OPINION OF THE COURT PLIVA, INC. V. MENSING 564 U. S. ____ (2011) SUPREME COURT OF THE UNITED STATES NOS. 09-993, 09-1039, AND 09-1501 PLIVA, INC., et al., PETITIONERS

															09–993 v. GLADYS MENSING ACTAVIS ELIZABETH, LLC, PETITIONER 09–1039   v. GLADYS MENSING ACTAVIS, INC., PETITIONER 09–1501   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 failure to provide adequate warning labels for generic
metoclopramide. 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 movement of food through the digestive system. The
Food and Drug Administration (FDA) first approved metoclopramide
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 diges- tive tract problems such as
diabetic gastroparesis and gastroesophageal reflux disorder.

															   Evidence has accumulated that
long-term metoclopramide use can cause tardive dyskinesia, a severe
neurological disorder. Studies have shown that up to 29% of
patients 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 Cisapride, 44 J. Am.
Pharmacists Assn. 661, 663 (2004) (noting 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 approved, 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 metoclopramide
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
generic drug manufacturers that produced the metoclopramide 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 dyskinesia 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
Manufacturers, 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 manufacturer’s duty to warn includes a duty
to provide adequate 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 Manufacturers 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 adequately 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 different, 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.[ Footnote 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.[ Footnote 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
manufacturers have different federal drug labeling duties. A
brand-name manufacturer seeking new drug approval is responsible
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 interprets 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).[ Footnote 3 ]

															1

															   First, Mensing and Demahy urge
that the FDA’s “changes-being-effected” (CBE) process allowed the
Manufacturers 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
contraindication, warning, [or] precaution,” 21 CFR
§314.70(c)(6)(iii)(A) (2006), or to “add or strengthen an
instruction about dosage 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
supplemental 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
generic drug manufacturer changes its label to match an updated
brand-name label or to follow the FDA’s instructions. 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 therefore 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 Manufacturers 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 “consistent 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 labels.
According to the FDA, the Manufacturers could have proposed—indeed,
were required to propose—stronger warning labels to the agency if
they believed such warnings 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
application, 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 fed- eral drug regulation is that the manufacturer bears
responsibility 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 strengthening 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 Hatch-Waxman Amendments. Ibid.; see 57 Fed. Reg. 17961 (“If a [generic drug
manufacturer] 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”). 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 pursuant 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 requirements 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 changing their generic drugs’ safety labels. But, we
assume, federal law also required the Manufacturers to ask for FDA
assistance in convincing the brand-name manufacturer 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 naturally 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.”[ Footnote 4 ] Freightliner Corp. v. Myrick , 514 U. S. 280 , 287
(1995) (internal quotation marks omitted).[ Footnote 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 metoclopramide. 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 Manufacturers 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
strengthening 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 Manufacturers’ 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
Manufacturers had asked the FDA for help in changing the
corresponding 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 manufacturer. Federal law
does not dictate the text of each generic 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 requirements 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 impossibility 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 warning label. Of course, it is also possible that the Manufacturers 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
argument 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
Supremacy Clause would have any force.[ Footnote 6 ] We do not read the Supremacy Clause to permit
an approach to pre-emption that renders conflict pre-emption all
but meaningless. The Supremacy Clause, on its face, makes federal
law “the supreme Law of the Land” even absent an express 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 contemplates 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 ob-stante 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]
together”); Ludlow’s Heirs v. Johnston , 3 Ohio
553, 564 (1828) (“[I]f by any fair course of reasoning the two
[statutes] can be reconciled, both shall stand”); Doolittle v. Bryan , 14 How. 563, 566 (1853)
(requiring “the repugnance be quite plain” before finding implied
repeal). A non obstante provision thus was a useful way
for legislatures 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 recognizing 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., concurring in judgment) (internal
quotation marks omitted).

															   To consider in our pre-emption analysis the
contingencies 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 inconsistent 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 contemplates that sort of contingent
supremacy. The non obstante provision suggests that
pre-emption analysis should not involve speculation about ways in
which federal 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 cannot 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.[ Footnote 7 ] Specifically, the CBE regulation, 21
CFR §314.70(c)(6)(iii), permitted a brand-name drug manufacturer
like Wyeth “to unilaterally 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.[ Footnote
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.[ Footnote 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 proceedings consistent with this
opinion. It is so ordered. * Justice Kennedy joins all
but Part III–B–2 of this opinion. Footnote
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. Footnote
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”). Footnote
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). Footnote
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). Footnote
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 preserve 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 statement 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. Footnote
6 The dissent asserts that we
are forgetting “purposes-and-objectives” pre-emption. Post , at 15–16. But as the dissent acknowledges,
purposes-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. Footnote
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 argument, and that type of pre-emption is
not argued here. Cf. post , at 16, n. 13 (opinion of
Sotomayor, J.). Footnote
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 necessarily 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. Footnote
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 ordinarily 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 PLIVA, INC. V. MENSING 564 U. S. ____ (2011) SUPREME COURT OF THE UNITED STATES NOS. 09-993, 09-1039, AND 09-1501 PLIVA, INC., et al., PETITIONERS

															09–993 v. GLADYS MENSING ACTAVIS ELIZABETH, LLC, PETITIONER 09–1039   v. GLADYS MENSING ACTAVIS, INC., PETITIONER 09–1501   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 generic-drug manufacturers from all state-law
failure-to-warn claims because they cannot unilaterally change
their la-bels. 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 Competi- tion 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 adminis-tration, 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);[ Footnote 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.[ Footnote 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 Bud-get Office, How Increased Competition
from Generic Drugs Has Affected Prices and Returns in the
Pharmaceutical Industry 27 (1998).[ Footnote 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.[ Footnote 4 ] 21 CFR §314.80(b);[ Footnote 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 re-port 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.[ Footnote 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, ef-fectiveness, 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 “changes-being-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.[ Footnote 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-to-warn claims because, under
federal law, the Manufac-turers 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 un- less 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 de-manding 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
Men-sing and Demahy because federal law prohibited them from
changing their labels unilaterally.[ Footnote 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
la-bels.[ Footnote 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.[ Footnote 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.[ Footnote
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 prin-ciples 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
pre-emption 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
bur-den to show impossibility, the majority invents a new
pre-emption 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 (empha- sis
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.[ Footnote
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 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 un-derstandably 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 re-quire 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
“meaning-less.” 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 pre-emption 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.[ Footnote 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 pre-emption 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
pre-empt 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.[ Footnote 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 mech-anism 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 generic-drug 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 product-liability 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
pre-scription 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 brand-name
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
brand-name drugs are the “same” in nearly all respects.[ Footnote 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]” pre-emption 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. Footnote 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). Footnote 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/ftpdoc/118xx/doc11838/09-15-PrescriptionDrugs.pdf.
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/state-medicaid-outpatient-prescription-drug-policies-findings-from-a-national-survey-2005-update-report.pdf. Footnote 3 Online at
http://www.cbo.gov/ftpdocs/6xx/doc655/pharm.pdf. Footnote 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). Footnote 5 Like the majority, I refer to the pre-2007
statutes and regulations. See ante , at 5, n. 1. Footnote 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 well-being 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]”). Footnote 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. Footnote 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. Footnote 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, how-ever, 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). Footnote 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. Footnote 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. Footnote 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
Manufactur-ing, 361 N. Eng. J. Med. 737, 738 (2009); see also GPhA,
Frequently Asked Questions About Generics,
http://www.gphaonline.org/about-gpha/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. Footnote 13 Justice 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. Footnote 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 presumption
against pre-emption. Footnote 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.

Summary: The Supreme Court ruled that federal drug regulations for generic drug manufacturers directly conflict with and preempt state tort law claims alleging inadequate warning labels. This decision protects generic drug manufacturers from liability for failure to provide adequate warning labels if they comply with federal drug regulations.