Costa Rican authorities have announced their intent to prohibit vaping, e-cigarette and other tobacco products containing synthetic nicotine in the country.
A proposed resolution will prohibit the “sale, use, commercialization, advertising, promotion, and sponsorship of vaping liquids containing synthetic nicotine and cannabinoids,” the Ministry of Health wrote in a statement.
It will also affect products that “have incorporated cannabinoid-type liquids” because they “represent a health risk,” according to the statement.
The provision will be in effect while the government prepares to reform the law regulating next-generation tobacco products and electronic nicotine delivery systems.
The National Anti-Tobacco Network (Renata) reacted positively to the decision in a statement, highlighting that it “applauds” the government for the new regulation.
“Costa Rica could be on the verge of experiencing a next epidemic of vaping patients,” they argued.
Retailers call the proposal an “injustice,” said Michael Araya, owner of the La Pegona chain of smokers’ stores, according to a media report.
“I’m totally frustrated,” he said. “A lot of people are going to be out of work; continuing in a smoke shop without selling smoking products doesn’t make sense, a very hard blow to all the investment,” Araya added.
A nicotine industry veteran answers some common questions concerning the rise of synthetic nicotine.
By Chris Howard
Since President Biden signed the fiscal year 2022 Consolidated Appropriations Act into law on March 15, 2022, questions surrounding the U.S. Food and Drug Administration’s Center for Tobacco Products’ (CTP) handling of enforcement with respect to products containing nontobacco-derived (NTN), or synthetic nicotine, have been pervasive. While the CTP has indicated that it is not engaging in enforcement discretion to address the exceptionally short compliance timeline Congress provided in the bill, the center’s actions and public statements provide insight into its enforcement priorities and how the industry can assess the position the center takes. In this article, I will answer some frequently asked questions formulated from an extensive review of public statements and enforcement actions.
What does the Consolidated Appropriations Act have to do with tobacco products containing synthetic nicotine?
The act provided the CTP jurisdiction over NTN products beginning April 14, 2022. It also established a period for compliance with the Federal Food, Drug and Cosmetic Act’s premarket review requirements for NTN on or introduced to the market by April 14, 2022.
The legislation provided that for a manufacturer to continue marketing NTN products after May 14, 2022, they must submit a premarket tobacco product application (PMTA) for such products by that date. In the event a manufacturer complied with this requirement, they were permitted to continue to market such a product through July 13, 2022 (provided the FDA didn’t previously deny the PMTA, refuse to file the PMTA or withdraw a marketing order for a previous version of the product at issue that utilized tobacco-derived nicotine). Just like tobacco-derived products that remain the subject of pending PMTAs beyond Sept. 9, 2021, NTN products that are the subject of pending PMTAs after July 13, 2022, technically must have received market orders to be legally marketed today.
Are tobacco products containing synthetic nicotine illegal?
Just like tobacco products containing tobacco-derived nicotine that are subject to pending PMTAs, all current tobacco products containing synthetic nicotine on the market in the United States are illegal. It is important to note, however, that this doesn’t mean that CTP intends to expend its limited enforcement resources to remove all such products from the market. Rather, the center has expressed its intent to move forward in accordance with a discrete set of priorities outlined more particularly below.
Does the FDA intend to treat enforcement of tobacco products containing synthetic nicotine differently than enforcement of tobacco products containing tobacco-derived nicotine?
No. CTP leadership has made it clear that it will apply its enforcement priorities identically with respect to both categories of products.
The CTP has been explicit that both tobacco products containing nicotine derived from tobacco (marketed after Sept. 9, 2021) and tobacco products containing nontobacco-derived nicotine (marketed after July 13, 2022) without premarket authorization (marketing orders) are considered by the FDA to be noncompliant and that manufacturers of both categories of products are subject to the same public health standards. The CTP’s position is set forth clearly in the below public statements:
Tobacco Products Containing Nicotine Derived from Tobacco
On Sept. 9, 2021, the FDA issued a statement entitled “FDA Makes Significant Progress in Science-Based Public Health Application Review, Taking Action on Over 90 Percent of More Than 6.5 Million ‘Deemed’ New Tobacco Products Submitted,” which you can review at the following link: https://www.fda.gov/news-events/press-announcements/fda-makes-significant-progress-science-based-public-health-application-review-taking-action-over-90. In this release, former Acting Commissioner Janet Woodcock and former CTP Director Mitch Zeller indicated: “All new tobacco products on the market without the statutorily required premarket authorization are marketed unlawfully and subject to enforcement action at the FDA’s discretion” (emphasis added).
On Oct. 14, 2022, the FDA issued a statement entitled “FDA Completes Initial Review of 95 Percent of Nontobacco Nicotine Product Applications; Agency Has Issued Over 60 Warning Letters to Manufacturers, Including for Products with a Submitted Application and Negative Action,” which you will find at https://www.fda.gov/tobacco-products/ctp-newsroom/fda-completes-initial-review-95-non-tobacco-nicotine-product-applications-agency-has-issued-over-60. Upon review, you will note that the FDA is speaking about tobacco products containing nontobacco-derived nicotine. As we discussed, the FDA used nearly the exact same language employed by Woodcock and Zeller in September 2021 to describe the agency’s views with respect to tobacco products containing nicotine derived from tobacco. In particular, the FDA states, “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” (emphasis added).
In a Feb. 3, 2023, email to the executive director of the National Association for Tobacco Outlets from a director in the CTP’s Office of Compliance and Enforcement, FDA leadership provides even more clarity:
“FDA is fully committed to implementing the new federal law clarifying its authority to regulate tobacco products containing NTN, including synthetic nicotine. Manufacturers of these products are now held to the same public health standards, including premarket review, as tobacco-derived nicotine (TDN) products. Irrespective of whether the product contains TDN or NTN, it is illegal to sell or distribute tobacco products that the FDA has not authorized. On Aug. 8, 2016, all deemed tobacco products, including e-cigarettes, became subject to FDA’s tobacco authorities.
“As a matter of enforcement discretion at the time, the agency stated that it intended to defer enforcement for a period of time of the premarket authorization requirement for certain deemed new products on the market as of Aug. 8, 2016. However, in light of later data on youth use and other information, FDA revised this policy in its 2020 enforcement priorities guidance. That guidance described how the agency intended to prioritize its limited enforcement resources regarding certain ENDS [electronic nicotine-delivery system] products. It also noted that all deemed new tobacco products on the market without authorization are illegally marketed and that the agency ‘retains discretion to pursue enforcement action at any time’ against such products.
“The same principle applies to NTN products; specifically, all illegally marketed NTN products are subject to enforcement ….”
Director Brian King has made similar statements in several open forums indicating that tobacco products without market authorization (regardless of whether they contain nicotine derived from tobacco or nontobacco-derived nicotine) are noncompliant. Based upon these ubiquitous public statements, it appears the FDA will continue to prioritize enforcement against manufacturers with products (a) not covered by timely filed pending PMTAs or (b) that are the subject of marketing denial orders—with an emphasis on products that are particularly attractive to youth.
What is the significance of the Aug. 8, 2016, effective date of the deeming regulation with respect to tobacco products containing synthetic nicotine?
The FDA did not have authority to regulate tobacco products containing synthetic nicotine upon the effective date of the deeming rule. Rather, the FDA obtained authority to regulate such products following the effective date of the Consolidated Appropriations Act. The relevant timelines established by the act did not include a period for continued marketing of unauthorized new products containing synthetic nicotine beyond July 13, 2022. As such, all tobacco products containing synthetic nicotine on the market without premarket authorization are illegal and subject to FDA enforcement.
What are CTP’s prioritieswhen enforcement against tobacco products containing synthetic nicotine without market orders?
Regardless of whether a product without market authorization contains synthetic or tobacco-derived nicotine, the FDA has indicated its intention to prioritize its enforcement efforts with respect to certain deemed tobacco products (1) not covered by timely filed PMTAs, (2) that have been the subject of marketing denial orders or those covered by PMTAs subject to negative determinations, including those rejected on procedural grounds (i.e., refuse-to-accept letters or refuse-to-file letters), and (3) that raise youth use concerns.
As we are all aware, even though the continued compliance policy for certain deemed new tobacco products ended on Sept. 9, 2021, and those products were subject to immediate enforcement action, the CTP has not, as of the date of the publication of this article, brought enforcement action against any of those products covered by still pending PMTAs. Based on the center’s handling of these products combined with the CTP’s recent public statements, it seems likely that the CTP will exercise a similar approach to NTN products covered by PMTAs that remain pending after July 13, 2022. Moreover, the CTP is likely to refrain from taking enforcement action against such products while it reviews the pending applications.
Chris Howard is the executive vice president of external affairs and new product compliance for Swisher International.
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.
Nicotine was first synthesized nearly 120 years ago and is now being considered a new tobacco product.
By Timothy S. Donahue
Synthetic nicotine has been under fire recently. News reports surrounding the product have been negative, and technically, all synthetic nicotine products are illegal in the U.S. Companies had until May 14 to submit a premarket tobacco product application (PMTA) to the U.S. Food and Drug Administration to keep their products on the market. Those that did not gain the FDA’s authorization for their synthetic nicotine products would have had to pull those products from the market by July 13. However, the FDA does seem to be using some discretion in its enforcement of synthetic nicotine products.
During a panel presentation on synthetic nicotine at the Next Generation Nicotine Delivery USA 2022 (NGN) conference in Miami, Florida, in June, Todd Cecil, the acting co-director for the FDA’s Center for Tobacco Products’ Office of Science, commenting from the audience, said that he could not confirm enforcement discretion for synthetic products. He said “everything” on the market after July 13 is illegal. However, he insisted that the agency would evaluate synthetic products based on the science.
“I can say that without doubt … the Office of Science will evaluate synthetic nicotine as you would any product, and [it] isn’t looked at with bias either for or against. It is up to the application to demonstrate that their product is APPH [appropriate for the protection of public health],” said Cecil. “And, like the rest of the FDA, no end verdict is evaluated in the absence of the dosage form in which it is administered.
“So, you may well find a lot of synthetic nicotine products coming off of the marketplace because they didn’t hit the requirements of submission, didn’t hit the requirements of data that’s in the rule, or that they have not demonstrated that it’s APPH, all of which is part of this analysis process. It’s not simply a ‘Well, it’s synthetic. That means it’s OK.’ It has to be evaluated as part of [the PMTA].”
George Cassels-Smith, CEO of Tobacco Technologies Inc., parent to eLiquiTech, the global distributor of SyNic products, said during the NGN panel that public misconceptions present a considerable challenge in the discussion about synthetic nicotine, adding that the FDA may be partly to blame because of the agency’s lack of clarity on the product’s safety and efficacy.
“Our role now is to work with the FDA and to educate people that [synthetic nicotine] is a viable alternative and that it’s got a good spot in the future of tobacco products and pharmaceutical products, that it ticks all the boxes,” explained Cassels-Smith. “But unless we can educate the consumer, we’ll continue working with a 90 percent misconception of what this product actually is.”
Tony Abboud
Tony Abboud, also speaking on the NGN panel, said that anti-vaping zealots, because of a few bad actors in the vaping industry, wrongly believe that synthetic nicotine was created only to evade the regulatory scope of the FDA. Companies like U.K.-based Zanoprima Lifesciences (the parent to SyNic) “have been manufacturing synthetic nicotine and perfecting the scientific process associated with it for years before the deeming regulation took effect, before the deeming regulation was fully implemented and long before the PMTA process kicked off,” said Abboud. “So that fact suggests that circumvention, again, is no longer an argument that is relevant.”
Synthetic explained
Synthetic nicotine is not new. Nicotine was first synthesized by Swiss chemist Ame Pictet in 1904. Since extracting nicotine from natural tobacco is efficient and inexpensive and synthesis from precursor compounds is relatively complex and expensive, for more than a century, synthetic nicotine had no commercial role, according to researchers at Stanford University in the U.S.
Molecules such as nicotine may exist in mirror image forms with identical chemical makeup but sometimes differing biological activity. The nicotine molecule possesses chirality, meaning it exists in two mirror image versions called enantiomers or stereoisomers. Nicotine comes in left (S) and right (R) forms. The (S) isomer of nicotine greatly predominates in tobacco leaf, which contains only small amounts of the (R) variant (0.1 percent to 1.2 percent).
Most synthetic nicotine has equal parts of both the (S) and (R) isomers. SyNic only has the (S) isomer—the one that holds all the psychotropic effects that nicotine consumers want, according to David Johnson, eLiquiTech’s president and chief scientific officer. SyNic USP/EP, SyNic nicotine bitartrate and SyNic polacrilex resin are manufactured in FDA-registered facilities using current good manufacturing practices. These products have confirmed purity levels of more than 99.9 percent, (S) levels of more than 99.7 percent and are free of tobacco-specific nitrosamines (TSNAs) and carcinogens, according to Johnson.
“The molecule is the same and the three-dimensional structure’s the same. It’s not different. There’s nothing new. And so all those studies that were done with tobacco-derived nicotine can be bridged to this synthetic product, so it creates some synergies, reduces some effort on the part [of] people who are generating reports and reduces some of the burden on the regulators in terms of assessing the data that’s generated as well,” explains Johnson. “So this seems to be a pretty straightforward case, right? You have a pure product in terms of the active ingredient. You have delivery mechanisms that clearly evolve at the low end of the risk containers, and you have a strong basic science upon which you compare the products and then evaluate them.”
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 difficult and costly because the impurities appear structurally similar to the nicotine molecule itself. But synthetic nicotine is virtually free of any impurities from the beginning, and none of its varieties are carcinogenic.
ELiquiTech 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. Zanoprima holds the patent, and eLiquiTech maintains the exclusive rights for global distribution to the tobacco and electronic nicotine-delivery system industries. ELiquiTech does not sell flavorings for e-liquids.
Cassels-Smith said the marketplace for synthetic nicotine has been a rollercoaster. He said SyNic does not make any sales to people that do not have an active PMTA. He said that when marketing denial orders for flavored tobacco-derived nicotine products began to come down from the FDA, the demand for synthetic nicotine was strong. However, SyNic only did business with companies that submitted a PMTA. Subsequently, the FDA opened a short window for new products to enter the marketplace.
“We saw a very robust sampling and ordering process for people to [bring new products to market]. Now, we are in a period where companies would be marketing that product. But surprisingly, I’m not seeing the demand that I experienced in the beginning,” said Cassels-Smith. “My guess is that people are waiting to find out how those applications will be reviewed before they come in. I think their concern is that if there’s a market denial order and they must remove the products from the shelves, they would have excessive inventory and a high exposure to potential cash flow issues.”
Globally, the United States has always been the country that “tosses the paddle in the water, and then we quickly see over in Europe the ripple effect,” according to Cassels-Smith. He said that he had recently spent time in Europe and was amazed at the number of vapers and heat-not-burn consumers there.
“The ratio of people that were smoking cigarettes was the smallest that I’ve ever seen in Europe. I was in Poland for the Global Nicotine Forum. Going to the conventions, I was in Birmingham for [the World Vape Show] two weeks prior. Synthetic nicotine was all the rage, and the U.K. is seeing smoking plummet because of its embracing of vapor products. World Vape Show Dubai had many synthetic products too … it’s very strong right now in the Middle East. And most recently, we see that China is licensing companies to produce an estimated 200 metric tons to [a rumored] 500 metric tons of synthetic nicotine. With those kinds of quantities, they must anticipate an extremely strong demand.”
Credit: NDABCREATIVITY
Forward thinking
The vapor industry is always changing. However, nicotine has always been a traditionally quiet segment. When some companies announced that they would use synthetic nicotine to circumvent FDA regulation, the U.S. Congress acted. It changed the definition of tobacco in the Tobacco Control Act to include synthetic nicotine. That change turned the synthetic nicotine market on its head.
Cassels-Smith predicts a bifurcation in the nicotine market. This is due to factors such as making the cost of synthetic production more affordable and the certain security guarantees that synthetic nicotine offers over its natural cousin. 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.
However, natural nicotine may not be the best option for nicotine-replacement therapy (NRT) and next-generation nicotine products. This is because nicotine extraction outside the U.S. comes from a supply of dust and recon. India, for example, has used its large stocks of tobacco dust to create a crude nicotine, which is then refined into a purer liquid nicotine extraction.
Several NRT products have been taken off the market by the FDA recently because they were found to contain TSNAs, residuals from the natural nicotine used in the NRT’s production. Synthetic nicotine has no TSNAs, the harmful, cancer-causing chemicals found in combustible tobacco products, because TSNAs are formed when tobacco leaves are grown, cured, aged and processed. The problem with the tobacco used in most naturally derived liquid nicotine is that the leaf used for extraction can’t be traced back to its origins.
“When you pick up a pack of cigarettes, you can tell that tobacco is grown in this farm, in this soil, with this seed, with this residual pesticide, with this amount of heavy metals … with a nicotine extraction, you have no idea. You can’t track and trace it,” explains Cassels-Smith. “So that’s an advantage to our product. And I think that you’re going to see more and more of tobacco grown from a specific area with a farmer with known residual pesticides and known heavy metal contents of the soil, and that will be extracted. And I call that the pedigree of natural nicotine. I do see an opportunity for a pedigree brand of natural nicotine to have a substantial seat at the table.”
Johnson said that having a manufacturing process that produces a synthetic nicotine offers a controlled process that’s repeatable, reproducible and well defined. Every raw material that goes into the production process can be traced by lot. Ingredients can all be tracked back to the source. “You’ve got batch records. You’ve got lot tracking. It meets that pharmaceutical model for producing a product that’s very well characterized [and] very reproducible,” said Johnson from the NGN panel stage. “The product that you produce is very low in impurities. It has no TSNAs, OK? Because those are not produced in this process.”
David Renteln, co-founder and CEO of Lucy Goods, said that a pure, consistent, traceable form of nicotine is both easier to work with and also better for the consumer. He said that if one were to consider what the future of farming is going to look like, it isn’t going to be the traditional growing on billions and billions of acres of land. And land that needs to be used for food won’t be taken up by tobacco.
“We’re still using farmland to grow tobacco, something that we’ve done for thousands of years [it’s labor intensive and bad for the environment]. The chemical production and synthetic production of key chemicals is something that will definitely not be done [in the future] by just growing plants on essentially two-dimensional plots of land,” said Renteln. “And as a result, the efficiencies are better for the environment, it’s better for human quality of life and labor practices. And when we reach scale, it will probably be less expensive, all the while being better for the manufacturer and the consumer.”
Credit: TTI
A closing cause
The benefits of synthetic nicotine could extend to other products, such as pharmaceuticals. The 1958 Food Additives Amendment requires the FDA to ban additives that are found to cause or induce cancer in humans or animals as indicated by testing, such as TSNAs.
Cassels-Smith said that this is why his company is preparing its drug master file for SyNic. The lack of track and traceability for natural nicotine has been a problem not only for the tobacco industry but also for the pharmaceutical industry and NRT manufacturers.
“I think a lot of data needs to be presented, but I think [an] argument clearly can be made that this is more helpful to use in a habitual way than a Nicorette gum or something else in the NRT space. So, yes, a rising tide will lift all ships,” he said. “We will eventually see pharmaceutical, as well as tobacco products, with a cleaner active ingredient because what’s good for the goose is good for the gander.”
Renteln said that the agency has the ability to do what it wants. It has a high degree of latitude to make decisions that it believes will help the agency achieve its mission: protecting public health. He said that the intent behind regulating vaping products is to ensure that these products that are APPH remain on the market and that those that aren’t APPH are not allowed to remain on the market.
“We should take an appropriate amount of time and get the burden of evidence that they need to make that decision. I think that there are, just using common sense, products that are more complicated and will require more time to assess, and then there are products where it would be kind of difficult to mess up,” he says. “I think enforcement priorities can make a great deal of sense. We’ve seen that work relatively effectively already, and so I think they’ve got a precedent that’s not perfect but good enough.”
Instead of overzealous regulatory actions, Renteln said he would like to see more action taken against the bad actors of the industry. Nobody seems to care if they get a warning letter. He thinks misinformation is a serious issue, claiming 90 percent of the doctors he has spoken with believe nicotine causes cancer and is extremely poisonous. He also doesn’t want the FDA’s decisions to be political.
“The problem we have is misconceptions and people telling false truths. Nicotine isn’t made in a microcosm; nicotine does have an addictive quality to it, but it’s super clean. It’s not carcinogenic,” said Renteln. “My biggest concern is just that there will be a great deal of pressure [on the FDA] to bow to political influences rather than scientific decision-making … that’s really the agency’s role; that’s their mission. That’s their approach to dealing with everything. I think that the scientists at the agency tend to feel very strongly that they’re going to make a decision based on science.”
One month into his new job, Brian King is already praising his agency’s hard work. The director of the U.S. Food and Drug Administration’s Center for Tobacco Products (CTP) released a statement that he wanted to make it “unequivocally clear” that the agency was “working diligently” to process synthetic nicotine premarket tobacco product applications (PMTAs).
“A substantial number of applications were submitted by May 14 – nearly one million from more than 200 separate companies – with some several thousand pages long,” King stated. “Preparing these applications for review takes several steps and submissions varied widely in their organization, size, and completeness of data, which impacts the time it takes to process the information.”
Amanda Wheeler, president of the American Vapor Manufacturers Association (AVM), Tweeted, “Read between the lines: Millions of applications submitted, ZERO approved, yet King assures us the system is working. We do know the only thing preventing vape products from saving lives is the FDA itself, rigging the system in favor of prohibition over harm reduction,” in response to King’s statement.
Despite the challenges of reviewing PMTAs, King stated that the agency was “making significant progress” in processing and reviewing the applications. The FDA has issued refuse-to-accept (RTA) letters for more than 88,000 products for applications that “do not meet the criteria” for acceptance. Applications are required to provide important information needed for processing and reviewing.
“Without the required information, applications cannot proceed past the acceptance phase of the review process,” King stated. “The RTA letters state that it is illegal to sell or distribute in the U.S. marketplace any new tobacco product that has not received premarket authorization.
Of the nearly a million applications submitted by May 14, the FDA only accepted an estimated 350, with the vast majority being for e-cigarette or e-liquid products, according to the statement. Accepted applications are then evaluated in the filing stage before going under scientific review.
“The substantive review phase includes evaluation of the scientific information and data in an application, which often results in follow-up questions and conversations with companies, including in situations where elements of an application raise questions needing clarification,” stated King. “It is only after the substantive phase that a company may be granted a marketing order. If no marketing order is granted, it remains illegal to market the product. To date, no non-tobacco nicotine product has received a marketing granted order.”
All bark, no bite
After July 13, 2022, a non-tobacco nicotine product can only be legally marketed in the United States if it has received a marketing order from the FDA. This means that it is illegal for a retailer or distributor to sell or distribute a synthetic nicotine products is in violation of the law and its manufacturer, retailer, or distributor may be subject to FDA enforcement.
King stated that the agency’s compliance and enforcement work is a multi-step process that cannot “happen overnight.” it takes time to ensure that any enforcement taken is supported by the available evidence with respect to the legal standards. Typically, the FDA will first issue warning letters to promote compliance and then follow up to ensure the violations addressed in the warning letter are corrected. If firms continue to violate the law, the FDA can pursue further actions, such as civil money penalties, seizures, and injunctions.
Many retailers simply ignore the FDA warnings. One owner told Vapor Voice that they “know” the agency is overworked and understaffed and is unlikely to follow up or pursue further steps. The agency has also made some very public mistakes over the past month, including its reversal of Juul’s marketing denial order (MDO), that has damaged the agency’s public perception.
While there isn’t much data surrounding what tobacco products remain on the market that have received warning letters, however, numerous companies on the agency’s MDO list still market products in the U.S.
It isn’t only for tobacco products that the agency doesn’t enforce its warnings. A considerable proportion of drug supplement products remain available for purchase after issuance of FDA warning letters, according to a research letter published in the July 26 issue of the Journal of the American Medical Association. Researchers found that the FDA issued warning letters regarding 31 supplement products. Only one of these 31 products was recalled by the manufacturer.
At a mean of six years following the issue of warning letters, nine of the products (29 percent) remained available for purchase online, according to the authors. Four of these nine products (44 percent) listed the presence of at least one prohibited ingredient on the label: One label declared the prohibited ingredient included in the FDA warning letter and three listed other FDA-prohibited ingredients. Five of the nine products were found to contain at least one FDA-prohibited ingredient after chemical analysis: Four products contained one prohibited ingredient and one product contained three. Two products contained the ingredient for which the FDA issued the warning letter.
Despite its challenges, the FDA issued 17 new warning letters on Aug. 1 to manufacturers for marketing products without FDA approval. On July 28, the agency issued 102 warning letters to retailers for illegally selling non-tobacco nicotine products to underage purchasers.
“Our goal is clear communication and transparency, and toward that end, we intend to include information about non-tobacco nicotine products in our regular metrics reporting in the future,” stated King. “To keep stakeholders and the general public informed, we also launched a non-tobacco nicotine product webpage that includes information about how synthetic nicotine is made and our regulation of non-tobacco nicotine products.”
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 [the Act] that gives the FDA authority over synthetic nicotine. The provision took effect in April and gave manufacturers until May 14, 2022, to submit premarket tobacco product applications (PMTAs) to the FDA.
Since no authorizations have been granted as of today, many industry experts question whether the FDA will use its enforcement discretion to continue reviewing PMTAs.
In a recent op-ed, Tony Abboud, president for Strategic Government Solutions, and executive director of the Vapor Technology Association (VTA), stated that the FDA should use its enforcement discretion for synthetic products that have submitted PMTAs.
“In a series of direct engagements with FDA since the passage, the VTA has provided a complete set of scientific and policy justifications for synthetic nicotine products, and specific recommendations on how FDA should use its enforcement discretion – just as it has in the past – to allow synthetic nicotine products to remain on the market during the PMTA review process,” explained Abboud.
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.”
Under the new law governing synthetic nicotine products signed on March 15, 2022, Congress imposed a short 60-day deadline for companies to file premarket tobacco product applications (PMTAs) and declared that if such applications were not approved within 120 days (the Act) they would be “in violation of” the Federal Food Drug & Cosmetic Act’s (FDCA) PMTA requirement.
Since no authorizations have been granted as of today, the question is will FDA use its enforcement discretion to continue reviewing PMTAs, or will it precipitously declare that all synthetic nicotine products must be removed from the market after July 13, 2022?
There is no question that the FDA should use its enforcement discretion. In a series of direct engagements with FDA since the Act’s passage, the Vapor Technology Association (VTA) has provided a complete set of scientific and policy justifications for synthetic nicotine products, and specific recommendations on how FDA should use its enforcement discretion – just as it has in the past – to allow synthetic nicotine products to remain on the market during the PMTA review process.
However, some have suggested that Congress mandated all products be removed from the market this week if they are not approved by FDA. But a close review of the Act reveals that the opposite is true: Congress did not require synthetic nicotine products with pending PMTAs to be removed from the market after July 13.
In interpreting laws, a court will first look to the plain language of the Act and, only if there is an ambiguity, will it look to Congressional intent to resolve such a question. Here, both support the FDA’s continued use of enforcement discretion for pending PMTAs.
The Plain Language Supports Enforcement Discretion
There are four relevant sections of the Act. First, under Section (d)(2)(A), Congress expressly stated that “as a condition to market” all manufacturers wishing to continue selling their products must file a PMTA no later than May 14, 2022.
Tony Abboud
Second, under Section (d)(2)(B), Congress expressly stated that companies which filed PMTAs “may continue to market” their products during what the Act calls a “transition period.”
Third, under Section (d)(2)(C), Congress expressly required that if a company did not file a PMTA for its synthetic products by May 14, 2022, that company is “not eligible for continued marketing.” In each of these sections, Congress expressly uses some variation of the term “market” to articulate its direction on what may (not) be marketed and when.
However, in the operative Section (d)(3), which addresses what happens after July 13, 2022, Congress makes no statement regarding marketing at all. Instead, it states that products with pending PMTAs not yet approved would be “in violation of…section 910” of the FDCA (21 USC 387g).
When presented with this question, a court likely would rule that because Congress did not expressly state that pending applicants are “not eligible for continued marketing” or that they “may not market” after July 13, as it clearly said in the immediately preceding sections, Congress did not require the removal of products with pending PMTAs.
This places synthetic nicotine products with pending PMTAs in precisely the same position as all other products with pending PMTAs which, for years, FDA has made clear are “illegal” (i.e., in violation of section 910) but are allowed to remain on the market at FDA’s enforcement discretion.
Even if a court finds that Section (d)(3) is ambiguous, there is nothing in Congressional intent that would lead to the conclusion that Congress intended for products with pending PMTAs to be removed from the market.
First, Congress could have banned synthetic nicotine products, if that is what it intended, but it did not do so. To the contrary, Congress expressly authorized manufacturers to bring new products to market after the Act’s passage. Thus, it would be folly to suggest that Congress intended all synthetic nicotine products be removed from the market without PMTA review.
Second, Congressional intent is generally divined by on the record statements made in committee hearings and in floor debate (not from press releases or media statements). But there is little to nothing which a court could rely on [with] this question because the provision was quietly slipped into the Ukraine-omnibus spending bill with no relevant hearing or floor debate.
Third, Congress was fully aware that FDA could not review PMTAs within 180 days (as required under the FDCA). In fact, the FDA told a court it will not be finished reviewing tobacco derived PMTAs until June of 2023. Thus, no one could suggest that there ever was any reasonable expectation or intent that the FDA would rule on synthetic nicotine PMTAs in 60 days.
Hence, the only reasonable conclusion that can be drawn from the plain language and Congressional intent is that Congress did not require removal of products with pending PMTAs but, rather, expected the FDA to continue to use its discretion in enforcing its PMTA regulation after July 13.
Congress did, however, expressly state that products for which no PMTA was timely filed have no continuing ability to market, authorizing the FDA to take immediate action. VTA has repeatedly communicated to the FDA the need for it to aggressively remove all tobacco products from the market for which no PMTA has been filed and to publish a list of all products covered by a synthetic nicotine PMTA so that retailers know which products can be sold.
A Careful and Complete Evaluation of Synthetic Nicotine PMTAs is Required
We live in a world that remains captive to [combustible] cigarettes. Congress won’t ban them and Congress has prevented the FDA from doing so. While electronic nicotine-delivery system (ENDS) products offer a technological solution to delivering nicotine in a substantially less harmful way, synthetic nicotine now represents the first technological innovation in nicotine itself.
Synthetic nicotine uniquely offers consumers the cleanest and purest form of nicotine with numerous benefits, i.e., the absence of heavy metals, nitrosamines, and pesticides. Synthetic nicotine uniquely offers consumers the opportunity to break free from the last remaining vestige of the tobacco plant.
Synthetic nicotine uniquely offers the FDA unprecedented product constituent clarity, replicability, and traceability down to the batch level. Not only does synthetic nicotine offer companies the opportunity to change the dynamics regarding total reliance on tobacco-derived nicotine for all tobacco and pharmaceutical nicotine products, but it also provides companies the ability to address their ESG [sustainability] goals and take a significant step to ameliorate the adverse environmental impacts of tobacco.
Our message to the FDA has been constructive and clear: it is critical to the adult smoker that FDA takes aggressive steps to create an orderly and regulated marketplace with a diversity of desirable nicotine alternatives.
Given recent history with tobacco derived PMTAs, the best way for FDA to realize that objective now is to avoid the blanket denial mistakes of the past which have mired the agency in protracted litigation. Such litigation will only delay the time until we achieve an orderly and regulated marketplace.
Instead, we have asked the FDA to work companies which timely filed synthetic nicotine PMTAs – the good actors – through the PMTA scientific process and provide them the requisite time and guidance to fulfill FDA’s requirements.
At the same time, we have asked the FDA to aggressively enforce against the non-compliant companies that have refused participate in the PMTA process – the bad actors – by interdicting such products at the border and removing such products from the market Congress has clearly required.
In the end, it is incumbent on the new FDA leadership to use its power to create an orderly marketplace by embracing scientific innovations, stimulating additional financial investment, accelerating authorizations of pending tobacco-derived PMTAs, and ensuring that synthetic nicotine products which now contain the cleanest and purest form of nicotine that science has created are available to adult smokers.
Tony Abboud serves as president for Strategic Government Solutions, Inc., and executive director of the Vapor Technology Association (VTA).
The U.S. Food and Drug Administration tomorrow is expected to officially close the loophole that allows synthetic nicotine to be sold. July 13 is the deadline for the regulatory agency to complete its approval process on synthetic nicotine products.
It is unlikely the FDA will have been able to have reviewed premarket tobacco product applications (PMTAs) that were submitted by the May 14 deadline. The agency has not yet completed reviews for many other electronic nicotine-delivery system (ENDS) products using tobacco-derived nicotine that submitted PMTAs by the Sept. 9, 2020 due date.
Attorneys in the vaping industry say Congress set unrealistic deadlines for manufacturers to submit PMTAs and for the FDA to review them. The law, which took effect April 14, gave companies until May 14 to submit a PMTA, and all existing products that haven’t garnered authorization must come off the market by July 13.
The FDA said last week that it’s still reviewing the “large number of applications” it received for synthetic nicotine products, but declined to share the total number submitted, according to media reports.
Synthetic nicotine products on the market after July 13 “without an FDA marketing granted order” would be considered in violation of federal law and “may be subject to FDA enforcement,” the agency stated.
It is expected that FDA will issue at least some marketing denial orders for companies that submitted a PMTA but didn’t include required data, such as an environmental impact assessment.
In March, the U.S. Senate approved a $1.5 trillion legislation by a 68-31 bipartisan margin that included language that changed the definition of a tobacco product to include synthetic nicotine.
The rule became law 30 days after the bill’s passage date. Congress further granted synthetic nicotine products a transition period in which such products would be allowed to stay on the market until July 13, 2022, provided that they submit the required PMTA by the May 14 deadline—unless the FDA had already denied a non-synthetic version of the same product (meaning those manufacturers were subject to enforcement 30 days after the passage of the bill).
The language of the Tobacco Control Act changed 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.”
Matthew Myers, president of the Campaign for Tobacco-Free Kids, said that the FDA needs to act on Congress’ rules for synthetic products.
“It would be outrageous if the FDA failed to enforce the law after Congress acted with urgency to address a growing threat to the health of our nation’s kids: E-cigarette manufacturers’ use of synthetic nicotine to evade FDA regulation and keep selling flavored products that attract and addict kids,” he said. “In recent years, a growing number of e-cigarette makers have switched to using synthetic nicotine – nicotine that is made in a lab, rather than derived from tobacco – after the FDA acted against their flavored products made with tobacco-derived nicotine.”
A bipartisan coalition of 31 attorneys general are calling on the U.S. Food and Drug Administration to reject marketing authorization for all non-tobacco nicotine products, which are currently being sold without regulation of their contents, manufacturing, health effects, required warning labels or marketing claims.
In a letter to the agency, the coalition argues that these products currently don’t meet the FDA’s public health standard, and the regulatory agency should not gamble on the unknown effects of the products. The letter specifically calls for the FDA to reject a request by product manufacturers to grant marketing authorization for non-tobacco nicotine products.
The letter also insists that if the agency does grant marketing authorizations for these products, it imposes the same restrictions required of tobacco-derived nicotine products including a ban on all products with a flavor other than tobacco and strict regulatory requirements regarding their contents, manufacturing, and effect on users’ health.
Products should carry warnings concerning their addictiveness, and manufacturers should be required to validate health claims made about their products, including claims that a product is safer than tobacco.
“E-cigarettes containing synthetic nicotine and other synthetic nicotine products are putting our kids’ health at risk,” said North Carolina Attorney General Josh Stein. “The FDA has the power to do more to protect them, and I hope it takes action to prohibit manufacturers and retailers from marketing and selling to young people, using youth-friendly flavors, and putting exorbitant amounts of nicotine in these products, especially because we don’t yet know how dangerous these products are. I appreciate that the FDA has started taking some steps, but it must do more to rein in this industry and keep our kids safe.”
All nontobacco nicotine is now subject to the same regulations as tobacco-sourced nicotine in the U.S.
By Timothy S. Donahue
It was both expected and unexpected. Everyone in the vaping industry knew that at some point the U.S. Congress and the Food and Drug Administration were going to decide on how to handle synthetic and nontobacco nicotine. It was generally believed that regulation would appear in an appropriations bill in September, meaning vaping advocates thought they had time to fundraise and prepare for a battle.
They did not. Instead, the language for changing the definition of the Tobacco Control Act (TCA) to include all nicotine products was buried on page 1,861 of the 2,741-page omnibus spending bill that was signed by President Joe Biden in March. How the rider found its way into the omnibus has caught the ire of many in the industry who say major tobacco companies are seizing the vaping industry away from the small business owners who got it started.
Senator Richard Burr was allegedly approached by R.J. Reynolds and Juul Labs representatives about getting the synthetic nicotine rider in the omnibus that at the time was winding its way through Congress. Burr joined forces with fellow senators Dick Durbin and Patty Murray and Representative Frank Pallone to get the nontobacco nicotine language into the omnibus, according to two Senate sources familiar with the discussions, as reported by Bloomberg Law.
Azim Chowdhury
Azim Chowdhury, a partner with the law firm Keller and Heckman, said he interprets the rule to mean that all synthetic products already on the market or newly marketed within 30 days after the enactment date can continue to be marketed during the 60-day period following the enactment date. The law became effective on April 14, and manufacturers will have until May 14, 2022, to either submit a premarket tobacco product application (PMTA) to the FDA for each vaping product that contains synthetic nicotine or pull their products from the market.
Manufacturers that submit PMTAs to the agency by the May 14 deadline can continue marketing their products until July 13, 2022. Beyond that date, all products must be removed from retail stores unless the FDA has issued a marketing authorization, according to Chowdhury.
“We do not anticipate FDA authorizing any synthetic nicotine products by the end of the 90-day period, though they may take another Fatal Flaw (the term Fatal Flaw was used by the FDA for PMTA submissions that didn’t have specific studies and were subsequently denied) approach to quickly deny applications,” said Chowdhury. “Significantly, the rider in its current form indicates that a synthetic nicotine version of a product that already went through the PMTA process and is subject to a refuse-to-accept, refuse-to-file, marketing denial order (MDO) or withdrawal of a marketing order would have to come off the market as of the effective date—i.e., after 30 days of the law’s enactment.
“In simpler terms, for products that were previously formulated with tobacco-derived nicotine—and the only change was a switch to synthetic nicotine—and whose PMTAs have already been refused or denied, those products will effectively be banned on the effective date—30 days after enactment—with no opportunity to submit a new PMTA. This is Congress’ way of punishing companies whose PMTAs were denied and then, in their view, sought to circumvent the law by switching to synthetic nicotine.”
MIchelle Minton / Credit: Competitive Enterprise Institute
Michelle Minton, writing for the Competitive Enterprise Institute, states that given the FDA’s sluggish track record, many of the applications may not even be reviewed, let alone approved, in that time, which would make the bill a de facto prohibition on those products. “FDA has made it painfully clear that there is no way for those companies to earn its approval,” Minton said. “All it will do is guarantee that companies and consumers are pushed in ever-greater numbers toward a growing illicit market where there are no consumer protections and no age restrictions—or back to smoking.”
Stately response
Beyond the PMTA conditions, if a marketing order is granted, manufacturers of synthetic nicotine products are also subject to all the regulations for tobacco products. Keller and Heckman interpret this to include all additional TCA requirements, including tobacco product establishment registration and product listing; ingredient listing; ensuring that labeling is compliant, including required warning statements; and health document submissions, among others.
Many states had already started to ban synthetic nicotine unless a product gets marketing approval from the FDA. Legislation has been introduced in four state capitals and enacted in one state, Alabama, that effectively bans all products containing synthetic nicotine. Patrick Gleason, vice president of state affairs at Americans for Tax Reform, said Alabama, then Mississippi, Maryland and Georgia, were the first states to introduce legislation effectively banning synthetic nicotine products. However, he says there will be no need for more state legislation to ban synthetic nicotine now that the federal government has added it to the TCA.
Yaël Ossowski
Yael Ossowski, deputy director of the Consumer Choice Center, said that making companies ask permission to sell harm reduction products in the 21st century is “asinine.” 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,” he noted, 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 hardworking American business owners will now be forced to close, depriving millions of adult consumers of harm-reducing options. Many will be forced back to cigarettes,” said Ossowski. “Synthetic nicotine is an innovative method of providing nicotine independent of tobacco, and millions of American adults now use these products as a less harmful method of consuming nicotine. A backdoor bureaucratic power move like this represents a sledgehammer to the men and women of our country who have sought out vaping devices to kick their cigarette habit.”
There is no sell-through period for retailers of synthetic nicotine products if the manufacturer does not file a PMTA with the FDA by May 14. While some manufacturers plan to end sales of their synthetic products by the deadline, as Ossowski suggests, others plan on submitting robust and timely applications. Patrick Mulcahy, CEO and co-founder of Streamline Group, parent to the Streamline Vape Co., wrote in an email that his company has been working toward a solution to navigate the regulatory landscape for newly deemed synthetic nicotine products.
“We have recently contracted with Accorto Regulatory Solutions to manage, submit and deliver a complete set of premarket tobacco [product] applications. To date, their track record of applications submitted have received zero MDOs. Their commitment to submitting a complete and robust PMTA is the level of service Streamline aims to provide the market with our current and future line of products,” he said.
“Streamline’s goal during this process is a commitment to provide full transparency, informational updates and other news related to these regulatory requirements as we progress through the various phases of the PMTA,” Mulcahy stated, adding that market confidence is a top priority for Streamline Group, which was submitting PMTAs for its Juice Head brand e-liquids, disposables and nicotine pouches along with its NIIN brand e-liquid and pouches.
Organized approach
April Meyers, SFATA
April Meyers, owner of Connecticut-based Northeast Vapor Supplies and CEO of the Smoke-Free Alternatives Trade Association (SFATA), told Vapor Voice that her organization believed the industry would have more time to hold discussions with legislators on the Clarifying Authority Over Nicotine Act of 2021 (HR 6286) introduced by Representative Mikie Sherrill in December of last year. SFATA members were aware of the mounting pressure on the subject of synthetic nicotine and had been developing strategies to counter the pressure.
Given the inclusion of vapor in the Prevent All Cigarette Trafficking (PACT) Act in the 2021 omnibus, the nonprofit vapor industry advocacy group was not completely surprised to learn that HR 6286’s language had been included in the 2022 omnibus bill, according to Meyers.
“We went immediately to work educating our members on the issue, executing a call to action and making a volley of calls to sources at the Capitol, including our contacts at the freedom caucus,” said Meyers. “Those sources confirmed that a handful of large vapor companies and several Big Tobacco companies were in support of the measure. We were also informed that the House and Senate votes would move quickly and that there was little opportunity to get the provision removed. This was discouraging, to say the least, but did not dissuade us from acting. This industry has learned to mobilize quickly and has achieved several victories under similar circumstances.”
Meyers said that while the sponsors of the synthetic nicotine rider claimed the intent was to close a loophole on synthetic nicotine-derived products from large companies now popular among youth, the rule, and others like it, are very unlikely to have that intended effect. Instead, she said, consumers using these products as a harm reduction option will suffer alongside all the small businesses that have always operated 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, gray and black markets emerge where there are no regulations requiring safe products or ID checks. The vapor industry is incredibly resourceful,” Meyers said. “SFATA believes our government should have learned its lesson from the 1920s that prohibitionist policies never work. In this country, and particularly, this industry, where there is a will, there is a way. Despite the attempt to bring the vapor industry to heel, adults have been vaping flavored products in the U.S. for [nearly 15 years]. It is delusional to think that will be snuffed out with the signing of a law. Our fear is that this will pave the way to a growing illicit trade market while simultaneously increasing smoking rates across the country as studies have already demonstrated in localities with flavor bans.”
Tony Abboud, VTA
Tony Abboud, president of the Vapor Technology Association (VTA), said that everyone who understands anything about PMTAs knows that an application cannot be filed within the 90-day time frame, particularly because the FDA requires at least six months of scientific data for such an application. He said the new rule could become a de facto ban on synthetic nicotine that would have some unintended consequences.
The VTA hired economic research firm John Dunham & Associates to evaluate the negative economic impacts that a synthetic nicotine ban would have in the U.S., according to Abboud. The results included 16,100 lost jobs, over $800 million in lost wages and $2.5 billion in lost economic output. It would also cost the U.S. more than $500 million in yearly taxes.
Amanda Wheeler
Amanda Wheeler, owner of Jvapes and president of American Vapor Manufacturers, said during the 103rd annual meeting of Vapor Voice’s parent company, TMA, that she hopes the FDA offers “some kind of enforcement discretion” to small businesses, especially those manufacturers that are trying to follow the rules.
“I can only plead with the FDA at this point not to repeat the mistakes of 2020 and 2021, finding an arbitrary reason to toss all of those applications out on their ear. The consequences this time are even more dire,” said Wheeler. “We have this serious handicap on our hands as far as the time frame … I think we need to treat businesses equitably and recognize that there is only so much that people can do in 60 days. And enforcement discretion would be the thing that’s most helpful to prevent companies from having to look for an alternative solution.”
