On March 9, the U.S. Food and Drug Administration (FDA) released a draft guidance document describing the agency’s perspective on premarket tobacco product applications (PMTAs) for flavored electronic nicotine delivery systems (ENDS). 

The document, titled “Flavored Electronic Nicotine Delivery Systems (ENDS) Premarket Applications – Considerations Related to Youth Risk: Draft Guidance for Industry,” available here (Draft Guidance), reflects FDA doubling down on its heightened expectations for flavored ENDS PMTAs.

Comparative Efficacy Standard

The Draft Guidance articulates FDA’s view that non-tobacco-flavored ENDS—particularly “ENDS products with fruit and candy/dessert/other sweet flavors that appeal to youth”—pose a greater risk to public health than tobacco-flavored ENDS. Flavored ENDS, FDA states, “played a major role” in the increase in youth ENDS use between 2017 and 2019. And, although youth ENDS use has declined significantly since 2019, FDA finds that “[n]ational surveillance and longitudinal studies confirm that flavors persist as a determinant of both initiation and persistence of youth vaping ….”Accordingly, when evaluating PMTAs for non-tobacco-flavored ENDS, FDA is primarily concerned with whether the applicant has “robust and reliable evidence” showing “that the flavored ENDS has an added benefit relative to tobacco-flavored ENDS in facilitating adults who use combusted cigarettes to completely switch or significantly reduce their combusted cigarette use.”

But how much added adult benefit is necessary for FDA to find that authorizing the products is “appropriate for the protection of the public health” (APPH)? The Draft Guidance indicates that FDA will employ a “sliding scale” approach to the evidentiary burden, based on how much risk to youth is posed by the flavor in question. In other words, PMTAs for ENDS imparting flavors that FDA views as highly appealing to youth—such as candy—must demonstrate a relatively greater adult switching benefit.

Conversely, PMTAs for ENDS with flavors that FDA views as less appealing to youth could face a relatively lower evidentiary burden with respect to adult switching. Some flavors “may be shown to have lower youth appeal, perhaps such as coffees, teas, or spices, such that they may pose a lower risk of appeal to youth and may be APPH if the added benefit they provide compared to tobacco-flavored products is relatively small.”

Potential Study Approaches

Regarding studies to assess the relative appeal of an applicant’s proposed flavored ENDS among various age demographics, the Draft Guidance states that FDA intends to consider emerging data on methodologies and “may issue future guidance, as appropriate, to clarify evidentiary expectations.”

Sensory perception and consumer response studies that leverage “common and validated methods (e.g., blinded sensory panel assessments),” the Draft Guidance says, could “provide useful information regarding the relative appeal and sensory characteristics of ENDS flavor formulations without requiring product use.” FDA further recommends that these studies include “benchmark flavors” of tobacco, fruit, candy, and “other common flavors.”

Novel Device Access Technology

FDA also discusses in the Draft Guidance the potential impact of age-restricted device access restrictions (DARs) on its consideration of flavored ENDS PMTAs. FDA has previously suggested that DAR technology could mitigate risks posed to youth by flavored ENDS. See, e.g., U.S. Food & Drug Admin., Technical Project Lead Review, NJOY LLC, PM0000616.PD1, PM0000617.PD1 (June 21, 2024) at 5-7 (“Thus far, FDA’s experience shows that advertising and promotion restrictions and sales access restrictions cannot mitigate the substantial risk to youth from flavored ENDS sufficiently to reduce the magnitude of adult benefit required to demonstrate APPH. Rather, for flavored ENDS, only the most stringent mitigation measures have such potential; to date, the only such measures identified with the potential for that kind of impact have been device access restrictions.”).

The Draft Guidance refines and narrows FDA’s previous position on DARs, indicating that DAR technology alone is not sufficient to mitigate the risks of an ENDS product that imparts a “high-risk” flavor like candy. FDA states that “an applicant whose high youth appealing flavored ENDS purports to rely solely on DAR technology to address risk to youth carries an especially high burden to demonstrate adequate mitigation of such risk based on valid and reliable evidence from robust scientific investigations.”

Why It Matters

The new Draft Guidance on flavored ENDS PMTAs demonstrates that FDA (even under the Trump Administration) is resolute in its comparative efficacy expectations for these submissions—even if the underlying principles were largely evident to stakeholders operating in this space.

The agency’s stance with respect to DAR technology is also notable. Prior to this Draft Guidance, FDA had indicated that incorporating DAR into flavored ENDS products might be sufficient to address youth access concerns without a showing of comparative efficacy. Now, however, FDA has clearly stated that utilizing DAR technology for candy/dessert/other sweet-flavored ENDS, “without adequate and substantial evidence demonstrating sufficient mitigation of youth risk,” is “insufficient to overcome the heightened concerns associated with these flavor categories.”

The comment period is open through May 11, 2026. If you have questions about the implications of the Draft Guidance as it pertains to your business, or would like assistance in submitting comments, our team is happy to assist.