Briefing: Reagan-Udall Foundation evaluation of FDA’s tobacco program – a response

Introduction

We welcome the Reagan-Udall Foundation’s operational evaluation of the FDA’s tobacco program. ¹ We commend your initiative in commissioning the evaluation and welcome the constructive and open-minded response from the Center for Tobacco Products. ² We hope the Reagan-Udall findings will prompt a strategic reassessment. To that end, we are writing with comments on the Reagan-Udall findings and suggested directions for FDA’s program. In response to the main recommendation, we propose an updated strategic framework that builds on the 2017 Comprehensive Plan.

The central concern of the Foundation’s experts was the absence of a coherent regulatory strategy for the Center for Tobacco Products (CTP).

CTP must invest the time, now, with staff and public input, to create and implement a Strategic Plan that identifies the Center’s strategic objectives and plots an operational roadmap of the steps CTP will take over the next five years to achieve those objectives.

Proposed four-part strategic framework for tobacco regulation

Goal: a relentless focus on reducing serious diseases and premature death

Consistent with the vision of CTP, ³ the purpose of the tobacco program should be to reduce the burden of tobacco-related disease and death as deeply and rapidly as possible. This goal is aligned with President Biden’s priorities as outlined in the briefing for the 2023 State of the Union address. ⁴

Tackling the biggest single driver of cancer deaths in this country – smoking. The Administration is preparing further action to help people avoid smoking in the first place and support Americans who want to quit.

We concur with the Administration’s focus on smoking as the primary driver of cancer and other serious tobacco-related diseases. The tobacco program would have four interrelated elements. We list these below and expand in the following paragraphs.

1. To degrade the attractiveness and addictiveness of cigarettes and other combustible tobacco products.
2. To promote transition pathways to smoke-free status.
3. To control risks arising from the ongoing use of smoke-free nicotine products.
4. To protect young people from tobacco-related health and welfare risks.

1. To degrade the attractiveness and addictiveness of cigarettes and all other combustible tobacco products

Around 3,000 lawfully available cigarette products continue to dominate the consumer nicotine market. ⁵ They are used by over 30 million adult smokers, causing 480,000 deaths every year - about 1 in 6 deaths - leaving 16 million living with smoking-related diseases. ⁶ Yet the regulation of these products is comparatively light compared to the heavy burdens of the pre-market application process for much safer non-combustible nicotine products. This disproportionate and distorting regime must become more “risk-proportionate.” This means increasing regulatory controls on harmful combustibles and making the regulation of safer, non-combustible products more efficient and proportionate.

FDA has several options for rulemaking and communications to achieve this aim. Using its power under Section 907 of the Tobacco Control Act, Tobacco Product Standards, ⁷ FDA could introduce a broader range of controls on ingredients or emissions. These could include the regulation of significant toxicants and addictive agents to reduce the toxic burden, limit addictiveness, and control abuse liability or aspects of product appeal. Using its powers under Section 906, ⁸ FDA could address aspects of cigarette marketing, including packaging and appearance, and impose more detailed or impactful consumer information.

The federal government as a whole should support action to limit the appeal of smoking, including through tax policy that is more in line with other high-income countries. ⁹ Such measures will be effective if, and only if, smokers are motivated to transition to a low-risk smoke-free status rather than to access illicit smoking products or to find workarounds. There must be diverse, competitive, and lawful low-risk options available for smokers to switch to. The success of rules to control the addictiveness or appeal of cigarettes will be contingent on the supportive measures that influence the behavioral pathways followed by smokers in response to toughened cigarette regulation. Tobacco product rulemaking cannot be separated from policies that affect the behavioral response to the rule.

2. To promote transition pathways to smoke-free status

FDA should aggressively prioritize achieving smoking cessation and smoke-free status for those at great risk of experiencing health problems due to smoking (i.e., those with pre- existing smoking-related health conditions and those with mental health or substance use disorders). This could incorporate CDER licensing of improved smoking cessation treatments and authorizing a diverse range of smoke-free alternatives to cigarettes. It could mean using its education and communication resources to reset the highly inaccurate public perceptions of risk and misunderstanding of nicotine and encourage switching to smoke-free alternatives for those who want to continue using nicotine. We must recognize that people who smoke will follow different pathways to smoke-free status. For many, stopping smoking will feel more like an evolution of their consumer smoking behavior as they become “accidental quitters.” ^{10 11}

3. To control risks arising from the ongoing use of smoke-free nicotine products

The demand for nicotine will be more persistent than the demand for cigarettes. Nicotine use has a long history and is likely to persist on account of actual or perceived benefits to the user. ^{12 13} While significantly less risky than smoked products, smoke-free products still impose controllable risks on the user. These should be reduced to the extent possible but consistent with enabling such products to displace smoking and meet the needs of consumers. The aim should be a diverse market of lawfully sold and regulated products with acceptable risks – mindful of the excess risks associated with illicit trade and informal manufacturing and supply. The regulation of the product itself should focus on the users’ interest in protection from chemical, electrical, thermal, and mechanical risks. In contrast, regulation designed to protect youth and non-users should focus less on product design and more on marketing, branding, packaging, and compliance with age and other point-of-sale restrictions.

Once established, such restrictions must be enforced. Currently, manufacturers who invest financial and human resources in compliance face competition from companies that do not even try to comply. We discuss enforcement as a supporting measure below.

4. To protect young people from tobacco-related health and welfare risks

No responsible adult wants young people to smoke, vape, or use nicotine in any form. This is the case for most youth risk behaviors. Despite adult disapproval, there is widespread risk- taking among a subset of adolescents. The strategy should adopt a more sophisticated real- world view of young people and their risk behaviors. It should recognize that some adolescents would likely become smokers or choose to use nicotine as adolescents, just as they use alcohol or other drugs. Other teenagers will engage in transient experimentation without long-term consequences. ¹⁴ Any understanding of youth vaping should consider both the frequency of use and propensity to use tobacco. ¹⁵ For some youth, vaping could be a diversion from smoking. ^{16 17} Youth smoking has fallen at an accelerated rate as vaping has increased, ^{18 19} leading to substantial overachievement of Healthy People targets for youth smoking. ²⁰ FDA should acknowledge that when prevention efforts fail, as should be expected in high-risk youth, it would be preferable that they use a safer non-combusted nicotine product rather than cigarettes. ²¹ No practical barrier can keep accurate, usable risk communications for adults away from youth. Adolescent experimentation with adult behaviors is inevitable but often transient and of little long-term consequence. It is not realistic to classify all youth as non-smokers for the purposes of regulating smoke-free products without considering what pathways they would follow in the absence of smoke-free alternatives.

The tobacco-related welfare of young people is also often contingent on parents or significant adults. Adults affect the welfare of children and adolescents through role modeling smoking, the impact of smoking on the household budget, and smoking-related harms, including caring responsibilities, grief, and secondhand smoke exposure. Young people grow up to be adults and may value having safer options when they are older. It is impossible to neatly separate youth and adult populations from a public health policy perspective.

We recommend that FDA takes a holistic view of the interests of young people, recognizing and carefully weighing benefits and detriments arising from the changing landscape of regulated nicotine products. Interventions should focus on age restrictions and controls on packaging, trademarks, and branding that are disproportionately attractive to youth.

Recognizing inter-relationships between the elements of a strategy

The interrelationships between these four elements are critical. A strategy strongly emphasizing smoking cessation must offer sound pathways to abstinence or smoke-free alternatives. An approach to smoking cessation that works through smoke-free alternatives must be subject to safeguards to discourage youth use and ensure products are acceptably safe. However, standards to control the risks of smoke-free products should maintain the value of these products as alternatives to cigarettes – the perfectly safe product that no one is willing to use has no public health impact. There must be a balance between risk and likelihood of use. ²² Equally, an approach to youth protection from vaping should not be so stringent that it favors the incumbent cigarette trade, imposes significant harm on adult or adolescent smokers, or leads to the engagement of young people in illicit trade or more dangerous workarounds. Unintended perverse consequences should be a primary consideration in designing a regulatory system. While these interrelationships should be a significant consideration during a strategy-forming process, the rigor and robustness will need to be validated throughout five years of implementation. We suggest regular stakeholder engagement and assessment of the routine performance of a strategic framework, but also as it faces novel risks or opportunities.

Balancing risks and benefits and making trade-offs

The Reagan-Udall evaluation highlighted a range of unavoidable trade-offs in making determinations under the “Appropriate for the Protection of Public Health” (APPH) standard.

This lack of clarity, transparency, and communication extends to questions about: how the Agency intends to balance individual risk/benefit against population risk/benefit while carrying out its public health mission; how the Agency will weigh concerns about youth uptake of nicotine products against the harm-reduction potential of non-combustible tobacco products, how the Agency views the science that must inform these decisions

We agree with the Reagan-Udall assessment that much of this is unclear and inconsistent in FDA’s approach to tobacco and nicotine regulation and its operationalization of the APPH test. To reconcile these trade-offs, we recommend a balanced approach to the science along the lines proposed by fifteen past presidents of the Society for Research in Nicotine and Tobacco (SRNT). ²³

In making its determinations, FDA must consider the following:

• The interests of adult smokers as well as risks arising from youth uptake of vaping.
• The interest of young people in adult smoking cessation, including parents and other significant adults.
• The interests of adolescent vapers who would otherwise become smokers.
• A realistic weighting of the harm to adult or adolescent vapers compared to risks to adult or adolescent smokers based on the likelihood that the behavior will lead to serious disease and premature death.
• The economic and population trend evidence suggests the net effect of vaping at the population level is to displace smoking and, overall, to contribute to a decline in smoking prevalence. ²⁴ E-cigarettes function as an economic substitute for cigarettes. ²⁵
• The potential unintended detrimental consequences of well-intentioned regulatory actions, including de facto bans on flavored e-liquids. Given the relative risks, only a minimal unintended increase in smoking, through reduced switching or quitting, could easily outweigh any benefits arising from reduced vaping.

Supporting measures

The four strategic pillars proposed above should be accompanied by four supporting measures listed below.

1. Education: undertake a concerted communications effort to better align public perceptions with scientific insight.
2. Efficiency: make immediate improvements in the efficiency, transparency, predictability, and proportionality of the PMTA process.
3. Enforcement: build a rational regulatory regime and then enforce it.
4. Engagement: proactively engage stakeholders.

1. Education: undertake a concerted communications effort to better align public perceptions with scientific insight

Risk perceptions influence choices made by tobacco and nicotine users. With reliable information, people can make choices in their best interests. There is never an ethical case to manipulate risk perceptions with false or misleading information to achieve a favored behavioral outcome. Not only is this likely to have unintended adverse consequences (more smoking), it violates the public health principle of autonomy and erodes trust in public health agencies and advice. ²⁶

For FDA to execute a strategy that reduces tobacco-related disease at the greatest possible rate, the public will need to understand the conceptual foundations of measures like lowering nicotine levels in cigarettes and encouraging smoking cessation by switching to smoke-free nicotine products.

It is concerning, therefore, that Americans have serious misperceptions about the relative risks of smoking, vaping, and smokeless tobacco, ^{27 28} and there is widespread misunderstanding of the role of nicotine in causing disease. ²⁹ Despite significant communications budgets, these perceptions have steadily deteriorated and departed from science-based findings. Adverse perceptions can underpin harmful behaviors, for example, by making people who smoke more reluctant to switch to e-cigarette use. ^{30 31}

We are concerned that communications targeted at youth go beyond what can be justified scientifically and that there are instances where specific messaging (for example, EVALI or gateway claims) have adversely and inappropriately influenced risk perceptions. ³²

Further, FDA generally accepts that tobacco products exist on a risk continuum and with a qualitative step between combustible and non-combustible products. FDA also acknowledges that there are misperceptions about the health impacts of nicotine. However, to our knowledge, the Centre for Tobacco Products has not conducted any mass communication or educational activity to rectify these misperceptions. In a refreshed strategy, that should change.

We believe the FDA and CDC should establish measurable goals to create more realistic and actionable risk perceptions to support individual behavior change and underpin a credible strategy for tobacco and nicotine.

2. Efficiency: make immediate improvements in the efficiency, transparency, predictability, and proportionality of the PMTA process

There is a clear asymmetry between the low regulatory burdens facing cigarettes and the high barriers to entry for novel and reduced-risk nicotine products. The FDA’s interpretation of its duties may create a regulatory protection for the incumbent cigarette trade and function as a barrier to the rapid reduction of smoking.

We recommend that the PMTA regime be simplified and made more proportionate by the following:

• Develop and communicate a principled, transparent, proportionate, and legally defensible strategy for APPH determinations. If applicants are clear on what is expected and how their applications will be evaluated, there will likely be fewer applicants and better-quality applications. A robust regulatory strategy is the structural solution to the backlogs, litigation, and overwhelming demands on FDA staff and applicants.
• Aim to create routine and expedited pathways through evaluation for products that are broadly similar and already well-established in the market. ³³ By avoiding unnecessary repetition, FDA could reserve its scientific and assessment resources for novel products that present either novel risks or new opportunities. FDA should be able to prioritize innovations that are likely to advance the public health agenda, for example, by reaching particular at-risk populations, highly dependent smokers, or nudging dual users into exclusive use of low-risk products.
• Improve the transparency of FDA’s evaluation criteria and how the agency maintains consistency between products, assessors, and over time. Any guidance to assessors (e.g., internal reviewer guides, briefs on the state of the science) should be made public and readily available to applicants.
• Use guidance to provide advisory standards-based pathways through the PMTA assessment. Such ‘soft standards’ or ‘heuristics’ would not be mandatory tobacco product standards under the Tobacco Control Act. Applicants and evaluators would use them to expedite and simplify the technical evaluation process by capitalizing on commonly accepted scientific findings. The approach would be “comply or justify,” meaning that additional evidence and scrutiny would be required for products that did not meet these soft standards.
• Such ‘soft standards’ could also inform priorities for the exercise of enforcement discretion. For example, a soft standard that creates a presumption against using cartoons or childish branding would signal manufacturers not to include such imagery in pre-market applications (or be prepared to justify it) and to expect priority enforcement action in the absence of a PMTA.
• Develop a range of mandatory tobacco product standards under the Tobacco Control Act Section 907. This approach should help to standardize assessments and avoid the cost and waste of applications that will fail. ³⁴
• Pre-market assessment should focus on risks to the individual (toxicity, safety, abuse liability). Where individual risks are likely to be much lower, population and behavioral effects should be assessed post-market using real-world data. If adverse effects emerge, FDA retains the power to take corrective action, including removing products from the market.
• Use a single market-wide post-market surveillance system funded by user fees rather than imposing significant surveillance burdens on each applicant. A single surveillance system will provide a better insight into population effects, effects arising at category rather than product level, and capture products without authorization.
• Introduce a simplified system for evaluating incremental improvements to authorized products so American consumers can benefit sooner from product innovations. This should apply to both the PMTA process for authorizations and the MRTP pathway for modified risk claims. FDA’s processes should encourage pro-health innovation, not obstruct innovation or deny Americans access to the best technologies available worldwide.
• Provide applicants with meaningful information on the progress of their applications with estimated decision dates. For many businesses, FDA’s decisions are mission-critical and may be the difference between business viability and failure. They are entitled to timely assessments and realistic expectations about decision-making.
• Engage consistently with applicants to address reasonable application deficiencies so that these can be remedied with a view to FDA granting marketing orders rather than as a reason for abrupt denial. FDA should be aiming for a regulated competitive market with a diverse range of compliant products. In addition, FDA should benchmark its processes against the requirements of good regulatory practice set out in relevant Executive Orders. ³⁵ In doing so, FDA should revisit the Regulatory Impact Analysis for the 2016 deeming rule to reassess value for money and efficiency in the light of experience and outturns. ³⁶

3. Enforcement: build a rational regulatory regime and then enforce it

FDA should use its powers to provide meaningful consumer and public health protections but also to promote fair competition between regulated entities in compliant products. There is little value in regulation without enforcement, and a regulator that tolerates non- compliance is fundamentally unfair to those who have invested financial and human resources in achieving compliance.

However, excessive, arbitrary, and unfair regulation creates widespread non-compliance, unstainable enforcement burdens, costly challenges through litigation, and potential loss of trust and support for regulation. The balancing act for FDA is to match an efficient, transparent, and proportionate regulatory regime with effective enforcement. The regulation must be reasonable and its enforcement manageable. The recent history of regulation following the 2016 Deeming Rule does not strike this balance.

Until a rational regulatory framework is in place, the scale of de facto non-compliance will make it necessary to take targeted enforcement action. We recommend the following order for enforcement priorities:

• Activity by criminal networks or well-organized illicit supply chains. It is essential to suppress the growth of illegal supply networks in advance of further rulemaking,
• Age-related restrictions, including effective communication of Tobacco 21 and mandating ID checks at point-of-sale for all tobacco products,
• Removal of products where guidance or standards would mean that the product would be unlikely to be authorized for sale in the United States
• Removal of products for which no pre-market application has ever been made,
• Removal of products for which a pre-market application has been made and rejected.

4. Engagement: proactively engage stakeholders to build consensus and secure buy-in

We would like to see FDA use its good offices and convening power to try to nurture a more supportive external environment. CTP could use its convening power to bring together experts, activists, and academics to seek common ground and narrow and articulate differences.

In 2018, the then CTP Director, Mitchell Zeller, posed six questions that would shape attitudes to nicotine and regulation. ³⁷ These questions remain relevant today and mostly remain unanswered in the mainstream of tobacco control. Today’s CTP leadership could update those questions and try to build a consensus on the answers.

FDA could play an ‘honest broker’ role in assessing and synthesizing research findings on controversial subjects ³⁸ - for example, setting out a factual assessment of the EVALI outbreak or claims about gateway effects. ³⁹ In 2021, 42 tobacco and nicotine policy experts called on the FDA to commission a follow-up to the 2001 Institute of Medicine Report, Clearing the Smoke, which forms a basis for tobacco harm reduction policy in the United States. ⁴⁰ A recent FOIA request shows that the FDA conducts or commissions high-quality scientific assessments for internal use. ⁴¹ Such reviews are valuable to all stakeholders and provide a common base of knowledge. They should be made public.

FDA could use the Tobacco Products Scientific Advisory Committee (TPSAC) ⁴² more creatively and routinely. For example, TPSAC could be asked for advice on regulatory strategy at the category level rather than on a product-by-product basis. TPSAC’s deliberations and findings could help to establish external consensus and buy-in to well- founded FDA regulatory policy and determinations.

Conclusion

We have summarized our proposals in the attached cover letter. We have set out a four-part strategic framework for tobacco and nicotine regulation focused on radically reducing the disease risk and premature deaths arising from smoking, the availability of attractive pathways out of smoking, proportionate regulation of low-risk alternatives to cigarettes, and the protection of youth. It is essential to recognize the inter-relationships between the elements of the strategy and to be candid and explicit about trade-offs between different regulatory goals. In addition to a four-part strategic framework, we advocate four supporting measures. These would improve risk communication, make a step change in process efficiency, take a more rational and manageable approach to enforcement, and use FDA’s formidable reputation to build consensus and buy-in.

The American public deserves and should expect a transparent, proportionate, and science- based regulatory system for tobacco and nicotine products. We hope the proposals contained in this briefing will assist FDA in implementing reform in response to the Reagan- Udall evaluation of the Center for Tobacco Products.