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Tag: PMTA

  • McKinney Hires Fearon as Chief Scientific Officer

    McKinney Hires Fearon as Chief Scientific Officer

    McKinney Regulatory Science Advisors stated today that it has appointed Ian Fearon as its new Chief Scientific Officer.

    Fearon will play a pivotal role in enhancing the regulatory science consulting firm’s capabilities and expanding its range of services to clients, according to a press release.

    “Fearon brings over 15 years of invaluable experience in the field of Tobacco Harm Reduction, with a specific focus on clinical and behavioral studies of these products,” the release states. “His deep understanding of regulatory submissions in the United States and Europe will enable McKinney Regulatory Science Advisors to provide unparalleled support and guidance to clients navigating the complex regulatory landscape.”

    Prior to joining McKinney, Fearon held key leadership positions at several industry organizations such as senior director of Clinical and Regulatory Affairs EMEA at Juul Labs, where he helped advance the scientific understanding of tobacco and nicotine products and supported the company’s premarket tobacco product application (PMTA) submission to the U.S. Food and Drug Administration.

    Fearon also served as the director of Tobacco Research at Celerion, where he contributed to the development of clinical evidence to support regulatory filings, and as principal scientist and head of Clinical Research at British American Tobacco.

    Fearon has published more than 60 papers, including more than 20 on tobacco/nicotine product assessment, which generated more than 3,200 citations, according to the release.

    “We are thrilled to welcome Ian as our Chief Scientific Officer,” said company CEO Willie McKinney. “His extensive experience and deep knowledge of tobacco and nicotine science and worldwide regulations make him an invaluable asset to our team. With Ian’s guidance, we will continue to provide exceptional scientific and regulatory consulting services to our clients, facilitating their success in bringing innovative consumer products to market.”

    As the Chief Scientific Officer at McKinney Regulatory Science Advisors, Fearon will oversee the company’s scientific operations, lead strategic initiatives, and drive innovation in the regulatory science domain, according to the release.

  • Reynolds Likely to Prevail in PMTA Lawsuit

    Reynolds Likely to Prevail in PMTA Lawsuit

    When the U.S. Court of Appeals for the 5th Circuit granted a stay to R.J. Reynolds Vapor Co. (RJRV) of the U.S. Food and Drug Administration’s denial of its 150,000-page premarket tobacco product application (PMTA) for its menthol Vuse products, the judges indicated that the court believes RJRV is likely to prevail on the merits when the full review is heard. 

    Tobacco harm reduction expert Clive Bates of Counterfactual said the substantive decision rests on three main arguments, as outlined by the judges granting the stay. The order states: “Specifically, RJRV demonstrates that the FDA failed to reasonably consider the company’s legitimate reliance interests concerning the need for longitudinal studies and marketing plans; failed to consider relevant evidence, inter alia, that youthful users do not like menthol-flavored e-cigarettes; and has created a de facto rule banning all nontobacco-flavored e-cigarettes without following APA notice and comment requirements.”

    The three main points argued by the court are outlined below:

    FDA changed the decision-making criteria after the application.

    1. Legitimate reliance interests

    “The FDA did not reasonably consider RJRV’s legitimate reliance interests before changing its position on the types of comparative studies and marketing plans critical to a compliant and complete PMTA.”

    Failure to consider Reynolds’ arguments adequately 

    2. Failure to consider relevant factors

    The FDA did not adequately address RJRV’s evidence that substantial health benefits would accrue to adult and youth cigarette smokers alike who switched to menthol Vuse while popularity among youth would remain low overall. For example, RJRV’s application contained studies that “switching from smoking to use of menthol Vuse Vibe substantially reduces toxicant exposure in a manner similar to smoking abstinence.” RJRV also submitted evidence of low popularity among youth relative to other flavored electronic nicotine-delivery systems (ENDS).

    Bates stated that at least one portion of the court’s argument looks troubling for Brian King, the newly appointed director of the FDA’s Center for Tobacco Products (CTP).

    “Then in July 2022, a new CTP director appeared on the scene and told OS that ‘the approach to menthol-flavored ENDS should be the same as for other flavored ENDS, i.e., the products could be found [appropriate for the protection of the public health] only if the evidence showed that the benefits of the menthol-flavored ENDS were greater than tobacco-flavored ENDS, which pose lower risk to youth.’ OS then changed its position.”

    FDA has been implementing a de facto tobacco product standard (a flavor ban) without using the rule-making process, public comment, etc. 

    3. “Tobacco product standard”

    RJRV has adduced evidence that the FDA has effectively banned all nontobacco-flavored e-cigarettes pursuant to its new and secret heightened evidentiary standard without affording affected persons any notice or the opportunity for public comment. There is no dispute that the TCA requires the FDA to abide by notice-and-comment rulemaking procedures before establishing a “tobacco product standard.” 8 21 U.S.C. § 387g(c)–(d). Similarly, it is clear that a ban on all but tobacco-flavored e-cigarettes would constitute a “tobacco product standard.” 

    Bates explains that the court justifies its assertion that the FDA is imposing a de facto standard with reference to the so-called “fatal flaw memo.” This was an expedited decision-making regime that stipulated that applications for nontobacco-flavored products must be supported with controlled trials or longitudinal studies showing a quitting or switching advantage over a tobacco flavor. Otherwise, they would be automatically denied. 

    “We conclude that the Fatal Flaw memo’s heightened evidentiary standard ‘bears all the hallmarks’ of a substantive rule. City of Arlington, 668 F.3d at 242. First, the memo is binding on its face by mandating that applications contain ‘the necessary type of studies.’ Second, it has been applied in a way that indicates it is binding; indeed, the subsequent, myriad Denial Orders refer to the same deficiencies identified as ‘fatal’ in the memo. Third, it took away the FDA reviewers’ former discretion to consider individual PMTAs solely on their merits and instead requires a cursory, box-checking review.

    “Finally, it affected the rights of literally hundreds of thousands of applicants whose PMTAs were denied. This is not a close call.”

    Bates stated that the third point the court makes is potentially “very” serious for the FDA and “not a close call,” as the court suggests. “A tobacco product standard under the TCA s.907 means that the burden is on the FDA to show that its de facto standard is appropriate for the protection of public health—e.g., considering the impact of closing down all vape shops, the likely impact on adults or youth who smoke, unintended consequences, illicit trade, etc.,” explains Bates. “It shifts the analysis from the individual applicant (PMTA) to the system-wide impact (Product Standard)—and FDA will find this difficult or impossible to meet, in my view.”

    Taking everything into account, the court weighs up its decision to grant the stay against four criteria, as Bates outlined: 

    “Our judgment is ‘guided by sound legal principles’ that ‘have been distilled into consideration of four factors: (1) whether the stay applicant has made a strong showing that he is likely to succeed on the merits; (2) whether the applicant will be irreparably injured absent a stay; (3) whether issuance of the stay will substantially injure the other parties interested in the proceeding; and (4) where the public interest lies.’”

    Bates stated that the first of these four criteria reflects the courts’ view on the merits discussed in the three above-stated substantive arguments. In the fourth: where the public interest lies, the court gives significant weight to the “highest public importance that federal agencies follow the law” and states: “In sum, ‘there is generally no public interest in the perpetuation of unlawful agency action,’ Texas v. Biden, 10 F.4th at 560. And there is no evidence that ‘Congress’s policy choice’ included an exemption from mandatory federal administrative procedures.”

    No date has been set for the court to complete its full review.

  • FDA: 99 Percent of Applications Decided

    FDA: 99 Percent of Applications Decided

    Image: manonteravest | Adobe Stock

    In an update, the U.S. Food and Drug Administration said it has made determinations on more than 99 percent of the nearly 26 million deemed products for which applications were submitted. To date, the agency has authorized 23 new e-cigarette products.

    This includes determination on applications for nearly 6.7 million products received by the Sept. 9, 2020, deadline, more than 18 million products received after the Sept. 9 deadline, and applications for nearly 1 million nontobacco nicotine products submitted by May 14, 2022, in accordance with the new federal law passed in April 2022.

    Under a federal court order, manufacturers of deemed new tobacco products that were on the market as of the deeming rule’s effective date (Aug. 8, 2016) were required to submit premarket review applications by Sept. 9, 2020.

    On Feb. 21, 2023, the FDA issued a refuse-to-accept (RTA) letter to one applicant notifying the company that their premarket tobacco product applications, which are associated with approximately 17 million individual tobacco products, do not meet the acceptance requirements outlined in the FDA’s regulations. The applications were for a grouped submission of e-liquids in varying size, nicotine strength and flavor combinations, each of which was treated as an individual product application according to existing premarket review processes.

    During the acceptance phase of application review, the FDA reviews applications to ensure they meet a minimum threshold for acceptability for FDA scientific review. If required contents for acceptance are missing, the FDA refuses to accept the application. This company was issued an RTA letter because the company’s applications for these products lacked required environmental assessments. The company may submit a new application for these products at any time; however, the products may not be marketed unless the FDA reviews the applications and determines that marketing of the products is appropriate for the protection of the public health.

    The latest updates on actions taken on these applications can be viewed on the FDA’s tobacco products marketing orders page.

  • PMTA Review Target Date Pushed Back

    PMTA Review Target Date Pushed Back

    Photo: Brian Jackson

    The U.S. Food and Drug Administration has submitted a new timeline for its review of premarket tobacco product applications (PMTAs).

    In prior status reports, the FDA indicated that it expected to have taken action on all covered applications by June 30, 2023. Filed with the Maryland Federal District Court on Jan. 24, 2023, the agency’s fourth report states that it now expects to have acted on PMTAs as follows:

    • 52 percent of covered applications by March 31, 2023
    • 53 percent of covered applications by June 30, 2023
    • 55 percent of covered applications by Sept. 30, 2023
    • 100 percent of covered applications by Dec. 31, 2023

    In response to litigation by public health groups, a Maryland Federal District Court in April 2022 ordered the FDA to file regular status reports on its progress in reviewing PMTAs for the most popular vapor products on the U.S. market, including Juul, Vuse, Njoy, Logic, Blu, Smok, Suorin or Puff Bar.

    The original target completion date for the review process was Sept. 9, 2021; however, the FDA was unable to meet it due to the extremely large number of PMTAs filed by manufacturers.

    The most recent delay is due in part to ongoing litigation and to the agency’s acceptance  of amendments to some already filed PMTAs, according to the report.

    The FDA is expected to give its next status update to the court on April 24.

  • ‘Implementation of Tobacco Act Flawed’

    ‘Implementation of Tobacco Act Flawed’

    Azim Chowdhury

    The U.S. Food and Drug Administration’s implementation of the 2009 Tobacco Control Act, which gave the agency authority to regulate tobacco products, has been fundamentally flawed from the beginning, according to Azim Chowdhury, a partner in the Keller and Heckman law firm.

    Writing in Filter, Chowdhury explains that the premarket authorization requirements for “new” products subjects potentially reduced-harm products to nearly insurmountable hurdles while allowing preexisting products, including combustible cigarettes, to mostly escape FDA scrutiny.

    In his article, Chowdhury suggests several ways in which the FDA can more effectively implement the Tobacco Control Act.

    For example, rather than conducting reviews in silo, the FDA should consider the totality of evidence in a premarket tobacco product application, according to Chowdhury.    

    “It is also critical that the FDA hamper the spread of counterfeit products, which may be riskier for consumers and are drowning out the small businesses and vape shops that continue to bear the brunt of FDA enforcement,” he writes.

    “Finally, the FDA should shift more resources to developing reasonable safety, quality and marketing product standards.”

  • Choosing Wisely

    Choosing Wisely

    Photo: manovankohr

    Are choices key to successful switching?

    By Cheryl K. Olson and Willie McKinney

    Like many people who smoke, Doug Halterman wanted to quit. “I tried other ways, even prescription drugs, and nothing worked.” When he decided to try vaping, “At first, it was a research and development stage. I had to figure out what ones best acted like a cigarette,” he recalled. “I started with menthol tobacco. I then liked the fruit flavors because it helped stay clear of cigarettes. After vaping fruity flavors, cigs tasted absolutely disgusting.”

    Halterman’s story of switching is one of several dozen generously shared via emails from members of the Consumer Advocates for Smoke-free Alternatives Association (CASAA). This exploration of what drives change was triggered by anecdotes and research suggesting that encountering and trialing a range of alternative nicotine products, or rotating among an engaging mix of options, can be key to ditching smoking. The typical successful quitting journey seems less like a thruway and more like a meandering river. The U.S. Food and Drug Administration’s Center for Tobacco Products’ approach to researching switching, described in its Final Rule guidance, assumes simple choices and straight lines.

    The Wrong Framework?

    Premarket tobacco product application (PMTA) behavior studies are supposed to describe likely changes (and related health risks) created by the marketing of a single novel tobacco product of a particular flavor and nicotine strength. This is not unlike studies the FDA’s Center for Drug Evaluation and Research (CDER) reviews, comparing effects of a new drug to a placebo on particular symptoms or endpoints.

    In a September 2021 PMTA Technical Review Summary available online, the FDA laid out a new standard that flavored electronic nicotine-delivery system (ENDS) products must meet. Balancing concerns about youth uptake demands “acceptably strong evidence that the flavored products have an added benefit relative to that of tobacco-flavored ENDS in facilitating smokers completely switching away from or significantly reducing their smoking.” What kind of evidence? “Most likely product specific evidence from a randomized controlled trial (RCT) or longitudinal cohort study.”

    Again, it’s like testing whether a medicine to treat gout or acne is superior to the current standard therapy, except it casts tobacco flavoring (the taste of cigarettes) as the standard and mango or vanilla as the unproven alternative. 

    Does an approach that may work for “safe and effective” prescribed drug authorizations make as much sense for a balance-of-risks consumer product standard? Does the CDER mindset serve well the end goal of moving people off combustibles? This pharma-influenced standard may be the wrong tool to address tobacco product effects.

    Comments from people’s real-world switching experiences (see sidebar) suggest that a test-in-isolation model fails to capture a lot of key information that could accelerate the move away from smoking and its unacceptably high risks of disease and death.

    Unlike pharmaceuticals and devices approved by other FDA centers, nicotine consumer products are not prescribed as a course of treatment. Tobacco users looking to switch aren’t making comparisons among two (or three) options. They meander through shops and gas stations, picking up nicotine products at will and whim. Many use multiple products to suit situations or prevent boredom. They learn through trial and error: How does this product work? What does it do for me? How does it fit into my life? And they choose again.

    Another problem: As Neil McKeganey of the Center for Substance Use Research pointed out recently, it’s not clear by how much the FDA values youth vaping prevention over adult smoking cessation. How obviously better would a flavored product need to be at helping smokers switch, compared to a tobacco flavor, to offset concerns about youth appeal? The recent longitudinal study of Juul, where over half of participants switched completely from cigarettes at one year, found that what flavor smokers chose did not significantly affect success.   

    Missing Variables

    Most studies aren’t designed to address the power of choices. Even large surveys that support the importance of flavors in switching tend to collapse flavors into categories (like “sweet” for fruit and candy) and ask about main flavor used, obscuring the paths taken by individual quitters. But there are tantalizing hints. For example, a six-week switching study of tobacco-free pouches found a link between trying more flavors and fewer daily cigarettes smoked. A 2018 study of MarkTen found that smokers who switched completely used more flavors.

    Based on her experience researching oral and vapor product behaviors (including MarkTen), “Most smokers don’t successfully switch and sustain their switching through one product category,” said Jessica Zdinak, chief research officer at Applied Research and Analysis Consulting. She notes that academic studies of smoker transitions often leave out important variables, such as previous quitting experiences or stressful changes in life circumstances.

    Adding Real-World Evidence

    FDA Commissioner Robert Califf has been quoted repeatedly as supporting greater reliance on real-world evidence to support drug regulation decisions. During his first stint as FDA head, Califf said at the 2016 Food and Drug Law Institute conference that “In the past, so-called ‘regulatory trials’ tended to focus on high-quality studies with detailed study procedures, restrictive inclusion and exclusion criteria and have been conducted in special study sites.” By contrast, he noted that “pragmatic clinical trials,” studies that look at treatments and outcomes in actual medical practice settings, “may be the most important source of knowledge in the future.”

    Another difference from pharmaceutical products: Many alternative nicotine products have been on the market for several years. Why not consider real-life evidence, as in natural choice situations over time, for tobacco product switching behavior? Don’t throw away tried-and-tested tools but see how they fit in a new context.

    Zdinak would like to see long-term randomized trials that incorporate this approach, showing the effect of having or lacking a range of options. To demonstrate the effects of flavors on switching, “What does the world look like if I’m a smoker of 30 years who enters a vape shop, and I have tobacco-flavored vapes as my sole option? Or what happens if I see citrus, mango, cinnamon, coffee and caramel?” She is currently in the design and review phase for one such realistic study.

    To quote prominent researchers Dorothy Hatsukami and Dana Carroll, “Most in the tobacco control community would agree that an immediate main goal is to rapidly eliminate tobacco-related death and disease.” If regulators agree, let’s look at what obstacles are preventing smokers from switching more rapidly. That includes tailoring methods and assumptions borrowed from pharma research to suit appropriate for the protection of public health (APPH) standards and goals.

    The Power of Choices: Stories from CASAA

    Founded in 2009, the Consumer Advocates for Smoke-free Alternatives Association (CASAA) is a 501(c)(4) consumer nonprofit organization that aims to “ensure the availability of a variety of effective, affordable reduced-harm alternatives to smoking.”

    In response to an emailed request from CEO Alex Clark, a number of former smokers took time to share their experiences of switching to vaping or other smoke-free products. One question posed by Clark was whether the variety of products was helpful in staying engaged with smoke-free options and reducing the temptation to return to smoking.

    Clark himself recently switched from vaping to using pouched snus. Along with a concern that overconsumption of stimulants, such as coffee and rapid-delivery nicotine products, were triggering heart palpitations, he said, “The hands-free nature of snus fits more with my needs. And I can still get all of the different flavors when I order from Sweden.”

    Here are excerpts from CASAA member comments, edited for length and clarity. No doubt, people who smoke have a range of goals and preferences that evolve in sometimes surprising ways through product exploration.

    Nancy S.: “I started vaping because I was unable to stop smoking tobacco cigarettes because I am so addicted to nicotine. And I don’t want to die from lung cancer like my father did. The products I tried were exactly what I was looking for. I wanted something that tasted like a real cigarette. No funny flavors.”  

    Roger M.: “I love the variety of products—both hardware and e-juices. My favs are black licorice, almond and bubble gum. They say only the kids like these flavors, but I have loved them since I started vaping 12 years ago. I am now 61.”

    Sara C.: I liked trying new flavors in the beginning then found my favorite [strawberries and cream] that I’ve stuck with for years.”

    Marc C.: I’ve tried the patch, the gum, hypnosis, as seen on TV products, medications and counseling. Nothing worked or works for me except vaping. I want my vape to taste like an authentic tobacco vape. But I’m okay with some flavor of tobacco, like coffee, vanilla, apple or maple. Almost like a pipe tobacco assortment.”

    Sean O.: “The first product I tried wasn’t all that good. Eventually, I found that using what’s called a ‘box mod,’ which takes two high-powered batteries … gave the great sensation in your throat of inhaling the same way a cigarette did. The large clouds of vapor that you can produce using these mods and tanks is incredible. [And] the variety of flavors is exactly what has kept me away from cigarettes.”

    Joni L.: “The device was key for me. I chose a Vaporesso Swag because of the size. It felt close enough to a pack of cigarettes for me, and a lot of my habit was actually reaching for my smokes. My first e-juice was a house-made vanilla custard tobacco; I was afraid to go too far away from tobacco flavors because I actually believe I liked the flavor of a cigarette. After three or four days, I went back to the vape shop and bought some mixed berry-flavored juice. That was it. It didn’t take long for my cigarette cravings to go away.”

    Kelly P.: “I did try a different device but went back to Juul. I liked the mint and found it better than the menthol cigarettes I had smoked. Also, Juul wasn’t one of those devices that you would blow out a cloud of smoke.”

    Glenn N.: “I believe that the first ‘e-cigarette’ I bought was the first Blu. I vaped that for a couple months, but it was missing something, and I thought I would go back to cigarettes. So I started looking online. With that ProVari, I knew that I would never smoke again. I found what I needed. I started with 36 mg liquid and went down to 12 mg in about a year.”

    Steve T.: “I will be 68 this year and feel I made a great decision with vaping. Access to flavors is a critical component necessary to transition away from cigarettes. I have reduced the nicotine levels from 18 mg to 3 [mg], and my Kona e-juice was replaced with dessert and blueberry flavors.”

    Jessie C.: “NRT [nicotine-replacement therapy] options like snus and nicotine gum/lozenges never worked for me as more than a way to avoid smoking at an event or during a long work shift. I’m very much a tech-oriented person, so the idea of having many options was stimulating for me. At the time, CE4 atomizer [tanks] and little pens were the most accessible items on the market [and did not meet expectations]. When the Kangertech Subox Mini hit the market, I was satisfied and stuck with that.”

    Cindi K.: I started vaping in 2014 not because I was looking to quit smoking but because I was avoiding convenience stores; I had just entered AA [Alcoholics Anonymous] and that is where I’d bought alcohol. Two doors down was a vapor store. I bought an eGo Tank and some tobacco-flavored e-liquid in 24 mg. I made friends in AA that were also vaping and noticed their liquids smelled much better than what I was using. I continued to be what I labeled a dual user for a few more months and decided to use flavored e-liquid and willpower to quit smoking. I also learned how to make my own flavors. I had about 12 I used in rotation and loved.”

    Tanya L.: “The first product I tried was in 2013: a vanilla-flavored vape liquid, Kanger T3S tank and coils, which I still use. I like vanilla. I just had to find the best vanilla.”

    Cheryl K. Olson is a California-based public health researcher who specializes in behavioral health issues and consults on tobacco product behaviors via McKinney Regulatory Science Advisors. She spent 15 years on the faculty of Harvard Medical School.
    Willie McKinney is the founder of McKinney Regulatory Science Advisors. He’s held senior regulatory roles at major tobacco product companies and served for three years as the industry representative on the FDA’s Tobacco Products Scientific Advisory Committee.
  • Confusion Persists About Magellan MDO

    Confusion Persists About Magellan MDO

    Photo: Damir Khabirov

    The U.S. Food and Drug Administration has confirmed that Magellan Technology received marketing denial orders (MDOs) on Oct. 6 for 32 products.

    In response to the FDA press statement announcing the order, Magellan Technology denied having received an MDO, saying the agency had refused to accept its premarket tobacco product application (PMTA) on a technicality without reviewing the PMTA on its merits.

    Magellan Technology demanded that the FDA not only retract the press announcement but also issue a corrective statement, making clear that the FDA did not issue an MDO to Magellan and that it has not yet conducted a scientific review of Magellan’s products.

    In response to an inquiry by Vaping360, the FDA reiterated that it had served Magellan Technology with an MDO.

    “After reviewing premarket tobacco applications for 32 Hyde e-cigarettes, FDA issued marketing denial orders for these applications submitted by Magellan Technology Inc. on Oct. 6,” the agency told Vaping360. “In addition to the MDOs issued on Oct. 6, as acknowledged by Magellan Technology Inc. in their statement, FDA also issued a Refuse to Accept letter for other Hyde e-cigarette products.”

  • The PMTA Mystery

    The PMTA Mystery

    Credit: Gustavo Frazao

    How effective must a product be in helping adult smokers quit to overcome the theorized level of harm to youth?

    By Neil McKeganey

    If there is one thing that you can say about the U.S. Food and Drug Administration’s premarket tobacco product application (PMTA) process, it is that it is exceedingly data heavy. E-cigarette manufacturers’ submissions under the PMTA process can run to the thousands of pages, reporting the results of research costing millions of dollars. To receive a marketing authorization, e-cigarette manufacturers have to be able to show that their product is “appropriate for the protection of the public health” (APPH).

    The APPH standard has become something of a modern-day mantra in the world of tobacco regulation, but what exactly does it mean? While nobody would accuse the FDA of excessive clarity in its communications with industry, this much is clear—in the simplest of terms, manufacturers need to be able to show that their product is helping adult smokers to quit, or at least to substantially reduce their smoking, and that their products are not being used by nonsmokers. This, in a nutshell, is what the FDA means when it talks about the importance of assessing the net public health impact of new tobacco products—the capacity to assess the likely overall impact of a new tobacco product on the nation’s health.

    The kind of evidence that manufacturers are required to present under the PMTA process ranges from longitudinal customer studies collecting data from consumers of their products over weeks or months to assess how those products are impacting on the individual’s smoking behavior. Alongside such customer studies are the randomized control trials that monitor changes in smokers’ behavior when they are using the new tobacco product under control conditions. The randomized trials are probably the sort of things most manufacturers have heard of before even if they have not carried them out. These studies are often presented as the gold standard in research evaluating the impact of a new drug. The shortcoming with the control trial design, though, is that it tells you about the impact of your product under controlled conditions; it does not tell you how people will use your product in their real life.

    The results of these studies can be presented to the FDA along with studies showing which population groups are currently using the new tobacco product and which ones are likely to start using the new tobacco product if it were approved. This is where the PMTA process starts to get more mysterious. One of the key groups that the FDA wants to know about is young people. With recent studies showing that more than one in 10 young people in the U.S. are using e-cigarettes, the FDA has repeatedly stressed that in deciding whether a manufacturer’s product is going to be judged as APPH, it needs to balance the impact of the product on adult smokers and young people. When the former FDA commissioner stated in 2018 that the “offramp” to adult smoking must not be achieved at the cost of the on-ramp to youth vaping, he was making it clear that the FDA would be prepared to deny approval to a new tobacco product that might be helping adult smokers to quit if at the same time it was being used by youth or likely to be used by youth.

    In a scenario where youth use of a new tobacco product can become a deal breaker for a company seeking regulatory approval for their new tobacco product, it is clear that the FDA is placing greater weight on youth vaping prevention than on adult smoking cessation. For many people, the greater value placed on youth vaping prevention may seem entirely fair—but the question at the heart of all this is by how much is the FDA valuing youth vaping prevention over adult smoking cessation? The answer to that question, or more accurately, the failure of the FDA to answer that question, is the mystery at the heart of the PMTA process. An e-cigarette manufacturer may be able to present stellar data to the FDA showing the benefit of their product in helping adult smokers to quit and still receive a marketing denial order on the basis that in the view of the FDA, the product poses too great a risk to youth.

    In interpreting the results of the empirical studies that manufacturers may have carried out, the FDA is trying to model the likely impact of the product on the total population—adults and youth. Modeling, though, is a mysterious process in which you try to anticipate what you think might happen in the future under various assumed conditions in the present. Some years ago, the National Academies of Science Engineering and Medicine carried out a modeling exercise to try to quantify the impact of e-cigarettes on population health in the U.S. This was a limited exercise carried out under precisely stated assumptions about how effective e-cigarettes might be in helping smokers to quit and how harmful they may be compared to combustible cigarettes. In contrast to such transparency, the FDA has never specified how it is weighing youth harm prevention against adult smoking cessation. As a result, e-cigarette manufacturers will never know how effective their product needs to be in helping adult smokers quit to overcome the theorized level of harm to youth to be judged APPH.

    Neil McKeganey is the director of the Center for Substance Use Research in Glasgow, Scotland.
  • A Second Chance

    A Second Chance

    Photo: andranik123

    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.
  • ‘FDA Failed to Consider Marketing Plans’

    ‘FDA Failed to Consider Marketing Plans’

    Photo: tanasin

    The U.S. Food and Drug Administration must reevaluate the premarket tobacco product applications (PTMAs) of six e-cigarette manufacturers after an appeals court ruled that the agency failed to adequately consider the companies’ marketing plans, reports Bloomberg Law.

    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. 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.

    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.