Amicus Curiae Brief — Merck Sharp & Dohme Corporation, Petitioner v. Doris Albrecht, et al.

No. 24-977

IN THE

Supreme Court of the United States

________________________________________

MERCK SHARP & DOHME CORPORATION,

Petitioners,

v.

DORIS ALBRECHT, ET AL.,

Respondent.

________________________________________

On Petition for a Writ of Certiorari to the United

States Court of Appeals for the Third Circuit

________________________________________

BRIEF FOR THE PHARMACEUTICAL

RESEARCH AND MANUFACTURERS OF

AMERICA AS AMICUS CURIAE IN SUPPORT OF

CERTIORARI

________________________________________

Paul W. Schmidt

Gregory L. Halperin

COVINGTON & BURLING LLP

The New York Times Building

620 Eighth Avenue

New York, NY 10018

Michael X. Imbroscio

Counsel of Record

Anand M. Balaji

COVINGTON & BURLING LLP

One CityCenter

850 Tenth Street, NW

Washington, DC 20001

mimbroscio@cov.com

(202) 662-6000

April 11, 2025

Counsel for Amicus Curiae

i

TABLE OF CONTENTS

Page

TABLE OF AUTHORITIES ...................................... iii

INTERESTS OF AMICUS CURIAE ..........................1

INTRODUCTION AND SUMMARY OF

ARGUMENT ........................................................3

ARGUMENT ...............................................................5

I.

II.

THE THIRD CIRCUIT’S DECISION

DIVERGES FROM SIX YEARS OF POSTALBRECHT CASE LAW, CREATING A

CIRCUIT SPLIT THAT DEMANDS

RESOLUTION. ....................................................5

A.

In Albrecht, the Supreme Court

Resolved a Longstanding Split on

Preemption. ..................................................5

B.

The Third Circuit’s Disregard of

Albrecht Disturbs Six Years of

Consistent Application. ................................6

THE

FOSAMAX

II

DECISION

DISREGARDS

FDA’S

LABELING

OBLIGATIONS AND THREATENS ITS

EFFECTIVENESS. ............................................11

A.

The Third Circuit’s Ruling Threatens

to Overwhelm the FDA’s Review

Capabilities. ................................................12

ii

B.

The FDA’s Obligations Under the

FDAAA

Already

Ensure

That

Labeling Is Accurate. .................................16

III. THE THIRD CIRCUIT’S

RULING

HAMPERS

MANUFACTURER

INNOVATION AND HARMS PATIENT

HEALTH. ...........................................................20

CONCLUSION ..........................................................24

iii

TABLE OF AUTHORITIES

Page(s)

Cases

Adkins v. Boehringer Ingelheim Pharms., Inc.,

2020 WL 1890681 (Conn. Super. Ct. Mar.

13, 2020) ............................................................ 23

Bates v. Dow Agrosciences LLC,

544 U.S. 431 (2005) ........................................... 18

Buckman v. Pls.' Legal Comm.,

531 U.S. 341 (2001) ........................................... 13

Bueno v. Merck & Co.,

746 F. Supp. 3d 853 (S.D. Cal. 2024) ........... 7, 10

Cerveny v. Aventis,

783 F. App'x 804 (10th Cir. 2019) ...................... 9

Cerveny v. Aventis, Inc.,

855 F.3d 1091 (10th Cir. 2017) ......................... 14

Dolin v. GlaxoSmithKline LLC,

901 F.3d 803 (7th Cir. 2018) ............................. 14

Dolin v. GlaxoSmithKline LLC,

951 F.3d 882 (7th Cir. 2020) ............................... 9

In re Fosamax (Alendronate Sodium) Prod.

Liab. Litig.,

852 F.3d 268 (3d Cir. 2017) ............................ 3, 5

Gibbons v. Bristol-Myers Squibb Co.,

919 F.3d 699 (2d Cir. 2019) .............................. 23

iv

Hickey v. Hospira Inc.,

102 F.4th 748 (5th Cir. 2024) ....................... 7, 10

In re Incretin-Based Therapies Prod. Liab.

Litig.,

2022 WL 898595 (9th Cir. Mar. 28, 2022) ......... 7

In re Incretin-Based Therapies Prod. Liab.

Litig., 524 F. Supp. 3d 1007 (S.D. Cal.

2021) ........................................................ 7, 10, 23

Knight v. Boehringer Ingelheim Pharms.,

Inc.,

984 F.3d 329 (4th Cir. 2021) ......................... 7, 23

Lofton v. McNeil Consumer & Specialty

Pharm.,

672 F.3d 372 (5th Cir. 2012) ............................. 16

Lyons v. Boehringer Ingelheim Pharms.,

Inc.,

491 F. Supp. 3d 1350 (N.D. Ga. 2020) ................ 7

Mahnke v. Bayer Corp.,

2019 WL 8621437 (C.D. Cal. Dec. 10,

2019) .............................................................. 7, 10

Mason v. SmithKline Beecham Corp.,

596 F.3d 387 (7th Cir. 2010) ............................... 5

Merck Sharp & Dohme Corp. v. Albrecht,

587 U.S. 299 (2019) ..... 3–8, 12, 14–15, 17–19, 23

Mutual Pharm. Co., Inc. v. Bartlett,

570 U.S. 472 (2013) ........................................... 20

v

PLIVA, Inc. v. Mensing,

564 U.S. 604 (2011) ........................................... 20

Ridings v. Maurice,

444 F. Supp. 3d 973 (W.D. Mo. 2020) ................. 7

Riegel v. Medtronic, Inc.,

552 U.S. 312 (2008) ........................................... 23

Warner v. Amgen Inc.,

2025 WL 490720 (D. Mass. Feb. 13,

2025) .................................................................. 10

Wyeth v. Levine,

555 U.S. 555 (2009) ................................... 5, 9, 18

In re Zofran (Ondansetron) Prods. Liab.

Litig.,

57 F.4th 327 (1st Cir. 2023) ................ 7, 9, 10, 23

Statutes

21 U.S.C. § 355 ....................................................... 17

Regulations

21 C.F.R. § 314.70 .............................................. 7, 15

21 C.F.R. § 314.80 .................................................. 17

21 C.F.R. § 314.110 ............................................ 8, 19

Requirements on Content and Format of

Labeling for Human Prescription Drug

and Biological Products, 71 Fed. Reg.

3922 (Jan. 24, 2006) .......................................... 15

vi

Other Authorities

Admin. Office of the U.S. Courts, Table C2A: U.S. District Courts-Civil Cases

Commences, by Nature of Suit, During

the 12-Month Periods Ending September

30, 2020 through 2024 (2024) ........................... 22

Daniel E. Troy, The Case for FDA

Preemption, in Federal Preemption:

States’ Powers, National Interests (2007) ......... 22

Duxin Sun et al., Why 90% of Clinical Drug

Development Fails and How to Improve

It, 12(7) Acta Pharm. Sinica B. 3049

(2021) ................................................................. 21

Joseph A. DiMasi et al., Innovation in the

Pharmaceutical Industry: New Estimates

of R&D Costs, 47 J. Health Econ. 20

(2016) ................................................................. 20

Mark Senak, Potayto-Potahto? The Meaning

of the FDA's “Complete Response”

Letters, 1(7) Am. Health Drug Benefits

30 (2008) ............................................................ 15

MedWatch: The FDA Safety Information

and Adverse Event Reporting Program,

FDA ................................................................... 17

Perryman Grp., Economic Benefits of Tort

Reform (Nov. 4, 2019) ....................................... 22

PhRMA, 2024 PhRMA Annual Membership

Survey (2024)................................................. 1, 21

vii

PhRMA, Biopharmaceutical Research &

Development: The Process Behind New

Medicines (2015) ............................................... 21

PhRMA, Biopharmaceuticals in Perspective:

Fall 2020 (2020) ................................................ 20

U.S. Jud. Panel on Multidist. Litig., MDL

Statistics Report: Docket Type Summary

(Apr. 1, 2025) ..................................................... 22

1

INTERESTS OF AMICUS CURIAE1

The Pharmaceutical Research and Manufacturers

of America (“PhRMA”) represents the country’s

leading innovative biopharmaceutical companies,

which are laser-focused on developing innovative

medicines that transform lives and create a healthier

world. Together, PhRMA is fighting for solutions to

ensure patients can access and afford medicines that

prevent, treat and cure disease. Over the last decade,

PhRMA member companies have invested more than

$800 billion in the search for new treatments and

cures, and they support nearly 5 million jobs in the

United States. See PhRMA, 2024 PhRMA Annual

Membership Survey 3 (2024), https://perma.cc/6NB63F6V.

This case presents a question of significant importance for PhRMA’s members: whether after this

Court’s 2019 decision in Merck v. Albrecht, pharmaceutical manufacturers can face state tort-law

liability for failing to include warning language on

their labeling after the Food and Drug Administration

(“FDA”) has determined that such a warning is not

medically justified. The burdens of product liability

1 Pursuant to Rule 37.6, amicus affirms that no counsel for a

party authored this brief in whole or in part and that no person

other than amicus, its members, or its counsel made any monetary contributions intended to fund the preparation or

submission of this brief. A list of PhRMA members is available

at http://www.phrma.org/about#members. Merck & Co. is a

member of PhRMA, but did not contribute financially to the preparation of this brief. The parties were timely notified of amicus’s

intent to file this brief.

2

litigation are already substantial for life sciences companies, and a regime that permits these companies to

be held liable for failing to do what the FDA has determined is not medically appropriate would disrupt

regulation, hamper innovation, and harm patient

health. The Court should grant certiorari and reverse

the Third Circuit’s judgment.

3

INTRODUCTION AND SUMMARY OF

ARGUMENT

Nearly six years ago in Merck Sharp & Dohme v.

Albrecht, this Court resolved widespread confusion on

how to apply the “clear evidence” standard to determine whether the FDA would have approved a change

to a medication’s labeling, thus preempting a statelaw failure to warn claim. 587 U.S. 299 (2019). In

Albrecht, the Third Circuit had held that a jury should

decide the preemption question, and that a jury would

have to find “clear and convincing evidence” that the

proposed warning was preempted. In re Fosamax

(Alendronate Sodium) Prod. Liab. Litig., 852 F.3d

268, 286 (3d Cir. 2017) (“Fosamax I”). This Court

firmly rejected that approach, and instead laid out a

test for courts to address the preemption question. Albrecht, 587 U.S. at 303.

Now, history repeats. The Third Circuit once

again veers sharply away from its sister circuits. In

this case, a continuation of the Fosamax litigation

against Merck, the Third Circuit found that a “heavy

Albrecht presumption” against preemption is determinative in cases where there is any ambiguity in the

FDA’s official response to a potential labeling change.

This stark holding is at war with both the text of Albrecht and how other lower courts have applied that

decision. By loading the dice with an effectively dispositive presumption and by paying little attention to

surrounding factual and statutory context, the Third

Circuit once again places itself as an extreme outlier.

Without intervention by this Court, what had become

a reasonably settled regime will be reshuffled and

4

cause mischief and chaos once again in the lower

courts.

In reaching its decision, the Third Circuit does not

contend with the realities of the pharmaceutical industry and the FDA’s obligations under the Food and

Drug Administration Amendments Act (“FDAAA”).

In taking a highly constrained view of FDA’s statutorily mandated decision making, the decision below

incentivizes companies to inundate the FDA with repeated submissions of every linguistic variation of a

label in hopes of heading off an argument in some future litigation that the FDA’s “No” didn’t really mean

“No.” This Court in Albrecht rejected such a nonsensical regime; it directed district courts to evaluate the

regulatory record and make its best factual determination, unencumbered by any case-steering

presumption. That is exactly what the district court

did here. The Third Circuit’s reversal of that factual

determination is not so much a critique of the district

judge’s performance of that duty as much as it is a denunciation of this Court’s mandate in Albrecht.

Such an outcome is highly detrimental to patient

safety, especially when the FDA is already statutorily

obligated under the FDAAA to mandate new labeling

if it identifies a new safety risk. The Third Circuit’s

presumptively-never preemption standard risks exposing manufacturers to unfair liability for health

outcomes the FDA has determined cannot be linked to

the medicine, which in turn will materially diminish

innovation and impact public health.

5

ARGUMENT

I.

THE THIRD CIRCUIT’S DECISION

DIVERGES FROM SIX YEARS OF POSTALBRECHT CASE LAW, CREATING A

CIRCUIT

SPLIT

THAT

DEMANDS

RESOLUTION.

A.

In Albrecht, the Supreme Court

Resolved a Longstanding Split on

Preemption.

The Supreme Court in Albrecht provided guidance

to resolve confusion in how lower courts were applying

the preemption analysis set forth in Wyeth v. Levine,

555 U.S. 555 (2009). In Wyeth, the Court laid out the

“clear evidence” test to assess whether the FDA would

have approved a change to a medication’s labeling,

and in that case found the FDA had never given “more

than passing attention” to the warning plaintiffs

sought. Wyeth, 555 U.S. at 571–72. Without guidance

about the type and quantum of evidence required to

meet this burden, lower courts varied in their interpretation of the “clear evidence” test in practice. See,

e.g., Fosamax I, 852 F.3d at 282 (the clear evidence

standard is “cryptic and open-ended, and lower courts

have struggled to make it readily administrable”);

Mason v. SmithKline Beecham Corp., 596 F.3d 387,

391 (7th Cir. 2010) (the Court “did not clarify what

constitutes ‘clear evidence.’ Therefore, the only thing

we know for sure is that the evidence presented in

Levine did not meet this exacting standard.”).

In Merck Sharp & Dohme Corp. v. Albrecht, 587

U.S. 299 (2019), this Court provided direction on how

6

to apply Wyeth’s clear evidence test. First, this Court

overturned the Third Circuit’s holding that the question of whether the FDA had rejected a warning was

one for the jury, instead stating that this was a legal

issue to be decided by the judge. Albrecht, 587 U.S. at

310. Second, and more crucially, this Court rejected

the notion that Wyeth’s clear evidence test was some

kind of heightened evidentiary standard, and instead

held that “the judge must simply ask himself or herself whether the relevant federal and state laws

irreconcilably conflict.” Id. at 315 (cleaned up). Finally, the Court in Albrecht provided a two-part test

for preemption which required evidence (1) “that the

drug manufacturer fully informed the FDA of the justifications for the warning,” and (2) that, in turn, an

action taken by the FDA “informed the drug manufacturer that the FDA would not approve a change to the

drug’s label to include that warning.” Id. at 303.

Since Albrecht, lower courts have applied its

preemption framework to contexts where the FDA indicated that a proposed additional warning—whether

specifically considered at the time by FDA or proposed

by some lawyer in some future litigation—would not

have been approved.

B.

The Third Circuit’s Disregard of

Albrecht Disturbs Six Years of

Consistent Application.

The lower courts have been routinely applying Albrecht in a manner consistent with the two-part test,

without layering on substantive canons against

preemption. Subsequent cases further refined the

analysis to track both the language of Albrecht and

7

the Changes Being Effected (“CBE”) regulation that

Wyeth explained provided the narrow pathway to

avoid preemption. See 21 C.F.R. § 314.70(c)(6)(iii)(A).

That test, since adopted by courts across the nation,

asks (1) is there “newly acquired information” such

that the CBE regulatory pathway can be invoked, and

if so, (2) whether there is “clear evidence” under Albrecht that the FDA would have rejected such a CBE

application. See, e.g., In re Zofran (Ondansetron)

Prods. Liab. Litig., 57 F.4th 327, 336 (1st Cir. 2023);

Knight v. Boehringer Ingelheim Pharms., Inc., 984

F.3d 329, 338–39 (4th Cir. 2021); In re Incretin-Based

Therapies Prod. Liab. Litig., 524 F. Supp. 3d 1007,

1017 (S.D. Cal. 2021), aff’d on other grounds, No. 2155342, 2022 WL 898595 (9th Cir. Mar. 28, 2022);

Hickey v. Hospira Inc., 102 F.4th 748, 754 (5th Cir.

2024) (per curiam).2

In postulating an effectively dispositive “strong

presumption” against preemption, while at the same

time simply casting aside the district court’s factual

determinations as to the regulatory record of the

FDA’s decision, the Third Circuit has become an outlier in its application of Albrecht. See Pet. App. 62a.

(holding that the “strong presumption [against

preemption] that the Supreme Court has established

will likely be determinative.”). Rather than place any

weight on the surrounding factual context or regulatory history or defer to the district court’s meticulous

2 See also Lyons v. Boehringer Ingelheim Pharms., Inc., 491 F.

Supp. 3d 1350, 1363 (N.D. Ga. 2020); Mahnke v. Bayer Corp.,

2019 WL 8621437, at *3 (C.D. Cal. Dec. 10, 2019); Bueno v. Merck

& Co., 746 F. Supp. 3d 853, 875 (S.D. Cal. 2024); Ridings v.

Maurice, 444 F. Supp. 3d 973, 991 (W.D. Mo. 2020).

8

evaluation of that record, the Third Circuit effectively

held that any ambiguities in the regulatory record—

here, FDA’s Complete Response Letter (“CRL”)3—

“are swept away by the heavy Albrecht presumption.”

Id. at 66a.

First, the Third Circuit’s reasoning is irreconcilable with Albrecht, which doesn’t mention any

presumptions and explicitly held that district judges

are best equipped “to understand and to interpret

agency decisions in light of the governing statutory

and regulatory context.” Albrecht, 587 U.S. at 315–

16. Albrecht does not apply a presumption against

preemption, and instead directs judges to “simply ask

… whether the federal and state laws irreconcilably

conflict.” Id. at 315 (cleaned up) (also noting that a

“hypothetical or potential conflict is insufficient”).

The Third Circuit instead contorts Albrecht by latching on to stray references to words like “difficult” and

“demanding” to create a “strong presumption,” even

though this Court never even used the word “presumption” in its Albrecht majority opinion. Pet. App.

62a. To the extent that any consideration of a presumption against preemption is necessary, Wyeth’s

3 A CRL is issued by the FDA in denying a labeling proposal, and

“describes[s] all of the specific deficiencies that the agency has

identified” and “when possible ... recommend[s] actions that the

applicant might take to place the application or abbreviated

application in condition for approval.” 21 C.F.R. § 314.110(a).

The CRL “reflects FDA’s complete review of the data submitted.”

Id. § 314.110(a)(2). After receiving a CRL, manufacturers have

the option to resubmit the application addressing all the

deficiencies, withdraw the application without prejudice to a

subsequent submission, or ask the agency for a hearing. Id. §

314.110(b).

9

“clear evidence” test itself already bakes in that notion. Wyeth, 555 U.S. at 565, 575. The irregularity of

this decision is only confirmed by the fact that no

other lower courts have applied Albrecht in this way.

Second, the Third Circuit’s deviation creates significant confusion on the application of Albrecht and

undoes the clarity this Court attempted to instill with

that decision. Other post-Albrecht cases do not invoke

a presumption against preemption in evaluating (1)

whether new information was acquired that would

permit a manufacturer to make a labeling change using the CBE process, and (2) whether the FDA would

have rejected such a labeling change. In Cerveny v.

Aventis, the Tenth Circuit rejected an argument to

narrowly read Albrecht as only applying to situations

where the drug manufacturer itself sought labeling

changes, and instead found preemption where the

FDA rejected a citizen petition seeking to provide a

warning for the health outcome at issue. 783 F. App’x

804, 808 n.9 (10th Cir. 2019). In affirming its prior

decision, the Tenth Circuit did not rely on any substantive presumptions which could skew the inquiry

against preemption. Id.

In Dolin v. GlaxoSmithKline LLC, the Seventh

Circuit applied Albrecht without a presumption

against preemption and affirmed a district court finding that the FDA had rejected a drug-specific warning

by mandating uniform class-wide labels. 951 F.3d

882, 891 (7th Cir. 2020). Similarly in In re Zofran

(Ondansetron) Prods. Liab. Litig., the First Circuit affirmed the district court’s preemption finding where

FDA had possession of the latest studies and approved

a label without the warning plaintiffs sought. 57

10

F.4th at 342. The First Circuit did not apply any presumptions or note the “difficulty” entailed in

establishing preemption and instead simply held that

the “FDA in approving the label stating ‘not-X’ necessarily rejected plaintiffs’ prominently presented case

for stating ‘X’.” Id. Notably, the First Circuit did not

require an express rejection of a proposed warning but

instead found an implied rejection based on the FDA’s

approval of a contrary label. Id.

Even more courts have both declined to apply a

presumption against preemption and also made ample use of extrinsic factual context when applying

Albrecht to determine whether manufacturers lacked

the newly acquired information necessary to invoke

the CBE process. See, e.g., Mahnke, 2019 WL

8621437, at *4 (examining universe of scientific literature in finding no newly acquired information); In re

Incretin-Based Therapies, 524 F. Supp. 3d at 1029–33

(holding that manufacturer did not have newly acquired information and there was clear evidence FDA

would not have approved CBE based in part on review

of extrinsic evidence); In re Zofran (Ondansetron), 57.

F4th at 26 (analyzing scientific studies to determine

manufacturer did not have newly acquired information); Bueno, 746 F. Supp. 3d at 877–80 (reviewing

state of scientific analysis in finding no newly acquired information and preemption); Warner v.

Amgen Inc., 2025 WL 490720, at *9–10 (D. Mass. Feb.

13, 2025) (reviewing published articles in finding no

newly acquired information); Hickey, 102 F.4th at

757–59 (analyzing pre-approval and post-approval

scientific literature in finding no newly acquired information).

11

By overlaying its dispositive “Albrecht presumption” and disregarding the relative weight of statutory

and factual context, the Third Circuit has created confusion and a significant circuit split.

PhRMA

members do not have the luxury of treating Fosamax

II as an aberration, both because it creates a higher

bar for preemption fundamentally inconsistent with

this Court’s decision in Albrecht and because a substantial number of PhRMA members are

headquartered in the Third Circuit. Absent intervention and review by this Court, the standard created by

Albrecht will evaporate in the face of drastically different presumptions and applications of the two-part

test.

II.

THE

FOSAMAX

II

DECISION

DISREGARDS

FDA’S

LABELING

OBLIGATIONS AND THREATENS ITS

EFFECTIVENESS.

The Third Circuit’s decision pays insufficient

weight to the FDA’s extensive labeling oversight and

corresponding statutory obligations under the

FDAAA. Instead of recognizing that the FDA is obligated to work with manufacturers to update warning

labels in light of new scientific evidence, the Fosamax

II decision encourages the submission of seriatim iterations of labeling language to try to anticipate and

head off how some creative plaintiff’s lawyer down the

road might second-guess the regulatory record. That

result risks straining the FDA’s review capabilities

and will ultimately impact public health.

12

A.

The

Third

Circuit’s

Ruling

Threatens to Overwhelm the FDA’s

Review Capabilities.

The FDA must strike a delicate balance in effectuating proper pharmaceutical labeling. Labeling must

impart critical information regarding safety and the

effective use of a medicine, while also communicating

this content in a manner that is helpful to healthcare

professionals. The FDA must be wary of including

warnings that are not supported by science, because

such “overwarning” carries serious risks for patients.

First, physicians may disregard lengthy labels full of

speculative warnings, and overlook important, scientifically validated safety information. See Albrecht,

587 U.S., at 304 (“the hierarchy of label information is

designed to prevent overwarning so that less important information does not overshadow more

important information”) (quotation marks omitted).

Second, warnings that are not grounded in science discourage the beneficial usage of medicines for patients

who need it. See id. (Label information is “designed to

exclude exaggeration of risk, or inclusion of speculative or hypothetical risks, that could discourage

appropriate use of a beneficial drug” (cleaned up)). All

medicines have risks, and the prescribing medical

professional must weigh those risks against a medicine’s potential benefit for a patient. Distorting this

balance by either overstating or understating the

risks inhibits medical professionals and in turn

threatens the wellbeing of patients.

The Third Circuit’s preemption ruling will distort

the incentives and lead manufacturers to submit multiple iterations of labeling supplements to protect

13

against state-law claims from enterprising plaintiff’s

lawyers. In Buckman v. Plaintiffs’ Legal Committee,

this Court recognized that state law “fraud-on-theFDA” claims were preempted because they would incentivize drug manufacturers to “submit a deluge of

information that the [FDA] neither wants nor needs”

out of “fear that their disclosures … will later be

judged insufficient in state court.” 531 U.S. 341, 351

(2001). The Third Circuit’s decision here will create

precisely the same incentives because of its narrow

reading of FDA’s response.

In the decision below, the Third Circuit rejected

the district court’s factual finding and instead concluded that the FDA’s CRL rejection letter was

ambiguous because it was possible that the FDA rejected Merck’s proposed warning based on a semantic

disagreement over the term “stress fractures.” Pet.

App. 61a–62a. The Third Circuit went so far as to admonish the district court for not reading the CRL “in

a manner that disfavors pre-emption.” Id. at 66a. In

other words, according to the Third Circuit, the district court erred not in its factual answer to the factual

question per se, but rather because it didn’t rig the

factual question in the first place.

In the same vein, the Third Circuit found fault in

the district court’s consideration of certain evidence in

the regulatory record—like a subsequent FDA phone

call and the FDA’s amicus brief which showed the

FDA did not believe there was sufficient evidence to

support a warning—because in its view “extrinsic evidence … cannot be determinative in a case like this.”

Id. at 66a–67a. The myopic refusal to permit consideration of any extrinsic evidence to interpret FDA’s

14

actions cannot be reconciled with this Court’s directive in Albrecht, which charges the district court as

factfinder to parse the regulatory record “to understand and to interpret agency decisions in light of the

governing statutory and regulatory context.” Albrecht, 587 U.S. at 315–16. Assessing the regulatory

record can be a complicated task—one reason this

Court rejected the Third Circuit’s original peculiar notion that a jury should sort this out—yet the Third

Circuit’s revised approach here would yield a similar

result: unless there is zero ambiguity in the regulatory record, a district court’s factual finding of clear

evidence must be reversed. But rarely will the regulatory record be bereft of some ambiguity that an

interested advocate after the fact could try to leverage. See, e.g., Dolin v. GlaxoSmithKline LLC, 901

F.3d 803, 814 (7th Cir. 2018) (plaintiffs arguing that

FDA labeling rejection was based on the placement location and not the content); Cerveny v. Aventis, Inc.,

855 F.3d 1091, 1101–02 (10th Cir. 2017) (plaintiffs arguing that FDA labeling rejection was not dispositive

because it was submitted by a citizen instead of a

manufacturer).

After all, CRLs are drafted by scientists, not lawyers versed in the nuances of preemption doctrine.

The scientists who draft these non-public letters are

not writing for courts, but to parties who have been

15

engaged in a back-and-forth dialogue with the FDA.4

A CRL reflects FDA’s complete review of the submitted data and must be read in context with FDA’s

broader statutory obligations. See Br. for the United

States as Amicus Curiae Supporting Pet’r at 32,

Merck Sharpe & Dohme Corp. v. Albrecht, 587 U.S.

299 (2019) (No. 17-290) (“[I]f FDA determines that a

safety-based labeling change is warranted based on

the data, FDA will attempt promptly to identify easily

correctible deficiencies in the proposed text and will

develop final labeling text with the manufacturer in

an iterative process.”).

For fear that any tinge of doubt would render an

FDA decision ambiguous, manufacturers will be incentivized to continually go back to the FDA and ask

again and again—“Are you sure?” “What about these

words?” This dynamic will extend regulatory interactions,

increase

meeting

requests,

delay

implementation of labeling changes, and multiply

submissions of labeling supplements that by law FDA

must devote resources to consider and respond to. See

21 C.F.R. § 314.70(b)(2)(v) (Prior Approval Supplement submissions); 21 C.F.R. § 314.70(c)(6)(iii)(A)

(CBE supplement submissions to reflect “newly acquired information”); see also Requirements on

Content and Format of Labeling for Human Prescription Drug and Biological Products, 71 Fed. Reg. 3922,

4 See Mark Senak, Potayto—Potahto? The Meaning of the FDA’s

“Complete Response” Letters, 1(7) Am. Health Drug Benefits 30–

31 (2008), https://pmc.ncbi.nlm.nih.gov/articles/PMC4106573

(“[T]he contents of a … complete response letter are considered

proprietary, and the FDA does not divulge the contents of such

letters, nor does it issue a press release.”).

16

3934 (Jan. 24, 2006) (“FDA reviews all [CBE] submissions….”). Eliciting endless “yes, we really meant it”

responses from FDA serves no public health purpose.

Indeed, diverting the FDA’s attention towards

such iterative submissions carries significant risks.

See Lofton v. McNeil Consumer & Specialty Pharm.,

672 F.3d 372, 380 (5th Cir. 2012) (When manufacturers are compelled “to flood the FDA with information

…. [the FDA] loses control over its ability, based on

scientific expertise, to prescribe—and intelligently

limit—the scope of disclosures necessary for its

work.”). The corresponding results of overwarning or

failing to include scientifically legitimate warnings on

medication labeling presents a serious threat to patient wellbeing.

B.

The FDA’s Obligations Under the

FDAAA

Already

Ensure

That

Labeling Is Accurate.

The FDA’s existing statutory obligations as set

forth in the FDAAA ensure that the kind of labeling

rejection in this case could not have been due to some

linguistic quibble. In addition to reviewing specific labeling changes that manufacturers propose, the FDA

independently has the statutory obligation to consider

17

whether labeling remains adequate in light of the existing scientific record.5 Under the FDAAA, once the

FDA “becomes aware of … new safety information …

that [it] determines should be included in the labeling

of the drug,” the FDA must promptly engage with the

manufacturer to amend the drug’s labeling. 21 U.S.C.

§ 355(o)(4)(A). If the FDA disagrees with the manufacturer’s response or other proposed changes, it

cannot stand idly by. Per § 355(o)(4)(C), the FDA

“shall initiate discussions to reach agreement on

whether the labeling for the drug should be modified

to reflect the new safety … information, and if so, the

contents of such labeling changes.” In addition, under

§ 355(o)(4)(E) the FDA is empowered to “issue an order directing the [manufacturer] to make such a

labeling change as the [FDA] deems appropriate to address the new safety … information.”

Taken together, the changes enacted by the

FDAAA obligate the FDA to effect warning labeling

changes if justified by the scientific evidence, irrespective of where it learns of the information and whether

a company has proposed a labeling change. If the FDA

were rejecting the labeling change based on a dispute

over word selection or because it needed more information from the manufacturer, § 355(o)(4) requires

immediate action or follow-up. See Albrecht, 587 U.S.

5 Manufacturers are required to report “serious and unexpected”

adverse events to the FDA within 15 days of receipt and to

periodically report all other adverse events. 21 C.F.R. § 314.80.

The FDA also receives adverse event reports through a voluntary

reporting system, MedWatch. MedWatch: The FDA Safety

Information and Adverse Event Reporting Program, FDA,

https://www.fda.gov/Safety/MedWatch/default.htm.

18

at 324 (Alito, J., concurring) (Finding that because of

§ 355(o)(4) “if the FDA declines to require a label

change despite having received considered information regarding a new risk, the logical conclusion is

that the FDA determined that a label change was unjustified.”). Such a conclusion is supported by the

“presumption of regularity” which holds that the FDA

acted in accordance with its statutory obligations. Id.

Instead of giving sufficient weight to the significant obligations imposed by § 355(o)(4) and the

finding that the statute was “highly relevant to the

pre-emption analysis,” id. at 325, the Third Circuit

gives it only passing consideration. The court turns to

§ 355(o)(4) only after it has already enshrined its

“heavy Albrecht presumption” against preemption

that renders the slightest ambiguity dispositive. Pet.

App. 66a. The Third Circuit’s side-stepping of Justice

Alito’s admonition only underscores the absurdity of

using a presumption against preemption in assessing

FDA actions. The cases that the Third Circuit cites

applying the presumption against preemption concern

the interpretation of statutes or regulations, rooted in

the idea that Congress generally does not intend to

displace traditional areas of state regulation. See,

e.g., Bates v. Dow Agrosciences LLC, 544 U.S. 431, 449

(2005); Wyeth, 555 U.S. at 575. Here, the FDA declines to amend labeling in the absence of sufficient

evidence all the time and indeed has a statutory obligation to do so. There is no reason for the Third

Circuit to have presumed that the FDA did not act

consistent with the FDAAA’s statutory imperative.

In justifying its disregard of the FDAAA, the Third

Circuit looked “beyond the letter” to examine extrinsic

19

evidence which purportedly showed that the FDA was

still considering the science on atypical femoral fractures. Pet. App. at 71a. The court found that the FDA

“had not formalized a decision” and was entitled to

“take its time.” Id. at 73a–74a. This conclusion is

seemingly in conflict with Justice Alito’s own takeaway from the factual evidence. See Albrecht, 587 U.S.

at 328 (Alito, J., concurring) (“for years the FDA was:

aware of this issue, communicating with drug manufacturers, studying all relevant information, and

instructing healthcare professionals and patients

alike to continue to use Fosamax as directed.”). In addition, the Third Circuit’s resort to extrinsic evidence

is inconsistent with its rejection of the district court’s

consideration of extrinsic evidence to conclude that

the FDA’s CRL foreclosed the label change. More fundamentally, if indeed the FDA was so uncertain, then

it would have been obligated to reject the sort of warning label Plaintiffs demand in this case. While the

FDA is considering what to do and evaluating the relevant scientific evidence, manufacturers are

forbidden from striking out on their own and changing

their labeling. See 21 C.F.R. § 314.110(b) (listing

available applicant actions after receiving a CRL as

resubmission, withdrawal, or request for a hearing).

The Third Circuit thus contorted the factual record,

the regulatory framework, and the evidentiary standard to find that somehow the manufacturer was still

permitted to make a label change notwithstanding the

FDA’s rejection of that change in a CRL.

20

III.

THE

THIRD

CIRCUIT’S

RULING

HAMPERS

MANUFACTURER

INNOVATION AND HARMS PATIENT

HEALTH.

The Third Circuit’s decision fundamentally undermines the rational preemption framework this Court

set forth in Albrecht. The fact that a large number of

PhRMA’s members are located within the Third Circuit makes this decision all the more troubling

because of the impact it will have on patient health

and innovation.

Bringing a new medicine to market is a lengthy

and expensive process. See Mutual Pharm. Co., Inc.

v. Bartlett, 570 U.S. 472, 476 (2013) (“The process of

submitting an NDA is both onerous and lengthy.”);

PLIVA, Inc. v. Mensing, 564 U.S. 604, 612 (2011) (“[A]

manufacturer seeking federal approval to market a

new drug must prove that it is safe and effective and

that the proposed label is accurate and adequate.

Meeting those requirements involves costly and

lengthy clinical testing.” (citations omitted)). On average, developing a new medicine and obtaining FDA

approval takes ten to fifteen years and costs $2.6 billion.6 PhRMA member companies invest more than

22% of their total annual domestic sales on research

and development—an estimated $71.3 billion in

6 PhRMA, Biopharmaceuticals in Perspective: Fall 2020, at 27

(2020), https://perma.cc/VD85-GA8E; see also Joseph A. DiMasi

et al., Innovation in the Pharmaceutical Industry: New Estimates

of R&D Costs, 47 J. Health Econ. 20 (2016).

21

2023.7 The drug development process involves several

steps including laboratory and animal studies, an Investigational New Drug application (“IND”), three

phases of human clinical trials, and finally a New

Drug Application (“NDA”) which can exceed 100,000

pages in length.8 The research efforts also involve significant risks, with a 90% failure rate for drugs that

enter clinical trials, let alone the many more preclinical candidates which fail earlier in the process.9

All of these efforts are geared towards getting the

science right: first, confirming the company and the

FDA understand the risk-benefit profile for a prospective medicine and determining that its benefits

outweigh its risks; second, ensuring that the labeling

accurately reflects those risks and benefits so physicians working with their patients can make the proper

decision whether the medicine is right for that patient. It is unfair and intolerable for a company to face

massive litigation exposure for claims that the medicine’s labeling should have included a warning that

the FDA has rejected. The current federal court

docket is loaded with tens of thousands of lawsuits

PhRMA, 2024 PhRMA Annual Membership Survey 4 tbl. 2

(2024), https://perma.cc/6NB6-3F6V.

7

PhRMA, Biopharmaceutical Research & Development: The

Process Behind New Medicines 14 (2015), https://perma.cc/P2375EVM.

8

9 Duxin Sun et al., Why 90% of Clinical Drug Development Fails

and How to Improve It, 12(7) Acta Pharm. Sinica B. 3049–62

(2021), https://pubmed.ncbi.nlm.nih.gov/35865092/.

22

against pharmaceutical manufacturers.10 Today, out

of sixty-seven pending product liability multidistrict

litigation proceedings, eighteen involve pharmaceuticals. See U.S. Jud. Panel on Multidist. Litig., MDL

Statistics Report: Docket Type Summary (Apr. 1,

2025), https://perma.cc/7LRS-9FWV.

This litigation risk bears heavily on a pharmaceutical company’s decision to invest in further

innovation. See Daniel E. Troy, The Case for FDA

Preemption, in Federal Preemption: States’ Powers,

National Interests 87 (2007) (“Massive tort verdicts

can dramatically skew the cost side of [the] equation

... pharmaceutical manufacturers may take overly

risk-averse positions with respect to drugs that, despite their unquestioned benefits, do not have the

potential to produce large revenue streams.”). Permitting an “overly aggressive tort environment” can

lead to “increased costs and risks of doing business in

an area,” “disincentives for innovations which promote consumer welfare,” and “deterrence of economic

development and job creation incentives. Perryman

Grp., Economic Benefits of Tort Reform 4 (Nov. 4,

2019), https://perma.cc/CMA6-XYMJ.

Both before and in the wake of Albrecht, courts applying a rational preemption framework as required

by Albrecht have tempered this trend and have ended

major litigations when the court has determined that

the warning sought by plaintiffs was not justified.

10 See Admin. Office of the U.S. Courts, Table C-2A: U.S. District

Courts-Civil Cases Commences, by Nature of Suit, During the 12Month Periods Ending September 30, 2020 through 2024 (2024),

https://perma.cc/4HQG-CXYC.

23

See, e.g., Gibbons v. Bristol-Myers Squibb Co., 919

F.3d 699, 709 (2d Cir. 2019) (ending Eliquis litigation); In re Zofran (Ondansetron), 57 F.4th at 343

(ending Zofran litigation); Knight, 984 F.3d at 341

(finding Pradaxa claims preempted); Adkins v.

Boehringer Ingelheim Pharms., Inc., 2020 WL

1890681 (Conn. Super. Ct. Mar. 13, 2020) (finding

Pradaxa warning claims preempted in consolidated

state court proceeding); In re Incretin-Based Therapies, 524 F. Supp. 3d at 1051 (ending incretin-based

therapies MDL).

The Third Circuit’s approach—and its effectively

case-dispositive presumption against preemption—is

a significant outlier. Holding manufacturers liable for

failing to include warning language based on a heavy

presumption against preemption and a narrow reading of FDA action would ultimately shift resources

away from innovation to instead pay for expensive litigation defense. The result of the Third Circuit’s

preemption framework is that juries will be left to

scrutinize whether a company should have altered

their labeling in the face of contrary guidance from the

FDA. That is precisely the opposite of the result this

Court intended in Albrecht, where it found lay jurors

are ill-equipped to make the sort of nuanced, complex

risk-benefit calculations that animate the FDA’s review of label change applications. See Albrecht, 587

U.S. at 316 (“The complexity of the preceding discussion of the law helps to illustrate why we answer this

question by concluding that the question is a legal one

for the judge, not a jury”); see also Riegel v. Medtronic,

Inc., 552 U.S. 312, 325 (2008) (whereas “the experts at

the FDA” apply a “cost-benefit analysis,” a jury “sees

only the cost of a more dangerous design, and is not

24

concerned with its benefits; the patients who reaped

those benefits are not represented in court”). By overlaying additional hurdles on top of Albrecht and

discounting the relevance of factual and statutory context, the Third Circuit’s decision risks undermining

innovation and patient wellbeing.

CONCLUSION

The petition for a writ of certiorari should be

granted.

Respectfully submitted,

.

Michael X. Imbroscio

Paul W. Schmidt

Gregory L. Halperin

Counsel of Record

Anand Balaji

COVINGTON & BURLING LLP

The New York Times Building COVINGTON & BURLING LLP

One CityCenter

620 Eighth Avenue

New York, NY 10018

850 Tenth Street, NW

Washington, DC 20001

mimbroscio@cov.com

(202) 662-6000

Counsel for Amicus Curiae