The scientific office of the CTP used to have to grant authorizations for e-liquids

The FDA’s Center for Tobacco Products (CTP) expected at some point to allow bottled e-liquids from manufacturers who submit premarket tobacco applications (PMTAs). The FDA’s Tobacco Center’s Office of Science has submitted a memo outlining a plan to expedite the review of e-liquids, according to an exclusive story by Alex Norcia in Filter.

The memo, titled “Grouping and Bracketing Approach for Review of Open PMTAs for ENDS E-Liquids,” outlines a process to expedite scientific review of PMTAs for e-liquids by grouping products based on characterizing flavors, using a “flavor wheel” first published in a 2019 paper by a group of Dutch scientists. FDA scientific reviewers could have looked at multiple products from a single manufacturer and then tied their findings to other products included in that company’s PMTA.

The plan was intended to save time for FDA scientific reviewers, but it also acknowledged the agency’s belief at the time that certain bottled e-liquids would be permitted.

The memo was signed by then-officer of science director Matthew Holman, who recently left the FDA to work for tobacco company Philip Morris International. Filter obtained the memo from the FDA through a Freedom of Information Act (FOIA) request. (The full memo can be read in the Filter article.)

The planned “grouping and bracketing” system for PMTA reviews was intended to make the work of the CTP easier, but its author also said it would “increase the likelihood of more tobacco products being reviewed and receiving orders to commercialization before the end of the compliance period”. ” (“Compliance Period” refers to the one-year period following the PMTA submission deadline of September 9, 2020 during which the submitted products could be sold without the threat of enforcement by the FDA .)

“Essentially,” writes Norcia, “CTP seems to have imagined a few years ago that an expedited process would effectively produce a large number of market refusals and clearances for open-system vapes and e-liquids.” Open system vapes are devices that can be refilled with bottled e-liquid and the bottled e-liquid itself.

It turns out that the FDA still hasn’t cleared a single open-system product, not even tobacco-flavored or unflavored products. Instead, the agency opted to implement a review system designed to reject PMTAs for all flavored products without any review – unless manufacturers submit costly and time-consuming studies to prove that their products offered “enough benefit to adult smokers that would overcome the risk posed to youth.”

Without randomized controlled trials or longitudinal cohort studies, the agency assumed (based on little evidence) that tobacco-free flavored products were not “appropriate for the protection of public health” and issued orders to marketing refusal (MDO). The FDA has rejected claims for millions of products submitted by hundreds of manufacturers and has been sued by dozens of small businesses.

Companies challenging the FDA in federal courts might have made good use of the “bundling and bracketing” memo — if they had seen it before their cases were decided. At the very least, it shows that the CTP had considered allowing some open system products (though not necessarily flavored products), but instead someone at the FDA rejected the idea in favor of the open system. standard refusal on which the agency settled.

The memo outlined a plan for CTP scientific reviewers from the Division of Product Science and the Division of Non-Clinical Sciences to randomly select products containing up to 24 PMTA signature flavors from a single company and then link the conclusions of the reviewers to other products included in the same application. The note’s author said there would be “no limit to the maximum number of tobacco products per PMTA for which findings can be reconciled.”

Manufacturers, of course, were not allowed to make assumptions about any of their own products based on information about other similar products submitted. This would have been a time and effort saving shortcut only given to hard working CTP examiners. But the very existence of the “grouping and bracketing” memo shows that the FDA recognized the folly of its demand that every (very similar) product be subjected to identical tests that would in all likelihood show exactly the same results. in a given company’s product line.

Aron M. Newman