When the U.S. Food and Drug Administration announced it was delaying premarket tobacco product application (PMTA) decisions, Iowa Attorney General Tom Miller says he become concerned about the impact the regulatory agency’s actions. What worried him was the unintended consequences of pulling from the market less harmful alternatives to combustible cigarettes.
Iowa AG Tom Miller
“We believe the best information available indicates that most youths are not getting e-cigarettes from vape shops and that a significant number of adults are using products from vape shops to move away from combustible cigarettes. Let’s not forget the overwhelming risk to public health: The CDC estimates the burden of tobacco use in the United States is 480,000 lives a year, all of which is due to the use of cigarettes,” Miller wrote in a statement. “We believe in the strong, science-based regulation of alternative tobacco products, and the FDA is the best agency to undertake that task. Policy makers must strike the right balance between making accessible potentially lifesaving lower-risk nicotine products while discouraging use by those who wouldn’t smoke, especially youth.”
On Sept. 9, the FDA finally made its announcement on the fate of millions of PMTAs. However, only small businesses that submitted PMTAs for flavored products got any answers. The FDA issued marketing denial orders (MDOs) to more than 130 companies requiring them to pull an estimated 946,000 products from the market. There were no updates provided on several high-profile submissions, such as those submitted by Juul Labs, BAT and Japan Tobacco International. The agency also offered no response to any submitted open-system hardware products or tobacco-flavored e-liquids.
The following day, the agency increased that number to 168 companies that were issued MDOs for an estimated 992,000 products. According to a press release, the regulatory agency released a revised listing of MDOs that includes 125 company names but not any specific products that were denied.
“We continue to work expeditiously on the remaining applications that were submitted by the court’s Sept. 9, 2020, deadline, many of which are in the final stages of review,” the agency wrote in its announcement. “For premarket tobacco product applications, our responsibility is to assess whether applicants meet the applicable statutory standard for marketing their new products. As we have said before, the burden is on the applicant to provide evidence to demonstrate that permitting the marketing of their product meets the applicable statutory standard.”
The U.S. Food and Drug Administration has now issued 168 companies marketing denial orders (MDOs) for an estimated 992,000 products. According to a press release, today the regulatory agency released a revised listing of MDOs that includes 125 company names but not any specific products that were denied.
Credit: FDA
The remaining 43 are expected to be for companies that did not currently have any electronic nicotine-delivery products on the market. “Several of the MDOs were issued to companies that are not confirmed to be currently marketing their products. To protect confidential commercial information (CCI), we cannot release additional information about those actions,” the agency stated.
Yesterday, the FDA announced it had issued MDOs to more than 130 companies requiring them to pull an estimated 946,000 products from the market. There were no updates provided on several high-profile submissions, such as those submitted by Juul Labs, BAT and Japan Tobacco International. The agency also offered no response to any submitted open-system hardware products or tobacco-flavored e-liquids.
“We continue to work expeditiously on the remaining applications that were submitted by the court’s Sept. 9, 2020, deadline, many of which are in the final stages of review,” the agency wrote in its announcement. “For premarket tobacco product applications, our responsibility is to assess whether applicants meet the applicable statutory standard for marketing their new products. As we have said before, the burden is on the applicant to provide evidence to demonstrate that permitting the marketing of their product meets the applicable statutory standard.”
The U.S. Food and Drug Administration is expected to ask for more time before deciding whether some “e-cigarettes from market leader Juul Labs Inc” and others can be sold in the United States, the Wall Street Journal reported today, citing people familiar with the matter. The FDA is expected today to announce the fate of more than 2 million vaping products that had submitted a premarket tobacco product application (PMTA).
Many businesses have already received marketing denial orders (MDO) from the FDA. Many companies have gone out of business, filed a lawsuit, or switched to synthetic nicotine after receiving MDOs.
Concerning the FDA asking more time for a Juul Labs PMTA review, Greg Conley, president of the American Vaping Association, tweeted, “I want Juul’s five applications to be authorized. I want Reynolds’ two or three dozen applications to be authorized. But to see them likely get more time from FDATobacco after good small businesses spent the last month getting wrecked … Just wrong. Good job, FDA.”
He also tweeted: “If I had the choice between 50,000 flavored vaping products being available or Juul surviving, I’d walk Juul over the plank myself. But that’s not the choice we have.”
After news of the FDA request was reported, Guy Bentley, director of consumer freedom research at the Reason Foundation, tweeted, “The FDA couldn’t get it together to make a decision on one of the biggest companies in this space. Complete shambles.”
No further information was provided. The FDA did not immediately respond to Reuters’ requests for comment.
In August, the U.S. Food and Drug Administration issued 29 warning letters to firms it says were manufacturing and selling unauthorized electronic nicotine delivery system (ENDS) products. The agency advised the companies that selling products which lack a marketing authorization is “illegal and therefore they cannot be sold or distributed in the U.S.” The companies did not submit a premarket tobacco product application (PMTA) by the Sept. 9, 2020 deadline.
Credit: Андрей Яланский
While each of these 29 warning letters cites specific products as examples of tobacco products that lack the required premarket authorization, collectively these firms have listed a combined total of more than 268,000 products, according to the FDA.
In a first for ENDS products, two of the warning letters went to companies for selling after their PMTAs were not accepted. “Both Vapor Boss, LLC, and Kaleidoscope Custom Vapor Lounge, LLC have continued to sell ENDS products after receiving “Refuse to Accept” (RTA) determinations from the agency following submission of their premarket tobacco applications,” the FDA stated. “These are the first warning letters issued for an application that was submitted by the Sept. 9, 2020 deadline that subsequently received a RTA determination.”
Companies who receive an RTA determination must remove any products currently on the market or risk enforcement action by FDA, according to the agency. Companies may resubmit a complete application for these products at any time, however the products may not be marketed unless they receive a marketing granted order.
FDA also issued the first warning letter to a company that submitted premarket applications for some, but not all, of its products. The company (Maduro Distributors d/b/a The Loon) submitted a premarket application covering 18 products, but it manufactures and sells additional products not covered by the premarket application and thus lacking premarket authorization.
From January through August 2021, FDA has issued a total of 169 warning letters to firms selling or distributing more than 17 million unauthorized electronic nicotine delivery system (ENDS) products and that did not submit premarket applications by the Sept. 9 deadline, according to the agency.
On FDA’s Warning Letters page, you can find all of these warning letters by entering “Center for Tobacco Products” in the “Issuing Office” box in the “Filter by” section of the search tool.
The U.S. Food and Drug Administration stated on Friday, Sept. 3 that it had issued another round of marketing denial orders to 31 companies encompassing an estimated 300,000 products. “After issuing marketing denial orders (MDOs) to three companies for their flavored [electronic nicotine-delivery systems] ENDS products last week, @FDATobacco issued MDOs to an additional 31 companies for approximately 300,000 flavored ENDS products from Aug 27 through Sept. 2,” the agency tweeted.
Credit: Chase4Concept
Several of the MDOs were issued to companies that are not confirmed to be currently marketing their products. The regulatory agency did not release the names of the companies.
According to it’s website, the FDA does plan to release the names of the companies that received MDO. Previously, the agency only gave the names of the three manufacturers who it sent the first series of MDOs for a vapor products. “FDA understands that the public may be interested in the specific names of the currently marketed products subject to the negative decisions,” the FDA website states. “However, before releasing this information, FDA needs to ensure the Agency is not releasing the applicant’s commercial confidential information. Given the large number of products involved, sharing this information requires additional time and resources. Accordingly, FDA is actively exploring options related to this issue.”
In a release, the FDA stated that companies receiving these MDOs may have submitted premarket applications for other products “(such as ENDS devices, tobacco-flavored ENDS, or menthol-flavored ENDS),” and those products, if still pending, remain under review at FDA.
“FDA continues to make substantial progress reviewing the unprecedented number of applications received by the Sept. 9, 2020, court-ordered deadline for submission of premarket applications for deemed new tobacco products,” the release states. “The aggregate information on these actions will be provided within our regular updates on the Tobacco Product Applications: Metrics and Reporting page.”
As of Sept. 3, the FDA website lists 27 companies that have been issued MDOs:
Great American Vapes
JD Nova Group LLC
Vapor Salon
Big Time Vapes
J-Vapor LLC dba North Shore Vapor
SS Vape Brands Inc. Dba Monster Vape Labs
Custom Vapors
The Vaping Tiger
Gothic Vapor
TrendSetters E-liquid LLC
SWT Global Supply
Diamond Vapor
American Vapor Group
MV Enterprises
Planet of the Vapes
CITTG dba Orgnx E Liquids
Vapors of Ohio Inc. dba Nostalgic Vapes
Buckshot Vapors Inc.
Royalty Premium E Juice
Imperial Vapors
Midwest Vape Supply
Dominant Vapor
Mountain Vaporz
Sir Vapes -A-Lot
Loveli Design LLC dba
Alice in Vapeland
Nicquid
The first MDOs were announced on Aug. 26. The products from JD Nova Group, Great American Vapes and Vapor Salon didn’t provide adequate information to show their products offered enough benefit to adult smokers sufficient to overcome the public health threat posed by the “well-documented, alarming levels” of youth use of such products.
The FDA has received applications from over 500 companies covering more than 6.5 million tobacco products. The agency refused to file more than 4.5 million applications from the JD Nova Group. The FDA has until Sept. 9, 2020 to make a decision on the remaining estimated 2 million remaining PMTAs.
All of the premarket tobacco product applications (PMTAs) that have received marketing denial orders (MDOs) from the U.S. Food and Drug Administration have been for flavored products other than tobacco. On Aug. 31, the agency issued MDOs to three companies for only their other-than-tobacco flavored e-liquids, bringing the total number of companies known to have received MDOs to six. According to Filter, approximately 800 PMTAs were denied in the recent round of denials.
Credit: Veeranggull
“Dimitris Agrafiotis, the self-described ‘Vapin’ Greek’ who runs International Vapor Solutions, a consultancy firm, told Filter that three e-liquid companies companies he represents—two of them large and one medium-sized—were sent marketing denial orders (MDOs) by the agency,” Alex Norcia writes. “None of the PMTAs Agrafiotis helped file were totally finished, and the companies’ intention was to send more data piecemeal to the agency as substantial product stability testing wrapped up. Agrafiotis said he could not reveal the names of the companies because of nondisclosure agreements.”
Norcia was able to confirm that the FDA had issued additional MDOs, after it issued its first-ever MDOs for products from JD Nova Group, Great American Vapes and Vapor Salon for an estimated 55,000 products on Aug. 26. In its first MDO release, the agency stated that more marketing decisions would be forthcoming. The agency stated it would continue to review other premarket tobacco applications for non-tobacco flavored electronic nicotine-delivery systems (ENDS) to determine whether there is sufficient product-specific scientific evidence of a benefit to adult smokers to overcome the risk posed to youth.
“If the applications contain evidence of this type, the FDA will conduct further in‐depth scientific evaluation as to whether the evidence satisfies that statutory standard for authorization,” the FDA spokesperson explained to Norcia. “But in the absence of this evidence, the agency intends to issue an MDO. We know that flavored tobacco products are very appealing to young people, therefore assessing the impact of potential or actual youth use is a critical factor in our decision-making about which products may be marketed.”
Many in the vaping industry believe that the FDA will not approve a PMTA for a non-tobacco flavored product. A major e-liquid manufacturer recently told Vapor Voice that the agency may not immediately enforce the marketing of some flavored e-liquids for open systems that have submitted a PMTA, but the agency “will never give marketing approval for a flavor other than tobacco and menthol.”
The FDA’s review of new tobacco products before they can be legally marketed ensures that they meet the standard Congress set in the law to protect the public health, according to the agency. The agency noted that “the evidence of benefits to adult smokers for such products would likely be in the form of a randomized controlled trial or longitudinal cohort study.” The FDA stated that there is the possibility that other types of evidence may exists that could be adequate if sufficiently robust and reliable. However, because the evidence was absent in these applications, the FDA issued MDOs.
The FDA has received applications from over 500 companies covering more than 6.5 million tobacco products. The agency refused to file more than 4.5 million applications from the JD Nova Group. According to the FDA release, the products subject to an MDO for a premarket application may not be introduced or delivered for introduction into interstate commerce. If the product is already on the market, the product must be removed from the market or risk enforcement.
In June, the Agrafiotis’s three clients got a letter from the FDA that their PMTAs had been received and would be moving onto the review stage, according to the Filter story. Last week, his clients drafted letters to the FDA, stating that they would be sending further information. “They have done substantial scientific work and testing,” Agrafiotis said. “They invested some real money in this.” One company, which filed 45 product applications, spent close to $1 million. “Some of the PMTAs were not complete, and some of them were more complete than others.” Of all his clients’ applications, only those for tobacco or menthol flavors now remain pending.
“It’s not clarified exactly why they were denied,” Agrafiotis said. “The FDA mentioned youth. The usual spiel. And I was honest with my clients that some of the product names might be considered appealing to youth by the FDA. I’m very honest with the industry.”
Agrafiotis added that now each company he represents is moving into the synthetic nicotine space. One of the large companies is totally transitioning to synthetic nicotine, a legal gray area, because it does not want to spend any more money on the PMTA process. The other was beginning to explore synthetic nicotine as a stopgap solution while pursuing legal action against the FDA. Numerous companies that have received either a warning letter or MDA from the FDA have chosen to start using synthetic nicotine in order to attempt to avoid FDA regulation.
The FDA has not stated whether or not it believes it has the authority to regulate synthetic nicotine.
The U.S. Food and Drug Administration issued the first marketing denial orders (MDOs) for electronic nicotine delivery system (ENDS) products today. In a press release, the regulatory agency determined that the premarket tobacco product applications (PMTAs) for about 55,000 flavored ENDS products from three applicants lacked sufficient evidence they appropriately protect public health.
The products from JD Nova Group, Great American Vapes and Vapor Salon subject to this action are non-tobacco-flavored ENDS and that include flavors such as Apple Crumble, Dr. Cola and Cinnamon Toast Cereal. The FDA states the products didn’t provide enough benefit to adult smokers sufficient to overcome the public health threat posed by the “well-documented, alarming levels” of youth use of such products.
Credit: Stan Cuic
“Congress gave the FDA the authority to regulate tobacco products to protect the public from the harmful effects of tobacco use through science-based regulation,” said acting FDA Commissioner Janet Woodcock. “Ensuring new tobacco products undergo an evaluation by the FDA is a critical part of our aim to reduce tobacco-related disease and death. We know that flavored tobacco products are very appealing to young people, therefore assessing the impact of potential or actual youth use is a critical factor in our decision-making about which products may be marketed.”
According to the TMA/Vapor Voice PMTA Tracker, Vapor Salon submitted 327 flavors in four sizes and 12 nicotine strengths covering approximately 47,108 submissions. Great American Vapes was also captured by the TMA/Vapor Voice PMTA Tracker with 150 flavors, including the Dr. Cola flavor mentioned in the CTP’s MDO release.
The FDA’s review of new tobacco products before they can be legally marketed ensures that they meet the standard Congress set in the law to protect the public health, according to the agency. The agency noted that “the evidence of benefits to adult smokers for such products would likely be in the form of a randomized controlled trial or longitudinal cohort study.” The FDA stated that there is the possibility that other types of evidence may exists that could be adequate if sufficiently robust and reliable. However, because the evidence was absent in these applications, the FDA issued MDOs.
The agency will continue to review other PMTAs for non-tobacco flavored ENDS to determine whether there is sufficient product-specific scientific evidence of a benefit to adult smokers to overcome the risk posed to youth. If the applications contain evidence of this type, the FDA will conduct further in‐depth scientific evaluation as to whether the evidence satisfies that statutory standard for authorization. But in the absence of this evidence, the agency intends to issue an MDO.
The FDA has received applications from over 500 companies covering more than 6.5 million tobacco products. The agency refused to file more than 4.5 million applications from the JD Nova Group. Although the agency has issued other negative actions for some applications, this is the first set of MDOs the FDA has issued for applications that have reached the substantive scientific review portion of premarket review.
According to the release, the products subject to an MDO for a premarket application may not be introduced or delivered for introduction into interstate commerce. If the product is already on the market, the product must be removed from the market or risk enforcement. The MDOs announced today do not include all ENDS products for which the companies submitted applications. Applications for the rest of the products remain under consideration.
Credit: FDA
“Flavored ENDS products are extremely popular among youth, with over 80 percent of e-cigarette users between ages 12 through 17 using one of these products. Companies who want to continue to market their flavored ENDS products must have robust and reliable evidence showing that their products’ potential benefit for adult smokers outweighs the significant known risk to youth,” said Mitch Zeller, director of the FDA’s Center for Tobacco Products. “The burden is on the applicant to provide evidence to demonstrate that the marketing of their product meets the statutory standard of ‘appropriate for the protection of the public health.’ If this evidence is lacking or not sufficient, the FDA intends to issue a marketing denial order, which requires the product to be taken off or not introduced to market.”
The agency also stated that the scientific review of menthol ENDS, as compared to other non-tobacco-flavored ENDS products, raises “unique considerations.” While menthol-flavored ENDS are not included in the these current FDA decisions, the regulatory agency stated that its reviews will “similarly examine whether the evidence in the application demonstrates a benefit to existing adult users that outweighs the known youth use” of ENDS products.
The American Lung Association commented via Twitter that it stands “firmly with the science that no flavored tobacco products are appropriate for the protection of public health, and all should be removed.”
Greg Conley, president of the advocacy group American Vaping Association, said the three companies targeted by FDA had minimal market share and chastised the agency for going after “low-hanging fruit.” Conley also stated via Twitter that its not a foregone conclusion that all or most pending flavored e-liquid applications will be rejected before the agency’s Sept. 9th deadline. He stated that how the FDA will handle products from manufacturers that submitted requests for extensions and have attempted to supplement their PMTAs are still unknown.
“The FDA never intended to fairly regulate open-system vape products. From the 2014 draft release of the agency’s Deeming Rule until today, the Center for Tobacco Products has looked forward to the moment it would eliminate the ‘wild west’ of the independent industry,” stated Conley.
Scott Gottlieb, who served as FDA commissioner during the Trump administration, blamed e-cigarette manufacturers for their predicament, saying “many companies had ample time, and the benefit of guidances that we issued, to provide a path toward compliance, so they could demonstrate their value as tools that could help current smokers quit combustible tobacco. Many of them chose to fight the laws Congress enacted, and the FDA, and they didn’t invest in demonstrating the public health benefits that they asserted.”
The FDA has until Sept. 9, 2020 to make a decision on the remaining estimated 2.5 million PMTAs.
The PMTA process has had some errors and challenges as the FDA’s decision deadline looms.
By Timothy S. Donahue
The U.S. Food and Drug Administration’s process for premarket tobacco product applications (PMTAs) has not been perfect. The regulatory agency has less than three weeks to complete its review of the more than 2 million PMTA submissions that remain of the more than 6 million received (the FDA refused to file more than 4 million submissions from the JD Nova Group). Given the unprecedented number of applications and other factors, the likelihood of the FDA reviewing all the applications by Sept. 9, 2021, is low.
“We will continue to allocate our resources with the goal of working as quickly as possible to transition the current marketplace for deemed products to one in which all products available for sale have undergone a careful, science-based review by [the] FDA,” an FDA spokesperson told Vapor Voice. “With that being said, as with all unauthorized products generally, if products are not authorized by Sept. 9, 2021, and do not come off the market at that time, they risk FDA enforcement.”
A court ruling requires the FDA to complete review of all submitted PMTAs by Sept. 9, 2021. Only a positive order issued by the FDA would allow a company to continue to be marketed according to the terms specified in the order letter.
“At a recent House hearing, acting FDA Commissioner Janet Woodcock pledged the FDA would make every effort to conclude review of the PMTAs from the top five vaping companies by the fall deadline,” said Gregory Conley, president of the American Vaping Association. “The FDA does not exactly have the best track record on keeping to their pledges, but it seems likely that decisions will be made on, at minimum, the tobacco and menthol varieties of Juul, Vuse, NJOY, etc., by September.”
Unfair warning
Complicating matters further, the regulatory agency has also recently been accused of issuing unwarranted warning letters, of leaving companies off its list of accepted PMTAs and of having technical issues with its PMTA filing software. As of July 26, the FDA had issued 135 warning letters for the marketing of illegal vaping products. The majority of those letters centered on e-liquids produced and sold online by small-sized vape shops. As the FDA continues its blitz, however, some companies who submitted PMTAs by the Sept. 9, 2020, deadline have allegedly received warning letters in error.
According to Facebook posts from the American Vaping Manufacturers Association (AVM), at least two companies have received warning letters for products for which they had submitted timely PMTAs. Posts acknowledged that the FDA corrected its mistake in a follow-up letter after receiving complaints from the companies. While the number may be small, it does suggest that the regulatory agency is overwhelmed by the number of submissions it is reviewing.
Credit: Chris Titze Imaging
According to the FDA spokesperson, there has been only one instance where the regulatory agency removed a warning letter from its website after it was discovered that the company had submitted a timely PMTA. The agency did not mention the company by name and said the error had been corrected.
The FDA said the list may change as some companies may not have responded to requests or have not had their PMTA accepted yet. It should be noted that in its guidance document released in January 2020 that identified its enforcement priorities for electronic nicotine-delivery system (ENDS) products, the FDA stated that it “may prioritize enforcement of certain new deemed tobacco products that are marketed without market authorization, including as warranted based on changed circumstances, new information or to better address minors’ use of those products.”
The FDA also recently started listing closeout letters for companies that had responded to warning letters on its website. When the FDA completes an evaluation of corrective actions via a follow-up inspection, it may issue a closeout letter if the agency’s evaluation shows that the issues noted in the warning letter have been addressed.
Recently, however, the agency removed those letters from its website. The FDA offered no explanation for the removal of the closeout letters. Companies such as Dr. Crimmy’s V-Liquid, Bulldog Vapor and CC Apothacary had closeout letters posted, but then it seemed they were removed.
The FDA spokesperson said that the letters are still on the website; however, accessing them changed slightly. Users must now use the search functions to access response and closeout letters. “Any closeout letters issued to firms since Sept. 9, 2020, including Dr. Crimmy’s V-Liquid, Bulldog Vapor [and] CC Apothecary, are still posted on [the] FDA’s website,” the spokesperson said. “On [the] FDA’s ‘Warning Letters’ page, you can find the closeout letters by listing ‘Center for Tobacco Products’ under ‘Issuing Office’ and filtering for ‘Closeout Letter’ under ‘Letters with Response or Closeout.’”
The FDA often lists only a few illegal products in a warning letter. It then states that there may be more, but it is impossible to know if the warnings encompass all the company’s registered products. The agency states that it is the responsibility of the company to only sell products with a submitted PMTA.
Companies that receive warning letters from the FDA have to submit a written response to the letter within 15 working days from the date of receipt describing the company’s corrective actions, including the dates on which it discontinued the violative sale and/or distribution of the products. The response must also detail the company’s plan for maintaining compliance with the Food, Drug and Cosmetic (FD&C) Act in the future.
Warning letters are expected to continue to be issued for illegal vapor products as the deadline for FDA action moves closer, and their volume is likely to pick up after the Sept. 9 deadline. The FDA has not said if it intends to ask for an extension on the deadline; however, the U.S. Small Business Administration recently sent a letter to the FDA asking the regulatory agency to request an extension.
Making the list
There are other issues with the FDA PMTA process as well. Recently, the FDA released a list of products that are legal for sale in the U.S. As of Aug. 9, 372 companies had submitted PMTAs for more than 6 million products. Of those products, 99.9 percent are standalone e-liquid products—and of those, 80 percent of the e-liquid submissions were from a single company, according to ECigIntelligence, a vapor industry data and research firm.
At least five companies that filed PMTAs were allegedly erroneously left off the list, according to social media posts by an AVM representative. In its own investigation, Vapor Voice found that Humble Juice Co. had submitted a timely PMTA, received an acceptance letter and was subsequently left off the FDA’s list of approved products. The FDA has corrected the error for Humble. The AVM did not name what companies were left off the list or had falsely received warning letters.
The FDA stressed it has not independently verified the information provided by applicants about the marketing status of their products. In addition, the list excludes entries of products from companies that did not provide information on the current marketing status of their products to the FDA so that the agency could determine whether the existence of the application could be disclosed. It is possible companies were left off the list because they did not respond to the FDA before publication of the list.
As stated on the FDA’s website, the lists are not comprehensive or intended to cover all currently marketed deemed tobacco products that a company generally might manufacture, distribute or sell without risking FDA enforcement. The FDA stated that it was making the list available to the public to be transparent and increase stakeholder knowledge of these products. However, the list is only one source of information, and retailers should discuss with their suppliers the current status of any particular tobacco product’s application and marketing authorization, according to the FDA.
“Due to the large volume of information that needed to be processed to generate the list, it is likely that some information may have been inadvertently excluded during the development of the list. After initial posting of the list, FDA has received inquiries from companies about certain products they believe should have been included on the public list,” the spokesperson said. “We are reviewing these requests, and will update the list, if appropriate, to ensure accuracy. In general, due to the large amount of data in the files, FDA has also stated minor edits and corrections may be made to the list files to ensure accuracy, and the files will also be updated to reflect actions taken on the applications for the products.”
Shaky submissions
The PMTA submission process has also suffered from technical problems. Several companies have complained that the FDA’s software that manufacturers must download to submit PMTA data has randomly left out some files that the companies are uploading. At least two companies that have helped prepare more than 500 PMTAs have acknowledged the issue and have presented the problem to the FDA.
“We did 15 PMTAs for various clients and just all of a sudden had somebody come up and they got a deficiency letter asking for information that was included in their submission. We started looking through it, and it’s missing. We then spent a bunch of time going through every single one and found several others that were missing one or two files,” one of the companies that discovered errors told Vapor Voice. “We reached out to the FDA, got a basic response … ‘we’re aware of this; we’ll get back to you’ type of thing. We believe it’s a bug in the agency’s eSubmitter program.”
The FDA spokesperson said that the agency’s Center for Tobacco Products (CTP) submitters have three options for electronic submissions:
1. FDA hosts the Electronic Submission Gateway (ESG) used by all FDA centers for the past 20-plus years. It requires registration and maintaining a security certificate, which has an associated fee. CTP receives electronic submissions directly through the ESG from a small number of companies.
2. CTP provides a simpler zero-cost alternative to using the ESG directly with the FDA eSubmitter software and the CTP Portal. Using the CTP Portal requires obtaining a free account and using the FDA eSubmitter tool to create a valid package of files, which the CTP Portal will upload. Submitters must download the FDA’s eSubmitter software if they intend to use the free CTP Portal. Instructions for use are on the FDA webpage, and detailed technical specifications for creating valid eSubmitter packages can be found under Electronic Submission File Format and Technical Specifications.
3. Electronic files can be mailed to CTP Document Control Center (DCC) on physical media such as CD, DVD or flash drive.
Credit: Yuri Hoyda
The eSubmitter errors that some companies have found may be user error, according to the FDA. The inclusion of invalid file types in the upload package may make it appear as if certain files were left off. A common invalid file type users attempt to include are zero-sized files, according to the FDA.
“A user may unintentionally include *.tmp files, which are temporary files of zero size that the user’s computer creates when it is moving files from one location to another. If a user moves files they are uploading during the loading process, the .tmp file their computer created will become part of the package manifest and appear in the eSubmitter file count,” the spokesperson said. “A user may think they are sending 500 application files, but if one is a .tmp file, they are only sending 499 files related to the application.”
The CTP eSubmissions help desk recommends submitters create a file list and review the file types to be used in the submission against the list of invalid file types. After uploading to the CTP Portal, they can compare the list of valid files against the CTP Portal upload manifest to ensure all files were included. If files were found to not be included, they could be submitted separately, according to the FDA.
“In general, FDA intends to send only one deficiency letter (if appropriate),” the spokesperson said. “It is the applicant’s responsibility to ensure all information has been submitted to FDA and to review all files that were uploaded to the software prior to submission to FDA.”
Because of these issues, some companies are offering free PMTA deficiency reviews for companies that submitted them to the FDA. Delphinus Consulting and Blackbriar Regulatory Services have said they have programs to help companies find faults in their PMTA submissions.
After the deadline
How the vaping industry changes on Sept. 9 remains to be seen. Large companies may soon dominate the U.S. vapor market while e-cigarettes produced by smaller companies may disappear, according to new research by ECigIntelligence. The data firm carried out an assessment of the FDA’s “accepted” list in order to understand how the U.S. market may change in a post-PMTA regulated market.
Analysis of PMTAs shows that more applications for simpler disposables and cigalike devices were submitted than applications for open systems. According to the research, the simpler products usually come from large companies while the open systems usually come from smaller businesses. Only about 30 open system brands have filed PMTAs, implying that 85 percent of open system brands will be removed from the market, even if all 30 filed PMTAs are approved.
“This may indicate the discouragement nontobacco companies face when applying for PMTA approval,” said ECigIntelligence’s managing director, Tim Phillips. “The PMTA process can be a grueling one for nontobacco companies without sufficient financial means or knowhow. And if smaller brands are to become less prevalent in this category, consumers may soon only have the option of a few models provided by a handful of big companies.”
While the industry awaits decisions from the FDA, vape sales are rising. IRI data for U.S. convenience stores shows that dollar and unit sales for electronic smoking devices each climbed approximately 14 percent for the four weeks ending June 13. A 12-week review revealed a gain of 16.3 percent in dollar sales and 18.6 percent in unit sales.
Whether these trends will continue after Sept. 9 is anyone’s guess.
The U.S. Food and Drug Administration has informed e-liquid manufacturer Bantam Vape that its non-tobacco flavored electronic nicotine delivery system (ENDS) products are now in the agency’s formal scientific review stage of the premarket tobacco product application (PMTA) process, according to a press release. Scientific review is the final step in the PMTA process prior to FDA’s decision to grant a marketing order.
Bantam is seeking marketing orders from FDA for its suite of e-liquid products. Credit: Bantam Vape
“Following the receipt of Bantam’s filing letter, it has waited in anticipation for FDA to begin the next step in the PMTA process – formal scientific review,” said Bantam spokesperson Anthony Dillon. “As we approach the one-year anniversary of the filing deadline, this action represents a critical stage in FDA’s consideration of Bantam’s request for a marketing order.”
The FDA completed a preliminary review of Bantam’s PMTAs in November 2020, making its applications eligible for formal substantive review. During the substantive review phase, FDA will conduct an in-depth evaluation of Bantam’s scientific studies and other materials it submitted in conjunction with the brand’s applications.
This includes FDA’s consideration of Bantam’s product testing for harmful and potentially harmful constituents (HPHCs) and physical characteristics of the e-liquids and aerosol at multiple time points; an analysis of leachable chemicals and stability testing of its e-liquids at multiple time points; microbial testing of the final e-liquids at multiple time points; in vitro toxicity testing including Ames, micronucleus and neutral red uptake (NRU) studies; four pharmacokinetic and topography studies for multiple flavors at various nicotine concentrations; and consumer surveys to understand the demographic and usage patterns of its e-liquids. Multiple comprehensive, quantitative risk assessments across many areas of potential risk for the Bantam products were also provided to FDA, demonstrating that Bantam products are appropriate for the protection of public health.
Additionally, to ensure Bantam’s ongoing ability to provide consumers with “high-quality, science-based e-liquid products” following the Sept. 9, 2021 deadline, the brand submitted a formal extension request to FDA. Bantam is hopeful that FDA will grant the extension, which would provide the regulatory agency with additional time to review Bantam’s complete applications and allow the brand’s products to remain on the market while the applications are under review.
“Entering the coveted scientific review phase is a significant development. This is especially true given FDA’s growing enforcement actions against non-compliant brands,” said Dillon. “Bantam remains confident in its PMTA submissions and will continue to engage with FDA in order to obtain the marketing orders needed to stay on the market moving forward.”
The U.S. Food and Drug Administration on Wednesday told Charlotte’s Web Holdings Inc. that its cannabidiol product cannot be sold as a dietary supplement, signaling that CBD reform may have to wait for congressional action.
Credit: Anankkml
“While we disagree with FDA’s reasoning, believing we provided extensive and credible scientific evidence that supported a different outcome, this decision affirms the path to regulatory clarity must come from Congress,” Charlotte’s Web CEO Deanie Elsner said in a statement.
The company’s bid to sell its full-spectrum hemp extract with CBD as a dietary supplement won’t be considered because of the FDA’s own prior decision to treat CBD as a drug, according to a letter posted on the agency’s website Wednesday, according to Fortune. The FDA’s latest decision rested in part on its prior approval of Epidiolex, a CBD drug to reduce seizures, which the agency said precludes it from authorizing CBD for dietary purposes.
Even if the drug hadn’t been approved, though, the FDA said in the letter to Charlotte’s Web dated July 23 that it “has concerns about the adequacy of safety evidence” that the company submitted. The agency would have wanted more data on potential liver and reproductive toxicity.
The decision isn’t expected to impact sales of Charlotte’s Web products or prevent other companies from continuing to sell CBD products. The market for CBD products has already grown to more than $6 billion as consumers seek help with everything from relaxation to focus to better sleep, according to reports. While generally an unregulated market, the FDA will periodically crackdown on companies that try to make unsubstantiated claims about the health benefits of CBD products.
