The agency issued a warning letter to Juul, saying that the company violated federal regulations because it had not received federal approval to promote and sell its vaping products as a healthier option.

The FDA’s action dealt a setback to the company’s efforts to rebrand itself after public outrage erupted over a surge in teenage vaping.

And it served as a reminder that the health effects of e-cigarettes are not established at a time when more than 400 people have been sickened by vaping-related illnesses. Five deaths have been linked to vaping and hundreds of people have been hospitalized. Public health investigators have yet to determine a specific cause, but they have cited the use of cannabis and nicotine vaping products as possibilities. No one product or company has been implicated.

The investigation into Juul’s practices preceded this summer’s spate of lung illnesses, and was prompted by concerns that the company’s marketing and sales practices targeted youths. It included a review of congressional testimony from Juul executives, consumers — students and parents — and anti-smoking activists.

“Regardless of where products like e-cigarettes fall on the continuum of tobacco product risk, the law is clear that, before marketing tobacco products for reduced risk, companies must demonstrate with scientific evidence that their specific product does in fact pose less risk or is less harmful,” said Dr. Ned Sharpless, the acting FDA commissioner. “Juul has ignored the law and, very concerningly, has made some of these statements in school to our nation’s youth.”

The agency Monday pointed to specific instances that it said violated restrictions on those health claims. It referred to a statement by Kevin Burns, the company’s chief executive, that had once been posted on the Juul website in which he said that the company’s vaping system was designed to “heat nicotine liquid and deliver smokers the satisfaction that they want without the combustion and harm associated with it.”

The letter also cited congressional testimony about a talk at a school: A Juul representative spoke at a school presentation and told students that Juul “was much safer than cigarettes” and that Juul was “totally safe.”

The agency said its concerns were amplified by the increased use of vaping products, including Juul’s, by teenagers, and by evidence that teenagers were particularly vulnerable to nicotine addiction.

Juul, which now commands more than 70% of the e-cigarette market in the United States, has long said that it did not deliberately target teenagers. In a statement, Matt David, a company spokesman, said, “We are reviewing the letters and will fully cooperate.”

The high levels of nicotine in Juul products are of particular concern for their effects on the still-developing brains of a generation of teenagers and as a potential gateway drug that could reverse decades of a steep decline in smoking rates.

Research into the long-term effects of e-cigarettes is at an early stage, which is one of the reasons the FDA is trying to restrict marketing assertions by Juul and other companies in the industry. The agency ordered the company to submit its plan to correct the issues outlined in the warning within 15 days.

In a second letter to Juul on Monday, the FDA sought further documents about the company’s practices, details about some of its products, including nicotine-salt e-liquids, and any scientific evidence it has amassed to prove its claims.

The agency singled out Juul’s ad campaign, “Make the Switch,” saying it may convey that its devices are less harmful than tobacco cigarettes and may also violate limits on health claims. The company’s switching campaign has also drawn fire from lawmakers and public health experts, who contend that the message implies that Juul’s products are a smoking cessation option.

“I have a hard time seeing the difference between quit and switch,” said Rep. Raja Krishnamoorthi, D-Ill. “Essentially what they are saying is, quit smoking and do something different.”

Joshua Raffel, another spokesman for Juul, disagreed.

“Switching is not another word for cessation or safer,” he said. “They mean very different things. For example, switching involves continuing to consume nicotine but from a different device, while cessation is about getting users to eliminate their nicotine consumption altogether.”

For more than a year now, Juul has been the central target of public health experts and the FDA over its products’ appeal to youths. With a sleek vaping device that has become ubiquitous as an accessory for many young people, Juul has had a meteoric rise, culturally and financially. Its product line was released in 2015, and the company’s sales took off. By 2018 it had a valuation of $16 billion. That is less than half of its current estimated valuation of $38 billion, making the company one of the most recent successful growth stories in Silicon Valley.

Juul has engendered further criticism by selling 35% of the company to Altria, one of the leading cigarette companies. The union fueled criticism that Juul ultimately cared about profits at the expense of public health, an assertion Juul denied. Altria and Philip Morris International are now in merger talks, which would give Juul extraordinary pipelines to overseas markets.

Whether the FDA’s action will dent Juul’s domestic sales remains unclear, although the company has already said that sales were hurt by its decision to stop shipping flavored pods to stores. The FDA warned that if Juul did not comply with laws governing vaping devices, it could impose civil penalties or an injunction, or seize the company’s products.

The growing popularity of e-cigarettes has been paralleled by an evolving and unfinished regulatory framework. The core question facing regulators and public health experts has been whether the potential benefits of the new technology, such as the possibility that it can reduce smoking-related deaths, will outweigh risks, like those posed to youths.

Several deadlines have been set for e-cigarette companies to submit evidence that their products would serve the public health and come under full regulatory authority, and Juul has yet to submit an application for approval to market its products as a healthier choice. In July, a federal judge ruled that the FDA must move up its deadline, calling for the companies to comply within 10 months, or by May 2020.

Juul’s defenders and advocates for e-cigarettes as a smoking cessation device argue that the regulatory policy in the United States has been unfair to both the company and to a larger public health message. David Sweanor, a tobacco-law expert at the University of Ottawa and an advocate for e-cigarettes as an alternative to smoking, said that “communicating that their products are certainly massively less hazardous than cigarettes is accurate and nonmisleading.”

And he noted that the severe lung illnesses linked to vaping had not yet been shown to be linked to mass-market nicotine e-cigarettes. Policymakers should not lose sight of the toll of smoking, which kills 1,300 people a day in the United States, he said.

Still, the hospitalizations across the country — in nearly three dozen states now — have prompted states and health agencies to issue warnings against e-cigarettes altogether.

When public health officials publicly released a report of the first possible vaping-related death on Aug. 30, the Centers for Disease Control and Prevention issued an extensive warning against vaping: “E-cigarette products should not be used by youth, young adults, pregnant women, as well as adults who do not currently use tobacco products. If you use e-cigarette products, monitor yourself for symptoms (e.g., cough, shortness of breath, chest pain) and promptly seek medical attention if you have concerns about your health.”

At the same time, authorities have singled out for concern vaping devices and liquids that are “off the street,” or have been modified or used in a way that the manufacturer did not intend.

Others are calling for stricter measures to be put in place before e-cigarettes can be dispensed. Dr. Nora Volkow, director of the National Institute on Drug Abuse, which is part of the National Institutes of Health, said e-cigarettes should be evaluated in randomized clinical trials for treating people who are unable to stop smoking with other means. And if they are shown to be effective, Volkow said, they should be available only by prescription.

“That’s the way we do it with stimulant drugs,” she said.

Lawmakers also are demanding additional action.

Late last week, Sen. Richard J. Durbin, D-Ill., wrote a letter to President Donald Trump urging him to replace Sharpless, the acting FDA commissioner, with someone who would be tougher on the e-cigarette issue. A deadline is approaching for the president to name a permanent replacement for Dr. Scott Gottlieb, who left earlier this year.

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