FDA Memos Reveal Its “Fatal Flaw” Rejection Plan for Flavored Vapes

There’s an ongoing theory about the Food and Drug Administration (FDA) within the vaping community: The agency did not anticipate the onslaught of 6 million-plus premarket tobacco product applications (PMTAs) it received by a September 2020 deadline, and had to devise some way to try to sort through them all by the following year. It would be no easy feat, but the bar for authorization would be set incredibly high—and that, in the FDA’s view, would help.

Documents obtained by Filter shed new light on how this murky process has looked from the heavily criticized agency’s perspective. For the first time, they also give an indication, from the agency itself, of something else the vaping community has long inferred: that the FDA—despite some protestations to the contrary—has taken a systemically different approach to PMTA applications for the flavored products on which so many former smokers depend.

The agency previously signaled the threshold to be met—being “appropriate for the protection of public health”—would largely involve a tricky balancing act. Reviewers at the FDA’s Center for Tobacco Products (CTP) would weigh the likelihood of a given product facilitating adult smokers to switch to a safer alternative versus its perceived potential to attract a new generation of nicotine users.

The FDA also made clear—even if many in the industry can argue it did so only after the September 2020 submission deadline—that tipping the scales toward authorization would likely require at least one of two types of studies: longitudinal cohort studies, which track large groups of people over an extended period of time, or randomized controlled trials (RCTs), another type of study that examines a specific group of people through intervals of time. Both are costly and require high levels of skill.

On September 9, however, Mitch Zeller stated in an update to the agency’s PMTA process that the FDA “does not foreclose the possibility that other types of evidence could be adequate if sufficiently robust and reliable.” But the agency has never really expanded on what kind of other evidence that would be.

FDA memos reviewed by Filter provide an inside look into the procedure, establishing explicitly how the agency handled the heavy volume of applications for flavored vaping products.

“[Office of Science] will conduct a Fatal Flaw review of PMTAs not in Phase III for non-tobacco-flavored ENDS products.”

Critically, the memo continues: “The Fatal Flaw review will be limited to determining presence or absence of such studies; it will not evaluate the merits of the studies.”

According to the FDA, there are three “phases” of the PMTA review: Phase I (Acceptance), which essentially means an application has been received; Phase II (Notification or Filing), which entails acknowledging a company had enough information for its applications to be formally filed; and Phase III (Review), which involves a substantive scientific evaluation, followed by a marketing granted order (MGO) or MDO. (In August, the agency refused to file—that is, move to Phase II—about 4.5 million vapor product applications filed by a single manufacturer, JD Nova, because an environmental assessment was not included.)

The memo continues to explain that CTP used “a database query to identify the top twelve manufacturers with the largest number of pending PMTAs not in Phase III for non-tobacco flavored e-liquid products,” which then represented 85 percent of all pending PMTA applications. The agency pulled these applications “out of their respective place in the PMTA priority list,” and once “Phase II filing was initiated,” they underwent the “Fatal Flaw” review.

A former CTP employee said that they had never heard of the “Fatal Flaw” standard until now. 

“Manufacturers are responsible for making their case within their application,” Eric Lindblom, a senior scholar at Georgetown’s O’Neill Institute for National and Global Health Law and a former director of the CTP’s Office of Policy, told Filter. “And the FDA is under no legal obligation to fill in any missing gaps or apply external studies or evidence to make the application fulfill application requirements … to make the application worthy of getting an order allowing marketing—to make a PMTA product’s marketing appropriate for the protection of the public health.”

Still, the Fatal Flaw standard appears to be new; it does not seem to have been employed by CTP in the past. A former CTP employee, speaking to Filter on condition of anonymity, said that they had never heard of the “Fatal Flaw” standard until now.

The FDA has denied the applications of most small- and medium-size producers, issuing identical marketing denial orders (MDOs) for their mostly flavored products, while indicating more time was needed to evaluate the players with the largest market share. (It has authorized just one vape, along with two tobacco-flavored cartridges.)

So the way this happened, previously shrouded in mystery, just became a whole lot clearer: CTP reviewers created what’s probably a new method to get through a backlog of millions of PMTAs, searched those applications for longitudinal cohort studies and RCTs without evaluating any other evidence, and for applications lacking them, did not advance them beyond Phase II and just sent out templated MDOs.

“The ‘Fatal Flaw’ standard was created out of a sense of embarrassment on the Hill by the acting commissioner.”

Some in the vapor industry wonder if the “Fatal Flaw” review emerged after Janet Woodcock, the agency’s acting commissioner, testified at a congressional hearing at the end of June. Many leading Democrats—including two of the most vocal vaping critics, Senator Dick Durbin and Congressman Raja Krishnamoorthi—scolded Woodcock and her agency for not doing enough to address youth vaping rates. There may have been, in other words, political pressure to act, even as youth vaping has fallen. Holman signed the memo a little over two weeks after the hearing.

“The ‘Fatal Flaw’ standard was created out of a sense of embarrassment on the Hill by the acting commissioner,” an industry insider, speaking on condition of anonymity given a pending PMTA application, told Filter.

“Janet Woodcock’s legacy won’t be vaccines or drug approvals,” they continued. “It will be involving herself politically in the vaping market and making it harder for products that adults use to quit smoking to remain on the market. She has politicized the FDA more than any of her recent predecessors, by far.”

Through a spokesperson, the FDA declined to comment, as the agency does not do so “on possible, pending or ongoing litigation.”

In the meantime, dozens of vapor companies have sued the FDA, mainly for acting in an “arbitrary and capricious manner,” and two so far have received full-blown rescissions, with the agency citing that the “FDA found relevant information that was not adequately assessed.”

Another company, Triton, which at the end of October received a full stay from a federal court of appeals to continue selling its products as its lawsuit made its way through the court system, revealed that at least some judges agree with the industry’s logic: The FDA did not adequately inform manufacturers that long-term data, in the form of longitudinal cohort studies or RCTs, would be totally necessary.

The new evidence of the FDA’s cut-and-paste methodology, which emerged through these lawsuits, further substantiates vaping advocates’ portrayal of the process as not only chaotic, but stacked against smaller companies and flavors.

Photograph by Penn State via Flickr/Creative Commons 2.0