Tag: PMTA

RAI Submits Applications for Velo Pouches

Photo: RAI
Reynolds American Inc. (RAI) has submitted a group of premarket tobacco product applications (PMTAs) to the U.S. Food and Drug Administration (FDA) seeking orders authorizing the marketing of Velo pouches. A grant of these marketing orders would allow these products to remain on the market after FDA review.
Velo is the group’s brand for modern oral products, designed to provide adult tobacco consumers with innovative alternatives to traditional combustible and smokeless tobacco products. A small, white pouch made with nicotine derived from tobacco but containing no tobacco leaf, Velo is placed between an adult tobacco consumer’s gum and lip. Unlike traditional dip, there is no need to spit the product and no lingering smell. The submitted group of applications includes varying nicotine strength levels and two flavors for Velo pouch products.
As with prior PMTA submissions, these commercially-proprietary applications provide the FDA with product analyses, information on human health risks, and assessments showing that these Velo pouches are appropriate for the protection of public health—including assessments on users and nonusers of tobacco products.
James Figlar (Photo: RAI)
“Velo represents an innovative space for us to identify what adult tobacco consumers want next—thus submitting the final group of Velo brand PMTAs was a great next step to help ensure adult tobacco consumers have consumer-acceptable products available that provide them with lifestyle choices and varying nicotine levels that make sense,” said James Figlar, RAI’s executive vice president and head of scientific and regulatory affairs, in a statement. “As the FDA begins evaluation of our industry’s collective PMTAs after the Sept. 9 deadline, it is critical that our chief regulatory agency continues to enforce against illegally marketed tobacco products introduced after Aug. 8, 2016.”
The PMTAs for Velo pouches are part of Reynolds’ ongoing submissions to the FDA seeking marketing orders following applications for Velo lozenges and Vuse Vibe, Ciro and Solo electronic nicotine delivery systems. The PMTA process allows the FDA to evaluate whether these products should remain on the market as part of the FDA’s public health mission. While these applications include relative risk information, the marketing orders sought make no claims of modified risk.
September 2, 2020
FDA to List PMTA Applicants

Mitch Zeller
The U.S. Food and Drug Administration (FDA) plans to publicly list all e-cigarette manufacturers that want permission to sell their products in the U.S., reports Bloomberg, citing a blog post published on Monday by Mitch Zeller, director of the FDA’s Center for Tobacco Products.
The move could help consumers and retailers spot illegal products.
Vapor product manufacturers who want to keep their products on the U.S. market will have to file requests for marketing authorization with the FDA by Sept. 9.
The FDA has received applications for about 2,000 e-cigarettes and other newly regulated tobacco products already. There are more than 400 million eligible items that would need to apply to stay on the market, according to Zeller.
Products whose applications were filed on time will have a one-year grace period to stay on the market while the FDA reviews them, unless the agency rejects the request. Large manufacturers, retailers who could be liable for selling illegal products and public-health groups had pushed the FDA to make the process more transparent.
In a letter to the FDA, several retail associations had asked the agency to release a list of manufacturers that have PMTAs on file so retailers can know what electronic nicotine delivery system (ENDS) brands can remain on store shelves.

September 1, 2020
A Journey, Not a Destination
Photo: BNS
Navigating successful post-market requirements for ENDS products
By Yvonne Wilding
This month marks the deadline for submitting premarket tobacco applications to the U.S. Food and Drug Administration (FDA). Many organizations have worked diligently to ensure their submissions are as complete and robust as possible. Their goal is to ensure that they are sufficiently complete to allow acceptance for filing and, following substantive review, that the product may be granted a market order by the FDA, allowing it be sold in the United States. By early September, hundreds of PMTAs for electronic nicotine-delivery systems (ENDS) had been submitted to the FDA, and a number are currently undergoing substantive review.
However, in this article I will remind applicants that their obligations do not stop at PMTA approval but persist for the entire life cycle of the product in market—and products can be removed from market potentially more easily than they can be brought to it.
During its PMTA review, the FDA extensively evaluates the provided experimental data to make a risk-benefit assessment of the new product and ascertain its suitability to be designated as “appropriate for the protection of public health” (APPH).
This includes scrutinization of the quality and compliance aspects of the manufacturing processes and review of extensive research information generated on the specific product to allow the FDA to evaluate any potential public health risks associated with the product. The research aspects are compiled by the applicant into different modules of the eTobacco Technical Dossier and include chemistry and manufacturing, toxicology risk assessment and clinical and human experience evidence.
There will be a series of investigations in human volunteers to look at the pharmacokinetics (PK) of the product and its delivery of nicotine compared to comparator products. The PK profile of a product has the potential to affect the abuse potential—i.e., how easily someone may become addicted to nicotine. In addition, there will typically be several human behavior studies to check that the users can operate the device safely and effectively and to assess their preference for this product against competing products. Additionally, there is a significant amount of research done in never-smokers to ascertain how likely they are to start smoking with this product. The numbers of volunteers in the studies are often very large and care is taken to look not only at a representative U.S. population from their demographics but also to incorporate a significant number of young adults in order to be able to make extrapolations to a youth (11–18 years of age) population.

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The research data provided to the FDA also includes extensive data on the performance of the device in laboratory-controlled conditions and its delivery of nicotine in each puff under different device settings and different coil components. Stability of the product on storage and extractables and leachables are measured, and quantitative data on the discharge of harmful and potentially harmful constituents (HPHCs)—a list of 33 chemicals of most toxicological concern detailed in the FDA guidelines) is collected. The toxicology and the chemistry data are linked to consumer behavior information and topography data to indicate how a consumer will use the product, enabling the estimation of the likely exposure to potentially hazardous aerosolized constituents and hereby the risk-benefit of this new product can be ascertained.
Assessing the actual product though, is only part of the information required. The product must also be assessed for risk-benefit alongside data from existing relevant tobacco-containing products, much of which is obtained from scientific publications. These comparator products would typically be combustible cigarettes or similarly performing ENDS. It would be wrong to assume that ENDS are without risk, but in a PMTA, the risk relative to other comparator products, e.g., combustible cigarettes, is described. Based on this assessment of these actual and relative risk estimates, the FDA will decide on whether the product is APPH. This approval process can be considered the first step of the journey.
There are several regulatory documents published by the FDA Center for Tobacco Products (CTP). These include Guidance for Industry and Proposed Rule, both of which have sections on post-marketing requirements, although most detail is provided in the Proposed Rule (Federal Register Vol. 84, No. 186, 25 Sep. 2019, Subpart D – Postmarket Requirements section, $1,114.39–$1,114.41).
Having been granted a market order from the FDA, there is an explicit ongoing commitment for each approved SKU to collect and provide information and submit it for regulatory review. Following each review, the FDA will consider whether it is appropriate that the product is maintained in market. Reasons why the FDA may decide to remove a product from market could include any of the following: the product is no longer considered to be APPH; there is inaccurate representation of factual data, the applicant has not set up a system for maintaining records and/or fails to make appropriate records and submit reports.

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The post-marketing updates required by the FDA can be put into three main categories: changes to manufacturing processes and controls; changes to the health risks associated with the product; and sales, distribution and marketing information.
Periodic reports need to be submitted to CTP within 60 calendar days of the reporting dates which will be specified in the applicant’s marketing order and must include the following:
Manufacturing and processes
A description of changes to the manufacturing, facilities or controls during the reporting period
An explanation of why the changes were made and why these change do not result in the generation of a new tobacco product that is different from the one for which the original order was granted
Health risks
An inventory of ongoing and completed studies by or on behalf of the applicant that have not previously been reported
Full reports of information published or known, or which should be reasonably known, to the applicant concerning scientific investigations and literature about the tobacco product that have not been previously reported
Significant findings from publications not previously reported
A summary and analysis of all serious and unexpected adverse experiences reported to the applicant or that the applicant is aware of
A statement of any changes to the overall risk associated with the product and a summary of the health risks, including the nature and frequency of the adverse experience and potential risk factors
Sales, marketing and distribution
A summary of sales and distribution of the tobacco product for the reporting period to include:
Total U.S. sales and demographic characteristics of purchaser
Specimens of labelling and detail of any changes
Full-color copies of all advertising material used with dates of dissemination
A description of advertising and marketing plans
Actions taken to restrict youth access and limit youth exposure to labelling, advertising or promotion
Use of social media
Use of partners, influencers or bloggers
An assessment of the impressions left by advertising and audience demographics
In addition to the above categories, there is also a requirement to provide any additional information specified or any additional requests under the terms of the marketing order and an overall assessment of how the product continues to be APPH.
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As well as the requirement for regular submission of post-marketing reports, if there are any serious and unexpected adverse events reported to the applicant, these must be reported to CTP’s Office of Science via the Health and Human Services Safety Reporting Portal within 15 days of the applicant having received the report.
There are strong concerns among the public, health policy makers and government that the potential health benefits of switching smokers from combustible cigarettes to a less harmful way of accessing nicotine may be dramatically offset by young nonsmokers being attracted to vapor devices and through use of these devices drive an increase in nicotine addiction in youth. Smoking volumes of combustible cigarettes have been falling for many years across the world, which will ultimately lead to significant improvements in health, although the evidence will take several years to become apparent. Understandably, there is much enthusiasm that the scourge of tobacco smoking-related diseases may be, if not eliminated, significantly reduced in future generations.
It is in the interest of consumers who may wish to move to a safer form of nicotine intake that PMTA applicants are fully compliant with the post-marketing requirements and continue to work with the FDA and lobbyists to contribute to and maintain an appropriate balance of risk reduction and health benefit realization. If these products, stated to be APPH, are no longer available to consumers, then the consumers’ opportunity to potentially improve their long-term health outlook is diminished.
Many of the larger companies manufacturing ENDS products may have specific regulatory compliance staff and sales and marketing departments that are fully trained, equipped and resourced to deal with the FDA requirements, but for the smaller organizations, without such infrastructure, this resource requirement, skill set, potential complexity and the associated costs, particularly if the organization has a large number of SKUs, can be particularly onerous.
The cost and resource requirements of maintaining established products in market has been recognized in the pharmaceutical industry for a very long time. As pharma companies typically prefer to invest in novel medicine development or in the enhancement of existing medicines to provide patent life extensions, some older, established products are still very successful and so the maintenance of the post-marketing requirements of these products from a regulatory and pharmacovigilance perspective is often outsourced to specialist contract research organizations (CROs) who collect and report this data on behalf of the pharma companies. These CROs can provide the necessary resources, expertise and experience to make this a cost-effective solution.
It will be interesting to see how many ENDS products are successful in receiving a positive market order decision from the FDA only to be subsequently removed from the market as they fail to satisfy their post-market approval requirements, causing these products to be potentially as ephemeral as the aerosols they disperse.

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Yvonne Wilding is director of product safety and compliance at Broughton Nicotine Services (BNS). BNS operates exclusively in the ENDS sector. Its team of scientific and regulatory experts, backed by its in-house, custom-built contract research organization facility, understands customers’ specific challenges and opportunities. With expertise across the U.S. and EU for tobacco products, medical devices and pharmaceuticals, BNS is committed to working with customers to increase the value of their business and advance a smoke-free future. For more information, visit www.broughton.com.
September 1, 2020
Premium Cigar Makers Get Reprieve from FDA

Photo: 13 Motortion – Dreamstime.com
The District of Columbia on Aug. 19 ruled that the U.S. Food and Drug Administration (FDA) cannot enforce premarket review requirements for premium cigars until it considers a “streamlined” process for cigar makers to equate their products to older ones.
The ruling means that premium cigar companies will not have to file for product approval on the Sept. 9, 2020, deadline. This ruling applies to almost all cigars found in humidors across the country except for flavored and infused cigars, which are not considered premium by the FDA.
Companies will not need to file paperwork with the FDA to prove that their products are premium; rather, any company selling a cigar that does not meet the definition of “premium cigar” will be subject to the Sept. 9 premarket approval deadline and will need to file for substantial equivalence or another approval pathway.
The ruling does not require the FDA to enact a “streamlined” process for premium cigars but says it must study the issue and cannot require premium cigars to go through substantial equivalence or another process until after that study is complete.
The ruling came from a lawsuit against the FDA by three cigar trade groups: Cigar Association of America, Cigar Rights of America and the Premium Cigar Association (PCA). “This is another monumental victory for the premium cigar industry,” said PCA’s Scott Pearce. “This comes on the heels of legal victories striking down warning labels for premium cigars.”
August 21, 2020
Regulator Urged to Reject Flavors

Photo: Laboko – Dreamstime.com
As manufacturers of e-cigarettes and certain other tobacco products face a Sept. 9, 2020, deadline to apply to the U.S. Food and Drug Administration (FDA) to keep their products on the market, six leading public health and medical organizations are urging the FDA not to authorize the sale of any flavored products.

“The FDA should not authorize the sale of any flavored tobacco product, including e-cigarettes or e-liquids, because of the clear evidence that flavored products appeal to youth and have driven the current epidemic of e-cigarette use among youth and young adults and the lack of evidence that flavored products help smokers quit,” the groups wrote in a joint statement.

“Research shows that 97 percent of youth e-cigarette users report using a flavored product in the past month, and 70 percent say they use e-cigarettes ‘because they come in flavors I like.’ In contrast, there is no credible evidence that flavored e-cigarettes help adult smokers quit. In a report issued earlier this year, the U.S. Surgeon General concluded, ‘there is presently inadequate evidence to conclude that e-cigarettes, in general, increase smoking cessation,’” the organizations wrote.

The groups also called on the FDA to take prompt enforcement action to remove from the market products for which applications are required but are not submitted by the Sept. 9 deadline.

The organizations that issued the statement are the American Academy of Pediatrics, the American Cancer Society Cancer Action Network, the American Heart Association, the American Lung Association, the Campaign for Tobacco-Free Kids and the Truth Initiative.
August 11, 2020
FDA Accepts Avail Tobacco Application

Photo: Bacho | Dreamstime
Avail Vapor has received its first premarket tobacco product application (PMTA) acceptance from the U.S. Food and Drug Administration (FDA) for its e-liquid nicotine products, reports Vapor Voice.
Blackbriar Regulatory Services led the highly strategic regulatory process for Avail’s submission. The application now moves to the substantive scientific review where the FDA will determine if Avail has scientifically proven that its nicotine vapor products are appropriate for the protection of public health.

James Xu
This is one of numerous applications that Avail plans to file prior to the Sept. 9, 2020 deadline. The products will provide a wide-ranging flavor portfolio to meet the needs of adults seeking alternative choices to combustible tobacco products.

“We started mapping out our regulatory framework and PMTAs in 2015, before nicotine vaping products became subject to the FDA’s tobacco authority,” said James Xu, chairman of Avail.

“We couldn’t be more pleased that the years of hard work, investment and dedication have gotten us to this point. Our end goal is to seek an FDA marketing order, which would allow us to continue to keep our products on the market for those adult smokers looking for alternatives to traditional tobacco products.”
August 11, 2020
Measuring Up

Photo: Broughton Nicotine Services
How instrumentation suppliers and laboratory service providers are supporting customers with their PMTA submissions
By Stefanie Rossel
Although there has been a 120-day extension due to the outbreak of the Covid-19 pandemic, Sept. 9 will definitely be the final day: If a company wants its “recent” tobacco products to remain in the U.S. market, it has to submit a premarket tobacco product application (PMTA) to the U.S. Food and Drug Administration (FDA) by then. In 2016, the FDA announced that all tobacco products not on the market prior to Aug. 8, 2016, would require authorization before entering the market and all products on the market prior to that date would have a grace period during which companies could prepare their PMTAs for submission.
The candidate products will all undergo a several-stage review during which they have to demonstrate with the help of scientific data that they are “appropriate for the protection of public health.” The FDA will consider the risks and benefits of the products not only to the individual but also to the overall population, including whether existence of the product will increase the likelihood of nonusers starting using them. The evaluation also includes reviews of product ingredients, constituents, toxicological profile, health impact, manufacturing and packaging processes as well as labeling.
Tobacco Reporter asked several instrumentation suppliers and providers of laboratory services how they experienced the run-up to the FDA’s extended deadline, which was originally set for May 12, 2020.
“The date for the premarket submission was set well in advance, so there was increased demand but no real ‘rush,’” says Tobias Krebs, managing director of German company Vitrocell, which specializes in in-vitro testing technology.

Ian TIndall
Ian Tindall, head of innovation and marketing at Cerulean, says there has been a noticeable demand for extra testing capacity in the U.S. but that most of this demand was generated in late 2019, and the extension to the submission date had not really been visible.
“The larger companies have had this well organized all the way along, and from our experience, the anticipated rush for testing at the contact research organizations has not been mirrored in a late rush for test equipment,” Tindall explains.
“I should note that the EVALI crisis at the back end of 2019 did generate demand for additional testing of vaping products and a consequent surge in instrument demand, and this did put pressure on the business, but we feel we met all the urgent demands successfully. More recently, some of the focus has moved away from vaping devices towards tobacco-heating products, and we have been increasing supply kits and specialist machines and upgrades for this sector of the industry.”
In February 2019, Cerulean teamed up with Tews, a leading supplier in the field of industrial microwave moisture and density measurement. Cerulean now exclusively markets Tews laboratory devices for the tobacco industry. Based in Hamburg, Germany, Tews also has a U.S. subsidiary. “We can now jointly address emerging requirements for density and moisture testing in the industry and work effectively with clients in this regard,” says Tindall.
Thomas Schmidt
Thomas Schmidt, director of scientific and technical affairs at Borgwaldt KC, a German manufacturer of high-end quality control instruments and precise measurement devices that is part of the Hauni group of companies, notes that the PMTA process was communicated early and the instruments used to generate the data were available. “Besides new developments like our next generation of analytical vaping machines, the NGX series, we have, however, made some modifications to existing instruments—on our LM5SP and LM5SF, for example, which are both intended to collect aerosol in different collections procedures and increased the flexibility in usage to meet the specific demands of certain customers,” says Schmidt.
Broughton Nicotine Services (BNS) has noted a definite increase in demand for its services in the runup to the PMTA deadline, according to Chris Allen, vice president of scientific and regulatory affairs. For many companies, he contends, the PMTA has been the first opportunity to truly characterize and stress test their products.
“This has inevitably led to clients learning more about their products and the need to understand further so that risks can be mitigated and improvements made in the future,” Allen says. “The extension has provided additional time for these companies to perform further characterization and bolster their applications. In addition, we’ve seen a wave of companies who had been delaying the PMTA process or having partial information take advantage of the extension in order to commit to the PMTA pathway.”

Photo: Borgwaldt KC
Heavy workload
Matters are complicated by the FDA’s requirement that applicants file a separate application for each brand variant. For suppliers of instrumentation equipment and labs, this has meant a lot of additional work in recent months. “This has had no impact on our business but has required software development to become FDA compliant,” says Eric Favre, managing director of Sodim, a French company specializing in metrology for the tobacco industry and, like Borgwaldt KC, part of the Hauni group of companies. Sodim has developed a specific device called VPA (vaping puff analyzer). “This device has required adaptations for new formats with specific sample holders,” says Favre.
“The established manufacturers of traditional tobacco products have lots of data available for marked products, which they can provide to the FDA. In [the] case of modified and new products, especially vaping products, the manufacturers were not all aware of what is expected,” Schmidt points out. “These products are newer to the market and do not have sufficient historical data available to refer to. Therefore, we were not surprised that this has led to an increased demand for our next-generation product (NGP) machines and has driven us to develop a new generation of analytical vaping machines, our NGX family and other innovations and modifications within the available Borgwaldt KC portfolio to meet the needs of the market.”
Allen says that although each product is unique, the FDA is accepting “bundled” submissions for multiple products, which enables clients to save cost and tell the “story” of a group of products. “Despite the ability to include multiple products under one submission, the level of analytical testing has been significant,” he says. “We had been planning our expansion in line with the PMTA since 2015 and moved into our new dedicated nicotine products facility in 2018.”
The expansion project was completed in January of 2019 following an investment of £10 million ($12.41 million) into people, facilities, analytical equipment, software development and quality standard certification. The company recruited more than 70 new team members, not only within the analytical function but also across clinical, nonclinical and project management.
Vitrocell observed increased demand for systems with higher output. “We needed to increase our development activities but could tie in new orders in our regular production scheme,” says Krebs.
“We are fortunate that in the way we have set up our supply chain and manufacturing facility we can redeploy resources quickly and keep customers satisfied with extending lead times,” Tindall says. “Some special requests have taken a little longer to fulfill than our standard lead time, but by switching capacity, say, from our standard smoking machines to vaping and THP testing machines, we have managed to meet our delivery commitments. That is not to say we have not met bumps in the road, but the unsung heroes in the back office who keep the production machine running have really risen to the challenge.”

A key part of the PMTA is to understand how your product behaves, what the risks are and therefore what quality control checks need to be in place.
Far-reaching measurements
Testing required for PMTA applications is manifold; it includes the analysis of tobacco and e-liquid constituents, ingredients and additives, especially the 33 substances listed by the FDA as harmful and potentially harmful constituents (HPHCs), smoke and vapor constituents as well as all physical parameters of the products, toxicological assessments and topographic data, notes Schmidt. “We have seen a remarkable increase in interest in our topography products as well as our NGP vaping devices,” he says.
In vitro data play a role in the application too. For Vitrocell, this translated into demand for its exposure solutions. Cerulean witnessed greater interest in its vaping machines, particularly with an accessory that determines the density of the vapor. “We have published a lot of work that shows how this device, primarily designed for showing when an e-cigarette stops effectively forming aerosol, can be used to monitor the full life delivery of aerosol of an e-cigarette device,” Tindall explains. “Beyond measurement is the need from our customers’ perspective for installation and servicing in line with good laboratory practice [GLP], with an installation qualification and an operational qualification step that is properly documented.”
According to Allen, the level of testing required to demonstrate the shelf life of the product, including extractables and leachables, should not be underestimated. “Having the analytical data available is just the start of the process. Conclusions need to be drawn from this data to understand the performance of the product and most importantly to risk assess from a toxicological perspective,” he says. “This is why we saw the creation of the integrated chemistry consultancy and toxicological teams of paramount importance as having these teams on-site enables us to design the analytical studies in line with the end purpose and perform ‘real-time’ risk assessments.” BNS has also developed ToxHQ, a unique internal software tool to complete rapid toxicological screening and risk assessment. The central repository holds chemical data used in e-liquid formulations, including chemical identifiers, properties and classifications, such as HPHC-registered chemicals, Allen says.

Chris Allen
Managing the data
Once the products have been authorized, further measurements will be needed to maintain compliance. “This will be an interesting development over the coming months and as we start to see FDA feedback on the PMTAs,” Allen points out. “It will very much depend upon the product sub-category, e.g., e-liquid, closed system or open device, but the critical point is demonstrating that you have control over the finished product. A key part of the PMTA is to understand how your product behaves, what the risks are and therefore what quality control checks need to be in place as either verification of incoming parts or ingredients, in-process controls or analysis of the manufactured product.”
As an instrumentation supplier, Tindall says the company must recognize that once equipment has been bought, its use might change subtly over time. “We have a mission to ensure that time does not make our products obsolete. Consequently, as part of our product development strategy, we have upgrade paths plotted for most equipment that allows adaptations as regulatory pressures change or research applications and the new products by research demand. One thing beyond ongoing measurement that should not be minimized is the need to ensure that the equipment used is running properly.”
In the course of a PMTA as well as during the control period afterward, massive amounts of data are generated, requiring expert management. Borgwaldt KC’s instrumentation features a data collection tool for this purpose. The company offers a variety of methods for collection, storage and submission of data to the customer’s data management system. “Our products are in compliance with the FDA requirements related,” Schmidt says, “but in general, the quantitative analysis of specific substances is requiring other analytical equipment in the labs.”
Vitrocell offers solutions that enable its systems to be operated with GLP compliance. “Beyond that, data management is performed using the current technology of the customer,” Krebs relates.

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“There is a lot of data generated, and we have worked with a number of customers to ensure that there is a seamless exchange of data with their laboratory information and management systems (LIMS),” Tindall states. “The vast number of LIMS suppliers has meant that we have had to do this on a case by case basis, and we feel we have been successful in this. We are very conscious of the increasing burden of data generation and storage. Our 21CFRpart11 packages, which are available on many of our products, create complex audit trails. The Internet of Things (IOT) and Industry 4.0 initiatives will increase the amount of data on machine performance that is available to an auditor, user or engineer, and this will be the next challenge to face.”
Allen says that the retention of records is critical within any regulatory process. As BNS evolved from its pharmaceutical facility Broughton Laboratories, retention of both hard and electronic data has always been an integral part of the company’s quality management system. “Over the past twelve months, we’ve generated in excess of 200,000 lines of HPHC data for our clients, so effective data management is key. The utilization of LabHQ LIMS, developed by our sister company Broughton Software, including integration with the laboratory instrumentation and dynamic reporting, enables us to manage such large datasets.”
The handful of PMTA approvals to date were granted after long and tedious reviewing processes. Thus far, only three products have received marketing authorization: Swedish Match’s General snus, Philip Morris’ IQOS device and Heatsticks along with two varieties of 22nd Century’s Moonlight cigarettes. What happens when the FDA gets overrun with submissions remains to be seen. Favre expects feedback from the FDA before the end of this year.
“There will be huge amounts of data for the regulators to review,” Schmidt says. “It will be a monumental task to say the least.”
“The FDA [is] undoubtedly going to see a significant number of applications,” Allen comments. “The PMTAs we’ve been working on consist of tens of thousands of pages, so this is going to be a large volume of data for [the] FDA to review. The big question will be how many PMTAs make it through to the review stage, which will impact most on [the] FDA’s resource. Once in substantive review, this very much depends on what additional data is requested by [the] FDA as any major amendment of an application, either by the applicant or at the FDA’s request, would result in a new 180-day review period.”
He concludes: “In the same manner that all regulated industries have had to evolve, the electronic nicotine-delivery systems market will be no different. The PMTA process is simply a starting point, and as the FDA learns more about the products and risks, we’re likely to see further guidance issued—for example, the addition of new analytes and a deeper understanding of other possible chemical reactions and their risks to human health.”
Stefanie Rossel is Tobacco Reporter’s editorial contributor. An experienced trade journalist, she combines sharp reporting skills with in-depth knowledge of the tobacco and vapor industries. Prior to joining Tobacco Reporter, Stefanie was editor-in-chief at Tobacco Journal International, where she worked for a decade. Fluent in English, German and French, Stefanie covers tobacco news around the world. She is based in Germany.

August 1, 2020
Counting Down

Photo: Tobacco Reporter archive
The nicotine industry prepares for a shakeout in the wake of the premarket tobacco product application deadline.
By Kenneth Robeson
Chris Allen
The phrase “time is money” has seldom been more apt for the tobacco industry.
The United States District Court recently granted the Food and Drug Administration’s (FDA) request for an extension of the premarket tobacco product application (PMTA) submission deadline for certain tobacco products, which the FDA requested due to the Covid-19 pandemic. Applications are now required to be filed by Sept. 9, 2020, for many e-cigarettes, cigars and other deemed tobacco products.
What does this mean for the tobacco industry? Several things—from a significant reduction in the products that retailers can place on store shelves to changes in management, manufacturing, R&D and marketing.
“Those working towards a PMTA have benefited most as this has either provided the time to complete existing studies or generate more data,” said Chris Allen, vice president of scientific and regulatory affairs for Broughton Nicotine Services, a privately owned laboratory delivering analytical, scientific and regulatory services for the electronic nicotine-delivery systems (ENDS) industry based in Lancashire, England. “Also, those that are intending to exit the market have a slight reprieve in that they can continue selling their products for an extra 120 days.”
In addition to a significant reduction in the product portfolio, said Allen, manufacturers are coming to the realization that they are going to need to invest “far more” in their quality-management systems as manufacturing guidance evolves. “Although it is not expected the manufacturing regulations will be as stringent as pharmaceutical GMP, it may be significantly higher than the standards that many companies currently work to.”

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‘The reality’
Barnaby Page
“The deadline change was triggered by the Covid situation and requested by the FDA, which stated, among other things, that it had refocused some of FDA CTP staff on other emergency matters related to Covid,” noted Patricia I. Kovacevic, a global legal and regulatory strategist and attorney and the founder of consulting firm Regulation Strategy, which has offices in Tampa, Florida, USA, and London. “While the extra time appears beneficial to the entire industry, the reality is that most clinical studies, testing labs and so on would not have carried on, at least during the three critical lockdown months, April to June.”
Thus, Kovacevic added, there is “a slight benefit” for the industry to have additional time to refine PMTA submissions. “But those who were not ready with the substantive work needed for PMTAs—including various clinical and nonclinical controlled trials—would not see their situation improve much due to the extension.”
“For vapor, it doesn’t substantively change the picture,” suggested Barnaby Page, editorial director of ECigIntelligence, a provider of detailed global market and regulatory analysis, legal tracking and quantitative data for the e-cig, heated-tobacco and combustible-alternatives sector worldwide, and TobaccoIntelligence. “Any company which was not already reasonably well prepared to submit by 20th May is unlikely to be able to make it by 9th September.”
However, Page added, “for those who were close, it will be welcome given that the run-up to the 20th May deadline came at possibly the most disruptive point of the Covid pandemic.”
According to George Parman, director of communications for Altria Client Services in Richmond, Virginia, USA, his company submitted PMTAs for 35 On! Nicotine Pouch products on May 15, and the FDA accepted them for scientific review in the second week of June. They are manufactured by Helix Innovations, an Altria joint venture responsible for the global On! nicotine pouch product portfolio. To support the applications, Altria submitted more than 66,000 pages of documentation, including six primary studies.
The On! nicotine pouches are tobacco leaf-free and available in seven flavors and five nicotine levels. The product line was distributed in over 28,000 stores at the end of the first quarter, including the top five convenience store chains by volume. According to IRI, total oral tobacco-derived nicotine category sales in 2019 grew approximately 275 percent compared to 2018.
“We believe the scientific evidence in these applications demonstrates that the marketing of On! is appropriate for the protection of public health,” said Paige Magness, senior vice president of regulatory affairs for Altria Client Services, in a release. “On! nicotine pouches are a key part of our vision to responsibly lead the transition of adult smokers to a noncombustible future.” The FDA will now undertake a substantive scientific review of the applications.

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‘Subjective term’
Maggie Gowen
And for those companies that will not be ready in time?
“Ready,” Kovacevic believes, “is a subjective term in this context.” Small manufacturers would not have had the resources needed to comply no matter what the deadline might have been “but would have enjoyed the additional time to participate in the market. The top five bestselling products manufacturers were preparing for this moment, some as early as 2013.”
If a company has not amassed the necessary science and assembled the right scientific and regulatory team beginning at least two years ago “or at least early last year, at this point it is too late to consider anything else but a last-moment attempt at litigation if even that were possible,” Kovacevic added.
Maggie Gowen, marketing director for Avail Vapor in Richmond, Virginia, USA, said that ENDS manufacturers who don’t submit a PMTA by the new date will be considered noncompliant. “It will be up to the FDA how they choose to enforce the industry after the deadline. Reasonable regulation is needed based on sound science.”
What comes next cannot help but be influenced by the Covid-19 pandemic, said Broughton’s Allen, who emphasized that ENDS products are designed to deliver chemicals deep into the lungs. “We may not like or agree with regulation, but it is inevitable for any major industry and there to protect us. There is undoubtedly a loss in consumer confidence in the safety of ENDS and no data on the risk of long-term use.”
The regulations, he added, must see to it that everything possible is done to ensure that “the safest of products are on the market [to] protect the public but also the long-term future of the industry.”
At the manufacturer level, ECigIntelligence’s Page predicted, there will be fewer companies, “probably many fewer, clear winners and losers from the PMTA process.” For retailers and consumers, the long-term changes “will not be so dramatic once the short-term shock of many brands disappearing has been adjusted to.” What he termed the “wildcard” is whether the FDA turns out to prefer certain kinds of devices to others. “For example, if it seems to favor open or closed systems. That could have a substantial effect on retailing if some channels end up with lots of legal products and others with many fewer.”
“The immediate—as in 10th September—impact on retailers and consumers is likely to be negligible,” Page said. “We don’t expect the FDA to start enforcement immediately on brands that have not submitted a PMTA application.” Over the longer term, of course, the number of available products will diminish. Just how long that “longer term” is remains an open question. “It could be a few months; it could even be a couple of years.”
Page and his colleagues think it likely that there will be “some tolerance” shown to applicants who miss the deadline “as long as they can demonstrate they are well advanced in preparing their application and are serious about doing it.” Retailers and consumers, however, “can’t really prepare with any confidence. The ball is in the manufacturers’ court right now and then the FDA’s.”

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‘Appetite for enforcement’
Patricia Kovacevic
Most c-stores and major chains primarily sell products manufactured by companies that will have met the PMTA submission deadline, noted Kovacevik, and may legally continue to sell their products “for at least one year thereafter and longer if FDA issues a marketing order following the review of the respective products’ PMTAs.”
At the same time, she noted, the FDA’s “appetite for enforcement is relatively low in general, and the product universe is so vast, with so many SKUs—potentially millions of SKUs—that it will take FDA months, if not years, to figure out what products need to be taken off the market because a PMTA or other type of premarket application was not filed by the respective deadline, and to issue warning letters, then to follow up with more stern enforcement action.”
Another factor to consider is that a new administration in Washington, D.C., might bring “interesting developments not necessarily favorable to the ENDS industry,” Kovacevik added, “and change is always challenging.”
Consumer choice will shrink, Avail Vapor’s Gowen concurred, because not every manufacturer will be able to afford the “enormous” expense of the PMTA process. “There is a big fear that we will see a shift back to deadly combustibles, unfortunately.” There is, she conceded, “a lot of politics in play at the executive, federal, state and local levels.” There is also what she called “an enormous amount” of misinformation about the vapor industry, which “as a whole has been unfairly blamed due to a few bad actors, and that includes the CDC [Centers for Disease Control and Prevention]. If a company wants to remain a player in the marketplace, the hope is they will submit a PMTA by the Sept. 9 deadline.”
And for the remainder of 2020?
“It’s difficult to tell at this point,” Gowen concluded. “It will certainly be an interesting year, as if it hasn’t been interesting enough.”
August 1, 2020
Juul Labs Submits PMTA for Juul system

Photo: Juul
Juul Labs has submitted a Premarket Tobacco Product Application (PMTA) to the U.S. Food and Drug Administration (FDA) for the company’s Juul system, an electronic nicotine delivery system (ENDS) product. The company’s submission includes comprehensive scientific evidence for the Juul device and Juul pods in Virginia Tobacco and Menthol flavors at nicotine concentrations of 5.0 percent and 3.0 percent, as well as information on its data-driven measures to address underage use of its products.
With its PMTA submission, Juul Labs has provided a scientific foundation for the FDA to evaluate whether these products are “appropriate for the protection of the public health” with respect to the risks and benefits to the population as a whole. The application includes detailed scientific data from over 110 studies totaling more than 125,000 pages evaluating the product’s impact on both current users of tobacco products and nonusers, including those who are underage.
As part of the PMTA process, Juul Labs has built a comprehensive research program focused on examining the public health impact of the Juul system. This includes research addressing the harm reduction potential of the product, including its ability to convert adult smokers from combustible cigarettes. This research is supplemented with information on the controlled design and repeatable manufacturing processes associated with the Juul system, as well as data-driven measures to limit unintended consequences to the overall population, including initiation among nonusers.
“In order to earn a license to operate in society, we need to be a science and evidence-based company, engage in open and transparent dialogue with our stakeholders, and take methodical and responsible actions to advance the potential for harm reduction for adult smokers while combating underage use. Our PMTA submission is a key part of that approach,” said Juul Labs CEO K.C. Crosthwaite.
“Juul Labs has committed all necessary resources to deliver the best possible PMTA based on rigorous scientific research and data-driven measures to address underage use,” said Joe Murillo, chief regulatory officer at Juul Labs. “We respect the PMTA process and believe it is the right forum to determine the role ENDS products can play in transitioning and completely switching adult smokers from combustible cigarettes to potentially less harmful alternative products while combating underage use.”
Late last year, the company, under Crosthwaite’s leadership, committed to resetting the vapor category and seeking to work cooperatively with regulators, legislators, attorneys general, public health officials, and other stakeholders to combat underage use and transition adult smokers from combustible cigarettes. As part of that process, the company reduced its product portfolio, halted television, print, and digital product advertising, built up its science and evidence-based capabilities, and supported the U.S. Administration’s final flavor policy for ENDS products, while taking a methodical approach to its global presence.
Juul Labs has built up its science and evidence-based capabilities and will use its research and data to explore additional pathways in other countries. The company will continue to share its research with regulators and the public health community globally through peer-reviewed journals, conferences, and one-on-one meetings.
July 31, 2020
FDA Accepts Premarket Applications for Leap

Photo: Bacho12345 | Dreamstime.com
E-Alternative Solutions (EAS) has received acceptance and filing letters from the U.S. Food and Drug Administration (FDA) for its Leap and Leap Go products.
EAS is now in the substantive review phase of the premarket tobacco product application (PMTA) process. If successful, this phase will result in marketing orders from the FDA authorizing the continued marketing and sale of these products.
“The substantive review is where our months of hard work assembling more than 100,000 pages of evidence will pay off in supporting our proposition that the Leap and Leap Go products are appropriate for the protection of public health,” said Chris Howard, vice president, general counsel and chief compliance officer at EAS.
“We are looking forward to continued collaboration with [the] FDA in the weeks and months to come and remain optimistic that the PMTA process will result in marketing orders.”
July 9, 2020