Court Opinion

ID: 4398532
Source: CourtListenerOpinion
Date Created: 2019-05-20 15:00:38.49403+00
Date Added: 2024-06-11T14:51:50.742739
License: Public Domain

(Slip Opinion)              OCTOBER TERM, 2018                                       1

                                       Syllabus

         NOTE: Where it is feasible, a syllabus (headnote) will be released, as is
       being done in connection with this case, at the time the opinion is issued.
       The syllabus constitutes no part of the opinion of the Court but has been
       prepared by the Reporter of Decisions for the convenience of the reader.
       See United States v. Detroit Timber & Lumber Co., 200 U. S. 321, 337.

SUPREME COURT OF THE UNITED STATES

                                       Syllabus

MERCK SHARP & DOHME CORP. v. ALBRECHT ET AL.

CERTIORARI TO THE UNITED STATES COURT OF APPEALS FOR
                  THE THIRD CIRCUIT

      No. 17–290.      Argued January 7, 2019—Decided May 20, 2019
Petitioner Merck Sharp & Dohme Corp. manufactures Fosamax, a drug
  that treats and prevents osteoporosis in postmenopausal women.
  However, the mechanism through which Fosamax treats and pre-
  vents osteoporosis may increase the risk that patients will suffer
  “atypical femoral fractures,” that is, a rare type of complete, low-
  energy fracture that affects the thigh bone. When the Food and Drug
  Administration first approved of the manufacture and sale of Fosa-
  max in 1995, the Fosamax label did not warn of the then-speculative
  risk of atypical femoral fractures associated with the drug. But
  stronger evidence connecting Fosamax to atypical femoral fractures
  developed after 1995. And the FDA ultimately ordered Merck to add
  a warning about atypical femoral fractures to the Fosamax label in
  2011.
     Respondents are more than 500 individuals who took Fosamax and
  suffered atypical femoral fractures between 1999 and 2010. Re-
  spondents sued Merck seeking tort damages on the ground that state
  law imposed upon Merck a legal duty to warn respondents and their
  doctors about the risk of atypical femoral fractures associated with
  using Fosamax. Merck, in defense, argued that respondents’ state-
  law failure-to-warn claims should be dismissed as pre-empted by fed-
  eral law. Merck conceded that the FDA regulations would have per-
  mitted Merck to try to change the label to add a warning before 2010,
  but Merck asserted that the FDA would have rejected that attempt.
  In particular, Merck claimed that the FDA’s rejection of Merck’s 2008
  attempt to warn of a risk of “stress fractures” showed that the FDA
  would also have rejected any attempt by Merck to warn of the risk of
  atypical femoral fractures associated with the drug.
     The District Court agreed with Merck’s pre-emption argument and
2           MERCK SHARP & DOHME CORP. v. ALBRECHT

                                 Syllabus

    granted summary judgment to Merck, but the Third Circuit vacated
    and remanded. The Court of Appeals recognized that its pre-emption
    analysis was controlled by this Court’s decision in Wyeth v. Levine,
    555 U. S. 555, which held that a state-law failure-to-warn claim is
    pre-empted where there is “clear evidence” that the FDA would not
    have approved a change to the label. The Court of Appeals, however,
    suggested that the “clear evidence” standard had led to varying lower
    court applications and that it would be helpful for this Court to
    “clarif[y] or buil[d] out the doctrine.” 852 F. 3d 268, 284.
Held:
    1. “Clear evidence” is evidence that shows the court that the drug
 manufacturer fully informed the FDA of the justifications for the
 warning required by state law and that the FDA, in turn, informed
 the drug manufacturer that the FDA would not approve a change to
 the drug’s label to include that warning. Pp. 9–15.
       (a) The Wyeth Court undertook a careful review of the history of
 federal regulation of drugs and drug labeling and found both a reluc-
 tance by Congress to displace state laws that would penalize drug
 manufacturers for failing to warn consumers of the risks associated
 with their drugs and an insistence by Congress that drug manufac-
 turers bear the responsibility for the content of their drug labels. Ac-
 cordingly, this Court held in Wyeth that “absent clear evidence that
 the FDA would not have approved a change” to the label, the Court
 “will not conclude that it was impossible . . . to comply with both fed-
 eral and state requirements.” 555 U. S., at 571. Applying that rule
 to the facts of that case, the Court said that Wyeth’s evidence of pre-
 emption fell short for two reasons. First, the record did not show that
 Wyeth “supplied the FDA with an evaluation or analysis concerning
 the specific dangers” that would have merited the warning. Id., at
 572–573. And second, the record did not show that Wyeth “attempt-
 ed to give the kind of warning required by [state law] but was prohib-
 ited from doing so by the FDA.” Ibid., and n. 5. Pp. 10–13.
       (b) Thus, in a case like Wyeth, showing that federal law prohibit-
 ed the drug manufacturer from adding a warning that would satisfy
 state law requires the drug manufacturer to show that it fully in-
 formed the FDA of the justifications for the warning required by state
 law and that the FDA, in turn, informed the drug manufacturer that
 the FDA would not approve changing the drug’s label to include that
 warning. These conclusions flow from this Court’s precedents on im-
 possibility pre-emption and the statutory and regulatory scheme that
 the Court reviewed in Wyeth. See 555 U. S., at 578. In particular,
 this Court has refused to find clear evidence of impossibility where
 the laws of one sovereign permit an activity that the laws of the other
 sovereign restrict or even prohibit. And as explained in Wyeth, FDA
                     Cite as: 587 U. S. ____ (2019)                    3

                                Syllabus

  regulations permit drug manufacturers to change a label to “reflect
  newly acquired information” if the changes “add or strengthen a . . .
  warning” for which there is “evidence of a causal association.” 21
  CFR §314.70(c)(6)(iii)(A). Pp. 13–14.
       (c) The only agency actions that can determine the answer to the
  pre-emption question are agency actions taken pursuant to the FDA’s
  congressionally delegated authority. The Supremacy Clause grants
  “supreme” status only to the “the Laws of the United States.” U. S.
  Const., Art. VI, cl. 2. And pre-emption takes place “ ‘only when and if
  [the agency] is acting within the scope of its congressionally delegat-
  ed authority.’ ” New York v. FERC, 535 U. S. 1, 18 (some alterations
  omitted). P 15.
    2. The question of agency disapproval is primarily one of law for a
  judge to decide. The question often involves the use of legal skills to
  determine whether agency disapproval fits facts that are not in dis-
  pute. Moreover, judges, rather than lay juries, are better equipped to
  evaluate the nature and scope of an agency’s determination, and are
  better suited to understand and to interpret agency decisions in light
  of the governing statutory and regulatory context. While contested
  brute facts will sometimes prove relevant to a court’s legal determi-
  nation about the meaning and effect of an agency decision, such fac-
  tual questions are subsumed within an already tightly circumscribed
  legal analysis and do not warrant submission alone or together with
  the larger pre-emption question to a jury. Pp. 15–17.
852 F. 3d 268, vacated and remanded.

   BREYER, J., delivered the opinion of the Court, in which THOMAS,
GINSBURG, SOTOMAYOR, KAGAN, and GORSUCH, JJ., joined. THOMAS, J.,
filed a concurring opinion. ALITO, J., filed an opinion concurring in the
judgment, in which ROBERTS, C. J., and KAVANAUGH, J., joined.
                       Cite as: 587 U. S. ____ (2019)                              1

                            Opinion of the Court

    NOTICE: This opinion is subject to formal revision before publication in the
    preliminary print of the United States Reports. Readers are requested to
    notify the Reporter of Decisions, Supreme Court of the United States, Wash-
    ington, D. C. 20543, of any typographical or other formal errors, in order
    that corrections may be made before the preliminary print goes to press.

SUPREME COURT OF THE UNITED STATES
                                  _________________

                                  No. 17–290
                                  _________________

  MERCK SHARP & DOHME CORP., PETITIONER v.
           DORIS ALBRECHT, ET AL.
 ON WRIT OF CERTIORARI TO THE UNITED STATES COURT OF
            APPEALS FOR THE THIRD CIRCUIT
                                [May 20, 2019]

   JUSTICE BREYER delivered the opinion of the Court.
   When Congress enacted the Federal Food, Drug, and
Cosmetic Act, ch. 675, 52 Stat. 1040, as amended, 21
U. S. C. §301 et seq., it charged the Food and Drug Admin-
istration with ensuring that prescription drugs are “safe
for use under the conditions prescribed, recommended, or
suggested” in the drug’s “labeling.” §355(d). When the
FDA exercises this authority, it makes careful judgments
about what warnings should appear on a drug’s label for
the safety of consumers.
   For that reason, we have previously held that “clear
evidence” that the FDA would not have approved a change
to the drug’s label pre-empts a claim, grounded in state
law, that a drug manufacturer failed to warn consumers of
the change-related risks associated with using the drug.
See Wyeth v. Levine, 555 U. S. 555, 571 (2009). We here
determine that this question of pre-emption is one for a
judge to decide, not a jury. We also hold that “clear evi-
dence” is evidence that shows the court that the drug
manufacturer fully informed the FDA of the justifications
for the warning required by state law and that the FDA, in
2       MERCK SHARP & DOHME CORP. v. ALBRECHT

                     Opinion of the Court

turn, informed the drug manufacturer that the FDA would
not approve a change to the drug’s label to include that
warning.
                              I
    The central issue in this case concerns federal pre-
emption, which as relevant here, takes place when it is
“ ‘impossible for a private party to comply with both state
and federal requirements.’ ” Mutual Pharmaceutical Co. v.
Bartlett, 570 U. S. 472, 480 (2013). See also U. S. Const.,
Art. VI, cl. 2. The state law that we consider is state
common law or state statutes that require drug manufac-
turers to warn drug consumers of the risks associated with
drugs. The federal law that we consider is the statutory
and regulatory scheme through which the FDA regulates
the information that appears on brand-name prescription
drug labels. The alleged conflict between state and federal
law in this case has to do with a drug that was manufac-
tured by petitioner Merck Sharp & Dohme and was ad-
ministered to respondents without a warning of certain
associated risks.
                               A
   The FDA regulates the safety information that appears
on the labels of prescription drugs that are marketed in
the United States. 21 U. S. C. §355(b)(1)(F); 21 CFR
§201.57(a) (2018). Although we commonly understand a
drug’s “label” to refer to the sticker affixed to a prescrip-
tion bottle, in this context the term refers more broadly to
the written material that is sent to the physician who
prescribes the drug and the written material that comes
with the prescription bottle when the drug is handed to
the patient at the pharmacy. 21 U. S. C. §321(m). These
(often lengthy) package inserts contain detailed infor-
mation about the drug’s medical uses and health risks.
§355(b)(1)(F); 21 CFR §201.57(a).
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                     Opinion of the Court

   FDA regulations set out requirements for the content,
the format, and the order of the safety information on the
drug label. §201.57(c). Those regulations require drug
labels to include, among other things: (1) prominent
“boxed” warnings about risks that may lead to death or
serious injury; (2) contraindications describing any situa-
tion in which the drug should not be used because the risk
of use outweighs any therapeutic benefit; (3) warnings and
precautions about other potential safety hazards; and
(4) any adverse reactions for which there is some basis to
believe a causal relationship exists between the drug and
the occurrence of the adverse event. Ibid.
   As those requirements make clear, the category in
which a particular risk appears on a drug label is an
indicator of the likelihood and severity of the risk. The
hierarchy of label information is designed to “prevent
overwarning” so that less important information does not
“overshadow” more important information. 73 Fed. Reg.
49605–49606 (2008).        It is also designed to exclude
“[e]xaggeration of risk, or inclusion of speculative or hypo-
thetical risks,” that “could discourage appropriate use of a
beneficial drug.” Id., at 2851.
   Prospective drug manufacturers work with the FDA to
develop an appropriate label when they apply for FDA
approval of a new drug. 21 U. S. C. §§355(a), 355(b),
355(d)(7); 21 CFR §314.125(b)(6). But FDA regulations
also acknowledge that information about drug safety may
change over time, and that new information may require
changes to the drug label. §§314.80(c), 314.81(b)(2)(i).
Drug manufacturers generally seek advance permission
from the FDA to make substantive changes to their drug
labels. However, an FDA regulation called the “changes
being effected” or “CBE” regulation permits drug manufac-
turers to change a label without prior FDA approval if the
change is designed to “add or strengthen a . . . warning”
where there is “newly acquired information” about the
4       MERCK SHARP & DOHME CORP. v. ALBRECHT

                     Opinion of the Court

“evidence of a causal association” between the drug and a
risk of harm. 21 CFR §314.70(c)(6)(iii)(A).
                              B
   Petitioner Merck Sharp & Dohme manufactures Fosa-
max, a drug that treats and prevents osteoporosis in
postmenopausal women. App. 192; In re Fosamax (Alen-
dronate Sodium) Products Liability Litigation, 852 F. 3d
268, 271, 274–275 (CA3 2017). Fosamax belongs to a class
of drugs called “bisphosphonates.” Fosamax and other
bisphosphonates work by affecting the “bone remodeling
process,” that is, the process through which bones are
continuously broken down and built back up again. App.
102, 111. For some postmenopausal women, the two parts
of the bone remodeling process fall out of sync; the body
removes old bone cells faster than it can replace them.
That imbalance can lead to osteoporosis, a disease that is
characterized by low bone mass and an increased risk of
bone fractures. Fosamax (like other bisphosphonates)
slows the breakdown of old bone cells and thereby helps
postmenopausal women avoid osteoporotic fractures. Id.,
at 102.
   However, the mechanism through which Fosamax de-
creases the risk of osteoporotic fractures may increase the
risk of a different type of fracture. Id., at 400–444, 661–
663. That is because all bones—healthy and osteoporotic
alike—sometimes develop microscopic cracks that are not
due to any trauma, but are instead caused by the mechan-
ical stress of everyday activity. Id., at 102. Those so-
called “stress fractures” ordinarily heal on their own
through the bone remodeling process. But, by slowing the
breakdown of old bone cells, Fosamax and other bisphos-
phonates may cause stress fractures to progress to com-
plete breaks that cause great pain and require surgical
intervention to repair. Id., at 106–109, 139, 144–145.
When that rare type of complete, low-energy fracture
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                      Opinion of the Court

affects the thigh bone, it is called an “atypical femoral
fracture.” Id., at 101.
   The Fosamax label that the FDA approved in 1995 did
not warn of the risk of atypical femoral fractures. 852
F. 3d, at 274–275. At that time, Merck’s scientists were
aware of at least a theoretical risk of those fractures.
Indeed, as far back as 1990 and 1991, when Fosamax was
undergoing preapproval clinical trials, Merck scientists
expressed concern in internal discussions that Fosamax
could inhibit bone remodeling to such a “ ‘profound’ ” de-
gree that “inadequate repair may take place” and “ ‘micro-
fractures would not heal.’ ” App. 111–113. When Merck
applied to the FDA for approval of Fosamax, Merck
brought those theoretical considerations to the FDA’s
attention. 852 F. 3d, at 274–275. But, perhaps because
the concerns were only theoretical, the FDA approved
Fosamax’s label without requiring any mention of this
risk. Ibid.
   Evidence connecting Fosamax to atypical femoral frac-
tures developed after 1995. Merck began receiving ad-
verse event reports from the medical community indicat-
ing that long-term Fosamax users were suffering atypical
femoral fractures. App. 122–125. For example, Merck
received a report from a doctor who said that hospital staff
had begun calling atypical femoral fractures the “ ‘Fosa-
max Fracture’ ” because “ ‘100% of patients in his practice
who have experienced femoral fractures (without being hit
by a taxicab), were taking Fosamax . . . for over 5 years. ’ ”
Id., at 126. Merck performed a statistical analysis of
Fosamax adverse event reports, concluding that these
reports revealed a statistically significant incidence of
femur fractures. 3 App. in No. 14–1900 (CA3), pp. A1272–
A1273, A1443. And about the same time, Merck began to
see numerous scholarly articles and case studies docu-
menting possible connections between long-term Fosamax
use and atypical femoral fractures. App. 106–110, 116–
6        MERCK SHARP & DOHME CORP. v. ALBRECHT

                      Opinion of the Court

122.
   In 2008, Merck applied to the FDA for preapproval to
change Fosamax’s label to add language to both the “Ad-
verse Reaction[s]” and the “Precaution[s]” sections of the
label. Id., at 670. In particular, Merck proposed adding a
reference to “ ‘low-energy femoral shaft fracture’ ” in the
Adverse Reactions section, and cross-referencing a longer
discussion in the Precautions section that focused on the
risk of stress fractures associated with Fosamax. Id., at
728. The FDA approved the addition to the Adverse Reac-
tions section, but rejected Merck’s proposal to warn of a
risk of “stress fractures.” Id., at 511–512. The FDA ex-
plained that Merck’s “justification” for the proposed
change to the Precautions section was “inadequate,” be-
cause “[i]dentification of ‘stress fractures’ may not be
clearly related to the atypical subtrochanteric fractures
that have been reported in the literature.” Id., at 511.
The FDA invited Merck to “resubmit” its application and
to “fully address all the deficiencies listed.” Id., at 512; see
21 CFR §314.110(b). But Merck instead withdrew its
application and decided to make the changes to the Ad-
verse Reactions section through the CBE process. App.
654–660. Merck made no changes to the Precautions
section at issue here. Id., at 274.
   A warning about “atypical femoral fractures” did not
appear on the Fosamax label until 2011, when the FDA
ordered that change based on its own analyses. Id., at
246–252, 526–534. Merck was initially resistant to the
change, proposing revised language that, once again,
referred to the risk of “stress fractures.” Id., at 629–634.
But the FDA, once again, rejected that language. And this
time, the FDA explained that “the term ‘stress fracture’
was considered and was not accepted” because, “for most
practitioners, the term ‘stress fracture’ represents a minor
fracture and this would contradict the seriousness of the
atypical femoral fractures associated with bisphosphonate
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                     Opinion of the Court

use.” Id., at 566. In January 2011, Merck and the FDA
ultimately agreed upon adding a three-paragraph discus-
sion of atypical femoral fractures to the Warnings and
Precautions section of the Fosamax label. Id., at 223–224.
The label now refers to the fractures five times as “atypi-
cal” without using the term “stress fracture.” Ibid.
                              C
   The respondents here are more than 500 individuals
who took Fosamax and who suffered atypical femoral
fractures between 1999 and 2010. Brief for Respondents
7. Respondents, invoking federal diversity jurisdiction,
filed separate actions seeking tort damages on the ground
that, during the relevant period, state law imposed upon
Merck a legal duty to warn them and their doctors about
the risk of atypical femoral fractures associated with using
Fosamax. Id., at 1. One respondent, for example, filed a
complaint alleging that she took Fosamax for roughly 10
years and suffered an atypical femoral fracture. One day
in 2009, when the respondent was 70 years old, she turned
to unlock the front door of her house, heard a popping
sound, and suddenly felt her left leg give out beneath her.
She needed surgery, in which doctors repaired her leg with
a rod and screws. She explained she would not have used
Fosamax for so many years if she had known that she
might suffer an atypical femoral fracture as a result. See
id., at 18–19.
   Merck, in defense, argued that respondents’ state-law
failure-to-warn claims should be dismissed as pre-empted
by federal law. Both Merck and the FDA have long been
aware that Fosamax could theoretically increase the risk
of atypical femoral fractures. But for some period of time
between 1995 (when the FDA first approved a drug label
for Fosamax) and 2010 (when the FDA decided to require
Merck to add a warning about atypical femoral fractures
to Fosamax’s label), both Merck and the FDA were unsure
8        MERCK SHARP & DOHME CORP. v. ALBRECHT

                      Opinion of the Court

whether the developing evidence of a causal link between
Fosamax and atypical femoral fractures was strong
enough to require adding a warning to the Fosamax drug
label. Merck conceded that the FDA’s CBE regulation
would have permitted Merck to try to change the label to
add a warning before 2010, but Merck asserted that the
FDA would have rejected that attempt. In particular,
Merck pointed to the FDA’s rejection of Merck’s 2008
attempt to amend the Fosamax label to warn of the risk of
“stress fractures” associated with Fosamax. On that basis,
Merck claimed that federal law prevented Merck from
complying with any state-law duty to warn the respond-
ents of the risk of atypical femoral fractures associated
with Fosamax.
   The District Court agreed with Merck’s pre-emption
argument and granted summary judgment to Merck, In re
Fosamax (Alendronate Sodium): Products Liability Litiga-
tion, 2014 WL 1266994, *17 (D NJ, Mar. 22, 2017), but the
Court of Appeals vacated and remanded, 852 F. 3d, at 302.
The Court of Appeals concluded that its pre-emption
analysis was controlled by this Court’s decision in Wyeth.
Ibid. The Court of Appeals understood that case as mak-
ing clear that a failure-to-warn claim grounded in state
law is pre-empted where there is “ ‘clear evidence that the
FDA would not have approved a change to the . . . label.’ ”
Id., at 280 (quoting Wyeth, 555 U. S., at 571). The Court of
Appeals, however, suggested that this statement had led
to varying lower court applications and that it would be
helpful for this Court to “clarif[y] or buil[d] out the doc-
trine.” 852 F. 3d, at 284.
   In attempting to do so itself, the Court of Appeals held
that “the Supreme Court intended to announce a standard
of proof when it used the term ‘clear evidence’ in Wyeth.”
Ibid. That is, the Court of Appeals believed that “[t]he
term ‘clear evidence’ . . . does not refer directly to the type
of facts that a manufacturer must show, or to the circum-
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                      Opinion of the Court

stances in which preemption will be appropriate.” Id., at
285. “Rather, it specifies how difficult it will be for the
manufacturer to convince the factfinder that the FDA
would have rejected a proposed label change.” Ibid. And
in the Court of Appeals’ view, “for a defendant to establish
a preemption defense under Wyeth, the factfinder must
conclude that it is highly probable that the FDA would not
have approved a change to the drug’s label.” Id., at 286.
Moreover and importantly, the Court of Appeals also held
that “whether the FDA would have rejected a proposed
label change is a question of fact that must be answered
by a jury.” Ibid.
  Merck filed a petition for a writ of certiorari. Merck’s
petition asked the Court to decide whether Merck’s case
and others like it “must . . . go to a jury” to determine
whether the FDA, in effect, has disapproved a state-law-
required labeling change. In light of differences and un-
certainties among the courts of appeals and state supreme
courts in respect to the application of Wyeth, we granted
certiorari. See, e.g., Mason v. SmithKline Beecham Corp.,
596 F. 3d 387, 391 (CA7 2010) (“The Supreme Court . . .
did not clarify what constitutes ‘clear evidence’ ”); Reckis v.
Johnson & Johnson, 471 Mass. 272, 286, 28 N. E. 3d 445,
457 (2015) (“Wyeth did not define ‘clear evidence’ . . . ”
(some internal quotation marks omitted)).
                            II
  We stated in Wyeth v. Levine that state law failure-to-
warn claims are pre-empted by the Federal Food, Drug,
and Cosmetic Act and related labeling regulations when
there is “clear evidence” that the FDA would not have
approved the warning that state law requires. 555 U. S.,
at 571. We here decide that a judge, not the jury, must
decide the pre-emption question.     And we elaborate
Wyeth’s requirements along the way.
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                     Opinion of the Court

                              A
   We begin by describing Wyeth. In that case, the plaintiff
developed gangrene after a physician’s assistant injected
her with Phenergan, an antinausea drug. The plaintiff
brought a state-law failure-to-warn claim against Wyeth,
the drug’s manufacturer, for failing to provide an adequate
warning about the risks that accompany various methods
of administering the drug. In particular, the plaintiff
claimed that directly injecting Phenergan into a patient’s
vein (the “IV-push” method of administration) creates a
significant risk of catastrophic consequences. And those
consequences could be avoided by introducing the drug
into a saline solution that slowly descends into a patient’s
vein (the “IV-drip” method of administration). A jury
concluded that Wyeth’s warning label was inadequate, and
that the label’s inadequacy caused the plaintiff ’s injury.
On appeal, Wyeth argued that the plaintiff ’s state-law
failure-to-warn claims were pre-empted because it was
impossible for Wyeth to comply with both state law duties
and federal labeling obligations. The Vermont Supreme
Court rejected Wyeth’s pre-emption claim. Id., at 563.
   We too considered Wyeth’s pre-emption argument, and
we too rejected it. In rejecting Wyeth’s argument, we
undertook a careful review of the history of federal regula-
tion of drugs and drug labeling. Id., at 566–568. In doing
so, we “assum[ed] that the historic police powers of the
States were not to be superseded by the Federal Act un-
less that was the clear and manifest purpose of Congress.”
Id., at 565 (internal quotation marks omitted). And we
found nothing within that history to indicate that the
FDA’s power to approve or to disapprove labeling changes,
by itself, pre-empts state law.
   Rather, we concluded that Congress enacted the FDCA
“to bolster consumer protection against harmful products;”
that Congress provided no “federal remedy for consumers
harmed by unsafe or ineffective drugs”; that Congress was
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                     Opinion of the Court

“awar[e] of the prevalence of state tort litigation;” and
that, whether Congress’ general purpose was to protect
consumers, to provide safety-related incentives to manu-
facturers, or both, language, history, and purpose all
indicate that “Congress did not intend FDA oversight to be
the exclusive means of ensuring drug safety and effective-
ness.” Id., at 574–575 (emphasis added). See also id., at
574 (“If Congress thought state-law suits posed an obsta-
cle to its objectives, it surely would have enacted an ex-
press pre-emption provision at some point during the
FDCA’s 70-year history”).
  We also observed that “through many amendments to
the FDCA and to FDA regulations, it has remained a
central premise of federal drug regulation that the manu-
facturer bears responsibility for the content of its label at
all times.” Id., at 570–571. A drug manufacturer “is
charged both with crafting an adequate label and with
ensuring that its warnings remain adequate as long as the
drug is on the market.” Id., at 571. Thus, when the risks
of a particular drug become apparent, the manufacturer
has “a duty to provide a warning that adequately de-
scribe[s] that risk.” Ibid. “Indeed,” we noted, “prior to
2007, the FDA lacked the authority to order manufactur-
ers to revise their labels.” Ibid. And even when “Congress
granted the FDA this authority,” in the 2007 Amendments
to the FDCA, Congress simultaneously “reaffirmed the
manufacturer’s obligations and referred specifically to the
CBE regulation, which both reflects the manufacturer’s
ultimate responsibility for its label and provides a mecha-
nism for adding safety information to the label prior to
FDA approval.” Ibid.
  In light of Congress’ reluctance to displace state laws
that would penalize drug manufacturers for failing to
warn consumers of the risks associated with their drugs,
and Congress’ insistence on requiring drug manufacturers
to bear the responsibility for the content of their drug
12      MERCK SHARP & DOHME CORP. v. ALBRECHT

                     Opinion of the Court

labels, we were unpersuaded by Wyeth’s pre-emption
argument. In Wyeth’s case, we concluded, “when the risk
of gangrene from IV-push injection of Phenergan became
apparent, Wyeth had a duty” under state law “to provide a
warning that adequately described that risk, and the CBE
regulation permitted it to provide such a warning before
receiving the FDA’s approval.” Ibid.
   At the same time, and more directly relevant here, we
pointed out that “the FDA retains authority to reject
labeling changes made pursuant to the CBE regulation in
its review of the manufacturer’s supplemental application,
just as it retains such authority in reviewing all supple-
mental applications.” Ibid. We then said that, nonethe-
less, “absent clear evidence that the FDA would not have
approved a change to Phenergan’s label, we will not con-
clude that it was impossible for Wyeth to comply with both
federal and state requirements.” Ibid. (emphasis added).
   We reviewed the record and concluded that “Wyeth has
offered no such evidence.” Id., at 572. We said that
Wyeth’s evidence of pre-emption fell short for two reasons.
First, the record did not show that Wyeth “supplied the
FDA with an evaluation or analysis concerning the specific
dangers” that would have merited the warning. Id., at
572–573. We could find “no evidence in this record that
either the FDA or the manufacturer gave more than pass-
ing attention to the issue of IV-push versus IV-drip admin-
istration”—the matter at issue in the case. Id., at 572
(internal quotation marks omitted). Second, the record
did not show that Wyeth “attempted to give the kind of
warning required by [state law] but was prohibited from
doing so by the FDA.” Ibid., and n. 5. The “FDA had not
made an affirmative decision to preserve” the warning as
it was or “to prohibit Wyeth from strengthening its warn-
ing.” Id., at 572. For those reasons, we could not “credit
Wyeth’s contention that the FDA would have prevented it
from adding a stronger warning about the IV-push method
                 Cite as: 587 U. S. ____ (2019)           13

                     Opinion of the Court

of intravenous administration.” And we could not con-
clude that “it was impossible for Wyeth to comply with
both federal and state requirements.” Id., at 573. We
acknowledged that meeting the standard we set forth
would be difficult, but, we said, “[i]mpossibility pre-
emption is a demanding defense.” Ibid.
                              B
   The underlying question for this type of impossibility
pre-emption defense is whether federal law (including
appropriate FDA actions) prohibited the drug manufac-
turer from adding any and all warnings to the drug label
that would satisfy state law. And, of course, in order to
succeed with that defense the manufacturer must show
that the answer to this question is yes. But in Wyeth, we
confronted that question in the context of a particular set
of circumstances. Accordingly, for purposes of this case,
we assume—but do not decide—that, as was true of the
warning at issue in Wyeth, there is sufficient evidence to
find that Merck violated state law by failing to add a
warning about atypical femoral fractures to the Fosamax
label. In a case like Wyeth, showing that federal law
prohibited the drug manufacturer from adding a warning
that would satisfy state law requires the drug manufac-
turer to show that it fully informed the FDA of the justifi-
cations for the warning required by state law and that the
FDA, in turn, informed the drug manufacturer that the
FDA would not approve changing the drug’s label to in-
clude that warning.
   These conclusions flow from our precedents on impossi-
bility pre-emption and the statutory and regulatory
scheme that we reviewed in Wyeth. See 555 U. S., at 578.
In particular, “it has long been settled that state laws that
conflict with federal law are without effect.” Mutual
Pharmaceutical Co., 570 U. S., at 480. But as we have
cautioned many times before, the “possibility of impossibil-
14      MERCK SHARP & DOHME CORP. v. ALBRECHT

                     Opinion of the Court

ity [is] not enough.” PLIVA, Inc. v. Mensing, 564 U. S. 604,
625, n. 8 (2011) (internal quotation marks omitted). Con-
sequently, we have refused to find clear evidence of such
impossibility where the laws of one sovereign permit an
activity that the laws of the other sovereign restrict or
even prohibit. See, e.g., Barnett Bank of Marion Cty.,
N. A. v. Nelson, 517 U. S. 25, 31 (1996); Michigan Canners
& Freezers Assn., Inc. v. Agricultural Marketing and Bar-
gaining Bd., 467 U. S. 461, 478, and n. 21 (1984).
   And, as we explained in Wyeth, 555 U. S., at 571–573,
federal law—the FDA’s CBE regulation—permits drug
manufacturers to change a label to “reflect newly acquired
information” if the changes “add or strengthen a . . . warn-
ing” for which there is “evidence of a causal association,”
without prior approval from the FDA.               21 CFR
§314.70(c)(6)(iii)(A). Of course, the FDA reviews CBE
submissions and can reject label changes even after the
manufacturer has made them. See §§314.70(c)(6), (7).
And manufacturers cannot propose a change that is not
based on reasonable evidence. §314.70(c)(6)(iii)(A). But in
the interim, the CBE regulation permits changes, so a
drug manufacturer will not ordinarily be able to show that
there is an actual conflict between state and federal law
such that it was impossible to comply with both.
   We do not further define Wyeth’s use of the words “clear
evidence” in terms of evidentiary standards, such as “pre-
ponderance of the evidence” or “clear and convincing evi-
dence” and so forth, because, as we shall discuss, infra, at
15–17, courts should treat the critical question not as a
matter of fact for a jury but as a matter of law for the
judge to decide. And where that is so, the judge must
simply ask himself or herself whether the relevant federal
and state laws “irreconcilably conflic[t].” Rice v. Norman
Williams Co., 458 U. S. 654, 659 (1982); see ibid. (“The
existence of a hypothetical or potential conflict is insuffi-
cient to warrant the pre-emption of the state statute”).
                  Cite as: 587 U. S. ____ (2019)             15

                      Opinion of the Court

  We do note, however, that the only agency actions that
can determine the answer to the pre-emption question, of
course, are agency actions taken pursuant to the FDA’s
congressionally delegated authority.          The Supremacy
Clause grants “supreme” status only to the “the Laws of
the United States.” U. S. Const., Art. VI, cl. 2. And pre-
emption takes place “ ‘only when and if [the agency] is
acting within the scope of its congressionally delegated
authority, . . . for an agency literally has no power to act,
let alone pre-empt the validly enacted legislation of a
sovereign State, unless and until Congress confers power
upon it.’ ” New York v. FERC, 535 U. S. 1, 18 (2002) (some
alterations omitted). Federal law permits the FDA to
communicate its disapproval of a warning by means of
notice-and-comment rulemaking setting forth labeling
standards, see, e.g., 21 U. S. C. §355(d); 21 CFR §§201.57,
314.105; by formally rejecting a warning label that would
have been adequate under state law, see, e.g., 21 CFR
§§314.110(a), 314.125(b)(6); or with other agency action
carrying the force of law, cf., e.g., 21 U. S. C. §355(o)(4)(A).
The question of disapproval “method” is not now before us.
And we make only the obvious point that, whatever the
means the FDA uses to exercise its authority, those means
must lie within the scope of the authority Congress has
lawfully delegated.
                              III
   We turn now to what is the determinative question
before us: Is the question of agency disapproval primarily
one of fact, normally for juries to decide, or is it a question
of law, normally for a judge to decide without a jury?
   The complexity of the preceding discussion of the law
helps to illustrate why we answer this question by con-
cluding that the question is a legal one for the judge, not a
jury. The question often involves the use of legal skills to
determine whether agency disapproval fits facts that are
16      MERCK SHARP & DOHME CORP. v. ALBRECHT

                     Opinion of the Court

not in dispute. Moreover, judges, rather than lay juries,
are better equipped to evaluate the nature and scope of an
agency’s determination. Judges are experienced in “[t]he
construction of written instruments,” such as those nor-
mally produced by a federal agency to memorialize its
considered judgments. Markman v. Westview Instru-
ments, Inc., 517 U. S. 370, 388 (1996). And judges are
better suited than are juries to understand and to inter-
pret agency decisions in light of the governing statutory
and regulatory context. Cf. 5 U. S. C. §706 (specifying
that a “reviewing court,” not a jury, “shall . . . determine
the meaning or applicability of the terms of an agency
action”); see also H. R. Rep. No. 1980, 79th Cong., 2d
Sess., 44 (1946) (noting longstanding view that “questions
respecting the . . . terms of any agency action” and its
“application” are “questions of law”). To understand the
question as a legal question for judges makes sense given
the fact that judges are normally familiar with principles
of administrative law. Doing so should produce greater
uniformity among courts; and greater uniformity is nor-
mally a virtue when a question requires a determination
concerning the scope and effect of federal agency action.
Cf. Markman, 517 U. S., at 390–391.
   We understand that sometimes contested brute facts
will prove relevant to a court’s legal determination about
the meaning and effect of an agency decision. For exam-
ple, if the FDA rejected a drug manufacturer’s supple-
mental application to change a drug label on the ground
that the information supporting the application was insuf-
ficient to warrant a labeling change, the meaning and
scope of that decision might depend on what information
the FDA had before it. Yet in litigation between a drug
consumer and a drug manufacturer (which will ordinarily
lack an official administrative record for an FDA decision),
the litigants may dispute whether the drug manufacturer
submitted all material information to the FDA.
                 Cite as: 587 U. S. ____ (2019)                 17

                     Opinion of the Court

   But we consider these factual questions to be subsumed
within an already tightly circumscribed legal analysis.
And we do not believe that they warrant submission alone
or together with the larger pre-emption question to a jury.
Rather, in those contexts where we have determined that
the question is “for the judge and not the jury,” we have
also held that “courts may have to resolve subsidiary
factual disputes” that are part and parcel of the broader
legal question.       Teva Pharmaceuticals USA, Inc. v.
Sandoz, Inc., 574 U. S. ___, ___–___ (2015) (slip op., at 6–
7). And, as in contexts as diverse as the proper construc-
tion of patent claims and the voluntariness of criminal
confessions, they create a question that “ ‘falls somewhere
between a pristine legal standard and a simple historical
fact.’ ” Markman, 517 U. S., at 388 (quoting Miller v.
Fenton, 474 U. S. 104, 114 (1985)). In those circum-
stances, “ ‘the fact/law distinction at times has turned on a
determination that, as a matter of the sound administra-
tion of justice, one judicial actor is better positioned than
another to decide the issue in question.’ ” Markman, 517
U. S., at 388 (quoting Miller, 474 U. S., at 114). In this
context, that “better positioned” decisionmaker is the
judge.
                            IV
  Because the Court of Appeals treated the pre-emption
question as one of fact, not law, and because it did not
have an opportunity to consider fully the standards we
have described in Part II of our opinion, we vacate its
judgment and remand the case to that court for further
proceedings consistent with this opinion.

                                                  It is so ordered.
                 Cite as: 587 U. S. ____ (2019)            1

                    THOMAS, J., concurring

SUPREME COURT OF THE UNITED STATES
                         _________________

                          No. 17–290
                         _________________

  MERCK SHARP & DOHME CORP., PETITIONER v.
           DORIS ALBRECHT, ET AL.
 ON WRIT OF CERTIORARI TO THE UNITED STATES COURT OF
            APPEALS FOR THE THIRD CIRCUIT
                        [May 20, 2019]

  JUSTICE THOMAS, concurring.
  I join the Court’s opinion and write separately to explain
my understanding of the relevant pre-emption principles
and how they apply to this case.
  The Supremacy Clause of the Constitution provides:
    “This Constitution, and the Laws of the United States
    which shall be made in Pursuance thereof; and all
    Treaties made, or which shall be made, under the Au-
    thority of the United States, shall be the supreme Law
    of the Land; and the Judges in every State shall be
    bound thereby, any Thing in the Constitution or Laws
    of any State to the Contrary notwithstanding.” Art.
    VI, cl. 2.
Under this Clause, “[w]here state and federal law ‘directly
conflict,’ state law must give way.” PLIVA, Inc. v. Mens-
ing, 564 U. S. 604, 617 (2011). Although the Court has
articulated several theories of pre-emption, Merck’s sole
argument here is that state law is pre-empted because it is
impossible for Merck to comply with federal and state law.
I remain skeptical that “physical impossibility” is a proper
test for deciding whether a direct conflict exists between
federal and state law. But even under our impossibility
precedents, Merck’s pre-emption defense fails.
2       MERCK SHARP & DOHME CORP. v. ALBRECHT

                    THOMAS, J., concurring

                              I
   As I have explained before, it is not obvious that the
“ ‘physical impossibility’ standard is the best proxy for
determining when state and federal laws ‘directly conflict’
for purposes of the Supremacy Clause.” Wyeth v. Levine,
555 U. S. 555, 590 (2009) (opinion concurring in judg-
ment). Evidence from the founding suggests that, under
the original meaning of the Supremacy Clause, federal law
pre-empts state law only if the two are in logical contra-
diction. See ibid.; Nelson, Preemption, 86 Va. L. Rev. 225,
260–261 (2000). Sometimes, federal law will logically
contradict state law even if it is possible for a person to
comply with both. For instance, “if federal law gives an
individual the right to engage in certain behavior that
state law prohibits, the laws would give contradictory
commands notwithstanding the fact that an individual
could comply with both by electing to refrain from the
covered behavior.” Wyeth, 555 U. S., at 590 (opinion of
THOMAS, J.).
   Merck does not advance this logical-contradiction
standard, and it is doubtful that a pre-emption defense
along these lines would succeed here. “To say, as the
statute does, that [Merck] may not market a drug without
federal approval (i.e., without [a Food and Drug Admin-
istration (FDA)] approved label) is not to say that federal
approval gives [Merck] the unfettered right, for all time, to
market its drug with the specific label that was federally
approved.” Id., at 592. Nothing in the federal brand-
name-drug “statutory or regulatory scheme necessarily
insulates [Merck] from liability under state law simply
because the FDA has approved a particular label.” Id., at
593. The relevant question would be whether federal law
gives Merck “an unconditional right to market [a] federally
approved drug at all times with the precise label initially
approved by the FDA,” id., at 592, or whether it instead
provides a federal floor that can be supplemented by dif-
                 Cite as: 587 U. S. ____ (2019)            3

                    THOMAS, J., concurring

ferent state standards, see Brief for Cato Institute as
Amicus Curiae 14, n. 4. Absent a federal statutory right to
sell a brand-name drug with an FDA-approved label, FDA
approval “does not represent a finding that the drug, as
labeled, can never be deemed unsafe by later federal
action, or as in this case, the application of state law.”
Wyeth, supra, at 592 (opinion of THOMAS, J.).
                               II
  Applying the Court’s impossibility precedents leads to
the same conclusion. The question for impossibility is
whether it was “lawful under federal law for [Merck] to do
what state law required of ” it. Mensing, 564 U. S., at 618.
Because “[p]re-emption analysis requires us to compare
federal and state law,” I “begin by identifying the [rele-
vant] state tort duties and federal labeling requirements.”
Id., at 611. Respondents’ claim here is “that state law
obligated Merck to add a warning about atypical femur
fractures” to the Warnings and Precautions section of
Fosamax’s label. In re Fosamax (Alendronate Sodium)
Prods. Liability Litig., 852 F. 3d 268, 282 (CA3 2017).
Under the Federal Food, Drug, and Cosmetic Act, a manu-
facturer of a brand-name drug “bears responsibility for the
content of its label at all times.” Wyeth, 555 U. S., at 570–
571 (majority opinion). The manufacturer “is charged
both with crafting an adequate label and with ensuring
that its warnings remain adequate as long as the drug is
on the market.” Id., at 571. Generally, to propose labeling
changes, the manufacturer can submit a Prior Approval
Supplement (PAS) application, which requires FDA ap-
proval before the changes are made. 21 CFR §314.70(b)
(2018). Alternatively, under the FDA’s Changes Being
Effected (CBE) regulation, if the manufacturer would like
to change a label to “add or strengthen a contraindication,
warning, precaution, or adverse reaction” “to reflect newly
acquired information,” it can change the label immediately
4       MERCK SHARP & DOHME CORP. v. ALBRECHT

                     THOMAS, J., concurring

upon filing its supplemental application with the FDA,
without waiting for FDA approval. §314.70(c)(6)(iii); see
Wyeth, supra, at 568. If the FDA later disapproves the
CBE application, “it may order the manufacturer to cease
distribution of the drug product(s)” with the new labeling.
§314.70(c)(7).
   Here, Merck’s impossibility pre-emption defense fails
because it does not identify any federal law that “prohibited
[it] from adding any and all warnings . . . that would satisfy
state law.” Ante, at 13. By its reference to “the Laws of
the United States,” the Supremacy Clause “requires that
pre-emptive effect be given only to those federal standards
and policies that are set forth in, or necessarily follow
from, the statutory text that was produced through the
constitutionally required bicameral and presentment
procedures.” Wyeth, supra, at 586 (opinion of THOMAS, J.).
Merck’s primary argument, based on various agency com-
munications, is that the FDA would have rejected a hypo-
thetical labeling change submitted via the CBE process.
But neither agency musings nor hypothetical future rejec-
tions constitute pre-emptive “Laws” under the Supremacy
Clause.
   As the Court describes, in 2008 Merck submitted PAS
applications to add certain language regarding fractures to
the Adverse Reactions and the Warnings and Precautions
sections of Fosamax’s label. Ante, at 6. In 2009, the FDA
sent Merck a “complete response” letter “agree[ing] that
atypical and subtrochanteric fractures should be added” to
the Adverse Reactions section. App. 510–511. But the
letter said that Merck’s proposed Warnings and Precau-
tions language, which focused on “the risk factors for stress
fractures,” was “inadequate” because “[i]dentification of
‘stress fractures’ may not be clearly related to the atypical
subtrochanteric fractures that have been reported in the
literature.” Id., at 511. In accord with FDA regulations,
the letter required Merck to take one of three actions: (1)
                  Cite as: 587 U. S. ____ (2019)             5

                     THOMAS, J., concurring

“[r]esubmit the application . . . , addressing all deficiencies
identified in the complete response letter”; (2) “[w]ithdraw
the application . . . without prejudice to a subsequent
submission”; or (3) “[a]sk the agency to provide . . . an
opportunity for a hearing,” after which “the agency will
either approve” or “refuse to approve the application.” 21
CFR §314.110(b); see App. 512. As this regulation sug-
gests and the FDA has explained, complete response
letters merely “infor[m] sponsors of changes that must be
made before an application can be approved, with no
implication as to the ultimate approvability of the applica-
tion.” 73 Fed. Reg. 39588 (2008) (emphasis added). In
other words, the 2009 letter neither marked “the consum-
mation of the agency’s decisionmaking process” nor de-
termined Merck’s “rights or obligations.” Bennett v. Spear,
520 U. S. 154, 178 (1997) (internal quotation marks omit-
ted). Instead, it was “of a merely tentative or interlocutory
nature.” Ibid. Therefore, the letter was not a final agency
action with the force of law, so it cannot be “Law” with
pre-emptive effect.
   Merck’s argument that the 2009 letter and other agency
communications suggest that the FDA would have denied
a future labeling change fares no better: hypothetical
agency action is not “Law.” As Merck acknowledges, it
could have resubmitted its PAS applications, sought a
hearing, or changed its label at any time through the CBE
process. See Reply Brief 13. Indeed, when Merck instead
decided to withdraw its PAS applications, it added atypi-
cal femoral fractures to the Adverse Reactions section
through the CBE process. That process also enabled
Merck to add language to the Warnings and Precautions
section, but Merck did not do so. If it had, it could have
satisfied its federal and alleged state-law duties—meaning
that it was possible for Merck to independently satisfy
both sets of duties. Merck’s belief that the FDA would
have eventually rejected a CBE application does not make
6         MERCK SHARP & DOHME CORP. v. ALBRECHT

                        THOMAS, J., concurring

an earlier CBE change impossible. As the Court correctly
explains, “ ‘the possibility of impossibility [is] not enough.’ ”
Ante, at 13–14. The very point of the CBE process is that
a manufacturer can “unilaterally” make a labeling change
that does not violate other federal law, Wyeth, 555 U. S.,
at 573; see id., at 570; e.g., 21 U. S. C. §352, at least until
the FDA rules on its application.*
   Because Merck points to no statute, regulation, or other
agency action with the force of law that would have pro-
hibited it from complying with its alleged state-law duties,
its pre-emption defense should fail as a matter of law.

——————
   *In 2007, Congress “granted the FDA statutory authority to require a
manufacturer to change its drug label based on safety information that
becomes available after a drug’s initial approval,” but even after this
amendment, brand-name-drug “manufacturers remain responsible for
updating their labels.” Wyeth, 555 U. S., at 567–568; see 21 U. S. C.
§355(o)(4). As I understand the Court’s opinion, if proper agency
actions pursuant to this amendment, or other federal law, “prohibited
the drug manufacturer from . . . satisfy[ing] state law,” state law would
be pre-empted under our impossibility precedents regardless of whether
the manufacturer “show[ed] that it fully informed the FDA of the
justifications for the warning required by state law.” Ante, at 13; see,
e.g., Wyeth, 555 U. S., at 576; id., at 582 (BREYER, J., concurring). Of
course, the only proper agency actions are those “that are set forth in,
or necessarily follow from, the statutory text,” and they must have the
force of law to be pre-emptive. Id., at 586 (opinion of THOMAS, J.). I am
aware of no such agency action here that prevented Merck from comply-
ing with state law.
                 Cite as: 587 U. S. ____ (2019)           1

               ALITO, J., concurring in judgment

SUPREME COURT OF THE UNITED STATES
                         _________________

                          No. 17–290
                         _________________

  MERCK SHARP & DOHME CORP., PETITIONER v.
           DORIS ALBRECHT, ET AL.
 ON WRIT OF CERTIORARI TO THE UNITED STATES COURT OF
            APPEALS FOR THE THIRD CIRCUIT
                        [May 20, 2019]

  JUSTICE ALITO, with whom THE CHIEF JUSTICE and
JUSTICE KAVANAUGH join, concurring in the judgment.
  I concur in the judgment because I agree with the
Court’s decision on the only question that it actually de-
cides, namely, that whether federal law allowed Merck to
include in the Fosamax label the warning alleged to be
required by state law is a question of law to be decided by
the courts, not a question of fact. I do not, however, join
the opinion of the Court because I am concerned that its
discussion of the law and the facts may be misleading on
remand.
                             I
  I begin with the law. The Court correctly notes that a
drug manufacturer may prove impossibility pre-emption
by showing that “federal law (including appropriate [Food
and Drug Administration (FDA)] actions) prohibited the
drug manufacturer from adding any and all warnings to
the drug label that would satisfy state law.” Ante, at 13.
But in expounding further on the pre-emption analysis,
the Court provides a skewed summary. While dwelling on
our decision in Wyeth v. Levine, 555 U. S. 555 (2009), see
ante, at 9–14, the Court barely notes a statutory provision
enacted after the underlying events in that case that may
have an important bearing on the ultimate pre-emption
2         MERCK SHARP & DOHME CORP. v. ALBRECHT

                   ALITO, J., concurring in judgment

analysis in this case.
  Under 21 U. S. C. §355(o)(4)(A), which was enacted in
2007, Congress has imposed on the FDA a duty to initiate
a label change “[i]f the Secretary becomes aware of new
information, including any new safety information . . . that
the Secretary determines should be included in the label-
ing of the drug.”* This provision does not relieve drug
manufacturers of their own responsibility to maintain
their drug labels, see §355(o)(4)(I), but the FDA’s “actions,”
ante, at 13, taken pursuant to this duty arguably affect the
pre-emption analysis. This is so because, if the FDA
declines to require a label change despite having received
and considered information regarding a new risk, the
logical conclusion is that the FDA determined that a label
change was unjustified. See United States v. Chemical
Foundation, Inc., 272 U. S. 1, 14–15 (1926) (“The pre-
sumption of regularity supports the official acts of public
officers and, in the absence of clear evidence to the con-
trary, courts presume that they have properly discharged
their official duties”). The FDA’s duty does not depend on
whether the relevant drug manufacturer, as opposed to
some other entity or individual, brought the new infor-
mation to the FDA’s attention. Cf. ante, at 13 (“the drug
manufacturer [must] show that it fully informed the FDA
of the justifications for the warning required by state
law”). Nor does §355(o)(4)(A) require the FDA to com-
municate to the relevant drug manufacturer that a label
change is unwarranted; instead, the FDA could simply
consider the new information and decide not to act. Cf.
ante, at 13 (“[T]he FDA, in turn, [must have] informed the
drug manufacturer that the FDA would not approve
——————
  *Prior to October 2018, §355(o)(4)(A)’s language contained slight
differences not relevant here. See Substance Use–Disorder Prevention
That Promotes Opioid Recovery and Treatment for Patients and Com-
munities Act, Pub. L. 115–271, §3041(b), 132 Stat. 3942–3943, effective
Oct. 24, 2018.
                  Cite as: 587 U. S. ____ (2019)             3

                ALITO, J., concurring in judgment

changing the drug’s label to include that warning”).
   Section 355(o)(4)(A) is thus highly relevant to the pre-
emption analysis, which turns on whether “federal law
(including appropriate FDA actions) prohibited the drug
manufacturer from adding any and all warnings to the
drug label that would satisfy state law.” Ante, at 13 (em-
phasis added). On remand, I assume that the Court of
Appeals will consider the effect of §355(o)(4)(A) on the pre-
emption issue in this case.
   Two other aspects of the Court’s discussion of the legal
background must also be mentioned. First, although the
Court’s discussion of the point is a bit opaque, the Court
holds—correctly, in my view—that Wyeth’s use of the
phrase “clear evidence” was merely a rhetorical flourish.
As the Court explains, a judge, in determining whether
federal law would permit a label change allegedly required
by state law, “must simply ask himself or herself whether
the relevant federal and state laws ‘irreconcilably con-
flic[t].’ ” Ante, at 14 (quoting Rice v. Norman Williams Co.,
458 U. S. 654, 659 (1982)). Standards of proof, such as
preponderance of the evidence and clear and convincing
evidence, have no place in the resolution of this question
of law.
   Second, for reasons that entirely escape me, the Court
refuses to acknowledge that there are two ways in which a
drug manufacturer may attempt to alter a drug’s label.
The Court notes that a manufacturer may proceed under
the FDA’s “ ‘changes being effected’ ” or “ ‘CBE’ ” regulation,
which permits a manufacturer to change a label without
prior FDA approval under some circumstances. See ante,
at 3–4, 14. But the Court refuses to note that a manufac-
turer may (and, in many circumstances, must) submit a
Prior Approval Supplement (PAS). 21 CFR §314.70(b)
(2018). As the name suggests, changes proposed in a
PAS must receive FDA approval before drug manufac-
turers may make the changes.              §314.70(b)(3).   And
4       MERCK SHARP & DOHME CORP. v. ALBRECHT

                ALITO, J., concurring in judgment

“[h]istorically,” the FDA has “accepted PAS applications
instead of CBE supplements, as occurred in this case,
particularly where significant questions exist on whether
to revise or how to modify existing drug labeling.” Brief
for United States as Amicus Curiae 5.
                              II
   I now turn to the facts. Resolution of the legal question
that the Court decides does not require much discussion of
the facts, but if the Court wishes to include such a sum-
mary, its presentation should be balanced. Instead, the
Court provides a one-sided account. For example, it high-
lights historical accounts dating back to the 1990s that
purportedly linked atypical femoral fractures with Fosa-
max use, see ante, at 5, 7, but it omits any mention of the
extensive communication between Merck and the FDA
during the relevant period.
   A reader of the Court’s opinion will inevitably be left
with the impression that, once the FDA rejected Merck’s
proposed warning in 2009, neither the FDA nor Merck
took any other actions related to atypical femoral fractures
“until 2011,” ante, at 6. But that is simply not true.
   While Merck’s 2008 proposal was pending, the FDA
remained in contact with Merck about the issue of atypical
femoral fractures, which Merck, at the time, labeled as a
type of stress fracture. See, e.g., App. 707, 746–748. An
internal Merck memorandum describes a phone call in
which an FDA official allegedly told Merck that “[t]he
conflicting nature of the literature does not provide a clear
path forward, and more time will be need[ed] for FDA to
formulate a formal opinion on the issue of a precaution
around these data.” Id., at 767. In an e-mail about a week
later, another FDA official told Merck that the FDA would
“close out” Merck’s applications if Merck “agree[d] to hold
off on the [Precautions] language at this time.” Id., at 508.
The official went on to say that the FDA “would then work
                 Cite as: 587 U. S. ____ (2019)           5

               ALITO, J., concurring in judgment

with . . . Merck to decide on language for a [Precautions]
atypical fracture language, if it is warranted.” Ibid.
   Then, months after the FDA rejected Merck’s proposed
warning, the FDA issued a Safety Announcement regard-
ing its “[o]ngoing safety review of oral bisphosphonates
and atypical subtrochanteric femur fractures.” Id., at 519.
The Safety Announcement stated that, “[a]t this point, the
data that FDA has reviewed have not shown a clear con-
nection between bisphosphonate use and a risk of atypical
subtrochanteric femur fractures.” Ibid. Nonetheless, the
Safety Announcement announced the FDA’s intent to
further study the issue alongside a task force formed to
address the atypical fractures. Id., at 519–520. And the
Safety Announcement concluded by admonishing
healthcare professionals to “continue to follow the recom-
mendations in the drug label when prescribing oral
bisphosphonates” and patients to “not stop taking their
medication unless told to do so by their healthcare profes-
sional.” Id., at 520–521.
   In September 2010, the task force published its report,
which concluded that, although there was no established
“causal association” between bisphosphonates and atypical
femoral fractures, “recent observations suggest that the
risk rises with increasing duration of exposure, and there
is concern that lack of awareness and underreporting may
mask the true incidence of the problem.” Id., at 284. The
same day, the FDA issued a statement acknowledging the
task force report and committing to “considering label
revisions.” Id., at 523–525. And in October 2010, the FDA
issued another Safety Announcement in which the FDA
stated that it would initiate changes in the Precautions
section of bisphosphonate drug labels to warn of atypical
femoral fractures. Id., at 246–249. It was not until then
that, pursuant to its §355(o)(4)(A) obligations, the FDA
instructed Merck to include a warning about such frac-
tures in its Fosamax drug labels. Id., at 526–534.
6       MERCK SHARP & DOHME CORP. v. ALBRECHT

               ALITO, J., concurring in judgment

  Thus, for years the FDA was: aware of this issue, com-
municating with drug manufacturers, studying all rele-
vant information, and instructing healthcare professionals
and patients alike to continue to use Fosamax as directed.
For this reason, the FDA itself, speaking through the
Solicitor General, takes the position that the FDA’s deci-
sion not to require a label change prior to October 2010
reflected the FDA’s “determin[ation]” that a new warning
“should [not] be included in the labeling of the drug,”
§355(o)(4)(A). See Brief for United States as Amicus
Curiae 30, 33–34.
  For these reasons, I concur in the judgment only.