A new webpage was published by the U.S. Food and Drug Administration of all the tobacco products-related citizen petitions received by the agency’s Center for Tobacco Products (CTP).
A citizen petition is a way for the FDA to give individuals, regulated industry representatives, or consumer groups to petition the agency to issue, amend, revoke a regulation, or take other administrative action. The requirements for a citizen petition are set out in the Code of Federal Regulations.
As part of CTP’s stated commitment to increase transparency, the webpage was developed to provide the public with more easily accessible and user-friendly information about tobacco product-related citizen petitions submitted to FDA and the center’s responses.
This webpage was one of the immediate actions toward transparency outlined by CTP Director Brian King in CTP’s Response to the Reagan-Udall Foundation’s report.
The new director of the U.S. Food and Drug Administration’s tobacco science division is Matthew Farrelly, former chief scientist and director of the Center for Health Analytics, Media, and Policy for RTI International.
In an announcement, the FDA’s Center of Tobacco Products (CTP) stated that Farrelly’s extensive work in the field of tobacco and nicotine science for more than 25 years, and being recognized internationally as an expert with proven leadership and organizational management skills will help him succeed as the director of the CTP’s Office of Science.
“He has led or been involved with numerous scientific endeavors related to tobacco control policies and regulatory approaches, including those related to graphic health warning labels, excise taxes, smoke-free policies, quitlines, state tobacco control programs, retail advertising, and flavored tobacco products,” the release states. “He has also extensively researched the influence of mass reach health campaigns, including FDA’s The Real Cost.”
Farrelly also has authored or co-authored over 120 articles in peer-reviewed scientific literature, according to the release. He earned his Ph.D. in Economics from the University of Maryland at College Park.
Farrelly will replace Matt Holman, who left the position last year to join Philip Morris International. Holman was hired in 2017 and took over for David Ashley.
Interested parties can now register for the Jan. 12 U.S. Food and Drug Administration seminar covering the ban of menthol flavors in tobacco products. “The Scientific Basis of Proposed Tobacco Product Standards to Prohibit Menthol as a Characterizing Flavor in Cigarettes and Flavors in Cigars” is the first FDA tobacco-related seminar of the year.
The presentation will provide an overview of the scientific evidence that informed the development of these proposed rules, with an explanation of the external peer review process the FDA utilized for review of the highly influential scientific assessments for these proposed rules.
Bridget Ambrose, director of the Division of Population Health Science in the Office of Science at the FDA’s Center for Tobacco Products, will be the speaker. Ambrose has over 20 years of experience in tobacco control and regulatory science, with specialized experience in longitudinal analyses of tobacco use.
The U.S. Food and Drug Administration’s Center for Tobacco Products (CTP) had relaxed its standards of review for certain tobacco products and stifled attempts by its scientists to raise concerns, according to an investigation conducted by the U.S. Office of Special Counsel (OSC). The OSC sent a letter to President Joe Biden and Congress outlining the findings.
The investigation began after a leading CTP toxicologist-turned-whistleblower disclosed to the OSC that a 2019 memorandum issued to the CTP’s scientists revised the process for evaluating potentially harmful ingredients in substantial equivalence applications used for certain tobacco products. According to the whistleblower, the memo directed scientists to stop using objective, quantitative data to evaluate applications and to instead use an approach that was more akin to “eyeballing it,” resulting in unclear review standards and less reliable decisions, according to the CTP.
The whistleblower also alleged that flaws in the CTP’s internal scientific dispute resolution process effectively prevented the whistleblower and several other concerned scientists from raising these issues within the agency. “This internal dispute process is intended to safeguard the integrity of CTP’s scientific evaluations, including consideration of certain tobacco products to ensure those authorized for market meet the applicable health and safety standards,” the CTP stated.
The OSC referred the whistleblower’s allegations for investigation. In response, the FDA convened an independent panel of scientific experts to evaluate allegations concerning the allegedly flawed tobacco application review process. The panel largely agreed with the whistleblower’s concerns, finding that the process lacked “quantifiable standards or criteria.” The expert panel made six recommendations, including a new process for resolving scientific discrepancies, which the agency largely adopted.
In response, the whistleblower acknowledged the CTP’s progress in giving scientists discretion to consider quantitative data in reviewing potentially harmful chemical compounds in substantial equivalence applications for new tobacco products. The CTP also revamped its scientific dispute procedures and created a mandatory training program for all CTP staff involved in scientific decision-making. While supportive of these steps, the whistleblower stated that FDA scientists will still need courage to challenge a system that “discourages dissenting voices.”
“The public depends on the FDA to vigorously implement and enforce our nation’s health and safety laws, especially when new tobacco products are being brought to market,” said Special Counsel Henry J. Kerner. “I am deeply troubled that FDA’s own scientific dispute process failed our whistleblower and fellow concerned scientists, and as a result failed the public. I commend the whistleblower for persevering in the face of these unnecessary obstacles. I also thank the FDA for taking the allegations seriously by convening an independent expert panel and for taking positive steps to repair its review process.”
The Reagan-Udall Foundation today submitted its recommendations to Robert Califf , commissioner of the U.S. Food and Drug Administration. The findings are what many in the industry are calling “meaningless” and “less than compelling.”
The report concludes that vaping industry stakeholders observed a lack of “consistent implementation” of what the industry understood to be the policies of the Center for Tobacco Products (CTP), particularly with respect to tobacco harm reduction and the requirements needed to navigate the premarket tobacco product application (PMTA) process.
The “Operational Evaluation of FDA’s Tobacco Program” was facilitated at Califf’s request. The announcement came as Califf attempted to push past several controversies that dominated his second stint running the agency, including his issuing of a marketing denial order (MDO) to e-cigarette maker Juul Labs and later having to rescind that order.
The report did highlight several wide-ranging problems that the report states hinder its ability to regulate the industry and reduce tobacco-related disease and death. The report stated that the CTP should make “process improvements and identify and address the policy and scientific questions” that underpin its regulatory framework. The review concluded that CTP’s implementation of its program also has been affected by “changes in leadership and administrations.” In its first 13 years, CTP has operated under seven different commissioners in three different administrations, and recently hired a third CTP director, Brian King.
“From the stakeholders’ perspective, policy shifts with broad impact on the industry occurred without notice. The Center has faced significant challenges in clearing its policies through the career and political infrastructure. It took years to establish requirements and standards governing application reviews, frustrating industry and creating problems for the Center itself when it received deficient applications,” the report states. “Issues in application reviews resulted in litigation necessitating re-review of some applications. The current environment reflects an unintended shift from what was structured by law as a pre-market authorization framework to the reality of a post-market regulatory environment, which is much more difficult to deal with given that there are few incentives for industry to come into compliance and many incentives for industry to delay the process.”
The evaluation and resulting recommendations focused on four program areas: regulations and guidance, application review, compliance and enforcement, and communication with the public and other stakeholders, according to the review. The review and recommendations are meant to assist the agency in making changes to better carry out its regulatory responsibilities; to strengthen its relationships with stakeholders
The report identified several fundamental issues that the center needs to address and it states that the report offers “cross-cutting as well as program-specific recommendations to help CTP operate more effectively,” according to the authors of the review.
The key points from the report can be summarized as follows:
The panel observes that CTP has been forced to operate primarily in a reactive mode, moving from one challenge to the next, mainly provoked by the outside forces. The Center should transition to becoming a more proactive and strategic program. With more substantial engagement with stakeholders and the public, CTP should take the time now to think strategically about where it is today and where it needs to go in the next several years.
Although CTP has a critical mission to protect the public health from tobacco-related disease and death and is regulating products that have no inherent benefit and huge societal costs, it is a government regulatory program with a duty to run efficiently, fairly, and transparently. This responsibility to function as an effective product regulator should be captured in the Center’s mission, vision, and goals and carried out to the best of the Center’s ability.
The panel recognizes that to improve the effectiveness of its application review, the Center should make process improvements and identify and address the policy and scientific questions that underpin its regulatory framework.
CTP needs to work with other entities on strategies to clear the market of illegal tobacco products more rapidly and provide more transparency to the public on its efforts to do so. This work is challenging but essential as CTP adopts a more strategic approach. While there is much the Center can do on its own, the panel notes that enforcement of the premarket requirements in the tobacco laws, particularly to help prevent youth use of tobacco products, requires the involvement and support of agencies other than FDA. The authors encourage the agency to elevate this issue and pursue a more comprehensive approach that leverages the resources of other agencies with a declared role in tobacco control.
“Overall, the panel is confident that many of the concerns raised in this report can be addressed by CTP’s talented and dedicated staff, with the support of FDA leadership,” the report states.
Numerous comments from purported staffers of the FDA for the Reagan Udall assessment claimed the regulatory agency is in a state of disarray and being influenced by outside forces, not scientific research. One comment stated that reviewers of premarket tobacco product applications (PMTAs) in the CTP Office of Science (OS) lack the autonomy to exercise “best scientific practices” in their reviews of PMTAs. The report fails to address these issues.
The panel was comprised of former federal public health leaders, regulatory strategists, and process improvement specialists. Lauren Silvis, served as chair of the group, which included Jane Axelrad, Keith Flanagan, Charlene Frizzera, and Alberto Gutierrez.
“The panel provided recommendations to help the Agency’s tobacco program strengthen its operations as it works to reduce the harm associated with tobacco use,” said Lauren Silvis. “The Center for Tobacco Products has made significant progress in establishing a regulatory program for tobacco products and our recommendations are intended to help the Center develop additional tools for achieving its public health objectives.”
Through multiple listening sessions, interviews, and an online portal, the group received and carefully reviewed input from a range of stakeholders, including FDA staff and the public, according to the report. The author’s claim the report offers “cross-cutting and program-specific recommendations” for the FDA to consider, “focusing on regulations and guidance, application review, compliance and enforcement, and communication with the public and other stakeholders.”
The report did not address tobacco policy issues, which are outside the scope of the evaluation, according to a Reagan-Udall Foundation.
One industry stakeholder, who asked not to be named for fear of retribution from the FDA for its brands under PMTA review by the agency, said the report’s findings were “a joke” and “completely ignorant of the real problems at the CTP.”
Califf said Monday he will review the recommendations with the aim of outlining the agency’s next steps by February.
Earlier this month, Reagan-Udall delivered its food report that was commissioned at the same time as the tobacco report. The food response suggests the agency’s leadership be restructured to improve its response to emergencies, including the recent shortage of baby formula
Reagan-Udall was created by Congress to help further FDA’s mission. The non-profit receives funding from both the FDA and the industries it regulates, including drugmakers.
Recently, U.S. Food and Drug Administration Commissioner Robert Califf announced an external evaluation of both the Human Foods Program and the Center for Tobacco Products (CTP). The FDA press release observed that “… even greater challenges lie ahead as we determine how the agency will navigate complex policy issues and determine enforcement activities for an increasing number of novel products that could potentially have significant consequences for public health. To that end, the review will push toward ‘organizational excellence.’”
Califf is right—the CTP clearly requires assistance. The purpose of this article is to review how the CTP arrived in this untenable situation and to suggest areas of focus for the review of the CTP processes.
How Did We Get Here?
There is little doubt that the CTP is in an unenviable position. No matter which way the agency turns, it is impossible to please everyone. The anti-tobacco/vaping groups will never be satisfied until all tobacco products are gone—so realistic harm reduction propositions from the center will always be met with opposition. And when the CTP tries to develop policies with a focus on efficiency, many in the industry claim that they are “prohibitionist” and that they have no regard for harm reduction and/or the human and economic consequences of their decision-making.
Recently, several court opinions and CTP actions have significantly contributed to the challenging environment for the CTP:
West Virginia v. EPA. While not directly related to the CTP, the West Virginia v. EPA Supreme Court decision has reopened the question as to whether discretion of regulatory agencies may become more limited in the future. The court seems poised to chip away at longstanding doctrines (or apply them more forcefully) to limit agency power and place policymaking back with the legislature.
Cigar Association of American v. FDA. More recently, in the Cigar Association of America v. FDA case, Judge Amit Mehta of the U.S. District Court for the District of Columbia examined whether the FDA’s decision not to exempt premium cigars from the Deeming Rule was arbitrary and capricious. The court ultimately found that the FDA ignored evidence in the rulemaking record—and ruled against the agency.
Juul v. FDA. Days later, the CTP found toxicological issues with Juul’s popular vapor products and issued marketing denial orders (MDOs) for those products. Not surprisingly, Juul immediately requested and received an emergency stay of the MDOs from the D.C. Circuit. Without missing a beat, the CTP promptly “… administratively stayed the marketing denial order. The agency [determined] that there are scientific issues unique to the Juul application that warrant additional review.” Several commentators questioned the CTP’s rationale for its decision to re-review Juul’s applications, and some have gone so far as to suggest that this quick reversal indicates a less than appropriate review of Juul’s data or worse—a lack of confidence in the CTP’s decision-making. Either way, the entire chain of events draws into question the CTP’s review process.
Finally, the CTP is still under pressure to complete decisions on premarket tobacco product applications (PMTAs) for those companies addressed in the Maryland court decision which, according to the CTP, will not be completed until next summer. Further compounding the CTP’s problems, the center continues “processing” approximately 1,000,000 synthetic nicotine PMTAs past the congressional deadline for marketing decisions on July 13, 2022. How the center will respond to this pressure is anyone’s guess. So far, it seems like the CTP continues to move at its own pace, following the Maryland court’s order to the best of its abilities.
These external and internal factors point to one conclusion that cannot be ignored—the CTP appears to be struggling and needs something to change. With the above in mind, the following are a few areas ripe for external (and internal) review at the CTP.
Credit: Fizkes
Operational Changes
Operationally, the CTP seems to have the resources (personnel and budget) to successfully regulate tobacco products. That said, certain policy choices and administrative actions (both self-inflicted and externally inflicted) appear to hamper the center’s ability to effectively manage the space. Importantly, effective regulation is hamstrung by the complexity of the U.S. tobacco regulatory scheme, a lack of clear standards for product testing and approval and a too opaque product application process.
The most challenging operational issues come from the existing regulatory scheme, which is too complex for tobacco products. The Tobacco Control Act dictates the parameters/guardrails, but the CTP has latitude in how the process is implemented. The comprehensive PMTA guidance and robust final rule demand a scientific depth that goes too far. The question is: Is all of the delineated scientific data really necessary to determine that a product is appropriate for the protection of public health (APPH)?
If comparing to combustible cigarettes, it would seem that most electronic nicotine-delivery product APPH determinations could be made based on chemistry alone. Piling on bench toxicology, human factors, pharmacokinetic and behavioral studies, it’s no wonder the review process takes so long.
Standards are not clear. Without clear standards, the CTP and industry both are left constantly employing guesswork and conjecture to facilitate decision-making. While understandably there is no simple formula for APPH, clear expectations would be beneficial and efficient. By way of example, which device characteristics really need testing? What is the depth of stability testing necessary? What constitutes a sufficient PK [pharmacokinetic] study? While the initial meeting with the Office of Science is often useful to help answer questions like these, better defining product-specific standards and setting minimums would go a long way to streamlining the approval process.
Transparency is lacking. While one can review the Technical Project Lead Reviews and some of the review standards memos that the CTP places on its website, few PMTA applicants have any idea what’s going on with their applications at any given time. Other than the initial pre-PMTA meeting and the sole deficiency letter, there is little that applicants know about the status (both administratively and substantively) of their applications. While more transparency about the status of applications would be welcome, more back and forth on issues in applications would benefit everyone—particularly the CTP. In the case of Juul, reports indicate that Juul provided thousands of pages of data related to the toxicological issue that the CTP raised in the MDOs. If the now outdated additional information requests were utilized by the CTP, Juul would have pointed out this data, and at least one issue could have been resolved well short of a trip to the courthouse.
Credit: Oleg
Policy Changes
It goes without saying that U.S. government policy can be fickle to say the least. Setting and maintaining long-term policy is difficult—especially in light of changing administrations every few years. Despite this, overriding policy tenants as they relate to harm reduction can, and should, form the cornerstone of tobacco regulatory policy. If harm reduction is the priority, then regulators need to prioritize pathways for reduced-harm products to enter the market, incentivize innovation and focus on providing offramps to combustible cigarette smokers seeking to quit smoking.
Harm reduction policy. During the tenure of former Commissioner Gottlieb at the FDA, many in the industry thought harm reduction would prevail and that all would recognize vapor products’ place at the opposite end of the continuum of risk from combustible cigarettes. Unfortunately, the significant uptick in youth experimentation with a few types of vapor products prodded the CTP into a tough position. Public health groups, dissatisfied with the CTP’s pace, forced the center into a corner via litigation.
Assuming the goal of the Tobacco Control Act remains to reduce smoking-related morbidity and mortality, harm reduction strategies are central to achieving that goal. Importantly, harm reduction strategies should be palatable to all stakeholders. While the CTP has several initiatives moving forward, is there a plan for initiatives dedicated to moving smokers to safer alternatives? Efforts to move smokers to less risky alternatives do nothing when those less risky alternatives cannot succeed via the PMTA pathway. Current tobacco policy is remarkably dissimilar from the variety of strategies employed for other unsafe behaviors where harm reduction is embraced as the primary alternative. In areas such as drug use and sexually transmitted diseases, our society generally accepts reduced-harm efforts, but for tobacco, collectively we are still searching for that sweet spot.
Given all the challenges that the CTP faces, working on harm reduction policies hand-in-glove with nongovernmental groups and industry probably does not seem like the best use of time. When the center was first formed, frequent scientific meetings were held on various issues (such as harmful and potentially harmful constituents). These have fallen off in recent years, likely in part due to Covid and also due to the onerous demands on the center. Prioritizing genuine and open conversations between the CTP, industry and tobacco control groups is critical to developing strong harm reduction policies. Holding scientific meetings (either through the CTP or the Tobacco Products Scientific Advisory Committee) on harm reduction plans and policies would add transparency and bring all ideas to the table.
The FDA should not let the perfect be the enemy of the good when considering reduced-harm products. At present, PMTA reviews appear to be searching for the perfect. Reviews seem to focus on the smallest details that might pose a risk while ignoring a more generalized comparison to combustible products with 70 known carcinogens (and a track record of 480,000 deaths per year). APPH does not mean no risk—it means less risk than the deadliest consumer product ever invented, the combustible cigarette. Reconsidering how APPH is adjudged would be an excellent first step in combatting morbidity and mortality attributable to smoking.
Investing in harm reduction must be incentivized. If one wants to develop a new product, the timeline is a hard stop. A year of product development, up to three years of PMTA testing (including two years of stability and time to plan, conduct and write up the studies) plus one year to three years of the CTP review before the possibility of a marketing order sounds like a pretty poor investment. The PMTA process must change to bring less risky products more rapidly to market.
Society must not forget about smokers. Youth tobacco issues are important, but the 1,300 smokers dying each day are important too. A balanced harm reduction policy—controlling youth access and exposure while moving combustible cigarette smokers to quitting tobacco altogether or moving to a less risky product is necessary.
Moving Forward
Hopefully the external review will be a fruitful exercise—one that provides robust alternatives for the CTP to consider. The review, if rightly focused, will address foundational issues that will, in the end, lead tobacco regulation to a reasonable, reduced-harm world where smokers are given hope for a future.
Chris Howard is vice president, general counsel and chief compliance officer at E-Alternative Solutions, an independent, family-owned innovator of consumer-centric brands.
Rich Hill is the compliance director and associate general counsel of E-Alternative Solutions.
The U.S. Food and Drug Administration’s Center for Tobacco Products and the National Institute of Health’s National Institute on Drug Abuse announced the availability and location of newly released and updated data files from the Population Assessment of Tobacco and Health (PATH) Study, including the following:
The Wave 5.5 Special Collection data were collected from youth participants ages 13 to 19 between July and December 2020. Data in the PATH-ATS were collected between September and December 2020 from a subsample of adult participants ages 20 and older, complementing the Wave 5.5 Special Collection. Additionally, Restricted-Use Files have been updated to include Wave 5 Ever/Never Reference Data, and the Restricted-Use and Public-Use Master Linkage Files have been updated.
Questions about the collection, content, weighting, documentation, or structure of PATH Study data (this excludes questions on statistical analysis or analytic guidance) may be submitted to PATHDataUserQuestions@Westat.com.
