Tag: synthetic nicotine

Korea to Treat Synthetic Nicotine as Tobacco

Photo: Purilum

The government of South Korea aims to regulate synthetic nicotine as tobacco, reports the Yonhap News Agency.
The Ministry of Health and Welfare and the Ministry of Economy and Finance want to revise the Tobacco Business Act to include synthetic nicotine in the definition of tobacco.
Tobacco in South Korea is governed by the National Health Promotion Act, under the jurisdiction of the health ministry, and the Tobacco Business Act governed by the finance ministry.
The current rules define tobacco as a product “manufactured in a state suitable for smoking, sucking, inhaling steam, chewing or smelling, by using tobacco leaves as all or any part of the raw materials.”
That language fails to capture the e-cigarette liquids made with synthetic nicotine, which is created in a laboratory rather than from tobacco leaves. As a result, vapes are not subject to product requirements, such as health warning labels, age restrictions and tobacco taxes, in South Korea.
The push for new legislation follows an announcement by BAT that it is mulling the launch of a new synthetic nicotine product in the country. South Korea is reportedly the only nation where the tobacco giant is considering a synthetic nicotine product.
“We have decided to push for the revision of the Tobacco Business Act when the 22nd National Assembly opens,” an official at the health ministry was quoted as saying. “We will provide necessary materials to the finance ministry, and there is already an abundance of evidence proving that synthetic nicotine is tobacco.”
The consumption of e-cigarettes has been rising steadily in South Korea, reaching 16.9 percent of tobacco sales in 2023.

May 16, 2024
The Promise of Synthetic Nicotine

Photo: Oksana Fedorchuk

As consumer demand for healthier and more environmentally friendly alternatives to combustible cigarettes increases, we should expect greater focus on the benefits of this man-made alternative.

By Derek Yach

Tobacco-derived nicotine has been the sole source of nicotine used by pharmaceutical and tobacco companies until recently. The naming of the sector (tobacco sector), the naming of companies (British American Tobacco for example) and the framing of public health policies as tobacco control all show how pervasive and deeply embedded the word tobacco has become despite its scientific name being Nicotiana.
The dominance of tobacco plants started to wane when pharmaceutical companies developed nicotine-replacement therapies (NRTs) as cessation products. That highlighted the fact that while nicotine is addictive, it is not the source of death and disease caused by the products of combustion. The advent of a wide range of consumer-facing products that also use nicotine (especially e-cigarettes and nicotine pouches) to help smokers switch and/or quit has further increased the focus on nicotine.
Initially, there was no debate about the source of nicotine since it was assumed to come from the plant. In recent years, several companies have started using patented laboratory processes to develop nicotine from scratch. Many, like Zanoprima, use green chemistry to convert plant-based molecules into synthetic nicotine. Other companies, such as Contraf-Nicotex-Tobacco (CNT), begin with plant-based molecules used in cosmetics and derived from vitamin B.
Nicotine, like many molecules, exists in two orientations: S-nicotine and R-nicotine; however, nicotine that occurs naturally in the tobacco plant is entirely S-nicotine. Prior to the popularization of synthetic nicotine, this distinction had not been of great practical importance due to its naturally occurring form. Pharmaceutical-grade synthetic nicotine manufacturers such as CNT and Njoy therefore treat R-nicotine as a byproduct of the S-nicotine manufacturing process while Zanoprima’s patented process does not produce R-nicotine at all. Other manufacturers may use methods that may well not meet the high-quality standards of the pharmaceutical industry.

What Benefits Does It Bring to Consumers and the Environment?
Consumers increasingly demand information about the supply chain of end products. Leading food companies have led in being transparent about the source of all ingredients in their products with a shift toward those where labor conditions on the farm are known, addition of chemicals are reported, water and greenhouse gas use associated with products are made public and the traceability of food product ingredients is independently audited. Investors are more likely to invest in companies with sound records on these issues.
So it will be for all future nicotine products.
For many combustible users, the incentive to switch to a reduced-risk product usually starts with a desire to lower health risks. But for a considerable number, environmental issues are fast becoming reasons to switch, often independent of their health concerns. Again, this has its analogy in the food sector, where companies like Whole Foods have built their main value proposition on an environmental benefit, with health credentials being dubious.
The tobacco industry emits 84 million metric tons of carbon dioxide (CO2) a year, which is equivalent to 0.2 percent of global CO2 emissions, according to researchers at Imperial College London. Of the total, 20.87 million tons of CO2 come from cultivation, and 44.65 million tons of CO2 come from curing, together amounting to 78 percent of all tobacco industry emissions. Synthetic nicotine has the potential to virtually eliminate these.
Synthetic nicotine brings tangible benefits to consumers: A better sensorial experience, assurances about the absence of contaminants and a stamp of quality good enough for pharmaceutical companies, to name a few.
The recent World Health Organization report Tobacco: Poisoning Our Planet paints a vivid picture of the harms of tobacco farming, curing and processing for the environment. More recently, the Foundation for a Smoke-Free World provided a qualitative summary of the potential sources of environmental harm associated with reduced-risk products. Both the WHO and the foundation advocate for the reduction in global tobacco farming, outlining the harms caused by tobacco growth and cultivation on arable land, workers’ rights and malnutrition. It is likely that products created with synthetic nicotine can mitigate many concerns in the product lifecycle. And as companies selling clean nicotine push harder to ensure their products are recyclable and/or reusable, the overall negative environmental footprint will decline further.

Where Is It Likely to Grow Fastest?
Today, synthetic nicotine is used in next-generation nicotine products by emerging nicotine pouch companies like NIIN and by mainstream vape companies like Njoy. This trend is set to continue and will gain traction as e-cigarettes and nicotine pouch companies seek medical licensing using synthetic nicotine.
One example is SMOOD, an up-and-coming next-generation e-cigarette and NRT company based in New York City. SMOOD creates its products as a comprehensive approach to address both health and environmental issues simultaneously. Synthetic nicotine, recyclable hardware and design features to support smokers to quit may well be a signal of what is to come. “We always used nontobacco nicotine due to the absence of minor tobacco alkaloids and metals, both of which are inherent in agricultural production,” says Martin Steinbauer, chief engineer of SMOOD. “Together with repeatable pharmaceutical production processes, nontobacco nicotine improves the toxicological safety of our devices and eliminates carbon emissions, water use and deforestation from tobacco growing. Most importantly, it offers a clean break of nicotine from tobacco finally.”
Snus and heated-tobacco products are unlikely to shift away from tobacco in the medium term but are lowering the health risks of the tobacco they use through processing changes in the case of snus and by eliminating combustion in the case of heated-tobacco products. For decades to come, tobacco plants will be used in these products as well as in combustibles like cigarettes and cigars where a significant demand from consumers is likely to remain even as overall demand declines.
Most major tobacco companies already support farmers to diversify. It will be interesting to watch the dynamic within companies with large and growing reduced-risk portfolios who will continue to sell combustibles even as they shift to reduced-risk products to a greater extent in later numbers for several decades. Altria’s purchase of Njoy, Philip Morris International’s acquisition of Swedish Match and BAT’s dominance in the U.S. vape space all signal that these companies will take a twin track approach to nicotine sourcing.

Who Makes It and How Do They See the Future?
CNT has stated that synthetic nicotine is currently a niche product with enormous potential. “We see enormous demand there and the capacity for the synthesis of chemical is unlimited.”
Zanoprima, the only company to use myosmine as the starting material believe that in time synthetic nicotine will become the main source of nicotine in pharmaceutical products as well as in products likely to be sold as both medically approved cessation products, and as recreational products for ex-smokers to use.

Isn’t It Expensive To Use?
No—prices have been dropping recently and will continue to do so as demand increases.

Conclusion
Health and environmental consumer demand combined with benefits in terms of quality and safety, suggest that synthetic nicotine is set to meet its potential in the coming years.

A global health expert and anti-smoking advocate for more than 30 years, Derek Yach is the owner of Global Health Strategies. Previously, Yach was the director of the Foundation for a Smoke-Free World and a World Health Organization cabinet director and executive director for noncommunicable diseases and mental health. He was deeply involved with the development of the Framework Convention on Tobacco Control.

August 1, 2023
From Plantations to Nicotine ’Plants’

Photo: Taco Tuinstra

Synthetic nicotine could help promote global food security.
By Sudhanshu Patwardhan
The tobacco industry is undergoing rapid transformation. Companies are increasingly offering safer nicotine alternatives to current consumers of risky forms of tobacco. Is it time for them to reassess their supply chains to procure nicotine from nonagricultural sources and in the process free up land for growing crops that can feed the world’s 8 billion people? A study of the economics of tobacco cultivation and nicotine consumption may give us practical answers.
Millions of hectares of rich, fertile land are used for growing tobacco to meet the nicotine needs of over 1.1 billion tobacco users globally. Except for Swedish-style snus and tobacco used in novel heated-tobacco products, most of the tobacco grown eventually harms public health due to the toxicants arising out of its curing and manufacturing (e.g., tobacco-specific nitrosamines, added chemicals in smokeless tobacco products) and use (e.g., harmful smoke components). On May 31, the World Health Organization marks World No Tobacco Day (WNTD) with an interesting theme: “We need food, not tobacco.”
Last year, for the first time ever, two U.N. bodies—the WHO and the U.N. Environment Programme)—published a list of the environmental harms from tobacco-related farming, manufacturing, supply chain and consumption. Tobacco-related harms to the environment start from the seed and go well beyond the cigarette and bidi smoke. The WHO notes that globally, an additional 200,000 hectares of land is cleared annually for growing tobacco and curing tobacco leaves that are used in making smoked and smokeless tobacco products. Rich and diverse natural habitats, including pristine rainforests, are being lost to meet the global tobacco demand. It is estimated that 3.7 liters of water are used to make one cigarette. Worldwide, trillions of cigarettes are sold and burned annually. The environmental pollution is not limited to the emitted smoke and the ash but also the cigarette butt litter that refuses to decompose for years. In South Asian countries, spitting smokeless tobacco imposes an additional burden on health and leaves unsightly marks in buildings and roads. Even the pharmaceutical grade nicotine used in medically licensed nicotine-replacement products and e-liquids for vaping products is obtained predominantly from tobacco plants.

Any slogan that simply calls for more food instead of tobacco oversimplifies the economics of tobacco.

This year’s WNTD theme intends to put a spotlight on the arable land locked in tobacco plantations that could instead provide food security to the world’s 8 billion people. Indeed, hunger and lack of nutritious food kill millions of people worldwide every year. Feeding the ever-growing world population without denuding forest land remains a big challenge for reasons ranging from environment and climate change to biodiversity. Therefore, in a world with finite arable land, repurposing tobacco farms for growing food are an obvious target for policymakers, environmentalists and economists.
Sadly, the WNTD theme creates a false dichotomy, unnecessarily pitting tobacco farmers against a hungry world. Alas, one cannot simply switch tobacco farms and farmers to grow alternative food crops with a snap of a finger. Global demand for tobacco continues relatively unabated, thus keeping suppliers invested in a profitable crop. It is also important to remember that tobacco is an unusually hardy plant. Not all food crops can withstand conditions that the tobacco plant can endure. Unlike edible vegetables and fruits, the produce from tobacco plantations is a leaf that is included as a raw material for further processing into a product, thus not subjecting the farmers to the whims and shameful wastage due to strict size and shape requirements of western supermarket buyers. The tobacco leaf markets are utility focused and well supported through longstanding relationships among stakeholders across a sophisticated global supply chain and have lifted millions out of poverty. Any slogan that simply calls for more food instead of tobacco oversimplifies the economics of tobacco.
The health harms from risky forms of smoked and smokeless tobacco products such as cigarettes, cigars, bidis, hookah, gutkha, khaini, mishri, zarda, etc. are already well known. That knowledge has not made these products or their use obsolete—even today, over a billion people around the world consume these risky products, and more than half of them die prematurely as a result. Nicotine is addictive but is not the cause of tobacco-related cancers, cardiovascular disease and lung disease.

Many doctors harbor misperceptions about nicotine, wrongly believing that nicotine in the tobacco products causes cancer.

The invention of nicotine-replacement therapy (NRT) products over three decades ago, in the form of nicotine gums, skin patches, lozenges and mouth sprays, was crucial in realizing nicotine’s role as a medicine in helping quit tobacco and finding these products a place on the WHO’s model essential medicines list. NRT enables smokers and smokeless tobacco users to better manage their cravings and withdrawal symptoms. Still, quitting tobacco and preventing relapse remains a big challenge globally for a variety of interlinked reasons: (i) Pharmaceutical investment and innovation in improved tobacco cessation tools and products has been lacking in recent years, (ii) universal access to affordable and appealing nicotine-replacement products remains poor, and (iii) healthcare professionals around the world are not adequately trained on how to advise their patients to use nicotine-replacement products.
In fact, many of the doctors themselves harbor misperceptions about nicotine, wrongly believing that nicotine in the tobacco products causes cancer. This limits doctors’ ability to confidently support their patients’ tobacco de-addiction journey using nicotine-replacement principles. The obvious question then is: How do we ensure that current users of tobacco get all the help they can from their healthcare advisers and governments to make quitting tools accessible, affordable, appealing and available? If done at a global level, quitting success will further inspire confidence among consumers, healthcare practitioners and policymakers to accelerate the decline of the demand for tobacco.
The WHO Framework Convention on Tobacco Control (FCTC) is often elegantly simplified as a treaty for demand reduction, supply reduction and harm reduction strategies. The largest demand arises from the billion-plus cohort of current users of risky tobacco products—and that’s where affordable cessation support and safer nicotine alternatives offer the highest likelihood of practical harm reduction. So, for the agricultural transformation much needed to free up arable land, a global reduction in demand for tobacco will be a key economic driver over time for farmers to actively seek other viable alternatives. It would then be crucial to provide government support and subsidy over a phased reduction in tobacco farming.
The FCTC dedicates two entire articles in the original treaty text to alternative livelihoods for those in the supply chain and addressing environmental impact—Articles 17 and 18. Particularly in implementing those two articles, little progress has been made in the past 20 years since the treaty came into force. That is because even lesser success has been achieved on a ground-level implementation of the FCTC’s Article 14 that calls for tobacco dependence treatment provision at a national level.
In recent years, many advances in chemistry and chemical engineering have resulted in new processes and patents issued for synthesizing nicotine from nontobacco raw materials. If the correct isomer of nicotine—the S-isomer—can be manufactured at scale using these processes, that can be revolutionary and indeed game changing. Using such synthetically manufactured nicotine, nicotine-replacement products that are innovative, suitably regulated and where necessary medically licensed can thus be introduced globally for tobacco cessation at low cost and in product formats appealing to current adult smokers and smokeless tobacco users. Agricultural transformation and enhanced food security will naturally follow this purely on economics principles.

Sudhanshu Patwardhan is a British-Indian, U.K.-licensed medical doctor who is passionate about helping people quit risky forms of tobacco. For the past two decades, he has lived and worked in three continents, doing senior roles in research, strategy and policy in the pharmaceutical and tobacco industries.

In his early years in tobacco harm reduction, his team of clinical researchers and lab scientists set the foundations for the assessment of reduced-risk products, now accepted by regulators and the industry as the definitive approach for duty of care and regulatory compliance. At Nicoventures, a wholly owned subsidiary of British American Tobacco, he was instrumental in enabling the first e-cigarette company acquisition by a global tobacco business. In his policy role there, Patwardhan shaped the creation of a global key opinion leader network in consumer advocacy and public health champions. .

With the British Standards Institution, Patwardhan led the creation of the world’s first vaping products’ standards for safety and quality in 2015 and the BSI Online Age Checking specifications in collaboration with the Westminster-based Digital Policy Alliance in 2018. .

In 2018, he co-founded the Centre for Health Research and Education that now has a team of over 40 medical and public health experts globally working in cancer prevention. Patwardhan splits time between the U.K. and South Asia on tobacco harm reduction projects that address the needs of the most disadvantaged tobacco users.

July 1, 2023
FDA Completes 95 Percent of Synthetic Nicotine Applications

Photo: pixelrobot

As of Oct. 7, the U.S. Food and Drug Administration has issued refuse to accept (RTA) letters for more than 889,000 non-tobacco nicotine (NTN) products in premarket tobacco product applications (PMTAs) that do not meet the criteria for acceptance, the agency announced on its website.
The agency has accepted over 1,600 applications, with the vast majority being for e-cigarette or e-liquid products.
“While the application review is ongoing, FDA remains vigilant in overseeing the market and will continue to use our compliance and enforcement resources to curb the unlawful marketing of [non-tobacco nicotine] NTN products,” the FDA wrote. “To date, FDA has issued a total of over 60 warning letters to manufacturers, including brands popular among youth such as Puff Bar. The manufacturer warning letters include those for products for which an application had been submitted but where the agency has taken a negative action, such as a [RTA].”
The FDA has also issued over 300 warning letters to retailers for violations in relation to their sale of NTN products to underage purchasers, and imposed civil money penalties against two retailers for sales of NTN products to underage purchasers.
“To date, the FDA has not authorized any NTN products. Therefore, all NTN products on the market are marketed unlawfully and risk FDA enforcement action,” the FDA stated. “It is illegal for a retailer or distributor to sell or distribute e-cigarettes that the FDA has not authorized, and those who engage in such conduct are at risk of FDA enforcement, such as a seizure, injunction, or civil money penalty.”

October 15, 2022
‘FDA Downplays PMTA Acceptance Numbers’

Amanda Wheeler (Photo: AVM)

The U.S. Food and Drug Administration is understating the number of nontobacco nicotine (NTN)-related premarket tobacco product applications (PMTAs) it has accepted for review in order to avoid criticism from tobacco control groups that seek prohibition of all vaping products, reports Vaping360, citing American Vapor Manufacturers Association (AVM) President Amanda Wheeler.
On Sept. 8, the FDA announced it has accepted over 350 PMTAs (out of nearly 1 million applications) for NTN products. Wheeler insists that AVM member companies alone have received acceptance letters for 4,700 PMTA submissions.
“Once again, the FDA and its Center for Tobacco Products are misleading the public and press on crucial data and methods in its approval process for vaping products,” Wheeler said in a statement. “The figures stated in its press release today on synthetic nicotine applications are demonstrably inconsistent with FDA letters to our own members indicating many thousands more applications successfully filed than FDA now claims.”
An acceptance letter indicates that the application has met the basic requirements to move forward in the review process. It does not authorize the applicant to market the product.
The AVM also says the FDA altered required PMTA forms close to the submission deadline to disqualify already-submitted applications. According to Wheeler, the application forms were “abruptly altered” without public notice, “apparently as a means to disqualify wide swaths of already-filed applications.”
In March, U.S. President Joe Biden signed legislation authorizing the FDA to regulate synthetic nicotine products. Manufacturers had until May 14 to submit PMTAs and were given two additional months to continue selling products with pending PMTAs. When the grace period ended July 13, all synthetic nicotine-based products became subject to FDA enforcement.

September 12, 2022
FDA Reports Progress With NTN Applications

Photo: Postmodern Studio

The U.S. Food and Drug Administration has sent more than 44 warning letters to manufacturers and over 300 warning letters to retailers for violations relating to nontobacco nicotine (NTN) products since President Joe Biden signed legislation authorizing the agency to regulate tobacco products containing nicotine from any source. Additionally, the FDA has issued new warning letters to 102 retailers for illegally selling NTN products to underage purchasers.
In an update, the agency detailed what it described as “significant progress” in processing and reviewing premarket tobacco product applications for synthetic nicotine products.
On March 15, 2022, a new federal law gave the FDA the authority to regulate tobacco products containing nicotine from any source. This law took effect April 14, 2022, and after July 13, 2022, any new NTN product that has not received premarket authorization from the FDA cannot be legally marketed.
The FDA says it received nearly 1 million NTN applications from more than 200 companies. To date, all applications submitted by May 14 have been processed, and more than 85 percent have been reviewed to determine if they meet the minimum requirements to be accepted for further review, according to the agency. In total, the FDA has issued refuse to accept (RTA) letters for more than 800,000 NTN products in applications that do not meet the criteria for acceptance.
In total, the FDA has accepted over 350 applications for NTN products, with the vast majority being for e-cigarette or e-liquid products. The agency stresses that acceptance is not a determination about the products’ authorization status. “Accepted applications will enter further review, which ensures certain criteria are met for applications to proceed with further review,” the FDA wrote in its update.
More information about the FDA’s premarket review progress and compliance and enforcement actions is available at the agency’s NTN product webpage.

September 8, 2022
First Warning Letters for Synthetic Nicotine

Photo: 103tnn

The U.S. Food and Drug Administration on July 13 sent its first warning letters to manufacturers for unlawfully marketing non-tobacco nicotine e-liquid products without the required authorization.
In March, President Joe Biden signed into law a spending bill that gives the FDA authority over synthetic nicotine. The provision took effect in April and gave manufacturers until May 14, 2022, to submit marketing applications to the FDA.
Products did not receive marketing authorization by July 13, 2022, are considered illegal and must be removed from the market.
The recipients of the FDA’s first warnings letters, AZ Swagg Sauce and Electric Smoke Vapor House, have listed a combined total of approximately 10,000 products with FDA. Neither company submitted a premarket application for its non-tobacco nicotine products by the deadline, according to the FDA.
In addition, the FDA issued 107 warning letters to retailers in the last two weeks for illegally selling non-tobacco nicotine products, including certain e-cigarette or e-liquid products, to underage purchasers.
“FDA has been fully committed to actively implementing this critical new law regulating non-tobacco nicotine products since its passage, and the warning letters announced today are just the beginning of our compliance and enforcement actions” said Brian King, director of the FDA’s Center for Tobacco Products, in a statement. “In the coming weeks, we will continue to investigate companies that may be marketing, selling, or distributing non-tobacco nicotine products illegally and will pursue action, as appropriate.”
The FDA says it is currently processing applications for approximately 1 million non-tobacco nicotine products submitted by more than 200 manufacturers by the May 14, 2022, deadline.
“FDA is working diligently to process the substantial number of applications submitted and, as always, will make marketing decisions based on the best available science and will pursue compliance and enforcement actions when warranted,” said King. “We remain fully committed to taking whatever steps are necessary to protect the public health and to provide timely updates on our ongoing progress regulating non-tobacco nicotine products.”

July 14, 2022
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