During an exclusive interview with the Associated Press, the director of the U.S. Food and Drug Administration’s Center for Tobacco Products (CTP), Brian King, said the FDA is well on its way in setting a foundation for substantial reductions in combustible tobacco smoking with the product standards such as a menthol ban and flavor bans for e-cigarettes and cigars.
Brian King / Credit: FDA
When asked about several surveys that have shown many adults think e-cigarettes are as dangerous as traditional cigarettes, King said he was fully aware of the misperceptions surrounding vaping products those misperceptions aren’t consistent with the known science.
“We do know that e-cigarettes — as a general class — have markedly less risk than a combustible cigarette product,” King said. “That said, I think it’s very critical that we inform any communication campaigns using science and evidence. It has to be very carefully thought out to ensure that we’re maximizing impact and avoiding unintended consequences.”
King also said he believes “there’s a lot of really important science and innovations” that have occurred in the vaping industry in recent years, adding that the most notable is nicotine salts in e-liquids.
“We know that when you smoke a tobacco product, it’s a very efficient way to deliver nicotine across the blood-brain barrier. So it’s been very difficult to rival that efficiency in another product,” said King. “But in the case of nicotine salts you have the potential to more efficiently deliver nicotine which could hold some public health promise in terms of giving smokers enough nicotine that they would transition completely.
“But you also have to consider the opposite side of the coin, which is the inherent risks of initiation among youth. So I do worry about that … there’s a lot happening and I think that it could be promise or peril. But I think it’s important that the science drives that.”
How companies can make the most of a recent court ruling requiring the FDA to reassess thousands of PMTA rejection notices.
By Neil McKeganey
It would be hard to overstate the threat that youth vaping in the United States poses to the use of e-cigarettes as a means of tobacco harm reduction. Respected national surveys have shown a rising trend in youth vaping, with the threat to the vaping industry as predictable as night following day.
Former Food and Drug Administration Commissioner Scott Gottlieb could not have been clearer in signaling that threat when he said that the offramp to adult smoking could not be justifiably achieved at the cost of the on-ramp of teen vaping. If anybody was in any doubt about the risks that youth vaping poses to the entire e-cigarette industry, those doubts would have surely been extinguished in the recent ruling against Juul Labs, which required the company to pay in excess of $438 million to compensate states for the harms caused by past marketing practices increasing the likelihood of youth using their eponymously named vaping device.
For vaping companies, the threat of youth vaping may have lifted slightly in a recent U.S. court ruling requiring the FDA to pay attention to what vapor companies are doing in trying to restrict youth access to their products. Odd as it may sound, after having encouraged vapor companies to pay attention to their marketing and sales practices in light of the rising trend in youth vaping, the FDA’s position appears to have been that those efforts were almost certainly doomed to fail, with youth accessing what are often easy-to-conceal vaping products with relatively little difficulty through their social networks.
With vapor companies having invested heavily in age verification software, point-of-sale restrictions and in the removal of flavored e-liquids, it would have been a bitter pill to swallow to be told that the regulators had largely ignored those efforts to reduce youth access to their products.
The logic behind the FDA’s decision seems to have been that it would be easier to expedite the large number of premarket tobacco product applications (PMTAs) by adopting a “Fatal Flaw” approach—rejecting those applications that did not present data from either longitudinal customer studies or randomized trial evaluations and simply ignoring what the companies were doing to lessen the likelihood that their products would be found in the hands of youth.
By ruling against the FDA in legal action initiated by six vapor companies that had received marketing denial orders without the FDA even paying attention to their youth sales restriction efforts, the judges have effectively provided vapor companies with a second chance to have their PMTA applications reassessed.
So, what should vapor companies do given the legal victory that has been dropped in their lap? Clearly, it is going to be important for companies to do all they can to restrict youth access to their vapor products. But actions taken by these companies is not the same thing as being able to present evidence to the FDA that their products are not being used by youth.
To this end, research undertaken by the Centre for Substance Use Research (CSUR) in Scotland may help many of the companies concerned. For the last two years, the CSUR has been measuring the prevalence with which over 200 e-cigarette devices are being used by youth and adults within the United States. This ongoing research provides vapor companies with product-specific data showing the extent to which their products are being used, or more crucially, are not being used by youth.
Valuable as the data from this study undoubtedly are, vapor companies also have to be able to show the benefit of their products to adult smokers. The fastest route to obtaining this data is through an actual use study in which adult smokers using a company’s vapor products are monitored over a number of weeks to determine how many smokers are able to quit or reduce their cigarette smoking through using the company’s vapor products.
To obtain a marketing authorization, vapor companies have to be able to show two things—that their products are not being used by youth and that they can help adult smokers in quitting or reducing cigarette consumption. Succeed in these two things and vapor companies can have a bright future. Fail in either one and the future looks a lot bleaker.
Neil McKeganey is the director of the Center for Substance Use Research in Glasgow, Scotland.
A U.S. appeals court denied a petition to review the Food and Drug Administration’s marketing denial order (MDO) to Illinois-based e-liquid manufacturer Gripum, reports Vaping360.
Gripum submitted premarket tobacco product applications (PMTAs) in September 2020 for about 200 bottled e-liquid products in nontobacco flavors. The company received an MDO on Sept. 8, 2021. Gripum filed a petition for review on Oct. 8 and was granted a stay of FDA enforcement in November 2021. The company participated in oral arguments before the court on April 20.
Gripum argued that the MDO was unfairly issued because Congress and the FDA did not establish any “ascertainable standards” to determine if the company’s products are “appropriate for the protection of public health.” The company also said that the agency changed the evidentiary standard for a successful PMTA after the application deadline had passed and that the agency failed to conduct individualized PMTA reviews as required by the Tobacco Control Act.
The 7th Circuit Court of Appeals rejected all of Gripum’s arguments, finding that the FDA’s approach to resolving the application was both reasoned and consistent with the Tobacco Control Act.
Gripum’s defeat follows a successful MDO challenge by six vapor companies. On Aug. 23, the U.S. Court of Appeals for the 11th Circuit granted petitions for review filed by Bidi Vapor, Diamond Vapor and four other companies challenging the FDA’s rejection of their e-cigarette applications.
The U.S. Food and Drug Administration’s Center for Tobacco Products (CTP) has updated the term “grandfathered tobacco product” to “pre-existing tobacco product” to describe these products more appropriately.
Additionally, the term “grandfathered,” when used to describe someone or something exempt from a new law or regulation has its roots in 19th century racist voting laws, according to the FDA.
Like the grandfathered products before it, a pre-existing tobacco product is any tobacco product (including those products in test markets) that was commercially marketed in the United States as of Feb. 15, 2007.
As was the case with submitting a grandfathered determination request, submitting a request to determine the pre-existing status of a tobacco product is voluntary and not required under the Federal Food, Drug and Cosmetic Act.
According to the CTP, the terminology update requires no additional action by companies with pending grandfathered determination request.
A split 11th Circuit on Tuesday told the U.S. Food and Drug Administration it shouldn’t have denied six e-cigarette companies’ premarket tobacco product applications (PTMAs) to sell flavored vaping products without first taking a look at their marketing and sales plans designed to minimize youth exposure and access.
The U.S. Court of Appeals for the Eleventh Circuit granted petitions for review filed by Bidi Vapor, Diamond Vapor and four other companies challenging the FDA’s rejection of their e-cigarette applications in a 2-1 decision. According to Chief Judge William Pryor, the agency didn’t assess “the companies’ marketing and sales-access-restriction plans designed to minimize youth exposure and access.”
The court explicitly labeled the FDA’s decision-making as “arbitrary and capricious.” Prior legal decisions have determined that FDA action must consider all relevant factors in order to be legally justifiable. In the case of these vape manufacturers, the court ruled that the FDA had not performed such consideration.
“These tobacco companies submitted survey information from their customers about smoking cessation, literature reviews, scientific studies about switching to e-cigarettes, smoking cessation, and the role of flavors, and details about its marketing and youth-access-prevention plans,” notes the court in its opinion. “For example, Diamond uses technology for its online sales that relies on public records to verify a purchaser’s age.”
Vapor industry advocates welcomed the decision. Gregory Conley, director of legislative and external affairs at the American Vapor Manufacturers Association said that while court ruling does not order the FDA to grant PMTAs—and that the agency is likely to deny the applications in the future—the companies involved could end up in the queue for review in 2025, which keeps them in business.
“Additionally, this leaves the door open for further litigation on these and other PMTAs,” Conley wrote on Twitter. “The FDA’s vague and undefined ‘appropriate for the protection of public health’ standard has long been open for attack. This is just the start.”
The 11th Circuit decision follows revelations that forced the FDA to admit to not considering all evidence when issuing marketing denial orders (MDOs) to vape products made by Juul and Turning Point Brands. In the interests of public health, future FDA decision-making must engage with all available evidence, not just evidence that leads to their preferred outcomes.
The court also recognized relevant distinctions between closed/cartridge systems and the e-liquids used in open systems. The court also found that the FDA’s refusal to review marketing plans was “error and not harmless” (disagreeing with Fifth and DC Circuits).
All petitioners’ appeals were granted, denial orders vacated and remanded.
In her dissent, Judge Robin Stacie Rosenbaum wrote that anyone who knows all the relevant facts of this lawsuit probably already knows how this case will eventually end.
“The Majority faults the FDA for not considering the companies’ proposed restrictions on kids’ use. And to be sure, the FDA said that factor would be relevant,” stated Rosenbaum. “But even assuming that the FDA erred when it didn’t consider the Companies’ proposed marketing and access-restriction plans, the FDA’s framework for evaluating pre-market tobacco product applications leaves no room for doubt that the FDA will deny—in fact, under the Family Smoking Prevention and Tobacco Control Act, must deny—the applications on remand. To paraphrase the Borg, then, remand is futile.”
The U.S. Food and Drug Administration Today issued a final guidance on Guidance perception and intention studies.
This guidance, “Tobacco Products: Principles for Designing and Conducting Tobacco Product Perception and Intention Studies,” is intended to help applicants design and conduct tobacco product perception and intention (TPPI) studies that may be submitted as part of a modified risk tobacco product (MRTP) application, a premarket tobacco product application (PMTA), or a substantial equivalence report (SE Report).
TPPI studies can be used to assess, among other things, individuals’ perceptions of tobacco products, understanding of tobacco product information (e.g., labeling, modified risk information), and intentions to use tobacco products, according to the FDA.
These studies provide critical information during the review of product applications and this guidance provides recommendations on how to perform these studies.
This final guidance addresses the following scientific issues for applicants to consider when designing and conducting TPPI studies to support tobacco product applications:
Developing study aims and hypotheses
Designing quantitative and qualitative studies
Selecting and adapting measures of study constructs
Determining study outcomes
Selecting and justifying study samples
Analyzing study results
This guidance document is intended to provide clarity to applicants regarding existing requirements under the law. FDA guidance documents, including this guidance, should be viewed as recommendations for consideration, unless specific regulatory or statutory requirements are cited.
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.
In establishing whether a nicotine product is appropriate for the protection of public health, the U.S. Food and Drug Administration held its Center for Tobacco Products (CTP) reviewers to a lower standard than the companies submitting premarket tobacco product applications, according to Alex Norcia writing in Filter.
Citing documents obtained through the Freedom of Information Act, Filter describes procedures such as batching and bracketing, which allowed the CTP to apply conclusions to categories of products rather than evaluating them separately. “Despite imposing extremely onerous bureaucratic requirements on applicants, the agency was happy to find ways to cut through its own paperwork,” writes Norcia.
“It’s clear that FDA allows itself efficient shortcuts that it has denied to applicants,” Clive Bates, director of The Counterfactual, told Filter.
“The problem has always been that FDA’s extraordinarily burdensome process was obviously tremendously wasteful for applicants, but of course it was always going to be unmanageable for the assessors in FDA. Without this sort of shortcut, the PMTA process would have become a human resources nightmare. So FDA has allowed itself the kind of efficiencies it should have offered to the applicants—batching and bracketing thousands of near-identical products.”
On July 26, the United States Court of Appeals for the District of Columbia rejected an appeal by four e-liquid manufacturers that challenged the FDA’s denial of their premarket tobacco product applications (PMTAs), ruling that the agency acted within Congress’ authorization, and its decisions were supported by evidence.
Prohibition Juice Co., Cool Breeze Vapor, ECig Charleston, and Jay Shore Liquids argued that the FDA lacked statutory authority to require that the manufacturers establish that their flavored liquids carry greater public health benefits than unflavored liquids.
According to the motion, the companies also challenged the PMTA denials as arbitrary and capricious, asserting that the FDA: (1) departed from an earlier guidance document, changing both the types of evidence the agency would accept and the substantive showing it expected parties to make; (2) underscored the potential importance of marketing plans including measures to limit youth access to their products but then failed to consider the plans petitioners submitted; and (3) overlooked various other aspects of the problem.
“We deny the petitions for review. The FDA plainly had statutory authority under the Tobacco Control Act to regulate as it did. As to the arbitrary and capricious challenges, we hold that the FDA did not change the evidentiary or substantive standard from its 2019 Guidance,” the court wrote in its motion. “We also hold that any error in the FDA’s failure to consider the marketing plans was harmless because the manufacturers failed to identify how individualized review of the plans they submitted could have made any difference.
“Finally, the FDA did not otherwise fail to consider important aspects of the problem. We accordingly deny the petitions for review.”
The D.C. Circuit has not stayed the enforcement of any MDO.
Fontem US had its request for an emergency motion for a stay of its marketing denial order (MDO) denied by the United States Court of Appeals for the District of Columbia. The court denied the stay mainly because Fontem waited too long to file the motion. The denial was filed July12.
Fontem Ventures, a subsidiary of Imperial Brands PLC and parent to Fontem US, owns the global e-cigarette brand blu. The ruling means that legally, Fontem should have to pull its Myblu products from store shelves that received MDOs from the FDA while the appeal of its MDO goes through the legal process.
“Fontem has demonstrated that the marketing denial order is causing it harm, but by waiting more than two months after the marketing denial order’s issuance to seek emergency relief, Fontem weakened its claim of irreparable harm,” the court wrote. “That delay also suggests it may have been practicable to seek a stay from the agency.”
The court stated that Fontem “has not made a strong showing” that it is likely to succeed in its appeal of the MDO issued by the U.S. Food and Drug Administration on merits, noting that as to the multiple bases for the MDO identified by the FDA, the agency likely afforded Fontem fair notice.
“Fontem US, LLC has not satisfied the stringent requirements for a stay pending court review,” the court wrote.
The FDA issued MDOs to several myblu brand products manufactured by Fontem US. Tobacco and vaping products subject to a negative action regarding a premarket tobacco product application (PMTA) submission, including those subject to an MDO, may not be offered for sale, distributed or marketed in the US.
“On April 8, FDA issued MDOs to Fontem US, LLC for several myblu electronic nicotine-delivery system (ENDS) products after determining their applications lacked sufficient evidence to show that permitting the marketing of these products would be appropriate for the protection of the public health,” the FDA stated in a release.
Fontem’s appeal is expected to move forward and the court is requiring the case to be expedited and the following briefing schedule is to apply:
Petitioner’s Brief August 10, 2022
Respondent’s Brief September 9, 2022
Petitioner’s Reply Brief September 30, 2022
Deferred Appendix October 7, 2022
Final Briefs October 14, 2022
“The Clerk is directed to calendar this case for oral argument on the first appropriate date following completion of briefing. The parties will be informed later of the date of oral argument and the composition of the merits panel,” the court wrote.
