Tag: synthetic nicotine

  • Hangsen Sued Over Synthetic Nicotine

    Hangsen Sued Over Synthetic Nicotine

    Photo: Tobacco Reporter archive

    Zanoprima Lifesciences filed a complaint for patent infringement against Hangsen International Group in the U.S. District Court in the Western District of Texas. In its complaint, Zanoprima Lifesciences alleges that Hangsen has violated its patent titled “Process for Making (S)-Nicotine” through Hangsen’s manufacture and importation into the U.S. market of products containing synthetic nicotine that are manufactured using Zanoprima Lifesciences’ process, according to a press release.

    “Over many years, Zanoprima has invested substantial time, resources, intellectual capital and scientific expertise into developing Zanoprima’s groundbreaking enzymatic patented process for synthesizing an (S)-nicotine that is devoid of tobacco-specific nitrosamines and other impurities,” said Ashok Narasimhan, CEO of Zanoprima. “Zanoprima’s legal action reflects our company’s dedication to vigorously protecting our intellectual property in the U.S. and around the world.”

    Zanoprima’s complaint alleges that, after publication of Zanoprima’s patent, Hangsen filed a Chinese patent application describing a process that copied the process invented by Zanoprima. But, as alleged in the complaint, Hangsen’s patent application was rejected by the Chinese Patent Office in June 2021, citing Zanoprima’s patent as prior art. The complaint also alleges Hangsen imports into the U.S. from China and sells products containing “alleged high-purity synthetic (S)-nicotine and nicotine products that are marketed and sold under various names, including as MOTiVO Synthetic S-Nicotine,” and that such imported products “are manufactured by a process that practices every step of claim 1” of the Zanoprima patent.

    In addition to seeking damages for infringement, Zanoprima’s complaint seeks preliminary and permanent injunctive relief to prevent Hangsen from continuing its infringing actions.

  • FDA Gets Authority Over Synthetic Nicotine

    FDA Gets Authority Over Synthetic Nicotine

    Photo: The White House

    U.S. President Joe Biden on Tuesday signed into law a spending bill that gives the Food and Drug Administration authority over synthetic nicotine.

    The language of the Tobacco Control Act will now change to define a tobacco product as “any product made or derived from tobacco, or containing nicotine from any source, that is intended for human consumption.”

    The amendment comes into effect 30 days after the bill’s enactment. Manufacturers of products made with synthetic nicotine will then have an additional 30 days to submit a premarket tobacco product application (PMTA) to the FDA. If FDA has not authorized the product within 90 days after the effective date, the product must be removed from the market.

    According to Bryan Haynes, a partner with Troutman Pepper, the measure could amount to an effective ban on synthetic nicotine products. “FDA is highly unlikely to authorize a PMTA in 90 days when other PMTAs for electronic nicotine delivery systems have been pending for more than two years,” he wrote on the law firm’s blog.

    April Meyers, board president for the Smoke-Free Alternatives Trade Association (SFATA) suspects the bill will have little effect on youth vaping, which is already down significantly since highs in 2015. “Although the sponsors of the bill claim the intent was to close the loophole on synthetic nicotine-derived products from large companies now popular among youth, the reality is that this bill—and others like it—aren’t likely to have the intended effect,” she said. “Instead, consumers using these products as a harm reduction option will suffer, as will licensed small businesses in full compliance with federal, state, and local laws.

    “The FDA created a problem by overregulating a product used by millions of adults who find vaping a safer alternative to smoking. When a market in high demand is overregulated, grey and black markets emerge where there are no regulations requiring safe products or ID checks.”

    The FDA appears keen to crack down on synthetic nicotine. During his Senate confirmation hearing, FDA Commissioner Robert Califf vowed to close what he described as the synthetic nicotine “loophole.”

  • Synthetic Nicotine Rule Clears Senate

    Synthetic Nicotine Rule Clears Senate

    Photo: lazyllama

    Synthetic nicotine products will soon require U.S. Food and Drug Administration marketing approval. The U.S. Senate approved a $1.5 trillion spending bill that includes language that changes the definition of a tobacco product to include synthetic nicotine. The legislation now heads to President Joe Biden, who looks forward to signing it into law, according to White House spokesperson Jen Psaki.

    Synthetic nicotine—nicotine that is made in a lab rather than derived from tobacco—has long existed in a legal gray area, and many companies started using it after their natural nicotine products were denied market access by the FDA. Public health groups have been warning that synthetic nicotine e-cigarettes, such as Puff Bar, have grown in popularity among teens while skirting FDA oversight.

    The Food, Drug and Cosmetic Act, which includes the 2009 Tobacco Control Act, defines a tobacco product as “any product made or derived from tobacco that is intended for human consumption, including any component, part or accessory of a tobacco product (except for raw materials other than tobacco used in manufacturing a component, part or accessory of a tobacco product).”

    At a time when FDA is under scrutiny from multiple federal courts for unlawful regulatory overreach on nicotine, handing the agency even more powers to prevent Americans from switching to vaping is like handing car keys and a bottle opener to your drunk uncle.

    Amanda Wheeler, president of the American Vapor Manufacturers Association

    Proponents of the policy change refer to it as closing a loophole. “By using synthetic nicotine, e-cig companies are avoiding public health protections for flavored tobacco products and still hooking teens,” tweeted billionaire philanthropist Michael Bloomberg. “With millions of kids still using e-cigs, we must get synthetic nicotine products off the market.”

    Critics contend that, given the flaws and deficiencies in the FDA approval process, the new rules will likely result in the prohibition of products that smokers have been using to quit cigarettes.

    Amanda Wheeler, president of the American Vapor Manufacturers Association, said banning synthetic products will drive millions back to combustible cigarettes.

    “At a time when FDA is under scrutiny from multiple federal courts for unlawful regulatory overreach on nicotine, handing the agency even more powers to prevent Americans from switching to vaping is like handing car keys and a bottle opener to your drunk uncle,” she said.

  • Synthetic Nicotine Regulation Clears House

    Synthetic Nicotine Regulation Clears House

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    The House of Representatives approved a $1.5 trillion spending package that would give the U.S. Food and Drug Administration authority to regulate synthetic nicotine. The bill now goes to the Senate.

    Synthetic nicotine—nicotine that is made in a lab rather than derived from tobacco—has long existed in a legal gray area, and many companies started using it after their natural nicotine products were denied market access by the FDA. Public health groups have been warning that synthetic nicotine e-cigarettes, such as Puff Bar, have grown in popularity among teens while skirting FDA oversight.

    The Food, Drug and Cosmetic Act, which includes the 2009 Tobacco Control Act, defines a tobacco product as “any product made or derived from tobacco that is intended for human consumption, including any component, part or accessory of a tobacco product (except for raw materials other than tobacco used in manufacturing a component, part or accessory of a tobacco product).”

    If the spending bill currently under consideration passes, the language of the Tobacco Control Act would change to define a tobacco product as “any product made or derived from tobacco, or containing nicotine from any source, that is intended for human consumption.”

    The synthetic nicotine provisions are set to take effect 30 days after the bill’s passage. Synthetic nicotine producers then have 60 days from its enactment—or 30 days after it becomes effective—to file premarket tobacco product applications with the FDA to legally stay on the market. Ninety days after the effective date, or 120 days after the bill’s passing, these manufacturers will have to stop selling their products if the FDA has not authorized them. At that point, the FDA can exercise its enforcement discretion.

    Anti-smoking activists welcomed the legislation. “By using synthetic nicotine, e-cig companies are avoiding public health protections for flavored tobacco products and still hooking teens,” tweeted billionaire philanthropist Michael Bloomberg. “With millions of kids still using e-cigs, we must get synthetic nicotine products off the market.”

    Consumer advocates, by contrast, warned the move would deny adult smokers access to lower risk alternatives. “Only the largest and most powerful vaping and tobacco companies can afford the lawyers and the time necessary to complete the paperwork necessary to pass the FDA’s process, meaning thousands of hard-working American business owners will now be forced to close, depriving millions of adult consumers of harm reducing options,” said Yael Ossowski, deputy director of the Consumer Choice Center.

    The FDA appears keen to crack down on synthetic nicotine. During his Senate confirmation hearing, FDA Commissioner Robert Califf vowed to close what he described as the synthetic nicotine “loophole.”

    Earlier, FDA Center for Tobacco Products Director Mitch Zeller indicated that the synthetic nicotine could be considered a component of e-cigarettes, which would have allowed the agency to assert authority over the substance under existing legislation.

  • FDA Likely to Regulate Synthetic Nicotine

    FDA Likely to Regulate Synthetic Nicotine

    Photo: Kristina Blokhin

    A bill intended to fund the U.S. government through September includes language that would give the Food and Drug Administration authority to regulate synthetic nicotine. The House of Representatives could vote on the legislation as early as today.

    Synthetic nicotine is currently not explicitly regulated by the FDA, and many companies started using it after their natural-nicotine products were denied market access by the agency. Public health groups have been warning that synthetic nicotine e-cigarettes such as Puff Bar have grown in popularity among teens while skirting FDA oversight.

    The Food, Drug & Cosmetic Act, which includes the 2009 Tobacco Control Act, defines a tobacco products as “any product made or derived from tobacco that is intended for human consumption, including any component, part, or accessory of a tobacco product (except for raw materials other than tobacco used in manufacturing a component, part, or accessory of a tobacco product).”

    If the spending bill currently under consideration passes, the language of the Tobacco Control Act would change to define a tobacco product as “any product made or derived from tobacco, or containing nicotine from any source, that is intended for human consumption.”

    The synthetic nicotine provisions would take effect 30 days after the bill’s passage. Synthetic nicotine producers would then have 60 days from its enactment—or 30 days after it becomes effective—to file premarket tobacco product applications with the FDA to legally stay on the market. Ninety days after the effective date, or 120 days after the bill’s passing, these manufacturers would have to stop selling their products if the FDA has not authorized them. At that point, the FDA could exercise its enforcement discretion.

    Consumer advocated have criticized the attempt to “sneak in” the synthetic nicotine provision into the spending bill.

    “The byzantine process of asking permission to sell harm reducing vaping products in the 21st century is asinine in itself,” said Yaël Ossowski, deputy director of the Consumer Choice Center. “But using sleight of hand during an emergency government funding bill to castigate millions of vapers and the entrepreneurs who make and sell the products they rely on is the definition of active harm.”

    “Only the largest and most powerful vaping and tobacco companies can afford the lawyers and the time necessary to complete the paperwork necessary to pass the FDA’s process, meaning thousands of hard-working American business owners will now be forced to close, depriving millions of adult consumers of harm reducing options.”

    The bill is purportedly backed by Juul Labs and Reynolds American, both of which face competition from Puff Bar and from e-liquid sold in vape shops and online.

  • U.S. States Target Synthetic Nicotine

    U.S. States Target Synthetic Nicotine

    Georgia, Maryland and Mississippi legislators recently introduced bills in their respective states that would only allow the sale of vapor products that are authorized by or pending authorization from the U.S. Food and Drug Administration, according to a Filter article.

    The pieces of legislation would also establish directories to inventory authorized vapor products, which would eventually be made public. On the surface, these bills look like they are reiterating what the FDA is already doing through its premarket tobacco product application (PMTA) process, through which the FDA has denied millions of products. However, many have noted that the bills serve as a roundabout way to ban synthetic nicotine.

    Many manufacturers have turned to synthetic nicotine as a way to continue selling their products since synthetic nicotine is not currently regulated.  

    “The elected officials sponsoring these bills may be under the mistaken impression that their proposals are only targeted at illicit and counterfeit dealers,” Greg Conley, president of the American Vaping Association, told Filter. “The reality is that these bills would shut down licensed small businesses that are operating in full compliance with federal, state and local laws.”

    The Republican lawmakers who introduced the bills—Maryland State Senator JB Jennings, Georgia State Senator Jeff Mullis and Mississippi Representative Nick Bain—have all received campaign funds ranging from $500 to $4,800 from Juul Labs, according to Filter. Some feel that Juul and other large companies want to see synthetic nicotine (and competition) diminished.

    “To preserve the harm reduction opportunity for adult smokers, Juul Labs supports a fully regulated, science-based marketplace,” a Juul spokesperson said. “Illegally marketed and illicit products and products designed to evade federal and state oversight undermine harm reduction and a responsible e-vapor category.”

  • Momentum Building in U.S. for Regulating Synthetic Nicotine

    Momentum Building in U.S. for Regulating Synthetic Nicotine

    Photo: Aliaksandr Barouski

    Momentum appears to be building for the regulation of synthetic nicotine in the United States.

    On Dec. 15, U.S. Representative Mikie Sherrill introduced a bill designed to give the U.S. Food and Drug Administration the authority to regulate synthetic nicotine products just as it regulates nicotine products made or derived from tobacco.

    “This bill will ensure all tobacco products, including products made with synthetic nicotine, are regulated by the FDA in order to protect kids in our communities and those who may seek to use these products,” Sherrill said in a statement.

    The Federal Food, Drug and Cosmetic Act (FDCA) currently defines “tobacco product” as “any product made or derived from tobacco that is intended for human consumption, including any component, part or accessory of a tobacco product.”

    In November, FDA Center for Tobacco Products Director Mitch Zeller suggested synthetic nicotine could be considered a component of e-cigarettes, which would allow the agency to regulate it.

    The FDA could also seek to regulate synthetic nicotine as a drug. The FDCA defines drugs, among other things, as “articles (other than food) intended to affect the structure or any function of the body.”

    In the 1990s, the FDA tried to regulate nicotine as a drug and cigarettes and smokeless tobacco as “drug delivery devices.” In FDA v. Brown & Williamson Tobacco Corp., the U.S. Supreme Court found that the FDA lacked such authority.

    The 2009 Family Smoking Prevention and Tobacco Control Act gave the FDA the authority to regulate tobacco products. Should the FDA regulate synthetic nicotine as a drug today, it could point to recent legislation from Congress giving the FDA a role in this space more broadly. So far, however, the FDA has not taken this approach.

    Following a flurry of marketing denial orders in which the FDA forced many products containing tobacco-derived nicotine off the market, several manufacturers have switched to synthetic nicotine to avoid the agency’s rigorous and costly premarket review process.

    In response to such moves, lawmakers have initiated investigations and called for regulation of the category. On Nov. 16, nine senators sent a letter to the FDA imploring the agency to regulate synthetic nicotine products. The authors expressed concerns that e-cigarette manufacturers like Puff Bar are switching to synthetic nicotine to skirt FDA oversight and premarket review requirements to continue selling their products—including flavored products—that they assert appeal to youth.

    That same day, the North Carolina attorney general launched an investigation into Puff Bar. On Nov. 8, he sent letters to e-cigarette manufacturers Puff Bar and Next Generation Labs requesting extensive records pertaining to the production and marketing of the companies’ synthetic nicotine products.

  • FDA Nominee Vows to Close Synthetic Nicotine Loophole

    FDA Nominee Vows to Close Synthetic Nicotine Loophole

    Robert Califf

    Robert Califf vowed to close the synthetic nicotine loophole if appointed commissioner of the U.S. Food and Drug Administration, according to a report by Vaping360.

    During Califf’s nomination hearing on Dec. 14, Wisconsin Senator Tammy Baldwin expressed concern over reports that companies are switching to making flavored synthetic nicotine products in the wake of FDA marketing denial orders.

    “As FDA commissioner, how would you work to address the rise in youth use of synthetic nicotine, and will you commit to working with Congress to ensure that the FDA has the authorities and resources it needs to crack down on these products?” Baldwin asked.

    In response, Califf first noted that is crucial to appoint the right person to succeed Center for Products Director Mitch Zeller, who plans to retire in April 2022.

    “Secondly,” Califf continued, “this is not limited to children. I may have some family members using synthetic nicotine, I learned as I was going through the paces here. And what people don’t realize is that there are two enantiomers of nicotine—one of which is not occurring in nature—that are in this product, and its properties are not known.

    “So we’ve got to close this loophole,” Califf added, “so that we make sure that we understand the risks and benefits, and particularly deal with the issues in children.”

    The Senate Health, Education, Labor & Pensions Committee will vote soon on whether to recommend Califf’s nomination to the full Senate. If the committee approves him, the former commissioner can expect full Senate confirmation to be the new commissioner soon, probably in January.

  • Acting Unnaturally

    Acting Unnaturally

    Photo: artefacti

    Synthetic versus tobacco-derived nicotine

    Cheryl K. Olson and Willie McKinney

    Every year, the National Youth Tobacco Survey gathers data from U.S. middle school and high school students about all sorts of nicotine products and how they’re used. In 2021, for the first time the most popular brand of e-cigarette among underage users was a synthetic nicotine vape. Puff Bar was named “usual brand” by 26.1 percent of underage vapers, equaling the sum of the next three most popular brands: Vuse (10.8 percent), Smok (9.6 percent) and Juul (5.7 percent). While the summary of these latest findings in Morbidity and Mortality Weekly Report didn’t mention the word “synthetic,” the U.S. Food and Drug Administration certainly took note.

    One reason the FDA pricked up its ears is that synthetic nicotine, also known as nontobacco nicotine, lives in a legal gray area. The Family Smoking Prevention and Tobacco Control Act of 2009 expanded the FDA’s authority to regulate products “made or derived from tobacco” and created its Center for Tobacco Products.

    This begs the question of whether the FDA has regulatory authority over synthetic nicotine. Predictably, manufacturers who use it in ENDS products claim that the FDA does not have that authority. If that’s true, those manufacturers can bypass the lengthy and expensive premarket tobacco product application process and go directly to market. But there are others, including attorneys who’ve studied this law, who believe that even if synthetic nicotine is technically not covered by the 2009 Tobacco Control Act, it meets the definition of a drug and is therefore subject to FDA regulation.

    The substitution of synthetic nicotine for tobacco-derived nicotine has profound implications both for manufacturers and distributors of reduced-harm nicotine products. Is it a smart workaround, a temporary shelter or a costly dead end? Here are some of the key issues as well as ways to limit your risk as a company.

    The Options

    Over the past few months, many makers of flavored e-cigarette products have received marketing denial orders (MDOs) or fear receiving one. An MDO gives that manufacturer a limited number of choices: reapply for approval, get out of the business or sue the FDA for redress—or search for what it hopes is a legal loophole to the FDA’s regulatory authority. Hence, the move to synthetic nicotine as a too clever by half solution that carries with it underlying scientific, economic, legal and ethical issues.

    Let’s start with an economic issue, which may trump all the others. Synthetic nicotine is expensive. In fact, it’s up to 10 times the cost of tobacco-derived nicotine, according to Kevin Burd, CEO of North America Nicotine. One reason is that tobacco-derived nicotine is made from leftover scraps from processing tobacco leaves—often literally the stuff left on the factory floor. Synthetic nicotine, most of which is manufactured in China, is created through a variety of proprietary chemical processes.

    “As volumes increase, I can’t see the price of chemicals used in synthetic coming down to the price of waste tobacco, including dust,” said Burd. “It’s highly unlikely ever to be competitive.”

    Both synthetic nicotine and tobacco-derived nicotine occur in two structural forms (enantiomers) known as R-nicotine and S-nicotine. More than 99 percent of the nicotine in tobacco is S-nicotine. In synthetic nicotine, that balance can be 50-50.

    “Little is known about the pharmacological and metabolic effects of R-nicotine in humans,” says a 2021 article on the rise of synthetic nicotine  in Tobacco Control (Jordt SE. Synthetic nicotine has arrived. Tobacco Control 2021. doi: 10.1136/tobaccocontrol-2021-056626). In other words, synthetic product users could be unwitting research subjects. There are inexpensive tests for distinguishing between R- and S- forms of the chemical and ways of separating the R-isomer from the S-isomer. By comparison, telling the difference between synthetic S-nicotine and tobacco-derived S-nicotine can be quite costly.

    This leads to an interesting paradox. We don’t know how much of the supposed synthetic nicotine is actually tobacco-derived nicotine. There’s a financial incentive for a manufacturer simply to replace the more expensive version with the cheaper chemical and mislabel it. In fact, on its website, Next Generation Labs warns prospective customers, “There are several companies from China claiming to have synthetic nicotine. NGL has tested several of these products and discovered they are made or derived from tobacco.”

    Burd adds, “Quite likely, many [products that claim to be synthetic] are not really synthetic.”

    Some companies are weighing the cost of regulatory compliance versus the higher manufacturing cost of using synthetic nicotine. That’s a false choice, for it underestimates the costs of unknown safety risks, product testing and emerging regulations. Simply marketing a new synthetic nicotine product without providing the necessary scientific and behavioral research data to the FDA will, at the very least, generate a warning letter.

    Remember that the key reason for generating research data on a new product is to explore whether it will harm people. The FDA uses the term APPH (appropriate for the protection of public health). Not doing so puts your business at risk not only from regulatory actions but from civil litigation if someone gets hurt.

    A regulatory update by FDA Center for Tobacco Products Director Mitch Zeller at an Oct. 27 Food and Drug Law Institute conference addressed the challenge posed by synthetic nicotine. Zeller’s slide deck makes clear his belief that e-liquids that do not contain tobacco-derived substances “may still be components or parts of tobacco products and, therefore, subject to FDA’s tobacco control authorities.” It also states that the FDA is “in discussions with Congress about a potential legislative fix.”

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    The Wild West

    Burd expressed concern that synthetic nicotine, and the regulatory uncertainty driving its use, have put the vaping industry “back to the Wild West.” Even the pure S synthetic may contain residues from the unknown solvents that some new manufacturers use. Burd recommends that manufacturers who use synthetic nicotine “test their incoming material (emphasizing impurities and solvents), audit the supplier, do a toxicology review for product safety and be sure to use S-nicotine only.”

    That type of analysis is impractical for end users, of course.

    Finally, there’s the issue of whether a company is a “bad actor” that focuses on short-term financial profits at the expense of both public health and the lives of their customers. The FDA runs the risk of encouraging such unethical behaviors if it broadly bans products from those companies making sincere efforts to reduce the harm done to smokers of combustible cigarettes while ignoring companies that look for legal loopholes.

    A Marketing Throwback?

    The issue of synthetic nicotine regulation is likely to be resolved fairly soon. One reason is that the attractiveness of e-cigarettes to youth is rightfully a major concern of the FDA. Marketing materials for synthetic nicotine products have the tone of advertising done by an earlier iteration of Big Tobacco when it claimed that paper filters, toasting and other irrelevant variables reduced cigarettes’ negative health effects.

    • American Tobacco Company (1930): “20,679 physicians say Luckies are less irritating. Toasting removes dangerous irritants.”
    • Liggett & Myers (1931): “Chesterfield Cigarettes are just as pure as the water you drink.”
    • Brown and Williamson (1949): “Viceroys filter the smoke. As your dentist, I’d recommend Viceroys.”
    • Puff Bar (2021): “Our nicotine products are crafted from a patented manufacturing process, not from tobacco. The result? A virtually tasteless, odorless nicotine without the residual impurities of tobacco-derived nicotine.”
    • Next Generation Labs (2021): “TFN Nicotine is not derived from tobacco leaf, stem, reconstituted sheet, expanded or postproduction waste dust. The nicotine is made using a patented manufacturing process that begins with a natural starter material and progressively builds around the molecules of that material to create a pure synthetic nicotine.”

    These claims (from company websites) about differences between synthetic and tobacco-derived nicotine misleadingly hint at safety without providing real data. They skirt the important scientific issues and focus on emotionally resonant phrases like “begins with a natural starter material,” “without the residual impurities” and “create a pure synthetic nicotine.”

    Adolescents in particular may make the false inferential leap that synthetic nicotine somehow carries less risk or is less addictive than tobacco-derived nicotine, according to new research from Rutgers University and the National Institutes of Health. This, in turn, may lead nonsmoking, nonvaping teens to use the products often enough to become addicted. The risk of any new product to children is a tried-and-true political plank, so it’s likely to gain the attention of members of Congress, who could pass a law declaring all forms of nicotine to be under the purview of the FDA. —WMK and CKO

    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.
    Cheryl K. Olson is a California-based public health researcher who specializes in behavioral health issues and consults on tobacco product behaviors. She spent 15 years on the faculty of Harvard Medical School.
  • Synthetic Nicotine May be Subject to Regulation

    Synthetic Nicotine May be Subject to Regulation

    Photo: Tobacco Reporter archive

    Synthetic nicotine could be considered a component of e-cigarettes, which would allow for the product to be regulated by the U.S. Food and Drug Administration. Mitch Zeller, director of the FDA’s Center for Tobacco Products, said the agency was concerned about the use of synthetic nicotine to avoid regulation and enforcement and is considering its options in dealing with its use.

    On Nov. 17, the first day of TMA’s “From Chance to Change” webinar, Zeller said that the Tobacco Control Act defines tobacco products as anything that is made or derived from tobacco and is intended for consumption. The FDA believes that it also includes components and parts (such as coils and batteries) and all the ingredients included in producing e-liquids (such as flavorings and vegetable glycerin) even if the product does not contain nicotine.

    “That’s an assessment that we need to make on a case-by-case basis based upon the totality of all the information that we have,” said Zeller.

    According to Zeller, synthetic nicotine represents a challenge for the agency because it is increasingly difficult to differentiate from naturally derived nicotine. “Historically, that hasn’t been a problem,” he said. “It’s not a problem now, but it could become a challenge for us going forward.”

    Zeller explained that nicotine is comprised of two isomers: R and S. Tobacco-derived nicotine is 99 percent S, and early synthetic nicotine had a 50-50 split between R isomers and S isomers. However, newer versions of synthetic nicotine have much higher proportions of S isomers (as high as 99.9 percent pure), making it harder to tell synthetic nicotine apart from natural nicotine. Tobacco-derived nicotine is also becoming higher in quality.

    “Tobacco-derived nicotine is now being made available at a higher quality … pharmaceutical grade from a purity standpoint. And with that, it may be harder for us to see that chemical fingerprint, if you will, whether it’s tobacco DNA or tobacco-specific nitrosamines,” he said. “We could see this as a problem going forward. Coupled with the clear intent of certain companies to do this to evade FDA regulation … We are concerned about what this means for product regulation, for the public health, and a product like Puff Bar proudly proclaiming its use of synthetic nicotine [and] being the No. 1 brand used by youth.”

    In the short term, Zeller said the FDA is talking internally about how to best address the growing number of products that are using synthetic nicotine to skirt FDA regulation. He said the agency is also responding to questions from Congress about synthetic nicotine and providing technical assistance to members when asked.

    “There are a lot of companies out there that pride themselves on playing by the rules. They have every right to expect that the playing field is going to be level. That’s where we come in with our compliance and enforcement authorities,” Zeller said. “We agree that one of the most important things that we can do, using our compliance and enforcement tools, is to level the playing field and to have our actions [in the e-cigarette space], hopefully, serve as a deterrent. There’s nothing that I can say from a compliance enforcement standpoint on synthetic nicotine other than we have ongoing investigations.”