Documents obtained by Filter provide insight into the Food and Drug Administration’s early planning of its much maligned premarket tobacco product application (PMTA) process to authorize e-cigarettes—or not—as “appropriate for the protection of public health.” They suggest, among other things, that the FDA may ultimately envisage a path to authorizing flavors other than tobacco and menthol, despite not having done so yet—and that the agency’s tendency to favor the largest companies, mostly with ties to the tobacco industry, has deep roots.
It’s been a fraught journey. At the end of June 2021, Janet Woodcock, the acting commissioner of the FDA, faced sharp questions from legislators at a congressional hearing about the agency’s failure to address youth vaping rates. It was just over a week later that the FDA’s Center for Tobacco Products (CTP) sent an internal memorandum, explaining how staff would deal with the backlog of the millions of PMTAs they had likely not anticipated. They would create a new “Fatal Flaw” strategy—in which they’d use “a database query to identify the top twelve manufacturers with the largest number of pending” PMTAs for non-tobacco flavored e-liquid products not in scientific review—and determine if any of them contained randomized control trials (RCTs) or longitudinal cohort studies.
None of those applications appeared to, and the agency issued marketing denial orders (MDOs) to them all. Many of the producers have since argued that the FDA never made it clear such studies would be required, and dozens have filed lawsuits in federal appeals courts, claiming this “Fatal Flaw” method was “arbitrary” and “capricious.”
Something along the way seems to have changed—a shift industry observers have tended to assign to Woodcock’s grilling on the Hill.
The PMTA process has been murky from the start, though the basic structure looked simple enough. There would be three distinct “phases”: Phase I (Acceptance), which essentially indicates an application has been received; Phase II (Notification or Filing), which acknowledges a PMTA has enough information to be formally filed; and Phase III (Review), which involves a thorough scientific evaluation. Companies expected that if their PMTAs were missing crucial elements, the FDA would issue Deficiency letters, allowing them to respond and potentially ameliorate any problems. Initially, that appears to have been the case.
But something along the way seems to have changed—a shift industry observers have tended to assign to Woodcock’s grilling on the Hill. In November, Filter received a redacted version of the “Fatal Flaw” memo, which showed how CTP’s Office of Science (OS) had apparently pivoted from its initial “Premarket Application Review Prioritization Plan.”
The exact contents of that original plan remained unknown. But through a Freedom of Information Act (FOIA) request, Filter has now acquired the “Premarket Application Review Prioritization Plan” from CTP’s Office of Science, signed by director Matthew Holman on August 31, 2020. The memo went out to staff a week or so prior to the September 9, 2020 PMTA submission deadline.
Though the general plan remains consistent with the FDA’s broad messaging—that its PMTA review process would focus on the companies with the largest market share—it reveals how rigid that prioritization became.The FDA did not respond to Filter’s request for comment.
“As the application submission deadline approaches, OS anticipates a significant increase in the number of premarket applications for all three premarket pathways,” the plan reads. “In preparation for the increase … OS determined that updates to the review process are necessary to ensure that we can efficiently initiate and complete review of as many applications as possible during the one-year compliance period while applying the same scientific rigor.”
The memo includes a list of “guiding principles”:
1. Simple: Selected approach should be easy to manage, explain, & implement
2. Defendable: Decisions are not arbitrary & capricious
3. Flexible: Process offers the opportunity to easily pivot and adjust the strategy, if needed
4. Supports our public health goals:
* Minimize youth initiation
* Ensure a variety of ENDS have an opportunity to remain on the market to facilitate adult smokers switching to less harmful tobacco products
It identifies six manufacturers for prioritization: Juul Labs, in which Altria holds a minority stake; Reynolds, a subsidiary of British American Tobacco (BAT) that produces Vuse; NJOY; Fontem Ventures, a subsidiary of Imperial Tobacco that makes blu; Cool Clouds Distributors, which manufactures Puff Bar; and Japan Tobacco International (JTI), which puts out Logic. (CTP ultimately excluded Puff Bar because it had discontinued sales in July 2020 and eventually switched to synthetic nicotine.)
It raises a tantalizing possibility about flavors.
The Prioritization Plan then outlines how, specifically, CTP would deal with PMTAs, dividing staff members into nearly a dozen teams and creating different queues by level of importance: Queue 1 addressed “ENDS products from the five manufacturers with the largest market share,” prioritizing “the earliest PMTAs received from each manufacturer;” Queue 2 handled “PMTAs for all marketed deemed and statutorily regulated tobacco products not in Queue 1,” selecting “PMTAs for review by randomizing each manufacturer”; and Queue 3 focused on “PMTAs deemed and statutorily regulated tobacco products not marketed,” prioritizing “ENDS products that included a device that incorporates age-verification technology.”
It’s that last point, concerning products in Queue 3, that raises a tantalizing possibility about flavors—widely blamed for a youth vaping “epidemic” in the United States and so far summarily rejected by the FDA, despite harm reductionists pointing out that most adults who switch from smoking prefer non-tobacco flavors.
Reading between the lines, it’s further acknowledgement of something CTP had already alluded to in its Technical Project Lead (TPL), guidelines published just two days before the September 9, 2020 deadline. Discussing “mitigation efforts to reduce the risk of youth initiation,” the TPL document reads, the FDA would consider “device access restrictions (e.g., technologies that require adult user identification by fingerprint or other biometric parameters in order to unlock and use a tobacco product).” The FDA has authorized a handful of tobacco-flavored e-cigarettes, and continues to punt on decisions for menthol vaping products. Because it has effectively deemed that marketing plans for other flavors would not be sufficient to dissuade youth use, it stands to reason that age-verification technology might be one of the only ways for manufacturers to receive authorization on flavors.
In other words: A device with sophisticated technology to keep it solely in the hands of adults—like the Juul2, available in the United Kingdom—could have the potential to see a flavor besides tobacco and menthol authorized.
“It strikes me as a legit approach that might gain FDA support,” Cliff Douglas, the director of the University of Michigan Tobacco Research Network and the American Cancer Society’s former vice president for tobacco control, told Filter.
CTP has not said any of this explicitly, nor do we know what these products are. But the possibility will likely divide the already-polarized groups in tobacco control. “I think these locking technologies are a really bad idea,” Clive Bates, the former director of the United Kingdom’s Action on Smoking and Health, told Filter. “No equivalent exists for cigarettes, and they would involve considerable complexity and barriers to access for many users.”
What is clear, though, in the PMTA Prioritization Plan is a pretty explicit timeline that reveals how the FDA adjusted its priorities. And we have compelling evidence of how the odds became ever more stacked against smaller manufacturers.
According to an addendum signed by Holman on September 24, 2020, which Filter also received through a FOIA request, products in Queue 2 would be randomized—and Deficiency letters would be sent for any incomplete PMTAs. “To ensure that OS completes two scientific review cycles for each PMTA bundle selected for review during the one-year compliance period, OS reduced the scientific review cycle for PMTAs to 90 calendar days and is allowing applicants 90 calendar days to respond to Deficiency letters,” the prioritization plan reads. “These timelines will enable OS to kick-off two bundles of PMTA scientific review for each of the ten teams, under the assumption that no extensions of time will be granted to respond to Deficiency letters.”
Prior to the mid-2021 “Fatal Flaw” memo, this seems to have been what happened: Filter also reviewed three Deficiency letters—dated between December 2020 and May 2021—which the FDA issued to manufacturers not identified as those with the largest market share. The letters were broadly identical, robust asks that called for things like “comparative health risk data,” more precise “ingredient characterization,” and “specific information about control parameters (e.g. temperature, humidity, duration) during storage of final manufactured products before shipping.”
“Even if a large company gets an MDO, they have the entire review to look at—a ‘favor’ small manufacturers did not get.”
But by the time of the “Fatal Flaw” memo, the FDA had stopped sending out such Deficiency letters and instead simply issued MDOs, many of which are currently or have been handled in court. Turning Point Brands, for instance, seems to have received an MDO through this revised process, and the agency eventually put its PMTAs back under review, after the company filed a lawsuit.
It was, evidently, down to the luck of the draw for smaller companies: Had a team at CTP reviewed your PMTA before the “Fatal Flaw” memo, because it had been randomly assigned in an early batch, you will have gotten a Deficiency letter; had it yet to be assigned, or was assigned after the “Fatal Flaw” memo, you had a solid chance of being outright denied.
“If you are a small- or medium-sized manufacturer who spent a lot of time and money doing studies but didn’t include an RCT—because you weren’t told you had to—now you have no idea what they thought of the rest of your application,” a former CTP employee, who requested anonymity so as not to harm their career in tobacco control, told Filter. “Were your HPHC studies done right? Did you explain your manufacturing correctly? What about your perception studies? Not evaluating and even giving comment on these is unfair to a lot of people. Even if a large company gets an MDO for some of their products, they have the entire review to look at—a ‘favor’ small manufacturers did not get.”
Premarket Application Review Prioritization Plan (August 31, 2020)
Filter also published two addenda online: from September 24, 2020 and May 11, 2021.
Photograph by Jerzy Gorecki via Pixabay
The Influence Foundation, which operates Filter, has received grants from Altria, Juul and Reynolds. Filter’s Editorial Independence Policy applies.