PLIVA, INC. v. MENSING

Opinion of the Court

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SUPREME COURT OF THE UNITED STATES
_________________

Nos. 09–993, 09–1039, and 09–1501

_________________

PLIVA, INC., ET AL., PETITIONERS
v.
GLADYS MENSING

09–993

ACTAVIS ELIZABETH, LLC, PETITIONER
09–1039
v.
GLADYS MENSING

09–1501

ACTAVIS, INC., PETITIONER
v.
JULIE DEMAHY

ON WRITS OF CERTIORARI TO THE UNITED STATES COURTS OF
APPEALS FOR THE EIGHTH AND FIFTH CIRCUITS

[June 23, 2011]

JUSTICE THOMAS delivered the opinion of the Court, ex ­ cept as to Part III–B–2.*

These consolidated lawsuits involve state tort-law claims based on certain drug manufacturers’ alleged fail ­ ure to provide adequate warning labels for generic meto ­ clopramide. The question presented is whether federal drug regulations applicable to generic drug manufacturers directly conflict with, and thus pre-empt, these state-law claims. We hold that they do. I

Metoclopramide is a drug designed to speed the move ­ ment of food through the digestive system. The Food and Drug Administration (FDA) first approved metoclopra ­ mide tablets, under the brand name Reglan, in 1980. Five years later, generic manufacturers also began producing meto­ clopramide. The drug is commonly used to treat digestive tract problems such as diabetic gastroparesis and gastroesophageal reflux disorder.

Evidence has accumulated that long-term metoclopra ­ mide use can cause tardive dyskinesia, a severe neurologi ­ cal disorder. Studies have shown that up to 29% of pa ­ tients who take metoclopramide for several years develop this condition. McNeil v. Wyeth, 462 F. 3d 364, 370, n. 5 (CA5 2006); see also Shaffer, Butterfield, Pamer, & Mackey, Tardive Dyskinesia Risks and Metoclopramide Use Before and After U. S. Market Withdrawal of Cis ­ apride, 44 J. Am. Pharmacists Assn. 661, 663 (2004) (not ­ ing 87 cases of metoclopramide-related tardive dyskinesia reported to the FDA’s adverse event reporting system by mid-2003).

Accordingly, warning labels for the drug have been strengthened and clarified several times. In 1985, the label was modified to warn that “tardive dyskinesia . . . may develop in patients treated with metoclopramide,” and the drug’s package insert added that “[t]herapy longer than 12 weeks has not been evaluated and cannot be recommended.” Physician’s Desk Reference 1635–1636 (41st ed. 1987); see also Brief for Petitioner PLIVA et al. 21–22 (hereinafter PLIVA Brief). In 2004, the brand ­ name Reglan manufacturer requested, and the FDA ap­ proved, a label change to add that “[t]herapy should not exceed 12 weeks in duration.” Brief for United States as Amicus Curiae 8 (hereinafter U. S. Brief). And in 2009, the FDA ordered a black box warning—its strongest— which states: “Treatment with metoclopramide can cause tardive dyskinesia, a serious movement disorder that is often irreversible. . . . Treatment with metoclopramide for longer than 12 weeks should be avoided in all but rare cases.” See Physician’s Desk Reference 2902 (65th ed. 2011).

Gladys Mensing and Julie Demahy, the plaintiffs in these consolidated cases, were prescribed Reglan in 2001 and 2002, respectively. Both received generic metoclo ­ pramide from their pharmacists. After taking the drug as prescribed for several years, both women developed tardive dyskinesia.

In separate suits, Mensing and Demahy sued the ge ­ neric drug manufacturers that produced the metoclopra ­ mide they took (Manufacturers). Each alleged, as relevant here, that long-term metoclopramide use caused her tar ­ dive dyskinesia and that the Manufacturers were liable under state tort law (specifically, that of Minnesota and Louisiana) for failing to provide adequate warning labels. They claimed that “despite mounting evidence that long term metoclopramide use carries a risk of tardive dyskine ­ sia far greater than that indicated on the label,” none of the Manufacturers had changed their labels to adequately warn of that danger. Mensing v. Wyeth, Inc., 588 F. 3d 603, 605 (CA8 2009); see also Demahy v. Actavis, Inc., 593 F. 3d 428, 430 (CA5 2010).

In both suits, the Manufacturers urged that federal law pre-empted the state tort claims. According to the Manu ­ facturers, federal statutes and FDA regulations required them to use the same safety and efficacy labeling as their brand-name counterparts. This means, they argued, that it was impossible to simultaneously comply with both federal law and any state tort-law duty that required them to use a different label.

The Courts of Appeals for the Fifth and Eighth Circuits rejected the Manufacturers’ arguments and held that Men­ sing and Demahy’s claims were not pre-empted. See 588 F. 3d, at 614; 593 F. 3d, at 449. We granted certiorari, 562 U. S. ___ (2010), consolidated the cases, and now reverse each.

II

Pre-emption analysis requires us to compare federal and state law. We therefore begin by identifying the state tort duties and federal labeling requirements applicable to the Manufacturers.

A

It is undisputed that Minnesota and Louisiana tort law require a drug manufacturer that is or should be aware of its product’s danger to label that product in a way that renders it reasonably safe. Under Minnesota law, which applies to Mensing’s lawsuit, “where the manufacturer . . . of a product has actual or constructive knowledge of danger to users, the . . . manufacturer has a duty to give warning of such dangers.” Frey v. Montgomery Ward & Co., 258 N. W. 2d 782, 788 (Minn. 1977). Similarly, under Louisiana law applicable to Demahy’s lawsuit, “a manu ­ facturer’s duty to warn includes a duty to provide ade ­ quate instructions for safe use of a product.” Stahl v. Novartis Pharmaceuticals Corp., 283 F. 3d 254, 269–270 (CA5 2002); see also La. Rev. Stat. Ann. §9:2800.57 (West 2009). In both States, a duty to warn falls specifically on the manufacturer. See Marks v. OHMEDA, Inc., 2003– 1446, pp. 8–9 (La. App. 3/31/04), 871 So. 2d 1148, 1155; Gray v. Badger Min. Corp., 676 N. W. 2d 268, 274 (Minn. 2004).

Mensing and Demahy have pleaded that the Manufac ­ turers knew or should have known of the high risk of tardive dyskinesia inherent in the long-term use of their product. They have also pleaded that the Manufacturers knew or should have known that their labels did not ade ­ quately warn of that risk. App. 437–438, 67–69, 94–96. The parties do not dispute that, if these allegations are true, state law required the Manufacturers to use a differ ­ ent, safer label.

B

Federal law imposes far more complex drug labeling requirements. We begin with what is not in dispute. Under the 1962 Drug Amendments to the Federal Food, Drug, and Cosmetic Act, 76 Stat. 780, 21 U. S. C. §301 et seq., a manufacturer seeking federal approval to market a new drug must prove that it is safe and effective and that the proposed label is accurate and adequate.1 See, e.g., 21 U. S. C. §§355(b)(1), (d); Wyeth v. Levine, 555 U. S. 555, 567 (2009). Meeting those requirements involves costly and lengthy clinical testing. §§355(b)(1)(A), (d); see also D. Beers, Generic and Innovator Drugs: A Guide to FDA Approval Requirements §2.02[A] (7th ed. 2008).

Originally, the same rules applied to all drugs. In 1984, however, Congress passed the Drug Price Competition and Patent Term Restoration Act, 98 Stat. 1585, commonly called the Hatch-Waxman Amendments. Under this law, “generic drugs” can gain FDA approval simply by showing equivalence to a reference listed drug that has already been approved by the FDA.2 21 U. S. C. §355(j)(2)(A). This allows manufacturers to develop generic drugs in ­ expensively, without duplicating the clinical trials already performed on the equivalent brand-name drug. A generic drug application must also “show that the [safety and efficacy] labeling proposed . . . is the same as the labeling approved for the [brand-name] drug.” §355(j)(2)(A)(v); see also §355(j)(4)(G); Beers §§3.01, 3.03[A].

As a result, brand-name and generic drug manufactur ­ ers have different federal drug labeling duties. A brand ­ name manufacturer seeking new drug approval is respon­ sible for the accuracy and adequacy of its label. See, e.g., 21 U. S. C. §§355(b)(1), (d); Wyeth, supra, at 570–571. A manufacturer seeking generic drug approval, on the other hand, is responsible for ensuring that its warning label is the same as the brand name’s. See, e.g., §355(j)(2)(A)(v); §355(j)(4)(G); 21 CFR §§314.94(a)(8), 314.127(a)(7).

The parties do not disagree. What is in dispute is whether, and to what extent, generic manufacturers may change their labels after initial FDA approval. Mensing and Demahy contend that federal law provided several avenues through which the Manufacturers could have altered their metoclopramide labels in time to prevent the injuries here. The FDA, however, tells us that it inter ­ prets its regulations to require that the warning labels of a brand-name drug and its generic copy must always be the same—thus, generic drug manufacturers have an ongoing federal duty of “sameness.” U. S. Brief 16; see also 57 Fed. Reg. 17961 (1992) (“[T]he [generic drug’s] labeling must be the same as the listed drug product’s labeling because the listed drug product is the basis for [generic drug] ap ­ proval”). The FDA’s views are “controlling unless plainly erroneous or inconsistent with the regulation[s]” or there is any other reason to doubt that they reflect the FDA’s fair and considered judgment. Auer v. Robbins, 519 U. S. 452, 461, 462 (1997) (internal quotation marks omitted).3 1

First, Mensing and Demahy urge that the FDA’s “changes-being-effected” (CBE) process allowed the Manu ­ facturers to change their labels when necessary. See Brief for Respondents 33–35; see also 593 F. 3d, at 439–444; Gaeta v. Perrigo Pharmaceuticals Co., 630 F. 3d 1225, 1231 (CA9 2011); Foster v. American Home Prods. Corp., 29 F. 3d 165, 170 (CA4 1994). The CBE process permits drug manufacturers to “add or strengthen a contraindica ­ tion, warning, [or] precaution,” 21 CFR §314.70(c)(6)(iii)(A) (2006), or to “add or strengthen an instruction about dos ­ age and administration that is intended to increase the safe use of the drug product,” §314.70(c)(6)(iii)(C). When making labeling changes using the CBE process, drug man­ ufacturers need not wait for preapproval by the FDA, which ordinarily is necessary to change a label. Wyeth, supra, at 568. They need only simultaneously file a sup ­ plemental application with the FDA. 21 CFR §314.70(c)(6).

The FDA denies that the Manufacturers could have used the CBE process to unilaterally strengthen their warning labels. The agency interprets the CBE regulation to allow changes to generic drug labels only when a ge ­ neric drug manufacturer changes its label to match an updated brand-name label or to follow the FDA’s instruc ­ tions. U. S. Brief 15, 16, n. 7 (interpreting 21 CFR §314.94(a)(8)(iv)); U. S. Brief 16, n. 8. The FDA argues that CBE changes unilaterally made to strengthen a generic drug’s warning label would violate the statutes and regulations requiring a generic drug’s label to match its brand-name counterpart’s. Id., at 15–16; see also 21 U. S. C. §355(j)(4)(G); 21 CFR §§314.94(a)(8)(iii), 314.150(b)(10) (approval may be withdrawn if the generic drug’s label “is no longer consistent with that for [the brand-name]”).

We defer to the FDA’s interpretation of its CBE and generic labeling regulations. Although Mensing and Demahy offer other ways to interpret the regulations, see Brief for Respondents 33–35, we do not find the agency’s interpretation “plainly erroneous or inconsistent with the regulation.” Auer, supra, at 461 (internal quotation marks omitted). Nor do Mensing and Demahy suggest there is any other reason to doubt the agency’s reading. We there ­ fore conclude that the CBE process was not open to the Manufacturers for the sort of change required by state law.

2

Next, Mensing and Demahy contend that the Manufac ­ turers could have used “Dear Doctor” letters to send ad ­ ditional warnings to prescribing physicians and other healthcare professionals. See Brief for Respondents 36; 21 CFR §200.5. Again, the FDA disagrees, and we defer to the agency’s views.

The FDA argues that Dear Doctor letters qualify as “labeling.” U. S. Brief 18; see also 21 U. S. C. §321(m); 21 CFR §202.1(l)(2). Thus, any such letters must be “consis ­ tent with and not contrary to [the drug’s] approved . . . labeling.” 21 CFR §201.100(d)(1). A Dear Doctor letter that contained substantial new warning information would not be consistent with the drug’s approved labeling. Moreover, if generic drug manufacturers, but not the brand-name manufacturer, sent such letters, that would inaccurately imply a therapeutic difference between the brand and generic drugs and thus could be impermissibly “misleading.” U. S. Brief 19; see 21 CFR §314.150(b)(3) (FDA may withdraw approval of a generic drug if “the labeling of the drug . . . is false or misleading in any particular”).

As with the CBE regulation, we defer to the FDA. Mensing and Demahy offer no argument that the FDA’s interpretation is plainly erroneous. See Auer, 519 U. S., at 461. Accordingly, we conclude that federal law did not permit the Manufacturers to issue additional warnings through Dear Doctor letters.

3

Though the FDA denies that the Manufacturers could have used the CBE process or Dear Doctor letters to strengthen their warning labels, the agency asserts that a different avenue existed for changing generic drug la ­ bels. According to the FDA, the Manufacturers could have proposed—indeed, were required to propose—stronger warning labels to the agency if they believed such warn ­ ings were needed. U. S. Brief 20; 57 Fed. Reg. 17961. If the FDA had agreed that a label change was necessary, it would have worked with the brand-name manufacturer to create a new label for both the brand-name and generic drug. Ibid.

The agency traces this duty to 21 U. S. C. §352(f)(2), which provides that a drug is “misbranded . . . [u]nless its labeling bears . . . adequate warnings against . . . unsafe dosage or methods or duration of administration or appli ­ cation, in such manner and form, as are necessary for the protection of users.” See U. S. Brief 12. By regulation, the FDA has interpreted that statute to require that “labeling shall be revised to include a warning as soon as there is reasonable evidence of an association of a serious hazard with a drug.” 21 CFR §201.57(e).

According to the FDA, these requirements apply to ge ­ neric drugs. As it explains, a “ ‘central premise of federal drug regulation is that the manufacturer bears re ­ sponsibility for the content of its label at all times.’ ” U. S. Brief 12–13 (quoting Wyeth, 555 U. S., at 570–571). The FDA reconciles this duty to have adequate and accurate labeling with the duty of sameness in the following way: Generic drug manufacturers that become aware of safety problems must ask the agency to work toward strengthen ­ ing the label that applies to both the generic and brand ­ name equivalent drug. U. S. Brief 20.

The Manufacturers and the FDA disagree over whether this alleged duty to request a strengthened label actually existed. The FDA argues that it explained this duty in the preamble to its 1992 regulations implementing the HatchWaxman Amendments. Ibid.; see 57 Fed. Reg. 17961 (“If a [generic drug manufacturer] believes new safety infor ­ mation should be added to a product’s labeling, it should contact FDA, and FDA will determine whether the label ­ ing for the generic and listed drugs should be revised”). The Manufacturers claim that the FDA’s 19-year-old statement did not create a duty, and that there is no evi ­ dence of any generic drug manufacturer ever acting pur ­ suant to any such duty. See Tr. of Oral Arg. 19–24; Reply Brief for Petitioner PLIVA et al. 18–22. Because we ultimately find pre-emption even assuming such a duty existed, we do not resolve the matter.

C

To summarize, the relevant state and federal require ­ ments are these: State tort law places a duty directly on all drug manufacturers to adequately and safely label their products. Taking Mensing and Demahy’s allegations as true, this duty required the Manufacturers to use a different, stronger label than the label they actually used. Federal drug regulations, as interpreted by the FDA, prevented the Manufacturers from independently chang ­ ing their generic drugs’ safety labels. But, we assume, federal law also required the Manufacturers to ask for FDA assistance in convincing the brand-name manufac ­ turer to adopt a stronger label, so that all corresponding generic drug manufacturers could do so as well. We turn now to the question of pre-emption. III

The Supremacy Clause establishes that federal law “shall be the supreme Law of the Land . . . any Thing in the Constitution or Laws of any State to the Contrary notwithstanding.” U. S. Const., Art. VI, cl. 2. Where state and federal law “directly conflict,” state law must give way. Wyeth, supra, at 583 (THOMAS, J., concurring in judgment); see also Crosby v. National Foreign Trade Council, 530 U. S. 363, 372 (2000) (“[S]tate law is natu ­ rally preempted to the extent of any conflict with a federal statute”). We have held that state and federal law conflict where it is “impossible for a private party to comply with both state and federal requirements.”4 Freightliner Corp. v. Myrick, 514 U. S. 280, 287 (1995) (internal quotation marks omitted).5

A

We find impossibility here. It was not lawful under federal law for the Manufacturers to do what state law required of them. And even if they had fulfilled their federal duty to ask for FDA assistance, they would not have satisfied the requirements of state law.

If the Manufacturers had independently changed their labels to satisfy their state-law duty, they would have violated federal law. Taking Mensing and Demahy’s allegations as true, state law imposed on the Manufac­ turers a duty to attach a safer label to their generic meto ­ clopramide. Federal law, however, demanded that ge ­ neric drug labels be the same at all times as the corres ­ ponding brand-name drug labels. See, e.g., 21 CFR §314.150(b)(10). Thus, it was impossible for the Manufac ­ turers to comply with both their state-law duty to change the label and their federal law duty to keep the label the same.

The federal duty to ask the FDA for help in strengthen ­ ing the corresponding brand-name label, assuming such a duty exists, does not change this analysis. Although requesting FDA assistance would have satisfied the Man ­ ufacturers’ federal duty, it would not have satisfied their state tort-law duty to provide adequate labeling. State law demanded a safer label; it did not instruct the Manufacturers to communicate with the FDA about the possibility of a safer label. Indeed, Mensing and Demahy deny that their state tort claims are based on the Manu ­ facturers’ alleged failure to ask the FDA for assistance in changing the labels. Brief for Respondents 53–54; cf. Buckman Co. v. Plaintiffs’ Legal Comm., 531 U. S. 341 (2001) (holding that federal drug and medical device laws pre-empted a state tort-law claim based on failure to properly communicate with the FDA).

B

1

Mensing and Demahy contend that, while their state ­ law claims do not turn on whether the Manufacturers asked the FDA for assistance in changing their labels, the Manufacturers’ federal affirmative defense of pre-emption does. Mensing and Demahy argue that if the Manufactur ­ ers had asked the FDA for help in changing the corre ­ sponding brand-name label, they might eventually have been able to accomplish under federal law what state law requires. That is true enough. The Manufacturers “freely concede” that they could have asked the FDA for help. PLIVA Brief 48. If they had done so, and if the FDA decided there was sufficient supporting information, and if the FDA undertook negotiations with the brand-name manufacturer, and if adequate label changes were decided on and implemented, then the Manufacturers would have started a Mouse Trap game that eventually led to a better label on generic metoclopramide.

This raises the novel question whether conflict pre ­ emption should take into account these possible actions by the FDA and the brand-name manufacturer. Here, what federal law permitted the Manufacturers to do could have changed, even absent a change in the law itself, depending on the actions of the FDA and the brand-name manufac ­ turer. Federal law does not dictate the text of each ge ­ neric drug’s label, but rather ties those labels to their brand-name counterparts. Thus, federal law would permit the Manufacturers to comply with the state labeling re ­ quirements if, and only if, the FDA and the brand-name manufacturer changed the brand-name label to do so.

Mensing and Demahy assert that when a private party’s ability to comply with state law depends on approval and assistance from the FDA, proving pre-emption requires that party to demonstrate that the FDA would not have allowed compliance with state law. Here, they argue, the Manufacturers cannot bear their burden of proving impos ­ sibility because they did not even try to start the process that might ultimately have allowed them to use a safer label. Brief for Respondents 47. This is a fair argument, but we reject it.

The question for “impossibility” is whether the private party could independently do under federal law what state law requires of it. See Wyeth, 555 U. S., at 573 (finding no pre-emption where the defendant could “unilaterally” do what state law required). Accepting Mensing and Demahy’s argument would render conflict pre-emption largely meaningless because it would make most conflicts between state and federal law illusory. We can often imagine that a third party or the Federal Government might do something that makes it lawful for a private party to accomplish under federal law what state law requires of it. In these cases, it is certainly possible that, had the Manufacturers asked the FDA for help, they might have eventually been able to strengthen their warn ­ ing label. Of course, it is also possible that the Manufac ­ turers could have convinced the FDA to reinterpret its regulations in a manner that would have opened the CBE process to them. Following Mensing and Demahy’s argu ­ ment to its logical conclusion, it is also possible that, by asking, the Manufacturers could have persuaded the FDA to rewrite its generic drug regulations entirely or talked Congress into amending the Hatch-Waxman Amendments.

If these conjectures suffice to prevent federal and state law from conflicting for Supremacy Clause purposes, it is unclear when, outside of express pre-emption, the Su ­ premacy Clause would have any force.6 We do not read the Supremacy Clause to permit an approach to pre ­ emption that renders conflict pre-emption all but mean ­ ingless. The Supremacy Clause, on its face, makes federal law “the supreme Law of the Land” even absent an ex ­ press statement by Congress. U. S. Const., Art. VI, cl. 2. 2

Moreover, the text of the Clause—that federal law shall be supreme, “any Thing in the Constitution or Laws of any State to the Contrary notwithstanding”—plainly contem ­ plates conflict pre-emption by describing federal law as effectively repealing contrary state law. Ibid.; see Nelson, Preemption, 86 Va. L. Rev. 225, 234 (2000); id., at 252–253 (describing discussion of the Supremacy Clause in state ratification debates as concerning whether federal law could repeal state law, or vice versa). The phrase “any [state law] to the Contrary notwithstanding” is a non obstante provision. Id., at 238–240, nn. 43–45. Eighteenth ­ century legislatures used non obstante provisions to specify the degree to which a new statute was meant to repeal older, potentially conflicting statutes in the same field. Id., at 238–240 (citing dozens of statutes from the 1770’s and 1780’s with similar provisions). A non obstante provision “in a new statute acknowledged that the statute might contradict prior law and instructed courts not to apply the general presumption against implied repeals.” Id., at 241–242; 4 M. Bacon, A New Abridgment of the Law 639 (4th ed. 1778) (“Although two Acts of Parliament are seemingly repugnant, yet if there be no Clause of non Obstante in the latter, they shall if possible have such Construction, that the latter may not be a Repeal of the former by Implication”). The non obstante provision in the Supremacy Clause therefore suggests that federal law should be understood to impliedly repeal conflicting state law.

Further, the provision suggests that courts should not strain to find ways to reconcile federal law with seemingly conflicting state law. Traditionally, courts went to great lengths attempting to harmonize conflicting statutes, in order to avoid implied repeals. Warder v. Arell, 2 Va. 282, 296 (1796) (opinion of Roane, J.) (“[W]e ought to seek for such a construction as will reconcile [the statutes] to ­ gether”); Ludlow’s Heirs v. Johnston, 3 Ohio 553, 564 (1828) (“[I]f by any fair course of reasoning the two [stat ­ utes] can be reconciled, both shall stand”); Doolittle v. Bryan, 14 How. 563, 566 (1853) (requiring “the repug ­ nance be quite plain” before finding implied repeal). A non obstante provision thus was a useful way for legisla ­ tures to specify that they did not want courts distorting the new law to accommodate the old. Nelson, supra, at 240–242; see also J. Sutherland, Statutes and Statutory Construction §147, p. 199 (1891) (“[W]hen there is inserted in a statute a provision [of non obstante] . . . . It is to be supposed that courts will be less inclined against recogniz­ ing repugnancy in applying such statutes”); Weston’s Case, 73 Eng. Rep. 780, 781 (K. B. 1576) (“[W]hen there are two statutes, one in appearance crossing the other, and no clause of non obstante is contained in the second statute . . . the exposition ought to be that both should stand in force”); G. Jacob, A New Law Dictionary (J. Morgan ed., 10th ed. 1782) (definition of “statute,” ¶6: “[W]hen there is a seeming variance between two statutes, and no clause of non obstante in the latter, such construction shall be made that both may stand”). The non obstante provision of he Supremacy Clause indicates that a court need look no further than “the ordinary meanin[g]” of federal law, and should not distort federal law to accommodate conflicting state law. Wyeth, 555 U. S., at 588 (THOMAS, J., concur ­ ring in judgment) (internal quotation marks omitted).

To consider in our pre-emption analysis the contingen ­ cies inherent in these cases—in which the Manufacturers’ ability to comply with state law depended on uncertain federal agency and third-party decisions—would be incon ­ sistent with the non obstante provision of the Supremacy Clause. The Manufacturers would be required continually to prove the counterfactual conduct of the FDA and brand ­ name manufacturer in order to establish the supremacy of federal law. We do not think the Supremacy Clause con ­ templates that sort of contingent supremacy. The non obstante provision suggests that pre-emption analysis should not involve speculation about ways in which fed ­ eral agency and third-party actions could potentially reconcile federal duties with conflicting state duties. When the “ordinary meaning” of federal law blocks a private party from independently accomplishing what state law requires, that party has established pre-emption.

3

To be sure, whether a private party can act sufficiently independently under federal law to do what state law requires may sometimes be difficult to determine. But this is not such a case. Before the Manufacturers could satisfy state law, the FDA—a federal agency—had to undertake special effort permitting them to do so. To decide these cases, it is enough to hold that when a party cannot satisfy its state duties without the Federal Government’s special permission and assistance, which is dependent on the exercise of judgment by a federal agency, that party can ­ not independently satisfy those state duties for pre ­ emption purposes.

Here, state law imposed a duty on the Manufacturers to take a certain action, and federal law barred them from taking that action. The only action the Manufacturers could independently take—asking for the FDA’s help—is not a matter of state-law concern. Mensing and Demahy’s tort claims are pre-empted.

C

Wyeth is not to the contrary. In that case, as here, the plaintiff contended that a drug manufacturer had breached a state tort-law duty to provide an adequate warning label. 555 U. S., at 559–560. The Court held that the lawsuit was not pre-empted because it was possible for Wyeth, a brand-name drug manufacturer, to comply with both state and federal law. Id., at 572–573.7 Specifically, the CBE regulation, 21 CFR §314.70(c)(6)(iii), permitted a brand-name drug manufacturer like Wyeth “to unilater ­ ally strengthen its warning” without prior FDA approval. 555 U. S., at 573; cf. supra, at 7–8. Thus, the federal regulations applicable to Wyeth allowed the company, of its own volition, to strengthen its label in compliance with its state tort duty.8

We recognize that from the perspective of Mensing and Demahy, finding pre-emption here but not in Wyeth makes little sense. Had Mensing and Demahy taken Reglan, the brand-name drug prescribed by their doctors, Wyeth would control and their lawsuits would not be pre-empted. But because pharmacists, acting in full accord with state law, substituted generic metoclopramide instead, federal law pre-empts these lawsuits. See, e.g., Minn. Stat. §151.21 (2010) (describing when pharmacists may substitute ge ­ neric drugs); La. Rev. Stat. Ann. §37:1241(A)(17) (West 2007) (same). We acknowledge the unfortunate hand that federal drug regulation has dealt Mensing, Demahy, and others similarly situated.9

But “it is not this Court’s task to decide whether the statutory scheme established by Congress is unusual or even bizarre.” Cuomo v. Clearing House Assn., L. L. C., 557 U. S. ___, ___ (2009) (THOMAS, J., concurring in part and dissenting in part) (slip op., at 21) (internal quotation marks and brackets omitted). It is beyond dispute that the federal statutes and regulations that apply to brand ­ name drug manufacturers are meaningfully different than those that apply to generic drug manufacturers. Indeed, it is the special, and different, regulation of generic drugs that allowed the generic drug market to expand, bringing more drugs more quickly and cheaply to the public. But different federal statutes and regulations may, as here, lead to different pre-emption results. We will not distort the Supremacy Clause in order to create similar pre ­ emption across a dissimilar statutory scheme. As always, Congress and the FDA retain the authority to change the law and regulations if they so desire.

* * *

The judgments of the Fifth and Eighth Circuits are reversed, and the cases are remanded for further proceed ­ ings consistent with this opinion. It is so ordered. * JUSTICE KENNEDY joins all but Part III–B–2 of this opinion.

1 All relevant events in these cases predate the Food and Drug Administration Amendments Act of 2007, 121 Stat. 823. We therefore refer exclusively to the pre-2007 statutes and regulations and express no view on the impact of the 2007 Act.

2 As we use it here, “generic drug” refers to a drug designed to be a copy of a reference listed drug (typically a brand-name drug), and thus identical in active ingredients, safety, and efficacy. See, e.g., United States v. Generix Drug Corp., 460 U. S. 453, 454–455 (1983); 21 CFR §314.3(b) (2006) (defining “reference listed drug”).

3 The brief filed by the United States represents the views of the FDA. Cf. Talk America, Inc. v. Michigan Bell Telephone Co., 564 U. S. ___, ___, n. 1 (2011) (slip op., at 1, n. 1); Chase Bank USA, N. A. v. McCoy, 562 U. S. ___, ___ (2011) (slip op., at 8). Although we defer to the agency’s interpretation of its regulations, we do not defer to an agency’s ultimate conclusion about whether state law should be pre-empted. Wyeth v. Levine, 555 U. S. 555, 576 (2009).

4 We do not address whether state and federal law “directly conflict” in circumstances beyond “impossibility.” See Wyeth, 555 U. S., at 582, 590–591 (THOMAS, J., concurring in judgment) (suggesting that they might).

5 The Hatch-Waxman Amendments contain no provision expressly pre-empting state tort claims. See post, at 9, 19 (SOTOMAYOR, J., dissenting). Nor do they contain any saving clause to expressly pre­ serve state tort claims. Cf. Williamson v. Mazda Motor of America, Inc., 562 U. S. ___, ___ (2011) (THOMAS, J., concurring in judgment) (discussing the saving clause in the National Traffic and Motor Vehicle Safety Act of 1966, 49 U. S. C. §30103(e)). Although an express state ­ ment on pre-emption is always preferable, the lack of such a statement does not end our inquiry. Contrary to the dissent’s suggestion, the absence of express pre-emption is not a reason to find no conflict pre­ emption. See post, at 19.

6 The dissent asserts that we are forgetting “purposes-and-objectives” pre-emption. Post, at 15–16. But as the dissent acknowledges, pur ­ poses-and-objectives pre-emption is a form of conflict pre-emption. Post, at 9, 16. If conflict pre-emption analysis must take into account hypothetical federal action, including possible changes in Acts of Congress, then there is little reason to think that pre-emption based on the purposes and objectives of Congress would survive either.

7 Wyeth also urged that state tort law “creat[ed] an unacceptable ‘obstacle to the accomplishment and execution of the full purposes and objectives of Congress.’ ” 555 U. S., at 563–564 (quoting Hines v. Davidowitz, 312 U. S. 52, 67 (1941)). The Court rejected that argu ­ ment, and that type of pre-emption is not argued here. Cf. post, at 16, n. 13 (opinion of SOTOMAYOR, J.).

8 The FDA, however, retained the authority to eventually rescind Wyeth’s unilateral CBE changes. Accordingly, the Court noted that Wyeth could have attempted to show, by “clear evidence,” that the FDA would have rescinded any change in the label and thereby demonstrate that it would in fact have been impossible to do under federal law what state law required. Wyeth, supra, at 571. Wyeth offered no such evidence. That analysis is consistent with our holding today. The Court in Wyeth asked what the drug manufacturer could independently do under federal law, and in the absence of clear evidence that Wyeth could not have accomplished what state law required of it, found no pre-emption. The Wyeth Court held that, because federal law accommodated state law duties, “the possibility of impossibility” was “not enough.” Post, at 10; see also Rice v. Norman Williams Co., 458 U. S. 654, 659 (1982) (rejecting “hypothetical” impossibility). But here, “existing” federal law directly conflicts with state law. Post, at 15 (“Conflict analysis neces ­ sarily turns on existing law”). The question in these cases is not whether the possibility of impossibility establishes pre-emption, but rather whether the possibility of possibility defeats pre-emption. Post, at 10.

9 That said, the dissent overstates what it characterizes as the “many absurd consequences” of our holding. Post, at 18. First, the FDA in ­ forms us that “[a]s a practical matter, genuinely new information about drugs in long use (as generic drugs typically are) appears infre­ quently.” U. S. Brief 34–35. That is because patent protections ordi­ narily prevent generic drugs from arriving on the market for a number of years after the brand-name drug appears. Indeed, situations like the one alleged here are apparently so rare that the FDA has no “formal regulation” establishing generic drug manufacturers’ duty to initiate a label change, nor does it have any regulation setting out that label ­ change process. Id., at 20–21. Second, the dissent admits that, even under its approach, generic drug manufacturers could establish pre ­ emption in a number of scenarios. Post, at 12–13.

SOTOMAYOR, J., dissenting

SUPREME COURT OF THE UNITED STATES
_________________

Nos. 09–993, 09–1039, and 09–1501

_________________

PLIVA, INC., ET AL., PETITIONERS
v.
GLADYS MENSING

09–993

ACTAVIS ELIZABETH, LLC, PETITIONER
09–1039
v.
GLADYS MENSING

09–1501

ACTAVIS, INC., PETITIONER
v.
JULIE DEMAHY

ON WRITS OF CERTIORARI TO THE UNITED STATES COURTS OF
APPEALS FOR THE EIGHTH AND FIFTH CIRCUITS

[June 23, 2011]

JUSTICE SOTOMAYOR, with whom JUSTICE GINSBURG, JUSTICE BREYER, and JUSTICE KAGAN join, dissenting.

The Court today invokes the doctrine of impossibility pre-emption to hold that federal law immunizes genericdrug manufacturers from all state-law failure-to-warn claims because they cannot unilaterally change their labels. I cannot agree. We have traditionally held defendants claiming impossibility to a demanding standard: Until today, the mere possibility of impossibility had not been enough to establish pre-emption.

The Food and Drug Administration (FDA) permits— and, the Court assumes, requires—generic-drug manufacturers to propose a label change to the FDA when they believe that their labels are inadequate. If it agrees that the labels are inadequate, the FDA can initiate a change to the brand-name label, triggering a corresponding change to the generic labels. Once that occurs, a generic manufacturer is in full compliance with both federal law and a state-law duty to warn. Although generic manufacturers may be able to show impossibility in some cases, petitioners, generic manufacturers of metoclopramide (Manufacturers), have shown only that they might have been unable to comply with both federal law and their state-law duties to warn respondents Gladys Mensing and Julie Demahy. This, I would hold, is insufficient to sustain their burden.

The Court strains to reach the opposite conclusion. It invents new principles of pre-emption law out of thin air to justify its dilution of the impossibility standard. It effectively rewrites our decision in Wyeth v. Levine, 555 U. S. 555 (2009), which holds that federal law does not pre-empt failure-to-warn claims against brand-name drug manufacturers. And a plurality of the Court tosses aside our repeated admonition that courts should hesitate to conclude that Congress intended to pre-empt state laws governing health and safety. As a result of today’s decision, whether a consumer harmed by inadequate warnings can obtain relief turns solely on the happenstance of whether her pharmacist filled her prescription with a brand-name or generic drug. The Court gets one thing right: This outcome “makes little sense.” Ante, at 18.

I

A

Today’s decision affects 75 percent of all prescription drugs dispensed in this country. The dominant position of generic drugs in the prescription drug market is the result of a series of legislative measures, both federal and state.

In 1984, Congress enacted the Drug Price Competition and Patent Term Restoration Act, 98 Stat. 1585— commonly known as the Hatch-Waxman Amendments to the Federal Food, Drug, and Cosmetic Act (FDCA)—to “make available more low cost generic drugs by establishing a generic drug approval procedure,” H. R. Rep. No. 98– 857, pt. 1, p. 14 (1984). As the majority explains, to accomplish this goal the amendments establish an abbreviated application process for generic drugs. Ante, at 5–6; see also 21 U. S. C. §355(j)(2)(A). The abbreviated approval process implements the amendments’ core principle that generic and brand-name drugs must be the “same” in nearly all respects: To obtain FDA approval, a generic manufacturer must ordinarily show, among other things, that its product has the same active ingredients as an approved brand-name drug; that “the route of administration, the dosage form, and the strength of the new drug are the same” as the brand-name drug; and that its product is “bioequivalent” to the brand-name drug. §§355(j)(2)(A)(ii), (iii), (iv). By eliminating the need for generic manufacturers to prove their drugs’ safety and efficacy independently, the Hatch-Waxman Amendments allow generic manufacturers to bring drugs to market much less expensively.

The States have also acted to expand consumption of low-cost generic drugs. In the years leading up to passage of the Hatch-Waxman Amendments, States enacted legislation authorizing pharmacists to substitute generic drugs when filling prescriptions for brand-name drugs. Christensen, Kirking, Ascione, Welage, & Gaither, Drug Product Selection: Legal Issues, 41 J. Am. Pharmaceutical Assn. 868, 869 (2001). Currently, all States have some form of generic substitution law. See ibid. Some States require generic substitution in certain circumstances. Dept. of Health and Human Servs., ASPE Issue Brief: Expanding the Use of Generic Drugs 7 (2010) (hereinafter Expanding the Use of Generic Drugs);1 see, e.g., N. Y. Educ. Law Ann. §6816–a (West 2010). Others permit, but do not require, substitution. Expanding the Use of Generic Drugs 7; see, e.g., Cal. Bus. & Prof. Code Ann. §4073 (West Supp. 2011). Some States require patient consent to substitution, and all States “allow the physician to specify that the brand name must be prescribed, although with different levels of effort from the physician.” Expanding the Use of Generic Drugs 7.2

These legislative efforts to expand production and consumption of generic drugs have proved wildly successful. It is estimated that in 1984, when the Hatch-Waxman Amendments were enacted, generic drugs constituted 19 percent of drugs sold in this country. Congressional Budget Office, How Increased Competition from Generic Drugs Has Affected Prices and Returns in the Pharmaceutical Industry 27 (1998).3 Today, they dominate the market. See Expanding the Use of Generic Drugs 2 (generic drugs constituted 75 percent of all dispensed prescription drugs in 2009). Ninety percent of drugs for which a generic version is available are now filled with generics. Id., at 3–4. In many cases, once generic versions of a drug enter the market, the brand-name manufacturer stops selling the brand-name drug altogether. See Brief for Marc T. Law et al. as Amici Curiae 18 (citing studies showing that anywhere from one-third to one-half of generic drugs no longer have a marketed brand-name equivalent). Reflecting the success of their products, many generic manufacturers, including the Manufacturers and their amici, are huge, multinational companies. In total, generic drug manufacturers sold an estimated $66 billion of drugs in this country in 2009. See id., at 15.

B

As noted, to obtain FDA approval a generic manufacturer must generally show that its drug is the same as an approved brand-name drug. It need not conduct clinical trials to prove the safety and efficacy of the drug. This does not mean, however, that a generic manufacturer has no duty under federal law to ensure the safety of its products. The FDA has limited resources to conduct postapproval monitoring of drug safety. See Wyeth, 555 U. S., at 578. Manufacturers, we have recognized, “have superior access to information about their drugs, especially in the postmarketing phase as new risks emerge.” Id., at 578– 579. Federal law thus obliges drug manufacturers—both brand-name and generic—to monitor the safety of their products.

Under federal law, generic manufacturers must “develop written procedures for the surveillance, receipt, evaluation, and reporting of postmarketing adverse drug experiences” to the FDA.4 21 CFR §314.80(b);5 see also §314.98 (making §314.80 applicable to generic manufacturers); Brief for United States as Amicus Curiae 6, and n. 2 (hereinafter U. S. Brief). They must review all reports of adverse drug experiences received from “any source.” §314.80(b). If a manufacturer receives a report of a serious and unexpected adverse drug experience, it must report the event to the FDA within 15 days and must “promptly investigate.” §§314.80(c)(1)(i)–(ii); see also Tr. of Oral Arg. 8. Most other adverse drug experiences must be reported on a quarterly or yearly basis.6 §314.80(c)(2). Generic manufacturers must also submit to the FDA an annual report summarizing “significant new information from the previous year that might affect the safety, effectiveness, or labeling of the drug product,” including a “description of actions the [manufacturer] has taken or intends to take as a result of this new information.” §314.81(b)(2)(i); see also §314.98(c).

Generic manufacturers, the majority assumes, also bear responsibility under federal law for monitoring the adequacy of their warnings. I agree with the majority’s conclusion that generic manufacturers are not permitted unilaterally to change their labels through the “changesbeing-effected” (CBE) process or to issue additional warnings through “Dear Doctor” letters. See ante, at 6–9. According to the FDA, however, that generic manufacturers cannot disseminate additional warnings on their own does not mean that federal law permits them to remain idle when they conclude that their labeling is inadequate. FDA regulations require that labeling “be revised to include a warning as soon as there is reasonable evidence of an association of a serious hazard with a drug.” 21 CFR §201.57(e) (2006), currently codified at 21 CFR §201.80(e) (2010); see also Wyeth, 555 U. S., at 570–571. The FDA construes this regulation to oblige generic manufacturers “to seek to revise their labeling and provide FDA with supporting information about risks” when they believe that additional warnings are necessary.7 U. S. Brief 20.

The Manufacturers disagree. They read the FDA regulation to require them only to ensure that their labels match the brand-name labels. See Brief for Petitioner PLIVA et al. 38–41. I need not decide whether the regulation in fact obliges generic manufacturers to approach the FDA to propose a label change. The majority assumes that it does. And even if generic manufacturers do not have a duty to propose label changes, two points remain undisputed. First, they do have a duty under federal law to monitor the safety of their products. And, second, they may approach the FDA to propose a label change when they believe a change is required.

II

This brings me to the Manufacturers’ pre-emption defense. State law obliged the Manufacturers to warn of dangers to users. See Hines v. Remington Arms Co., 94– 0455, p. 10 (La. 12/8/94), 648 So. 2d 331, 337; Frey v. Montgomery Ward & Co., 258 N. W. 2d 782, 788 (Minn. 1977). The Manufacturers contend, and the majority agrees, that federal law pre-empts respondents’ failure-towarn claims because, under federal law, the Manufacturers could not have provided additional warnings to respondents without the exercise of judgment by the FDA. I cannot endorse this novel conception of impossibility pre-emption.

A

Two principles guide all pre-emption analysis. First, “ ‘the purpose of Congress is the ultimate touchstone in every pre-emption case.’ ” Wyeth, 555 U. S., at 565 (quoting Medtronic, Inc. v. Lohr, 518 U. S. 470, 485 (1996)). 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.’ ” Wyeth, 555 U. S., at 565 (quoting Lohr, 518 U. S., at 485; some internal quotation marks omitted; alterations in original).

These principles find particular resonance in these cases. The States have traditionally regulated health and safety matters. See id., at 485. Notwithstanding Congress’ “certain awareness of the prevalence of state tort litigation” against drug manufacturers, Wyeth, 555 U. S., at 575, Congress has not expressly pre-empted state-law tort actions against prescription drug manufacturers, whether brand-name or generic. To the contrary, when Congress amended the FDCA in 1962 to “enlarg[e] the FDA’s powers to ‘protect the public health’ and ‘assure the safety, effectiveness, and reliability of drugs,’ [it] took care to preserve state law.” Id., at 567 (quoting 76 Stat. 780); see Pub. L. 87–781, §202, 76 Stat. 793 (“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 and such provision of State law”). Notably, although Congress enacted an express pre-emption provision for medical devices in 1976, see Pub. L. 94–295, §521, 90 Stat. 574, 21 U. S. C. §360k(a), it included no such provision in the Hatch-Waxman Amendments eight years later. Cf. Wyeth, 555 U. S., at 567, 574–575. Congress’ “silence on the issue . . . is powerful evidence that [it] did not intend FDA oversight to be the exclusive means of ensuring drug safety and effectiveness.” Id., at 575.

B

Federal law impliedly pre-empts state law when state and federal law “conflict”—i.e., when “it is impossible for a private party to comply with both state and federal law” or when state law “stands as an obstacle to the accomplishment and execution of the full purposes and objectives of Congress.” Crosby v. National Foreign Trade Council, 530 U. S. 363, 372–373 (2000) (internal quotation marks omitted). The Manufacturers rely solely on the former ground of pre-emption.

Impossibility pre-emption, we have emphasized, “is a demanding defense.” Wyeth, 555 U. S., at 573. Because pre-emption is an affirmative defense, a defendant seeking to set aside state law bears the burden to prove impossibility. See ibid.; Silkwood v. Kerr-McGee Corp., 464 U. S. 238, 255 (1984). To prevail on this defense, a defendant must demonstrate that “compliance with both federal and state [law] is a physical impossibility.” Florida Lime & Avocado Growers, Inc. v. Paul, 373 U. S. 132, 142–143 (1963); see also Wyeth, 555 U. S., at 573. In other words, there must be an “inevitable collision” between federal and state law. Florida Lime, 373 U. S., at 143. “The existence of a hypothetical or potential conflict is insufficient to warrant” pre-emption of state law. Rice v. Norman Williams Co., 458 U. S. 654, 659 (1982); see also Gade v. National Solid Wastes Management Assn., 505 U. S. 88, 110 (1992) (KENNEDY, J., concurring in part and concurring in judgment). In other words, the mere possibility of impossibility is not enough.

The Manufacturers contend that it was impossible for them to provide additional warnings to respondents Mensing and Demahy because federal law prohibited them from changing their labels unilaterally.8 They concede, however, that they could have asked the FDA to initiate a label change. If the FDA agreed that a label change was required, it could have asked, and indeed pressured, the brand-name manufacturer to change its label, triggering a corresponding change to the Manufacturers’ generic labels.9 Thus, had the Manufacturers invoked the available mechanism for initiating label changes, they may well have been able to change their labels in sufficient time to warn respondents. Having failed to do so, the Manufacturers cannot sustain their burden (at least not without further factual development) to demonstrate that it was impossible for them to comply with both federal and state law. At most, they have demonstrated only “a hypothetical or potential conflict.” Rice, 458 U. S., at 659.

Like the majority, the Manufacturers focus on the fact that they cannot change their labels unilaterally—which distinguishes them from the brand-name-manufacturer defendant in Wyeth. They correctly point out that in Wyeth we concluded that the FDA’s CBE regulation authorized the defendant to strengthen its warnings before receiving agency approval of its supplemental application describing the label change. 555 U. S., at 568–571; see also 21 CFR §314.70(c)(6). But the defendant’s label change was contingent on FDA acceptance, as the FDA retained “authority to reject labeling changes made pursuant to the CBE regulation.” Wyeth, 555 U. S., at 571. Thus, in the long run, a brand-name manufacturer’s compliance with a state-law duty to warn required action by two actors: The brand-name manufacturer had to change the label and the FDA, upon reviewing the supplemental application, had to agree with the change.10 The need for FDA approval of the label change did not make compliance with federal and state law impossible in every case. Instead, because the defendant bore the burden to show impossibility, we required it to produce “clear evidence that the FDA would not have approved a change to [the] label.” Ibid.

I would apply the same approach in these cases. State law, respondents allege, required the Manufacturers to provide a strengthened warning about the dangers of long-term metoclopramide use.11 Just like the brand-name manufacturer in Wyeth, the Manufacturers had available to them a mechanism for attempting to comply with their state-law duty to warn. Federal law thus “accommodated” the Manufacturers’ state-law duties. See ante, at 18, n. 8. It was not necessarily impossible for the Manufacturers to comply with both federal and state law because, had they approached the FDA, the FDA may well have agreed that a label change was necessary. Accordingly, as in Wyeth, I would require the Manufacturers to show that the FDA would not have approved a proposed label change. They have not made such a showing: They do “not argue that [they] attempted to give the kind of warning required by [state law] but [were] prohibited from doing so by the FDA.” Wyeth, 555 U. S., at 572.

This is not to say that generic manufacturers could never show impossibility. If a generic-manufacturer defendant proposed a label change to the FDA but the FDA rejected the proposal, it would be impossible for that defendant to comply with a state-law duty to warn. Likewise, impossibility would be established if the FDA had not yet responded to a generic manufacturer’s request for a label change at the time a plaintiff’s injuries arose. A generic manufacturer might also show that the FDA had itself considered whether to request enhanced warnings in light of the evidence on which a plaintiff’s claim rests but had decided to leave the warnings as is. (The Manufacturers make just such an argument in these cases. See, e.g., Brief for Petitioner Actavis et al. 11.) But these are questions of fact to be established through discovery. Because the burden of proving impossibility falls on the defendant, I would hold that federal law does not render it impossible for generic manufacturers to comply with a state-law duty to warn as a categorical matter.

This conclusion flows naturally from the overarching principles governing our pre-emption doctrine. See supra, at 8. Our “respect for the States as ‘independent sovereigns in our federal system’ leads us to assume that ‘Congress does not cavalierly pre-empt state-law causes of action.’ ” Wyeth, 555 U. S., at 565–566, n. 3 (quoting Lohr, 518 U. S., at 485). It is for this reason that we hold defendants asserting impossibility to a “demanding” standard. Wyeth, 555 U. S., at 573. This presumption against preemption has particular force when the Federal Government has afforded defendants a mechanism for complying with state law, even when that mechanism requires federal agency action. (The presumption has even greater force when federal law requires defendants to invoke that mechanism, as the majority assumes in these cases.) In such circumstances, I would hold, defendants will usually be unable to sustain their burden of showing impossibility if they have not even attempted to employ that mechanism. Any other approach threatens to infringe the States’ authority over traditional matters of state interest—such as the failure-to-warn claims here—when Congress expressed no intent to pre-empt state law. C

The majority concedes that the Manufacturers might have been able to accomplish under federal law what state law requires. Ante, at 12–13. To reach the conclusion that the Manufacturers have nonetheless satisfied their burden to show impossibility, the majority invents a new preemption rule: “The question for ‘impossibility’ is whether the private party could independently do under federal law what state law requires of it.” Ante, at 13 (emphasis added). Because the Manufacturers could not have changed their labels without the exercise of judgment by the FDA, the majority holds, compliance with both state and federal law was impossible in these cases.12

The majority’s new test has no basis in our precedents. The majority cites only Wyeth in support of its test. As discussed above, however, Wyeth does not stand for the proposition that it is impossible to comply with both federal and state law whenever federal agency approval is required. To the contrary, label changes by brand-name manufacturers such as Wyeth are subject to FDA review and acceptance. See supra, at 11–12. And, even if Wyeth/i> could be characterized as turning on the fact that the brand-name manufacturer could change its label unilaterally, the possibility of unilateral action was, at most, a sufficient condition for rejecting the impossibility defense in that case. Wyeth did not hold that unilateral action is a necessary condition in every case. With so little support in our case law, the majority understandably turns to other rationales. None of the rationales that it offers, however, makes any sense. First, it offers a reductio ad absurdum: If the possibility of FDA approval of a label change is sufficient to avoid conflict in these cases, it warns, as a “logical conclusion” so too would be the possibility that the FDA might rewrite its regulations or that Congress might amend the Hatch-Waxman Amendments. Ante, at 14. The logic of this conclusion escapes me. Conflict analysis necessarily turns on existing law. It thus would be ridiculous to conclude that federal and state law do not conflict on the ground that the defendant could have asked a federal agency or Congress to change the law. Here, by contrast, the Manufacturers’ compliance with their state-law duty to warn did not require them to ask for a change in federal law, as the majority itself recognizes. See ante, at 13 (“[F]ederal law would permit the Manufacturers to comply with the state labeling requirements if, and only if, the FDA and the brand-name manufacturer changed the brand-name label to do so”). The FDA already afforded them a mechanism for attempting to comply with their state-law duties. Indeed, the majority assumes that FDA regulations required the Manufacturers to request a label change when they had “reasonable evidence of an association of a serious hazard with a drug.” 21 CFR §201.57(e).

Second, the majority suggests that any other approach would render conflict pre-emption “illusory” and “meaningless.” Ante, at 14. It expresses concern that, without a robust view of what constitutes conflict, the Supremacy Clause would not have “any force” except in cases of express pre-emption. Ibid. To the extent the majority’s purported concern is driven by its reductio ad absurdum, see ante, at 14, n. 6, that concern is itself illusory, for the reasons just stated. To the extent the majority is concerned that our traditionally narrow view of what constitutes impossibility somehow renders conflict pre-emption as a whole meaningless, that concern simply makes no sense: We have repeatedly recognized that conflict preemption may be found, even absent impossibility, where state law “stands as an obstacle to the accomplishment and execution of the full purposes and objectives of Congress.” Crosby, 530 U. S., at 373 (internal quotation marks omitted); see, e.g., Geier v. American Honda Motor Co., 529 U. S. 861, 886 (2000); Barnett Bank of Marion Cty., N. A. v. Nelson, 517 U. S. 25, 31 (1996); Hines v. Davidowitz, 312 U. S. 52, 67 (1941). The majority’s expansive view of impossibility is thus unnecessary to prevent conflict pre-emption from losing all meaning.13

Third, a plurality of the Court adopts the novel theory that the Framers intended for the Supremacy Clause to operate as a so-called non obstante provision. See ante, at 15–17 (citing Nelson, Preemption, 86 Va. L. Rev. 225 (2000)). According to the plurality, non obstante provisions in statutes “instruc[t] courts not to apply the general presumption against implied repeals.” Ante, at 15 (internal quotation marks omitted); see also ante, at 16 (stating that when a statute contains a non obstante provision, “ ‘courts will be less inclined against recognizing repugnancy in applying such statutes’ ” (quoting J. Sutherland, Statutes and Statutory Construction §147, p. 199 (1891)). From this understanding of the Supremacy Clause, the plurality extrapolates the principle that “courts should not strain to find ways to reconcile federal law with seemingly conflicting state law.” Ante, at 15.

This principle would have been news to the Congress that enacted the Hatch-Waxman Amendments in 1984: Our precedents hold just the opposite. For more than half a century, we have directed courts to presume that congressional action does not supersede “the historic police powers of the States . . . unless that was the clear and manifest purpose of Congress.” Rice v. Santa Fe Elevator Corp., 331 U. S. 218, 230 (1947); see also Gade, 505 U. S., at 111–112 (KENNEDY, J., concurring in part and concurring in judgment). We apply this presumption against pre-emption both where Congress has spoken to the preemption question and where it has not. See Wyeth, 555 U. S., at 566, n. 3. In the context of express pre-emption, we read federal statutes whenever possible not to preempt state law. See Altria Group, Inc. v. Good, 555 U. S. 70, 77 (2008) (“[W]hen the text of a pre-emption clause is susceptible of more than one plausible reading, courts ordinarily ‘accept the reading that disfavors pre-emption’ ” (quoting Bates v. Dow Agrosciences LLC, 544 U. S. 431, 449 (2005))); see also Cipollone v. Liggett Group, Inc., 505 U. S. 504, 518 (1992). And, when the claim is that federal law impliedly pre-empts state law, we require a “strong” showing of a conflict “to overcome the presumption that state and local regulation . . . can constitutionally coexist with federal regulation.” Hillsborough County v. Automated Medical Laboratories, Inc., 471 U. S. 707, 716 (1985).

The plurality’s new theory of the Supremacy Clause is a direct assault on these precedents.14 Whereas we have long presumed that federal law does not pre-empt, or repeal, state law, the plurality today reads the Supremacy Clause to operate as a provision instructing courts “not to apply the general presumption against implied repeals.” Ante, at 15 (internal quotation marks omitted; emphasis added). And whereas we have long required evidence of a “clear and manifest” purpose to pre-empt, Rice, 331 U. S., at 230, the plurality now instructs courts to “look no further than the ordinary meaning of federal law” before concluding that Congress must have intended to cast aside state law, ante, at 16 (internal quotation marks and alteration omitted).

That the plurality finds it necessary to resort to this novel theory of the Supremacy Clause—a theory advocated by no party or amici in these cases—is telling. Proper application of the longstanding presumption against pre-emption compels the conclusion that federal law does not render compliance with state law impossible merely because it requires an actor to seek federal agency approval. When federal law provides actors with a mechanism for attempting to comply with their state-law duties, “respect for the States as ‘independent sovereigns in our federal system’ ” should require those actors to attempt to comply with state law before being heard to complain that compliance with both laws was impossible. Wyeth, 555 U. S., at 565–566, n. 3 (quoting Lohr, 518 U. S., at 485).

III

Today’s decision leads to so many absurd consequences that I cannot fathom that Congress would have intended to pre-empt state law in these cases.

First, the majority’s pre-emption analysis strips genericdrug consumers of compensation when they are injured by inadequate warnings. “If Congress had intended to deprive injured parties of [this] long available form of compensation, it surely would have expressed that intent more clearly.” Bates, 544 U. S., at 449. Given the longstanding existence of product liability actions, including for failure to warn, “[i]t is difficult to believe that Congress would, without comment, remove all means of judicial recourse for those injured by illegal conduct.” Silkwood, 464 U. S., at 251; see also Bruesewitz v. Wyeth LLC, 562 U. S. ___, ___ (2011) (slip op., at 16) (noting our previously expressed “doubt that Congress would quietly preempt productliability claims without providing a federal substitute”). In concluding that Congress silently immunized generic manufacturers from all failure-to-warn claims, the majority disregards our previous hesitance to infer congressional intent to effect such a sweeping change in traditional state-law remedies.

As the majority itself admits, a drug consumer’s right to compensation for inadequate warnings now turns on the happenstance of whether her pharmacist filled her prescription with a brand-name drug or a generic. If a consumer takes a brand-name drug, she can sue the manufacturer for inadequate warnings under our opinion in Wyeth. If, however, she takes a generic drug, as occurs 75 percent of the time, she now has no right to sue. The majority offers no reason to think—apart from its new articulation of the impossibility standard—that Congress would have intended such an arbitrary distinction. In some States, pharmacists must dispense generic drugs absent instruction to the contrary from a consumer’s physician. Even when consumers can request brand-name drugs, the price of the brand-name drug or the consumers’ insurance plans may make it impossible to do so. As a result, in many cases, consumers will have no ability to preserve their state-law right to recover for injuries caused by inadequate warnings.

Second, the majority’s decision creates a gap in the parallel federal-state regulatory scheme in a way that could have troubling consequences for drug safety. As we explained in Wyeth, “[s]tate tort suits uncover unknown drug hazards and provide incentives for drug manufacturers to disclose safety risks promptly.” 555 U. S., at 579. Thus, we recognized, “state law offers an additional, and important, layer of consumer protection that complements FDA regulation.” Ibid. Today’s decision eliminates the traditional state-law incentives for generic manufacturers to monitor and disclose safety risks. When a generic drug has a brand-name equivalent on the market, the brandname manufacturer will remain incentivized to uncover safety risks. But brand-name manufacturers often leave the market once generic versions are available, see supra, at 4–5, meaning that there will be no manufacturer subject to failure-to-warn liability. As to those generic drugs, there will be no “additional . . . layer of consumer protection.” Wyeth, 555 U. S., at 579.

Finally, today’s decision undoes the core principle of the Hatch-Waxman Amendments that generic and brandname drugs are the “same” in nearly all respects.15 See Brief for Rep. Henry A. Waxman as Amicus Curiae 9. The majority pins the expansion of the generic drug market on “the special, and different, regulation of generic drugs,” which allows generic manufacturers to produce their drugs more cheaply. Ante, at 19. This tells only half the story. The expansion of the market for generic drugs has also flowed from the increased acceptance of, and trust in, generic drugs by consumers, physicians, and state legislators alike.

Today’s decision introduces a critical distinction between brand-name and generic drugs. Consumers of brand-name drugs can sue manufacturers for inadequate warnings; consumers of generic drugs cannot. These divergent liability rules threaten to reduce consumer demand for generics, at least among consumers who can afford brand-name drugs. They may pose “an ethical dilemma” for prescribing physicians. Brief for American Medical Association et al. as Amici Curiae 29. And they may well cause the States to rethink their longstanding efforts to promote generic use through generic substitution laws. See Brief for National Conference of State Legislators as Amicus Curiae 15 (state generic substitution laws “have proceeded on the premise that . . . generic drugs are not, from citizens’ perspective, materially different from brand ones, except for the lower price”). These consequences are directly at odds with the Hatch-Waxman Amendments’ goal of increasing consumption of generic drugs.

Nothing in the Court’s opinion convinces me that, in enacting the requirement that generic labels match their corresponding brand-name labels, Congress intended these absurd results. The Court certainly has not shown that such was the “clear and manifest purpose of Congress.” Wyeth, 555 U. S., at 565 (internal quotation marks omitted; emphasis added). To the contrary, because federal law affords generic manufacturers a mechanism for attempting to comply with their state-law duties to warn, I would hold that federal law does not categorically pre-empt state-law failure-to-warn claims against generic manufacturers. Especially in light of the presumption against pre-emption, the burden should fall on generic manufacturers to show that compliance was impossible on the particular facts of their case. By holding that the “possibility of possibility” is insufficient to “defea[t]” preemption in these cases, ante, at 18, n. 8, the Court contorts our pre-emption doctrine and exempts defendants from their burden to establish impossibility. With respect, I dissent.

1 Online at http://aspe.hhs.gov/sp/reports/2010/GenericDrugs/ib.pdf (all Internet materials as visited June 17, 2011, and available in Clerk of Court’s case file).

2 In addition, many insurance plans are structured to promote generic use. See Congressional Budget Office, Effects of Using Generic Drugs on Medicare’s Prescription Drug Spending 9 (2010), online at http:// www . cbo .gov / f tpdo c /118xx /do c11838 /09 -15 -Prescr ip t ionDrug s .pd f . State Medicaid programs similarly promote generic use. See Kaiser Comm’n on Medicaid and the Uninsured, State Medicaid Outpatient Prescription Drug Policies: Findings from a National Survey, 2005 Update 10 (2005), online at www.kff.org/medicaid/upload/statemedicaid-outpatient-prescription-drug-policies-findings-from-a-nationalsurvey-2005-update-report.pdf.

3 Online at http://www.cbo.gov/ftpdocs/6xx/doc655/pharm.pdf.

4 An adverse drug experience is defined as “[a]ny adverse event associated with the use of a drug in humans, whether or not considered drug related.” 21 CFR §314.80(a) (2006).

5 Like the majority, I refer to the pre-2007 statutes and regulations. See ante, at 5, n. 1.

6 At congressional hearings on the Hatch-Waxman Amendments, representatives of the generic drug manufacturers confirmed both their obligation and their ability to conduct postapproval investigation of adverse drug experiences. See Drug Legislation: Hearings on H. R. 1554 et al. before the Subcommittee on Health and the Environment of the House Committee on Energy and Commerce, 98th Cong., 1st Sess., 45 (1983) (statement of Kenneth N. Larsen, chairman of the Generic Pharmaceutical Industry Association (GPhA)) (generic manufacturers “are sensitive to the importance of looking at adverse reactions”); id., at 47–48 (“[W]e will do and provide whatever is required to be performed to meet the regulatory requirement to provide for the safety and wellbeing of those that are using the drug, this is our role and responsibility. This is an obligation to be in this business”); id., at 50–51 (statement of Bill Haddad, executive officer and president of GPhA) (“Every single generic drug company that I know has a large research staff. It not only researches the drug that they are copying, or bringing into the market but it researches new drugs, researches adverse reaction[s]”).

7 The FDA’s construction of this regulation mirrors the guidance it provided to generic manufacturers nearly 20 years ago in announcing the final rule implementing the abbreviated application process for generic drugs: “If an ANDA [i.e., application for approval of a generic drug] applicant believes new safety information should be added to a product’s labeling, it should contact FDA, and FDA will determine whether the labeling for the generic and listed drugs should be revised. After approval of an ANDA, if an ANDA holder believes that new safety information should be added, it should provide adequate supporting information to FDA, and FDA will determine whether the labeling for the generic and listed drugs should be revised.” 57 Fed. Reg. 17961 (1992). FDA’s internal procedures recognize that the Office of Generic Drugs will have to consult with other FDA components on “some labeling reviews.” Manual of Policies and Procedures 5200.6, p. 1 (May 9, 2001). Consultations involving “possible serious safety concerns” receive the highest priority. Id., at 3.

8 In its decision below, the Eighth Circuit suggested that the Manufacturers could not show impossibility because federal law merely permitted them to sell generic drugs; it did not require them to do so. See Mensing v. Wyeth, Inc., 588 F. 3d 603, 611 (2009) (“The generic defendants were not compelled to market metoclopramide. If they realized their label was insufficient but did not believe they could even propose a label change, they could have simply stopped selling the product”); see also Geier v. American Honda Motor Co., 529 U. S. 861, 873 (2000) (describing “a case of impossibility” as one “in which state law penalizes what federal law requires” (emphasis added)). Respondents have not advanced this argument, and I find it unnecessary to consider.

9 At the time respondents’ cause of action arose, the FDA did not have authority to require a brand-name manufacturer to change its label. (It received that authority in 2007. See Pub. L. 110–85, §901, 121 Stat. 924–926, 21 U. S. C. §355(o)(4) (2006 ed., Supp. III). It did, however, have the equally significant authority to withdraw the brand-name manufacturer’s permission to market its drug if the manufacturer refused to make a requested labeling change. See 21 U. S. C. §355(e) (2006 ed.); 21 CFR §314.150(b)(3).

10 A brand-name manufacturer’s ability to comply with a state-law duty to warn would depend on its own unilateral actions only during the period after it should have changed its label but before the FDA would have approved or disapproved the label change. The claim in Wyeth does not appear to have arisen during that period.

11 Respondents’ state-law claim is not that the Manufacturers were required to ask the FDA for assistance in changing the labels; the role of the FDA arises only as a result of the Manufacturers’ pre-emption defense.

12 These cases do not involve a situation where a brand-name manufacturer itself produces generic drugs. See Okie, Multinational Medicines—Ensuring Drug Quality in an Era of Global Manufacturing, 361 N. Eng. J. Med. 737, 738 (2009); see also GPhA, Frequently Asked Questions About Generics, http://www.gphaonline.org/aboutgpha/about-generics/faq (“Brand-name companies make about half of generic drugs”). In that case, the manufacturer could independently change the brand-name label under the CBE regulation, triggering a corresponding change to its own generic label.

13JUSTICE THOMAS, the author of today’s opinion, has previously expressed the view that obstacle pre-emption is inconsistent with the Constitution. See Williamson v. Mazda Motor of America, Inc., 562 U. S. ___, ___ (2011) (opinion concurring in judgment) (slip op., at 2–5); Wyeth v. Levine, 555 U. S. 555, 604 (2009) (opinion concurring in judgment). That position, however, has not been accepted by this Court, and it thus should not justify the majority’s novel expansion of impossibility pre-emption.

14 The author of the law review article proposing this theory of the Supremacy Clause acknowledges as much. See Nelson, Preemption, 86 Va. L. Rev. 225, 304 (2000) (“The non obstante provision rejects an artificial presumption that Congress did not intend to contradict any state laws and that federal statutes must therefore be harmonized with state law”). The plurality, on the other hand, carefully avoids discussing the ramifications of its new theory for the longstanding presump tion against pre-emption.

15 According to the GPhA, both the FDA and the generic drug industry “spend millions of dollars each year . . . seeking to reassure consumers that affordable generic drugs really are—as federal law compels them to be—the same as their pricier brand-name counterparts.” Brief for GPhA as Amicus Curiae on Pet. for Cert. in Nos. 09–993, 09–1039, pp. 2–3.

Print this transcript Transcript: 

ORAL ARGUMENT OF JAY P. LEFKOWITZ ON BEHALF OF THE PETITIONERS

Chief Justice John G. Roberts: We'll hear argument first this morning in Case 09-993, Pliva, Incorporated v. Mensing, and the consolidated cases.

Mr. Lefkowitz.

Mr. Lefkowitz: Mr. Chief Justice, and may it please the Court:

This case involves the ordinary operation of the Supremacy Clause.

As the government agrees, Hatch-Waxman's plain text requires generic drugs to have the same warnings as their brand-name equivalents, so State law can't require generic drugs to use different warnings.

After all, generics can't simultaneously comply with a Federal duty to be the same and a State duty to be different.

Chief Justice John G. Roberts: Well, that makes a lot of sense, but we do have our Wyeth decision that seems to cut the other way.

Mr. Lefkowitz: Well, Your Honor, the Wyeth decision is premised on the fundamental conclusion that Federal law obligates and accommodates the brand manufacturer to utilize a specific regulation, the CBE regulation, in order to make a warning change, in order to comply with its obligations under 201.57.

And, as the government agrees, we don't have the opportunity or the authority to use a CBE regulation change.

Justice Ruth Bader Ginsburg: But you have another -- you have another route, and that's what the government is telling us: That you could propose a revision of the label, and if you did that, then you would be home free.

You would not be subject to the State suit.

Mr. Lefkowitz: Justice Ginsburg, the government agrees with us that we can't actually change the label.

What they say is, we could have an obligation, or they actually, in -- for the very first time ever in their brief in this Court at the merit stage, said that there is a--

Justice Ruth Bader Ginsburg: No, it was in the -- at the cert stage as well.

Mr. Lefkowitz: --Well, Your Honor, I didn't read the cert stage as saying we had quite the same duty to ask the FDA, although clearly they now believe that we have a duty to ask the FDA.

And of course that's not a duty that appears in any of their notice and comment rulemaking.

Justice Anthony Kennedy: Can we call this the take steps -- is this the take-steps doctrine, for purposes of discussion here?

Mr. Lefkowitz: Yes, Justice Kennedy, this is the take-steps.

Justice Anthony Kennedy: It's not clear to me whether you say that that is preempted or just that it was not well-pled.

I'm not -- I'm not sure of your position on that point.

Mr. Lefkowitz: Thank you, Justice Kennedy.

We maintain that a claim that under State law a generic company can be liable for not asking the FDA to make a labeling change is preempted under this Court's decisions both in Buckman and in ArkLa, because what the -- what the Court has said is that the disclosure obligations between a Federal agency and a Federally regulated party are inherently Federal in character, and this is not a subject of traditional State tort law.

Justice Elena Kagan: Well, Mr. Lefkowitz, why should--

Justice Antonin Scalia: Would the -- excuse me, Justice.

Would the Federally licensed drug manufacturer have a similar obligation to lobby the FDA for a change?

Mr. Lefkowitz: No, Your Honor, and in fact that was in part what was -- what came up in the briefing in the Wyeth case.

Wyeth initially said it didn't have the obligation and couldn't use the CBE, and then Ms. Levine said: Well, in that case you could have asked the FDA to make a change, and the Court didn't need to even address that issue, because the Court found that there actually was a regulation on point that gave the brand manufacturer the ability to change.

Justice Antonin Scalia: But assume there hadn't been.

Assume there hadn't been such a regulation.

Do you understand it to be the government's position that the licensed drug manufacturer is not protected from State suits, even though it has a Federal permission to give certain warnings, unless it has lobbied the FDA to change those warnings?

Mr. Lefkowitz: Your Honor, I -- I don't see anything in the history, the 27-year history of Hatch-Waxman, where the Federal government has ever said that there is a legal obligation to lobby the FDA for a labeling change.

Justice Sonia Sotomayor: Excuse me.

There is a legal obligation to advise the FDA when you have reports of adverse results that suggest the label may be wrong.

Are you disavowing your -- your obligation to tell the FDA when something's wrong?

Mr. Lefkowitz: Absolutely not, Justice Sotomayor.

Justice Sonia Sotomayor: So please describe what the difference between that obligation and the obligation to suggest a label change when you know it's been misbranded.

Mr. Lefkowitz: Under the FDA Regulation 314.80 and 314.98, we have a myriad of disclosure obligations.

Any time a generic learns about an adverse report, it has to report it to the FDA, it has to investigate it, and if it doesn't do that then it's not in compliance with its Federal obligations and the FDA has plenary authority to take all sorts of action.

But just as the Court said in the Buckman decision, without dissent, when a company doesn't make appropriate disclosures to the FDA, even if people are hurt by that, even if it's -- if it causes people to be injured and States might otherwise want to compensate them for them, those disclosure obligations are up to the FDA with its discretion to enforce.

And the Court looked directly to Congress in section 337.

Justice Sonia Sotomayor: So what's -- so what's the conflict with State law, meaning you have an obligation to keep your label as it is, but if you also have a Federal obligation to advise the FDA of adverse -- of adverse results and of needs for change, why can't you then comply with a duty to warn obligation because you can go to the -- to the FDA?

Mr. Lefkowitz: Well, first of all, there's a little bit of a difference between reporting all of the adverse events, which we clearly do, and asking the FDA to make a determination that the FDA has said is only for the FDA to make with respect to generic companies.

Justice Elena Kagan: --Do you contest, Mr. Lefkowitz, your ability to make that request?

I know that you contest your obligation to make that request, but do you think you could go to the FDA and make that request and set a process in motion?

Mr. Lefkowitz: Your Honor, there's no question that we could certainly ask the FDA, and in fact if we had reason to believe that a label was not accurate, not strong enough, we would certainly do that.

The question is whether or not there's either a Federal obligation or a State duty to do this, and--

Justice Elena Kagan: Well, if you could go to the FDA, why shouldn't we look at this suit in this way: That the plaintiffs are bringing a standard failure to warn claim; that you then have a preemption defense, that you'll say it's impossible; and then in order to litigate that preemption defense, the question will be, well, if you had gone to the FDA, what would the FDA have done?

Would it in fact have required both brand names and generics to change the label?

And if it would have, you would not have had -- been put in an impossible position.

Mr. Lefkowitz: --Your Honor, that is the precise set of issues that this Court addressed both in Buckman and in ArkLa, in a situation where all we could have done, and we weren't obligated to do, was ask the FDA.

For a State to hold us liable for not asking the FDA is asking a State jury to put itself into the shoes of the FDA, to speculate how the FDA would have decided hypothetical issues, which ArkLa says is foreclosed in an area where the Federal Government, the Federal agency, has exclusive authority.

And in Buckman, the Court said that would disrupt and usurp the discretion of the agency to decide whether to punish and how to punish disclosure.

Chief Justice John G. Roberts: Well, Buckman -- Buckman was arguably a little bit different, in that there's a concern expressed in that case that requiring allowing the State suit to go forward would cause manufacturers to basically inundate the agency with proposals and warning revisions, so that there would be so many things that the agency wouldn't even be able to process them, and they would become meaningless to the consumers.

That doesn't seem to me to be a concern in this case.

Mr. Lefkowitz: Well, Your Honor, the government had articulated that proposition in the Buckman case and again several years later in the Warner-Lambert case.

Obviously, they're taking a different position here.

But I would submit, Your Honor, that what lay at the core of the Buckman decision was that the relationship, the disclosures, between the Federal agency and its regulated party, are inherently Federal and States simply don't have a business trying to enforce those obligations, because that does take away from the authority and the discretion.

And the Court looked to section 337 as evidence that Congress intended that violations of the FDCA be enforced by the Federal Government.

Justice Ruth Bader Ginsburg: The Federal agency says that these suits complement, they're not at odds with, the Federal regime, because they give the manufacturers an incentive to come forward.

Everyone is interested in making sure that only safe drugs are marketed.

So, far from detracting from the Federal regime, the agency responsible says, this helps us; it encourages manufacturers to report.

Mr. Lefkowitz: Well, we know from the current FDA database that there were over 1600 requests for labeling revisions that the FDA has not acted on, and that's just in the aftermath of Wyeth.

And there are far more generic manufacturers who would be burdened by this new obligation.

But, Your Honor, I would--

Justice Anthony Kennedy: Is -- is there any breakdown as to how many of those requests are generic and how many from branded?

Mr. Lefkowitz: --Your Honor, almost all of them I would believe are from branded manufacturers, because generic manufacturers until the briefing in this Court have never believed that they have any obligation to ask the FDA.

In fact, interestingly, the FDA has addressed what happens in the marketplace when a brand exits the market and the only drugs left are the 10 or 15 generics.

And what the FDA has said, and they have published 52 Federal Register notices -- we cite one of them in our reply brief -- they have said: In such a situation, we will designate one of the generics to be the leader for purposes of establishing the label, and everyone else has to follow.

But critically, what the FDA has said is: In those situations, we, the FDA, will tell you when the label needs to change.

Justice Stephen G. Breyer: So what are you supposed to do if your company happens by chance to come across a very, very high correlation between people who take your generic drug and who get seriously ill?

And now what you know is that nobody else has really found that, but, my goodness, there you are; it happened that it was associated, a special group or something.

What are you supposed to do?

Mr. Lefkowitz: Your Honor, we have an obligation, actually, to provide all of that information to the FDA.

Generics, unlike brand companies, aren't equipped in the same way, necessarily, to evaluate the--

Justice Stephen G. Breyer: And so are they saying that you -- is it conceded in this case that you did tell the FDA everything you knew about that?

Mr. Lefkowitz: --Well, no.

We--

Justice Stephen G. Breyer: Or is that a point in dispute?

Mr. Lefkowitz: --The plaintiffs allege that we violated Federal disclosure obligations.

Of course, there's no basis for a State claim for that.

In fact, to -- to address Justice Ginsburg's question--

Justice Stephen G. Breyer: Well, how would it conflict?

Suppose the State said: Here is what we want; we notice that it says in the Federal law that you must keep your warnings up to date, and if you find an association, you must revise your warning.

Now, we understand you can't do that without FDA approval.

But as far as our State is concerned, we think that when you come across this serious problem you have to tell the FDA in some form or other, a reasonable form, about it.

Would that law -- is there anything Federal that that law would conflict with?

Mr. Lefkowitz: --I think that law, Your Honor, would conflict with the Buckman principles and the ArkLa principles.

Justice Antonin Scalia: I thought you said you had to tell the FDA about it.

Mr. Lefkowitz: If the -- I understood Justice Breyer's question to be asking whether -- not only did we have to tell the FDA, which we clearly do, but whether we then had some additional duty to ask the FDA to change the warning.

Justice Antonin Scalia: Okay.

I didn't understand that.

Justice Stephen G. Breyer: What I wonder -- see, I wonder if that's this case.

I wonder if this case is what they're saying is: Oh, we concede you told the FDA every single thing, so they were just as informed as you are about the risks here, but you did not add the words: And please change our -- your permission, so that we can change the warning.

Is that what this case is about?

Mr. Lefkowitz: Well, I think that's what they're suggesting.

But even if it were just the former--

Justice Stephen G. Breyer: When they come up here they might say this isn't just what this case is about.

Mr. Lefkowitz: --Even if it's just the former, Your Honor, even if it's just the failure to disclose adverse reports--

Justice Stephen G. Breyer: Yeah.

Mr. Lefkowitz: --which we know we have an obligation to do, there is no history of State regulation of communications between Federal -- Federal agencies and the regulated parties.

Those are not the kinds of parallel claims cases, like in Lohr v. Medtronic--

Justice Stephen G. Breyer: So your argument is that if we run across this tremendous, really serious -- I can make an imaginary as serious as you want -- really a serious problem, and you're saying the State has no right to say -- even if we purposely didn't tell anybody, they can't get involved because they can't get involved with our failure to tell the FDA anything because that's Federal, and we can't -- they can't get involved with our failure to try to change the warning because that's taken care of by our obligation to tell them, which we didn't fulfill?

Mr. Lefkowitz: --Justice Breyer, correct, because that's exactly -- remember, in Buckman what happened was an individual was injured because the company had not accurately disclosed, in fact had misled the agency about the purpose of marketing these bone screws.

Clearly there was a State interest in protecting and providing a remedy to that consumer, a State interest in ensuring accurate disclosures to the government, and in fact an allegation that had there been accurate disclosures to the government, the FDA would have made a different safety and labeling determination.

Justice Antonin Scalia: So you say that if the claim here is simply that you did not disclose properly, that claim could be brought?

Mr. Lefkowitz: Not in a State court, Your Honor.

Chief Justice John G. Roberts: To disclose -- I'm sorry.

To disclose to the FDA?

Mr. Lefkowitz: Correct.

Justice Antonin Scalia: To disclose to the FDA.

Mr. Lefkowitz: A claim, Your Honor, of disclosure to the FDA relates to the inherently Federal relationship.

Justice Antonin Scalia: But you just described Buckman as -- as involving precisely that, failure to tell the FDA the purpose of the screws.

You said that the State -- the State suit would lie because of that failure.

Mr. Lefkowitz: No, I said the State suit -- I apologize.

I meant to say and I thought I said the State suit would not lie because Buckman preempts that type of lawsuit.

Buckman says even in that terrible situation, misleading to the FDA, failure to disclose what the FDA requires you to disclose, there is no State cause of action because this is a uniquely Federal area and States can't supplant the FDA in its enforcement discretion.

Justice Elena Kagan: But Mr. Lefkowitz, I think what the Respondents would say is that you are mischaracterizing their complaint and making it into something that it's not.

Their complaint is a standard state failure to warn claim.

Now, you have a preemption defense to that claim, and in that preemption defense there's going to be questions about your disclosure obligations and whether the FDA would have responded in a certain way to your disclosure obligations, but it's in a fundamentally different posture than the one that you're suggesting.

Mr. Lefkowitz: Justice Kagan, I would agree with you that what they pled below was a traditional failure to warn.

A failure to warn claim means you did not warn the public in the way that we think under State law you should have.

And whereas in Wyeth the Congress through the FDA has said a brand manufacturer ultimately is responsible for the warnings it issues and therefore can change the warning and therefore can be held liable, we don't have -- and the government agrees with us -- we don't have any mechanism under law to change the warnings.

So to the extent this is a traditional failure to warn claim, it has to be preempted under simple Supremacy Clause principles.

Justice Elena Kagan: Well, I agree that you don't have any ability yourself to change the warning, but here's what the FDA has said.

The FDA has said if an ANDA applicant -- and that's you; you're an ANDA applicant -- believes new safety information should be added to a product's labeling, presumably because they've gotten information that suggests that the product's labeling is wrong, then it should contact the FDA, and the FDA will determine whether the labeling for the generic and listed drugs should be revised.

Mr. Lefkowitz: Your Honor, that is exactly what the FDA says.

They point for that to a preamble in 1992 to a rulemaking that didn't address the relevant 201.57 regulation, a preamble that was issued without notice and comment rulemaking, and a preamble that doesn't actually impose a duty.

It says if, subjunctively, we believe that there should be a label change, we should do something, we should ask the FDA.

Not we must, not we shall.

And even then it said: And the FDA will then make a decision, which makes clear that this is not a decision for State juries to make.

Your Honor, the FDA has articulated a Federal duty today in its briefing in this case that is very much at odds with what it has specifically said about what a generic's obligation is under 201.57.

In the two notice and comment rulemakings at issue during the relevant time period here, in 2000 and 2006, what the FDA said very specifically was a generic's obligation under 201.57 is to use the brand label, even if the brand label isn't the most up-to-date.

And the reason is the policy underlying Hatch-Waxman is that brand companies do safety and efficacy testing; generics do sameness testing.

Generics are required to make copies of the drugs and by definition make copies of the labels, because it wouldn't make any sense to go into a drugstore to buy Advil and to see 15 different generic ibuprofen and to have 15 different sets of warnings.

Justice Sonia Sotomayor: Counsel, do you think--

Justice Anthony Kennedy: Buckman was a case -- I'm pronouncing it right, I think, Buckman -- where it was a branded manufacturer, was it not?

Mr. Lefkowitz: It was a medical device manufacturer.

Justice Anthony Kennedy: A medical device manufacturer.

So there it was -- it was an FDA process, and we said there's no State cause of action for saying that the FDA process -- that's slightly different from saying that you have a duty to warn the FDA.

You might say it's a fortiori.

Mr. Lefkowitz: Your Honor, I do think it's a fortiori.

Buckman involves the branded process of coming on with an equivalent medical device under the 510K process.

This is actually a situation where, after intensive back and forth with the FDA, the brand company crafts the label that the FDA approves and the generic is given one responsibility by Congress.

The responsibility is to maintain the same label as the brand.

That's the critical difference.

Justice Sonia Sotomayor: --Counsel, do you think Congress really intended to create a market in which consumers can only sue brand-named products?

Because if that's the case, why would anybody ever take a genetic?

And why in the world would Congress create a different, or even the FDA, a different obligation on brand-named products or generic products to give them information about labels when they know there's been a misbranding?

What the government says is you start by instructing a jury that there had to actually have been information that proved a misbranding.

That's the first step of the tort suit according to the government.

So why should you or why would Congress or the FDA have intended to treat the two differently?

Mr. Lefkowitz: Justice Sotomayor, I want to take both halves of your question.

In 27 years of enforcement under Hatch-Waxman, the FDA has never once said that a generic drug that uses the brand label, as required under 505(j) of the statute is misbranded.

And the -- look, I understand that from the consumer's perspective it may not make a lot of sense.

But what Congress specifically said is that a generic has to bear the same label, and it's because they do have different purposes, different functions.

Congress said that whenever there is a brand drug on the market that no longer is protected by its patent monopoly but has been selling for $10 or $20 a pill, we want to have generics selling for pennies for the pill, and they've given branded and generics different obligations.

And the different obligations are seen most clearly through the prism of the Wyeth case.

The Wyeth case was -- it was critical in the Wyeth case that this Court found that the brand company had the ability, had the obligation, to use the CBE regulations to actually change the label, whereas here what the FDA has said time and time again is: We'll tell a generic when the generic has to change the label, because we don't assume that the generics are going to know when the label should change because they don't have the same basis of clinical testing and results.

Justice Ruth Bader Ginsburg: Mr. Lefkowitz, there's a certain overlap, is there not?

Some of the generics are made by the same people that make the brand-name drugs, isn't that so?

Mr. Lefkowitz: That is correct, Your Honor.

Justice Ruth Bader Ginsburg: And at least for those people, they have the means.

Mr. Lefkowitz: Your Honor, I don't know whether or not the -- the FDA or this Court would hold differently in a case where the generic at issue was an authorized generic, a generic manufactured by a brand company that had, in fact, done all the clinical safety testing and might have a different basis for assessing the occasional adverse reports that they get.

But, again, the keys to understanding the -- the generic industry -- generics rarely even get adverse reports because if a doctor prescribes a drug, the doctor prescribes it as the brand, and then checks off the box that says a generic can be issued.

If a patient comes and tells him about an adverse report, the doctor has no idea which generic of the 15 that might be in the market actually was dispensed, so he'll actually tell the brand company.

He'll report the adverse event to the brand company.

Justice Sonia Sotomayor: Counsel, all you're arguing is that this rule will have little practical effect, that there is going to be very few lawsuits that could be brought against your companies because you're just not going to have enough information to suggest a label change.

Mr. Lefkowitz: Your Honor, what I'm arguing is that for the FDA to impose a new Federal obligation that will significantly change the way generic companies conduct their business should go through notice and comment rulemaking.

It should not rely on a preamble to a different rulemaking that didn't go through notice and comment.

It should not rely on briefs that are filed at the merits stage, because this would totally change the way generics do business.

Generics don't have a practice -- they're not even set up -- to go and figure out what label changes would be appropriate.

They are set up to report adverse events to the FDA, and what Congress has said and what the FDA has said is violations of those statutes, violations of those regulations, are exclusively within the province of the Federal government.

That's what Buckman says very clearly when it looks at Section 337.

If I may, I would like to reserve my time.

Chief Justice John G. Roberts: Thank you, Mr. Lefkowitz.

Mr. Bograd.

ORAL ARGUMENT OF LOUIS M. BOGRAD ON BEHALF OF THE RESPONDENTS

Mr. Bograd: Mr. Chief Justice, and may it please the Court:

The central issue in this case is that Petitioners, in the face of considerable information that the warnings on their products were inadequate, did nothing.

The generic drug companies' position is that they -- no matter how much they know, no matter how grave the risk, they are under no obligation to do anything to warn of the dangers of the products they sell.

Justice Antonin Scalia: Well, they're -- they're -- they're under the obligation to report to the FDA the facts which establish the grave risk, right?

Mr. Bograd: Yes, they are, Your Honor.

They're obliged under--

Justice Antonin Scalia: So the argument here is whether it -- it will be the FDA ultimately that determines whether there was a grave enough risk to modify the -- the label or whether that call will be made by -- by a State court guessing what the FDA would have done, right?

Mr. Bograd: --No, Your Honor, that's not correct.

What this Court said in Wyeth v. Levine is that State juries are a perfectly appropriate vehicle for assessing whether warnings in the past were adequately given.

We do -- we do not dispute that the issue about what language will be on a label going forward rests with the agency.

Justice Antonin Scalia: Yeah, but -- but -- no, but -- but surely you have to establish not only that the generic manufacturer requested a label change, but that a label change would have been approved.

Otherwise there's no causation.

Surely--

Mr. Bograd: That's correct, Your Honor.

Justice Antonin Scalia: --that's part of your case, isn't it?

Mr. Bograd: No, it's not, Justice Scalia.

The -- as Petitioners concede in the brief, under traditional State law failure to warn claim, our affirmative case is that the warnings that were given to the doctor and to the patient were inadequate, and that because adequate warnings weren't given, the patient was injured.

Justice Antonin Scalia: No, but -- but their -- their preemption claim is we had to give these warnings, and you don't contest that.

They had to give the warnings that they gave, unless the FDA said that the warnings must be changed, so--

Mr. Bograd: Your Honor--

Justice Antonin Scalia: --I mean, I don't see how you can hold them liable, so long as they continued to give the warnings that they had to give.

Mr. Bograd: --Your Honor--

Justice Antonin Scalia: And they could have lobbied the FDA to say, you know, change the warning, but if the FDA said -- suppose the -- suppose they did tell the FDA, please modify the label, and the FDA said no.

Would your lawsuit still proceed?

Mr. Bograd: --No, it would not, Your Honor.

Justice Antonin Scalia: No.

Mr. Bograd: Once the FDA said no, we would have clear evidence that the FDA would have rejected the warning--

Justice Antonin Scalia: I would say--

Mr. Bograd: --which is what this Court said in Levine is the touchstone.

Justice Antonin Scalia: --All right.

You're drawing a line between the FDA rejecting a warning and the FDA not accepting the warning; is that the line you're drawing?

Mr. Bograd: Yes, Your Honor, for purposes of impossibility.

In order for the -- preemption is an affirmative defense, and for the defendants to establish that it was impossible, i.e., that the duties under State and Federal law were in direct conflict, they have to show that the FDA would have rejected--

Justice Stephen G. Breyer: It appears also that the -- it's Buckman, it seems to me, the relevant case, not Wyeth, because what -- if -- you're now saying, I've learned, that -- that they have a set of FDA duties; they must tell the FDA every detail.

Mr. Bograd: --Well--

Justice Stephen G. Breyer: That sounds awfully familiar to Buckman, where the State claim was basically a claim of fraud on the FDA.

And we said it's not up to the State to -- to -- they can't bring -- have a claim for fraud on the FDA.

The FDA has to enforce their own stuff.

And why isn't the same true here, that the FDA has to enforce their own legal requirement to tell us everything you know?

What's the answer to that?

Mr. Bograd: --Well, there are two answers, Your Honor.

First -- first, this Court's decision in Levine is inconsistent with that sweeping reading--

Justice Stephen G. Breyer: No, because Levine involves the Wyeth case, right?

Mr. Bograd: --Yes.

I'm sorry, I--

Justice Stephen G. Breyer: No.

The -- the difference there is the difference that the SG points out: There is a broad-ranging obligation for the initial drugmaker to tell the FDA all kinds of things and change the warnings.

But here the FDA tells us they have no power to change their warnings.

They can't, unlike Levine.

They have to copy the original maker.

So -- I'm -- I'm just referring there to the whole SG brief.

Mr. Bograd: --Your Honor, let me respond to that in -- in two ways.

First--

Justice Stephen G. Breyer: Be sure you answer, please, my original question.

Mr. Bograd: --I -- I will, Your Honor.

The -- to focus first on the CBE issue, one of the things this Court noted in Levine is that even under the CBE process, the ultimate decision about whether the labeling is changed rests with the FDA, not with the manufacturer.

The -- the fundamental issue in Levine was that the primary responsibility for labeling rested with the manufacturer, not with the agency, subject to the agency's review.

And we don't dispute that the agency has the right to review and can reject a label.

The -- what was at the core and what this Court cited, although the -- the number has changed in Wyeth v. Levine, is the obligation under 21 CFR 201.57(e), which you call 201.80(e) because they -- they renumbered it -- that the label warnings shall be revised as soon as there's reasonable evidence of an association of a serious hazard with the drug.

The government says, and the regulatory structure makes clear, that that provision applies with full force to generic drug manufacturers, not just to name-brand drug manufacturers.

It is the regulatory implementation of the obligation under the Federal misbranding statute, 21 U.S.C. 352(f)(2) that says you can't sell a drug that doesn't have adequate warnings about its risks.

So, when you're -- when the manufacturer is confronted with information that the warnings on its drug are not adequate, it -- the way it -- the way it should respond is by immediately going to the FDA and saying to the agency: We have this new information; we ask you, not that we want a different warning from the name brand, but we ask you to approve a stronger warning on both the name-brand product and its generic equivalents.

Chief Justice John G. Roberts: But what happens--

Mr. Bograd: And had they done so, we would know -- one of two things would have happened.

Either the agency would have approved the warning, stronger warnings would have been given and our clients -- my clients likely would not have been injured; or they would have said, no, we don't think there's sufficient information to justify this warning.

Chief Justice John G. Roberts: --How long does it take -- how long typically does it take the FDA to respond to a request from a generic manufacturer that it -- it ask the branded manufacturer to change the label?

Mr. Bograd: Your Honor, as you just heard from Mr. Lefkowitz, generic manufacturers typically haven't been fulfilling this obligation and have not been asking the agency.

But the latest data from the agency, and this is from its -- its web site, is that under -- they've been publishing performance data since 2007, and they now say that safety labeling changes, which are the labeling changes required under FD -- under FDA, are processed typically in a matter of months, 94 percent within 3 months.

Chief Justice John G. Roberts: Are those the ones that are submitted by generic manufacturers?

Mr. Bograd: They're -- they are -- they could be ones submitted by generic manufacturers.

Those are ones where the information that comes to the agency triggers a -- a labeling revision process.

Justice Anthony Kennedy: Does the -- does the--

Chief Justice John G. Roberts: --whether about--

Mr. Bograd: I'm sorry, what was that?

Chief Justice John G. Roberts: --I was just going to ask, does the FDA give you an up or a down, or does it just not take action sometimes if you submit one of these requests?

Mr. Bograd: Your Honor, my understanding -- there were certainly procedures available that would have required an up-or-down: The citizens petition process, for example, the supplement process, for example.

The -- what -- the government has represented that even if the request came in a more informal form, the government would nevertheless take a request for a -- a labeling change to reflect a serious inadequacy in label warning seriously and act on it promptly.

Justice Antonin Scalia: Just so I understand what you've said, this 3-month turnaround that you mentioned, they are all requests from labeled manufacturers, right?

Mr. Bograd: No, Your Honor, these are -- these are actually--

Justice Antonin Scalia: I thought you said that generic manufacturers don't make any requests.

Mr. Bograd: --I -- they could be -- they could be from name-brand companies; they could be from private citizens.

Justice Antonin Scalia: Oh, okay.

Mr. Bograd: It's whenever the agency becomes aware of information.

Justice Antonin Scalia: Oh, I see.

Mr. Bograd: But the agency also processes supplement requests, according to its web site, in 97 percent of the cases or something, within 4 months.

It's not -- it's -- it is a matter of months, not -- not years.

Justice Sonia Sotomayor: Can you, and I think that this is part of what your adversary has been talking about when he says we don't usually receive adverse incident reports; they go to the brand manufacturer.

So tell me what you view as your main obligation.

This is a little bit like what Justice Scalia was asking.

You come in and you say there's a drug, it has an adverse effect, there should have been a warning about it because look at all of this literature, look at all of this proof--

Mr. Bograd: Uh-huh.

Justice Sonia Sotomayor: --that this drug is, in fact, in some way plausibly or otherwise causing this incident, and the label was inadequate to tell me not to do it.

Is that your obligation completely?

You don't have an obligation to show that this particular manufacturer knew that in some way?

Mr. Bograd: Well, under most -- under the law of most States, and this is true in both Louisiana and Minnesota, there is a reasonableness element in a failure to warn claim, but it's -- the standard is "knew or should have known", so that the manufacturer -- manufacturers are typically held to the -- to the knowledge of an expert in the field of the products they manufacture.

And here the -- our contention has been that if the generic manufacturers had merely examined the publicly available FDA database of adverse event reports, and merely paid attention to reports in the published literature that had since 19 -- the early 1990s had documented a serious association between long-term use of metoclopramide and tardive dyskinesia, they would have had more than sufficient information to say to the agency, we need a change here.

Justice Antonin Scalia: Does a generic manufacturer have to be an expert in the field in which it manufactures?

Mr. Bograd: Under State law, yes, it does, Your Honor.

Justice Antonin Scalia: What does -- what does being an expert mean?

Mr. Bograd: It means--

Justice Antonin Scalia: In this context, being an expert means being able to produce exactly the drug that has been approved by the FDA, right?

You don't have to be expert in anything else?

Mr. Bograd: --That's incorrect, Your Honor.

They have to be--

Justice Antonin Scalia: What else do they need?

Mr. Bograd: --They have to remain informed of the dangers posed by the products they sell.

They have obligations--

Justice Antonin Scalia: That doesn't make them an expert.

I'm talking about what expertise does -- does the company have to -- to possess.

It surely has to possess the chemical expertise to produce exactly the product that the -- that the -- that has been approved by the FDA.

What other expertise is necessary?

Mr. Bograd: --Well, Your Honor, one of their obligations under Federal law is to go to the agency every year and identify significant new information that would affect the safety or efficacy or labeling of their product, which means they have to have the capacity to evaluate information that is out there, and that--

Justice Antonin Scalia: I don't think that'd take any expertise.

You have people who complain, I've taken -- I've taken your pill, and it -- it, you know, it's caused -- this is expertise?

That's not what I normally think of.

Whereas a drug manufacturer does, indeed, require expertise, conducting tests and knowing what changes will produce what results and so forth; right?

Mr. Bograd: --No, Your Honor.

In fact, in this particular context we're talking about a use that was never approved by the FDA.

We're talking about use beyond 12 weeks, which had never been evaluated.

So there's really no basis to assume that the name-brand manufacturer here had any more expertise--

Justice Stephen G. Breyer: Suppose they had.

Suppose that -- is a generic required to file adverse incident reports?

Mr. Bograd: --Yes, they are, Your Honor.

Justice Stephen G. Breyer: Okay.

Now, imagine a company that files every adverse incident report, complies completely; period.

Now, in your view does it have an additional obligation?

Mr. Bograd: Yes, it does, Your Honor.

Justice Stephen G. Breyer: And what is that?

Mr. Bograd: It has an obligation under 201.57(e) to initiate a label change--

Justice Stephen G. Breyer: Okay.

Mr. Bograd: --process whenever it has reasonable--

Justice Stephen G. Breyer: Now, their argument is that in respect to their failure to do the first, that's Buckman.

That is similar to Buckman.

Mr. Bograd: --All right.

If we -- we were talking about--

Justice Stephen G. Breyer: Now.

And that's what I -- now, as to the second, it just doesn't add anything.

The FDA has all that information.

Mr. Bograd: --Oh, that's -- that's incorrect, Justice Breyer.

Justice Stephen G. Breyer: All right.

Now, why is it?

Mr. Bograd: It's -- well, as this Court said in Levine, the FDA has 11,000 drugs it needs to monitor and stay on top of, and it doesn't have the resources necessary to pay attention to every adverse event report it gets and every report that is published in the scientific literature.

The reason that manufacturers bear the primary responsibility is because they -- they need to trigger the FDA's focus on a particular issue here.

Here this information was available since the mid '90s.

Justice Stephen G. Breyer: Your basic argument, I'm getting this now, that -- I think -- is that the failure is, where State law has a right to enter, is to require them to keep track of adverse incidents and other things in the -- and do their best to change the label, which will consist of going to the FDA, likely, and asking them to change.

Mr. Bograd: Exactly, Your Honor.

Their obligation -- their obligation under State law is to provide a warning.

What they should have done, and if you take -- what they should have done is go to the FDA and ask the FDA to approve a stronger warning.

If the FDA had said no, they would have a preemption.

Chief Justice John G. Roberts: Counsel--

Justice Samuel Alito: Suppose a generic -- suppose that the FDA issued a rule that says a generic drug manufacturer has no obligation to request a change in labeling.

Could a generic drug manufacturer be held liable on a failure to warn claim on the theory that it could have lobbied the FDA to change the rule that says that the generic drug manufacturer has no obligation to ask for a change in labeling?

Mr. Bograd: I -- I don't have an immediate answer to that, Justice Alito.

The -- the -- the State -- the -- I -- the question is whether there would be a direct conflict between State and Federal law.

It seems to me unless -- I'm sorry.

Oh, that's the 5 minute light.

Unless the--

Justice Samuel Alito: Isn't that why -- isn't that where your theory leads?

Mr. Bograd: --My -- my theory leads to the -- to the proposition that, unless Federal law precludes them from -- from going to the process of strengthening their warning label, then the State may legitimately enforce its obligation to protect its citizens' health and safety.

I think it's important in this regard--

Justice Samuel Alito: But your theory is that they have a duty to pursue an informal process that is nowhere provided for under the FDA rules; and so I don't -- so it's a duty to lobby the FDA basically to change the rules, isn't that right?

Mr. Bograd: --Justice Alito, well, as you know, we disagree with the government about whether certain formal processes were available.

But--

Justice Samuel Alito: Assuming that they're correct in their interpretation of their own regulations.

Mr. Bograd: --But assuming -- but -- but if we're talking -- but there may not be a formal process, but there is a formal obligation, both under statute, not to sell a misbranded drug, and under regulation, to revise your labeling as soon as there's reasonable evidence of an association of a serious hazard with the drug.

And I think it's--

Justice Anthony Kennedy: --What is your -- what is your explanation for why Buckman isn't applicable here?

Mr. Bograd: --Because, Your Honor, this is -- and I should start by saying that in Buckman there was -- the suit was not against the manufacturer; the suit in Buckman was against a consultant that -- that helped the manufacturer get FDA approval.

There was a separate product liability action against the manufacturer that had already been litigated and settled.

The -- Buckman said: We're not talking about traditional causes of action, State law causes of action like in Lohr, or like in -- or as this Court again said in Wyeth v. Levine; we're talking about a case where the whole centrality of the claim is premised on the relationship between the company -- or the defendant and the agency.

This is not that case.

We're -- this case is about the -- the duty that the company owes to my clients and their doctors to provide them with adequate warnings.

That duty, which is -- has been recognized by this Court innumerable times, complements the FDA statutory scheme by creating incentives for companies like the Petitioners to--

Justice Anthony Kennedy: Well, the suit was brought by the injured person in Buckman.

Mr. Bograd: --But--

Justice Anthony Kennedy: And it's similar in that respect.

And in Buckman there was a -- a formal relationship which did not permit the cause of action, and it seems to me you could at least argue that a fortiori there should be no cause of action when there an informal relationship.

Mr. Bograd: --I -- I'm not sure I follow the a fortiori point in this context, Your Honor.

But in Buckman there was no relationship whatsoever between the consultant, the Buckman Company, and the injured person.

The Buckman Company's dealing were -- had been exclusively with the agency.

They had had no dealing whatsoever -- they had not failed to warn.

That's why we -- the plaintiffs had created this bizarre cause of action, and it's -- we think it's a wholly distinguishable case.

I think it's important to remember, first off, the world in which we live today.

70 percent of all prescriptions are filled with generic drugs.

A third of generic drugs no longer have name-brand competitors at all, because the economic -- because the name brands have withdrawn from the market, so that--

Justice Antonin Scalia: Somebody has been appointed in all those cases to sort of carry the flag, right?

Mr. Bograd: --Somebody has been appointed to be the reference-listed drug.

They have not been appointed to have obligations distinct from the other generic companies as far as updating label claims.

Justice Antonin Scalia: Don't they have a distinct obligation to propose labeling changes when they -- when they think they're necessary?

Mr. Bograd: I -- Your Honor, that would be a question better directed to Mr. Kneedler, but I don't believe -- I don't believe that there's a -- there's a difference.

Any -- we have a system today where every State has a drug substitution law that drives prescriptions to be filled with generics rather than name-brand products.

We have a system where Medicare, Medicaid, and insurers force or encourage the substitution of generics through -- through price incentives.

If generics are not responsible, in many of these cases no one is responsible.

The -- we -- the position that the generics are proposing here is one in which they would be immune from liability for selling a product with inadequate warnings, even though the name-brand company selling the same drug with the same warnings would be liable.

There is no suggestion anywhere in the record, Your Honor, anywhere in the legislative history or in the text of Hatch-Waxman or in FDA regulations that that distinction was ever contemplated by Congress, that it was ever sanctioned by the FDA.

I would like to make one final point, Your Honor.

In Bates -- and I apologize; we didn't address this specifically in our briefs, because I didn't notice it until later -- the statutory scheme at issue in Bates, under FIFRA, was almost identical to the -- I'm sorry.

I see my time has expired.

May I finish my point, Your Honor?

Chief Justice John G. Roberts: --You can finish your sentence.

Justice Antonin Scalia: Make it a long sentence, with a lot of "ands".

[Laughter]

Mr. Bograd: There was no CBE equivalent in Bates in the -- under the FIFRA statutory scheme, and yet this Court upheld against a motion to dismiss on preemption grounds a failure to warn claim, admittedly under an express preemption provision.

This Court upheld a claim against a pesticide manufacturer even though the pesticide manufacturer could not have changed its warning without prior EPA approval, exactly the same situation that confronts the generics here.

Thank you, Your Honor.

Chief Justice John G. Roberts: Thank you, counsel.

Mr. Kneedler.

ORAL ARGUMENT OF EDWIN S. KNEEDLER, ON BEHALF OF THE UNITED STATES, AS AMICUS CURIAE, SUPPORTING THE RESPONDENTS

Mr. Kneedler: Mr. Chief Justice, and may it please the Court:

The Hatch-Waxman Amendments were designed to facilitate the entry of generic drugs onto the market.

They do not absolve a manufacturer of his responsibilities after entry onto the market to maintain the safety of the drug and the adequacy of -- of the label.

Justice Elena Kagan: Mr. Kneedler, suppose that I'm not sure I agree with you that there is an obligation of the kind that you say for a generic drug manufacturer to come forward and request a label, but I do think that there's an opportunity for that manufacturer to come forward and ask the FDA to revise a label.

If that's the way I read the law, does your result follow?

Do you think, then, that State law claims should be able to go forward?

Mr. Kneedler: Yes, we do, because the ultimate question in the preemption case is whether there's a conflict.

And if the -- if the manufacturer has an opportunity to come to FDA, even if -- even if the Court were to conclude it didn't have an obligation to do so, if it had the opportunity to do so and did nothing when -- when dramatic evidence, you know, by hypothesis, came to its attention, it wasn't prohibited from doing so.

There was no--

Justice Antonin Scalia: Well, I assume that the patient's physician has the same opportunity.

Anybody could go to the FDA and say this label ought to be changed, right?

So the -- the physician taking care of this plaintiff didn't -- had the opportunity to go to the FDA and didn't.

Is there a cause of action against him?

Mr. Kneedler: --Well, the -- the FDCA does not regulate the responsibilities of physicians in those situations.

The whole point of the labeling--

Justice Antonin Scalia: I'm not talking about what the -- the FDCA regulation.

We're talking about what State law would allow, and State law would allow a suit against the physician because he did not take advantage of the opportunity to go to the FDA and propose a label change.

Mr. Kneedler: --No, I think State law would -- would impose an obligation on the physician to adequately advise the patient, but what's so different is, the physician relies upon the labeling.

If the physician has the information, the physician, on his own initiative, could tell the patient or warn the patient about what's going on without -- without having to go to FDA at all.

Chief Justice John G. Roberts: So if your theory of the case is accepted, this is what will happen: Every time a generic manufacturer gets an adverse incident report, it will send that on to the FDA, and there will be a boilerplate sentence at the end of it saying, We think you should consider revising the labels because of this, and then, under your theory, that manufacturer is completely protected from State suits?

Mr. Kneedler: Several things.

The manufacturer does, of course, have the obligation to furnish the adverse event information that it receives.

Chief Justice John G. Roberts: Sure.

Mr. Kneedler: But if -- if the standard in regulation 57(e) is met, where there's evidence, reasonable evidence, of a serious hazard, it has an obligation--

Chief Justice John G. Roberts: Well, they're not going to take a chance.

They're going to say, if you're the FDA, you look at it.

We're just telling you what we know, and we think you ought to consider revising the label.

Mr. Kneedler: --But they are -- they are to propose -- in our view, are to propose a labeling change, which means that the--

Chief Justice John G. Roberts: Okay.

We think you should revise the label; if you agree, this is what it should look like.

Mr. Kneedler: --Yes, and we don't -- we don't think it will lead to a flood of such requirements in the wake of this--

Chief Justice John G. Roberts: Does it lead to preemption?

Mr. Kneedler: --Pardon me?

Chief Justice John G. Roberts: Does it lead to preemption?

Mr. Kneedler: If the -- if FDA rejected the request, there would -- there would be preemption, because FDA -- it would have been submitted to the expert agency, as we think is required.

Chief Justice John G. Roberts: Right.

Wouldn't you -- if you were the generic company's lawyer, you would advise them to do that in every case, right?

Mr. Kneedler: I don't think I -- I don't think in every case.

I think it's -- if -- but here, here we have a situation where, at least according to the allegations, there were published studies of long-term use of this product.

Chief Justice John G. Roberts: No, I know that's what this case is, but if -- a reasonable generic manufacturer would be worried about every case, and it would just add this boilerplate language at the end of every letter, and as I understand your theory, they would be protected.

Mr. Kneedler: It's not just boilerplate evidence at the bottom of the -- as part of a letter.

What the -- what the Federal Register notice told the manufacturer to do was to -- was to submit the proposal to FDA with supporting information.

In other words, suppose it's the sort of submission that would -- that would be like--

Justice Antonin Scalia: That would be the -- the prologue -- the prologue to the rule said that, and the rule was never submitted for notice and comment.

Is that what you're relying on, that prologue?

Mr. Kneedler: --Well, I -- I think, to put it in context, these were the regulations actually implementing the Hatch-Waxman statute, and there was a proposal to allow the manufacturers to deviate from the -- from the NDA holders' label and put their own on it.

And the -- and FDA said, no, you can't do that, but what you should do is bring it to FDA, and FDA will decide whether to change the labels for everyone.

And so this was part and parcel of the notice and comment rulemaking: How should -- how should a generic manufacturer deal with a situation where it has information that may deviate from the NDA holder's -- how should it--

Justice Samuel Alito: Has the FDA made any calculation of the economic consequences of imposing this duty on generic drug manufacturers?

I don't know whether this is a good idea or not, but it does seem to me that it may significantly increase the costs for generic drug manufacturers, and therefore counteract one of the objectives of the statute, which was to provide generic drugs at a low cost.

Mr. Kneedler: --To my knowledge, FDA has not done an analysis.

But it's important to understand the duty here derives from the misbranding provisions.

A generic drug manufacturer is not exempt from the misbranding requirements of the act, which prohibit distributing a drug that does not have adequate -- adequate warnings, and rule 57(e) requiring a manufacturer to propose a warning or to make a warning change if there is evidence of a serious hazard implements that misbranding requirement.

So this is not an imposition by FDA.

This is an underlying requirement of the act.

I would--

Justice Sonia Sotomayor: Am I -- am I to understand -- and I think I am understanding you.

There is a legal obligation in the statute to report adverse events.

You're saying that the statute also requires every manufacturer, of whatever type, to monitor the safety of the drug they're selling?

Is that what you're saying?

Mr. Kneedler: --State--

Justice Sonia Sotomayor: And if reasonable evidence, whether directly in their possession or in the marketplace--

Mr. Kneedler: --The -- the FDA regulations do not explicitly require monitoring of literature, but -- but there's no conflict in State law imposing a duty to do that.

If I -- if I may just discuss Buckman for a minute, because--

Justice Antonin Scalia: How do you decide whether a generic manufacturer ought to have proposed a -- a labeling change?

Mr. Kneedler: --If the standard--

Justice Antonin Scalia: This is a generic manufacturer.

He doesn't know anything about -- about science.

He knows how to replicate this pill exactly.

That's all -- that's all he really knows.

Now, what is the test you're going to impose to -- to a jury to decide whether this generic manufacturer ought to have -- ought to have proposed a labeling change?

Mr. Kneedler: --It's the--

Justice Antonin Scalia: Is it -- is it, well, you know, if he had been as well armed scientifically as the original manufacturer of the labeled drug, he should have known or, you know, does this guy who graduated from high school and can replicate a pill, should he have known?

What -- what's the--

Mr. Kneedler: --It's the standard in 57(e) if there's evidence of a serious hazard, we think State law can impose on a generic manufacturer which is putting a potentially dangerous product on the market the obligation to -- to investigate.

I would -- I would like to talk about Buckman for just a minute, please, because it's -- it's come up.

Buckman is fundamentally different.

There was no independent State law duty to warn at issue in Buckman.

It was solely a tort based on lying to the FDA.

It is a tort that depended entirely on the existence of the FDA.

Chief Justice John G. Roberts: And in the brief -- and in the brief that you filed you said one of the concerns is that people are going to flood the FDA with all these warnings and -- and whatever, and that would interfere with the FDA's ability.

Now you're telling me -- you -- you said when you started out that you think it's unlikely or you don't think it's likely.

In your brief it said SG language you said we're not prepared to predict that a ruling would do this.

So, why is that a difference between those two cases?

Mr. Kneedler: Well, Buckman was a situation of a collateral attack on a decision that had actually been made by FDA.

There was no independent duty -- State law or duty to warn, no relationship between the person submitting information to FDA.

It was just a State making the tort to lie to the FDA, and you would have had the State regulating nothing but the relationship between the manufacturer and FDA.

Here State law is regulating the relationship between the manufacturer and -- and the patient through the doctor, and that's a traditional area of State regulation, duty to warn, and, Justice Kagan, I think you're right, the question then is whether there is an affirmative defense of -- of preemption, and the preemption comes in.

It's very different from Buckman in that situation.

It's up to the defendant to prove, it's not an element of the cause of action as in Buckman.

It's part of the defense for the defendant to prove that -- that it is -- that the cause of action is preempted.

And in our view it's not preempted if the standard in 57(e) is met to propose a labeling change that is an obligation that extends to all manufacturers generic or not.

Chief Justice John G. Roberts: Well, but it's not -- the regulation doesn't say propose a labeling change.

It says labeling shall be revised, and the one thing we know is that the generic manufacturer can't revise the labeling from the branded one.

Mr. Kneedler: It can't revise the labeling, but that doesn't mean it can do nothing.

Impossibility preemption kicks in only when it's genuinely impossible, and if the manufacturer could go to FDA and propose a labeling change, it is not impossible for to it do that.

At that point it's up to FDA and preemption would kick in.

Chief Justice John G. Roberts: Thank you, Mr. Kneedler.

Mr. Lefkowitz, you have your 5 minutes remaining.

REBUTTAL ARGUMENT OF JAY P. LEFKOWITZ ON BEHALF OF THE PETITIONERS

Mr. Lefkowitz: Thank you.

Mr. Kneedler has basically postulated a situation where we're going to have jury trials about whether a Federal duty to the FDA was breached.

And it's interesting, he says that this isn't Buckman, but of course, Buckman involved the same duty not to sell a dangerous product, and the same issue of lack of disclosure to the FDA.

Now, he says it was a collateral attack, but actually that was the premise of Justice Stevens' concurrence, where Justice Stevens said I get to the same result for a different reason.

What the Court said was nothing about a collateral attack.

Justice Sonia Sotomayor: Counsel, the difference, as I see it, is that they're not suing you for a failure to tell the FDA.

They're suing you for a failure to tell them.

It's you who are interposing a defense and saying I manufacture a dangerous drug, and I have no obligation to monitor and ensure that the label is accurate.

And what the government is saying, as I understand it is, no, you do.

Yes, we understand you want to sell more cheaply, but not at the cost of public health.

So what's wrong with that argument?

Mr. Lefkowitz: Justice Sotomayor, respectfully, what's wrong with the premises, if they're claiming failure to warn, it's a very simple case of impossibility preemption.

We couldn't warn, and the government's brief makes clear we had no ability to warn.

What the government is now doing is it's taking a regulation, 201.57, which doesn't say the word "ask" in it.

It actually says "revise".

And it says revise because it's a regulation written for brand manufacturers that have the CBE option available to them, and they are then trying to incorporate the words "duty to ask" through this brief without, as Justice Alito says, taking into any account through notice and comment rulemaking the effect of this.

Well, we know that there are over 1,600 requests for labeling revisions pending at the FDA now, 650 of them are pending for more than 6 months.

And at the relevant time of this case, Your Honor, not only would we have had to ask the FDA, but then the FDA would have had to negotiate with the brand, because prior to the FDAAA amendments, the FDA couldn't order a brand to change, so we would have had to make the request, the FDA would have had to negotiate the brand change, and then we would have had to follow.

Justice Elena Kagan: Well, Mr. Lefkowitz, if you had asked, you would be in a different situation.

If you had asked and the FDA had sat on it or was negotiating, then you could say, look, we've done all we can right now.

But you're not in that situation.

You, in fact, have not done all you can right now to change the label because you never wrote that letter.

Mr. Lefkowitz: Your Honor, and again just to pick up on -- on what Chief Justice Roberts said and Justice Scalia said, we have done everything we are required to do, which is to provide all of the information about adverse reports that we have and all of the results of our investigations to the government.

And if the government wants to impose a new duty through notice and comment rulemaking saying, and now we have a duty to ask for a label change, in addition--

Justice Ruth Bader Ginsburg: The government is taking the position that there's no clash between the government, the State, and Federal law.

It's not saying that you commit some kind of Federal offense if you don't file this law.

The government is saying, the question is preemption.

Is there a clash between Federal and State law to traditional Federal warn you have a preemption defense if you tell the FDA, and if either the FDA does nothing or tells you, no, we're not going to change the label?

Mr. Lefkowitz: --Your Honor, Buckman makes very clear that a State trying to regulate disclosure obligations to the Federal Government is simply off limits, and in fact--

Justice Ruth Bader Ginsburg: The -- the -- Buckman was about, was a -- it was a very odd case to be brought under State law for fraud on a Federal agency.

Mr. Lefkowitz: --Your Honor, it was a case brought by a plaintiff who was injured claiming that the company had not made proper, adequate disclosures to the FDA.

It's the same thing here, and I just want to point--

Justice Antonin Scalia: Mr. Lefkowitz, do you agree with Justice Ginsburg's characterization of the government's position?

I thought the government was saying that there was an obligation on the part of the generics to propose changes.

Mr. Lefkowitz: --Absolutely.

What they are saying--

Justice Antonin Scalia: Otherwise, the government would be saying you have an obligation to lobby, and I don't think they're saying that.

Mr. Lefkowitz: --Well, in a sense the government is really saying we -- to lobby or to propose changes is a -- is a very fine distinction.

Clearly, what the government is now saying is they are reading a regulation that they've always interpreted as being only applicable to brand companies and saying now it's applicable to their companies and it incorporates new language that says not just revise but ask.

Chief Justice John G. Roberts: Thank you, Mr. Lefkowitz.

Counsel, the case is submitted.

Print this transcript Transcript: 

Justice Clarence Thomas: This case has come to us on a -- on writs of certiorari to United States Court of Appeals -- Courts of Appeals for the Fifth Circuit and the Eighth Circuit.

Respondents were prescribed the drug Reglan to treat digestive tract problems.

Each received generic Reglan from her pharmacist.

After taking the drug for several years, each developed a serious neurological disorder.

Respondents then sued the manufacturers of the generic drugs in a state court alleging that the manufacturers failed to provide an adequate warning label.

The question presented here is whether Federal Drug Statutes and Regulations conflict with and thus pre-empt these state tort lawsuits.

The Fifth and Eighth Circuits found no pre-emption and allowed the lawsuits to proceed.

In an opinion filed with the clerk today, we reversed the judgments of the Courts of Appeals.

The generic manufacturers have demonstrated a conflict between state and federal law.

State law requires the manufacturers to change their warning labels but the Federal Drug Regulations prevent them from independently doing so.

The manufacturers could potentially have complied with state law but only with the help of the brand name Reglan manufacturer and the special permission and assistance of the Food and Drug Administration, a federal agency.

We find that federal law pre-empts the state law, state tort lawsuits here.

The Supremacy Clause of the Constitution instructs the federal law -- that federal law is the supreme law of the land, in a state law to the contrary notwithstanding.

It would distort the plain text of the Supremacy Clause to find no pre-emption simply because a federal agency has the discretion to resolve an existing conflict between federal and state law on a case by case basis.

Justice Kennedy joins all but Part III–B–2 of the opinion.

Justice Sotomayor has filed a dissenting opinion in which Justices Ginsburg, Breyer and Kagan joined.