FDA’s comprehensive plan on tobacco and nicotine regulation, three years later
By Beth Oliva and Philip Langer
In July 2017, FDA unveiled its “Comprehensive Plan on Tobacco and Nicotine Regulation”—a plan that, in FDA’s words, “places nicotine, and the issue of addiction, at the center of the agency’s tobacco regulations.”1 While the comprehensive plan outlined several areas of focus (such as regulation of flavored products and the use and impacts of premium cigars), in announcing the comprehensive plan, FDA placed significant emphasis on two specific issues. First was the prospect of reducing nicotine levels in combustible cigarettes to nonaddictive levels through “achievable products standards;” second was “fostering innovation where innovation could truly make a public health difference.”2 When introducing the plan, former FDA Commissioner Scott Gottlieb said this:
Looking at ways to reduce nicotine levels in cigarettes so that they are minimally or nonaddictive, while not altering the nicotine content of noncombustible products such as e-cigarettes, is a cornerstone of our new and more comprehensive approach to effective tobacco regulation.
[W]e must recognize the potential for innovation to lead to less harmful products, which, under FDA’s oversight, could be part of a solution. While there’s still much research to be done on these products and the risks that they may pose, they may also present benefits that we must consider.3
Nearly 3.5 years after FDA’s rollout of the comprehensive plan, it is worthwhile to explore what FDA has done—and not done—in pursuing its quest to reduce nicotine in combustible cigarettes and foster innovation for noncombustible products. Has FDA made meaningful progress toward achieving the ambitious goals it set in 2017? Or has FDA simply paid lip service to the comprehensive plan without any serious action? A review of FDA activity over the last few years suggests a mixed record of accomplishment in the development of a national reduced nicotine standard and progress toward turning the vision of reduced-risk tobacco products into a reality. FDA in its public-facing comments remains steadfastly committed to the initiative, and while progress on complex issues such as these must be measured over years rather than months, it has been slow. Recent developments and the current posture of tobacco regulation, however, suggest the coming years will be critical to the success or failure of the comprehensive plan.
2018—Progress in the exploration of a reduced nicotine standard
There is no question that FDA has taken steps to explore the reduction of nicotine in combustible cigarettes since announcing the comprehensive plan in July 2017. The first significant step was in March 2018 when FDA issued an Advance Notice of Proposed Rulemaking (ANPRM), seeking public comment on the development of a reduced nicotine product standard.4 Specifically, FDA sought comments, research and data on myriad topics, including a potential appropriate maximum nicotine level; whether a nicotine product standard should cover other combustible tobacco products; and what unintended consequences could result from a nicotine product standard (such as illicit trade or increase in smoking). The comment period remained open for about four months and by its close, the public docket had garnered nearly 8,000 comments.5
Around the same time, FDA funded research and an article by agency researcher Benjamin Apelberg and others in The New England Journal of Medicine titled “Potential Public Health Effects of Reducing Nicotine Levels in Cigarettes in the United States.”6 The article acknowledged “a continuum of risk for products that deliver nicotine” and used a simulation model to conclude that “enacting a regulation to lower the nicotine content of cigarettes to minimally addictive levels in the United States would lead to a substantial reduction in tobacco-related mortality, despite uncertainty about the precise magnitude of the effects on smoking behaviors.”7
In a continued show of dedication to the prospect of developing a reduced nicotine standard, in May 2018, Center for Tobacco Products Director Mitch Zeller submitted an article to the Society for Research on Nicotine and Tobacco titled “The Future of Nicotine Regulation: Key Questions and Challenges.”8 In the article (eventually published in 2019), Zeller stated that FDA’s “renewed focus on nicotine” was premised on the “continuum of risk” and invited FDA’s stakeholders to contribute perspective as FDA continued to “shape its tobacco regulatory strategy.” In the article, Zeller stated that a policy centered on nicotine was the priority in FDA’s tobacco regulatory strategy and that “FDA’s strategic regulatory approach is designed to support innovation in developing products with net public health benefits.”9
Overall, throughout 2018, FDA appeared to “hit the ground running” in exploring reduced nicotine levels in cigarettes through a national product standard. The ANPRM, along with funding research and submitting content to scientific journals, indicated a strong start. Yet at the same time, little was being done publicly on the second prong of the comprehensive plan—encouraging innovation in new products with potential public health benefits.
2019—FDA hits a stall
While 2018 showed commitment to the first prong of the plan, 2019 did not build on the prior year’s advances. The agency did, however, move forward in certain ways in encouraging innovation for potentially reduced-risk products.10 In 2019, FDA issued the draft guidance on enforcement priorities for e-cigarettes (March 2019); the proposed substantial equivalence (SE) rule (April 2019); the proposed premarket tobacco product applications (PMTA) rule (September 2019); and the final guidance document for PMTAs for e-cigarettes. These documents showed an expanded FDA focus from the reduced nicotine prong of the comprehensive plan to also encouraging at least some limited innovation in potentially reduced-risk products. The agency also, helpfully, began to look at providing more transparency and predictability to tobacco regulation. While FDA has issued draft rules, however, nothing has been finalized; in addition, the final PMTA guidance document for e-cigarette products is just that—only useful for those products and not any other potentially reduced-risk product.11 Further demonstrating that FDA’s focus shifted is that while FDA’s spring 2019 unified agenda included a potential regulation to reduce or “cap” nicotine in cigarettes (as did the 2018 agenda), such a regulation was entirely absent from FDA’s fall 2019 unified agenda.
What FDA most notably accomplished in 2019 was the approval of two PMTAs and the granting of the first modified-risk tobacco product (MRTP) order. First, in April 2019, FDA issued PMTA marketing orders for the IQOS tobacco-heating system and charger along with the Marlboro Heatsticks in regular, smooth menthol and fresh menthol flavors, finding that “the marketing of the products is appropriate for the protection of the public health.”12 In December 2019, FDA authorized the marketing of 22nd Century’s two reduced nicotine cigarettes—Moonlight and Moonlight Menthol, similarly finding that “the marketing of the products is appropriate for the protection of the public health.” Second, in October 2019, FDA issued the first MRTP orders, authorizing Swedish Match North America to use specific modified-risk messaging on its General snus products—the culmination of a five-year process for the company and FDA.
Regarding the reduced nicotine standard, however, there was no public indication by FDA of progress toward promulgation of a standard. In response to inquiries from the public on why the initiative did not appear on the fall 2019 unified agenda, FDA stated that the omission of a reduced nicotine standard regulation did not mean FDA was not continuing to work on the initiative. Still, this shift change was understandably interpreted by the public as a possible wavering in FDA’s dedication to the initiative.
2020—A continued stall and concern from the public
In response to a reduced nicotine regulation being absent from FDA’s fall 2019 unified agenda, Congressman Frank Pallone submitted a letter to FDA Commissioner Stephen Hahn in February 2020 to “voice [his] concern” that FDA “appears to be reconsidering regulations that would set a maximum nicotine level in cigarettes in order to make them less addictive.”13 In a similar vein, John Pritchard—vice president of regulatory science at 22nd Century—penned an op-ed in November 2020 noting, “late last year, without warning or significant explanation, the FDA abruptly removed the proposed rule-making to reduce nicotine levels in cigarettes from its regulatory agenda. Even before the Covid-19 pandemic struck, policymakers decided there were more immediate priorities than cigarette addiction and the roughly half [a] million Americans who die from it each year.”14 Pritchard pleaded with FDA to revisit its plan and accelerate its own actions.
Last year brought the unexpected tragedy of the pandemic, which obviously and understandably impacted all FDA efforts. Perhaps partly as a result, it also brought little public progress with respect to FDA’s development of a reduced nicotine standard. There were no requests for proposal, research or articles released in conjunction with the nicotine reduction initiative, and the initiative continued to remain absent from FDA’s unified list and long-term actions list throughout the year.
On the innovation front, in July 2020, FDA did issue an MRTP order authorizing IQOS to be marketed with a reduced exposure claim, but not a reduced-risk claim. The MRTP application by Philip Morris International included requests for MRTPs for both claims. While this second MRTP order is undoubtedly an important step, to date, FDA has still not decided upon the separate MRTP applications for the 22nd Century reduced nicotine cigarettes. Such an approval would be a significant endorsement of the reduced nicotine approach and its impact on harm reduction.
Closing out 2020—a renewed interest?
After this period of inactivity on the reduced nicotine standard, the end of 2020 brought an unexpected move from FDA: In December 2020, 22nd Century announced that FDA (along with the National Institute on Drug Abuse) submitted an order for 3.6 million very low nicotine research cigarettes. FDA stated that the cigarettes are to be used for numerous research initiatives, including the potential implementation of a national reduced nicotine standard. Further, at the Food and Drug Law Institute’s Tobacco and Nicotine Products Conference in September 2020, Zeller confirmed that FDA remained committed to everything contained in the comprehensive plan, including focus on reduction of nicotine in combustible cigarettes. Starting research on this issue would indicate a step toward that commitment.
On the issue of potentially reduced risk products, however, FDA has not yet indicated how it will look at the hundreds of thousands (if not millions) of PMTAs it received in September 2020 for products across the continuum of risk. These include applications for e-cigarettes as well as tobacco-free nicotine pouches, nicotine toothpicks, nicotine dissolvable products and other innovative products to deliver nicotine without the combustion elements of cigarettes. No further guidance documents have been issued from the agency nor has the agency provided further clarity on how it will determine if these products are “appropriate for the protection of the public health.”
Therefore, FDA closed out 2020 with continued public-facing dedication to the initiative as well as a potentially significant step toward achieving it. The reduced nicotine regulation continues, however, to be absent from FDA’s unified agenda and long-term actions list, including that released in December 2020. That unified agenda does, however, indicate FDA’s intention to continue to work on other important rules, such as the final rule for PMTAs, the final rule for SEs and a proposed rule for MRTPs.
In summary, FDA’s progress toward developing and implementing a reduced nicotine product standard and encouraging innovation for potentially reduced-risk products and products authorized to use modified risk or exposure claims has arguably been unsteady. Of course, the public does not have insight into FDA’s internal workings, and there is the distinct possibility (or perhaps probability) that progress is occurring (such as continued review of comments to the ANPRM, development of a proposed rule and other research initiatives as well as developing guidance documents for other noncombustible products) out of public sight.
FDA’s recent order of 3.6 million research cigarettes is a promising step as was the granting of the first MRTP orders. The new year, which will include agency evaluation of PMTAs, will hopefully demonstrate continued advancement toward the goals of the 2017 comprehensive plan. While some may have expected that the agency would already be much further along, measuring progress is a subjective exercise. There should be agreement by all, however, that in 2021, FDA must show—by action, not just word—its continuing commitment to the public health goals outlined in 2017.
1 FDA news release, July 27, 2017
2 Speech of former FDA Commissioner Scott Gottlieb, July 27, 2017.
4 FDA special announcement, March 15, 2018
5 Federal Register Docket No. FDA-2017-N-6189, “Tobacco Product Standard for Nicotine Level of Combusted Cigarettes”
6 Apelberg, Benjamin J., Feirman, Shari P., Salazar, Esther, et al., “Potential Public Health Effects of Reducing Nicotine Levels in Cigarettes in the United States,” May 3, 2018
8 Zeller, Mitch, “The Future of Nicotine Regulation: Key Questions and Challenges,” Nicotine & Tobacco Research, 2019, 331-332, Oxford
9 Id. at 332.
10 In order to receive a marketing order, any innovative new tobacco product must be found to be “appropriate for the protection of the public health” and thereby at least demonstrate the potential to be a reduced-risk product.
11 On Dec. 31, 2020, FDA sent both the “Final Rule on Content and Format of Substantial Equivalence Reports” and the “Final Rule on Premarket Tobacco Product Applications and Record Keeping Requirements” to the Office of Management and Budget for its review.
12 In December 2020, FDA issued a further PMTA order for the IQOS 3 device (the initial order was on the IQOS 2.4 device), finding “the similarities in the product designs of IQOS 2.4 and IQOS 3, as well as the fact that the same Heatsticks are used in both devices, make it unlikely there are new concerns related to health effects, product quality, human factors or product misuse for IQOS 3 as compared to IQOS 2.4. As the two devices have similar operating procedures, use the same tobacco sources and produce comparable aerosols, FDA has no reason to believe the IQOS 3 device will result in different nicotine exposure, use patterns, user populations or abuse liability.”
13 Letter from Congressman Frank Pallone to Stephen Hahn, Feb. 25, 2020
14 Pritchard, John, “It’s Time for the Government to Refocus on Respiratory Health,” Nov. 19, 2020