Tag: synthetic nicotine

Synthetic Nicotine Applications Due Soon

Photo: Brian Jackson

Premarket tobacco product applications (PMTAs) for nontobacco nicotine products are due May 14, the U.S. Food and Drug Administration announced on its website.
Legislation enacted on March 15 empowers the FDA to regulate tobacco products containing nicotine from any source.
Effective April 14, not new nontobacco nicotine products may enter the market, as portions of the new law take effect.
The May 14 deadline applies to applicants using the FDA’s electronic submission process. Hardcopy applications must be received by FDA no later than 4 p.m. EDT on May 13.

April 17, 2022
What’s Next for Synthetic Nicotine

Nveed Chaudhary (Photo: Broughton)

Broughton’s Nveed Chaudhary explains how the FDA’s new powers to regulate synthetic nicotine will impact the industry.
Contributed
In mid-March, the U.S. Congress moved to close the loophole on the use of synthetic nicotine in electronic nicotine-delivery systems (ENDS) in the United States, bringing it into line with tobacco-derived nicotine products. In this article, Nveed Chaudhary, chief scientific and regulatory officer at Broughton, an independent life sciences contract research organization, explains what this regulatory change means for the next-generation nicotine-delivery industry in the U.S. market.
What has happened in the U.S., and when will the changes take effect?
The U.S. Congress has extended the Food and Drug Administration’s authority over tobacco products to include synthetic nicotine in products such as vapes, heated products and oral nicotine pouches. This will bring these products into line with tobacco-derived nicotine next-generation nicotine-delivery products. The new regulation was passed as part of a U.S. lawmaker’s long-term spending bill signed into law by President Joe Biden on March 15. It takes effect immediately, and manufacturers of synthetic nicotine vapes and oral nicotine pouches have 60 days from March 15 to submit a premarket tobacco product application (PMTA) dossier to keep their products on the U.S. market.
Was the industry expecting this regulatory change?
The ENDS industry had been watching U.S. regulators with interest around this issue for some time and expected a change to come at some point. The speed with which it has been passed took the industry by surprise. It was included in a long-term spending bill that contained hot-button issues like funding for Ukraine, Covid support and regular government running expenses, enabling it to be passed without debate or amendment. That being said, U.S. lawmakers would possibly argue that ENDS manufacturers have had almost two years since the PMTA regulations were published to start collecting data on their products.
What is synthetic nicotine?
Synthetic nicotine, also called tobacco-free nicotine, is a synthesized form of nicotine produced via a chemical process instead of extraction from tobacco. Recent improvements in manufacturing processes have enabled producers to mimic the enantiomeric ratio of tobacco-derived nicotine. Synthetic nicotine is not new, with it first synthesized in 1904, but the production on a mass scale is relatively recent. Most e-cigarette manufacturers do not use synthetic nicotine because it tends to be more expensive than tobacco-derived nicotine. There is also far less infrastructure to create synthesized nicotine from scratch than the well-established facilities for harvesting nicotine from tobacco plant materials.
Why have U.S. regulators chosen to close the synthetic nicotine loophole now?
Previously, the FDA defined “any product made or derived from tobacco and intended for human consumption, including any component, part or accessory of a tobacco product” as a tobacco product. Under this description, e-cigarettes containing tobacco-derived nicotine e-liquids were subject to the PMTA regulatory framework while those containing tobacco-free nicotine were not. However, some U.S. lawmakers and nonprofit organization lobbyists have long discussed closing this loophole because it enabled manufacturers to introduce tobacco-free nicotine products to the market without regulatory oversight. Following the publication of the recent National Youth Tobacco Survey (NYTS) data, there is particular concern about the youth usage of synthetic nicotine disposable vape products, e-liquid flavors and marketing, which the FDA has had no authority to challenge. As we saw with tobacco-derived nicotine ENDS products, there is rightly intense scrutiny around products that are found to be attractive to youth, and this has become an area of significant political focus in the U.S. The fact that it appeared that some manufacturers were using the loophole to get around regulatory control is likely to have increased the speed with which lawmakers felt they had to act.
What can synthetic nicotine manufacturers do now?
If a product is already on the market in the U.S., manufacturers have 60 days to file a PMTA. If a manufacturer was in the process of commercializing a new synthetic nicotine product in the U.S., they have a 30-day window to launch the product and then 30 days to file their PMTA. This 60-day deadline for data submission will be very challenging for most tobacco-free nicotine ENDS manufacturers to meet but may not be impossible. At Broughton, we are currently in discussions with several clients about the regulation and what they will need to do to submit a PMTA within the timeframe allowed.
Is it possible to prepare a PMTA dossier within this short timeframe?
We believe it is, but manufacturers need to act immediately, and there are no guarantees of success. Especially as many of the manufacturers who submitted PMTA dossiers for their tobacco-derived nicotine ENDS products still don’t know if they have passed the FDA requirements to be awarded a marketing authorization. The first question is how much data a synthetic nicotine ENDS manufacturer already has available about their product and then to build analytical studies to fill gaps to file an adequate submission in the timeframe available. There is always a possibility that the FDA wants to close this NGP (next-generation product) market area completely, but that seems unlikely. It’s more likely they want to ensure that tobacco-free nicotine products are regulated in the same way tobacco-derived nicotine products are. Responsible manufacturers should welcome this opportunity to prove their product’s quality, safety and efficacy in relation to tobacco harm reduction objectives.
What will be the long-term impact of FDA authority over synthetic nicotine products?
The industry has been debating how governments will respond to regulating synthetic nicotine products for some time. It isn’t made from tobacco, but how else could lawmakers regulate it? It’s a classic dilemma for regulators; needing to respond to a technical innovation quickly, having less information than the industry it’s regulating, and then relying on existing regulation to act quickly and fill the gap. This has been the problem for the entire next-generation product category. We believe that all nicotine-containing products, regardless of tobacco-derived nicotine or synthetic-derived nicotine, should be treated in the same way. Regardless of where the nicotine comes from, the impact on population health needs to be measured in a consistent way. Synthetic nicotine is still not cost-effective to manufacture, and only a few companies currently produce synthetic nicotine due to patents around the manufacturing process. It’s estimated that synthetic nicotine is up to 13 times more expensive to manufacture than tobacco-derived nicotine. It will be interesting to see if ENDS manufacturers now abandon using synthetic nicotine because of the regulatory change or stick with it. A large part of this may be decided by how the FDA evaluates the PMTA submissions they receive and if there appears any difference in how synthetic nicotine and tobacco-derived nicotine PMTA applications are evaluated.
This article was contributed by Broughton, an independent life sciences contract research organization.

March 28, 2022
E-LiquiTech: Synthetic Nicotine in Stock

Photo: Tobacco Reporter archive

E-LiquiTech says it has large quantities of Zanoprima’s SyNic in stock to help companies introduce new products to the U.S. market ahead of the mid-April deadline imposed by a new law.
On March 15, 2022, President Joe Biden signed into law a spending bill that includes a provision to regulate products containing synthetic nicotine the same as products containing tobacco-derived nicotine. This means that companies selling products containing synthetic nicotine will be required to file a premarket tobacco product application in order to keep their product(s) on the market. The deadline for filing such applications is less than 60 days away.
According to E-LiquiTech, SyNic is the same chemical composition of (S)-nicotine as natural tobacco-derived nicotine but without any of the impurities. Specifically, SyNic achieves a purity profile of 99.9 percent and is devoid of tobacco-specific nitrosamines, heavy metals and other impurities that are present in tobacco-derived nicotine.
SyNic is manufactured through a patented process in a cGMP facility approved by the U.S. Food and Drug Administration and meets or exceeds the U.S. Pharmacopeia monograph, making SyNic a 1-to-1 replacement for tobacco-derived nicotine and enabling manufacturers to use it as a CAS number substitute, according to E-LiquiTech.
The company says all of the scientific data that is applicable to tobacco-derived nicotine is equally applicable to SyNic. The manufacturing process is replicable from batch to batch, and every batch of SyNic is fully trackable and traceable.
Earlier this month, Zanoprima filed a patent lawsuit against Hangsen International in the U.S. District Court for the Western District of Texas to enforce Zanoprima’s patented process for manufacturing (S)-nicotine, demonstrating its long-term commitment to the U.S. market.

March 23, 2022
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.

March 18, 2022
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.”

March 16, 2022
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.

March 11, 2022
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.

March 10, 2022
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.

March 8, 2022
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.”

March 4, 2022
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.

January 4, 2022