FDA vape regulation "untethered from reality"

FDA's proposals to regulate flavored vapes exist in an imaginary world untethered from reality-based behaviors, real-world markets, and predictable unintended consequences of excessive regulation.

This is a long article; a comment on the FDA’s Draft Guidance for Industry: Flavored ENDS Premarket Applications – Considerations Related to Youth Risk

Comment by: Clive Bates, Stefanie Miller, Brad Rodu, Sally Satel, and David Sweanor. Available as a PDF (18 pages) at the download link below.

FDA Flavored Ends PMTA Guidance Comment Final 8 May 2026

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Regulations.gov Docket: FDA-2026-D-1817. Comment submitted on May 8, 2026 - Tracking number mov-yo5z-3kkf.

Summary - the Draft Guidance is untethered from reality

The health and well-being of over 60 million Americans, by far the majority being adults, are directly affected by Draft Guidance that shapes the lawful market for safer alternatives to smoking, including popular flavored ENDS.

Figure 1: US adult nicotine use (NSDUH, 2023)

Despite the importance of these policies to millions of Americans, the Draft Guidance is untethered from reality and is not fit for purpose. The public health standard, “Appropriate for the Protection of Public Health” (APPH), must reflect real-world market conditions, actual human behavior, and the most likely consequences of authorization decisions on public health.

In summary, the guidance is defective in the following seven ways, which also form the framework for our full-length response, which continues below this summary.

1. A gross mischaracterization of ENDS risk to youth. For many young people who report current nicotine use, ENDS use has displaced smoking: in the absence of ENDS, they would likely be smoking today. This is a major public health benefit, yet the FDA ignores it.

2. An inadequate basis for claiming that flavors cause ENDS uptake. There is no compelling evidence that flavors cause vaping uptake or that denying flavored products prevents uptake, only that young people have preferences for certain flavors. Nicotine use is driven by a wide range of psychosocial risk factors that flavor policies cannot address.

3. An insufficient focus on reducing adult smoking. There are 34 times as many adult tobacco and nicotine users (≥18) as youth (<18). Adult smoking is the most urgent public health problem in terms of the number of people at immediate and severe risk and the opportunity to make health gains through switching to regulated ENDS products.

4. A disturbing indifference to the vast illegal market for ENDS products. The Draft Guidance includes no accounting of the impacts of the dominant illicit market that serves users of all ages with unregulated flavored vaping products. The FDA’s effort to “protect youth” from flavored products exposes them to risky, unregulated products and to criminal activity.

5. A perverse regulatory imbalance in favor of deadly combusted tobacco products. There are vastly more smoking products available for sale legally (15,000) than ENDS (45), pouches (30), or heated tobacco (19). There are two orders of magnitude more smoking products, yet smoke-free products face far higher barriers to entry and a process that takes so long that many are obsolete by international standards.

6. An unworkable framework for testing comparative efficacy. The tests for comparative efficacy are so poorly specified as to be unworkable for most manufacturers. Nothing in the Tobacco Control Act requires or justifies these burdensome tests.

7. The unlawful creation of a product standard outside the required rulemaking process. The Draft Guidance creates a poorly specified de facto product standard, but without the required rulemaking procedure. FDA has not subjected its own policymaking to an assessment of whether it is “appropriate for the protection of public health.”

In conclusion, we propose a range of non-marginal reforms consistent with the Tobacco Control Act and based on a recent report for the American Enterprise Institute, Regulating the Tobacco and Nicotine Market in the American Public Interest: A Reform Agenda for the FDA (September 2025). To summarize:

• Focus pre-market evaluation on product safety, packaging, branding, and marketing, and address most behavioral and population effects post-market.

• Establish market-wide surveillance, including illicit trade, to catch real-world problems as they emerge.

• Address adverse population trends through post-market corrective action (authorized products) or enforcement (illicit products) rather than pre-market guesswork.

• Give due weight to the much larger adult smoking population at far greater and more imminent risks in assessing APPH.

• Regain control of the market by crowding out illicit trade: design a process capable of authorizing c. 4,000 ENDS products, removing barriers to entry and achieving a ten-fold reduction in application costs, while meeting the statutory 180-day timetable.

1. Gross mischaracterization of ENDS risk to youth

The characterization of ENDS risk to youth does not account for the likelihood that many young people who have taken up vaping since 2011 would otherwise have taken up smoking. This beneficial diversion effect is highly significant for public health, yet is ignored in the Draft Guidance. It is possible to argue that its magnitude is small (though we doubt it is), but our point is that the FDA does not even acknowledge this effect.

When assessing the impact of a technology, the appropriate comparison is with a counterfactual (what happens without the technology’s introduction), not with a hypothetical idealized world in which there is no nicotine use or smoking. The impact of the technology arises from how it modifies likely pathways followed by young people as they age (including through their young adult years) and on adults who are already nicotine users compared to the counterfactual.

The history of youth vaping from the early part of the past decade (Figure 2, below) suggests that vaping has substantially displaced smoking among youth. Youth smoking is now at a very low level - and much of that success is likely attributable to youth vaping. The public health impact of youth vaping cannot be assessed without considering its effects on youth smoking, as well as on adult smoking.

Figure 2: Evolution of US youth smoking and vaping (chart by Brad Rodu, Tobacco Truth)

It is trivially obvious that everyone is born a non-user. However, there are two distinct types of youth ENDS users: those who, in the absence of ENDS, would have taken up combustible tobacco use and those who would have remained nicotine-abstinent. Vaping provides a large benefit to the former and a relatively small detriment to the latter, given the respective risks of smoking and vaping.

The sources cited by the FDA to underpin its interpretation [Park-Lee et al. 2024, Brostron et al. 2020] do not address what would happen in the absence of ENDS and, therefore, do not provide a basis for characterizing the risks posed by ENDS to young people.

Questions for FDA to address in final guidance:

• Does the FDA recognize that some young people with a high propensity to smoke or use nicotine have benefited from vaping instead of smoking?

• Does the FDA accept that the APPH framework requires the assessor to consider the displacement of smoking by vaping in young people as part of an evaluation of the public health standard? If not, with what justification?

• If displacement of smoking by vaping in young people is recognized as a public health benefit, how should its magnitude be assessed and incorporated into decision-making about authorizing flavors?

• If vaping has had a net positive effect on young people because of the near eradication of smoking, what are the implications for the FDA’s policy on flavored ENDS?

2. Inadequate basis for claiming that flavors cause vaping uptake

In section 1 above, we show why it is inappropriate in the context of APPH to assume that ENDS uptake is harmful to youth. However, the guidance makes a further conceptual error in assuming that observations of flavor preferences provide causal explanations for youth vaping (or nicotine) uptake or that not authorizing such products would reduce vaping or nicotine use. In fact, repeatedly, the Draft Guidance refers to flavored ENDS products as a “known” and “substantial” risk to youth. However, neither the Draft Guidance nor the current body of scientific literature, including the review of real-world youth use, supports this assertion.

The fact that young people choose flavored vaping products is well established and not contested. However, this observation alone cannot show what they would do in the absence of popular flavored vapes. FDA implicitly assumes they would remain nicotine-abstinent if flavored ENDS were unavailable or if the FDA does not authorize flavored vaping products.

In response to a de facto ban on flavors deemed appealing to youth (the current situation), adolescents may adopt a wide range of behavioral responses. These include using authorized vapes, using illicit flavored vapes, adding their own flavors, trying cigarette smoking, using heated tobacco, using FDA-authorized pouches, or adopting a different form of risk behavior, such as cannabis use. The guidance does not even recognize this fluidity in behavioral responses, let alone build it into guidance on the assessment of APPH.

In fact, the FDA unintentionally undermines its own case. Even though no lawfully available flavored ENDS products existed at the time of publication of the Draft Guidance, flavored ENDS have dominated youth use for years:

87.6% of youth who currently used ENDS in 2024 reported using flavored products, among which fruit (62.8%) and candy, desserts, or other sweets (33.3%) flavors were the most common. (Draft Guidance, page 10)

There are several reasons to doubt the centrality of flavors in nicotine uptake:

• Research provides other, more important, reasons for youth nicotine uptake. The propensity to use nicotine is driven by a range of well-characterized psychosocial risk factors, including genetic liability, personality traits, mental health comorbidity, and family environment. In the case of smoking, Wellman et al. 2018 summarize:

Ninety-eight conceptually different potential predictors were identified in 53 studies. An increased risk of smoking onset was consistently (i.e., in four or more studies) associated with increased age/grade, lower SES, poor academic performance, sensation seeking or rebelliousness, intention to smoke in the future, receptivity to tobacco promotion efforts, susceptibility to smoking, family members’ smoking, having friends who smoke, and exposure to films. In contrast, higher self-esteem and high parental monitoring/supervision of the child appeared to protect against smoking onset.

The wide range of risk factors that underpin nicotine use has also been covered in depth in several authoritative reports:

• Surgeon General, 2012. Chapter 4 “Social, Environmental, Cognitive, and Genetic Influences on the Use of Tobacco Among Youth.”

• NASEM, 2018, chapter 16 “Combustible Tobacco Cigarette Smoking Among Youth and Young Adults.”

• In the past, over one-third of adolescents were smokers (36.5% of 12th-grade students were past 30-day smokers in 1997, Monitoring the Future). This high level of tobacco use arose without there being widespread uptake of fruit or other supposedly youth-appealing flavors, and it shows young people are willing to use “tobacco flavor,” in the historic case, the flavor of cigarette smoke, if they wish to use nicotine.

• Critically, the sharp decrease in youth vaping that occurred from 2020 to 2025 coincided with a dramatic increase in the number of flavored vaping products available in the market as illicit Chinese flavored vape imports surged. If there were in fact a correlative relationship between the availability of “youth-appealing flavors” and youth use, recent real-world evidence would show it to be a near-perfectly negative relationship. Far more likely, there is no correlation between flavor availability and ENDS initiation, let alone an established causal relationship.

The guidance does not address the issue that has emerged in quasi-experimental economic literature in relation to the effect of ENDS flavor bans on smoking, which indicates that ENDS and cigarettes function as economic substitutes - see, for example, Friedman et al. 2026:

Our findings reveal that ENDS flavor restrictions yield substantial decreases in total ENDS sales, primarily owing to significant declines in flavored ENDS sales alongside nonsignificant increases in unflavored ENDS sales. Further analyses find that ENDS flavor restrictions increase sales of combustible cigarettes, a more harmful product: 11 to 15 additional cigarettes are purchased for every 1 less 0.7 mL ENDS pod sold because of these policies. This uptick in cigarette sales stems primarily from non-menthol cigarettes and includes brands disproportionately used by underage youth.

If the FDA’s policy on flavors functions as a near-total flavor ban, then any possible public health benefit may be overwhelmed by a rebound to smoking, which is substantially more risky.

To make an APPH case against flavored products, the FDA must show that flavors cause vaping uptake AND that the behavioral response to making flavors unavailable legally would not lead to a more harmful pattern of tobacco and nicotine use, for example, smoking or use of unregulated, criminally supplied ENDS. This has not been attempted in the Draft Guidance.

Questions for FDA to address in final guidance:

• What are the underlying causes of youth vaping or nicotine use, and how do limitations on flavored ENDS products modify these causal factors?

• If the Draft Guidance leads to only a limited range of flavored vaping products available in the United States, how would young people respond, and what risks would arise from these responses? How are these risks factored into an assessment of APPH?

3. Insufficient focus on reducing adult smoking

If the FDA is to succeed in its public health mission, it needs to proceed with clarity about the primary public health problem. By any metric of risk and opportunity, the primary public health problem is continuing adult smoking. Flavors are an integral part of the market-wide migration from smoking to smoke-free nicotine use. FDA should consider the following:

First, there are vastly more adults than youth nicotine users (34x). Adult smoking remains the pre-eminent, urgent public health concern, with 38 million Americans continuing to smoke (2023 data, see Figure 3 below using a survey that covers both adults and youth).

Figure 3: Tobacco and nicotine use - youth versus adults

Second, there are orders-of-magnitude differences in risk across tobacco products. Cigarette smoking is the most dangerous by far, and any change to exclusive smoke-free use will yield a substantial reduction in health risk, while uptake of a smoke-free product presents much lower risk.

Third, middle-aged smokers are where the greatest public health opportunities will be lost or gained. The risks of serious smoking-related disease accumulate after age 40 and are reversed with relatively short periods of sustained smoking cessation [see Cho et al. 2024].

Cessation at every age was associated with longer survival, particularly cessation before 40 years of age. Among all ages and compared with continued smoking, cessation of fewer than 3 years potentially averted 5 years of life lost and cessation for 10 or more years averted about 10 years of life lost, yielding survival similar to that of never-smokers.

However, rates of switching from high-risk to low-risk use have been relatively rapid in younger age groups (an unintentional public health success), but slower among older adults (a failure); see Mok et al., 2026; Rodu & Plurphanswat, 2024; and Foxon et al., 2024. The public health priority should be adult smoking cessation by any means available – including via consumer pathways to smoke-free products – and the FDA should not be obstructing this process.

Fourth, the market reveals strong adult preferences for flavored ENDS. We know that adults overwhelmingly prefer flavored vape products as alternatives to smoking (see Figure 4 below, based on Farsalinos et al. 2025.

Figure 4: Adult preferences for flavored vaping products, United States

This survey analyzed flavor preferences from a convenience sample of over 50,000 adult vapers. Among those who had quit smoking, there was a clear revealed preference for fruit, dessert, and candy flavors, precisely the products for which the FDA intends to set a near-impossible evidential hurdle.

Fifth, “reach” matters. The public health impact of ENDS is a function of both the efficacy as alternatives to smoking and the “reach,” the number of people willing to try the alternative. The public health effect cannot be characterized solely by comparative efficacy from a trial in which subjects are allocated to trial arms. What matters is the products that people wish to use.

Sixth, a realistic basis for APPH would lead to a greater focus on adult smoking. If trade-offs in evaluating APPH were made using an objective measure of health, such as discounted quality-adjusted life-years (QALYs), then the FDA would be designing regulations to dismantle barriers to adults accessing a wide range of flavored vaping and pouch products, all while continuing to account for the known risks of smoke-free nicotine use to youth.

Questions for FDA to address in final guidance:

• What are the consequences of denying adult smokers the most popular flavored vaping products? Will this prolong smoking and the related disease burden in adults, promote illicit trade, and drive legitimate American suppliers and retailers out of business?

• What are the effects of the FDA’s severe limits on authorized flavored vapor products on adult risk perceptions of ENDS products compared to continued cigarette use?

• How does the FDA resolve the trade-offs implicit in the public health standard, and why hasn’t it published a transparent methodology? How does the FDA account for the needs of the much larger adult smoking population and for youth who would otherwise smoke if they were not using ENDS (see Section 1, above)?

4. Disturbing indifference to the vast illegal market for ENDS

The FDA’s Draft Guidance is strongly at odds with reality regarding the illegal market that dominates ENDS use in the United States, which likely accounts for at least 80% of the total ENDS market when tracked and untracked sales are considered (see Figure 5 below).

Figure 5: The US vape market is dominated (88%) by products not authorized by the FDA

The obvious problem with a highly restrictive regulatory approach to flavored ENDS is that people (adults and youth) will source the flavored products they want from illicit suppliers. This illegal supply chain already meets the flavored ENDS product demand of around 20 million Americans, with tens of thousands of products. Experience from Australia suggests that restrictive measures can turn the ENDS market almost fully illicit.

The scale of the illicit market means consumers will access unregulated, unsupervised products through informal or criminal networks, with no consumer protections or redress. Many illicit products are acceptable from a safety, marketing, and design perspective and would be on sale lawfully in other jurisdictions. However, others would not meet acceptable standards and may pose unnecessary risks. Consumers have no way to know which is which. It is always better to have lawfully available products that meet adult consumer demand than to have that demand channeled into unregulated products that are supplied illegally.

Will more enforcement work?

It might be argued that the FDA and other agencies intend to shut down this illicit trade and confine the ENDS market to those products authorized by the FDA. So far, enforcement has had only a marginal moderating effect in slowing the uptake of illicit vapes. However, some tobacco company analysis suggests this has helped moderate the decline in cigarette volumes [Altria, First Quarter 2026 Earnings Call]. But suppose enforcement were much more successful in shutting down illicit ENDS as intended: how would the 20 million Americans who access illicit vapes (most of whom are adults) respond? The effect would likely be a rebound to smoking.

The failure of enforcement-based approaches is evident in illicit drug markets. Youth cannabis use persists despite its illegality and the lack of flavors: 12th-grade past-30-day prevalence has been around 20% since 1995, with daily use at around 5% [Monitoring the Future].

Figure 6: 30 years of persistent unflavored illegal youth cannabis use

A reasonable assumption is that young people use cannabis for its psychoactive effects, rather than any particular attribute of a cannabis product, and source it socially or illegally if necessary. As with cannabis, a persistent demand for its psychoactive effects would be a more appropriate way to conceptualize youth nicotine use.

Questions for FDA to address in final guidance:

• How has the Draft Guidance incorporated the market reality of a large illicit market in flavored vape products that are popular with adults (see Figure 5, above)?

• If the FDA denies nearly all fruit, candy, and dessert ENDS, what happens to the demand for a wide range of fruit, candy, and dessert-flavored ENDS?

• To what extent has the FDA’s refusal to authorize the flavored products that adults prefer created the illegal market in flavored disposable vapes, largely sourced from China?

• Will the FDA allow companies to clearly market their products as “FDA Authorized” (similar to the “FDA Approved” language for drugs) to help consumers distinguish between legitimate and illicit products? Conversely, can the FDA require manufacturers of illicit vapes to market their products as “Not Authorized by FDA” (similar to language used for supplements)?

5. Perverse regulatory imbalance in favor of deadly combusted tobacco products

The number of dangerous, combustible products that can be lawfully sold in the United States is orders of magnitude greater than that of modern, safer, non-combustible products.

Figure 7: Number of products that can be lawfully placed on the U.S. market

There is no justification for such a pronounced asymmetry in access and regulatory barriers to entry. The FDA should focus on designing an authorization regime that allows and encourages the ongoing market in tobacco and nicotine to migrate from high-risk to safer forms of delivery.

International experience

The FDA has not considered relevant experience in other jurisdictions. The UK regulator’s database (accessed 16 April 2026) showed 47,531 different vape products were available for lawful sale in the UK, mostly flavored. UK adult vaping prevalence now exceeds smoking prevalence.

Questions for FDA to address in final guidance:

• What is the public health and ethical justification for imposing far higher barriers to entry to safer nicotine products, while there are thousands of highly dangerous combustible products widely available?

• What effect do severe restrictions on flavored ENDS products have on smoking rates?

• How has the FDA interpreted quasi-experimental economic evidence that state-wide ENDS flavor bans are associated with increases in smoking?

• What adverse effects has the FDA found in a marketplace with tens of thousands of flavored ENDS available? Has the FDA learned anything from jurisdictions that have a restrictive approach to ENDS access, such as Australia?

6. Unworkable framework for testing comparative efficacy

Though the Draft Guidance is intended to clarify the FDA’s approach to the assessment of flavored ENDS products, it provides only vague conceptual assertions. The guidance lacks the precision and specificity needed to enable an applicant to operationalize the Draft Guidance efficiently by running trials or developing other evidence satisfactory to the FDA.

No clarity on what defines an elevated risk to youth

The Draft Guidance appears to segment the ENDS market into three broad flavor categories:

1. Tobacco flavored

2. Flavors posing low risk for youth appeal, such as menthol, mint, coffee, tea, and spices

3. Flavors posing a high risk for youth appeal, such as fruit, candy, and dessert

The Draft Guidance is vague about how these categories will be defined and how to characterize differences within and between the categories. FDA suggests using perception and consumer response studies, including sensory panels. But it is unclear how such information would be used to characterize increased risk to youth, especially as such testing would not be able to gauge the behavioral response to the FDA denying marketing orders for flavored products. It is also unclear why flavors popular with adults would be unpopular with youth. Tobacco-flavored products are not especially popular with either adults or youth.

Amidst all the vagueness, the FDA promises further guidance, acknowledging the incompleteness of the Draft Guidance now open for comment.

The Agency intends to consider input and emerging data regarding appropriate methodologies for such characterization and may issue future guidance, as appropriate, to clarify evidentiary expectations.

No useful information on designing a trial

Having failed to clarify how risk to youth should be characterized, the Draft Guidance then fails to clarify how benefits to adults should be characterized. It has little to say about which comparative efficacy studies will be acceptable and what thresholds must be met.

FDA is therefore open to evidence that a particular product may increase the likelihood that adult smokers will switch to that product and sustain complete abstinence from combusted cigarettes because it adds to the flavor options available to adult smokers.

The FDA described its comparative efficacy test in a press release from August 26, 2021, announcing the denial of 55,000 ENDS products.

Based on existing scientific evidence and the agency’s experience conducting premarket reviews, the evidence of benefits to adult smokers for such products would likely be in the form of a randomized controlled trial or longitudinal cohort study. However, the agency does not foreclose the possibility that other types of evidence could be adequate if sufficiently robust and reliable.

Surely, the purpose of the Draft Guidance is to provide clarity on what this highly generalized statement means in practice. But the Draft Guidance does nothing to clarify what this means in practice. For example, the Draft Guidance provides no information on the FDA’s criteria for the following in relation to a trial:

• The required effect size and acceptable statistical significance

• The comparator products (is it any tobacco-flavored product or the manufacturer’s?)

• The preferred trial duration and follow-up

• The acceptable end-points (which definition of smoking cessation, what weight is placed on cutting down or migration from exclusive smoking to dual use?)

• The selection criteria for the study population (are they people wanting to quit or people who smoke?)

• The handling of non-compliance (in the highly likely event that people assigned to either the control or experimental trial arms use flavors other than those assigned to them)

Though longitudinal cohort studies are mentioned, these are only possible with products already on the market, so this will, at best, serve as a legacy method and can only support pre-market applications if studies conducted outside the United States can be used.

No clarity on operationalizing “appropriate for the protection of public health.”

Though APPH has been at the heart of tobacco policy since 2009, the FDA has never clarified how trade-offs and optimization within this framework will be done. The Draft Guidance provides little concrete advice on what applicants would need to do to meet the “comparative efficacy test” for each of the three flavor categories, and how much additional benefit to adults would be required to meet the APPH standard. For example, it states:

Consistent with the FDA’s risk-based approach to evaluating whether marketing a product meets the APPH standard, the extent of evidence needed to demonstrate sufficient adult benefit may vary based on the relative magnitude of youth risks posed by the product’s flavor characteristics.

However, the Draft Guidance does not specify how the required adult benefit would be assessed and how much it must increase, or how the relative magnitude of youth risks should be characterized.

There is no guidance on how to weigh the respective detriments and benefits in an APPH assessment. If, for example, variations in discounted QALYs over the life-course are used as a currency of harm or benefit, then the costs of a net additional young person taking up ENDS are very low and distant. However, the benefit of an adult aged 50 switching from smoking to vaping is high and far more immediate. The possibility of young people with a high propensity to smoke taking up vaping instead is not even recognized, let alone integrated into an assessment framework. No allowance is made for the likely behavioral response to the FDA denying most flavored ENDS, which is that users seeking flavored ENDS will access the illicit market or, possibly, remain as smokers or take up smoking, thereby increasing risks.

The failure to articulate a clear methodology for APPH, grounded in market and behavioral realities, is part of a wider, long-standing problem: FDA has never set out, in detail or even in principle, how it believes the benefit-cost assessment implicit in APPH should be made, and this guidance does not address this deficit at all.

Policy on Device Access Restriction betrays underlying policy intent

The Draft Guidance notes that Device Access Restrictions (DAR), which would include identity verification and age-gating via a Bluetooth-enabled device, smartphone, and app, are not sufficient alone to satisfy the FDA, even though these interventions would make it substantially more difficult for youth and young adults under 21 to use ENDS products.

DARs submitted for ENDS products with those types of youth-appealing flavors, without adequate and substantial evidence demonstrating sufficient mitigation of youth risk, are insufficient to overcome the heightened concerns associated with these flavor categories.

Such excessive caution suggests disproportionate risk-aversion: it appears the FDA does not intend to authorize flavored products without DAR, and only reluctantly with DAR, even though these flavors are by far the most popular among adults and widely available in the illicit market.

On May 5, 2026, the FDA authorized two flavored products that have device access restrictions [news release]. These authorizations suggest a narrow path to market for a limited number of flavored ENDS products that have this restrictive technology. Yet if this is the only feasible route to market, it will greatly limit the number and diversity of flavored products likely to receive FDA authorization. The flip side of that constraint will be a strengthened demand for products in the illicit ENDS market (with unrestricted flavors and no access controls) and for other, riskier tobacco products.

It remains unclear how much weight the FDA places on a DAR age-gating feature in notionally reducing youth risk versus comparative efficacy evidence demonstrating an increase in adult benefit. Nor is it clear how the inclusion of DAR would modify or remove the requirement for a demonstration of comparative efficacy. Without such clarity, the process is wasteful and inefficient, as applicants cannot determine the optimal way to show APPH to the FDA’s satisfaction.

Note: perversely, DAR age-gating technology could provide a significant barrier to adult uptake and reach in the most important smoker populations (older adults and those experiencing disadvantage), and would likely reduce the public health benefit for adults at worst, or continue to drive consumers to illegal options with no access restrictions at best.

Flavor descriptors and branding are a better way to control youth risk

FDA further fails to account for the fact that – unlike combusted cigarettes made from tobacco leaves, which themselves produce a flavor when burnt – all vapor products are the result of a two-pronged approach to flavoring: a chemical formulation to create a sensory flavor experience, and marketing communications (branding, labeling, descriptors) to tell the user what to expect. In our view, given the distrust bred by decades of tobacco companies’ marketing and consumer communications practices, the FDA should focus on ensuring ENDS product flavors are branded and described accurately and literally, not on constraining the availability of a robust range of flavor experiences available to adults.

Summary

To summarize: FDA is asking applicants to undertake high-cost, resource-intensive trials and to endure long delays to market access, without providing clear design guidance or success criteria. The evidential hurdles remain high, arbitrary, and capricious.

Questions for FDA to address in final guidance:

• What are the design criteria for a trial comparing a flavored ENDS and a tobacco-flavored ENDS?

• What are the success criteria for showing that a flavored ENDS is APPH?

• How do device access restrictions affect the requirements of a comparative efficacy test? How should applicants account for the existence of thousands of illicit flavored products on the market without DARs when assessing whether a product is APPH?

• Given that young people initially encounter flavored ENDS through marketing, branding, and flavor descriptors, why does the Draft Guidance ignore this? How would the FDA incorporate these factors into an APPH assessment?

7. Unlawful creation of a product standard outside the required rulemaking process

The comparative efficacy test functions as a product standard, though with key criteria unknown to the applicant. There are three ways to characterize this test as a product standard:

1. The comparative efficacy test itself is a product standard. An application for a flavored ENDS product that the FDA deems risky to youth must demonstrate that the product has a higher smoking cessation impact among adults, though how much higher is not specified. The fact that the FDA has been imprecise about every aspect of this test (see section 6 above) does not make it any less of a standard; it just makes it a poorly specified standard. This vagueness and ambiguity would be addressed through the proper rulemaking process.

2. The consistent likely outcome of applying the comparative efficacy test creates a de facto prohibition. If the FDA were more precise about its standard, it would likely become clear that the evidential requirements are so demanding or burdensome that the comparative efficacy hurdle is, in practice, insurmountable. In that case, there is a de facto standard: a ban on flavored ENDS products that the FDA deems risky to youth.

3. In practice, device access restrictions may offer the only feasible pathway to market for flavored products. Such a de facto requirement would amount to a technical product standard and would also require rulemaking.

All would constitute de facto rulemaking, thereby skirting the notice-and-comment requirements of the Administrative Procedures Act. Besides being unlawful, there are multiple reasons for concern about the creation of a product standard outside the rulemaking process:

• The FDA has relieved itself of the burden of showing that its approach is appropriate for the protection of public health. Under TCA Section 907 Product Standards, the burden of proof rests with the FDA to show that its flavor-related standards are consistent with APPH. The rulemaking process would provide a means to address the concerns raised in this comment: the true risk to youth, the appropriate weight to give to adult smoking cessation, the illicit market, and the proportionality of the comparative efficacy test.

• The FDA has incorporated a vaguely specified but onerous comparative efficacy test into the evidence requirements expected of PMTA applicants under Section 910, and is doing so without the proper checks integral to the rulemaking process. The FDA has imposed the evidentiary burden of meeting these standards on applicants on a product-by-product basis. In contrast, the law requires the FDA to demonstrate that the standards themselves are APPH. Moreover, the impact of flavored ENDS arises at the level of the whole category and must be seen in the context of the market as a whole, including the illicit market. For this reason, the burden of proof should fall on the FDA.

• Under the rulemaking procedures for a product standard, FDA would need to be far more precise in defining the standard, allowing applicants to make informed judgments about the likelihood of success and to avoid over-specifying expensive trials when the success criteria are unknown. The articulation of a standard would improve efficiency, predictability, and transparency. The lack of a properly specified standard is wasteful.

• The lack of precision and transparency allows the FDA to avoid accountability - opening the way to arbitrary, capricious, and political decision-making. There is persistent evidence that the FDA makes political decisions at the whim of its leadership rather than based on a scientific assessment of APPH. See, for example, White House Pushes for Flavored Vapes Blocked By FDA Head (Wall Street Journal, April 16, 2026); Marty Makary: The FDA’s Quiet Blockade on Safer Nicotine, Roger Bate, Brownstone Institute (April 17, 2026); Trump Pressures FDA Commissioner to Approve Flavored Vapes (Wall Street Journal, May 5, 2026). While the eventual authorization of two flavored ENDS is overdue, the process that led to it was wholly unsatisfactory and vulnerable to legal challenges, given the role of politics in overriding science-based decision-making.

The FDA began a rulemaking process for flavors in 2018 with an Advanced Notice of Proposed Rulemaking titled “Regulating Flavors in Tobacco Products.” That approach was abandoned without explanation. Yet the publication of the ANPRM shows intent, and the practice since 2018 suggests the same goals have been pursued through alternative, less accountable and transparent means - imposing burdens on applicants rather than justifying a product standard.

Questions for FDA to address in final guidance:

• How does this Draft Guidance differ from de facto rulemaking pursued without the procedural safeguards of the Administrative Procedures Act?

• Why was a product standard for flavors abandoned, and why is it right to control flavors through guidance on PMTA applications rather than rulemaking?

• How has the FDA satisfied itself that the Draft Guidance would be appropriate for the protection of public health and not cause more harm than good?

Conclusion - non-marginal reform is required

We believe that the Draft Guidance is incompatible with the Tobacco Control Act, fails to provide a realistic way to operationalize the public health standard (APPH), and does not serve the public interest. We recommend a more substantial reform agenda to drive out smoking at all ages and to crowd out the illicit trade with regulated and lawfully available products that adults wish to use, including thousands of flavored products. The PMTA assessment process needs non-marginal re-engineering so that at least 4,000 ENDS products can be authorized (to compete against as many as 100,000 illicit products), that barriers to entry and application costs need to fall by a factor of at least ten (in line with the 2016 Deeming Rule Impact Analysis), and so that applications can be processed within 180 days (in line with the law).

Our recommendations for reform are drawn from a recent report for the American Enterprise Institute, Regulating the Tobacco and Nicotine Market in the American Public Interest: A Reform Agenda for the FDA (September 2025), by Sally Satel, Clive Bates, Don Kenkel, and Brad Rodu. The report makes fifteen recommendations, which are summarised as follows:

1. Focus premarket assessment solely on the product’s characteristics: safety, quality, packaging, and marketing. Its population impact can be assessed only post-market.

2. Start with the information requirements Congress specified in the Tobacco Control Act and apply the least-burdensome principle to make regulations more efficient.

3. Use guidance to establish norms or “soft standards” that can be used to expedite applications if met, but require further substantiation and investigation if those standards are not met.

4. Avoid requiring human studies when possible; concentrate on characterizing emissions and chemistry. Emissions offer a reasonable proxy for human exposure.

5. Reallocate population and behavioral aspects of “appropriate for the protection of public health” to post-market assessment based on real-world outcomes.

6. Conduct in-depth market surveillance to ensure regulatory and enforcement agencies are informed about what they are responsible for.

7. Use post-market corrective action to address adverse market developments.

8. Abandon the comparative efficacy test for flavored products; it is a significant barrier to entry, supports Chinese illicit products, and is not grounded in science.

9. Provide greater precision in application requirements. The FDA should be far more precise about what is required of applicants.

10. Avoid endless repetition. Build the application review process on a series of category-wide findings that are broadly applicable to all products in a category.

11. Formally recognize the status of products pending scientific review for more than the statutory 180 days. Apply enforcement discretion and list these in the tobacco products database to provide clarity for retailers and consumers.

12. Prioritize the review of products in the greatest demand in the illicit market to improve the competitiveness of the lawful market.

13. Take a more collaborative approach with the law-abiding noncombustible nicotine companies. They are in a three-cornered fight with incumbent smoking products and the illicit trade, and the FDA should be working with them, not against them.

14. Establish an expedited risk communication pathway for modified risk tobacco products to enable manufacturers to promote products that are authorized as appropriate for the protection of public health.

15. Educate health professionals and the public about the risks of nicotine and the differential risks between smoking and smoke-free products.
    

About the authors

Clive Bates is a UK-based consultant and advocate for sound policymaking in sustainability and public health, with special emphasis on tobacco and nicotine. He is the Director of Counterfactual Consulting Limited and operates the Counterfactual website and Substack.

Stefanie Miller is an independent consultant. She previously led U.S. external affairs at Juul Labs Inc. Prior to that, she advised institutional shareholders of the world’s largest tobacco companies on the U.S. political and regulatory environment and its role in the industry’s transition away from combusted cigarettes to less harmful nicotine products.

Brad Rodu is a Professor Emeritus of Medicine at the University of Louisville. He published research on tobacco harm reduction for three decades, and at the 2022 Global Forum on Nicotine, he received the Michael Russell Award in honor of his substantial and innovative contribution to the science and understanding of safer nicotine products.

Sally Satel is a senior fellow at the American Enterprise Institute. A practicing psychiatrist and lecturer at the Yale University School of Medicine, Dr. Satel examines mental health policy and political trends in medicine. She has a longstanding interest in tobacco and nicotine policy.

David Sweanor is an adjunct professor of law at the University of Ottawa and has been a key figure in global public policy efforts to reduce cigarette smoking since the early 1980s.