Amicus Curiae Brief — Relentless, Inc., et al., Petitioners v. Department of Commerce, et al.

No. 22-1219

In the

Supreme Court of the United States

________

RELENTLESS, INC., ET AL.,

Petitioners,

v.

DEPARTMENT OF COMMERCE, ET AL.,

Respondents.

________

On Writ of Certiorari to the

United States Court of Appeals

for the First Circuit

________

BRIEF OF DR. RESHMA RAMACHANDRAN

AND DR. JOSEPH S. ROSS AS AMICI CURIAE

IN SUPPORT OF RESPONDENTS

________

Victoria S. Nugent

Counsel of Record

Robin F. Thurston

Will Bardwell

Benjamin M. Seel

Democracy Forward Foundation

P.O. Box 34553

Washington, DC 20043

(202) 448-9090

vnugent@democracyforward.org

December 2023

Counsel for Amici Curiae













i

TABLE OF CONTENTS

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

INTEREST OF AMICI CURIAE .....................................1

INTRODUCTION AND SUMMARY OF THE

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

ARGUMENT .....................................................................8

I.

The FDA’s implementation of the FDCA

reinforces the sensibility of Chevron

deference......................................................8

A. Deference is appropriate for the FDA’s

regulation of drugs and medical devices

as they implement a complex scheme

that requires expertise. .........................9

B. The FDCA confers broad authority to

carry out its ambitious public health

mission, which warrants deference.....12

i. New drug approvals ...................... 12

ii. Fast Track drug approval .........14

iii. Drug labeling: setting standards

for prescribing information ......16

iv. Drug labeling: Medication

Guides .......................................18

II.

Overruling or substantially modifying

Chevron undermines congressional intent













ii

and is not necessary to resolve Petitioners’

stated concerns ..........................................20

A. Deference to the FDA under Chevron

animates the FDCA’s purpose in several

ways......................................................21

B. In practice, deference under Chevron

has allowed the FDA to faithfully and

reliably administer the FDCA.............23

C. Overruling or substantially modifying

Chevron is not necessary to resolve

Petitioners’ stated concerns ................26

CONCLUSION ...............................................................28













iii

TABLE OF AUTHORITIES

Cases

Braeburn Inc. v. FDA,

389 F. Supp. 3d 1 (D.D.C. 2019) ..........................27

Chevron U.S.A., Inc. v. Nat. Res. Def. Council, Inc.,

467 U.S. 837

(1984) ....... 3, 5, 7, 8, 9, 10 17, 18, 20, 21, 23, 26, 27

City of Arlington v. FCC,

569 U.S. 290 (2013) .................................................... 20

Decker v. Nw. Env’t Def. Ctr.,

568 U.S. 597 (2013) ............................................6, 9

Ford Motor Credit Co. v. Milhollin,

444 U.S. 555 (1980) ..............................................21

Kisor v. Wilkie,

139 S. Ct. 2400 (2019) .... 6, 7, 10, 11, 14, 21, 23, 27

Martin v. OSHRC,

499 U.S. 144 (1991) ..............................................10

Mylan Lab’ys, Inc. v. Thompson,

389 F.3d 1272 (D.C. Cir. 2004) .................. 4, 10, 11

Otsuka Pharm. Co. v. Burwell,

302 F. Supp. 3d 375 (D.D.C. 2016) ................11, 12

Otsuka Pharm. Co. v. Price,

869 F.3d 987 (D.C. Cir. 2017) .................... 7, 11, 12













iv

Perez v. Mortg. Bankers Ass’n,

575 U.S. 92 (2015) ................................................22

Pharmanex v. Shalala,

221 F.3d 1151 (10th Cir. 2000)......................23, 26

POM Wonderful LLC v. Coca-Cola Co.,

573 U.S. 102 (2014) ..........................................4, 11

Prevor v. FDA,

67 F. Supp. 3d 125 (D.D.C. 2014) ........................27

Serono Lab’ys, Inc. v. Shalala,

158 F.3d 1313 (D.C. Cir. 1998) ........................7, 10

Stat-Trade Inc. v. FDA,

869 F. Supp. 2d 95 (D.D.C. 2012) ........................27

Thomas Jefferson Univ. v. Shalala,

512 U.S. 504 (1994) ......................................7, 9, 21

United States v. Genendo Pharm., N.V.,

485 F.3d 958 (7th Cir. 2007)..........................25, 26

United States v. Shimer,

367 U.S. 374 (1961) ................................................3

Whitaker v. Thompson,

353 F.3d 947 (D.C. Cir. 2004) ........................24, 26

Statutes, Rules, and Regulations

5 U.S.C. § 553 ........................................................4, 22

21 C.F.R. § 10.30 .......................................................22













v

21 C.F.R. § 201.57 .....................................................17

21 C.F.R. § 201.57(a) ...........................................16, 17

21 C.F.R. § 201.57(b) .................................................16

21 C.F.R. § 201.57(c) .................................................17

21 C.F.R. § 208.20 .....................................................19

21 C.F.R. § 208.20(b)(6) ............................................19

21 C.F.R. § 208.20(b)(7) ............................................19

21 C.F.R. § 208.24(b) .................................................19

21 C.F.R. § 312.80 .....................................................15

21 C.F.R. § 312.84 .....................................................15

21 C.F.R. § 314.126(b)(2) ..........................................13

21 C.F.R. § 314.126(b)(4) ..........................................13

21 C.F.R. § 314.126(d) ...............................................13

21 U.S.C. § 301 ............................................................4

21 U.S.C. § 352 ......................................................4, 19

21 U.S.C. § 352(f) ......................................................16

21 U.S.C. § 353 ............................................................4













vi

21 U.S.C. § 353(a)......................................................25

21 U.S.C. § 355 ......................................................4, 19

21 U.S.C. § 355(a)................................................12, 25

21 U.S.C. § 355(d)................................................12, 13

21 U.S.C. § 356(b)(1) .................................................14

21 U.S.C. § 356(b)(3) .................................................15

21 U.S.C. § 356(e)(1) .................................................15

21 U.S.C. § 393(b)(2) .................................................11

21 U.S.C. § 393(b)(4) .................................................22

Other Authorities

Brett M. Kavanaugh,

Fixing Statutory Interpretation,

129 Harvard L. Rev. 2118 (2016) ..........................6

Daniel P. Carpenter, Reputation and

Power: Organizational Image and

Pharmaceutical Regulation at the

FDA (Princeton Univ. Press, 2010) .................4, 10

FDA, 80 Years of the Federal Food,

Drug, and Cosmetic Act (July 11,

2018), https://tinyurl.com/ykz8w9v7 .....................5

FDA, Centers of Excellence in Regulatory

Science and Innovation (CERSIs)













vii

(accessed on Dec. 17, 2023),

https://tinyurl.com/bda95a69 ................................2

FDA, How Do I Use Prescription Drug

Labeling (Mar. 29, 2023),

http://tinyurl.com/f5hzf555 ..................................17

FDA, Stakeholder Engagement Staff (Nov. 15, 2023),

http://tinyurl.com/2p9ahunh ...............................23

Holly Fernandez Lynch et al., Letter to the

Editor: The Limits of Acceptable Political

Influence Over the FDA,

27 Nature Medicine 186 (Feb. 2021) .....................5

John R. Manthei et al., Latham & Watkins,

Recent FDA Guidance Signals Increased

Willingness to Engage Industry

Stakeholders (Oct. 25, 2023),

http://tinyurl.com/mrxyb3dn ...............................22

Liam Bendicksen et al., FDA and

Chevron Deference: A Case Review,

78 Food & Drug L. J. 371 (2023) ..... 4, 6, 10, 11, 23

Prescription Drug Product Labeling;

Medication Guide Requirements,

63 Fed. Reg. 66,378 (Dec. 1, 1998) ................18, 19

Requirements on Content and Format

of Labeling for Human Prescription Drug and

Biological Products, 71 Fed. Reg. 3,922 (Jan. 24,

2006) .....................................................................17













viii

Tanvee Varma et al., Metrics, Baseline Scores, and a

Tool to Improve Sponsor Performance on Clinical

Trial Diversity: Retrospective Cross Sectional

Study, BMJ Medical, Nov. 2022 ..........................18













1

INTEREST OF AMICI CURIAE1

Amici curiae are practicing physicians and leading

experts in pharmaceutical and regulatory policy, who

have studied and written extensively on the

relationship between regulatory standards for drug

and medical device approvals and patient safety and

medical product efficacy. Amici have been published

widely in both top-tier medical and public health

journals and national media outlets, platforms which

they have used to comment on, and sometimes

critique, U.S. Food and Drug Administration (FDA)

regulatory policy. Nevertheless, they understand that

it is vastly preferable, especially for public health and

patient safety, if the FDA receives deference from

courts when it implements broad or ambiguous

statutory authority in a reasonable manner.

Amicus curiae Reshma Ramachandran, MD, MPP,

MHS is an Assistant Professor of Medicine at Yale

School of Medicine, a practicing board-certified family

physician, and the co-director of the Collaboration for

Regulatory Rigor, Integrity, and Transparency

(CRRIT) at the Yale School of Medicine, which is an

interdisciplinary initiative that brings together

clinicians, epidemiologists, researchers, legal experts,

and others to study how federal agencies evaluate,

regulate, and cover drugs and devices and how this

impacts patient health outcomes. She has led

research projects on FDA regulatory policy and its

1 No counsel for any party authored this brief in whole or in part,

and no such counsel or party made a monetary contribution

intended to fund the preparation or submission of this brief. No

person other than Amici Curiae or their counsel made a

monetary contribution to the preparation or submission of this

brief.













2

impact

on

patient

outcomes

and

clinical

decision-making, as well as around pharmaceutical

policy, including on economic and regulatory

incentives to foster innovation of novel health

technologies. Dr. Ramachandran has testified before

Congress multiple times to discuss her research and

its implications for regulatory policy. She also serves

as the chair of Doctors for America’s FDA Task Force,

an initiative representing over 27,000 physicians and

medical trainees that provides unbiased expertise in

evaluating and responding to the FDA regulatory

process in a way that maximizes meaningful clinical

outcomes for patients.

Amicus Curiae Joseph S. Ross, MD, MHS is a

Professor of Medicine and of Public Health at Yale

School of Medicine, a practicing board-certified

general internist, the Deputy Editor of the Journal of

the American Medical Association (JAMA), and,

along with Dr. Ramachandran, a co-director of

CRRIT. He also co-directs the Yale-Mayo Clinic

Center for Excellence in Regulatory Science and

Innovation (CERSI)—an FDA-funded program that

seeks “to foster robust and innovative approaches to

advance regulatory science” through collaboration

between FDA scientific experts and funding offices,

FDA, Centers of Excellence in Regulatory Science and

Innovation (CERSIs), https://tinyurl.com/bda95a69—

and serves as a member and Chair of the Medicare

Evidence Development and Coverage Advisory

Committee for the Centers for Medicare and Medicaid

Services (CMS), where he provides independent

guidance and expert advice to CMS on specific clinical

topics including on FDA-regulated medical products.

His influential and oft-cited research has illuminated

the numerous ways in which FDA policies are













3

advancing public health and generating evidence to

inform clinical decision-making.

Dr. Ramachandran and Dr. Ross are thus well

positioned to explain how judicial deference under

Chevron U.S.A., Inc. v. Nat. Res. Def. Council, Inc.,

467 U.S. 837 (1984) has allowed FDA to exercise its

statutory authority in a manner that protects public

health and keeps patients safe, and the risks to public

health and patient safety if Chevron is overruled.

INTRODUCTION AND SUMMARY OF THE

ARGUMENT

For nearly 40 years, courts have followed the

doctrine set forth in Chevron to defer to an agency’s

reasonable interpretations of ambiguous statutes and

those conferring broad authority. As the Court

explained, this deferential approach is a matter of

respect for Congress’s “express delegation of

authority” to agencies so that they may “elucidate a

specific provision of the statute by regulation.” Id. at

843-44. The Court further acknowledged that “the

principle

of

deference

to

administrative

interpretations” was long-standing and appropriately

applied “‘whenever * * * a full understanding of the

force of the statutory policy in the given situation has

depended upon more than ordinary knowledge

respecting the matters subjected to agency

regulations.” Id. at 844 (quoting United States v.

Shimer, 367 U.S. 374, 382 (1961)).

The FDA’s regulatory record demonstrates the

wisdom in this doctrine and in continued judicial

deference to agencies’ interpretations of broad and

complicated statutory authority, as well as to their

difficult and complex policy judgements, which are













4

informed by stakeholder engagement, including

under the Administrative Procedure Act (APA), 5

U.S.C. § 553, and scientific expertise. Indeed, judicial

deference to FDA regulation has contributed

significantly to its global status as “the gold standard

for health care regulation and evidence-based

decision making relating to drugs, devices, and other

medical products.” Liam Bendicksen et al., FDA and

Chevron Deference: A Case Review, 78 Food & Drug L.

J. 371 (2023) (citing Daniel P. Carpenter, Reputation

and

Power:

Organizational

Image

and

Pharmaceutical Regulation at the FDA 301 (Princeton

Univ. Press, 2010)).

The FDA has done this acclaimed and crucial work

through its implementation of the Federal Food,

Drug, and Cosmetic Act (FDCA), 21 U.S.C. §§ 301 et

seq., a statutory scheme “designed primarily to

protect the health and safety of the public at large.”

POM Wonderful LLC v. Coca-Cola Co., 573 U.S. 102,

108 (2014). “There is no denying the complexity of

th[at] statutory regime,” or “the FDA’s expertise” to

administer it. Mylan Lab’ys, Inc. v. Thompson, 389

F.3d 1272, 1280 (D.C. Cir. 2004). For instance, to

carry out its public health mission, FDA is tasked

with approving new drugs, including by evaluating

whether drugs seeking approval for market have the

necessary indicia of safety and efficacy. 21 U.S.C.

§ 355. The FDA is also responsible for ensuring that

the risks and benefits of the drugs and devices it

approves are not then marketed, packaged, or labeled

in a way that is confusing or misleading. See, e.g., 21

U.S.C. §§ 352, 353, 355.

The FDA’s administration of the FDCA has been

remarkably successful. No longer are “Americans * *

* inundated with ineffective and dangerous drugs,” as













5

they were prior to the FDCA’s enactment. See FDA,

80 Years of the Federal Food, Drug, and Cosmetic Act

(July 11, 2018), https://tinyurl.com/ykz8w9v7. And

the elimination of toxic drugs and “quack devices,” id.,

has not come at the cost of advancements in science

or medicine. To the contrary, the FDA has helped

drug companies bring countless numbers of

innovative, new therapies to market during this time.

But the FDA’s successes have been hard won.

Among other constraints, the FDA operates in a

setting where hasty process or lack of scientific rigor

might expose patients to a dangerous or ineffective

drug, but too deliberative of a process could stymie

innovation and prevent promising, life-saving

therapies from reaching patients in time. See Holly

Fernandez Lynch et al., Letter to the Editor: The

Limits of Acceptable Political Influence Over the FDA,

27 Nature Medicine 186, 189 (Feb. 2021) (noting the

“dual nature of the FDA’s decision-making”).

Balancing these statutory priorities cannot be

appropriately struck unless the FDA understands

and adapts to rapid advancements in science and

medicine, which inform whether and when a drug or

device is safe and effective. And it must also take care

to ensure that regulated parties provide information

about approved products in a way that is practically

useful to different audiences, both in terms of what is

expressed and how it is expressed. In short, every

aspect of the work Congress has tasked the FDA with

doing demands the exercise of true scientific, medical,

and public health expertise.

Amici submit their experience with the FDA’s

regulatory framework to the Court because a decision

overruling Chevron threatens to destabilize this

framework—which

ensures

the

safety

and













6

effectiveness of drugs and devices upon which

virtually everyone relies at some point in their life.

Amici believe that the broad outcome urged by the

Petitioners will lead to “a diminished deference

regime,” that “could adversely affect public health”

through the curtailment of FDA’s discretion over drug

and medical device regulation. Bendicksen et al.,

supra, at 378.

The FDA’s regulatory record underscores the

wisdom of continued judicial reluctance to undo by

court order regulations developed rigorously and

methodically by agencies tasked with making

complex policy judgments and based on their

scientific or technical expertise. In particular,

deference to an agency’s reasonable interpretation, in

light of its expertise and experience with matters

within its purview, is appropriate where the statutory

authority at issue broadly delegates policy decisions.

See Brett M. Kavanaugh, Fixing Statutory

Interpretation, 129 Harvard L. Rev. 2118, 2152 (Jun.

2016) (concluding that Chevron “makes a lot of sense”

in this circumstance); see also Kisor v. Wilkie, 139 S.

Ct. 2400, 2448-49 (2019) (Kavanaugh, J., concurring)

(observing that broad “terms afford agencies broad

policy discretion”). The FDCA does just this by

charging the FDA, among many other complex

assignments, with line-drawing as to when drugs are

sufficiently safe and effective to be made available to

potentially desperate consumers.

Continued deference is also particularly

appropriate where the statutory authority at issue,

like the Clean Air Act amendments in Chevron, is

part of “a lengthy, detailed, technical, complex, and

comprehensive response to a major social issue.”

Chevron, 467 U.S. at 848; see also Decker v. Nw. Env’t













7

Def. Ctr., 568 U.S. 597, 618–19 (2013) (Scalia, J.,

concurring in part and dissenting in part) (the

conclusion that an “agency possesses special expertise

in administering its ‘complex and highly technical

regulatory program’ * * * is true enough, and it leads

to the conclusion that agencies and not courts should

make regulations”) (quoting Thomas Jefferson Univ.

v. Shalala, 512 U.S. 504, 512 (1994)); Gov’t Br. at 16

(collecting examples of cases where “Chevron has

played a critical role in resolving many interpretive

questions in complex and technical areas of federal

law,” including drug regulation).

The FDCA is a paradigmatic example of “a

lengthy,

detailed,

technical,

complex,

and

comprehensive response to a major social issue.”

Chevron, 467 U.S. at 848. In addition to the

complexity of the regime as a whole, arriving at an

understanding of individual FDCA provisions often

requires an “‘evaluation[] of scientific data within

[FDA’s] area of expertise,’” or a “statutory phrase [to]

be read in the context of the kind of drug at issue.”

Serono Lab’ys, Inc. v. Shalala, 158 F.3d 1313, 1320

(D.C. Cir. 1998); see Kisor, 139 S. Ct. at 2410

(suggesting that courts are not competent to evaluate

if “a company created a new ‘active moiety’ by joining

a previously approved moiety to lysine through a

non-ester covalent bond”); see also Otsuka Pharm. Co.

v. Price, 869 F.3d 987, 993-995 (D.C. Cir. 2017)

(examining same question).

Beyond interpreting technically sophisticated

terms like “active moiety,” Kisor, 139 S. Ct. at 2410,

the FDCA also requires the FDA to interpret its

authority to develop technically sophisticated

solutions to complex public health problems, and to do

so using their expertise to ensure that their approach













8

is supported by the best available science, in a

landscape where the science may be rapidly changing.

Amici highlight below some of these programs and

authorities, which benefit from the deference afforded

to agency experts under Chevron.

The Court should avoid the potential for

destabilizing a regulatory regime that the FDA has

capably used for nearly a century to foster scientific

and medical innovation, while also ensuring that

dangerous or ineffective drugs and medical devices do

not routinely threaten public health, as they once did.

The Court should affirm the Court of Appeals.

ARGUMENT

I. The FDA’s implementation of the FDCA

reinforces the sensibility of Chevron

deference.

Congress has assigned to the FDA an important

and ambitious task: Protect the public health by

keeping unsafe or ineffective drugs and devices off the

market. Although the FDA’s broad mission has

remained fixed over time, the landscape around it has

shifted dramatically through advances in scientific

understanding, the emergence of novel public health

threats, and the development of innovative therapies

that carry both risk and benefit. Accordingly, through

the FDCA, Congress has given the FDA broad

authority, to which it has applied its considerable

expertise in science, medicine, and public health. For

nearly 40 years, that combination has caused courts

to defer to an agency’s reasonable interpretations of

ambiguous statutes and those conferring broad

authority under the framework established in













9

Chevron.

As

outlined

below,

the

FDA’s

implementation of the FDCA reinforces the wisdom of

that framework.

A. Deference is appropriate for the FDA’s

regulation of drugs and medical devices

as they implement a complex scheme that

requires expertise.

Under the Chevron framework, deference to an

agency’s reasonable interpretation of its statutory

authority is particularly appropriate where the

authority at issue is part of “a lengthy, detailed,

technical, complex, and comprehensive response to a

major social issue.” Chevron, 467 U.S. at 848; see also

Decker, 568 U.S. at 618–19 (Scalia, J., concurring in

part and dissenting in part) (the conclusion that an

“agency possesses special expertise in administering

its ‘complex and highly technical regulatory

program’ * * * is true enough, and it leads to the

conclusion that agencies and not courts should make

regulations”) (quoting Thomas Jefferson Univ., 512

U.S. at 512); Gov’t Br. at 16 (collecting examples of

cases where “Chevron has played a critical role in

resolving many interpretive questions in complex and

technical areas of federal law,” including drug

regulation).

The reasons for this sensible approach are

severalfold, see id. at 7-8, but fundamentally reflect

respect for the separation of powers and a sense of

judicial humility, which calls on courts to recognize

that, often times, “[j]udges are not experts in the field”

and are ill-equipped to discern meaning from

ambiguously worded and technically complex

statutory schemes. Chevron, 467 U.S. at 865.

Accordingly, where the “traditional tools of statutory













10

construction,” id. at 843, are insufficient to answer

the interpretive question posed, courts have wisely

restricted their role to evaluating the reasonableness

of the interpretation offered by the agency possessing

the special, technical knowledge necessary to

understand the meaning of a statutory provision.

Kisor, 139 S. Ct. at 2415.2 The FDCA is a

paradigmatic example of the sort of “lengthy,

detailed, technical, complex, and comprehensive

response to a major social issue,” Chevron, 467 U.S. at

848, which has provided reason for courts to defer to

the FDA’s regulatory judgment since long before

Chevron. See Bendicksen et al., supra, at 372 n. 9

(“‘[T]he twentieth-century FDA received nearly

unparalleled judicial deference in its regulation of

drugs.’” quoting Carpenter, supra, at 729).

Because of the FDCA’s undeniable complexity,

Mylan Lab’ys, 389 F.3d at 1280, understanding the

authority it confers often requires an “‘evaluation[] of

scientific data” or a “statutory phrase [to] be read in

the context of the kind of drug at issue.” Serono

Lab’ys, Inc., 158 F.3d at 1320. These are competencies

“within [FDA’s] area of expertise,’” id., but will

understandably be out of reach for many courts, see

Kisor, 139 S. Ct. at 2410 (suggesting that courts are

not competent to evaluate if “a company created a new

‘active moiety’ by joining a previously approved

2 Amici agree, as the Government rightly observes, that Chevron

deference is sensible even in cases “that do not implicate

scientific or technical questions,” in light of the “‘historical

familiarity’ and ‘expertise’ that can yield interpretive insights.”

Gov’t Br. at 17 (describing Petitioners’ arguments and quoting

Martin v. OSHRC, 499 U.S. 144, 153 (1991)).













11

moiety to lysine through a non-ester covalent bond”);

see also Otsuka Pharm. Co. v. Price, 869 F.3d 987,

993-995 (D.C. Cir. 2017) (examining same question).

The special challenge of understanding the FDCA

comes not only from its use of technically

sophisticated terms, like “active moiety,” Kisor, 139 S.

Ct. at 2410, but also from its requirement that the

FDA develop scientifically sound solutions to complex

public health problems, which often arise in an

environment where both the scientific understanding

and shape of the public health problem are subject to

rapid change.

The breadth of the issues addressed by the FDCA

adds to its complexity. Giving effect to its ambitious

purpose of “protect[ing] the health and safety of the

public at large,” POM Wonderful LLC, 573 U.S. at

108, thus requires the FDA, as the agency charged

with executing the FDCA’s public health objectives, to

exercise expertise that is both deep and wide. See 21

U.S.C. §§ 393(b)(2) (directing the FDA to “protect the

public health by ensuring” the safety and efficacy of

“foods,” “human and veterinary drugs,” devices

intended for human use,” “cosmetics,” and “electronic

product radiation”). Indeed, considering only the

FDA’s regulation of drugs and devices, the subject of

Amici’s expertise, is sufficient to appreciate the

breadth and complexity of the issues Congress has

asked the FDA to regulate.

The FDA, which has been routinely recognized by

courts and others “as a scientific decisionmaker and a

champion of public health,” has historically been up

to that task. Bendicksen et al., supra, at 372; see also

Mylan Lab’ys, Inc., 389 F.3d at 1280 (“There is no

denying* * * the FDA’s expertise.”); Otsuka Pharm.













12

Co. v. Burwell, 302 F. Supp. 3d 375, 403 (D.D.C. 2016)

(Jackson, J.) (“[T]he FDA is an expert agency charged

with making precisely these sorts of highly technical

determinations.”), aff’d sub nom. Otsuka Pharm. Co.,

869 F.3d at 987.

B. The FDCA confers broad authority to

carry out its ambitious public health

mission, which warrants deference.

Befitting its ambitious statutory mandate, the

FDCA grants the FDA authority sufficient to regulate

drugs and medical devices comprehensively and at

every point in their lifecycle. From clinical trials and

drug development to approval of new drugs,

marketing, and labeling, to post-marketing

surveillance, FDA regulations set the standards by

which the products are regulated, and public health

is protected. But while the broad reach of the

statutory authority is clear, many provisions are

subject to multiple, plausible interpretations. As the

several FDA regulations reviewed herein underscore,

reasonable and well-supported regulations often

interpret statutory language that is amenable to

other, plausible interpretations.

i. New drug approvals.

Under the FDCA, no “new drug” can be marketed

in the United States unless it has first been approved

by the FDA. See 21 U.S.C. § 355(a). To gain approval,

applicants must provide FDA with, among other

things, “substantial evidence that the drug will have

the effect it purports or is represented to have under

the conditions of use prescribed, recommended, or

suggested in the proposed labeling thereof.” 21 U.S.C.

§ 355(d) (emphasis added). “[S]ubstantial evidence”

means “evidence consisting of adequate and













13

well-controlled investigations, including clinical

investigations, by experts qualified by scientific

training and expertise to evaluate the effectiveness of

the drug involved.” Ibid. (emphasis added).

At a high level of generality, that authority is clear

enough. Congress wants the FDA to make sure only

safe and effective drugs are marketed. But, apart

from specifying that scientific experts should be

involved, Congress did not say what it meant for an

investigation to be “adequate and well-controlled.”

See ibid.

The FDA filled in those details, specifying in

regulations that an “adequate and well-controlled”

study must generally have, at a minimum, “a design

that permits a valid comparison with a control to

provide a quantitative assessment of drug effect,” 21

C.F.R. § 314.126(b)(2); comparisons of at least two

dosages, 21 C.F.R. § 314.126(b)(2)(i); minimization of

bias to allow for comparability between groups of

different ages, sexes, severities of disease, etc., 21

C.F.R. §314.126(b)(4); and that the test drug “be

standardized as to identity, strength, quality, purity,

and dosage form to give significance to the results of

the investigation,” 21 C.F.R. § 314.126(d).

Notwithstanding the reasonableness of the FDA

regulations, the breadth of the statutory authority

leaves room for other plausible arguments to be

advanced in litigation. Placing those arguments on

equal footing, as Petitioners hope to do, risks courts

acting as policymakers, asserting the final say on

whether clinical investigations provide sufficient

indicia of the drug’s safety and effectiveness to make

it available to the public. See 21 U.S.C. § 355(d).













14

That raises cross-cutting concerns because courts,

which lack the requisite technical expertise, could be

persuaded to allow a potentially dangerous drug into

the market just as easily as they might erroneously

hold up approval of a drug to which patients

desperately need access. Indeed, since the same issue

may come before different courts, inconsistent results

are likely. Kisor, 139 S. Ct. at 2414 (plurality opinion)

(observing that courts “are most likely to come to

divergent conclusions when they are least likely to

know what they are doing”). Divergent outcomes

across courts will both increase compliance costs for

pharmaceutical companies intent on marketing drugs

nationwide and cause manufacturers to hesitate

before taking the kinds of risks that lead to real

innovation. That will, in turn, increase drug costs and

decrease drug access and options for patients, which

harms public health, in contravention of the FDCA’s

core purpose.

ii. Fast Track drug approval.

The traditional drug approval process is not the

only way that a drug can be approved for market.

Manufacturers may also pursue authorization under

the FDCA’s “Fast Track” authority, which provides

that, “at the request of the sponsor of a drug,” the FDA

“shall * * * expedite the development and review of [a]

drug” if (1) “it is intended, whether alone or in

combination with one or more other drugs, for the

treatment of a serious or life-threatening disease or

condition,” and (2) “it demonstrates the potential to

address unmet medical needs for such a disease or

condition.” 21 U.S.C. § 356(b)(1). If these criteria are













15

met, the FDA may also act on its own initiative to

place a drug on this “fast track.” 21 U.S.C. § 356(b)(3).

The FDA has interpreted this language in light of

the Fast Track program’s purpose—spurring

innovation and the development of live-saving

therapies, 21 U.S.C. § 356(e)(1)—and the context in

which the program operates—finding treatments for

those with life-threatening diseases and no good

treatment options, 21 C.F.R. § 312.80. It has thus

recognized that “physicians and patients are

generally willing to accept greater risks or side

effects” in this situation and that it should,

accordingly, evaluate “the benefits of the drug need *

* * in light of the severity of the disease being

treated.” Id. Ultimately, FDA has determined that

this calls for it to make “a medical risk-benefit

judgment in making the final decision on

approvability.” 21 C.F.R § 312.84.

As with other statutes, that seems reasonable and

consistent with the statutory authority. But it

nevertheless creates difficult line-drawing problems

when the FDA must approve or deny a Fast Track

application, which leave ample room for an aggrieved

applicant to challenge the FDA’s interpretation.

Without the deference recognized under Chevron, a

court that is persuaded, even marginally so, by the

applicants’ litigation position, will find itself acting as

drug policymaker, without any of the requisite

expertise to serve in that role. As with drug approval,

generally, additional judicial scrutiny of decisions

reached under the FDA’s Fast Track authority will

unleash a host of bad results that undermine

Congress’s purpose in enacting the FDCA. See supra

at 12-14.













16

iii.

Drug labeling: setting standards for

prescribing information.

Whether a drug is safe and effective is, in many

cases, context dependent. For instance, a drug that is

safe at one dose might be dangerous if taken at a

higher dose. Similarly, a drug that is effective on its

own might be rendered ineffective or even dangerous

if taken alongside another medication. Accordingly,

the FDCA provides that a company selling an

approved drug will nevertheless be subject to

penalties for marketing a “misbranded” drug:

[u]nless its labeling bears (1) adequate

directions for use; and (2) such adequate

warnings against use in those pathological

conditions or by children where its use may be

dangerous to health, or against unsafe dosage

or methods or duration of administration or

application, in such manner and form, as are

necessary for the protection of users[.]

21 U.S.C. § 352(f).

What constitutes “adequate directions for use” and

“adequate warnings against use” are not defined by

the statute, see ibid., and, while they can likely be

understood as a general matter, a functional

definition that serves the FDCA’s public health goal

must go beyond that and reflect an understanding of

the science underlying a drug approval, as well as the

clinical setting in which the drugs will be used or

prescribed. The FDA regulations demonstrate that

greater degree of expertise by setting up a

comprehensive and uniform labeling layout, which

includes “[h]ighlights of prescribing information,” 21

C.F.R. § 201.57(a), a table of contents of the

prescribing information, C.F.R. § 201.57(b); and













17

“[f]ull prescribing information,” C.F.R. § 201.57(c).

See FDA, How Do I Use Prescription Drug Labeling

(Mar. 29, 2023), http://tinyurl.com/f5hzf555.

As the name suggests, the “highlights” section

provides a quick way for a clinician to understand “the

most important aspects of a drug,” id., such as the

drug name, dosage information, indications and

contraindications, and “black box” warning, a

prominently displayed warning (enclosed in a black

box) about any risks of death or serious injury. 21

C.F.R. § 201.57(a). The requirements for full

prescribing information go further in depth, such as

by describing special considerations for those who are

pregnant, and the clinical studies “that support

effectiveness * * *, including discussion of study

design, population, endpoints, and results[.]” 21

C.F.R. § 201.57.

There are certainly other plausible ways that the

FDA could have applied the FDCA’s requirement that

drugs come with directions and warning labels. The

FDA’s approach may not even be the very best

formulation. But the question under Chevron is

whether it is a reasonable application of the FDA’s

statutory authority, and if it is the product of the

FDA’s expertise. See Requirements on Content and

Format of Labeling for Human Prescription Drug and

Biological Products, 71 Fed. Reg. 3,922, 3,930-31 (Jan.

24, 2006) (responding to drug manufacturer

opposition to highlights section by noting that, in

developing the rule, it had used focus groups, surveys,

and public meetings to “carefully evaluate[]the drug

information needs of physicians and ways to best

address those needs in prescription drug labeling”).













18

Like with drug approval decisions, judicial

intervention in labeling decisions, without the

safeguards of the Chevron framework, will produce

bad results. A lack of uniformity in labeling

requirements across courts will increase compliance

costs, to be sure. But ad-hoc judicial disruptions to

labeling requirements are also a public health

concern. Prescriber information labels, for instance,

are critical, carefully constructed documents that

allow informed prescribing decisions to happen safely

in a clinical setting. They contain, among other

things, information about the clinical trial

populations on which the drug was first assessed,

which will inform the clinician’s understanding of

whether the drug was shown to be safe and effective

for their patient’s profile. See Tanvee Varma et al.,

Metrics, Baseline Scores, and a Tool to Improve

Sponsor Performance on Clinical Trial Diversity:

Retrospective Cross Sectional Study, BMJ Medical,

Nov. 2022, at 1 (noting that clinical trial populations

often exclude those who have other underlying

conditions, take multiple other medicines, or are

older, female, or racially diverse). Disruption to this

authority increases the risk of prescribing errors,

which fundamentally undermines the FDCA’s public

health purpose.

iv.

Drug labeling: Medication Guides.

Whereas prescriber information is meant to help

healthcare providers, the FDA also uses its labeling

authority to require Medication Guides, which enable

“patients to use their medications safely and

effectively.” Prescription Drug Product Labeling;

Medication Guide Requirements, 63 Fed. Reg. 66,378

(Dec. 1, 1998). To that end, the FDA has promulgated













19

detailed regulations prescribing the “[c]ontent and

format of a Medication Guide,” which require that

these guides provide information that the FDA has

determined is most necessary to assist consumers in

correctly taking their medication. See 21 C.F.R.

§ 208.20. These regulations provide baseline

conditions that Medication Guides must include,

including headings for things and activities to avoid

while taking the medication, and a description of

possible side effects. 21 C.F.R. §§ 208.20(b)(6), (7).

The regulations also provide the means by which the

Medication Guides must be made available to each

patient. See 21 C.F.R. § 208.24(b).

Although this seems a reasonable exercise of the

FDA’s authority to regulate against misbranded

drugs or misleading labels and packaging, see 21

U.S.C. §§ 352, 355, when promulgated, commenters

asserted that the FDA lacked authority to require

pharmacists to make these Medication Guides

available, Prescription Drug Product Labeling;

Medication Guide Requirements, 63 Fed. Reg. at

66,382. As with the FDA’s authority to dictate the

prescribing information that appears on drug labels,

patients will be worse off if the contents of Medication

Guides are shaped by individual courts instead the

FDA’s expertise.

***

As this discussion shows, the FDA’s important work

relies to a great extent on broad statutory language,

which the FDA has worked diligently to interpret and

clarify through regulations that reflect its expert

judgment and reasonable approach to implementing

the FDCA. Despite its diligence and reasonableness,

the FDA’s ability to continue fostering drug and













20

device innovation, while protecting public health, will

come rapidly under attack, if Chevron falls.

II. Overruling or substantially modifying

Chevron undermines Congressional intent

and is not necessary to resolve Petitioners’

stated concerns.

Petitioners would have the Court replace the

“stable background rule” provided by the Chevron

framework, City of Arlington v. FCC, 569 U.S. 290, 296

(2013), with a chaotic environment where the

reasoned decisions the FDA makes (at nearly every

point in the lifecycle of a drug or device) will be subject

to challenge and delay. That risks judicial

intervention into everything from which drugs are

approved to what information appears on a warning

label, undermining the FDA’s collaborative

regulatory process along the way. Supra at 12-20.3

None of that—and particularly not the supplanting of

the FDA’s expertise—accords with congressional

intent. Nor is it necessary. The Court can address

Petitioners’ concerns about Chevron “forcing courts

to rubber-stamp” agency decisions, Pet. Br. at 4, by

emphasizing, as it has before, that “hard interpretive

conundrums, even relating to complex rules, can often

To be clear, Amici do not suggest that any particular FDA

regulatory authority would necessarily succumb to such

litigation. The FDA’s authority, while often broad, is typically

clear, and good reasons for deference to its expertise and

policymaking charge will remain, even if Chevron is formally

overturned. Nevertheless, a broad ruling for Petitioners will

undoubtedly encourage litigation, increase inconsistent lower

court applications of any new standard of review, and deliver

destabilizing effects.

3













21

be solved.” Kisor, 139 S. Ct. at 2415 (plurality

opinion).

A. Deference to the FDA under Chevron

animates the FDCA’s purpose in several ways.

The Court has recognized that the chaotic result

Petitioners request should be avoided on separation

of powers grounds, given “Congress’s frequent

‘preference for resolving interpretive issues by

uniform administrative decision, rather than

piecemeal by litigation,’” a preference that “may be

strongest when the interpretive issue arises in the

context of a ‘complex and highly technical regulatory

program’” where “judges are most likely to come to

divergent conclusions” because “they are least likely

to know what they are doing.” See Kisor, 139 S. Ct. at

2413–14 (plurality opinion) (first quoting Ford Motor

Credit Co. v. Milhollin, 444 U.S. 555, 568 (1980), and

then quoting Thomas Jefferson, 512 U.S. at 512).

Furthermore, any rule the Court adopts that

promotes judicial, rather than administrative,

regulation will also put distance between regulated

parties and the regulatory process in a way that

Congress did not intend. That will be a significant

loss. Like other agencies, see Gov’t Br. at 18, FDA’s

regulations are the product of robust engagement

with the many stakeholders with an interest in a

regulatory regime that appropriately balances drug

safety and effectiveness with enabling life-saving

pharmaceutical advances, including regulated

entities like pharmaceutical companies and patients

and their advocates.

Indeed, stakeholder engagement is legally

required in some contexts as various provisions of the

FDCA provide expressly that FDA should carry out













22

its authority “in consultation with experts in science,

medicine, and public health, and in cooperation with

consumers, users, manufacturers, importers, packers,

distributors, and retailers of regulated products.” See,

e.g., 21 U.S.C. § 393(b)(4). And, of course, the FDA

must also provide the public with notice and an

opportunity to comment on proposed regulations, 5

U.S.C. § 553, and must consider and “respond to

significant comments.” Perez v. Mortg. Bankers Ass’n,

575 U.S. 92, 96 (2015).

In addition, the FDA also receives and responds to

citizen petitions, meets with stakeholders, conducts

informational workshops, and holds open meetings of

its various advisory committees. See, e.g., 21 C.F.R.

§ 10.30 (citizen petitions); FDA, Stakeholder

Engagement Staff (Nov. 15, 2023), http://tinyurl.com/

2p9ahunh; John R. Manthei et al., Latham &

Watkins, Recent FDA Guidance Signals Increased

Willingness to Engage Industry Stakeholders (Oct. 25,

2023), http://tinyurl.com/mrxyb3dn.

The ability of the interested public to engage in the

regulatory process is a good thing, and not only in

some abstract sense or because it is legally required

in some cases. The joinder of stakeholder input and

engagement with agency expertise delivers specific

benefits for both the public and the FDA. The FDA’s

public engagement “procedures give the public

greater and less costly opportunities to be heard,” and

“also enable the agency to synthesize various

comments and consider more nuanced regulatory

approaches than may be possible in piecemeal

litigation of the same issues by individual parties in

different courts.” Gov’t Br. at 18. Their ability to

undertake extensive information gathering exercises













23

before reaching a decision is yet another way in which

federal agencies have “comparative advantages * *

* over courts” in the regulatory context, which has

long served to justify the deference they have

received. See Kisor, 139 S. Ct. at 2413 (plurality

opinion).

B. In practice, deference under Chevron has

allowed the FDA to faithfully and reliably

administer the FDCA.

An examination of cases decided by Courts of

Appeal at step two of the Chevron framework further

illustrate that, in practice, Chevron has guided courts

toward outcomes that support the FDCA’s public

health purpose. See Bendicksen et al., supra, at 371,

378 (collecting cases since 2000 in which “federal

appellate courts have applied the [Chevron]

framework * * * in litigation involving FDA actions”).

Amici focus here on three such cases, which involve

challenges to the FDA’s assertion of its authority to

regulate a product as a “drug.”

First, in Pharmanex v. Shalala, the Tenth Circuit

considered a case brought by Pharmanex, a company

hoping to “market[] a product, Cholestin, that [wa]s

intended to promote healthy cholesterol levels.”

Pharmanex v. Shalala, 221 F.3d 1151 (10th Cir.

2000). Cholestin contained a natural substance that

was chemically identical to the active ingredient in a

prescription drug, Mevacor. Id. at 1153. Pharmanex

sought to market Cholestin as a dietary supplement,

but the FDA determined that the product qualified as

a drug under the FDCA, which subjected it to more

rigorous pre-market regulation. Id.

As Chevron instructs, the Tenth Circuit applied

“the traditional tools of statutory construction,” id. at













24

1154 (citing Chevron, 467 U.S. at 842), concluding

that the statute contained ambiguous terms like

“article” and “drug,” and deferred to the FDA’s

interpretation, which it found to be reasonable. Id. at

1155-56. The court found that Pharmanex’s

interpretation was “linguistically possible,” but would

have amounted to “an end-run around the strictures

of the new drug approval process,” id. at 1160, which

was a result that would undermine the FDCA’s public

health purpose, see id. at 1158-59.

Second, in Whitaker v. Thompson, the D.C. Circuit

considered whether the FDA had misinterpreted the

FDCA when it refused to allow the marketing of “‘saw

palmetto,’ an extract from the pulp and seed of the

dwarf American palm,” as a “health claim.” Whitaker

v. Thompson, 353 F.3d 947, 948 (D.C. Cir. 2004). The

manufacturer wished to market the saw palmetto as

a supplement able to “improve urine flow, reduce

nocturia and reduce voiding urgency associated with

mild benign prostatic hyperplasia,” or an enlarged

prostate. Id. The FDA argued that claiming a product

would help “to maintain health and to ‘prevent’

disease” constituted a “health claim,” whereas “claims

that a product could ‘treat’ a disease” constituted

“drug claims.” Id. at 948-49. In the FDA’s view, the

claims concerning the saw palmetto extract were

“drug claims,” meaning that it could not be sold for its

stated use unless it first received “approval as a drug.”

Id. at 949.

In a unanimous panel decision, which was joined

by then-Judge John G. Roberts, Jr., the D.C. Circuit

held that the FDCA’s overlapping definitions of “drug

claims” and “health claims” created a statutory

ambiguity, which “the ‘traditional tools of statutory













25

construction’” could not resolve. Id. at 950 (quoting

Chevron, 467 U.S. at 843 n.9). Accordingly, the court

deferred to the FDA’s position, which it found

reasonable, albeit not “a knock-down argument” or

necessarily one that “would be sufficient to overcome

a strong textual or structural inference in favor of a

different interpretation.” Id. at 951.

Third, in United States v. Genendo Pharm., N.V.,

the Seventh Circuit considered a pharmaceutical

company’s attempt “to import prescription drugs

intended for sale in other countries into the United

States for repackaging and distribution.” United

States v. Genendo Pharm., N.V., 485 F.3d 958, 960

(7th Cir. 2007). The FDA seized the drugs, arguing

that they were “an ‘unapproved new drug,’” id.

(quoting 21 U.S.C. § 355(a)), because they “deviated

from the FDA-approved [new drug application (NDA)]

in several important respects,” including the

manufacturing facility, packaging, labeling, and

expiration dates of the imported drugs, id. at 961.

Genendo argued that the “deviations from the

requirements in the FDA-approved NDA” fell under a

statutory “exemption from all labeling and packaging

requirements * * *, including the NDA requirements,

so long as a drug is en route to or being held at an

authorized drug repackager.” Id. at 961 (citing 21

U.S.C. § 353(a)). The court found both Genendo and

the FDA’s interpretations “plausible” and, on that

basis, “enough ambiguity in the statute” to confine its

review to “whether the FDA’s interpretation is based

on a permissible construction of the statute.” Id. at

964. The court also observed that adopting Genendo’s

interpretation of the FDCA would permit drugs to be

repackaged outside of the FDA approved facilities,













26

even though approval of such facilities would

otherwise be required as part of the comprehensive

drug approval process. Id.

***

What these cases collectively show is that

deference under Chevron has consistently allowed the

FDA to fulfill its public health mission and carry out

the FDCA in a faithful way. In each of these cases, the

reviewing court found that both parties—FDA and

the company seeking to avoid pre-market approval

requirements—had

put

forward

plausible

interpretations that would have led to opposite

outcomes. Had any of those courts applied a lower

level of deference, or reviewed the interpretations

without

any

deference,

the

manufacturers

challenging FDA might have been permitted to

market drugs to consumers without the protections of

FDA’s stringent pre-market safety and effectiveness

reviews, Pharmanex, 221 F.3d at 1158-60; Whitaker,

353 F.3d at 948-49, and allowed a loophole for

supervision and approvals of packaging facilities,

Genendo Pharm., 485 F.3d at 960. The flexibility

afforded to the FDA under Chevron has benefitted the

public health goals of the FDCA greatly, while at the

same time, preserving the judiciary’s proper role of

ensuring the agency is engaged in reasoned

decision-making that is within its statutory

authority.

C. Overruling or substantially modifying

Chevron is not necessary to resolve

Petitioners’ stated concerns.

There is no doubt that the FDA has frequently

enjoyed success when courts find ambiguity in the

FDCA. But that does not make Chevron the













27

“rubber-stamp” that Petitioners claim it to be. See

Pet. Br. at 4. Courts are plainly willing and able to

strike down unreasonable FDA interpretations, even

where the operative FDCA language is ambiguous.

See, e.g., Braeburn Inc. v. FDA, 389 F. Supp. 3d 1, 27

(D.D.C. 2019) (rejecting FDA interpretation at Step

Two because it had “not reasonably interpreted the

statute”); see also Prevor v. FDA, 67 F. Supp. 3d 125,

137 (D.D.C. 2014) (finding statute clear but noting

that, had it found the statute ambiguous, it would

have vacated the FDA action as unreasonable); StatTrade Inc. v. FDA, 869 F. Supp. 2d 95, 107 (D.D.C.

2012) (similar).

Further, any perceived “mismatch,” Pet. Br. at 39,

between instances in which Chevron is appropriately

applied to technically complex statutes and those in

which courts have rushed to “‘wave the ambiguity

flag” merely because a statute appears to be

‘impenetrable on first read,’” is no reason to throw out

the doctrine altogether, Gov’t Br. at 14 (quoting Kisor,

139 S. Ct. at 2415). That misapplication of Chevron is

better corrected by the Court emphasizing that “hard

interpretive conundrums, even relating to complex

rules, can often be solved.” Kisor, 139 S. Ct. at 2415

(plurality opinion); see also id. at 2448 (Kavanaugh,

J., concurring in the judgment) (“If a reviewing court

employs all of the traditional tools of construction, the

court will almost always reach a conclusion about the

best interpretation of the regulation at issue.”).

Finally, Petitioners cannot reasonably deny that

in some cases “the law runs out, and policy-laden

choice is what is left over.” Kisor, 139 S. Ct. at 2415

(plurality opinion). At least in those cases—which, as

explained above, are likely to arise when the FDA













28

gives effect to the FDCA’s broad public health

mandate—the Court should preserve a mechanism

for non-expert courts to give some measure of

deference to the expertise of federal agencies, like the

FDA.

CONCLUSION

For the foregoing reasons, Amici respectfully

request that the Court affirm the judgment of the

Court of Appeals.

Victoria S. Nugent

Counsel of Record

Robin F. Thurston

Will Bardwell

Benjamin M. Seel

Democracy Forward Foundation

P.O. Box 34553

Washington, DC 20043

(202) 448-9090

vnugent@democracyforward.org

Counsel for Amici Curiae

December 2023