Mark Blackburn v. Shire US Inc, et al

[DO NOT PUBLISH]
In the
United States Court of Appeals
For the Eleventh Circuit
____________________
No. 20-12258
____________________
MARK BLACKBURN,
Plaintiff-Appellant,
versus
SHIRE U.S., INC.,
SHIRE, LLC,
Defendants-Appellees,
SHIRE DEVELOPMENT, LLC, et al.,
Defendants.
____________________
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2 Opinion of the Court 20-12258
Appeal from the United States District Court
for the Northern District of Alabama
D.C. Docket No. 2:16-cv-00963-MHH
____________________
Before J ILL PRYOR , L UCK , and B RASHER , Circuit Judges.
BRASHER, Circuit Judge:
This appeal returns to us after the Supreme Court of Ala-
bama answered two questions we certified for its review.
See
Blackburn v. Shire U.S., Inc., 18 F.4th 1310, 1322 (11th Cir. 2021),
certified question answered sub nom. Blackburn v. Shire U.S., Inc.,
No. 1210140, --- So. 3d --- (Ala. Sept. 30, 2022).
As we explained in our previous opinion, Mark Blackburn
was diagnosed with advanced-stage kidney disease after taking
LIALDA, a drug manufactured by Shire Pharmaceuticals, to treat
Crohn’s disease. Blackburn attributes his injuries to inadequacies in
LIALDA’s warning label. Blackburn does not contend that Shire
failed to warn of the risk of kidney disease. Instead, he contends
that if the LIALDA label had more explicitly instructed doctors to
monitor patients’ kidney function, his physician would have
treated him differently, discovered this side effect, and instructed
him to stop taking LIALDA.
The district court granted summary judgment to Shire. Alt-
hough it concluded that Alabama law supported Blackburn’s fail-
ure-to-warn theory, the district court also concluded that Black-
burn could not demonstrate a causal link between his injuries and
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20-12258 Opinion of the Court 3
the label’s shortcomings because Blackburn’s physician did not
read the LIALDA label before prescribing the drug.
We disagreed with the district court. We held that issues of
disputed fact should have prevented summary judgment.
See
Blackburn, 18 F.4th at 1319–21. But we asked the Supreme Court
of Alabama to tell us whether Blackburn’s failure-to-warn claim
was viable under Alabama law.
Id. at 1321–22. Specifically, we
asked the Supreme Court of Alabama to answer the following two
questions:
(1) Consistent with the learned intermediary doctrine, may
a pharmaceutical company’s duty to warn include a duty
to provide instructions about how to mitigate warned-of
risks?
(2) May a plaintiff establish that a failure to warn caused his
injuries by showing that his doctor would have adopted
a different course of testing or mitigation, even though
he would have prescribed the same drug?
Id. at 1321.
The Supreme Court of Alabama has answered both ques-
tions “yes.”
See Blackburn v. Shire U.S., Inc., No. 1210140, --- So.
3d --- (Ala. Sept. 30, 2022). In the words of the Supreme Court of
Alabama, a failure-to-warn claim under Alabama law “may include
allegations of inadequate instructions about how to mitigate
warned-of risks.”
Id., slip op. at 26. And “it follows that a plaintiff
may establish causation by showing that his or her physician would
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4 Opinion of the Court 20-12258
have adopted a different course of testing or mitigation, even
though the physician would have prescribed the same drug.”
Id.
Accordingly, Alabama law recognizes Blackburn’s cause of action.
There is only one remaining question: whether federal law
preempts this state-law cause of action. We expressly reserved this
issue in our previous opinion.
See Blackburn, 18 F.4th at 1319 n.1.
And, because of the Supreme Court of Alabama’s answers to our
certified questions, we must answer it now.
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.”
PLIVA, Inc. v. Mensing, 564 U.S. 604, 617
(2011) (quotation omitted). A direct conflict exists, and state law is
preempted, when it is “impossible for a private party to comply
with both state and federal requirements.”
Merck Sharp & Dohme
Corp. v. Albrecht, 139 S. Ct. 1668, 1672 (2019) (quotations and cita-
tions omitted);
see Wyeth v. Levine, 555 U.S. 555, 571 (2009).
“[T]he possibility of impossibility is not enough.”
Albrecht, 139 S.
Ct. at 1683 (Thomas, J., concurring) (cleaned up).
For a medication to be lawful, the Food and Drug Admin-
istration must approve its label. 21 U.S.C. §§ 355(a), 355(b)(1)(F); 21
C.F.R. § 314.50(c)(2)(i) (2016). The label must disclose, among
other things, warnings and precautions related to the drug’s effects.
See 21 C.F.R. § 201.56(d)(1) (2015). Once a label is approved, the
manufacturer is generally not permitted to alter it without the
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20-12258 Opinion of the Court 5
Administration’s approval. The “default rule” is that substantive
changes to a drug’s label must go through the Administration.
Dolin v. GlaxoSmithKline LLC, 901 F.3d 803, 806 (7th Cir. 2018);
21 C.F.R. § 314.70(b)(2)(v)(A) (2016). However, under the changes-
being-effected regulation, a manufacturer can make certain
changes to its label without prior approval. 21 C.F.R. §
314.70(c)(6)(iii) (2016). During this process, manufacturers need
not wait for the Administration’s preapproval; instead, they can file
a supplemental application with the Administration.
Wyeth, 555
U.S. at 568; 21 C.F.R. § 314.70(c)(6) (2016). Through this process, a
manufacturer may “add or strengthen a contraindication, warning,
[or] precaution,” 21 C.F.R. § 314.70(c)(6)(iii)(A) (2016), or “add or
strengthen an instruction about dosage and administration that is
intended to increase the safe use of the drug product,”
id.
§ 314.70(c)(6)(iii)(C). Language added through the changes-being-
effected process must be in response to “‘newly acquired infor-
mation’ about the ‘evidence of a causal association’ between the
drug and a risk of harm.”
Albrecht, 139 S. Ct. at 1673 (quoting 21
C.F.R. § 314.70(c)(6)(iii)(A)). “Newly acquired information” is de-
fined as “data, analyses, or other information not previously sub-
mitted to the agency, which may include (but is not limited to) data
derived from new clinical studies, reports of adverse events, or new
analyses of previously submitted data . . . .” 21 C.F.R. § 314.3(b)
(2016).
Because the “changes-being-effected” regulation permits la-
bel changes, “a drug manufacturer will not ordinarily be able to
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6 Opinion of the Court 20-12258
show that there is an actual conflict between state and federal law
such that it was impossible to comply with both.”
Albrecht, 139 S.
Ct. at 1679. Impossibility preemption exists only where there is
“clear evidence that the FDA would not have approved a change.”
Wyeth, 555 U.S. at 571. Whether “clear evidence” exists is a “mat-
ter of law for the judge to decide.”
Albrecht, 139 S. Ct. at 1679. The
Administration’s actions can affect the answer to the pre-emption
question.
Id. Nevertheless, manufacturers “cannot propose a
change that is not based on reasonable evidence.”
Id. (citing 21
C.F.R. § 314.70(c)(6)(iii)(A)).
Shire contends that it could not have supported a label
change with newly acquired information, or, at the least, Black-
burn failed to identify any. This argument is belied by the record.
Benjamin England, a regulatory expert retained by Blackburn, tes-
tified that Shire could have changed the label to include a stronger
monitoring instruction. His expert report noted that sufficient evi-
dence, including “a growing body of medical literature,” supported
a stronger monitoring instruction. England also identified reports
of renal impairment that Shire received between the label’s initial
approval and Blackburn’s injury. He concluded that sufficient evi-
dence would have led to a label change, had Shire sought one. Eng-
land further opined that the Administration would have approved
a label change based on adverse event reports and medical litera-
ture available to Shire after the label’s initial approval. For example,
an article from 2009 recommended the monthly monitoring sched-
ule that Blackburn asserts should have been part of Shire’s warning.
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20-12258 Opinion of the Court 7
Our review is circumscribed by the standard for summary
judgment. Taking England’s testimony in Blackburn’s favor as we
must, we cannot say that Blackburn’s claim is preempted. The reg-
ulations’ broad definition of newly acquired information includes
the sources England relied on. 21 C.F.R. § 314.3(b) (2016). We
therefore conclude that the record contains examples of infor-
mation available to Shire that could have formed the basis for seek-
ing a label change.
Moreover, the Administration never indicated that it would
not have accepted the change. Shire seemingly contends that the
Administration already rejected the change, but its argument is not
persuasive. It suggests that the evidence of mesalamine products’
impact on renal function is so pervasive that the Administration
must have determined that Blackburn’s suggested label change was
inappropriate. It notes that the “long history of human experience
with mesalamine-containing products” reveals that the Admin-
istration knew of the risk before LIALDA was approved. But Shire
does not contend that it ever attempted to strengthen the monitor-
ing instruction. The changes-being-effected regulation places the
onus on the manufacturer to “ensur[e] that its warnings remain ad-
equate as long as the drug is on the market.”
Wyeth, 555 U.S. at
570–71 (rejecting an argument that would shift “primary responsi-
bility [over] drug labeling” to the Administration). Importantly, be-
tween LIALDA’s initial approval in 2007 and Blackburn’s prescrip-
tion in 2013, the label changed in only one significant way: the Ad-
ministration “request[ed]” that Shire add “renal failure” to the
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8 Opinion of the Court 20-12258
warnings section of the label. This change suggests that the Admin-
istration may have been inclined to accept a stronger monitoring
instruction, had Shire offered it.
We further reject Shire’s alternative argument that it was
precluded from changing the warning because it was contained in
the “Highlights” section of the LIALDA label.
See 21 C.F.R.
§ 314.70(b)(2)(v)(C) (2016). The relevant regulation states that “[a]
supplement must be submitted for” three categories of “labeling
changes.”
Id. §§ 314.70(b)(1), (b)(2)(v). Shire focuses on subsection
(b)(2)(v)(C), which requires a supplement for “[a]ny change to the
information required by” the Highlights section, 21 C.F.R.
§ 201.57(a). But Shire overlooks subsection (b)(2)(v)(A), which ex-
empts “[c]hanges in labeling . . . described in paragraph[] (c)(6)(iii).”
Id. § 314.70(b)(2)(v)(A). Subsection (c)(6)(iii), of course, is the very
subsection at issue here, regarding “changes-being-effected.” And
one of the categories in the “changes-being-effected” regulation
permits “add[ing] or strengthen[ing] an instruction about dosage
and administration that is intended to increase the safe use of the
drug product.”
Id. § 314.70(c)(6)(iii)(C). Blackburn’s proposed lan-
guage fits into that category because it is a recommendation for
how to administer LIALDA in a way that increases its safe use.
On this summary judgment record, we cannot say that fed-
eral law preempts Blackburn’s state-law cause of action. Based on
this conclusion, our previous opinion, and the Supreme Court of
Alabama’s answers to our certified questions, we REVERSE and
REMAND for further proceedings.
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