Last week’s announcement from FDA regarding the authorization of on! PLUS was very encouraging. With more authorizations likely soon, a greater focus on enforcement, and the rejection of frivolous applications, a market can be created that rewards responsible companies serious about creating high-quality products for the benefit of combustible and traditional oral tobacco product users.
After reviewing the FDA Technical Project Lead review summary for the on! PLUS PMTAs, I gained several important insights into this review and what it signifies about the evolving PMTA landscape for nicotine pouches.
1 Review pace
One of the most striking aspects of this review was the speed with which it was completed, as well as the fact that it appears to have proceeded through one substantive review cycle. Unlike many PMTAs that span multiple years and review rounds, this evaluation was completed efficiently, supported by frequent interaction between FDA and the applicant. The structure of the review suggests that issues were addressed as they arose rather than being deferred to subsequent cycles, enabling a much faster outcome.
2 Rapid amendments signal substantive dialogue
While the summary does not list each amendment in detail, the number of rapid amendments strongly indicates ongoing scientific dialogue throughout the review. Rather than a formal back-and-forth through multiple deficiency letters, this approach reflects continuous engagement. It is a clear example of how frequent communication can reduce review cycles without compromising scientific scrutiny.
3 No toxicological review performed
Notably, the Technical Project Lead determined that a standalone toxicological consult was not required. Based on the chemistry and ingredient information submitted, no toxicological red flags were identified that warranted escalation. This reinforces that product category context matters and that, for certain nicotine pouch products, a robust chemistry package can be sufficient to address toxicological considerations. Unsurprisingly, due to the route of administration, this is significantly different from the toxicological assessment of ENDS, where greater scrutiny is placed on the toxicology assessment.
4 Child-resistant packaging
Although child-resistant packaging is not a statutory requirement, it was clearly a crucial element of the APPH assessment. The review highlights how certified child-resistant packaging helped mitigate the risk of accidental nicotine exposure in young children. This suggests that, while not mandated by law, child-resistant packaging is increasingly expected when making a credible public health argument.
5 Importance of product specific analysis
The review relied heavily on data generated on the actual products under review. Manufacturing consistency, stability, and harmful and potentially harmful constituent levels were assessed at the product level rather than relying solely on category wide arguments. This reinforces the importance of generating high quality, product specific analytical data to support PMTA decisions.
6 Clinical bridging was accepted
FDA accepted a clinical bridging approach rather than requiring complete clinical datasets for every individual variant. Where products shared similar formulation and nicotine characteristics, data from representative products were used to support conclusions across the range. This highlights the value of a focused and well justified clinical strategy that aligns with FDA expectations around similarity.
7 Abuse liability assessed against moist smokeless tobacco
Abuse liability was assessed relative to moist smokeless tobacco. This comparator reflects a realistic consumer context and allows FDA to conclude that the products were likely to have lower abuse liability than an appropriate existing tobacco product category. Additionally, previous theories that FDA may only be amenable to a maximum strength of 6 mg/pouch have been debunked, with the on! PLUS authorizations for both the 6 and 9 mg strengths. This indicates that the FDA will not make direct assessments on label claims, but the scientific substantiation of appropriately designed products.
8 Microbial methods and validation still matter
While water activity data were accepted as a strong indicator of microbial stability, the microbial methods themselves were not fully validated for tobacco products. Although this did not prevent a marketing authorization in this case, it reinforces the importance of using adequately validated methods, particularly for microbiology, to avoid unnecessary risk in future submissions.
9 Stability data underpins multiple review conclusions
The review makes clear that stability data are central to demonstrating product quality over the proposed shelf life. FDA relied on stability studies to confirm that key attributes such as nicotine content, pH, moisture related parameters, and chemical constituents remained within acceptable ranges over time. This supported the conclusion that the marketed product would remain consistent with the product evaluated during review.
The key message is that stability data are not supplemental. They are foundational to FDA confidence in product consistency and shelf life, and insufficient stability data would be likely to generate additional review questions or delay authorization.