New Jersey Congresswoman Mikie Sherrill, on Dec. 15, introduced the Clarifying Authority Over Nicotine Act of 2021 — a bipartisan bill designed to give the U.S. Food and Drug Administration (FDA) the authority to regulate synthetic nicotine products just as it regulates nicotine products made or derived from tobacco. In a press release, Rep. Sherrill stated, “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.”
Credit: DedMityay
In a blog post, Bryan Haynes and Michael Jordan, attorneys with Troutman Pepper, state that, as it stands, the Federal Food, Drug, and Cosmetic Act (FDCA) 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.” 21 U.S.C. § 321(rr)(1) (emphasis added). As the FDA concedes on its website, “it’s possible that a disposable, closed system device that contains an e-liquid with truly zero nicotine (or synthetic nicotine) would not be regulated by the FDA as a tobacco product.”
That said, there are other ways FDA might try to regulate synthetic nicotine, whether under its authority to regulate a “component” of a tobacco product or as a “drug.” In November, FDA Center for Tobacco Products Director Mitch Zeller discussed the “component” aspect of the FDCA’s definition of “tobacco product” and suggested “that components and parts could include everything from coils and batteries to all the ingredients comprised in producing e-liquids (such as flavorings and vegetable glycerin) even if the product does not contain nicotine.” He added, “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.”
FDA could also seek to regulate synthetic nicotine as a drug. The FDCA defines drug, among other things, as “articles (other than food) intended to affect the structure or any function of the body.” 21 U.S.C. § 321(g)(1). To the extent synthetic nicotine is intended to affect a consumer’s body, FDA could attempt to assert jurisdiction. Indeed, in the 1990s, FDA tried to regulate nicotine as a “drug” and cigarettes and smokeless tobacco as “drug delivery devices.” The Supreme Court in FDA v. Brown & Williamson Tobacco Corp. found FDA lacked such authority, but one of the Court’s key findings was that Congress had passed “tobacco-specific legislation [that] effectively ratified the FDA’s previous position that it lacks jurisdiction to regulate tobacco.” Today, things are different. The 2009 Family Smoking Prevention and Tobacco Control Act gave FDA the authority to regulate tobacco products. Should FDA regulate synthetic nicotine as a drug today, it could point to recent legislation from Congress giving FDA a role in this space more broadly. So far, however, FDA has not taken this approach.
With FDA having ordered more than five million tobacco-derived, e-cigarette products off the market, several manufacturers appear to have turned to synthetic nicotine to avoid FDA’s rigorous (and costly) premarket review process. In general, that process requires those who seek to market new tobacco products to demonstrate that their sale is “appropriate for the protection of public health” with the support of scientific evidence. 21 U.S.C. §387j(c)(4), (5). After receiving a denial from FDA of his premarket review applications, one vaping company owner took to Facebook to announce the company’s switch to synthetic nicotine, adding: “We never wanted to switch to [synthetic nicotine], but the FDA forced us to make that decision as we have so many adults relying on us [for alternatives to cigarettes].”
Lawmakers have taken notice. In November, a flurry of investigations and calls to regulate synthetic nicotine products reached a new high. On November 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 pre-market 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 for similar reasons. And, on November 8, the House Oversight Committer’s Subcommittee on Economic and Consumer Policy sent letters to e-cigarette manufacturers Puff Bar and Next Generation Labs LLC, requesting extensive records pertaining to the production and marketing of the companies’ synthetic nicotine products.
Time will tell if Congress will pass Rep. Sherrill’s Clarifying Authority Over Nicotine Act of 2021. Given the uptick in scrutiny of synthetic nicotine products, however, there is a strong chance Congress could give FDA a clear mandate to regulate synthetic nicotine in 2022.
Experts say Congress’ latest attempt to tax nicotine is complicated, confusing and harmful to public health.
By Timothy S. Donahue
To help pay for an infrastructure bill, the U.S. Congress has again introduced an excise tax on next-generation nicotine products, such as e-cigarettes and snus. The excise tax would apply to nicotine vapor products using both natural and synthetic nicotine as well as nicotine pouches. Experts say the provision, which would ultimately be paid by tobacco consumers, goes against U.S. President Biden’s campaign promise to not increase taxes on those making less than $400,000, negatively impact tobacco harm reduction efforts, increase sales of combustible tobacco products and boost an already growing black market.
The nicotine tax has been removed and reintroduced to Biden’s Build Back Better (BBB) legislation at least three times. The proposed vapor tax provision is now part of the latest version of the administration’s social spending and climate bill. According to Ulrik Boesen, a senior policy analyst with the Center for State Tax Policy at the Tax Foundation, taxes on tobacco and nicotine products tend to serve at least two purposes: to improve public health and raise revenue. He claims that a nicotine tax could do that if it is properly designed.
Ulrik Boesen / Credit: Tax Foundation
“A good design means internalizing externalities related to consumption of a product,” Boesen stated. “With tobacco and nicotine product consumption, these externalities are the health risks connected to frequent use and [the] quantity consumed. Nicotine is the addictive substance in the products but not the harmful ingredient. In other words, the proposal does not target the harmful behavior directly.”
Taxing based on nicotine content would favor low-nicotine liquids and could encourage increased consumption in the quantity of liquid, according to Boesen. “For example, a vapor pod that has a nicotine content of 3 percent and contains 1 mL of liquid would be taxed at $0.83 whereas a vapor pod that has a nicotine content of 5 percent and also contains 1 mL of liquid would be taxed at $1.39 even if there is no difference, or even a negative differential, in broader health effects of the two pods,” he states, adding that the effects of the tax are most substantial for nicotine pouches, such that the category is unlikely to survive.
Other estimates show that a 60 mL bottle of e-liquid with 12 mg of nicotine e-liquid would be taxed at $20.02. A four-pack of 8 mL pods with 5 percent nicotine salt pods would be taxed at $4.45 and a 15-pouch can of 8 mg nicotine pouches would be taxed at $3.34 (alongside state and local taxes, the cost of a single can could grow to $20 in some states).
Bryan Haynes, a partner with the law firm Troutman Pepper who specializes in tobacco and vapor regulations, said that, at a minimum, the proposed nicotine tax is “a hastily written addition” that will “have a negative impact on tobacco harm reduction efforts and public health.” He said that it’s the first time the tobacco industry has seen an excise tax placed on an ingredient instead of a finished good. “This is an unprecedented type of tax that will ultimately drive former smokers back to combustible products,” said Haynes, adding that taxing an ingredient could also cause unforeseen issues for manufacturers, such as moving material between factories.
Bryan Haynes / Credit: Troutman Pepper
“If a company is producing nicotine or even synthetic nicotine, moving product from one factory to another could trigger the need for an Alcohol and Tobacco Tax and Trade Bureau (TTB) license, and when product is removed, so to speak, from their factory, they would be responsible for remitting the taxes,” explained Haynes. “There may be a way, for example, if the company removed the nicotine from their factory and transported it in-bond to another TTB factory that you could make that work. But it’s just not clear. There is the potential for a lot of unforeseen issues to arise the way the tax is currently being proposed.”
States often tax nicotine products by its cost. Boesen says the tax on the product will pyramid since the federal tax would be levied at the manufacturer level and the state tax is levied at the distribution level. “In effect, the state tax base includes the federal tax and becomes a tax on a tax. This means that even if the taxes on tobacco and other nicotine products are approximately equal at the federal level, by the time it reaches the consumer, the nicotine product will carry a higher tax (and often a higher price),” he states. “This is highly problematic when considering that cigarettes are much more harmful than nicotine products. That makes the federal tax proposal look like a harm-maximizing strategy.”
Credit: Tax Foundation
The bill also subjects synthetic nicotine products to the nicotine tax. Many in the industry have expressed concern that this provision could allow the U.S. Food and Drug Administration to assert authority over the substance. Synthetic nicotine is covered not only in the proposed tax bill but also in the Prevent All Cigarette Trafficking (PACT) Act, which bans the U.S. Postal Service from mailing any vaping products.
Azim Chowdhury, a partner at the law firm Keller and Heckman who specializes in vapor, nicotine and tobacco product regulation, said that’s just not possible and Haynes agrees. “The definition of a tobacco product in the Tobacco Control Act (TCA) is clear. It’s just not ambiguous; a product must be made or derived from tobacco, or a component or part of a tobacco product, to be a tobacco product,” said Chowdhury.
Azim Chowdhury
“Congress would have to change the Tobacco Control Act’s definition of a tobacco product in order to give FDA’s Center for Tobacco Products the authority to regulate synthetic nicotine products as tobacco products. That won’t happen overnight. I also see a scenario where synthetic nicotine could be regulated as a drug and that would be a whole different and more onerous regulatory regime.”
The FDA could, however, cite the inclusion of synthetic products in the PACT Act and the latest nicotine tax proposal in its lobbying efforts to change the TCA’s definition of tobacco, said Haynes. “I could see the FDA telling Congress, ‘You just amended the Internal Revenue Code to make these products subject to federal excise taxes just like tobacco-derived nicotine, so it’s not a big stretch to amend the Tobacco Control Act’ in the same way,” he explains. “That’s how I would do it. It’s not really a legal argument, but it could be a decent lobbying argument.”
It isn’t just vapers, business owners and attorneys that find fault with the proposed nicotine tax; researchers suggest the tax could also harm public health. Michael Pesko, an associate professor in the Department of Economics at Georgia State University, used a $1.4 million dollar grant from the National Institutes of Health (NIH) to conduct e-cigarette policy evaluation research, including the evaluation of e-cigarette taxes (Pesko receives no funding from the tobacco industry or related groups). Pesko found that e-cigarettes and other nicotine vaping products function as what economists call “substitutes” for conventional cigarettes.
“In practical terms, if e-cigarettes and cigarettes are substitutes, then raising the price of one on average leads people to increase use of the other. Given extensive peer-reviewed evidence indicating that these products are substitutes, an unintended but inevitable effect of increasing taxes on e-cigarettes is to increase cigarette use,” Pesko said. “Given that cigarettes are believed to be substantially more harmful than e-cigarettes, this effect on [combustible] cigarette use is concerning …. A wide array of research suggests that this boost in cigarette use as a result of large e-cigarette tax increases would significantly increase overall tobacco-related death and disease.”
Michael Pesko / Credit: GSU
These findings prompted Pesko to send a letter to Congress concerning the proposed vape tax. In the letter, he states that his research team’s economic evaluations of existing state and county e-cigarettes taxes found that increasing e-cigarette taxes to parity with the combustible cigarette tax rate would “sizably increase cigarette use across teens, adults and pregnant women compared to taxing tobacco products differentially in proportion to their health risk.”
Pesko said researchers found several concerning consequences of large e-cigarette tax increases:
Simulating the current bill’s e-cigarette tax on teen tobacco use indicates that this policy would reduce teen e-cigarette use by 2.7 percentage points but that two in three teens who do not use e-cigarettes due to the tax would smoke cigarettes instead. This would result in approximately a half million extra teenage smokers overall. This finding that teens substitute to cigarettes in response to e-cigarette taxes has also been documented using National Youth Tobacco Survey data.
The tax would raise the number of daily adult cigarette smokers by 2.5 million nationally and reduce adult e-cigarette users by a similar number.
For every e-cigarette pod eliminated by an e-cigarette tax, more than 5.5 extra packs of cigarettes are sold instead.
For every three pregnant women that do not use e-cigarettes due to an e-cigarette tax, one smokes cigarettes instead (study).
Pesko told Vapor Voice he was surprised to find that increased e-cigarette tax consistently resulted in substitution across various data sources. “And the magnitudes are fairly sizable,” he noted. “This is an unusual level of accordance for academic research.” Pesko believes that any tax on nicotine products should be based on quantity.
Boesen agreed. He stated that for vapor products, the “obvious choice” is taxing the liquid by volume (per mL), and for nicotine pouches, a tax by weight or per pouch is a straightforward solution. “It is the administratively simplest and most straightforward way for the federal government to tax these goods as it does not require valuation and as such does not require expensive administration,” he stated. “The nicotine tax proposal in the Build Back Better Act neglects sound excise tax policy design and by doing so risks harming public health. Lawmakers should reconsider this approach to nicotine taxation.”
Chowdhury said that the industry must do more and that interested stakeholders and consumers should reach out and push back on the nicotine tax because it will be devastating to the vapor industry. “It seems like the general industry feels like [this nicotine tax] won’t get through somehow, that some people will prevent it from being in the final bill, but I think it’s a huge risk,” said Chowdhury. “Without serious pushback, it could end up there; it could very well end up becoming law.”
Haynes said that if the nicotine tax bill ever makes it to Biden’s desk, “he’s going to sign it.”
U.S. Representative Raja Krishnamoorthi, chair of the subcommittee on economic and consumer policy, has sent letters to two companies that manufacture or sell synthetic nicotine products, requesting information about the companies and their sale of these products.
One letter was addressed to Next Generation Labs, the self-declared market leader in the production and sale of synthetic nicotine. The company claims its unregulated synthetic nicotine is used in more than 60 products and projects its sales to increase by 1,800 percent this year.
“In response, some e-cigarette and e-liquid manufacturers, banned from legally selling their products, reportedly plan to switch to synthetic nicotine in an effort to avoid FDA regulation,” Krishnamoorthi wrote in his letter to Next Generation Labs.
“Next Generation Labs appears to support this approach, with its co-founder, Ron Tully, offering the following thoughts on the FDA laws and regulations governing nicotine: ‘If the statute has been ill-conceived, and the regulation has been ill-drafted, it is not the responsibility of the industry to conform to some kind of idea that you can’t innovate in those spaces where the legislation doesn’t occur.’”
Krishnamoorthi also sent a letter to Puff Bar, whose products have replaced Juul as the vape of choice for many young people after Juul Labs discontinued certain flavored products. In 2020, the Food and Drug Administration ordered Puff Bar to pull its products from the market. Earlier this year, the company introduced new versions of its products using synthetic nicotine.
In a recent profile by The Wall Street Journal, Puff Bar co-CEO Patrick Beltran described the Puff Bar ingredient change as “a forced innovation,” saying that the FDA gave the company no choice. Because the Tobacco Control Act specifically gives the FDA authority to regulate nicotine “made or derived from tobacco,” most people believe the agency’s Center for Tobacco Products cannot regulate products that use synthetic nicotine—at least not without serious legal challenges, according to Vaping360.
“You have apparently made the vile decision to continue enriching yourselves by poisoning children,” Krishnamoorthi wrote in his letter to Puff Bar. “Puff Bar’s meteoric rise in popularity among kids resulted in $156 million in sales in 2020 alone. Puff Bar should not be allowed to continue harming children due to FDA’s failure to regulate synthetic nicotine, and I intend to put an end to your predatory practices.”
In his letter to Next Generation Labs, Krishnamoorthi requested information regarding the company’s sales and new business. In his letter to Puff Bar, Krishnamoorthi requested information regarding the company’s ownership and operations as well as support for the company’s assertion that it is using synthetic nicotine, and requested the company’s co-chief executive officers appear for transcribed interviews.
Greg Conley, the president of the American Vaping Association, said Krishnamoorthi lacked evidence that the targets of his investigation have broken any laws. “As per the usual, he is playing politics, and we are hopeful the demands specified in his letter will be resisted,” Conley told Filter.
“With youth vaping numbers and the associated moral panic continuing to decline,” he continued, “it remains to be seen whether Representative Krishnamoorthi’s primary goal—getting media attention focused on Representative Krishnamoorthi—will actually be met with this campaign.”
In the wake of marketing denial orders, many U.S. e-liquid manufacturers are turning to synthetic nicotine.
By Timothy S. Donahue
In 2015, Mitch Zeller, the director of the U.S. Food and Drug Administration’s Center for Tobacco Products (CTP), was asked what the FDA’s position was on synthetic nicotine. “I’ll let you figure that one out for yourselves,” he said, hinting that the agency would regulate it as a drug. Today, vaping products, especially disposable devices, using tobacco-free nicotine (TFN) are one of the fastest-growing segments on the market.
After the FDA began issuing marketing denial orders (MDOs) to companies whose premarket tobacco product applications (PMTAs) failed to satisfy the agency’s concern about youth use, many rejected applicants hinted that they would start using synthetic nicotine—nicotine made in a lab and not derived from tobacco—in their flavored e-liquids.
Vapor Salon, for example, announced on Facebook that it would be switching to synthetic nicotine less than 24 hours after the FDA ordered the company to remove its products from the market.
“The main purpose of this is to be outside of the FDA’s regulations with their hefty PMTA requirement, which takes full effect on Sept. 9, 2021, with needing an approved PMTA or your product can no longer be sold,” the company wrote.
In July 2020, Puff Bar announced that it would cease all online sales and distribution in the U.S. until further notice after receiving a warning letter from the FDA. However, the brand resumed sales on its website in February of this year with an altered product. To get around the ban on its products, Puff Bar began using tobacco-free nicotine. As of this writing, Puff Bar continues to hawk its products both on its website and in convenience stores around the U.S.
Meanwhile, the popular online vaping retail website Element Vape.com has at least 11 brands offering several synthetic nicotine e-liquids in different flavors, including fruits, cereals and candies. Pioneer e-liquid manufacturer Five Pawns reformulated its vape juice using synthetic nicotine even before the Sept. 9, 2020, PMTA submission deadline.
“Synthetic nicotine products still must abide by nationwide age restrictions, but the Center for Tobacco Products lacks the ability to regulate them as ‘tobacco products,’” said Greg Conley, president of the American Vaping Association. “Unless and until the FDA authorizes a sufficient number of flavored products to keep current ex-smokers off of cigarettes, we will support efforts by small businesses to keep offering their products to adult customers.”
Tony Abboud, executive director of the Vapor Technology Association, said that synthetic nicotine has been available and on the market since as early as 2014, and while the FDA and U.S. Congress could have elected to regulate synthetic nicotine at any time, they have chosen not to confront the issue.
“If it wasn’t for the innovation of the vapor industry, cigarette companies would not today be saying, ‘We want to get rid of combustibles.’ Synthetic nicotine is simply the next level of innovation, and it’s not surprising the government is behind it. The [U.S.] government is always behind companies in any industry that is technological and that innovates,” explains Abboud. “There’s no surprise here. There’s no loophole here. There’s no evasion here. The marketplace is what the marketplace is. It’s up to the government to figure out if and how it wants to catch up.”
Credit: Myvisuals
Anti-tobacco groups, by contrast, vowed to halt the spread of synthetic nicotine. In a recent letter to the FDA, the Campaign for Tobacco-Free Kids (CTFK), the American Academy of Pediatrics and the American Lung Association, among other organizations, argued that e-cigarette manufacturers are using “a loophole” to avoid government regulations.
“As FDA denies marketing applications for e-cigarettes, manufacturers are exploring using synthetic nicotine in order to continue marketing their products while avoiding FDA regulation,” the letter states. “This development makes it even more imperative that FDA take immediate action against illegal, synthetic nicotine products.”
Matthew Myers, president of CTFK, said synthetic nicotine is not a safer product, and his organization has sent at least three letters since 2018 to the FDA concerning synthetic nicotine products, none of which has received a response from the regulatory agency. “It is totally designed to circumvent government regulation,” he said. “The companies that have used nicotine derived from tobacco to [now] nicotine made in a laboratory are the companies whose products have been denied because of their appeal to youth and their lack of evidence that they actually help smokers quit.”
Conley said that there is a reason the CTFK’s and other letters have gone unanswered through two different presidential administrations. “Tobacco-free nicotine was invented to eliminate trace levels of impurities that are present in traditional nicotine sources, not to evade regulation. Rather than expanding the futile war on drugs to nicotine, we believe all nicotine products should be regulated as consumer products and sold only to adult consumers 21 years and over.”
Defining tobacco products
Whether the FDA will allow products with synthetic nicotine to stay on the market remains to be seen. Despite its growing popularity, the category current operates in a regulatory void. Because the product is not derived from tobacco, it does not necessarily fall under the 2009 Family Smoking Prevention and Tobacco Control Act or meet the requirements of the Federal Food, Drug and Cosmetic Act’s definition of a tobacco product.
When synthetic nicotine first appeared on the market in 2016, the product was marketed as a way to circumvent the FDA’s proposed deeming rule for next-generation tobacco products by at least one company. The FDA’s definition of “tobacco product” includes any product made or derived from tobacco [that is intended for human consumption], including any component, part or accessory of a tobacco product. E-liquids that do not contain nicotine or other substances made or derived from tobacco may still be components or parts and, therefore, subject to the FDA’s tobacco control authorities, according to the agency.
“However, it’s possible that a disposable, closed system device that contains an e-liquid with truly zero nicotine (or synthetic nicotine) would not be regulated by the FDA as a tobacco product if it is not intended or reasonably be expected to be used in such a fashion,” the FDA states on its website. “[The] FDA intends to make these determinations on a case-by-case basis, based on a totality of the circumstances.”
In late 2016, Next Generation Labs (NGL), the maker of proprietary TFN Nicotine—nontobacco derived synthetic nicotine liquid and crystals—noted court statements made by the FDA in the NicoPure Labs LLC v. U.S. Food & Drug Administration that seemed to confirm that products not made or derived from tobacco fall outside of the FDA’s deeming rule.
Credit: NDABCREATIVITY
TFN claimed that in a response brief to the court dated Nov. 1, 2016, the FDA had stated that not all nicotine-free e-liquids (NFLs) were subject to the deeming rule. “Assuming an NFL is not made or derived from tobacco, it is subject to the rule only if it meets the definition of a ‘component or part’—that is, if it is ‘intended or reasonably expected’ either … (1) to alter or affect [a] tobacco product’s performance, composition, constituents or characteristics; or (2) to be used with or for the human consumption of a tobacco product; and is not an accessory,” the FDA was quoted as having said.
Experts have also said that the FDA could potentially assert jurisdiction over synthetic nicotine as a tobacco product and argue that, when the legislation was written, nobody had the foresight to think about synthetic nicotine. Eric Lindblom, a senior scholar at Georgetown’s O’Neill Institute for National and Global Health Law and a former director of the FDA’s Center for Tobacco Products Office of Policy, said that, in response to such moves by vapor companies, the FDA could either assert jurisdiction over synthetic nicotine as a tobacco product or push for synthetic nicotine to be regulated like any other drug.
Congress could eventually pass a nationwide ban on synthetic nicotine. A more likely scenario, however, according to industry insiders, is that individual states ban the sale of synthetic nicotine products. On May 17 of this year, the governor of Alabama signed into law Act No. 2021–453, which was backed by Altria, with that purpose in mind.
The legislation, which went into effect Sept. 1, states that “no e-liquid, e-liquid in combination with an electronic nicotine-delivery system, or alternative nicotine product that, in the case of any such product, contains synthetic nicotine or nicotine derived from a source other than tobacco may be sold or otherwise distributed” in Alabama if products have not been approved by the “FDA for sale as a drug, device or combination product.”
Abboud says vapor companies may not want to face the drug regulatory pathway. “Drug protocols are absurd, and if companies cannot even survive this PMTA process, then how would they ever possibly survive the other one?” he questioned. “Are you going to blame a company that spent millions of dollars trying to comply with [the] FDA’s opaque regulatory process, find that the FDA changed the rules at the last moment after the fact, and then and you’re going to criticize that company for doing something that’s currently lawful?”
For the time being, synthetic nicotine e-liquids will likely keep flavored e-liquids on the market despite the FDA’s efforts to remove them. However, Conley warned manufacturers against publicly advertising or celebrating their decision to switch to synthetic nicotine.
“A note to manufacturers planning to use TFN—don’t make public pronouncements about what you’re planning to do over the next month. Just do it,” he tweeted. “[The] FDA may have no respect for you, but there’s no need to blast them publicly. Plenty of harm reduction advocates can handle that.”
Sidebar
What is synthetic nicotine?
A major argument for synthetic nicotine is that it is safer than tobacco-sourced nicotine. The synthetic nicotine has no tobacco-specific nitrosamines (TSNAs), the harmful, cancer-causing chemicals found in combustible tobacco products. TSNAs are formed when tobacco leaves are grown, cured, aged and processed.
Research has shown that all nicotine is highly addictive, and regardless of the form, should be consumed with caution. However, the chemical does not directly cause cancer, which instead results from inhaling the byproducts of combustion.
Whether manufactured naturally or artificially, the nicotine molecule has the same chemical structure, C10H14N2, meaning that it comprises 10 carbon atoms, 14 hydrogen atoms and two nitrogen atoms. What makes it special, independent of its origin, is that it is a “chiral” molecule: It has two stereoisomers that are mirror images of each other.
The most prevalent form is (S)-nicotine, the physiologically active variant. Its mirror isomer, (R) nicotine, also occurs in plant-derived nicotine in small amounts but is considered physiologically ineffective. Synthetic nicotine is made with a combination of niacin, ethanol, sulfuric acid and a few other chemicals.
Traditionally, a problem for the producers of synthetic nicotine has been that the production process is both complicated and expensive. As a chiral molecule, nicotine is far easier to produce as a synthetic nicotine with equal amounts of both (R) isomers and (S) isomers compared to a nearly pure (S)-nicotine.
Naturally derived nicotine and synthetic nicotine are identical on a molecular level. The differences are the individual or potential impurities. Nicotine derived from tobacco can contain potentially harmful impurities. Purification can be difficult and costly because the impurities appear structurally very similar to the nicotine molecule itself. But synthetic nicotine is virtually free of any impurities from the beginning, and none of the impurities are carcinogenic.
Currently, two types of synthetic nicotine are on the market: an (S) only synthetic nicotine and a 50 percent (S) and 50 percent (R) synthetic nicotine. In the early years of the vaping industry, the cost of the process to produce synthetic nicotine was prohibitively expensive when compared to tobacco-derived nicotine extraction methods.
Today, that’s no longer the case. Synthetic nicotine can be purchased for nearly the same price as tobacco-derived nicotine and in some instances for even less. This is due to advancements in the commercially scaled bulk production of synthetic nicotine for use in the tobacco, vaping, pharmaceutical and scientific research industries.
In November 2020, eLiquiTech, a wholly owned subsidiary of Tobacco Technology Inc. (TTI), released its recently patented SyNic synthetic (S)-nicotine. Because SyNic has greater than 99.7 percent (S), an e-liquid needs only half the amount of SyNic to create the same effect for users as current 50/50 synthetic nicotine offerings on the market.
A new version of synthetic nicotine eliminates the cancer-causing impurities in leaf-derived nicotine.
By Timothy S. Donahue
No tobacco-specific nitrosamines (TSNAs). A new synthetic nicotine coming to market has none of the possible cancer-causing impurities that are found in traditional leaf-derived nicotine. In November, eLiquiTech, a wholly owned subsidiary of Tobacco Technology Inc. (TTI), will release its newly patented SyNic synthetic (S)-nicotine. The announcement has the potential to revolutionize next-generation tobacco products, such as electronic nicotine-delivery systems (ENDS), oral nicotine-delivery systems and heat-not-burn (HnB) products.
SyNic USP/EP, SyNic nicotine bitartrate and SyNic polacrilex resin are manufactured in U.S. Food and Drug Administration (FDA)-registered facilities using current good manufacturing practices (cGMP). These products have confirmed purity levels of more than 99.9 percent, (S) levels of more than 99.7 percent and are free of TSNAs and carcinogens, according to eLiquiTech CEO George Cassels-Smith. “What is the value of noncarcinogenic nicotine base to any tobacco product manufacturer?” he asks. “What is a noncarcinogenic tobacco product portfolio worth to the tobacco consuming public? But high-purity, pedigreed natural nicotine will continue to have a large seat at the table nevertheless.”
SyNic got its start seven years ago when e-LiquiTech began working with U.K.-based Zanoprima Lifesciences with the goal of developing a unique and patented portfolio of synthetic nicotine products. The group wanted those products to cover the entire nicotine value chain with a focus on next-generation tobacco products.
E-LiquiTech, through TTI, is committed to Zanoprima to serve as SyNic’s global distributor and the manufacturer of record for synthetic nicotine bitartrate and synthetic nicotine polacrilex resin as well as proprietary SyNic e-liquid formulas. “Ensuring that synthetic nicotine is readily available is the right thing to do for our industry—and now also is the right time to do it,” said Cassels-Smith.
Zanoprima holds the patent and eLiquiTech maintains the exclusive rights for global distribution to the tobacco and ENDS industries, but the product won’t be available to everyone, according to Cassels-Smith.
“This will not be available directly to the consumer market. We will soon post a set of standards online that manufacturers must meet to purchase our synthetic nicotine,” he says. “This product is not intended to circumvent the rules governing the tobacco and ENDS industries nor evade regulation. We will not sell it to companies that have that intent.”
SyNic will refrain from entering the highly contentious U.S. vapor market until its potential customers can show they have an accepted for review premarket tobacco product application (PMTA) submitted to the FDA’s Center for Tobacco Products. “Our objective is to work with the FDA, not around it,” says Cassels-Smith.
When synthetic nicotine first appeared on the market in 2016, the product was marketed as being a potential way to circumvent the FDA’s proposed deeming rule for next-generation tobacco products. The FDA’s definition of “tobacco product” includes any product made or derived from tobacco, including any component, part or accessory of a tobacco product. E-liquids that do not contain nicotine or other substances made or derived from tobacco may still be components or parts and, therefore, subject to the FDA’s tobacco control authorities.
Cassels-Smith says that Zanoprima has filed multiple global patents for its technologies and has also begun the process of filing drug master files with the FDA for SyNic nicotine, SyNic bitartrate and SyNic polacrilex resin. “Coupled with e-LiquiTech’s exclusive distribution, competitive pricing and carrying the e-LiquiTech guarantee, these products will be available only to responsible partners operating within the regulatory guidelines of the global tobacco industry,” said Cassels- Smith. “The synthetic nicotine is cleaner than naturally derived nicotine because it has no TSNAs. These nitrosamines have the potential to turn into carcinogens. SyNic will not have any nitrosamines and is 100 percent carcinogenic-free by design.”
E-LiquiTech’s synthetic nicotine resembles its naturally derived cousin. Like a naturally derived liquid nicotine, e-LiquiTech’s new synthetic nicotine is more than 99 percent pure (S)-nicotine. This purity of (S)-nicotine has a better effect on the body, and SyNic carries fewer impurities than naturally derived nicotine that comes from leaf tobacco.
“Nicotine exists in nature in two forms, (R) isomer and (S) isomer. One is basically a mirror image of the other, but the nicotine desired by vapers and smokers alike is the (S)-nicotine alone. Naturally grown tobacco contains over 99 percent (S)-nicotine, and the rest is very little (R),” says Cassels-Smith. “The body considers (R)-nicotine a filler with substantially less physiological effect. It’s considered a waste product, and [the body] does not absorb it. SyNic is slightly superior to the (S)-nicotine content found in a naturally derived nicotine because of its higher levels of (S)-nicotine with qualified and quantified impurities.”
Traditionally, a problem for the producers of synthetic nicotine has been that the entire production process is both complicated and expensive. As a chiral molecule, nicotine is far easier to produce as a synthetic nicotine with equal amounts of both (R) isomers and (S) isomers compared to a nearly pure (S)-nicotine. “(R)-[nicotine]/(S)-nicotine requires additional refining processes, which [are] time consuming and expensive to convert it to a true synthetic (S)-nicotine,” explains Cassels-Smith. “Also, because (R)-nicotine has substantially [fewer] physiological properties, it takes twice as much 50/50 synthetic nicotine in an e-liquid to achieve parity with SyNic. Because SyNic has greater than 99.7 percent (S), it only needs half the amount of SyNic to create the same effect for users as current synthetic nicotine offerings on the market.”
Naturally derived nicotine and synthetic nicotine are identical on a molecular level. The differences are the individual or potential impurities. Nicotine derived from tobacco can contain potentially harmful impurities if it is not purified sufficiently. That can be very difficult and costly because the impurities appear structurally very similar to the nicotine molecule itself. But synthetic nicotine is virtually free of any impurities from the beginning and none are carcinogenic.
SyNic, by design, carries no heavy metals and contains no residual pesticides. Additionally, unlike tobacco-derived nicotine that uses harsh acids and chemical solvents in its process, SyNic, is produced using a “green chemistry” method. “Its manufacturing is environmentally friendly, and any solvent used is recovered completely before being recycled for future use,” explains Cassels-Smith. “The SyNic process makes the tobacco-derived nicotine process appear dirty by comparison.”
SyNic will help manufacturers meet the FDA’s goals by consistently creating high-quality nicotine to deliver to the consumer without the possibility of potential carcinogens, according to Cassels-Smith. “We will allow vaping products to have the cleanest delivery and the best delivery,” he says. “That isn’t going to happen with the old technology. SyNic is a new frontier and a perfect tool for this industry to reinvent itself. It is constantly developing and reinventing itself. This product can help make all tobacco products better.”
Because of its unique patented process, Cassels-Smith says SyNic can achieve price parity with tobacco-derived nicotine. He adds, however, that this synthetic product will always be marketed at a higher cost than naturally derived nicotine to ensure there will always remain a naturally derived pedigreed nicotine market where the tobacco farmer can sell his crops.
“We have a lot of respect for the natural product and foresee our synthetic nicotine being a compliment to those that wish to remain all natural. There is enough room in the market for everybody. SyNic, with its known qualities, will have a place at the table alongside pedigreed natural tobacco-derived nicotine. But there are issues with nicotine sourced from scrap and dust as traceability is impossible and controlling pesticide and heavy metal contamination is problematic,” Cassels-Smith explains. “I foresee a future requiring the tracing of [natural] nicotine’s origin from the seed and soil through the extraction process and also quantifying impurities, all in cGMP facilities.”
SyNic’s potential is unlimited in the number of products in which it could be used. Cassels-Smith says that he cannot think of a single nicotine product that could not benefit from SyNic. In a heat-not-burn product, for example, during the rod-making process, SyNic could augment the prevalent nicotine source—or even be the sole source.
“Zanoprima has adapted their SyNic technology and patented an extremely unique and stable nicotine salt that does not use organic acids and retains pH stability,” he says. “SyNic also has the potential for being associated with superior purity and shelf life stability in all tobacco products of the future. SyNic will raise the bar, and we are just scratching the surface. It is a great tool that emerges at the perfect time for every tobacco product designer. The portfolio of potential products that can utilize SyNic is infinite.”
