The U.S. Food and Drug Administration today stated it has made determinations on more than 99 percent of the nearly 26 million deemed tobacco products for which premarket tobacco products applications (PMTAs) were submitted. The agency has said previously that reviews for some of the most popular vaping products may take until the end of the year.
The FDA also announced it issued a refuse-to-accept (RTA) letter on Feb. 21, to one applicant notifying a company that their PMTAs, which are associated with approximately 17 million individual tobacco products, do not meet the acceptance requirements outlined in FDA’s regulations.
“The applications were for a grouped submission of e-liquids in varying size, nicotine strength, and flavor combinations, each of which was treated as an individual product application according to existing premarket review processes,” the FDA wrote in a statement.
The agency’s overall determinations include authorizing 23 new e-cigarette products and devices, and issuing refuse to accept (RTA) letters, refuse to file letters, or marketing denial orders for millions of products.
The data includes determinations on applications for nearly 6.7 million products received by the Sept. 9, 2020, deadline, more than 18 million products received after the Sept. 9 deadline, and applications for nearly 1 million non-tobacco nicotine products submitted by May 14, 2022, in accordance with the new federal law passed in April 2022.
Under a federal court order, manufacturers of deemed new tobacco products that were on the market as of the deeming rule’s effective date (Aug. 8, 2016) were required to submit premarket review applications by Sept. 9, 2020.
Registration is open for U.S. Food and Drug Administration’s upcoming public oral hearing on April 12, 2023, from 9:30 am to 5 pm.
The hearing is an opportunity for the public to verbally comment on the agency’s proposed rule “Requirements for Tobacco Product Manufacturing Practice.” The FDA is proposing new requirements for vaping and other tobacco product manufacturers regarding the manufacture, design, packing and storage of their products. Registration also includes a “listen-only” option for those who want to attend the session but do not want to request to speak.
Speaking spots are limited, and the FDA says it cannot guarantee that it will be able to accommodate all requests. Groups and organizations should select a single spokesperson to help the agency hear as many different perspectives as possible. While speaking spots are limited, listening spots are unlimited. Registration to provide oral comments will close on March 31, 2023.
The oral session will be recorded, and a transcript will be added to the docket of the proposed rule.
The U.S. regulatory agency will seek input on the proposed rule from both its advisory committee and the public.
The U.S. Food and Drug Administration is proposing new requirements for tobacco product manufacturers regarding the manufacture, design, packing and storage of vaping and other tobacco products.
The proposed requirements would help protect public health by, among other things, minimizing or preventing contamination and limiting additional risks by ensuring product consistency, according to an FDA statement.
“While no tobacco product is safe, this proposed rule is intended to minimize or prevent additional risks associated with these products,”
Brian King / Credit: FDA
said Brian King, director of the FDA’s Center for Tobacco Products. “Once finalized, it would establish requirements for tobacco product manufacturers that will help protect public health.”
The proposed new requirements would help manufacturers comply with the Federal Food, Drug, and Cosmetic Act by helping minimize or prevent the manufacture and distribution of tobacco products contaminated with foreign substances—such as metal, glass, and plastics—which have been found in tobacco products. T
The proposed rule would also help address issues related to inconsistencies between e-liquid product labeling and the actual concentrations in e-liquids, “Such variability can be misleading to consumers, potentially intensifying addiction and exposure to toxins,” the agency states.
The proposed rule would also establish several requirements related to the identification, tracing and corrective actions for tobacco products that don’t meet specifications or are contaminated, including for tobacco products that have already been distributed.
In the event of an issue, these requirements would require manufacturers to take corrective actions, which may include conducting a recall.
The proposed requirements apply to manufacturers of finished and bulk vaping and other tobacco products. As laid out in the proposed rule, a finished tobacco product is a tobacco product, including any component or part, sealed in final packaging; for example, an e-cigarette, a pack of cigarettes or a can of moist snuff.
A bulk tobacco product is a tobacco product that isn’t sealed in final packaging, but is otherwise suitable for consumer use.
The proposed rule establishes a framework for manufacturers to adhere to, including:
establishing tobacco product design and development controls;
ensuring that finished and bulk tobacco products are manufactured according to established specifications;
minimizing the manufacture and distribution of tobacco products that don’t meet specifications;
requiring manufacturers to take appropriate measures to prevent contamination of tobacco products;
requiring investigation and identification of products that don’t meet specifications to institute appropriate corrective actions, such as a recall; and
establishing the ability to trace all components or parts, ingredients, additives and materials, as well as each batch of finished or bulk tobacco product, to aid in investigations of those that don’t meet specifications.
The FDA will hold a public oral hearing on April 12 to gather additional comments from stakeholders, including industry, the scientific community, advocacy groups, and the public.
The proposed rule also will be available for public comment for 180 days. The agency will review all comments as part of the rulemaking process for this foundational rule.
“We remain committed to transparency and stakeholder engagement, including providing clarity to industry so that they are equipped to comply with the law,” said King. “We encourage all interested individuals and organizations to participate in the rulemaking process. When the public submits a comment based on sound grounds, that can make an important difference in the agency’s decision-making.”
The FDA will also hold a meeting of the Tobacco Products Scientific Advisory Committee (TPSAC) on May 18 to seek recommendations from the agency’s outside panel of experts on the requirements laid out in the proposed rule. As part of the TPSAC meeting, the public will have an opportunity to make oral presentations. The FDA intends to make TPSAC meeting materials available on its website no later than 48 hours before the meeting.
The U.S. Food and Drug Administration has posted a new webinar to help manufacturers and vape shop owners respond to warning letters from the agency’s Center for Tobacco Products (CTP).
The webinar outlines the appropriate items for a response to a warning letter, which should be received by FDA within 15 business days. The webinar also includes an explanation of proper documentation concerning corrective actions that entities have taken.
There may soon be a licensed medicinal inhaled nicotine product on the market if Qnovia finds success.
By Timothy S. Donahue
The story of the vaping industry tends to be dominated by two countries—the United States and the United Kingdom. In the U.S., the world’s largest vaping market, misinformation and a regulatory roller coaster continue to rattle the business of electronic nicotine-delivery systems (ENDS). Meanwhile, in the U.K., vaping products are being embraced as a harm-reduction tool to end the use of combustible cigarettes.
Elsewhere, the gamut of vaping regulations ranges from complete bans to minimal rules. There has not been any advocacy group, research project or product development that has been able to bring global regulators under one unified ENDS umbrella.
Many experts have said over the years that licensing ENDS as medicinal products could lend credibility to vaping products and their tobacco harm reduction potential. Approval from both the U.K.’s Medicines and Healthcare products Regulatory Agency (MHRA) and the Center for Drug Evaluation and Research (CDER), the drug approval division of the U.S. Food and Drug Administration, could provide consumers with confidence that ENDS have the potential to be an effective nicotine-replacement therapy (NRT) product.
Although several media outlets reported that Johnson & Johnson’s Nicorette QuickMist is the first medically licensed vaping product, it isn’t a vaping product. It’s a mist sprayed into the mouth and is not inhaled. One product, however, does have the potential to make the dream of a medicinal ENDS product a reality. U.S.-based Qnovia is presently working with both the CDER and the MHRA to bring its RespiRx nicotine-containing cessation device to market.
Qnovia’s goal is for RespiRx to be the first inhaled prescription smoking cessation therapy product, according to Qnovia CEO Brian Quigley. Instead of using heat to create vapor, the RespiRx device uses an orientation-agnostic vibrating mesh nebulizer. The aerosolizing engine is nothing like a traditional e-cigarette that heats a coil to atomize nicotine based in PG and/or VG.
RespiRx is activated when a user inhales on the device. To aerosolize the nicotine, it sends an electrical current that causes the perforated piezo mesh to vibrate more than 100,000 times a second. “It’s that vibrating action of the mesh that then forces the liquid to the holes, creating an aerosol that appears vapor-like, allowing it to be inhaled,” says Quigley. That, he says, is fundamentally different from a traditional e-cigarette product, where the heating process can create undesired thermal byproducts.
RespiRx uses proprietary software to deliver a precise dose of nicotine. Every time it’s activated, the device fires for three seconds and delivers a targeted dose of the drug. The base is reusable and serves as the housing for the battery and software. The RespiRx nebulizer sits within the pod that houses the nicotine drug product.
“The nebulizing unit (cartridge) gets replaced by the patient every one to two days. That interface means that the patient doesn’t have to clean the nebulizer,” explains Quigley. “The biggest challenge with other vibrating mesh products is that they require cleaning if used over an extended period. We’re mitigating that through the design of the interface. There is no cleaning required. We do believe that this will result in RespiRx having a very long use life.”
Mario Danek, Qnovia’s founder and chief technical officer, agrees that eliminating the cleaning requirement was a priority. “The idea was to create a technology that emulates the form factor of a successful high-adoption consumer product but that is imbued with technologies that would pass CDER’s stringent standard for safety—combined with Qnovia’s purposeful design features, it should bring patient adherence and quit rates to new highs, which historically have been found lacking in NRT,” he says. “Additionally, from a drug delivery platform perspective, those CDER-aligned device safety requirements are just as imperative to Qnovia’s API expansion strategy into other indication areas.”
RespiRx is a “step-down” therapy, like many NRT products. However, instead of buying different pods with varying levels of nicotine, Qnovia’s device has a dosage-monitoring system programmed into the device. Uniquely, the use regimen is determined based on how much a smoker is smoking, says Quigley. For example, a one-pack-a-day smoker would start with 20 doses per day. The two-pack-a-day smoker would start with 40 doses per day.
“Then the device will, over the 12 weeks, gradually reduce the available number of doses to that patient. It is a much more manageable step-down over the 12 weeks, unlike currently available cessation methods. And the device itself will prevent the patient from using more than they’re supposed to use,” says Quigley. “Patients would also have the on-device LCD screen interface to help them understand how to use their doses. That, too, is another benefit of our product versus the existing smoking cessation therapies.”
Brian Quigley
Every smoker smokes differently. One smoker may have their first cigarette after their morning coffee. Another may have to light up the moment they wake up. Quigley says that Qnovia patients can use their daily doses to replace each occasion where they’re used to having their combustible cigarette. They have hand-to-mouth action. They get reinforcements to those behavioral cues that smokers have become accustomed to.
“With a piece of gum or a patch, if you have a patch on and you’re having your cup of coffee and you’re fighting through your cravings, it just doesn’t work. I think there’s a lot of benefits to this type of therapy to really help the patient replace their occasion when they need to smoke and then stick with that 12-week step-down program,” says Quigley.
Choosing sides
In the U.K., Quigley says the process to become a medicine is less challenging than in the U.S. “Whereas in the U.S., we have to go through a pretty rigorous process and really our competition is once that patient decides they want to try to quit smoking [and] we’re competing against the existing NRTs, which every smoker has tried. Consumers know that none of them are as effective as an inhalable product,” he says.
If RespiRx decided to be a tobacco product instead of medicine in the U.S., the device may have already been on the market. The FDA’s premarket tobacco product application process is less stringent than the CDER approval process. However, drugs gain approval all the time, while the FDA has approved only 23 vaping products for market, and most of those are technologically obsolete. An NRT comes with less baggage than a tobacco product, and as far as the FDA’s Center for Tobacco Products (CTP) is concerned, vaping products are tobacco products.
“I think the unfortunate reality facing reduced-risk products is that FDA on the CTP side—they’re in a very tough spot. The industry is kind of stuck in the middle where, yes, the FDA needs to review these applications and approve reduced-risk products, but over the long term, I think FDA will ultimately continue to constrain that industry,” says Quigley. “Ultimately, I think the long-range path of CTP will be to continue to tighten regulations on all tobacco products. That would be a very challenging environment. That space presents a lot of risk.”
While a much longer and more expensive process, Quigley says the CDER standard is straightforward. It’s about safety and efficacy. It’s a balance between scientific risk and regulatory risk. When the CDER asks a question, it usually requires a study to answer. Studies can be very expensive. “I think that another potential challenge will be that we’ll generate data, and we expect the FDA will be very conservative,” he says. “They could ask us questions that require us to generate additional data that we didn’t think we had to generate. But our view is that we’re going to do this right. If they need data, we’re going to generate it for them. The biggest risk is really the time and money to get through the approval process … but I do believe that we are taking a proactive scientific approach.”
For Qnovia, the premise that the CDER must be more directly involved with a company working on a new drug than the CTP needs to be when working with the e-cigarette industry was important. Quigley says that he also believes that having less harmful vaping products on the market available to consumers is important in the fight to end combustible tobacco use. He says having e-cigarettes available to former or current smokers who want to continue to have nicotine be part of their life is important. But for Qnovia, its client base is those smokers who are saying they want to end their addiction to nicotine.
“CDER, for example, has timelines it must adhere to. When we give CDER information, they stick to these timelines. I think it’s a more responsive center than CTP needs to be with e-cigarette manufacturers,” explains Quigley, adding that the company likes the engagement opportunity with the CDER to advance a potential breakthrough therapy for smoking cessation. “The conversation we have with FDA on helping to provide more effective cessation tools is very different than a conversation a tobacco company would have. I do think that we have the opportunity to be viewed as an ally with FDA in their fight against smoking. We’re trying to help solve a problem that is important.”
Mario Danek
One of the main issues that the FDA has with vaping products is heat. E-liquid is heated, and that heating process has the potential to create harmful and potentially harmful constituents in the vapor. Quigley says that this is why he doesn’t ever see a vaping product with an atomizer that heats the liquid to vaporize being approved as an NRT product. While e-cigarettes are surely less harmful than combustible cigarettes, there are still potential constituents in the e-liquid aerosol, and the CDER would have a problem approving a vaping product with the potential to have those constituents.
Qnovia is preparing to submit its investigational new drug application to the FDA. It also expects to begin human clinical trials this year, according to Quigley. Ultimately, Qnovia’s goal is to have its new drug application, its final drug application, submitted to the FDA in 2025.
“The IND, basically, is where we give them all of our safety data, all of our drug manufacturing and device characterization data. And after that application is submitted, once the FDA gives us the approval, then we can begin human clinicals,” says Quigley. “And we have a phase one, phase two and phase three human clinical plan that we will have to execute.”
A pharmaceutical company seeking FDA approval to sell a new prescription drug must complete a five-step process: discovery/concept, preclinical research, clinical research, FDA review and FDA postmarket safety monitoring. Importantly, a major difference between the CTP and the CDER pathways to market is that drug applicants have safety standards that e-cigarette manufacturers don’t have. For example, for RespiRx, the container that holds the nicotine needs to be sterilized. It needs to be filled aseptically in an ISO 5 cleanroom environment. The vaping industry would only require an ISO 6-certified lab.
“I think another element is our airpath safety. It’s something that FDA really cares about on the drug side. When the patient is actually inhaling on the device, not only the aerosol but even the breath path, where they’re drawing air from, has to be totally sealed off and isolated from electronics and other materials,” says Quigley “That’s not the case with standard e-cigarettes. Everything, the breath-activation function and all the electronics have to be sealed off entirely from the drug-containing reservoir and the patient’s airpath. These are more stringent safety requirements that have forced us to do extra work from a design perspective and a safety perspective.”
Forward thinking
Qnovia was founded in 2018 in Los Angeles by Danek as Respira Technologies. Danek invented the underlying technology. He rebranded the company as Qnovia last year. The company also moved to Richmond, Virginia, in part because that state offers a more business-friendly environment, according to Quigley, whose tobacco career included a six-year stint as CEO of Altria’s U.S. Smokeless Tobacco Co. subsidiary.
In addition, many of the partners the company works with are on the East Coast. Qnovia contracts with a Boston manufacturer to make its device and a firm in Pennsylvania to create the medicine administered through the device.
One controversial aspect of e-cigarettes is unlikely to be a problem for Qnovia: The role RespiRx is to play in a medical context offers an opportunity to make use of flavors. Quigley says flavors could potentially help a smoker make the transition from combustibles and stick through the therapy and ultimately quit.
“I think that the lens is those flavors; it just becomes a safety question. Which is, you just have to make sure that whatever flavors you wanted to include, you’re actually generating the safety data to support new questions of safety by including those flavors. You have to check the safety box,” says Quigley. “E-cigarettes or e-vapor products are a different experience than what our smoker is used to, and flavors play or can play an important role in helping smokers switch to that reduced-risk platform.
“There’s also a lot of data that show that flavors are an important part of helping smokers move to reduced-risk products. But now the industry has been put in a very tight, constricting box. Over time, hopefully, that will kind of correct itself, but it’s going to have to happen with data. I think that the industry understands that—regulators and public health officials look at flavors as a youth appeal issue.”
The industry now must figure out how to ensure that it’s not creating a youth appeal issue but still creating a product that is going to be appealing to a smoker trying to switch to reduced-risk products, according to Quigley. “I think it’s going to be a long, slow road, but vapor products will continue to be a part of the reduced-risk product landscape in the U.S., but I think it’s going to be challenging,” he says.
RespiRx is expected to hit the market as a prescription-only treatment. Qnovia is also interested in exploring how the technology can be used for asthma, pain management, vaccines and other applications. As far as using synthetic nicotine, Quigley says it is not out of the question but says he is concerned that currently, the FDA doesn’t know enough about synthetic nicotine to be able to approve a synthetic product.
“We’re using pharma-grade nicotine. It is tobacco derived. I think with synthetic nicotine, the FDA may have lots of questions whereas they have a deep body of evidence and understanding of tobacco-derived nicotine,” says Quigley. “However, if there was data to show that synthetic nicotine is safer because it in no way can have any kind of nitrosamines, for example, it’s something we could consider in the future with strong safety data.”
In a long suspected move, Altria Group Inc. is in advanced talks to buy e-cigarette manufacturer NJOY Holdings Inc for at least $2.75 billion, the Wall Street Journal reported on Monday, citing people familiar with the matter.
The deal for NJOY, one of the few non-tobacco-company-affiliated vapor makers whose products have received a marketing order from the U.S. Food and Drug Administration, could be announced as soon as this week, the report said, adding that the talks could still fall apart.
It’s reported that the proposed deal includes an additional $500 million earnout if regulatory milestones are met.
In October Juul was readying to file for Chapter 11 bankruptcy, while searching for an alternative – such as a sale, investment or loan,
In July, NJOY reportedly hired bankers for a possible sale of the company, adding that the privately held firm is likely to be valued at up to $5 billion.
Some manufacturers of e-liquids could soon be paying nearly $20,000 per violation for selling vaping products without approval. Today, the U.S. Food and Drug Administration announced it has filed civil money penalty (CMP) complaints against four tobacco product manufacturers for manufacturing and selling e-liquids without marketing authorization.
This marks the first time the regulatory agency has filed CMP complaints against tobacco product manufacturers to enforce the Federal Food, Drug, and Cosmetic (FD&C) Act’s premarket tobacco product application (PMTA) process.
The FDA previously warned each of the companies that, by making and selling their e-liquids without marketing authorization from the FDA, they were in violation of the FDA’s PMTA requirements and that failure to correct these violations could lead to enforcement action, such as a CMP, according to a press release.
Despite the agency’s warning, the companies continue to make and sell their unauthorized e-liquids to consumers.
“Holding manufacturers accountable for making or selling illegal tobacco products is a top priority for the FDA,” said Brian King, Ph.D., M.P.H., director of the FDA’s Center for Tobacco Products. “We are prepared to use the full scope of our authorities to enforce the law—especially against those who have continued to violate the law after being warned by the agency.”
As of Feb. 21, the FDA has filed CMP complaints against the following four manufacturers:
BAM Group LLC doing business as VapEscape
Great American Vapes LLC doing business as Great American Vapes
The Vapor Corner Inc. doing business as Vapor Corner Inc., The Vapor Corner, and Vapor Corner
13 Vapor Co. LLC doing business as 13 Vapor
Currently, under the FD&C Act, the maximum CMP amount is $19,192 for a single violation relating to tobacco products. The FDA typically seeks the statutory maximum allowed by law and is doing so in these four cases.
The companies the FDA has filed CMP complaints against can pay the penalty, enter into a settlement agreement, request an extension of time to file an answer to the complaint, or file an answer and request a hearing. Companies that do not take action within 30 days after receiving the complaint risk a default order imposing the full penalty amount.
“These latest enforcement activities are part of a comprehensive approach to actively identify violations and to deter illegal conduct,” said King. “These actions should be a wakeup call that all tobacco product manufacturers—big or small—are required to obey the law.”
Manufacturers that continue to violate the law risk subsequent enforcement, according to the FDA. In addition to CMPs, the agency also has the authority to take other enforcement action, as appropriate, including seizures, injunctions, and criminal prosecutions.
A new House bill would require the FDA to update its enforcement guidance to prioritize its enforcement against disposable electronic nicotine delivery system (ENDS) products.
U.S. Rep. Sheila Cherfilus-McCormick (D-Fla.) introduced the bill that would also close a legal loophole that allows for the sale of flavored e-cigarettes if the delivery device is disposable.
“Too many of our youth are forming nicotine addictions, increasing their risk of future addiction to other drugs,” Cherfilus-McCormick said in a news release. “I am even more troubled by the fact that Chinese manufacturers and suppliers are flooding the U.S. market with unregulated, harmful substances that are altering our children’s brain development and lives, according to a release.
The bill, known as HR 901, was referred last week to the House Committee on Energy and Commerce for review and consideration. The bill wouldn’t ban disposable vapes or give the FDA additional authority if passed.
The bill could find support from some House members and tobacco companies. Last week, R.J. Reynolds filed a formal FDA citizen petition asking the agency to prioritize enforcement against disposable vapes.
The new director of the U.S. Food and Drug Administration’s tobacco science division is Matthew Farrelly, former chief scientist and director of the Center for Health Analytics, Media, and Policy for RTI International.
In an announcement, The FDA’s Center of Tobacco Products (CTP) stated that Farrelly’s extensive work in the field of tobacco and nicotine science for more than 25 years, and being recognized internationally as an expert with proven leadership and organizational management skills will help him succeed as the director of the CTP’s Office of Science.
“He has led or been involved with numerous scientific endeavors related to tobacco control policies and regulatory approaches, including those related to graphic health warning labels, excise taxes, smoke-free policies, quitlines, state tobacco control programs, retail advertising, and flavored tobacco products,” the release states. “He has also extensively researched the influence of mass reach health campaigns, including FDA’s The Real Cost.”
Farrelly also has authored or co-authored over 120 articles in peer-reviewed scientific literature, which have been cited over 10,000 times. He earned his Ph.D. in Economics from the University of Maryland at College Park.
Farrelly will replace Matt Holman, who left the position last year to Philip Morris International. Holman was hired in 2017 and took over for David Ashley.
The U.S. Food and Drug Administration has submitted a new timeline for its expected finish to the review of premarket tobacco product applications (PMTAs) in a court-mandated status report. As previously reported by Vapor Voice, the agency doesn’t expect to complete PMTAs for the most popular vaping products until the end of the year.
In prior status reports, the FDA indicated that it expected to finalize actions on all covered applications by June 30, 2023. Filed with the Maryland Federal District Court on Jan. 24, 2023, the agency’s fourth report states that it now expects to have taken action on PMTAs as follows:
52 percent of Covered Applications by March 31, 2023
53 percent of Covered Applications by June 30, 2023
55 percent of Covered Applications by Sept. 30, 2023
100 percent of Covered Applications by Dec. 31, 2023
The FDA is expected to give its next status update to the court on April 24.
The FDA is under a Maryland Federal District Court order to file regular status reports on the agency’s review of PMTAs. The court case that ended in a court-imposed deadline for the FDA was filed by health groups seeking a timeline for the review of the PMTAs that were filed with the agency by Sept. 9, 2020.
In the order requiring the FDA to submit status reports, the Maryland court stated that covered applications are limited to applications for products that are sold under the brand names JUUL, Vuse, NJOY, Logic, Blu, SMOK, Suorin or Puff Bar. Additionally, any product with a reach of 2 percent or more of total “Retail Dollar Sales” in Nielsen’s Total E-Cig Market & Players or Disposable E-Cig Market & Players’ reports.
The original completion date was Sept. 9, 2021, however, the FDA was unable to meet it due to the extremely large number of PMTAs filed by manufacturers.
The most recent delay is partially being caused by ongoing litigation and by the agency accepting some amendments to already filed PMTAs that the agency now needs to review, according to the report.
