Two important memos dated October 25, 2022 detail internal FDA deliberations about how FDA considers specific menthol e-cigarettes in the context of the larger scientific literature on menthol. The two memos, one from the leadership of the Office of Science and another from Center for Tobacco Products Director Brian King and Deputy Director Michelle Mital have been released in connection with litigation by JTI’s Logic e-cigarettes.
These memos show longstanding tension between the FDA Office of Science, then led by Matt Holman (who has since left FDA to work for Philip Morris International) and the Director’s office on how to assess whether individual menthol e-cigarettes are “appropriate for the protection of public health” (APPH, the legal standard).
The memo from the Office of Science sums up the status quo well before FDA’s decision not to authorize JTI’s menthol Logic e-cigarettes:
In August 21, OS [the Office of Science] began issuing marketing denial orders on certain PMTAs [Premarket Tobacco Product Applications] for ENDS with flavors other than tobacco or menthol, deferring decisions on menthol products to allow more time to consider whether there were any aspects unique to menthol-flavored ENDS that would affect the assessment of whether authorizing the marketing of such products would be appropriate for the protection of public health (APPH). Specifically, OS needed more time to assess whether and to what extent any evidence in the peer-reviewed scientific literature might, in concert with the evidence provided in specific product applications, support a finding of benefit from menthol-flavored ENDS for adult menthol-flavored cigarette smokers sufficient to outweigh the risk to youth from the marketing of such a product.
In considering this issue, OS conducted a thorough review of the scientific literature regarding menthol-flavored cigarette smokers and menthol-flavored ENDS use to determine whether it established that menthol-flavored ENDS provide a sufficient benefit for adult smokers relative to that of tobacco-flavored ENDS. OS concluded that the existing literature supports that menthol-flavored cigarette smokers show a preference for menthol-flavored ENDS relative to tobacco-flavored ENDS. But OS did not find that the current literature supports that use of menthol-flavored ENDS by adult smokers is associated with greater likelihood of complete switching or significant cigarette reduction relative to tobacco-flavored ENDS. [emphasis added]
Footnote a in the memo reports that Logic did not submit evidence demonstrating that Logic menthol e-cigarettes would have any different effects than menthol e-cigarettes in general:
On the question of potential benefit and Logic’s PMTA, OS did not consider the differential preference for menthol ENDS in the literature in isolation, but instead in combination with Logic’s product-specific evidence of significant reduction in cigarettes smoked per day. However, Logic’s evidence did not include a statistical comparison between menthol-flavored ENDS and tobacco flavored ENDS and all cohorts in Logic’s studies reduced cigarettes smoker per day to a similar degree. The evidence [in Logic’s PMTA] therefore did not demonstrate a sufficient benefit from menthol-flavored ENDS use relative to tobacco-flavored ENDS use. [emphasis added]
In other words, the product-specific information Logic submitted was consistent with the broader scientific literature.
Nevertheless, as I suspected, in contrast to its earlier summary of the science showing no switching benefit for menthol cigarette smokers, OS still was supportive of menthol e-cigarettes cigarettes despite the lack of evidence that these products were more effective than tobacco-flavored ENDS because of evidence that smokers “preferred” menthol e-cigarette. This policy position may have reflected then-OS Director Holman’s policy goal of “ensuring” some e-cigarettes remain on the market :
From a policy perspective, OS believed at the time [when Holman was still director] that as long as menthol-flavored cigarettes remain on the market, menthol-flavored ENDS could be a direct substitute for them, providing a less harmful alternative for menthol-flavored cigarette smokers, who are less likely to successfully quit than smokers of non-menthol cigarettes. [emphasis added]
Because the Office of the Center Director not OS was the ultimate decisionmaker in the agency and because a decision on the Logic menthol e-cigarette PMTA would set a precedent for other products, this issue was the subject of discussion with the Director’s Office (while Mitch Zeller was still director), which raised questions about OS recommendations.
It is important to note that there appeared to be agreement within the agency about the three key scientific questions: (1) E-cigarettes appealed to youth; (2) menthol smokers express a preference for menthol e-cigarettes; and (3) the evidence did not support a conclusion that menthol-flavored e-cigarettes are more effective at helping smokers quit than tobacco-flavored e-cigarettes. Given these agreed upon scientific conclusion, the debate was whether to authorize the marketing of these products as “appropriate for the protection of public health” or to treat these products as the agency was treating other flavored products and deny the application unless the manufacturer could prove these products were more effective at helping smokers quit than tobacco flavored products that pose less of a risk to youth.
The discussion continued after Brian King became director. In addition to being a scientist (Zeller is a lawyer), King had published specific research on menthol, including menthol e-cigarettes.
The memo continues,
OS shared its views with the new Center [for Tobacco Products] director [Brian King] and engaged in a open discussion on topics including the general body of literature, Logic’s clinical studies, risks to youth, and potential postmarketing requirements. After that meeting, the OCD [Office of Center Director] Senior Science Advisor shared OCD’s views with OS, articulating that, in light of the substantial risk to youth, and the lack of robust evidence of actual differential use to quit or significantly reduce cigarettes per day, the approach to menthol-flavored ENDS should be the same as for other flavored ENDS, i.e., the products could be found to be APPH only if the evidence showed that the benefits of the menthol-flavored ENDS were greater than tobacco-flavored ENDS, which pose lower risk to youth
OS, on its own initiative, then reassessed and decided it was reasonable and consistent to treat menthol-flavored ENDS PMTAs in the same way as other non-tobacco flavored ENDS PMTAs regarding the evidence needed to show a potential benefit to adult smokers.
At the same time, under the law, if a particular manufacturer can demonstrate with sufficient scientific evidence that their specific product is APPH, FDA may authorize it. However, that requires the manufacturer to show that their specific product has a more beneficial impact on smokers than tobacco-flavored products despite the lack of evidence in the most current scientific literature to support that conclusion in general.
The King/Mital memo (in the same PDF) provides more details on the process used to reach this decision, including how the FDA leadership bent over backwards to give staff who supported authorizing menthol a chance to make their case. It also demonstrates that the Logic decision was based on a product-specific reviewof the evidence submitted in the PMTA in light of the evolving evidence on menthol and its similarity to other flavored e-cigarettes, which is what FDA is legally required to do when assessing individual product PMTA applications.
This is a scientifically appropriate and important step forward for FDA’s approach to assessing menthol in specific new tobacco products.
A few postscripts:
The fact that I did not comment on FDA’s assumptions about e-cigarettes as a consumer product leading to complete switching or substantially reducing cigarette consumption does not mean that I accept their positions. The empirical evidence does not support their assumptions, but that is a separate question.
The logic described in these memos is consistent with arguments that FDA should drop the proposed exemptions for new tobacco products from its proposed menthol cigarette product standard.
I found out about these memos from an article by Alex Norcia in Filter, “Memos Show FDA Overruled Science-Office Call to OK Menthol Vapes.” I emailed Mr. Norcia and he kindly provided the memos.