FDA roundtable spotlights small‑manufacturer struggles with PMTA evidence needs
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Summary
Small ENDS manufacturers urged the FDA Center for Tobacco Products to give clearer, more predictable standards for PMTA submissions while agency scientists described existing technical expectations and urged pre‑submission engagement; toxicology, pharmacology, manufacturing consistency and adult‑benefit evidence emerged as the main hurdles.
Matthew Farley, director of the Office of Science at the FDA Center for Tobacco Products, opened a daylong roundtable on premarket tobacco product applications by laying out a two‑part objective: explain the scientific evidence the agency uses to judge whether a product is appropriate for the protection of public health (APPH) and hear directly from small manufacturers about obstacles they face in preparing PMTAs. "We will not be discussing logistics of a submission," the moderator said, but agency staff repeatedly encouraged companies to request pre‑submission meetings to discuss product‑specific plans.
Manufacturers repeatedly pressed the agency for greater predictability and lower testing costs. Small‑business representatives said they lacked capital to run the full suite of laboratory and clinical studies FDA has relied on in recent reviews, and they asked whether the agency would consider numerical benchmarks—temperature ceilings, emissions targets or standardized test methods—that could serve as predictable pathways for lower‑risk products. FDA scientists replied that APPH is not a single numerical threshold and that formal standards or rules would require public processes such as guidance or rulemaking; however, agency staff pointed to existing resources and pilot programs intended to increase transparency and early communication.
Technical panels explained the science reviewers look for. The Office of Science’s product‑characterization team listed required elements for PMTAs: complete design specifications, a full ingredients list with CAS numbers and suppliers, nicotine source and form, validated analytical methods and measured harmful and potentially harmful constituents (HPHCs) with means, standard deviations and numbers of replicates. The manufacturing panel described expectations for quality‑management systems, standard operating procedures, certificates of analysis, batch records and stability testing across shelf life. The pharmacology panel outlined pharmacokinetic (PK) study templates—prescribed‑use sessions followed by ad‑libitum use, with blood draws to measure Cmax and Tmax—and stressed that abuse‑liability assessments require both quantitative PK data and qualitative measures of use behavior. The adult‑benefit panel summarized the kinds of randomized trials and cohort or actual‑use studies FDA considers most persuasive when a manufacturer claims added benefit for adult smokers. Toxicologists presented a hazard‑tiering approach and a screening method for excess lifetime cancer risk (ELCR) that uses available inhalation potency values or a TTC fallback (1.5 micrograms/day) when potency estimates are not available.
Panelists pressed for operational help: access to validated method lists, clarity about which assays and sample sizes reviewers will favor, and a way to triage which of many flavors or SKUs a small company should advance for testing. FDA staff said meeting requests, the public docket and pilot transparency efforts are the practical avenues to discuss product‑specific strategies. Agency toxicologists acknowledged legal limits on publishing some internal memos but said they are evaluating how to provide useful public tools and suggested collaboration with standards bodies such as ISO or USP.
The session closed with a call for continued engagement and greater predictability. Commissioner McCary briefly joined to thank participants and reaffirm the agency’s goal of balancing youth protections with opportunities for adult smokers to access lower‑risk products. FDA officials said they will consider the roundtable feedback as they prioritize future guidance and reviewer tools.
