On June 21, 2024, FDA issued marketing granted orders (MGOs) to NJOY LLC for two non-tobacco flavored electronic nicotine delivery system (ENDS) products, the DAILY 4.5% and DAILY EXTRA 6% disposable devices, along with two ACE 2.4% and 5% pre-filled pods. All four of these NJOY ENDS products are menthol flavored. This FDA action, the first of its kind since the Tobacco Control Act (TCA) was enacted in 2009, marks the only instance in which FDA, which has rejected over 26 million premarket tobacco product applications (PMTAs) to date, has concluded that a non-tobacco flavored ENDS product meets the heightened “fatal flaw” or comparative efficacy review standard. In other words, this represents the first time that FDA has found that non-tobacco flavored ENDS products provide a significant added benefit for adult smokers relative to tobacco-flavored ENDS that outweighs the presumed risk that flavors pose to youth. Prior to this, FDA has authorized only 23 ENDS products and components, all of which have been tobacco flavored.

Following what it describes as an “extensive” scientific review, FDA’s Center for Tobacco Products (CTP) laid out the basis for its appropriate for protection of the public health (APPH) determination in what appears to be a more-than-usual detailed and comprehensive analysis set forth in the 71-page Technical Project Lead (TPL) review. Until now, FDA stated that it had excluded menthol products from application decisions to allow the Agency more time to consider how factors unique to menthol (such as disproportionate use by certain populations) would affect the APPH assessment.

Specifically, FDA considered the fact that menthol‐flavored combustible cigarettes are the only non‐tobacco flavored cigarettes that can legally be marketed currently, unlike other non‐tobacco characterizing flavors that are prohibited by the TCA for use in cigarettes. (See our previous post regarding the Agency’s effort to ban menthol cigarettes). FDA also noted that menthol is the most widely used flavor among African-American smokers. When evaluating the public health impact, however, FDA found during its review of the scientific literature that, while adults who use menthol cigarettes show a preference for menthol‐flavored ENDS, the existing literature does not appear to support that menthol‐flavored ENDS differentially facilitate completely switching or significant cigarette reduction. This led FDA to conclude that the APPH analysis for menthol‐flavored ENDS should be the same as for other non‐tobacco flavored ENDS: the fatal flaw standard. Thus, the NJOY applications were reviewed pursuant to the same comparative efficacy standard that applies to all other non-tobacco flavored ENDS.

To support its application, NJOY submitted two clinical studies to inform users’ health outcomes, and seven (two adult and five youth) observational studies to inform user population outcomes. To address comparative efficacy, NJOY submitted data and analyses from an online, observational longitudinal cohort study that assessed rates of switching when adults were using the menthol‐flavored new products and tobacco‐flavored NJOY DAILY products over a six-month period. NJOY’s data suggested a higher rate of absolute switching for the NJOY DAILY products (21‐32%), compared to the estimates for ENDS in general in the literature. Further, NJOY’s comparison analyses suggested that the menthol‐flavored NJOY DAILY ENDS products were associated with statistically significant and substantially higher rates (32‐43%) of complete switching when compared to the rate (21‐37%) for tobacco‐flavored NJOY DAILY ENDS products at 3 or 6 months. These comparison analyses demonstrated a 24%‐50% substantial added benefit. While acknowledging the risk to youth posed by menthol-flavored ENDS per recent NYTS data (showing 20% of youth use menthol-flavored ENDS products) and the fact that NJOY was the 10th most‐reported brand used in the past 30 days among middle and high school students based on the 2023 NYTS, FDA nevertheless concluded that risk to youth is outweighed by the statistically significant (i.e., approximately 24%‐50%) higher switching rate in adult users of the menthol‐flavored new products than that in adult users of tobacco‐flavored NJOY DAILY products. FDA also noted that the new NJOY products facilitate complete switching (i.e., combustible cigarette cessation) at rates above those in the general ENDS literature, indicating that exclusive use of the new products is more likely than with other ENDS. Accordingly, the Agency highlighted the fact that health benefits are expected with exclusive use of the new products.

The APPH finding was also supported by the abuse liability of the products, which based on NJOY’s clinical study, survey, and literature reviews was determined to be similar to, though lower than, that of combustible cigarettes, which FDA concluded may facilitate complete switching compared to other ENDS with lower abuse liability. The Agency also noted the products’ nicotine salt formulation as a favorable factor during its APPH analysis, reasoning that the nicotine salt formulation’s similar nicotine delivery patterns to cigarettes suggests that the new products may offer adult users a similar use experience to cigarettes (i.e., greater substitutability), thereby facilitating switching or cigarette reduction. Another supporting factor – ironically, given the current enforcement landscape – was the fact that these products are disposable ENDS. FDA stated that the disposable nature of these products meant that they are non‐rechargeable and not serviceable by the user for any purpose, including customizing the atomizer, or modifying/refilling the e‐liquid. In addition, the design minimizes the risk of accidental exposure to e‐liquid by containing the e‐liquid in a manner that results in the e‐liquid being inaccessible through customary or reasonably foreseeable handling or use, as the e‐liquid quantity is only 0.94 mL and it is contained in a sponge and is not free‐flowing.

The Agency also noted that NJOY’s Marketing Plan was robust and expected to limit youth exposure to the new products and the products’ labeling, advertising, marketing, and promotion. In its marketing plan, NJOY detailed measures to restrict youth access and limit youth exposure, including prohibiting use of cartoons, requiring human models to appear to be age 45+ years, maintaining distributor and retailer policies governing selection and oversight of tobacco retailers that carry NJOY DAILY products, limiting number of products that can be purchased in a given time period or transaction (i.e., bulk transactions), among other measures. Significantly, FDA noted that while these marketing restrictions are likely to further limit youth use, they do not change the required showing for non-tobacco flavored ENDS (comparative efficacy).

In sum, FDA found that, based on a totality of the evidence, the menthol-flavored NJOY ENDS products could support a benefit to adults because, compared to the new tobacco‐flavored product, use of the new flavored products was associated with greater likelihood of either of these behavioral outcomes for adults who use combustible cigarettes: (1) complete switching from cigarettes to exclusive use of the new product or (2) significant reduction in cigarettes per day. Interestingly, FDA maintained this conclusion despite noting that the data showed that a large number of NJOY DAILY users (likely >40%) may become dual users with cigarettes (i.e., not switch completely), similar to what is reported in the literature, and thus may not experience the full range of health benefits. Nevertheless, the Agency found higher rates of absolute switching in users of the NJOY DAILY ENDS products than users of ENDS in general, owing in part to the products’ high abuse liability (which while high, may be somewhat lower than combustible cigarettes, mitigating concern of greater nicotine exposure and addiction potential than combustible cigarettesamong non‐tobacco users, including youth).

While the recent NJOY menthol ENDS authorization provide hope for non-tobacco flavored ENDS and, in particular, menthol-flavored ENDS, as well as for disposables, FDA’s news release is careful to caution that because each new tobacco product application is reviewed on a case-by-case basis, its authorization is limited to the four NJOY products and does not apply to any other menthol-flavored ENDS products. In addition, public health groups have already been quick to express their disapproval of the NJOY menthol authorizations, arguing that youth are drawn to menthol-flavored ENDS and thus the risk to youth is insurmountably high to reach an APPH determination. Regardless, the NJOY authorizations make clear that it is indeed possible to successfully support the fatal flaw or comparative efficacy showing for non-tobacco flavored ENDS products pursuant to FDA’s current requirements.