA

*478approved several generic sulindacs, including one manufactured by Mutual Pharmaceutical. 678 F.3d 30, 34 (C.A.1 2012) (case below); App. to Pet. for Cert. 144a-145a. In a very small number of patients, NSAIDs-including both sulindac and popular NSAIDs such as ibuprofen, naproxen, and Cox2-inhibitors-have the serious side effect of causing two hypersensitivity skin *2472reactions characterized by necrosis of the skin and of the mucous membranes: toxic epidermal necrolysis, and its less severe cousin, Stevens-Johnson Syndrome. 678 F.3d, at 34, 43-44; Dorland's Illustrated Medical Dictionary 1872 (31st ed. 2007); Physicians' Desk Reference 146-147, 597 (6th ed. 2013); Friedman, Orlet, Still, & Law, Toxic Epidermal Necrolysis Due to Administration of Celecobix (Celebrex ), 95 Southern Medical J. 1213, 1213-1214 (2002).

In December 2004, respondent Karen L. Bartlett was prescribed Clinoril for shoulder pain. Her pharmacist dispensed a generic form of sulindac, which was manufactured by petitioner Mutual Pharmaceutical. Respondent soon developed an acute case of toxic epidermal necrolysis. The results were horrific. Sixty to sixty-five percent of the surface of respondent's body deteriorated, was burned off, or turned into an open wound. She spent months in a medically induced coma, underwent 12 eye surgeries, and was tube-fed for a year. She is now severely disfigured, has a number of physical disabilities, and is nearly blind.

At the time respondent was prescribed sulindac, the drug's label did not specifically refer to Stevens-Johnson Syndrome or toxic epidermal necrolysis, but did warn that the drug could cause "severe skin reactions" and "[f]atalities." App. 553; 731 F.Supp.2d 135, 142 (D.N.H.2010) (internal quotation marks omitted). However, Stevens-Johnson Syndrome and toxic epidermal necrolysis were listed as potential adverse reactions on the drug's package insert. 678 F.3d, at 36, n. 1. In 2005-once respondent was already suffering from toxic epidermal necrolysis -the FDA completed a "comprehensive review of the risks and benefits, *479[including the risk of toxic epidermal necrolysis ], of all approved NSAID products." Decision Letter, FDA Docket No. 2005P-0072/CP1, p. 2 (June 22, 2006), online at http://www.fda.gov/ohrms/dockets/dockets/05p0072/05p-0072-pav0001-vol1.pdf (as visited June 18, 2013, and available in Clerk of Court's case file). As a result of that review, the FDA recommended changes to the labeling of all NSAIDs, including sulindac, to more explicitly warn against toxic epidermal necrolysis. App. 353-354, 364, 557-561, 580, and n. 8.

Respondent sued Mutual in New Hampshire state court, and Mutual removed the case to federal court. Respondent initially asserted both failure-to-warn and design-defect claims, but the District Court dismissed her failure-to-warn claim based on her doctor's "admi[ssion] that he had not read the box label or insert." 678 F.3d, at 34. After a 2-week trial on respondent's design-defect claim, a jury found Mutual liable and awarded respondent over $21 million in damages.

The Court of Appeals affirmed. 678 F.3d 30. As relevant, it found that neither the FDCA nor the FDA's regulations pre-empted respondent's design-defect claims. It distinguished PLIVA, Inc. v. Mensing, 564 U.S. ----, 131 S.Ct. 2567 -in which the Court held that failure-to-warn claims against generic manufacturers are pre-empted by the FDCA's prohibition on changes to generic drug labels-by arguing that generic manufacturers facing design-defect claims could simply "choose not to make the drug at all" and thus comply with both federal and state law. 678 F.3d, at 37. We granted certiorari. 568 U.S. ----, 133 S.Ct. 694, 184 L.Ed.2d 496 (2012).

III

The Supremacy Clause provides that the laws and treaties of the United States "shall be the supreme Law of the Land ... any Thing in the Constitution or *2473Laws of any State to the Contrary notwithstanding." U.S. Const., Art. VI, cl. 2. Accordingly, it has long been settled that state laws that *480conflict with federal law are "without effect." Maryland v. Louisiana, 451 U.S., at 746, 101 S.Ct. 2114; McCulloch v. Maryland, 4 Wheat. 316, 427, 4 L.Ed. 579 (1819). See also Gade v. National Solid Wastes Management Assn., 505 U.S. 88, 108, 112 S.Ct. 2374, 120 L.Ed.2d 73 (1992) ("[U]nder the Supremacy Clause, from which our pre-emption doctrine is derived, any state law, however clearly within a State's acknowledged power, which interferes with or is contrary to federal law, must yield" (internal quotation marks omitted)).

Even in the absence of an express pre-emption provision, the Court has found state law to be impliedly pre-empted where it is "impossible for a private party to comply with both state and federal requirements." English v. General Elec. Co., 496 U.S. 72, 79, 110 S.Ct. 2270, 110 L.Ed.2d 65 (1990). See also Florida Lime & Avocado Growers, Inc . v. Paul, 373 U.S. 132, 142-143, 83 S.Ct. 1210, 10 L.Ed.2d 248 (1963) ("A holding of federal exclusion of state law is inescapable and requires no inquiry into congressional design where compliance with both federal and state regulations is a physical impossibility for one engaged in interstate commerce").

In the instant case, it was impossible for Mutual to comply with both its state-law duty to strengthen the warnings on sulindac's label and its federal-law duty not to alter sulindac's label. Accordingly, the state law is pre-empted.

A

We begin by identifying petitioner's duties under state law. As an initial matter, respondent is wrong in asserting that the purpose of New Hampshire's design-defect cause of action "is compensatory, not regulatory." Brief for Respondent 19. Rather, New Hampshire's design-defect cause of action imposes affirmative duties on manufacturers.

Respondent is correct that New Hampshire has adopted the doctrine of strict liability in tort as set forth in Section 402A of the Restatement (Second) of Torts. See 2 Restatement (Second) of Torts § 402A (1963 and 1964) (hereinafter Restatement 2d). See Buttrick v. Arthur Lessard & Sons, Inc., 110 N.H. 36, 37-39, 260 A.2d 111, 112-113 (1969).

*481Under the Restatement-and consequently, under New Hampshire tort law-"[o]ne who sells any product in a defective condition unreasonably dangerous to the user or consumer or to his property is subject to liability for physical harm thereby caused" even though he "has exercised all possible care in the preparation and sale of the product." Restatement 2d § 402A, at 347-348.

But respondent's argument conflates what we will call a "strict-liability" regime (in which liability does not depend on negligence, but still signals the breach of a duty) with what we will call an "absolute-liability" regime (in which liability does not reflect the breach of any duties at all, but merely serves to spread risk). New Hampshire has adopted the former, not the latter. Indeed, the New Hampshire Supreme Court has consistently held that the manufacturer of a product has a "duty to design his product reasonably safely for the uses which he can foresee." Thibault v. Sears, Roebuck & Co., 118 N.H. 802, 809, 395 A.2d 843, 847 (1978). See also Reid v. Spadone Mach. Co., 119 N.H. 457, 465, 404 A.2d 1094, 1099 (1979) ("In New Hampshire, the manufacturer is under a general duty to design his product reasonably safely for the uses which he can foresee" (internal quotation marks omitted));

*2474Chellman v. Saab-Scania AB, 138 N.H. 73, 78, 637 A.2d 148, 150 (1993) ("The duty to warn is part of the general duty to design, manufacture and sell products that are reasonably safe for their foreseeable uses"); cf. Simoneau v. South Bend Lathe, Inc., 130 N.H. 466, 469, 543 A.2d 407, 409 (1988) ("We limit the application of strict tort liability in this jurisdiction by continuing to emphasize that liability without negligence is not liability without fault"); Price v. BIC Corp., 142 N.H. 386, 390, 702 A.2d 330, 333 (1997) (cautioning "that the term 'unreasonably dangerous' should not be interpreted so broadly as to impose absolute liability on manufacturers or make them insurers of their products"). Accordingly, respondent is incorrect in arguing that New Hampshire's strict-liability system *482"imposes no substantive duties on manufacturers." Brief for Respondent 19.1

B

That New Hampshire tort law imposes a duty on manufacturers is clear. Determining the content of that duty requires somewhat more analysis. As discussed below in greater detail, New Hampshire requires manufacturers to ensure that the products they design, manufacture, and sell are not "unreasonably dangerous." The New Hampshire Supreme Court has recognized that this duty can be satisfied either by changing a drug's design or by changing its labeling. Since Mutual did not have the option of changing sulindac's design, New Hampshire law ultimately required it to change sulindac's labeling.

Respondent argues that, even if New Hampshire law does impose a duty on drug manufacturers, that duty does not encompass either the "duty to change sulindac's design" or the duty "to change sulindac's labeling." Brief for Respondent 30 (capitalization and emphasis deleted). That argument cannot be correct. New Hampshire imposes design-defect liability only where "the design of the product created a defective condition unreasonably dangerous to the user."

*483Vautour v. Body Masters Sports Industries, Inc., 147 N.H. 150, 153, 784 A.2d 1178, 1181 (2001) ; Chellman, supra, at 77, 637 A.2d, at 150. To determine whether a product is "unreasonably dangerous," the New Hampshire Supreme Court employs a "risk-utility approach" under which "a product is defective as designed if the magnitude of the danger outweighs the utility of the product." Vautour, supra, at 154, 784 A.2d, at 1182 (internal quotation marks omitted). That risk-utility approach requires a "multifaceted balancing process involving evaluation of many conflicting factors." Ibid. (internal quotation marks omitted); see also Thibault,supra, at 809, 395 A.2d, at 847 (same).

*2475While the set of factors to be considered is ultimately an open one, the New Hampshire Supreme Court has repeatedly identified three factors as germane to the risk-utility inquiry: "the usefulness and desirability of the product to the public as a whole, whether the risk of danger could have been reduced without significantly affecting either the product's effectiveness or manufacturing cost, and the presence and efficacy of a warning to avoid an unreasonable risk of harm from hidden dangers or from foreseeable uses." Vautour,supra, at 154, 784 A.2d, at 1182; see also Price, supra, at 389, 702 A.2d, at 333 (same); Chellman, supra, at 77-78, 637 A.2d, at 150 (same).

In the drug context, either increasing the "usefulness" of a product or reducing its "risk of danger" would require redesigning the drug: A drug's usefulness and its risk of danger are both direct results of its chemical design and, most saliently, its active ingredients. See 21 C.F.R. § 201.66(b)(2) (2012) ("Active ingredient means any component that is intended to furnish pharmacological activity or other direct effect in the diagnosis, cure, mitigation, treatment, or prevention of disease, or to affect the structure of any function of the body of humans" (italics deleted)).

In the present case, however, redesign was not possible for two reasons. First, the FDCA requires a generic drug to have the same active ingredients, route of administration, *484dosage form, strength, and labeling as the brand-name drug on which it is based. 21 U.S.C. §§ 355(j)(2)(A)(ii) - (v) and (8)(B) ; 21 C.F.R. § 320.1(c). Consequently, the Court of Appeals was correct to recognize that "Mutual cannot legally make sulindac in another composition." 678 F.3d, at 37. Indeed, were Mutual to change the composition of its sulindac, the altered chemical would be a new drug that would require its own NDA to be marketed in interstate commerce. See 21 C.F.R. § 310.3(h) (giving examples of when the FDA considers a drug to be new, including cases involving "newness for drug use of any substance which composes such drug, in whole or in part"). Second, because of sulindac's simple composition, the drug is chemically incapable of being redesigned. See 678 F.3d, at 37 ("Mutual cannot legally make sulindac in another composition (nor it is apparent how it could alter a one-molecule drug anyway)").

Given the impossibility of redesigning sulindac, the only way for Mutual to ameliorate the drug's "risk-utility" profile-and thus to escape liability-was to strengthen "the presence and efficacy of [sulindac's ] warning" in such a way that the warning "avoid[ed] an unreasonable risk of harm from hidden dangers or from foreseeable uses." Vautour, supra, at 154, 784 A.2d, at 1182. See also Chellman, 138 N.H., at 78, 637 A.2d, at 150 ("The duty to warn is part of the general duty to design, manufacture and sell products that are reasonably safe for their foreseeable uses. If the design of a product makes a warning necessary to avoid an unreasonable risk of harm from a foreseeable use, the lack of warning or an ineffective warning causes the product to be defective and unreasonably dangerous" (citation omitted)). Thus, New Hampshire's design-defect cause of action imposed a duty on Mutual to strengthen sulindac's warnings.

For these reasons, it is unsurprising that allegations that sulindac's label was inadequate featured prominently at trial. Respondent introduced into evidence both the label for *485Mutual's sulindac at the time of her injuries and the label as revised in 2005 (after respondent had suffered her injuries). App. 553-556. Her counsel's opening statement informed the jury that "the evidence will show you that Sulindac *2476was unreasonably dangerous and had an inadequate warning, as well.... You will hear much more evidence about why this label was inadequate in relation to this case." Tr. 110-112 (Aug. 17, 2010). And, the District Court repeatedly instructed the jury that it should evaluate sulindac's labeling in determining whether Mutual's sulindac was unreasonably dangerous. See App. 514 (jury instruction that the jury should find "a defect in design" only if it found that "Sulindac was unreasonably dangerous and that a warning was not present and effective to avoid that unreasonable danger"); ibid . (jury instruction that no design defect exists if "a warning was present and effective to avoid that unreasonable danger"). Finally, the District Court clarified in its order and opinion denying Mutual's motion for judgment as a matter of law that the adequacy of sulindac's labeling had been part of what the jury was instructed to consider. 760 F.Supp.2d 220, 231 (2011) ("if the jury found that sulindac's risks outweighed its benefits, then it could consider whether the warning-regardless of its adequacy-reduced those risks ... to such an extent that it eliminated the unreasonable danger").2 *486Thus, in accordance with New Hampshire law, the jury was presented with evidence relevant to, and was instructed to consider, whether Mutual had fulfilled its duty to label sulindac adequately so as to render the drug not "unreasonably dangerous." In holding Mutual liable, the jury determined that Mutual had breached that duty.

C

The duty imposed by federal law is far more readily apparent. As PLIVA made clear, federal law prevents generic drug manufacturers from changing their labels. See 564 U.S., at ----, 131 S.Ct., at 2577 ("Federal drug regulations, as interpreted by the FDA, prevented the Manufacturers from independently changing their generic drugs' safety labels"). See also 21 U.S.C. § 355(j)(2)(A)(v) ("[T]he labeling proposed for the new drug is the same as the labeling approved for the [approved brand-name] drug"); 21 C.F.R. §§ 314.94(a)(8)(iii), 314.150(b)(10) (approval for a generic drug may be withdrawn if the generic drug's label "is no longer consistent with that for [the brand-name] drug"). Thus, federal law prohibited Mutual from taking the remedial action required to avoid liability under New Hampshire law.

D

When federal law forbids an action that state law requires, the state law *2477is "without effect." Maryland, 451 U.S., at 746, 101 S.Ct. 2114. Because it is impossible for Mutual and other similarly *487situated manufacturers to comply with both state and federal law,3 New Hampshire's warning-based design-defect cause of action is pre-empted with respect to FDA-approved drugs sold in interstate commerce.4 *488IV

The Court of Appeals reasoned that Mutual could escape the impossibility of complying with both its federal- and state-law duties by "choos[ing] not to make [sulindac] at all." 678 F.3d, at 37. We reject this "stop-selling" rationale as incompatible with our pre-emption jurisprudence. Our pre-emption cases presume that an actor seeking to satisfy both his federal- and state-law obligations is not required to cease acting altogether in order to avoid liability. Indeed, if the option of ceasing to act defeated a claim of impossibility, impossibility pre-emption would be "all but meaningless." 564 U.S., at ----, 131 S.Ct., at 2579.

The incoherence of the stop-selling theory becomes plain when viewed through the lens of our previous cases. In every instance in which the Court has found impossibility pre-emption, the "direct conflict" between federal- and state-law duties could easily have been avoided if the regulated actor had simply ceased acting.

*2478PLIVA is an obvious example: As discussed above, the PLIVA Court held that state failure-to-warn claims were pre-empted by the FDCA because it was impossible for drug manufacturers like PLIVA to comply with both the state-law duty to label their products in a way that rendered them reasonably safe and the federal-law duty not to change their drugs' labels. Id., at ----, 131 S.Ct., at 2577-2578. It would, of course, have been possible for drug manufacturers like PLIVA to pull their products from the market altogether. In so doing, they would have avoided liability under both state and federal law: such manufacturers would neither have labeled their products in a way that rendered them unsafe nor impermissibly changed any federally approved label.