Inside FDA’s ENDS Roundtable: What Small Manufacturers Need to Know Now

On February 10, 2026, FDA’s Center for Tobacco Productsconvened a full-day Small Manufacturer ENDS PMTA Roundtable. The objective was straightforward but significant: hear directly from small manufacturers and clarify what FDA expects across the major PMTA evidence categories: product characterization, manufacturing controls, pharmacology, adult benefit, and toxicology. Our CEO, Chris Allen, Toxicology Manager, Dean Hatt, and Regulatory Expert Consultant, Lillian Ortega, have provided a comprehensive breakdown of the roundtable.

The overarching message was not that the bar is beinglowered. It is not. Instead, FDA is working to provide greater transparency around how that bar is applied and where predictability is beginning to emerge.

A Complete Product Story Is the Starting Point

FDA made it clear that product characterization is foundational. Applications will not move forward without a complete descriptionof the product. That means detailed design specifications with defined upper and lower limits, measured manufacturing data aligned to those limits, a complete ingredient list including CAS numbers and supplier information, validated HPHC methods, and stability data that covers the beginning, middle, and end of the claimed shelf life.

There are still no fixed numerical APPH thresholds, no imminent product standards for ENDS, and no substantial equivalence pathway.PMTA remains the only route. While the HPHC list is being refined and extended, applicants were cautioned not to wait for definitive lists or “safe” numbers. The expectation is clear: each application must stand on its own scientificcompleteness.

Manufacturing Controls: Where Predictability Is Improving

The ManufacturingControls panel provided practical clarity on key considerations. FDA emphasized that quality systems must be demonstrably operational. It is not enough to have SOPs and templates; the agency expects real, completed documentation showing the system works in practice. Nicotine specifications must be defined with clear targets and acceptance ranges, supported by real batch release data and in-process controls. Stability studies must be real-time, method-validated, andcover both chemical and microbial considerations.

Risk analysis is not optional. FDA expects manufacturers to demonstrate that foreseeable hazards have been identified and appropriately mitigated, ensuring that the product assessed in the PMTA is representative of what will ultimately be manufactured and marketed. This is critical from apublic health perspective: variability in nicotine delivery, for example, mayraise abuse liability concerns, while inconsistencies in device performance canpresent broader safety risks. Robust risk management therefore underpins FDA’s confidence in both product consistency and consumer protection.

Pharmacology and Adult Benefit: Evidence Must BeDesigned, Not Added Later

Nicotine pharmacokinetics remain central to abuse liabilityassessment. Well-designed crossover studies measuring Cmax, Tmax, and AUC continue to carry weight, but FDA reinforced that assessment is based on the totality of evidence. Product liking, craving relief, use topography, andappropriate participant selection all matter. Study populations should reflectreal-world users, particularly experienced ENDS users who often achieve highernicotine exposure levels.

For flavored products, the expectation remains demanding. Manufacturers must demonstrate that adult switching or cigarette reduction exceeds that of tobacco-flavored comparators. Randomized controlled trials, cohort studies, and actual-use designs were all discussed as acceptable approaches, provided they are appropriately powered and of sufficient duration to capture meaningful behavioral change.

Toxicology: Equal Weight, Structured Logic

FDA reiterated that toxicology carries equal importance to product design and manufacturing controls in determining whether a product is Appropriate for the Protection of Public Health (APPH).

The agency confirmed the value of Excess Lifetime Cancer Risk (ELCR) framework, but emphasized the importance of relevance, especially route of administration e.g inhalation. Tiering of genotoxic chemicals during ELCR evaluation is critical not only for understanding evidentiary strength but also for determining whether certain Tier 4D or 4E chemicals can justifiably be excluded from cumulative ELCR calculations.

Importantly, design decisions directly influence thesecalculations. Ingredient selection, flavor tiering, material quality, and temperature controls all shape toxicological risk outcomes.

Several important nuances emerged. Hazard evaluation isdynamic; there are often delays between emerging research, IARC reclassification, and updates to HPHC listings. As a result, toxicological assessment cannot be static but based on recent judgment. This led to an acknowledgment by FDA that there is no realistic path to a single static “acceptable ingredient list"

FDA also addressed in vitro testing of complex mixtures (aerosols). A negative result in an Ames test on a mixture containing known genotoxicants (formed during the heating process) may be of limited value (due to dilution effects), and therefore does not indicate low lifetimecarcinogenicity risk. While acknowledging in vivo studies would fill this gap, the FDA confirmed the emphasis remained firmly on robust, desk-based ELCR risk assessment.

The FDA also agreed that where toxicological data are limited or uncertainties remain, conservative approaches such as the 1.5 µg/day Threshold of Toxicological Concern (TTC) are typically applied. This reinforces the importance of a proactive toxicological strategy during product development, ensuring risk is designed out early, rather than defended later in the PMTA process.

Regulatory Tone: Communication, Not Concessions

Throughout the day, small manufacturers pressed for more predictable, standards-like benchmarks to manage cost and development planning.FDA acknowledged those concerns and emphasized its willingness to engage, but stopped short of promising immediate policy change or written guidance. Statutory APPH requirements constrain flexibility.

That said, there were signals of improved communication. Pre-review meetings with Regulatory Health Project Managers are encouraged. Thepublic docket remains open for comment. FDA referenced lessons learned from the Fall 2025 Nicotine Pouch Pilot Program and suggested that similar transparency and dialogue mechanisms could inform future ENDS review processes.

Commissioner Dr. Makary’s surprise appearance reinforced this dual message: public health protection, especially for youth, remains paramount, but predictability and scientific clarity are also necessary for responsible innovation and harm reduction in a rapidly evolving marketplace.

What This Really Means

The scientific expectations have not softened. There will be no universal ingredient safe list, no shortcut thresholds, and no substitute for a well-constructed, evidence-based submission.

However, the framework is becoming clearer. Manufacturing documentation and ELCR toxicology logic are emerging as the areas of greatest structural predictability. Bridging is viable, but only with strong scientificboundaries.

For small manufacturers, success will depend on treating product characterization, quality management, toxicological modelling, pharmacology and adult benefit as one coherent, scientifically defensible story.

The regulatory bar for ENDS products remains high and, in practice, beyond the reach of many small manufacturers without the appropriate infrastructure and expertise. However, with a strategically designed product and a well-integrated scientific programme, Marketing Granted Orders are demonstrably achievable.

If you are preparing an ENDS PMTA, success depends on a scientifically integrated strategy that aligns product design, manufacturing controls, toxicology, pharmacology and regulatory requirements from the outset. At Broughton, we support manufacturers with GMP-compliant testing, ELCR toxicological assessment, stability studies and regulatory expertise to build robust, defensible submissions. Contact our team to discuss how we can supportyour PMTA programme.