by Aster O’Leary*
In response to what has been dubbed a “youth vaping epidemic,” the Food and Drug Administration (“FDA”) has recently cracked down on non-tobacco-flavored Electronic Nicotine Delivery Systems (“ENDS”), which middle and high school students prefer over tobacco-flavored ENDS products. Recognizing that the ENDS industry is relatively new and constantly evolving, the FDA declined to mandate the inclusion of certain types of scientific studies in its guidance to the industry. However, many flavored ENDS manufacturers feel that the FDA pulled a “surprise switcheroo” when denying many of their Premarket Tobacco Product Applications (“PMTA”).1 In the denials, the FDA explained that the applications lacked long-term studies and/or controlled investigations that demonstrated that the flavored products were “appropriate for the protection of the public health.”2 Additionally, the manufacturers complained that for many of their applications, the FDA refused to consult their marketing plans, which the FDA had previously emphasized were of tantamount importance. This Contribution argues that the FDA did not violate the Administrative Procedure Act (“APA”) by modifying its approach to PMTA review. It first demonstrates denying PMTAs because they lacked long-term studies is permitted under the FDA’s flexible approach to weighing ENDS’ risks and benefits to society as a whole. It then argues that the FDA’s refusal to consult manufacturers’ marketing plans, while arbitrary and capricious, is in most cases harmless error. It concludes by questioning whether the FDA should be tasked with regulating an inherently harmful category of products in the first place.
The Family Smoking Prevention and Tobacco Control Act of 2009 (“TCA”) amended the Food, Drug, and Cosmetics Act (“FDCA”) to officially place tobacco products within the Food and Drug Administration’s (“FDA”) regulatory jurisdiction.3 Specifically, the TCA authorizes the FDA to regulate tobacco products including “cigarettes, cigarette tobacco, roll-your-own tobacco, and smokeless tobacco,” as well as any other tobacco products that the FDA deems to be subject to the TCA.4 Electronic Nicotine Delivery Systems (“ENDS”) skyrocketed in popularity after the TCA’s passage but remained unregulated. Alarmed by high youth usage rates, the FDA used its deeming authority under the TCA to bring ENDS products within its regulatory purview in 2016.5 Specifically, the FDA’s “Deeming Rule” designated ENDS products and their component e-liquids as “new tobacco products” subject to FDA regulation.6
Once subject to the TCA, manufacturers of “new tobacco products” must submit Premarket Tobacco Product Applications (“PMTA”) and receive authorization from the FDA before releasing their products on the market.7 Because all ENDS products, including those already on the market in 2016, were newly subject to the PMTA requirement, the FDA agreed to defer enforcement against certain manufacturers for a specified “compliance period,” ending on September 9, 2020.8
The FDA must deny a PMTA if it finds “there is a lack of showing that permitting such tobacco product to be marketed would be appropriate for the protection of the public health.”9 To determine whether a tobacco product is appropriate for the protection of the public health, the FDA must examine “the risks and benefits to the population as a whole, including users and non-users of the tobacco product,” considering “the increased or decreased likelihood that existing users of tobacco products will stop using such products,” and “the increased or decreased likelihood that those who do not use tobacco products will start using such products.”10
After promulgating the Deeming Rule, the FDA developed a series of enforcement priorities and guidance documents aimed at helping ENDS manufacturers to comply with PMTA requirements. While the FDA initially took a laissez-faire approach to PMTA review and enforcement, it ultimately changed course due to new data revealing a “78 percent increase in current e-cigarette use among high school students and a 48 percent increase among middle school students.”11 In 2019, the FDA issued guidance on PMTAs, which recommended that manufacturers include “well-controlled investigations” and “other ‘valid scientific evidence’ if found sufficient to evaluate the tobacco product.”12 The FDA also stated that, given the newness of ENDS products and the evolving nature of the market, it did “not expect that applicants [would] need to conduct long-term studies to support an application.”13 In the months that followed, e-cigarette use among youth continued to skyrocket.14 In April 2020, the FDA issued a final enforcement guidance, which outlined its intention to crack down on the ENDS products most attractive to youth: flavored,15 cartridge-based vapes and e-cigarettes.16 Nonetheless, the FDA reiterated that its PMTA review process was flexible and that it would continuously adjust its enforcement priorities and review process to accommodate new information.
By September 2021, the FDA had issued Marketing Denial Orders (MDOs) in response to 946,000 PMTAs submitted by flavored ENDS manufacturers.17 As of January 2024, not a single flavored ENDS manufacturer had received authorization to market their product.18 In many MDOs, the FDA applied a “comparative efficiency” framework.19 In doing so, it found the applicant did not show that their flavored ENDS product was better than tobacco- or menthol-flavored ENDS products at promoting smoking cessation in adults and, even if it was, the flavored product’s purported benefits did not outweigh the risk of use by minors.20 In several MDOs, the FDA stated that “robust and reliable evidence could have been provided using a randomized controlled trial and/or longitudinal cohort study that demonstrated the benefit of [a manufacturer’s] flavored ENDS products over an appropriate comparator tobacco-flavored ENDS.”21 This language, while ambiguous, implies that such evidence may have changed the FDA’s decision.
Aggrieved flavored ENDS manufacturers challenging their MDOs in federal circuit courts argue that the FDA’s comparative efficiency framework went beyond the scope of its statutory authority and that the FDA unfairly imposed new testing requirements on flavored ENDS manufacturers without proper notice.22 Additionally, manufacturers argue that the FDA unfairly denied their applications without considering their marketing plans, which the FDA had previously stated were of tantamount importance in its 2019 PMTA Guidance.23 ENDS manufacturers dubbed the FDA’s actions an arbitrary and capricious “surprise switcheroo,” in violation of the Administrative Procedure Act (“APA”).24
Some manufacturers also contend that the FDA violated the APA by failing to notify flavored ENDS manufacturers that they would be subject to heightened evidentiary standards in the PMTA review process.25 The Fifth Circuit agreed in Wages & White Lion Investments, LLC, v. FDA, determining that FDA guidance documents unfairly imposed new requirements on petitioner ENDS manufacturers to provide long-term comparative efficacy studies without adequate notice or justification for the change in the agency’s position.26 The Fifth Circuit pointed to discrepancies between the 2019 PMTA Guidance, which specified the FDA did not expect longitudinal studies to be a necessary component of PMTAs, with an August 2021 press release touting the issuance of 55,000 MDOs to flavored ENDS manufacturers which stated, “[b]ased on existing scientific evidence and the agency’s experience conducting premarket reviews, the evidence of benefits to adult smokers for such products [that the FDA would consider to be adequate] would likely be in the form of a randomized controlled trial or longitudinal cohort study. . . .”27 Because manufacturers did not provide such evidence, their PMTAs were denied.
However, the FDA never changed its policy towards ENDS manufacturers in the first place — it simply fulfilled its statutory mandate to only approve PMTAs for products whose benefits to the population as a whole outweigh their risks. As the Fourth Circuit explained in Avail Vapor, LLC v. FDA, the “FDA never guaranteed that manufacturers could carry their evidentiary burden under the TCA without providing long-term data.”28 Because flavored ENDS products pose a greater health risk than non-flavored ones due to their unique appeal to youth, it makes sense that “it is especially challenging for marketers to make a case that those products are appropriate for the protection of public health.”29 Moreover, the 2019 PMTA Guidance neither states nor implies that the FDA must approve PMTA applications that contain scientific evidence manufacturers consider compelling. Rather, it affords the FDA discretion to evaluate evidence on a case-by-case basis and make determinations in the public’s best interest.30
Even if the FDA did violate the APA by neglecting to evaluate flavored ENDS manufacturers’ marketing plans as part of the PMTA review process, such a violation would be harmless error. In its pre-MDO guidance, the FDA did state that manufacturers’ marking plans were “critical to the success of e-cigarette applications,31 and that it “will review . . . marketing [plans] to evaluate potential youth access to, and youth exposure to the labeling, advertising, marketing, or promotion of, a new tobacco product.”32 However, the FDA denied PMTAs en masse due to deficiencies in scientific evidence alone, without reviewing manufacturers’ marketing plans. Two internal memoranda from 2021, both rescinded not long after circulation, stated the FDA did not evaluate marketing plans “for the sake of efficiency” because it was “not aware of access restrictions that, to date, have been successful in sufficiently decreasing the ability of youth to obtain and use [electronic nicotine-delivery systems].”33
While failing to consider marketing plans constitutes a policy change that should have been properly communicated to ENDS manufacturers ex ante, it is clear that even the best marketing plan would have been insufficient when weighed against the risk of youth use. Under its flexible mandate to approve only ENDS products it deems appropriate for the protection of the public health, the FDA reasonably concluded that no marketing plan, regardless of its ingenuity, could overcome other deficiencies in the PMTA.34 In Magellan Tech, Inc. v. FDA, the Second Circuit held exactly that: because there was no indication that petitioner’s marketing plan would have made up for other deficiencies identified in the application, the FDA’s disregard of said marketing plan—if an error at all—was harmless.35
For the Magellan Tech court, it was easy to make a “harmless error” determination. In that case, petitioner submitted a cookie cutter marketing plan that consisted only of strategies the FDA had explicitly deemed insufficient in previous guidance.36 This negated petitioner’s argument that it had a legitimate reliance interest in its marketing plans being considered in the PMTA review process.37 However, in Bidi Vapor LLC v. FDA, which involved a more innovative marketing plan, the Eleventh Circuit held that the FDA could not determine said plan was inadequate without consulting it first.38 That Court analogized the FDA’s reliance on experience — namely, that it has yet to see a marketing plan good enough to offset risk of youth appeal —– to “a federal district court judge refusing to hear a convicted criminal defendant at sentencing about his reformation plans or the impact on his family because, in the judge’s experience, he found that those things do not matter.”39
This criminal defendant analogy is an obvious exaggeration, as the denial of one’s liberty is not comparable to the denial of a vape manufacturer’s PMTA. Additionally, while criminal sentencing is extremely difficult to appeal, an ENDS manufacturer can simply file a new PMTA if denied FDA approval, this time with an eye for the substance, including scientific studies, which the FDA deems most probative of whether a product is appropriate for the protection of the public health.40 In FDA v. Wages & White Lion Investments, LLC, currently before the Supreme Court after the FDA appealed the Fifth Circuit’s ruling to set aside its MDOs, Justice Brett Kavanaugh questioned vape manufacturers’ counsel about the decision to pursue litigation instead of simply filing a new PMTA.41 White Lion explained that if forced to start again from scratch, they would have to “close their doors since the FDA routinely takes 3–4 years to review PMTAs.”42 This would place a heavy burden on the PMTA reapplicant, but a justified one. Otherwise, unsafe ENDS products might end up on the market donning with the FDA’s seal of approval. Additionally, as science evolves and the FDA continues streamlining its PMTA review process, reapplicants like White Lion may receive marketing authorization on an expedited timeline.43
Ultimately, the FDA’s approach to regulating ENDS is clearly within the bounds of the APA, or alternatively constitutes harmless error. However, despite their illegality, flavored ENDS products are easily obtained both in physical retail establishments and online, often by minors. Even though the FDA has broad discretion under its statutory mandate to regulate ENDS products, the agency’s current approach leaves much to be desired. This reality raises an important, overarching question: is the FDA — an agency historically tasked with ensuring socially beneficial drugs and devices are safe and effective — the right agency to regulate this inherently harmful category of products in the first place?
* Aster O’Leary is a J.D. Candidate (2025) at New York University School of Law. This Contribution is an abbreviated, updated version of a longer paper written as part of the Seminar FDA Law, Policy, and Advocacy: An Introduction to Food and Drug Law and How FDA Regulates (Fall 2023). This Contribution distills one view on a multifaceted regulatory challenge, and the views herein do not necessarily represent the author’s views.
1. Wages & White Lion Invs., L.L.C. v. FDA, 90 F.4th 357, 362 (5th Cir. 2024) cert. granted, 144 S. Ct. 2714 (2024).
2. 21 U.S.C. § 387j(c)(2)(A).
3. Federal Food, Drug, and Cosmetic Act, 21 U.S.C. § 387.
4. 21 U.S.C. § 387a(b).
5. Reagan-Udall Found., Operational Evaluation of Certain Components of FDA’s Tobacco Program 8 (Dec. 2022).
6. 21 C.F.R. §§ 1100, 1140, & 1143 (2016).
7. 21 U.S.C. § 387j(a)(2).
8. See Am. Acad. of Pediatrics v. Food & Drug Admin., 379 F. Supp. 3d 461, 472 (D. Md. 2019).
9. 21 U.S.C. § 387j(c)(2)(A).
10. 21 U.S.C. § 387j(c)(4)(A)–(B).
11. Press Release, Scott Gottlieb, Comm’r, Food & Drug Admin, Statement from FDA Commissioner Scott Gottlieb, M.D., on proposed new steps to protect youth by preventing access to flavored tobacco products and banning menthol in cigarettes, U.S. Food & Drug Admin. (Nov. 15, 2018), https://www.fda.gov/news-events/press-announcements/statement-fda-commissioner-scott-gottlieb-md-proposed-new-steps-protect-youth-preventing-access.
12. 21 U.S.C. § 387j(c)(5)(A)–(B).
13. U.S. Food & Drug Admin., Premarket Tobacco Product Applications for Electronic Nicotine Delivery Systems (Revised)* 14 (2023).
14. U.S. Food & Drug Admin., Enforcement Priorities for Electronic Nicotine Delivery System (ENDS) and Other Deemed Products on the Market Without Premarket Authorization (Revised)* 8–9 (2020).
15. Id. at 3 defines “flavored” as any flavor that is not tobacco or menthol.
16. See generally id.
17. Press Release, Mitch Zeller, Director, Food & Drug Admin. Ctr. for Tobacco Prods. (CTP), Perspective: FDA’s Progress on Tobacco Product Application Review and Related Enforcement, U.S. Food & Drug Admin. (Sep. 9, 2021), https://www.fda.gov/tobacco-products/ctp-newsroom/perspective-fdas-progress-tobacco-product-application-review-and-related-enforcement.
18. Brendan Pierson, FDA ordered to reconsider denial of approval for vape products, Reuters (Jan. 3, 2024), https://www.reuters.com/legal/fda-ordered-reconsider-denial-approval-vape-products-2024-01-03/.
19. See Avail Vapor, LLC v. FDA, 55 F.4th 409, 418 (4th Cir. 2022) (summarizing contents of petitioner ENDS manufacturers’ MDOs).
20. Id.
21. Id.
22. Id.
23. See Wages & White Lion Invs., 90 F.4th at 362 (holding that the FDA violated the APA by imposing heightened evidentiary requirements on flavored ENDS manufacturers without notice).
24. Id. at 386.
25. Id. at 378.
26. Id. at 370.
27. FDA News Release, FDA Denies Marketing Applications for About 55,000 Flavored E-Cigarette Products for Failing to Provide Evidence They Appropriately Protect Public Health, U.S. Food & Drug Admin. (Aug. 26, 2021), https://perma.cc/LCD8-VWGQ.
28. Avail Vapor, 55 F.4th at 422 (emphasis added).
29. See Prohibition Juice Co. v. FDA, 45 F.4th 8, 13 (D.C. Cir. 2022) (holding that the FDA properly weighed the risks and benefits of flavored ENDS products to the population as a whole in issuing MDOs).
30. For an example of such phrasing, see U.S. Food & Drug Admin., Premarket Tobacco Product Applications for Electronic Nicotine Delivery Systems (Revised)* at 14 (“These studies, used as a basis to support a PMTA, should be relevant to the new tobacco product”).
31. Premarket Tobacco Product Applications and Recordkeeping Requirements, 84 Fed. Reg. 50566, 50619 (proposed Sep. 25, 2019) (to be codified at 21 C.F.R. §§ 1100, 1107, & 1114).
32. Id. at 50581 (emphasis added).
33. See Bidi Vapor LLC v. FDA, 47 F.4th 1191, 1201 (11th Cir. 2022).
34. See Id. (internal quotations omitted) (describing how the FDA justified denying PMTAs because the PMTAs lacked sufficient evidence demonstrating that the products’ benefits to adult users outweighed their risks to youth, it could not “find that permitting the marketing of [the] new tobacco products would be appropriate for the protection of the public health,” even if the manufacturer proffered an extremely innovative marketing plan).
35. See 70 F.4th 622, 631 (2d Cir. 2023).
36. Id. at 631 (stating that as part of determining the FDA’s actions, if in error, were harmless, the court notes that petitioner does not explain how its marketing strategies differ from similar measures the FDA had uniformly rejected or why conditions had changed such that the measures would now be effective).
37. See U.S. Food & Drug Admin., Enforcement Priorities for Electronic Nicotine Delivery System (ENDS) and Other Deemed Products on the Market Without Premarket Authorization (Revised)* at 41 (mentioning that sales-access restrictions on their own had failed to reduce youth use and would therefore be unlikely to tip the balance between adult benefits and youth risks).
38. Bidi Vapor LLC, 47 F.4th at 1205—1206.
39. Id. at 1204.
40. Amy Howe, Justices hear FDA case on flavored vapes, SCOTUSblog (Dec. 2, 2024), https://www.scotusblog.com/2024/12/justices-hear-fda-case-on-flavored-vapes/.
41. Transcript of Oral Argument at 76–77, FDA v. Wages & White Lion Invs., LLC, No. 23-1038 (U.S. argued Dec. 2, 2024).
42. Id. at 76.
43. Press Release, Food & Drug Admin. Ctr. for Tobacco Prods. (CTP), FDA Plans to Launch Updated Submission Portal for New Tobacco Product Applications in 2025, U.S. Food & Drug Admin. (July 15, 2024).