FDA Begins Regulating E-Cigarettes Made With Synthetic Nicotine (2022)

In March 2022 Congress changed the law so that the U.S. Food and Drug Administration (FDA) can regulate tobacco products that contain nicotine “from any source,” including synthetic nicotine made in a laboratory rather than taken from the tobacco plant. Between April and October 2022 the FDA put the change into practice: it set a May deadline for premarket applications, refused to accept applications covering more than 889,000 products, and sent warning letters to more than 60 manufacturers and over 300 retailers. The substance itself is described on the site’s Nicotine page, and dependence on its Nicotine Addiction and Withdrawal page.

This page reports what the FDA’s own documents say: what the law changed and when, why the FDA says the change was needed, what sellers had to do, how the application deadline and review worked, the enforcement steps the FDA reported through October 2022, what the change does not do, its status as of October 18, 2026, and how it fits earlier and later FDA tobacco actions. No company, brand or product is named here.

Table of Contents

  1. What Happened Between March and October 2022
  2. The Law Behind It: Congress, Not an FDA Rule
  3. Why the FDA Says the Change Was Needed
  4. What Sellers Had to Do From April 14, 2022
  5. The May 14 Deadline and the July 13 Cut-Off
  6. How an Application Moves Through Review
  7. Warning Letters, Refusals and Penalties
  8. The Count as of October 2022
  9. What the Change Does Not Do
  10. Dates and Legal Status as of October 18, 2026
  11. How It Fits Earlier and Later FDA Tobacco Actions
  12. Primary Documents
  13. Key Research Papers
  14. Connections
  15. Featured Videos

1. What Happened Between March and October 2022

On March 18, 2022, the FDA’s Center for Tobacco Products (CTP) announced that on March 15 the President had signed H.R. 2471, the Consolidated Appropriations Act, 2022. As a result, the CTP wrote, the Federal Food, Drug, and Cosmetic Act (FD&C Act) “now includes specific language that makes clear the U.S. Food and Drug Administration can soon regulate tobacco products containing nicotine from any source, which includes synthetic nicotine.” The provision took effect on April 14, 2022.

From that date the FDA treated products made with what it calls non-tobacco nicotine (NTN) — “nicotine not made or derived from tobacco, such as synthetic nicotine” — in the same way as other tobacco products. Over the following months the agency reported a series of steps:

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2. The Law Behind It: Congress, Not an FDA Rule

The change did not come from an FDA regulation. It came from a provision in a spending law passed by Congress, the Consolidated Appropriations Act, 2022 (H.R. 2471), signed on March 15, 2022. The FDA’s April 13 update describes it as “New legislation enacted on March 15” that “makes clear that FDA can regulate tobacco products containing nicotine from any source.” The FDA wrote no new rule in 2022 to bring this about; its 2022 steps were the deadline, application processing and enforcement described below.

This page describes the law as the FDA describes it in its own updates. The text of the statute itself was not read for this page.

In a perspective of August 3, 2022, the CTP director wrote that the law “closed a loophole that several companies were using to try to evade regulation,” and that “Now manufacturers of tobacco products containing non-tobacco nicotine are held to the same public health standards, including premarket review, that we’ve worked so hard to implement for other tobacco products.”

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3. Why the FDA Says the Change Was Needed

The CTP’s March 18 announcement gives the reason in one sentence: “Reports of e-cigarette manufacturers switching to nicotine not derived from tobacco in an attempt to evade FDA regulation revealed a critical need to clarify FDA’s authority over these products.” It adds that the change ensures “products that are similar except for the source of nicotine will be regulated as tobacco products.”

The same announcement states that “Youth tobacco product use remains a serious public health concern, and millions of American youth report use of electronic nicotine delivery systems (ENDS) products, including e-cigarettes.” By July the FDA wrote that “a growing number of companies–including manufacturers of some of the e-cigarette brands most popular with kids–began using synthetic nicotine to make their products in an attempt to evade the U.S. Food and Drug Administration’s regulation.”

On the substance itself, the CTP director, Brian King, wrote on August 3, 2022 that the new authority mattered “because nicotine, regardless of its source, is extremely addictive, especially when used by youth.” The July 13 update also pointed to the FDA’s e-cigarette public education campaign, aimed at “the nearly 10.7 million youth age 12-17 who have ever used e-cigarettes or are open to trying them.” The research on nicotine dependence is gathered on the site’s Addiction and Nicotine Toxicity and Safety pages.

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4. What Sellers Had to Do From April 14, 2022

The CTP’s April 13 update lists what manufacturers, distributors, importers and retailers of non-tobacco nicotine products had to do from April 14, 2022, “such as”:

In addition, owners and operators of establishments that make, prepare, compound or process these products had to register with the FDA and list every such product they make for sale. Manufacturers who wanted to keep selling had to submit a premarket application — formally a premarket tobacco product application, or PMTA — and obtain FDA authorization, “or they will be subject to FDA enforcement.”

A premarket application is the file a manufacturer sends the FDA asking permission to sell a new tobacco product. The FDA’s August 3 perspective lists examples of what it must contain: “information on product formulation, product testing and analysis, and evaluation of the health risks of the product both at the individual and population levels.”

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5. The May 14 Deadline and the July 13 Cut-Off

For non-tobacco nicotine products already on the market, the April 13 update set the application deadline at Saturday, May 14, 2022 for electronic submissions; an application sent in hard copy had to reach the FDA by 4:00 p.m. EDT on Friday, May 13, 2022.

The response was large. The CTP reported that by May 14 it had received applications for “nearly one million” products “from more than 200 separate companies,” “with some several thousand pages long.” The August 3 perspective explains that the submissions “varied widely in their organization, size, and completeness of data, which impacts the time it takes to process the information.”

The second date was July 13, 2022. The FDA’s update of that day states: “After today, July 13, 2022, any new non-tobacco nicotine product that has not received premarket authorization from FDA cannot be legally marketed.” The August 3 perspective restates it: after July 13, a non-tobacco nicotine product “can only be legally marketed in the United States if it has received premarket authorization from FDA,” and it is illegal for a retailer or distributor to sell one that does not have a marketing granted order (MGO) — the FDA’s written authorization to sell.

Two of the manufacturers that received the first warning letters on July 13 had, together, listed about 10,000 products with the FDA; neither had submitted an application by the May 14 deadline.

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6. How an Application Moves Through Review

The CTP director’s August 3 perspective describes the stages an application passes through:

  1. Acceptance. Applications “are required to provide important information needed for processing and reviewing. Without the required information, applications cannot proceed past the acceptance phase.” An application that fails this step receives a refuse-to-accept (RTA) letter. The RTA letters, the FDA says, “state that it is illegal to sell or distribute in the U.S. marketplace any new tobacco product that has not received premarket authorization.”
  2. Further review. Accepted applications “then enter further review, which ensures certain criteria are met.” The FDA stresses that acceptance “is not a determination about the products’ authorization status.”
  3. Substantive review. Applications that meet the criteria move on to a review that includes “consideration of the impact to the population as a whole, such as risks to youth and potential benefits to adult smokers,” and an evaluation of the scientific information and data, which “often results in follow-up questions and conversations with companies.”
  4. Decision. “It is only after the substantive phase that a company may be granted a marketing order. If no marketing order is granted, it remains illegal to market the product.”

As of August 3, 2022, the perspective states, “no non-tobacco nicotine product has received a marketing granted order.”

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7. Warning Letters, Refusals and Penalties

The August 3 perspective explains the usual order of steps when companies are found to be marketing FDA-regulated products illegally: “we first issue warning letters to promote compliance. We then follow up to ensure the violations addressed in the warning letter are corrected.” Companies are asked to respond, typically within 15 working days, with the steps they will take. If firms continue to violate the law, the FDA lists further actions it can pursue, “such as civil money penalties, seizures, and injunctions”; the July 13 update adds no-tobacco-sale orders, and that unauthorized products “detected for import into the United States can be detained or refused admission.”

The FDA’s 2022 updates report this sequence:

The CTP director was quoted on July 13 as saying that the warning letters were “just the beginning of our compliance and enforcement actions,” and that the FDA “will make marketing decisions based on the best available science.”

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8. The Count as of October 2022

The FDA’s October 14, 2022 update gives the year’s last running total found for this page. Its figures, as of October 7, 2022:

The update concludes: “To date, the FDA has not authorized any NTN products. Therefore, all NTN products on the market are marketed unlawfully and risk FDA enforcement action.” These counts are a snapshot of 2022, not a current figure.

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9. What the Change Does Not Do

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10. Dates and Legal Status as of October 18, 2026

Status as of October 18, 2026: in effect. The statutory change has applied since April 14, 2022. A check of the Federal Register through October 18, 2026 for FDA documents on non-tobacco nicotine found the two March 2023 conforming documents and other routine notices, a proposed rule on import data and a testing-methods guidance, and no document that reverses or suspends the change. The application and enforcement counts on this page are the FDA’s 2022 figures.

A Federal Register docket is the public file for an action, where its documents and public comments are kept on regulations.gov. A guidance document describes how the FDA reads and applies a law; it does not itself create new legal requirements.

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11. How It Fits Earlier and Later FDA Tobacco Actions

The CTP director’s August 2022 perspective places the change in the history of the agency’s tobacco work: “In the 13 years since the landmark Tobacco Control Act was signed into law, CTP has done significant work to effectively regulate a complex and rapidly changing tobacco product landscape.” The 2022 law extended the same premarket review to products whose nicotine does not come from tobacco.

Other FDA tobacco actions of 2022 are reported on their own pages: the April 2022 proposals to ban menthol cigarettes and flavored cigars and the June 2022 marketing denial for a leading e-cigarette maker and its stay.

The story continues on later pages. The 2023 page on flavored e-cigarette denials and youth-appealing disposables reports the March 2023 conforming rule and the FDA’s later enforcement. The 2025 authorization of the first nicotine pouches shows the premarket pathway ending in a marketing order, and the 2025 withdrawal of the menthol, flavored cigar and nicotine cap rules reports what became of the 2022 proposals.

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12. Primary Documents

  1. U.S. Food and Drug Administration, Center for Tobacco Products. New Law Clarifies FDA Authority to Regulate Synthetic Nicotine. CTP Newsroom, March 18, 2022 — fda.gov CTP Newsroom, March 18, 2022
  2. U.S. Food and Drug Administration, Center for Tobacco Products. Requirements for Products Made with Non-Tobacco Nicotine Take Effect April 14. CTP Newsroom, April 13, 2022 — fda.gov CTP Newsroom, April 13, 2022
  3. U.S. Food and Drug Administration, Center for Tobacco Products. FDA Continues to Implement Law, Regulate Non-Tobacco Nicotine Products, Warns Retailers and Manufacturers Against Illegal Sales. CTP Newsroom, July 13, 2022 — fda.gov CTP Newsroom, July 13, 2022
  4. King B, Director, Center for Tobacco Products. Perspective: Update on FDA Review and Enforcement of Non-Tobacco Nicotine Products. CTP Newsroom, August 3, 2022 — fda.gov CTP Newsroom, August 3, 2022
  5. U.S. Food and Drug Administration, Center for Tobacco Products. FDA Continues to Implement Law Regarding Non-Tobacco Nicotine Products. CTP Newsroom, September 8, 2022 — fda.gov CTP Newsroom, September 8, 2022
  6. U.S. Food and Drug Administration, Center for Tobacco Products. FDA Completes Initial Review of 95% of Non-Tobacco Nicotine Product Applications; Agency Has Issued Over 60 Warning Letters to Manufacturers. CTP Newsroom, October 14, 2022 — fda.gov CTP Newsroom, October 14, 2022
  7. Food and Drug Administration, HHS (2023). Definition of the Term “Tobacco Product” in Regulations Issued Under the Federal Food, Drug, and Cosmetic Act. Technical amendment. Federal Register 88 FR 16551, March 20, 2023. Docket No. FDA-2022-N-3262 — FR Doc. 2023-03950
  8. Food and Drug Administration, HHS (2023). Definition of the Term “Tobacco Product” in Guidances Issued Under the Federal Food, Drug, and Cosmetic Act. Notice. Federal Register 88 FR 16636, March 20, 2023. Docket No. FDA-2022-N-3261 — FR Doc. 2023-03951
  9. Public docket FDA-2022-N-3262 — regulations.gov FDA-2022-N-3262

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Key Research Papers

  1. Jordt SE (2023). Synthetic nicotine has arrived. Tobacco Control 32(e1):e113-e117 — PubMed PMID: 34493630
  2. Cheetham AG, Plunkett S, Campbell P, Hilldrup J, Coffa BG, Gilliland S 3rd, Eckard S (2022). Analysis and differentiation of tobacco-derived and synthetic nicotine products: Addressing an urgent regulatory issue. PLoS One 17(4):e0267049 — PubMed PMID: 35421170
  3. Morean ME, Bold KW, Davis DR, Kong G, Krishnan-Sarin S, Camenga DR (2022). Does it come from tobacco? Young adults’ interpretations of the term “tobacco-free nicotine” in a cross-sectional national survey sample. PLoS One 17(5):e0268464 — PubMed PMID: 35559988
  4. Camenga DR, Krishnan-Sarin S, Davis DR, Bold KW, Kong G, Morean ME (2022). Curiosity, use, and perceptions of “tobacco-free nicotine” E-cigarettes among U.S. young adults. Preventive Medicine 164:107296 — PubMed PMID: 36216122
  5. Ma S, Qiu Z, Chen J, Shang C (2023). Synthetic nicotine e-liquids sold in US online vape shops. Preventive Medicine Reports 33:102222 — PubMed PMID: 37181243
  6. Liakoni E, Christen SE, Benowitz NL (2024). E-cigarettes, synthetic nicotine, heated-tobacco and smokeless nicotine delivery products: the nicotine landscape beyond combustible cigarettes. Swiss Medical Weekly 154:3583 — PubMed PMID: 39835719
  7. Harrington T, Ferketich AK, Lu B, Wagner DD, Roberts ME (2025). Prospective associations between nicotine type and the continuation of youth e-cigarette use. BMC Public Health 25(1):4158 — PubMed PMID: 41299554

The first paper describes the arrival of synthetic nicotine on the market, and the second the laboratory methods for telling tobacco-derived nicotine from synthetic nicotine. The third and fourth are U.S. surveys of how young adults understand and use products labelled “tobacco-free nicotine.” The fifth looks at synthetic nicotine e-liquids sold online, the sixth is a review of nicotine products other than combustible cigarettes, and the seventh follows youth e-cigarette use by nicotine type over time.

PubMed Topic Searches

  1. PubMed: synthetic nicotine
  2. PubMed: “tobacco-free nicotine” e-cigarettes
  3. PubMed: e-cigarette premarket tobacco product applications

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Connections

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