FDA takes new action against Juul while experts worry about teen addiction and health effects. But the e-cigarette market is very mature in the United States.

The U.S. tobacco industry is at an inflection point. While financial forecasters expect revenue to continue to grow by about $4 billion a year through 2026, the way this mighty industry thrives is constantly changing.

About one in five Americans at the time were current tobacco users of any type, according to an assessment from the 2020 National Health Interview Survey. But only 12.5 percent of adults use combustible cigarettes — the lowest prevalence among smokers in nearly 60 years of data. Among the newest generation of users, there are fewer and fewer traditional methods of tobacco delivery.

A cross-sectional analysis released last month showed that while current e-cigarette use (defined as any use in the past 30 days) is trending down among young U.S. adults, daily use is climbing.

This suggests a shift in the priority of tobacco delivery in the context of reducing everyday combustible cigarette use. Young people stop trying e-cigarettes; they use them habitually in place of combustible products.

"The transition from occasional use to daily use suggests some form of nicotine dependence, because now you have to use it every day," Ellen Boakye, MD, MPH, a postdoctoral fellow at the Johns Hopkins Ciccarone Center, told HCPLive. "Research shows that daily e-cigarette users, especially young adults, are more likely to transition to combustible cigarettes."

For decades, groups of organizations, experts and legislators have implemented a multifactorial and comprehensive public health strategy to reduce the rate and burden of combustible cigarette use among young people, adolescents and children.

E-cigarettes are becoming a common tobacco-delivery product among the next generation of nicotine-addicted users, just a decade after the regulatory powers of the U.S. Food and Drug Administration (FDA) failed to meet their entry into the market.

Now, strategic or coincidental, new federal efforts to curb tobacco use among young Americans are in direct conflict with this major shift in tobacco product preferences. The FDA is trying to inspect e-cigarettes and flavored tobacco before long-term damage to smoking cessation efforts nationwide. But is it too little, too late?

The Family Smoking Prevention and Tobacco Control Act, signed into law in June 2009, imposes clearer restrictions on the marketing of tobacco products to children. Key state provisions of the Act include prohibition of sales to minors; sponsorship of sports, entertainment or other social/cultural events by tobacco brands; promotional giveaways of sample tobacco products and more. It also improves the FDA's ability to regulate nicotine and ingredient levels in tobacco products, as well as ban product flavor profiles other than menthol and tobacco.

The 2009 law first authorized the FDA to regulate tobacco and nicotine products, and just as importantly, it replaced state and territorial regulatory standards for tobacco product manufacturers.

"The usual argument for preemption is that companies struggle to comply with different regulations in different regions," Crane and his colleagues wrote. "However, such consideration should not be given to an industry that promotes nicotine addiction. Taking effective measures to reduce nicotine use in youth is a far more important priority."

According to the annual National Youth Tobacco Survey (NYTS), tobacco product use among current U.S. high school students dropped from 24.2 percent in 2011 to 19.6 percent in 2017 in the years following the act's implementation. In those seven years, cigarette use among high school students halved from 15.8% to 7.6%.

The significance and timing of these changes mean that the public health strategy and marketing standards set out in the 2009 Act are responsible—and to some extent, they are. But that rules out the whole truth. From 2011 to 2013, as teen use of combustible cigarettes plummeted, e-cigarette use skyrocketed—according to The New York Times, use among middle and high school nonsmoking students tripled during that time period .

Erika Sward, assistant vice president of national advocacy at the American Lung Association (ALA), told HCPLive that early e-cigarette marketing and messaging was mostly excluded from the strict regulations mandated by the Family Smoking Prevention and Tobacco Control Act. Sward cited a 2010 federal ruling that the FDA cannot regulate e-cigarettes as drug delivery devices.

The lawsuit comes after the FDA seized vaping devices for nicotine inhalation from Smoking Everywhere Inc. and NJOY in 2008; the agency claimed the devices were unsafe and unapproved products were falsely advertised as combustible cigarette alternatives Taste.

The ruling judge at the time said the FDA had provided no evidence that e-cigarettes posed a more immediate threat to public health and safety than traditional cigarettes.

Sward described the influx of vaping products and unclear FDA regulatory standards as the perfect storm for rampant teen use.

So, once that court case came out in 2010, the FDA was trying to figure out how to regulate e-cigarettes as a tobacco product, she said. And then we went through years of stagnation, but at the time, the products that were used early on were very, very bad.

Over the next decade, competing ideas about the efficacy and health risks of e-cigarettes led to new and more limited legislation.

States like New York set a precedent for indoor vaping and vaping bans similar to cigarettes. San Francisco outright banned flavored vapor products, including menthol.

Thirty states have passed taxes on vaping devices or vaping. Finally, the Federal Food, Drug, and Cosmetic Act was amended in 2019 to raise the federal minimum age for purchasing tobacco products to 21 and impose severe fines and penalties on non-compliant retailers.

Meanwhile, the FDA announced in July 2017 a five-year extension to tobacco product review applications for vaping and smokeless products — meaning companies that offered products under less clear regulatory standards six years ago have until this month Submit a premarket application for FDA review.

Sward described the move as an open welcome to the market, albeit with less regulation of manufacturers. After a decades-long war over combustible cigarette safety and marketing standards, the agency's actions against e-cigarettes have been tempered by agency capacity and timelines for action.

"I think there's an inherent false belief that once the FDA allows a product to enter the market, it's safe," Sward said. "But I don't think there is an inherent right to sell products that are harmful to consumers. And there is a role... The federal government has a role to play in protecting the public health of the country, whether it's through vaccinations, or by cleaning the air, or by ensuring that Comprehensive and strict regulation of tobacco products.”

Public health officials were also intimidated by the initial marketing behind the first generation of e-cigarettes. Sward likens the industry's messages to those used by tobacco companies in the 1950s and 1960s: "To claim they are less harmful without any scientific evidence, while also targeting a younger demographic with unique and appealing tastes. "

Whether e-cigarettes are safe, less harmful than combustible cigarettes, or a beneficial tool for quitting smoking are 3 entirely different ideas that are often lumped together at 1 because of their reduced regulation of the U.S. market. Still, experts are cautious about even if any of this information is entirely true.

"I really believe that if e-cigarettes are safe, or effective in helping smokers quit, and someone is aware of that, they'll go straight to the (FDA) Center for Drug Evaluation and Research very quickly," Sward said. "Because they'll know that they can ultimately help smokers quit smoking by selling the product."

Sward added that discussions around the safety risks of vaping are often confused by the fact that vaping devices are heterogeneous; Juul and NJOY create products with different functions and cartridges with different compositions and chemical exposures. Her belief that any of these devices are safer than combustible cigarettes is an industry-disseminated claim—a claim the FDA has had the opportunity and evidence to challenge for more than a decade.

“I mean, the FDA not only opened the barn doors, but actively drove the horses out,” she said.

Electronic Cigarettes: Pros and Cons

The role of defining e-cigarettes as an alternative to smoking or a tool to quit smoking is more complex, according to clinical experts. Boakye points to her colleagues' upcoming research showing that combustible cigarette users who want to quit are generally more successful when transitioning to e-cigarettes. This result will change the perception of 2 facts that have been established so far, that the use of combustible cigarettes is gradually declining, while the use of daily e-cigarettes is climbing - especially if the latter trend is affected by the smoking of former combustible cigarettes pusher.

However, if the climb in daily e-cigarette use is represented by non-smokers, there is a greater potential risk. Addiction to any nicotine product is very common, and there are currently no evidence-based or expert-supported ways to quit smoking for young, everyday e-cigarette users.

"There's a lot of evidence that actually supports the gateway hypothesis, which is that young people who use e-cigarettes are more likely to transition to combustible cigarettes, so if they use it every day," Boakye said. "But some people are looking at the other end of the spectrum among combustible cigarette users who want to quit their daily use, and it might actually help."

There's also the added health risk of users alternating between combustible cigarettes and e-cigarettes, no matter which one they start with. "The benefits of e-cigarettes are really only realized when smokers are able to fully transition to e-cigarettes, not when they use both cigarettes," Boakye said.

Boakye's team is trying to explain the effects of e-cigarettes more complexly, assessing the role of personal device characteristics and patient demographics in the transition from occasional to everyday use. “Because if we understand device characteristics, the FDA can regulate those characteristics so that people who are trying e-cigarettes are less likely to switch to more harmful modes of use,” she explained.

For clinicians, investigators, regulators and users, it will be futile to completely ignore the unique factors of vaping as vaping becomes more defined, Boakye said. She stressed the need for frontline doctors to question the complexities of tobacco use by patients.

“Healthcare providers should focus on conversations, they should be comforted when they ask patients, and they should be able to respond to patients who are curious about vaping because it’s so important,” she said.

FDA battle today

Recent events have only highlighted the issue of clearly defining the FDA's role in regulating e-cigarettes. The agency issued a marketing denial order to Juul Labs in late June, requiring the country's most popular e-cigarette and vaping device company to withdraw all of its products from retail and marketing.

The FDA issued an unprecedented order after reviewing Juul's premarket tobacco product application, which the agency deemed insufficient evidence to support the toxicological profile of Juul's products. The FDA describes insufficient and conflicting data on the genotoxicity of e-cigarettes and vaping devices, as well as user exposure to harmful chemicals through proprietary e-cigarette cartridges.

Additionally, they cited concerns about the potentially harmful use of third-party vape cartridges versus Juul devices—and vice versa—similar to Sward’s concerns about heterogeneous products with similar usability but different components.

Shortly after the ruling, Juul challenged the FDA's injunction and received a temporary marketing suspension from the U.S. Court of Appeals while the agency investigates the product's safety. While much of the ban has focused on the composition, prevalence and burden of the few chemicals observed in companies' e-cigarettes, the general view on the effects of e-cigarettes can be seen in the arguments on both sides -- and they are somewhat It doesn't matter.

The FDA will argue that Juul caters to younger, non-smoking users without sufficient evidence of its positive benefit-risk profile, and Juul sees e-cigarettes as a successful smoking cessation tool for smokers.

Juul, which accounts for two-thirds of the U.S. e-cigarette market as of 2020, says about 2 million adult smokers have quit combustible cigarettes through its products. Joe Murillo, chief regulatory officer at Juul Labs, said in a statement.

Meanwhile, the agency and supporting experts appear focused on the long-term public health impact of a potential ban on Juul. Former FDA Commissioner Scott Gottlieb, MD, tweeted at the time of the original marketing ban that Juul was the fulcrum of the youth vaping crisis, driven by the company's products and marketing practices.

"The FDA is right to be cautious," he wrote. "Electronic devices offer adult smokers an opportunity to move away from combustible products, but must be conceived and marketed by responsible actors."

Dr. Kevin Walton, head of the National Institute on Drug Abuse (NIDA) clinical research grants division, discussed the action against Juul, consistent with another FDA decision earlier this year: a proposed ban on menthol-flavored cigarettes. The popular arguments against menthol flavorings are the same as flavored e-cigarettes and e-cigarette cartridges: they can serve as a gateway to everyday use.

"Banning menthol is part of a regulatory effort to make cigarettes less attractive," Walton said. "It's very common for young people who use (cigarettes) to start menthol because it's less pungent. So it's easier to start smoking with that idea."

While Walton is interested in learning more from upcoming studies and the FDA's consideration of Juul and similar vaping products, he insists that key regulatory priorities should be fixing nicotine levels for any approved products, as well as improving Access to smoking cessation treatment – especially among underserved populations who may be adversely affected by, for example, menthol cigarettes and e-cigarette marketing.

"I think these changes that the FDA is proposing could have a very large positive impact on smoking reduction, and we'll just have to see how these processes progress," he said. "Reducing the addictiveness and appeal of tobacco seems like an appropriate way forward."

Boakye shares the view that the real key to combating any public health impact of cigarette products should focus on nicotine. Quitting smoking is a major achievement for an individual, but quitting smoking completely is the ultimate goal.

Lost in the debate that e-cigarettes are a beneficial smoking cessation tool is that some e-cigarette users are also trying to quit the products, she said. There needs to be more options to help them whenever available.

Sward has been hopeful that some of the tobacco products currently targeted by the FDA will eventually be pulled from the market, saying this is the closest we as a nation to a new beginning in a public health push for relief.

But regardless of the FDA's battle with Juul, menthol, and everything in between, affected users deserve the help they've been lacking for years.

"As a country, we need to do more to develop smoking cessation policies and institutions," Sward said. "And I think that's what we owe to people who are basically allowed to be addicted to a country that doesn't always pay attention to what the tobacco companies are doing."