Prohibition Juice Co. v. FDA

United States Court of Appeals

FOR THE DISTRICT OF COLUMBIA CIRCUIT

Argued April 21, 2022 Decided July 26, 2022

No. 21-1201

PROHIBITION JUICE CO.,

PETITIONER

v.

UNITED STATES FOOD AND DRUG ADMINISTRATION,

RESPONDENT

Consolidated with 21-1203, 21-1205, 21-1207

On Petitions for Review of an Order

of the Food & Drug Administration

Jerad Wayne Najvar argued the cause and filed the briefs

for petitioners.

J. Gregory Troutman was on the brief for amici curiae 36

National and State Electronic Nicotine Delivery System

Product Advocacy Associations in support of petitioners.

Scott P. Kennedy, Trial Attorney, U.S. Department of

Justice, argued the cause for respondent. With him on the brief

were Brian M. Boynton, Principal Deputy Assistant Attorney

2

General, and Hilary K. Perkins, Assistant Director. Courtney

Dixon, Kathleen Gilchrist, Alisa B. Klein, Joshua M. Koppel,

and Lindsey Powell, Attorneys, entered appearances.

William B. Schultz and Andrew N. Goldfarb were on the

brief for amici curiae Medical and Public Health Groups in

support of respondent.

Before: HENDERSON, PILLARD, and KATSAS, Circuit

Judges.

Opinion for the Court filed by Circuit Judge PILLARD.

Concurring opinion filed by Circuit Judge KATSAS.

PILLARD, Circuit Judge: More than 3.6 million young

people in the United States reported using e-cigarettes in 2020,

including nearly one in five high school students. That makes

e-cigarettes “the most widely used tobacco product among

youth by far.” FDA, Technical Project Lead (TPL) Review of

PMTAs (2021) (FDA Technical Review), at 6. The public

health consequences are dire: Tobacco is quickly and

powerfully addicting, and e-cigarettes can permanently

damage developing adolescent brains, cause chronic lung

diseases, and hook young users for life. Given the scale and

severity of the problem, by 2018 the Surgeon General had

already decried an “epidemic” of youth e-cigarette use. 1 And

1

Surgeon General of the United States Public Health Service,

Surgeon General’s Advisory on E-cigarette Use Among Youth (Dec.

2018), https://www.cdc.gov/tobacco/basic_information/e-cigarettes/

surgeon-general-advisory/pdfs/surgeon-generals-advisory-on-e-

cigarette-use-among-youth-2018-h.pdf [https://perma.cc/3FPK-

7MRL]; see also Scott Gottlieb, Statement from FDA Commissioner

Scott Gottlieb, M.D., on New Steps to Address Epidemic of Youth E-

3

the FDA declared in 2021 that “preventing tobacco use

initiation in young people is a central priority for protecting

population health.” FDA Technical Review at 6.

Flavored tobacco products lie at the heart of the problem.

A vast body of scientific evidence shows that flavors encourage

youth to try e-cigarettes and, together with the nicotine, keep

them coming back. With names like Brain Freeze Caramel

Cone, Crazy Bubble Grape, and Green Apple Gummy Guts,

flavors play a “fundamental role” in driving youth interest in e-

cigarette use. FDA Technical Review at 8. The FDA has

concluded that the availability of flavored products “is one of

the primary reasons for the popularity of [e-cigarettes] among

youth.” Id. at 6.

Congress has called on the FDA to regulate e-cigarette

products pursuant to the Family Smoking Prevention and

Tobacco Control Act, Pub. L. No. 111-31, 123 Stat. 1776

(2009) (Tobacco Control Act or Act). Under the Act,

manufacturers must apply for FDA authorization to sell new

tobacco products, which the FDA grants only if it determines

that doing so would be “appropriate for the protection of the

public health.” 21 U.S.C. § 387j(c)(2)(A). The agency makes

that determination by weighing, on a population-wide basis,

any benefits of such products against their harms. Id.

§ 387j(c)(4).

Prohibition Juice makes flavored liquids containing

nicotine derived from tobacco, which it sells for use in e-

cigarettes, or Electronic Nicotine Delivery Systems (ENDS).

cigarette Use (Sept. 11, 2018), https://www.fda.gov/news-

events/press-announcements/statement-fda-commissioner-scott-

gottlieb-md-new-steps-address-epidemic-youth-e-cigarette-use

[https://perma.cc/RL2A-4Y8F].

4

Along with the three other e-liquid manufacturer petitioners,

Prohibition applied in September 2020 for FDA authorization

to market several flavors in a range of sizes. The FDA denied

those applications a year later. 2 In view of flavored tobacco

products’ serious, well-documented, and lasting risks to youth,

the FDA requires applicants to present reliable evidence of

robust public health benefits exceeding known risks. The

manufacturers describe their products as a beneficial

alternative to combustible cigarettes that offer comparative

health benefits to existing smokers. Finding the manufacturers

had presented insufficient evidence that their flavored products

are more effective than unflavored products in helping adult

cigarette smokers decrease or quit harmful tobacco uses, the

FDA denied the applications.

The manufacturers petition for review of those denials.

They first argue that the FDA lacked statutory authority to

require that parties establish that their flavored liquids carry

greater public health benefits than unflavored liquids. They

also challenge the application denials as arbitrary and

capricious, asserting that the FDA (1) departed from an earlier

guidance document, changing both the types of evidence the

agency would accept and the substantive showing it expected

parties to make; (2) underscored the potential importance of

marketing plans including measures to limit youth access to

their products but then failed to consider the plans petitioners

submitted; and (3) overlooked various other aspects of the

problem.

2

The FDA applied a common Technical Project Lead memorandum

to the four manufacturers’ applications, and the record includes four

copies, as sent to each of four petitioners. See J.A. 34-53, 819-38,

1016-34, 1223-42.

5

We deny the petitions for review. The FDA plainly had

statutory authority under the Tobacco Control Act to regulate

as it did. As to the arbitrary and capricious challenges, we hold

that the FDA did not change the evidentiary or substantive

standard from its 2019 Guidance. We also hold that any error

in the FDA’s failure to consider the marketing plans was

harmless because the manufacturers failed to identify how

individualized review of the plans they submitted could have

made any difference. Finally, the FDA did not otherwise fail

to consider important aspects of the problem. We accordingly

deny the petitions for review.

I. BACKGROUND

A. Statutory Background

In 2009, Congress enacted the Tobacco Control Act to

regulate the sale of tobacco products. Pub. L. No. 111-31, 123

Stat. 1776. Congress concluded that the “use of tobacco

products by the Nation’s children is a pediatric disease of

considerable proportions that results in new generations of

tobacco-dependent children and adults.” Id. § 2, 123 Stat. at

1777. We canvassed the history of the Tobacco Control Act in

Nicopure Labs, LLC v. FDA, 944 F.3d 267 (D.C. Cir. 2019),

where we recounted that Congress acted based on extensive

evidence that tobacco is widely used, highly addictive, and

destructive of human health. See id. at 270-79. The enacting

Congress knew that kids are key: The FDA had already shown

that the vast majority of adults who smoke have their first

cigarette before the age of 18, and that “[v]irtually all new users

of tobacco products are under the minimum legal age to

purchase such products.” Id. at 272 (quoting the Tobacco

Control Act, Pub. L. No. 111-31, §§ 2(3), (4), 123 Stat. at 1777

(alteration in original)). Businesses seeking to make a profit

selling tobacco products know that, too, and face powerful

6

economic incentives to reach younger customers. A core

objective of the Tobacco Control Act is to “ensure” tobacco

products will not be “sold or accessible to underage

purchasers.” Pub. L. No. 111-31, § 3(7), 123 Stat. at 1782.

Under the Act, a “new tobacco product” may not be

marketed in interstate commerce unless the manufacturer

obtains premarket authorization from the FDA. 21 U.S.C.

§ 387j(a)(1)-(2). The FDA in turn “shall deny” an application

to market a new tobacco product unless the agency finds “that

permitting such tobacco product to be marketed would be

appropriate for the protection of the public health.” Id.

§ 387j(c)(2). The statute explains how the FDA is to determine

whether approving a product is, on balance, appropriate for the

protection of public health:

For purposes of this section, the finding as to whether

the marketing of a tobacco product for which an

application has been submitted is appropriate for the

protection of the public health shall be determined

with respect to the risks and benefits to the

population as a whole, including users and nonusers

of the tobacco product, and taking into account—

(A) the increased or decreased likelihood that

existing users of tobacco products will stop

using such products; and

(B) the increased or decreased likelihood that those

who do not use tobacco products will start

using such products.

Id. § 387j(c)(4)(A)-(B).

7

That statutory directive reflects the fact that tobacco is

highly addictive and generally harmful to human health. Proof

that a new tobacco product has public health benefit thus

depends on favorable substitution effects, such as evidence that

the new product is less harmful to existing users than current

products, and that it either draws existing users away from the

more harmful tobacco products or helps them to quit altogether.

Any such benefit must be shown to offset the product’s public

health harms to new users, including youth.

The statute also directs manufacturers to include in their

applications “full reports of all information . . . concerning

investigations which have been made to show the health risks

of such tobacco product and whether such tobacco product

presents less risk than other tobacco products.” Id.

§ 387j(b)(1)(A). The Act grandfathered tobacco products on

the market as of February 15, 2007, excusing them from the

premarket authorization requirement. Id. § 387j(a)(1). But no

product brought to market after that date may lawfully be sold

unless and until it receives FDA premarket authorization.

B. Regulatory Background

Electronic cigarettes subject to the Tobacco Control Act

deliver nicotine to their users by vaporizing a liquid derived

from tobacco. See Nicopure Labs, 944 F.3d at 270, 272. These

devices are either disposable (closed) or refillable (open).

Open systems are refilled either by inserting a pod or cartridge

containing the liquid into the device or by manually pouring in

the liquid. For current purposes, the liquids inside those

devices are treated as either non-flavored, meaning they taste

like tobacco, or as flavored because they carry a distinctive,

often sweet, flavoring. Flavored liquids are the subject of this

challenge. The FDA is separately addressing applications for

menthol-flavored devices, see FDA Technical Review at 3 n.ii,

8

and is re-evaluating whether it mistakenly included some

tobacco- and menthol-flavored products in the denial order

challenged here, see FDA Br. 16 n.6. (This opinion does not

address those products.)

A hallmark of flavored liquids is their disproportionate

appeal to children. The FDA cited clear scientific consensus

that such products hold “extraordinary popularity” among

youth. FDA, Enforcement Priorities for Electronic Nicotine

Delivery Systems (ENDS) and Other Deemed Products on the

Market Without Premarket Authorization (Revised) (2020)

(2020 Guidance). One study found that 93.2% of youth e-

cigarette users and 83.7% of young adult users (ages 18-24)

reported their first e-cigarette was flavored, and 84.7% of high

school e-cigarette users reported using a flavored product in

2020. FDA Technical Review at 6. The agency also surveyed

compelling evidence that youth are more likely than adults to

use flavored products. Id. It accordingly concluded that, for

flavored products, “the risk of youth initiation and use is

substantial.” Id. at 10.

In view of flavored tobacco products’ appeal to young

people, it is especially challenging for marketers to make a case

that those products are appropriate for the protection of public

health. Applicants seeking to market e-cigarettes have

generally sought to show that their products cause users of

existing, less safe tobacco products to transition to safer use

patterns without enticing new users, especially children. That

is, again, because the FDA may approve a new product only if

the applicant succeeds in showing that its benefits to the

population as a whole outweigh its risks.

In 2016, the FDA promulgated a “deeming rule”

designating e-cigarettes and their component e-liquids as “new

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tobacco products” under the Act. 3 That means Prohibition

Juice and other e-liquid manufacturers may not lawfully market

their products without FDA approval. We rejected a challenge

to that deeming rule in Nicopure Labs, sustaining both the

Tobacco Control Act and its application to e-cigarettes. 944

F.3d at 272.

As a matter of enforcement discretion, however, the FDA

announced it would not enforce the Act against new (post-

2007) products for staggered two-to-three-year periods. See

Deeming Rule, 81 Fed. Reg. at 28,977-78. Following a further

FDA extension in 2017 of up to six years, a suit by the

American Academy of Pediatrics garnered a court-ordered

deadline, which in turn was adjusted due to the COVID-19

pandemic. See Am. Acad. of Pediatrics v. FDA, 399 F. Supp.

3d 479, 487 (D. Md. 2019), appeal dismissed sub nom. In re

Cigar Ass’n of Am., 812 F. App’x 128 (4th Cir. 2020). The

deadline for manufacturers to submit their marketing

applications ultimately settled on September 9, 2020. See

Breeze Smoke, LLC v. FDA, 18 F.4th 499, 504 (6th Cir. 2021).

Meanwhile, a wave of new e-cigarette products flooded the

market without scientific review or premarket authorization,

causing e-cigarette use to hit the highest levels ever seen. See

2020 Guidance at 6-9.

Central to the manufacturers’ claims is a nonbinding

guidance document the FDA issued in 2019 to help

manufacturers prepare applications ahead of the deadline.

FDA, Premarket Tobacco Product Applications for Electronic

3

See Deeming Tobacco Products to Be Subject to the Federal Food,

Drug, and Cosmetic Act, as Amended by the Family Smoking

Prevention and Tobacco Control Act; Restrictions on the Sale and

Distribution of Tobacco Products and Required Warning Statements

for Tobacco Products (Deeming Rule), 81 Fed. Reg. 28,974 (May

10, 2016).

10

Nicotine Delivery Systems: Guidance for Industry (June 2019)

(2019 Guidance). Prohibition Juice highlights two pieces of

that guidance. First, it points to the FDA’s discussion of the

types of evidence that applicants should consider submitting.

2019 Guidance at 12-13. In relevant part, the agency wrote:

Given the relatively new entrance of [e-cigarettes] on

the U.S. market, FDA understands that limited data

may exist from scientific studies and analyses. If an

application includes, for example, information on

other products (e.g., published literature, marketing

information) with appropriate bridging studies, FDA

intends to review that information to determine

whether it is valid scientific evidence sufficient to

demonstrate that the marketing of a product would

be [appropriate for the protection of public health].

Nonclinical studies alone are generally not sufficient

to support a determination that permitting the

marketing of a tobacco product would be appropriate

for the protection of the public health. Nonetheless,

in general, FDA does not expect that applicants will

need to conduct long-term studies to support an

application.

2019 Guidance at 12-13 (footnote omitted).

Second, the manufacturers focus on how the agency

recommended that applicants compare their products to other

tobacco products to help identify and account for their own

product’s relative health risks. In a section titled “Comparison

Products,” the agency wrote:

As part of FDA’s consideration under 910(c)(4) of

the FD&C Act of the risks and benefits of the

marketing of the new tobacco product to the

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population as a whole, including users and nonusers

of tobacco products, FDA reviews the health risks

associated with changes in tobacco product use

behavior (e.g., initiation, switching, dual use,

cessation) that are likely to occur with the marketing

of the new tobacco product. We recommend an

applicant compare the health risks of its product to

both products within the same category and

subcategory, as well as products in different

categories as appropriate. . . . This comparative

health risk data is an important part of the evaluation

of the health effects of product switching. . . . For

example, for [an application] for an e-liquid, FDA

recommends the product’s health risks be compared

to those health risks presented by other e-liquids used

in a similar manner.

2019 Guidance at 13-14.

The FDA followed up with a 2020 guidance document

setting out the agency’s enforcement priorities. FDA,

Enforcement Priorities for Electronic Nicotine Delivery

Systems (ENDS) and Other Deemed Products on the Market

Without Premarket Authorization (Revised) (2020) (2020

Guidance). The FDA issued that guidance after industry

manufacturers, at FDA’s urging, had identified a variety of

measures, including age verification, they said they would use

to try to restrict minors’ access to their products. See 2020

Guidance at 7. The 2020 Guidance emphasized that,

notwithstanding such measures, youth e-cigarette use “has hit

the highest levels ever recorded.” Id. at 8. With the rising wave

of youth vaping, the “extraordinary popularity” of flavored

products driving that rise, and industry’s measures proving

insufficient to stem it, the FDA announced that flavored

products would be an enforcement priority. Id. at 13, 18-21.

12

As a result, by the September 9, 2020, deadline for

submitting applications, the FDA had publicly highlighted the

particular dangers of flavored products and noted the types of

rigorous scientific evidence it would accept in support of

applications to market such products. The FDA received

applications from more than five hundred companies, many

submitted shortly in advance of that deadline, including those

of the four petitioners here. Enforcement was suspended for an

additional year following the deadline to allow the FDA time

to review and act on the applications. See Deeming Rule, 81

Fed. Reg. at 28,9778.

C. Procedural History

Prohibition Juice, ECig Charleston L.L.C., Cool Breeze

L.L.C., and Jay Shore Liquids L.L.C. manufacture flavored e-

liquid products. In September 2020, the manufacturers applied

for approval to market a large set of variously flavored e-liquid

products. A small sampling of the flavors the manufacturers

seek to sell includes Prohibition Juice’s Boozehound, Sweet

Thang, White Lightning, and Black Market (J.A. 3-24); Cool

Breeze’s Awesome Sauce (Peach, Raspberry, Strawberry),

Brain Freeze Caramel Cone, Buncha Crunch (Crunch Fruit

Cereal), Crazy Bubble Grape, Giggle Juice, Jolly Apple, and

Sugar Rush Peach Ring Candy (J.A. 472-807); ECig’s

Cinnamon Pear, Banana Strawberry, Cloud Chaser, and

Fireball Cinnamon (J.A. 986-1006); and Jay Shore’s Blueberry

Dream Cake, Green Apple Gummy Guts, Pink-Burst, and

Rootbeer Float (J.A. 1197-213).

Each manufacturer submitted a marketing plan as part of

its application. See J.A. 268-76 (Prohibition); J.A. 861-64

(Cool Breeze); J.A. 1036-41 (ECig); J.A. 1264-77 (Jay Shore).

The marketing plans described measures each manufacturer

13

was taking to limit youth access to their products. See Pet’rs

Br. at 39. As examples, the manufacturers highlighted their use

of age-verification “gating” on their websites (accepting any

qualifying birthdate) and “dull, less vibrant colors” without

“mascots and similar characters” on their labeling to avoid

appealing to youth. Id. (internal quotation omitted). Other e-

cigarette companies are developing novel technologies, such as

requiring age verification assisted by facial recognition

software to unlock their products, which they assert could

prevent underage use. The FDA noted those developments and

explained that it communicates with tobacco companies to

keep abreast of measures that might better control youth access

to their products. See Oral Argument Tr. at 31-32. Petitioners

acknowledge that their marketing plans proposed no such novel

controls. See Oral Argument Tr. at 12.

In September 2021, the FDA denied petitioners’

applications. It did so based on a common memorandum it

issued to all four manufacturers setting out the analytic

framework under which the agency assessed their applications.

It also issued each manufacturer a separate denial letter and

review memorandum.

The FDA’s common memorandum began by surveying the

well-known risks of flavored electronic nicotine delivery

systems to youth. FDA Technical Review at 4-9. It noted the

data showing dramatic and accelerating rates of youth use of e-

cigarette products, notwithstanding the decrease in cigarette

smoking by youth. Id. at 4-7. The memorandum also

referenced evidence that flavors drive youth uptake, intensity

of use, and addiction, and that flavored products appeal more

to youth than they do to adults. Id. The FDA surveyed the

substantial damage nicotine causes to the adolescent brain. Id.

at 8-9. It emphasized that the youth preference for flavor

remained “consistent” across different types of devices. Id. at

14

7. While there may be “variability” in the popularity of

different device types among youth, young people consistently

use whichever products will allow them to enjoy flavors that

appeal to them—evidence the FDA described as “underscoring

the fundamental role of flavor in driving appeal.” Id. at 7-8.

Based on this evidence, the FDA concluded that flavored e-

liquids “pose a significant risk to youth.” Id. at 9.

The FDA then considered how best to weigh that known

risk against potential benefits to adult smokers. It concluded

that “any risks posed by a new product to youth would need to

be overcome by a sufficient benefit to adult users, and as the

known risks increase, so too does the burden of demonstrating

a substantial enough benefit.” FDA Technical Review at 10.

And because flavored products carry a “substantial” risk of

youth initiation, the FDA determined that such products would

be approved only if a manufacturer could show “that the

significant risk to youth could be overcome by likely benefits

substantial enough such that the net impact to public health

would be positive.” Id. In sum, the FDA required that

manufacturers produce evidence that is scientifically rigorous;

compares flavored liquids to non-flavored liquids; and

establishes that flavored products have substantial benefits

over non-flavored ones to fully overcome flavored products’

known risks.

In separate denial orders to each manufacturer, the FDA

explained how each had failed to make that showing. The FDA

concluded that the manufacturers had not submitted rigorous

evidence demonstrating benefits of their flavored products as

compared to unflavored products—be that evidence from

randomized controlled trials, longitudinal studies, or some

other form of analysis. Without reliable, probative evidence of

benefits outweighing the products’ known risks, the FDA

denied the applications.

15

The FDA also declined to review the manufacturers’

marketing plans, stating its rationale in a footnote:

Limiting youth access and exposure to marketing is

a critical aspect of product regulation. It is

theoretically possible that significant mitigation

efforts could adequately reduce youth access and

appeal such that the risk for youth initiation would be

reduced. However, to date, none of the [applications]

that FDA has evaluated have proposed advertising

and promotion restrictions that would decrease

appeal to youth to a degree significant enough to

address and counter-balance the substantial

concerns, and supporting evidence, discussed above

regarding youth use. Similarly, we are not aware of

access restrictions that, to date, have been successful

in sufficiently decreasing the ability of youth to

obtain and use [e-cigarettes]. Accordingly, for the

sake of efficiency, the evaluation of the marketing

plans in applications will not occur at this stage of

review, and we have not evaluated any marketing

plans submitted with these applications.

FDA Technical Review at 11 n.xix.

The manufacturers timely petitioned this court for review,

and we consolidated the cases.

D. Decisions in Parallel Cases

Under the Tobacco Control Act’s judicial review

provision, a party subject to a marketing denial order may

petition for review either in this court or in the circuit in which

its principal place of business is located. See 21 U.S.C.

16

§ 387l(a)(1)(B). Other manufacturers have sought review in

other circuits of orders denying approval to market flavored

ENDS, with some courts denying and others granting stays of

enforcement pending review. See Breeze Smoke, LLC v. FDA,

18 F.4th 499 (6th Cir. 2021) (opinion denying stay), cert.

denied, 142 S. Ct. 638 (2021) (mem.); My Vape Order v. FDA,

No. 21-71302, ECF No. 18 (9th Cir. 2021) (order denying stay

of enforcement); Gripum LLC v. FDA, No. 21-2840, 2021 WL

8874972 (7th Cir. Nov. 4, 2021) (order granting stay), Bidi

Vapor LLC v. FDA, No. 21-13340-DD (11th Cir. Feb. 1, 2022)

(order granting stay).

To date, only the Fifth Circuit has reached the merits of

FDA denial orders like those challenged here. On the eve of

issuance of this opinion, that court in Wages & White Lion

Investments, LLC d/b/a Triton v. FDA (Triton), No. 21-60766,

2022 WL 2799797 (July 18, 2022), denied two e-liquid

manufacturers’ petitions for review. Id. at *1. The court

rejected as “blatantly wrong” the manufacturers’ contention

that the Tobacco Control Act does not authorize the FDA to

consider comparative cessation benefits of flavored over

unflavored or tobacco-flavored products. Id. at *4. And the

court denied the manufacturers’ various arbitrary and

capricious challenges. See id. at *5-11. It held that the FDA

adequately explained the shortcomings of the manufacturers’

study, considered relevant differences between “open” and

“closed” e-cigarette device types, did not assess applications

under evidentiary or substantive requirements different from

those communicated to the regulated parties, and adequately

justified its decision not to review the manufacturers’

marketing plans (or, alternatively, committed only harmless

error). Id. The court accordingly denied the manufacturers’

petitions for review. Id. at *11.

17

Judge Jones dissented on the ground that, in her view, the

orders are arbitrary and capricious. Id. at *12-19; see 16 F.4th

1130 (5th Cir. 2021) (motions panel granting stay on similar

reasoning). She would have held the FDA’s decision to not

review the manufacturers’ marketing plans “obviously illogical

and unreasonable,” 2022 WL 2799797 at *16, and rejected the

majority’s view that any error was harmless, id. at *17. She

also would have held that the FDA took a “meandering

administrative course” that, without notice, altered the

substantive and evidentiary requirements manufacturers were

expected to meet. Id. at *18. Her analysis tracked that of the

earlier motions panel in the same case, which had stayed the

FDA’s order and held the manufacturers were likely to succeed

on their arbitrary and capricious claims. See id. at *16 (quoting

and citing 16 F.4th at 1137).

The only other published opinion to date on flavored

ENDS product marketing orders is the Sixth Circuit’s opinion

in Breeze Smoke, LLC v. FDA, denying an e-liquid

manufacturer’s petition for a stay based on its failure to show a

likelihood of success. 18 F.4th at 503. For reasons later

adopted by the Fifth Circuit merits panel in Triton, the court

sustained the FDA’s determination that Breeze failed to meet

its evidentiary requirements, explaining that the FDA’s

statement in its 2019 Guidance that it was willing to “consider”

additional forms of evidence did not require it to accept such

evidence as sufficient to meet the statute’s requirement. Id. at

507. Relatedly, the court was unpersuaded that the FDA’s

Guidance had changed applicants’ evidentiary burden without

notice. The agency, the court observed, has consistently

required applicants to submit randomized controlled trials,

longitudinal studies, or other similarly rigorous evidence. Id.

at 506-07. Commenting that the FDA probably should have

more thoroughly considered applicants’ marketing and youth

prevention plans or better explained why it did not, the court

18

held that potential shortcoming did not in any event establish a

likelihood of success to justify a stay. Id. at 507-08.

II. DISCUSSION

A. Jurisdiction, Standing, and Standard of Review

The Tobacco Control Act confirms our jurisdiction to

review the FDA’s denial orders. See 21 U.S.C.

§ 387l(a)(1)(B). And the manufacturers have standing to

challenge the FDA’s marketing denial orders, which deny them

the authorization the Tobacco Control Act requires before they

may lawfully sell their products.

The manufacturers assert that the FDA exceeded its

statutory authority under the Tobacco Control Act by requiring

applicants to show their flavored e-liquids carry sufficiently

greater benefits than non-flavored e-liquids to outweigh their

relatively greater risks. Because we conclude the statute is best

read to support the FDA’s action, we need not consider whether

or how much deference to accord its interpretation. The

manufacturers also argue that the FDA’s denial order was

arbitrary and capricious in several respects. We review such

challenges to the FDA’s exercise of its Tobacco Control Act

authority under the ordinary APA standard of review. 21

U.S.C. § 387l(b) (citing 5 U.S.C. § 706(2)(A)). Under section

706 we assess whether the agency offered a “satisfactory

explanation for its action” and hold arbitrary and capricious

explanations that “entirely fail[] to consider an important

aspect of the problem.” Motor Vehicle Mfrs. Ass’n v. State

Farm Mut. Auto. Ins. Co., 463 U.S. 29, 43 (1983). In so doing,

we must “judge the propriety of [an agency’s] action solely by

the grounds invoked by the agency.” SEC v. Chenery Corp.,

332 U.S. 194, 196 (1947). Our review incorporates the APA’s

prejudicial error rule, under which the “burden of showing that

19

an error is harmful normally falls upon the party attacking the

agency’s determination.” Shinseki v. Sanders, 556 U.S. 396,

409 (2009) (citing 5 U.S.C. § 706).

B. Challenge to FDA’s Statutory Authority

Congress directed the FDA to authorize the marketing of

only those new tobacco products that an applicant has shown

“would be appropriate for the protection of the public health.”

21 U.S.C. § 387j(c)(2)(A). The distinct public health hazards

of flavored tobacco products, especially to young people, are

extensively documented. Given those risks, purveyors of

flavored products cannot show they are appropriate in public

health terms without establishing that they have substantial

public health benefits that overcome their risks. The FDA

accordingly requires applicants seeking to market flavored

tobacco products to show their products are more beneficial to

the public health than non-flavored products.

Petitioners challenge that requirement as contrary to the

Act. They assert that the FDA lacks statutory authority to

consider a product’s “relative effectiveness at promoting

cessation of combustible cigarette use versus another product

with an otherwise similar health risk profile and labeling.”

Pet’rs Br. at 50. But the Tobacco Control Act itself instructs

that, in seeking an FDA determination that their product is

appropriate for the protection of the public health, an applicant

must supply “full reports of all information . . . concerning

investigations which have been made to show the health risks

of such tobacco product and whether such tobacco product

presents less risk than other tobacco products.” 21 U.S.C.

§ 387j(b)(1)(A) (emphasis added). The Act then provides that

the FDA “shall deny an application . . . if, upon the basis of the

information submitted . . . and any other information before the

[FDA],” it concludes that the applicant has failed to “show[]

20

that permitting [the] product to be marketed would be

appropriate for the protection of the public health.” Id.

§ 387j(c)(2). In other words, the statute not only allows but

expressly instructs the FDA to consider evidence regarding just

the comparison that the manufacturers say the FDA lacks

statutory authority to make.

The FDA acted well within that statutory directive when it

compared the claimed cessation benefits of flavored and non-

flavored products. The FDA has found that flavored products

present greater risks than other tobacco products, based on a

robust array of literature showing the dangers those products

pose of hooking new users, especially youth. See FDA

Technical Review at 5-9. Instead of stopping there and

denying the applications for flavored products as

comparatively risky, it addressed their asserted upsides,

reasoning that a product could still be net beneficial if its large

risks were overcome by larger benefits to current users. See id.

at 10-14. By contrast, if the new product carried greater risks

but no overmatching greater benefits, authorizing it would not

on balance serve public health. That is precisely the type of

analysis the statute calls for.

The manufacturers contend that the statutory phrase “the

health risks of such tobacco product” limits the FDA to

comparing only the “physiological health risks” of individual

tobacco products without taking account of a “broader concept

of risk that encompasses initiation and cessation behaviors.”

Pet’rs Reply Br. at 12-13. The statutory text is to the contrary.

The degree to which a harmful product entices and addicts new

users is inarguably a component of the “health risk” it poses.

That is plain from Congress’s express directive that the FDA

determine whether a product is “appropriate for the protection

of the public health,” a population-wide inquiry. 21 U.S.C.

§ 387j(c)(2)(A) (emphasis added); see also Health, BLACK’S

21

LAW DICTIONARY (11th ed. 2019) (defining “public health” as

“[t]he health of the community at large” or “the general body

of people or the community en masse”).

The manufacturers are wrong that the FDA applied a

standard akin to or more stringent than the “safe and effective”

standard to which new drugs are subject or conflated its

statutory inquiry with the “modified risk tobacco products”

inquiry. See Pet’rs Br. at 50-54 (citing 21 U.S.C.

§§ 355(b)(1)(A), 387k). Those distinct standards apply to

other kinds of approvals contingent on evidentiary showings

that do not apply here and that the FDA did not demand. See

21 U.S.C. § 355(b)(1)(A) (requiring evidence that new drug is

effective for therapeutic use, which the manufacturers do not

claim of e-cigarette liquids); id. § 387k (requiring evidence

substantiating specific modified risk claims, which the

manufacturers do not seek to make here). Moreover, the fact

that the FDA has other authorities through which it can approve

other products, like those designed and approved specifically

as smoking cessation products, does not release the FDA from

following its statutory mandate here to approve only tobacco

products the sale of which it determines “would be appropriate

for the protection of the public health.” 21 U.S.C. § 387j(c)(2).

The manufacturers give us no persuasive reason to think that

those other authorities somehow limit the inquiry the FDA may

make in reaching a § 387j determination.

C. Arbitrary and Capricious Challenges

The manufacturers also contend that the FDA’s denial of

their marketing applications was arbitrary and capricious.

They raise two principal arguments. First, they argue the FDA

misdirected applicants by altering both the types of evidence it

would accept and the comparison it required applicants to

make. Second, they argue the FDA failed to reasonably explain

22

its decision not to review the manufacturers’ individual

marketing plans. They more briefly make a handful of other

arguments, also addressed below.

We hold that the FDA did not misdirect applicants. And,

assuming the FDA insufficiently explained its non-review of

applicants’ marketing plans, we hold that error was harmless.

The manufacturers’ other arbitrary and capricious challenges

fail as well. We accordingly deny the petitions for review.

1. The “Surprise Switcheroo” Challenge Fails

The manufacturers argue that the FDA’s 2019 Guidance

rendered its denial orders arbitrary and capricious because the

guidance steered them astray. Agencies must explain changes

in position, particularly once a prior position has engendered

regulated parties’ reliance. See FCC v. Fox Television Stations,

Inc., 556 U.S. 502, 514-16 (2009); PHH Corp. v. CFPB, 839

F.3d 1, 44-49 (D.C. Cir. 2016), vacated and reinstated in

relevant part, 881 F.3d 75, 83 (D.C. Cir 2018) (en banc). The

manufacturers assail the FDA’s denial orders as departing from

its 2019 Guidance in two ways: They argue the FDA (1)

changed the types of evidence it expected applicants to

produce, and (2) changed the substantive comparison it

expected applicants to make. Because those changes conflicted

with the 2019 Guidance, the manufacturers say, the FDA acted

without fair notice of the requirements their applications had to

meet to gain approval. See Pet’rs Reply Br. at 3 (citing SNR

Wireless LicenseCo., LLC v. FCC, 868 F.3d 1021, 1043 (D.C.

Cir. 2017)).

The manufacturers’ notice claim effectively boils down to

an assertion that the FDA’s 2019 Guidance affirmatively

misdirected them. They do not claim insufficient notice based

on the statutory standard or the FDA’s deeming rule. Indeed,

23

they seem to acknowledge that, had the agency not issued its

2019 Guidance, they would have no claim of inadequate notice.

See Oral Argument Tr. at 5-6. The manufacturers instead argue

that the FDA’s 2019 Guidance suggested the agency would

approve the type of application they filed, making its rejections

unexpected and arbitrary. But the FDA’s final determinations

were consistent with the 2019 Guidance, undercutting their

claim.

a. No change to requisite types of evidence

The manufacturers argue that the FDA without warning

altered the types of evidence it would accept. Specifically, they

claim that the 2019 Guidance suggested that applicants need

not produce data from randomized controlled trials or

longitudinal studies, and that the FDA here suddenly reversed

course by effectively requiring those forms of evidence.

We disagree. The FDA did not reverse course. The 2019

Guidance said that randomized controlled trials or longitudinal

studies would not be necessary if applicants submitted

similarly rigorous “valid scientific evidence.” 2019 Guidance

at 12. In the orders under review, the agency found that these

applicants’ evidence was not similarly rigorous. As the Sixth

Circuit reasoned in Breeze Smoke, the FDA said only that “it

might accept evidence other than long-term studies, if that

evidence had sufficient scientific underpinnings” to meet the

statutory standard. 18 F.4th at 506-07. The FDA nowhere

guaranteed that unspecified other forms of evidence would

necessarily be sufficient—only that they might be, so the FDA

would consider them. 2019 Guidance at 12-13.

The text of the FDA’s 2019 Guidance makes that clear.

The agency stated that it “intends to review” evidence in forms

other than randomized controlled trials or longitudinal studies

24

“to determine whether it is valid scientific evidence sufficient

to demonstrate that” the statutory standard is met. 2019

Guidance at 12. The FDA thereby broadened the types of

evidence it would consider: Instead of limiting applicants to

the two types of evidence it usually requires, the agency

allowed manufacturers to submit evidence in other forms. But

at the same time the agency made clear it would not relax the

scientific rigor of the requisite public health demonstration.

The agency’s finding that the evidence was insufficiently

rigorous does not reflect a changed standard, but the

manufacturers’ failure to meet the standard the agency

consistently applied.

Nor did the FDA act arbitrarily and capriciously by finding

the manufacturers’ evidence insufficiently rigorous.

Prohibition Juice’s own literature review concluded that “there

is not enough evidence from well-designed studies to

determine whether e-cigarette flavors aid in smoking

cessation.” J.A. 469. The manufacturers argue that the FDA

failed to credit data they collected through online voluntary

surveys. But the FDA explained that one-time assessments and

consumer perception surveys “do[] not enable reliable

evaluation of behavior change over time” and that their lack of

product-specific comparisons deprive them of probative

weight. FDA Technical Review at 12-13. The FDA

accordingly concluded that, “in contrast to the evidence related

to youth initiation—which shows clear and consistent patterns

of real-world use that support strong conclusions—the

evidence regarding the role of flavors in promoting switching

among adult smokers is far from conclusive.” Id. at 11.

Considered in light of the evidence before the agency, that

conclusion was entirely reasonable.

The manufacturers argue that, even if the FDA nominally

claimed it would accept other evidence, the agency effectively

25

engaged in an arbitrary “fatal flaw” analysis to reject

applications lacking either of the two leading types of evidence.

Pet’rs Br. at 16. As they see it, the FDA in practice considered

only whether applicants had submitted data from randomized

controlled trials or longitudinal cohort studies. Id. But the

material the manufacturers rely on itself directly refutes that

characterization.

First, they point to the check-box forms the FDA used to

assess applications. But they omit that those forms looked

beyond randomized trials and longitudinal studies to list a third

category of potential support: “Other evidence in the

[application] related to potential benefit to adults.” See J.A.

32-33, FDA Br. at 43. The manufacturers’ problem, per that

document, was not their failure to include longitudinal or

randomized controlled studies. It was their failure to include,

as the FDA consistently required, studies sufficiently rigorous

to show a benefit of flavored e-cigarette products sufficient to

overcome their risks.

Second, the manufacturers point to an internal agency

guidance memorandum dated July 9, 2021, as evidence of this

fatal flaw approach. See J.A. 159-60. The July memorandum’s

prediction that applications lacking evidence from randomized

controlled trials or longitudinal studies would “likely” be

denied did not necessarily foreclose reliance on other forms of

rigorous evidence. Id. at 160. In any event, the FDA replaced

that memorandum the next month, on August 17, 2021, with

superseding guidance that expressly required the agency to

consider other forms of evidence if sufficiently robust. See J.A.

161-62; see also J.A. 162 n.ix. That August memorandum

preceded the FDA’s rejection of petitioners’ applications.

The manufacturers also contend the FDA imposed an

evidentiary “double standard” by using literature reviews as

26

evidence for flavored products’ risks but eschewing literature

reviews as evidence of their benefits. The FDA explained that

its treatment of various materials depended on the nature and

conclusiveness of the findings they reported. From its study of

reviews of the scientific evidence on the risks of flavored

products, the agency concluded that those risks “are understood

as a matter of scientific consensus.” Breeze Smoke, 18 F.4th at

508; see FDA Technical Memorandum at 11 (noting that risks

to youth are “clear and consistent”). But the reports of

evidence of flavored products’ benefits, the agency found, were

“far from conclusive” and “quite mixed,” particularly due to

relevant differences from product to product. FDA Technical

Memorandum at 11. The agency reasonably drew differing

conclusions from evidence of differing strength.

Finally, the manufacturers urge us to adopt the reasoning

of the Fifth Circuit panel in its decision to grant a stay in Triton.

That stay was in place as this case was briefed and argued, but

has been superseded by the decision on the merits.

Nonetheless, we consider on its own terms and are unpersuaded

by the stay panel’s analysis. See 2022 WL 2799797 at *5-11;

18 F.4th at 506-07. The stay panel, and merits dissent in

accord, over-read the FDA’s statement that it would consider

evidence other than long-term studies as announcing that

“long-term studies were likely unnecessary.” 16 F.4th 1140-

41. Against that asserted baseline, the stay opinion concluded

that the FDA’s rejection of Triton’s application showed the

agency “changed its mind and required the very thing it said it

would not—namely, long-term studies of e-cigarettes.” Id. at

1135. But again, the FDA has all along required “valid

scientific evidence,” and its denial orders explained how the

survey data petitioners submitted fell short of the mark.

27

b. No change to substantive standard

The manufacturers also argue that the FDA pulled a bait-

and-switch of the substantive standard it applied in reviewing

their applications. See Pet’rs Reply Br. at 4-8. The

manufacturers argue they relied on the FDA’s 2019 Guidance,

which included a section describing the types of “comparison

products” applicants should reference to show their products’

benefits. See 2019 Guidance at 13-14. There, the FDA

emphasized that applicants should compare their products to

“tobacco products in the same category or subcategory.” Id. at

13. But the manufacturers claim they were unfairly surprised

to see the FDA explain in its denial order that it looked for

evidence “that could potentially demonstrate [an] added benefit

to adult users of flavored ENDS [electronic nicotine delivery

system] over an appropriate comparator tobacco-flavored

ENDS.” Pet’rs Reply Br. at 5 (citing J.A. 47, 823, 1029, 1236).

The manufacturers contend that “nobody reading [the 2019

Guidance] would believe that it was necessary to compare a

particular e-liquid to a tobacco-flavored e-liquid,” id. at 6-7,

and that accordingly “FDA flunked Petitioners for failing to

answer a question that it never even asked,” id. at 8. They

claim that doing so both worked a change to the substantive

standard of review and upset their interest in reliance on the old

standard.

This argument is far off base. The governing statute

expressly asks for evidence concerning whether an applicant’s

“tobacco product presents less risk than other tobacco

products,” 21 U.S.C. § 387j(b)(1)(A), and the FDA’s 2019

Guidance told manufacturers that the agency would look for

comparisons between the proposed product and “tobacco

products in the same category or subcategory,” 2019 Guidance

at 13. Petitioners knew they needed to show that their flavored

e-liquids were sufficiently beneficial to adult smokers to offset

28

the risks from flavored products’ particular attractiveness to

youth. It was widely known when petitioners prepared and

submitted their applications that the FDA had identified e-

cigarette flavors as a driver of soaring youth rates of tobacco

uptake, use, and addiction. Petitioners’ own unflavored or

tobacco-flavored e-liquids were an obvious, otherwise-similar

comparator against which to gauge whether the added risks of

their flavored e-liquids are overcome by those products’ added

benefits to adult smokers. The manufacturers’ own insistence

that device type is the primary feature driving ENDS popularity

among youth does not render arbitrary or surprising the FDA’s

attention to the relative risks and benefits of flavored versus

unflavored products of the same type.

The manufacturers cannot identify any misdirection in the

2019 Guidance. The FDA’s product-specific analysis in the

denial orders is fully consistent with its Guidance. The 2019

Guidance identified what types of comparisons the FDA would

be looking for. The denial orders applied that guidance to

examine whether the added risk of these manufacturers’

flavored e-liquids over otherwise-comparable products without

flavoring is outweighed by greater added benefit to adult

smokers of the flavored over unflavored versions. That is a

straightforward application of the FDA’s stated standard.

There was nothing new about the FDA’s review of the

manufacturers’ applications that deprived them of fair warning.

See Breeze Smoke, 18 F.4th at 507. Because the 2019 Guidance

gave fair notice of the analysis the agency would perform and

the purpose of those comparisons, we hold the agency did not

create unfair surprise by focusing on comparisons between

otherwise similar flavored and nonflavored products.

29

2. The FDA’s Decision Not to Review Each Youth Access

Plan Was Immaterial

The manufacturers also argue that the FDA acted

arbitrarily and capriciously by failing to reasonably explain

why it did not review their individual marketing plans. They

make plausible arguments that the agency erred in acting as it

did without a more persuasive explanation. But the

manufacturers did not show that that error prejudiced them in

any way. We accordingly hold that, even assuming the FDA’s

explanation was error, that error was harmless.

In their briefing, and even when specifically pressed on the

point at argument, the manufacturers were unable to identify

any prejudice they suffered from the FDA’s lack of

individualized review of their plans to prevent youth access to

their flavored e-liquids. The Tobacco Control Act applies the

APA’s standard of review, see 21 U.S.C. § 387l(b), which

instructs courts to take “due account . . . of the rule of

prejudicial error” and thereby incorporates a harmless error

rule, 5 U.S.C. § 706; see Nat’l Assn. of Home Builders v.

Defenders of Wildlife, 551 U.S. 644, 659-60 (2007). Under that

rule, “the burden of showing that an error is harmful normally

falls upon the party attacking the agency’s determination.”

Shinseki v. Sanders, 556 U.S. 396, 409 (2009); see Air Canada

v. Dep’t of Transp., 148 F.3d 1142, 1156 (D.C. Cir. 1998).

When an agency’s mistake plainly “had no bearing” on the

substance of its decision, we do not grant a petition for review

based on that mistake. See Mass. Trs. of E. Gas & Fuel Assocs.

v. United States, 377 U.S. 235, 248 (1964).

We apply that harmless error rule consistent with SEC v.

Chenery Corp., which requires courts to refrain from assessing

agency action on bases the agency itself did not supply. 332

U.S. at 196. “[W]ith limited exception,” our circuit has noted,

30

Chenery “does not allow us to affirm an agency decision on a

ground other than that relied upon by the agency.” Manin v.

NTSB, 627 F.3d 1239, 1243 (D.C. Cir. 2011). But “when there

is not the slightest uncertainty as to the outcome of a

proceeding on remand, courts can affirm an agency decision on

grounds other than those provided in the agency decision.” Id.

at 1243 n.1 (quoting Envirocare of Utah, Inc. v. Nuclear Regul.

Comm’n, 194 F.3d 72, 79 (D.C. Cir. 1999)) (formatting

modified); accord Grossmont Hosp. Corp. v. Burwell, 797 F.3d

1079, 1086 (D.C. Cir. 2015). Chenery, the Supreme Court has

elaborated, was designed to “assur[e] that initial administrative

determinations are made with relevant criteria in mind.” Mass.

Trs. of E. Gas & Fuel, 377 U.S. at 248. When an asserted error

clearly did not affect the outcome, applying Chenery and its

progeny “would not advance the purpose they were intended to

serve.” Id. In short, “Chenery does not require that we convert

judicial review of agency action into a ping-pong game,”

lobbing the matter from agency to court and back. NLRB v.

Wyman-Gordon Co., 394 U.S. 759, 766 n.6 (1969). Where a

petitioner had ample opportunity yet failed to show that an

agency error harmed it, vacatur and remand to give the agency

an opportunity to fix the error is unwarranted.

The manufacturers raise serious arguments that the FDA

erred in deciding not to review their marketing plans on the

ground that they presented nothing new, and that its

explanation for the non-review fell short insofar as the FDA

assumed the contents of plans without reading them. But those

plans are in the record for all to read, and they vindicate the

FDA’s assumption. Even the manufacturers do not claim that

FDA’s consideration of their marketing plans could have

changed the agency’s decision on their applications. The

measures they highlight in their marketing plans are not

materially different from those the FDA had previously found

insufficient to stem the surge in youth e-cigarette use. In their

31

briefing and at argument petitioners identified examples of the

youth access limitations they proposed and that they assert the

FDA erred in not specifically reviewing. See Pet’rs Br. at 39;

Oral Argument Tr. at 12. Yet their plans—to require

customers’ self-verification of age at the point of sale and to

use what they characterize as less vibrant marketing

unappealing to youth—track measures the FDA in its 2020

guidance deemed inadequate to prevent or otherwise materially

limit youth access to flavored ENDS. Compare Pet’rs Br. at

39, with 2020 Guidance at 42-44. The manufacturers fail to

explain why their proposals will prevent youth access where

other, similar measures did not.

Petitioners thus cannot identify how they were harmed

from the FDA’s failure to consider essentially the same

measures it had previously rejected. Indeed, they offered no

refutation whatsoever to the FDA’s pointed assertions that the

manufacturers “do not claim to have proposed access measures

different from those that FDA previously found inadequate,”

and accordingly that “there is no basis to conclude that any

harm flowed from the asserted failure-to-consider error.”

Compare FDA Br. at 38-39, with Pet’rs Reply Br. at 8-9. In

response to questioning on the point at oral argument, the

manufacturers again did not identify any harm they

experienced from FDA’s failure to have reviewed their

marketing plans, instead simply referring to the familiar and

demonstrably inadequate measures listed in their opening brief.

See Oral Argument Tr. at 12 (responding “well, no” to the

question whether manufacturers’ plans had proposed “anything

qualitatively different” from measures the FDA had previously

examined and deemed lacking); id. at 15 (responding “no” to

the question whether manufacturers’ marketing plans would

alone have altered the FDA’s analysis enough to warrant

granting the petition, absent their other challenges to purported

changing FDA guidance). In light of that failure, the

32

petitioners have also forfeited any argument that the alleged

error prejudiced them.

We accordingly assume without deciding that the FDA

erred in not individually reviewing the manufacturers’

marketing plans and offering an apparently circular

explanation for that approach. The manufacturers’ inability to

identify how the FDA’s denial orders could have come out

differently if only it had known the contents of their plans

defeats their request for vacatur and remand to the FDA for

further consideration.

3. The Other Arbitrary and Capricious Challenges Fail

None of the manufacturers’ other arbitrary and capricious

challenges has merit. See Pet’rs Br. at 34-49; Reply Br. at 8-11.

The manufacturers contend the FDA ignored a material

distinction between open and closed systems. These

manufacturers seek to market e-liquids used to refill open

systems, and they say the FDA erred in treating public health

data regarding the risks of youth access to flavored closed-

system e-cigarettes as applicable to flavored products used with

open systems. But the FDA did acknowledge the distinct

products, noting in its denial orders that “there may be

differential appeal of certain product styles.” FDA Technical

Memorandum at 7. The FDA then reasonably explained that it

nonetheless found the scientific literature about public health

risks to youth applicable to petitioners’ products, because

“across these different device types, the role of flavor is

consistent.” Id. The FDA cited data from the 2020 National

Youth Tobacco Survey, among other sources, to support its

conclusion that youth preference for flavor “is consistently

demonstrated across large, national surveys and longitudinal

cohort studies.” Id.

33

By contrast, the FDA noted that youth preferences for

different device types are “fluid,” and that youth readily shift

among devices. Id. at 8. For example, the FDA cited data

showing that “the removal of one flavored product option

prompted youth to migrate to another [device type] that offered

their desired flavor options.” Id. This fact “underscore[d] the

fundamental role of flavor in driving appeal.” Id. The FDA

supported its conclusion with substantial evidence, and we

have no basis to second-guess it.

The FDA also did not impermissibly treat like products

differently, as the manufacturers contend. The FDA concedes

that it inadvertently denied approval to some manufacturers

who had submitted results from randomized controlled trials

comparing their flavored products to non-flavored cigarettes;

the agency reports that it is reconsidering those applications

separately. See FDA Br. at 47-48; see also FDA 28(j) Letter

(dated Apr. 13, 2022) at 2. But the manufacturers here do not

contend that they submitted similar studies for their products.

Accordingly, there is no inconsistency between the FDA’s

distinct treatment of these different applications.

Finally, the FDA was not required to consider alternative

regulatory approaches before denying the manufacturers’

applications for premarket approval. The statute requires that

applicants make a certain showing before their products can be

approved for sale and provides that, where an applicant fails to

make that showing, the FDA “shall deny” the application. See

21 U.S.C. § 387j(c)(2)(A). After reviewing their applications,

the FDA here found that these manufacturers had failed to

make the requisite showing. The statute requires no more.

34

III. CONCLUSION

For all of the above reasons, we deny the petitions for

review.

So ordered.

KATSAS, Circuit Judge, concurring: This case arises from

the Food and Drug Administration’s denial en masse of

thousands of applications for permission to sell flavored e-

cigarettes or liquid cartridges for use in flavored e-cigarettes.

The FDA denied the applications primarily because flavored e-

cigarettes appeal to children. Yet the agency refused even to

consider any of the proposed marketing plans for these

products, which bear critically on the risk that they pose to

children. The FDA reasoned that because marketing plans it

had previously reviewed were inadequate, the agency could

simply stop reviewing the plans for other products, “for the

sake of efficiency.” FDA, Technical Project Lead (TPL)

Review of PMTAs (2021), at 11 n.xix (J.A. 44). The FDA earns

points for candor, but the Administrative Procedure Act

requires more. As the Fifth Circuit has explained, “it’s

unreasonable for the FDA to stop looking at proposed

[marketing] plans because past ones have been

unpersuasive.” Wages & White Lion Invs., LLC v. FDA, 16

F.4th 1130, 1137 (5th Cir. 2021); see also Breeze Smoke, LLC

v. FDA, 18 F.4th 499, 507 (6th Cir. 2021) (“The FDA likely

should have more thoroughly considered Breeze Smoke’s

marketing plan.”). 1

Despite the FDA’s obvious error, I join the Court’s

opinion in full. As Judge Pillard persuasively demonstrates,

the petitioners here made no serious argument that the FDA’s

failure to consider their marketing plans was prejudicial, as

required for them to obtain relief under the APA. See 5 U.S.C.

§ 706 (“due account shall be taken of the rule of prejudicial

1

The Fifth Circuit later held that the FDA’s failure to consider

the full marketing plans at issue in Wages & White Lion Investments

was not arbitrary. Wages & White Lion Invs., LLC v. FDA, No. 21-

60766, slip op. at 19–23 (5th Cir. 2022); but see id. at 32–35 (Jones,

J., dissenting). In that case, however, the FDA claimed to have

reviewed at least “a summary of the marketing plans.” Id. at 22

(majority). Here, the FDA did not claim to have done even that.

2

error”). Moreover, I agree that the petitioners’ other arguments

lack merit. In joining the Court’s opinion, I do not understand

it to foreclose the possibility of our finding prejudicial error in

other cases where manufacturers press the prejudice point more

forcefully.