Beth S. Rose, Charles J. Falletta
June 26, 2019
In an eagerly anticipated preemption
decision relating to Merck Sharp & Dohme Corp.’s (“Merck”) Fosamax
medication, the U.S. Supreme Court in Merck
Sharp & Dohme Corp. v. Albrecht, 2019 U.S. LEXIS 3542 (May 20, 2019), unanimously
determined that the issue of whether state law failure to warn claims were
preempted by federal law is a question of law to be decided by the court, and
not a question of fact to be decided by a jury.
In addition, the Court clarified what it meant over ten years ago in Wyeth v. Levine, 555 U.S. 555 (2009), by
the statement that “absent clear evidence that the FDA would not have approved
a change to . . . [the] label, we will not conclude that it was impossible
for Wyeth to comply with both federal and state requirements.” Id.
at 571. The Albrecht Court instructed that “clear evidence” was not an
evidentiary standard like a “preponderance of the evidence” or “clear and
convincing evidence”. Albrecht, 2019 U.S. LEXIS 3542, at
**25-26. Rather, the Court held that
“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.” Id.
The Court did not determine
whether plaintiffs’ state failure-to-warn claims were preempted as a matter of
law and remanded to the Third Circuit for further proceedings. It remains to be seen whether Merck will
prevail on its preemption defense, but drug manufacturers should be encouraged
that courts, not juries, will resolve preemption motions in the future, and
that the Court defined what it meant by “clear evidence” in Wyeth v. Levine.
is an FDA approved medicine prescribed to treat and prevent osteoporosis in
postmenopausal women. Fosamax affects
the bone remodeling process by slowing down the breakdown of old bone cells and
helping postmenopausal women avoid osteoporotic fractures.
*10. Fosamax, however, may increase the
risk of atypical femoral fractures because it may cause certain stress factors,
that typically heal on their own, to progress to complete fractures.
At the time of
Fosamax’s approval in 1995, the label did not warn of the risk of atypical
femoral fractures even though Merck was aware of the “theoretical risk” of such
fractures as early as 1990 and 1991. Id. at *11. Merck informed the FDA about these
theoretical risks, but the FDA did not require them to be mentioned in the
approved Fosamax label. Id. at *11-12.
receiving evidence connecting atypical femoral fractures with long term Fosamax
use, Merck attempted to update the Fosamax label by submitting a Prior Approval
Supplement (“PAS”) to the FDA in 2008.
at *12-13. A PAS requires FDA approval before the label
changes can be made.
21 C.F.R. §314.70(b). Merck proposed
to add information related to “low-energy femoral shaft fracture” in the
Adverse Reactions section and additional information in the Precautions section
focusing on the association between Fosamax and the risk of stress
at *13. The FDA approved
the Adverse Reactions section changes, but determined that Merck’s
justification for changing the Precautions section was “inadequate.”
FDA informed Merck that it could resubmit the
PAS and address FDA’s concerns.
Instead of resubmitting its PAS and addressing the issues identified by
the FDA, Merck withdrew its application and made changes to the Adverse
Reactions section through the Changes Being Effected (“CBE”) process, which
permits a label change without FDA approval where there is “newly acquired
information” about the “evidence of a causal association” that will “add or
strengthen a . . . warning”.
at *9-10, *13;
21 C.F.R. §314.70(c)(6)(iii)(A).
include more than 500 women who alleged that Merck failed to warn about the
risk of atypical femoral fractures between 1999 and 2010.
2019 U.S. LEXIS 3542, at *14. While
Merck conceded that it could have tried to change the label before 2010 to add such
a warning, Merck argued before the U.S. District Court of New Jersey that the
FDA would have rejected the change and that because federal law prevented it
from complying with any state-law duty to warn of the association between
Fosamax and atypical femoral fractures, respondents claims were preempted.
at *15-16. In particular, Merck argued
that the FDA’s rejection of its 2008 PAS to the Fosamax label to warn of
“stress fractures” prevented Merck from complying with any state law duty to
warn of atypical femoral fractures associated with Fosamax.
at 16. The District Court agreed and
granted Merck summary judgment.
The Third Circuit
vacated and remanded. Id.
The Third Circuit explained that under Wyeth v. Levine, a state law failure to warn claim would only be
pre-empted if there was “clear evidence that the FDA would not have approved a
change to the . . . label.” Id. (quoting Wyeth v. Levine, 555 U.S. at 571).
Noting that lower courts had interpreted this language differently and
that it would be helpful for the U.S. Supreme Court to clarify what it meant,
the Third Circuit determined that “[t]he term ‘clear evidence’ . . . does not
refer directly to the type of facts that a manufacturer must show, or to the
circumstances in which preemption will be appropriate”, but “[i]t specifies how
difficult it will be for the manufacturer to convince the factfinder that the
FDA would have rejected a proposed label change.” Id.
at *16-17 (quoting In re Fosamax
Alendronate Sodium Prods. Liab. Litig., 852 F.3d 268, 285-86 (3d Cir. 2017)). The Third Circuit further held that “whether
the FDA would have rejected a proposed label change is a question of fact that
must be answered by a jury.’” Id. at *17 (quoting In re Fosamax Alendronate Sodium Prods. Liab. Litig., 852 F.3d at
Preemption Determinations Are Matters Of
Law For the Court To Decide
The U.S. Supreme Court
described the “determinative question” before the Court as follows: “Is the question of agency disapproval [FDA
rejection of the proposed label] primarily one of fact, normally for juries to
decide, or is it a question of law, normally for a judge to decide without a
at *27. In holding that this
was a question of law, the Court stated:
The question often involves the use of
legal skills to determine whether agency disapproval fits facts that are 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 normally produced by
a federal agency to memorialize its considered judgments. And judges are better suited than are juries
to understand and to interpret agency decisions in light of the governing
statutory and regulatory context. 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 normally a virtue when a question requires a determination concerning the
scope and effect of federal agency action.
at *27-28 (citations omitted). Moreover,
the Court held that any factual disputes relevant to the judges’ determination
of this legal issue were “subsumed” in the judge’s legal analysis, and not to
be submitted to a jury. Id. at *29.
Unanswered Questions in
Wyeth v. Levine
Wyeth v. Levine
, the Court held that
state law failure-to-warn claims were pre-empted by federal law and regulations
“when there is ‘clear evidence’ that the FDA would not have approved the
warning that state law requires.”
at *18 (citing
Wyeth v. Levine
, 555 U.S. at 571).
gangrene after a physician’s assistant improperly injected her with Penergan,
an anti-nausea medication.
Plaintiff alleged that Wyeth failed to warn of the significant risk of
catastrophic consequences if Phenergan was directly injected into a person’s
vein (“IV-push”), which risks could be avoided by administering the medication
through a saline solution intravenous drip method (“IV-drip”).
at *19. After a jury determined that
Wyeth’s warning label was inadequate as a matter of state law, Wyeth appealed
and argued that the plaintiff’s state law failure-to-warn claim was pre-empted
“because it was impossible for Wyeth to comply with both state law duties and federal
Both the Vermont
Supreme Court and the U.S. Supreme Court rejected Wyeth’s pre-emption
argument. In particular, the Court
determined that Wyeth had a duty under state law to update its label and
provide an adequate warning while the drug was on the market, and that the
federal CBE process permitted Wyeth to provide such a warning before FDA
approval. Id. at *21-22. In so
holding, the Wyeth Court had noted
that “the FDA retains authority to reject labeling changes pursuant to the CBE
regulation in its review of the manufacturer’s supplemental application, just
as it retains such authority in reviewing all supplement applications.” Id.
at *22 (quoting Wyeth v. Levine, 555
U.S. at 571). But without defining what
it meant, the Wyeth Court also noted
that “absent clear evidence that the FDA would not have approved a change to
Phenergan’s label, we will not conclude that it was impossible for Wyeth to
comply with both federal and state requirements.” Id.
Wyeth’s pre-emption defense, the Wyeth
Court determined that the record did not show that Wyeth “supplied the FDA with
an evaluation or analysis concerning the specific dangers” to support the
warning or that “either the FDA or the manufacturer gave more than passing
attention to the issue of IV-push versus IV-drip administration.” Id.
at *22-23 (citing Wyeth v. Levine,
555 U.S. at 572-73). As a result, the Wyeth Court could not conclude that it
“was impossible for Wyeth to comply with both federal and state
requirements.” Id. at *23 (quoting Wyeth v.
Levine, 555 U.S. at 573).
Meaning of “Clear Evidence” Clarified
Court clarified that “clear
evidence” was not, as some courts had postulated, an evidentiary standard, such
as “preponderance of the evidence” or “clear and convincing evidence”.
at *25. The Court instructed that when
faced with preemption defenses, the trial court must determine whether there is
“evidence that shows . . . 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.”
Further, the Court
noted that only agency actions within the FDA’s congressionally delegated
authority can be used to determine whether federal law prohibited a
manufacturer from adding warnings to comply with state law. Id. at *26.
These include: 1) FDA
communicating its disapproval of a warning through a “notice-and-comment
rulemaking setting forth labeling standards”; 2) “by [FDA] formally rejecting a
warning that would have been adequate under state law”; or 3) “with other
agency action carrying the force of law.”
Id. at *26-27 (citing 21 U.S.C. §355(d), 21 C.F.R. §§201.57, 314.105; 21
C.F.R. §§314.110(a), 314.125(b)(6); 21 U.S.C. §§355(o)(4)(A)).
Opinion: Justice Thomas
Justice Thomas wrote
separately to explain that in his view, Merck’s preemption defense should fail
as a matter of law because Merck failed to identify any federal law or FDA
disapproval prohibiting it from adding a warning that would satisfy state
at *34-35. Justice Thomas rejected Merck’s argument that
the FDA would have rejected a CBE labeling change because “neither agency
musings nor hypothetical future rejections constitute pre-emptive ‘Laws” under
the Supremacy Clause.”
Justice Thomas noted that Merck acknowledged that “it could have
resubmitted its PAS application, sought a hearing, or changed its label at any
time through the CBE process.”
at *36. If Merck had re-submitted its PAS
application, sought a hearing, or utilized the CBE process, in Justice Thomas’s
view, “it could have satisfied its federal and alleged state-law duties –
meaning it was possible for Merck to independently satisfy both sets of
Opinion: Justice Alito
joined by Chief Justice Roberts and Justice Kavanaugh, concurred in the
judgment but did not join the Court’s opinion “because [he was] concerned that
its discussion of the law and the facts may be misleading on remand.”
at *38. In particular, Justice Alito took
issue with the Court’s failure to address the following issues: 1) Under 21 U.S.C. §355(o)(4)(A), Congress imposed
on the FDA a duty to initiate a label change where justified, which FDA did not
do here until 2010; 2) despite receiving and considering information related to
a new risk, FDA decided not to impose a label change, which demonstrates that FDA
had determined that a label change was not justified; and 3) although a
manufacturer may change a label through the CBE process, as Merck did here, a
manufacturer “may (and, in many circumstances, must) submit a Prior Approval
Supplement”, which requires FDA approval, “where significant questions exist on
whether to revise or how to modify existing drug labeling.”
Justice Alito also
took exception with the Court’s omission of balancing facts that demonstrated
that Merck and the FDA had “extensive communications” during the relevant time
period, which support the position that the “FDA’s decision 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.” Id.
at *45. (citations omitted). Justice Alito explained that while the FDA
was considering Merck’s 2008 proposed label changes, Merck and the FDA continued
discussing the issue. Id. at *42-43. Indeed, there were several communications
between Merck and the FDA, in which FDA expressed the need for more time to
analyze the data and determine whether a precaution was warranted. Id.
at *43. Justice Alito noted that several
months after rejecting Merck’s labeling proposal, FDA issued a Safety
Announcement concerning its safety review of this class of drugs
(bisphosphonates) and atypical femoral fractures, and its plan to further study
the issue along with a task force. Id.
The FDA also announced that the data at that time did not show a “clear
connection” to the risk of atypical femoral fractures, and that healthcare
professionals should continue to follow the current label. Id. The task force published its report in
September 2010, and concluded that the risk of atypical femoral fractures rose
with long term use of bisphosphonates even though a causal association had not
been established. Id. at *44. In response, the
FDA issued a statement that committed to considering a label change and a month
later, in October 2010, issued another Safety Announcement, stating that it
would be making changes to the Precautions section of bisphosphonate labels. Shortly thereafter, FDA instructed Merck to
include a warning of atypical femoral fractures in the Fosamax label. Id.
Court’s decision is significant, but narrow.
On the one hand, the Court made clear that questions of impossibility
preemption are questions of law to be decided by judges not juries. The Court also clarified what it mean by
“clear evidence” in
Wyeth v. Levin. On the other hand, the Court did not offer an
opinion on whether respondents’ claims were pre-empted by federal law. It will be interesting to see how the Third
Circuit responds to the Court’s ruling. We
will continue to monitor this issue as it makes its way through the Third
Circuit on remand and will advise of any important updates.
This Client Alert has been prepared by Sills Cummis & Gross P.C. for informational purposes only and does not constitute advertising or solicitation and should not be used or taken as legal advice. Those seeking legal advice should contact a member of the Firm or legal counsel licensed in their state. Transmission of this information is not intended to create, and receipt does not constitute, an attorney-client relationship. Confidential information should not be sent to Sills Cummis & Gross without first communicating directly with a member of the Firm about establishing an attorney-client relationship.