On January 16, 2025, the FDA’s Center for Tobacco Products (CTP) authorized the marketing request for 20 Zyn pouch products. The authorized products included several flavors beyond the tobacco and mint/menthol profiles that have characterized successful PMTA applicants’ products thus far. The Marketing Granted Order (MGO) therefore marks a turning point for tobacco and nicotine product regulation in the USA. The Zyn TPL provides insight into the FDA’s thinking on this topic and the kinds of evidence that supported their determination that Zyn’s flavored products meet the APPH standard. Two areas in particular warrant close scrutiny.
Comparator products selected for testing in abuse liability assessments
Strategic bridging strategies
The FDA CTP’s reviewers determined that overall, the Zyn pouch products had a lower or equal abuse liability compared to comparator products based on behavioral use patterns, PK study results, and study participants’ intentions to buy the product. Specifically, in the 10-week actual use study, the frequency and duration of use for the candidate products were statistically equivalent across flavors and strengths, remaining consistent throughout the study. This usage pattern indicated a low potential for abuse, which the TPL considered to be independent of the characterizing flavor profile.
Additionally, the results from the PK study and nonclinical toxicology studies suggested that the abuse liability of the Zyn products was lower or equal to that of the comparator products (snus and moist snus). The comparator products selected for the PK study and the other nonclinical toxicology studies were considered appropriate and justified. Some of the justifications for the use of general and moist snus were that they have similar flavors to the comparator product, have comparable nicotine content, and are used similarly. In the PK study, rather than testing each individual flavor, data from the analysis of wintergreen and smooth flavored products at the 6mg nicotine strength were selected to ‘bridge’ to the other flavors with the same nicotine content. The justification for the selection of these two flavors was that these two flavors represented different characterizing flavors from each other. Additionally, all of the new products being submitted contained flavor ingredients that produced a cooling sensation or mintlike flavor, thus, providing a similar user experience.
The application for Zyn pouch products provided evidence that marketing authorization would be appropriate for the protection of public health (APPH). A low risk for abuse liability was illustrated by the evidence for product use patterns being relatively stable between flavors, subjective effects, and physiological responses. Nicotine exposure produced by the new products was comparable to the smokeless tobacco comparator products and therefore lower than combustible cigarettes. Cigarette users reported higher intentions to buy Zyn pouches compared to other nicotine and tobacco product users.
The authorization of reduced harm products with characterizing flavors other than mint/menthol was based, in part, on proffered evidence that flavors support CPD reduction and smoking cessation more effectively than unflavored or tobacco-flavored products. The FDA’s determination must also be considered in the context of the wider population trends surrounding youth use of nicotine pouches. Based on historic and current self-reported consumption data, a far lower proportion of US youth experiment with pouch products relative to ENDS (e-cigarettes or ‘vapes’). Perhaps that prompted the FDA to consider nicotine-pouch flavors in a more positive light than flavored e-cigarettes. But the National Youth and Tobacco Survey (NYTS) rates from 2024 of youth vaping show a decline by approximately two-thirds since peaking in 2019. In light of the evidence that flavors support smoking cessation, perhaps we will see MGOs for flavored RHPs in other categories too. Applicants hoping to achieve MGOs for flavored products may be interested in the ‘lessons learned’ from the Zyn TPL, especially the bridging strategies and use of multiple comparator products. ARAC, for our part, incorporates such insights, and maintains an on-going discourse with the FDA CTP to ensure that we can help our clients develop the robust evidence base necessary for an APPH determination, MGO and market-success.
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