Business units of Big Tobacco companies British American Tobacco , Imperial Brands and Japan Tobacco are among the manufacturers that received letters. Juul, the clear market leader, did not receive a letter because regulators already obtained the information during a recent surprise inspection of the company's San Francisco headquarters.

The FDA sent letters on Friday to 21 e-cigarette manufacturers requesting information to investigate whether they illegally introduced more than 40 new devices and nicotine liquids to the market without receiving agency approval.

The Food and Drug Administration is threatening to pull new e-cigarette products from shelves if the companies don't prove they're selling the items legally.

E-cigarettes introduced after Aug. 8, 2016, are supposed to first undergo FDA review in order to be marketed. Products that were already available were supposed to start applying retroactively this year, but the FDA extended the deadline last year to 2022. New product features, formulations or flavors that were launched after Aug. 8, 2016, may be violating the FDA's policy.

This the latest move in the FDA's crackdown on youth use of e-cigarettes, which officials say has reached epidemic levels.

Possible actions include the FDA reversing its application extension and pulling flavored e-cigarettes from the market.

"Companies are on notice — the FDA will not allow the proliferation of e-cigarettes or other tobacco products potentially being marketed illegally and outside of the agency's compliance policy, and we will take swift action when companies are skirting the law," Commissioner Dr. Scott Gottlieb said in a statement.

Some products may appear to have been introduced after the August deadline. However, they may have been on the market just not widely available or advertised.

Manufacturers may also have rebranded e-cigarettes or bought them from another company and given them a new name and are now marketing them as new. To clarify these situations, the FDA in its requests suggests that companies provide evidence on the marketing status of their products.

"If products are being unlawfully marketed and outside the FDA's compliance policy, we'll act to remove them," Gottlieb said.

A BAT spokesman in a statement said the company will provide the FDA with the information requested "to demonstrate our compliance." A Japan Tobacco spokeswoman in a statement said "all our products were commercialized and marketed in line with the FDA's requirements" and the company will respond to the FDA accordingly. Imperial Brands did not immediately respond to CNBC's request for comment.

Over the past year, the number of high school students who have used e-cigarettes in the previous 30 days has skyrocketed by about 75 percent, according to preliminary data from the Centers for Disease Control and Prevention's annual National Youth Tobacco Survey.

In response, the FDA has ordered five brands — Juul, British American Tobacco's Vuse, Altria's MarkTen, Imperial Brands' Blu E-cigs and Japan Tobacco's Logic — to submit plans within 60 days detailing how they will prevent teens from using their products.

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