E-Alternative Solutions (EAS) has submitted premarket tobacco product applications (PMTAs) to the U.S. Food and Drug Administration (FDA) seeking authorization for the marketing and sale of its portfolio of Leap and Leap Go vapor products.
“We are pleased to take this important step in demonstrating our commitment to the vapor industry, retailers and adult smokers seeking an alternative to combustible cigarette smoking with our Leap and Leap Go vapor products,” said Jacopo D’Alessandris, president and CEO of EAS.
“At EAS, we have always held ourselves to high standards, from supplying adult consumers with products they can trust to consistently following ethical marketing practices. We are confident in the strong merits of our PMTAs and want to thank our compliance and research teams for developing and delivering thorough submissions.”
According to EAS, the PMTAs plays support the proposition that Leap and Leap Go vapor products are appropriate for the protection of public health. “The collective 75,000-plus-page PMTA submissions for Leap and Leap Go are the result of months of hard work and investigation that included an assessment of the stability of the products over time, toxicological formula reviews, toxicology testing, an assessment of abuse liability, label comprehension studies and behavioral studies,” the company wrote in a statement.
In addition, EAS undertook an extensive review of available literature on vapor products related to health effects, behavioral factors and toxicological end points. Further, an exacting risk assessment was conducted across many areas of potential risk for Leap and Leap Go products.
“Our PMTA submissions provide a robust analysis of the Leap and Leap Go products that will enable [the] FDA to conclude these products are appropriate for the protection of public health,” said Chris Howard, vice president, general counsel and chief compliance officer at EAS. “The PMTA process sets a high bar and holds companies accountable, ensuring vapor product manufacturers follow the rules and act in good faith. Looking ahead, a robust collaboration with [the] FDA will help build a strong future for both the vapor industry and adult consumers.”
The FDA signed off March 18 on a new set of 11 graphic warning labels for traditional cigarettes that are toned down considerably from its first attempt in 2012, which was abandoned after an industry legal challenge.
The new set of warnings contains images of diseased lungs, a man experiencing erectile dysfunction, a man with surgical stitches from heart or lung surgery and a child with an oxygen mask. But there is no smoke coming out of a tracheal hole, no cadaver and no photo of a man who appears deathly ill, as the FDA proposed.
The labels must cover the top 50 percent of the front and rear panels of packages, as well as at least 20 percent of the top of advertisements. The messages must be randomly and equally displayed and distributed on cigarette packages and rotated quarterly in cigarette advertisements.
The warnings were mandated by a federal judge for cigarette packaging and marketing. The ruling does not affect other tobacco products, such as electronic cigarettes.
Initially, the agency set a deadline for June 18, 2021. However, on April 3, Philip Morris USA, R.J. Reynolds Tobacco Co., ITG Brands and Liggett Group filed a joint motion requesting a preliminary injunction on implementing the labels and a ruling to prohibit enforcement. The manufacturers insist that the labels violate the First Amendment of the U.S. Constitution, which guarantees free speech.
On May 8, the FDA and the manufacturers filed a joint motion to extend the deadline by 120 days. The manufacturers said the pandemic has complicated their ability to meet the June 18, 2021, deadline.
Despite the postponement of the deadline, the FDA urged manufacturers to submit plans for compliance as soon as possible.
“Early submission will facilitate timely FDA review of plans prior to the effective date of the required warnings, encourage dialogue with entities regarding any implementation concerns, and provide time to consider proposals by entities in a timely manner,” the FDA said.
The U.S. Food and Drug Administration (FDA) has asked a federal judge in Texas to delay the effective date of a rule requiring graphic health warnings on cigarette packages due to the outbreak of Covid-19, reports Reuters.
The FDA and tobacco companies that are suing the agency have asked the court to delay the effective date from June 18, 2021, to Oct. 16, 2021.
The Fourth Circuit on Monday dismissed an appeal from various vaping groups challenging a compliance deadline for vapor products. The decision states that January directives from the U.S. Food and Drug Administration (FDA) have rendered the appeal moot.
In a per curiam opinion, the appellate judges held that guidance issued by the FDA in January moots the vape groups’ appeal because that guidance supersedes older directives from August 2017 at issue in the appeal and leaves “no possible meaningful relief” that the court could grant, according to law360.com.
“Any ruling by this court as to the procedural or substantive reasonableness of the August 2017 guidance would amount to nothing more than an advisory opinion,” the court said.
The appeal stems from a Maryland district court ruling that ordered the agency to set a May 2020 deadline for premarket tobacco product applications (PMTA) on smokeless tobacco products. The FDA, along with various health and anti-vaping groups, had argued that the January guidance restricting the sale of flavored, cartridge-based vapes rendered moot the vape groups’ appeal.
“Because the enforcement timetable for e-cigarettes set out in the January 2020 guidance is independent of the district court’s order, an order by this court reversing the district court would have no effect on FDA’s enforcement of the statute and regulations against e-cigarette manufacturers,” the agency had previously said.
But the vape groups disagreed, saying the January guidance was enacted without proper notice-and-comment procedures, according to the opinion.
While the court said it can’t offer the vape groups relief in this case, the panel added in a footnote that the groups can challenge the January guidance in a separate action in federal court. The panel also ruled that a Maryland district court did not abuse its discretion in denying cigar industry groups’ motion to intervene, saying those groups did not intervene in a timely manner.
Counsel for the cigar and vape groups and a representative of the FDA did not immediately respond to requests for comment Monday.
Last month, a Maryland federal judge said that in light of the coronavirus pandemic, he would grant a 120-day extension to the May 12 deadline for e-cigarette PMTAs, which have proceeded slowly since the FDA first determined vapes should be regulated like tobacco products. The new deadline is Sept. 9, 2020.
The FDA had previously asked the Fourth Circuit for approval for the lower court to extend the May deadline, saying it would not affect the merits of the appeal brought by the industry groups. The FDA said many of the laboratories and research organizations conducting the clinical trials for the regulatory applications have shut down or otherwise halted in-person testing in light of the COVID-19 pandemic.
Public health groups previously sought to accelerate the FDA’s regulation of vaping products under the Tobacco Control Act, citing vaping-related lung injuries that sickened thousands of people and left nearly 70 dead in 2019. In July 2019, a Maryland district judge effectively allowed the FDA to set the May 2020 deadline, prompting the vape groups to claim the decision was an arbitrary overextension of both the FDA and the court’s authority.
The vape groups had also argued that the May deadline left too little time for manufacturers to file complete applications. Cigar industry groups that filed joint briefs on appeal argued that the district court’s order on deadlines unfairly ensnared cigar and pipe tobacco manufacturers as well.
Today, the U.S. Food and Drug Administration (FDA) issued 10 warning letters to retailers and manufacturers who sell, manufacture and/or import unauthorized electronic nicotine delivery system (ENDS) products targeted to youth or likely to promote use by youth.
The warning letters were sent to establishments marketing unauthorized products, such as a backpack and sweatshirt designed with stealth pockets to hold and conceal an e-cigarette, ENDS products that resemble smartwatches, or devices appearing as children’s toys such as a portable video game system or fidget spinner.
Warning letters were also issued to companies marketing e-liquids that imitate packaging for food products that often are marketed and appeal to youth, such as candy, or feature cartoon characters like SpongeBob SquarePants.
“The FDA is focused on manufacturers and retailers that make and sell ENDS products that are targeted to youth and increase their appeal. The public should really be outraged by these products. The FDA is especially disturbed by some of these new products being marketed to children and teens by promoting the ease with which they can be used to conceal product use, which appeals to kids because it allows them to conceal tobacco product use from parents, teachers, law enforcement or other adults,” said Mitch Zeller, director of the FDA’s Center for Tobacco Products. “Even in the midst of the COVID-19 pandemic, we have not lost our focus on protecting youth against the dangers of e-cigarettes and will do everything we can to take action. These warning letters should send a clear message to all tobacco product manufacturers and retailers that the FDA is keeping a close watch on the marketplace. If you’re marketing or selling these products to youth, the FDA will not tolerate it.”
The following retailers and/or manufacturers or importers received a warning letter:
Shenzhen Uwell Technology Co., Ltd. d/b/a DTD Distribution Inc. (importer, retailer)
The FDA has also issued warning letters to 73 brick-and-mortar retailers for selling unauthorized flavored, cartridge-based ENDS products. This follows 22 warning letters that FDA issued last month for similar violations to online and brick-and-mortar retailers and manufacturers across the country. These warning letters are part of a series of ongoing actions consistent with the FDA’s recently issued policy of enforcement priorities for e-cigarettes and other deemed products on the market.
The U.S. Food and Drug Administration (FDA) has suspended domestic compliance checks and vape shop inspections amid the spread of coronavirus.
The FDA has temporarily deferred all domestic routine surveillance facility inspections and postponed most foreign inspections through April. Administrative work can continue for two weeks, though, according to the Center for Tobacco Products.
The US Food and Drug Administration’s Center for Tobacco Products is due to explain the processes it uses in the review of tobacco product applications.
In a press note, the FDA said it planned to hold a meeting of the Tobacco Products Scientific Advisory Committee (TPSAC) on April 6.
‘During this meeting, representatives from the FDA’s Center for Tobacco Products will present information to the Committee, which includes several new members, on the processes CTP uses in the review of tobacco product applications, including substantial equivalence (SE), modified risk tobacco product (MRTP) and premarket tobacco applications (PMTA),’ the note said.
‘Topics will include the statutory standards applicable to the different types of applications; the scientific basis for review decisions, with a focus on PMTA and MRTPA; and the role of the committee in the review process.
‘People interested in presenting data, information, or views, either in person or in writing, must send in their submissions by March 15 or March 23, respectively.’
The US Food and Drug Administration has sought to clarify what in its view tobacco products and products derived from tobacco are, and which part of the agency deals with those products.
The clarification comes in the form of a recently issued final rule entitled: Clarification of When Products Made or Derived From Tobacco Are Regulated as Drugs, Devices, or Combination Products; Amendments to Regulations Regarding ‘Intended Uses’.
‘This rule describes circumstances in which a product made or derived from tobacco is subject to regulation by the FDA’s Center for Drug Evaluation and Research, Center for Devices and Radiological Health, or Center for Tobacco Products,’ the FDA said in a recent posting.
‘This rule is intended to help manufacturers and researchers better understand which regulatory standards apply to their products or studies, respectively.
‘The agency also anticipates that the rule will help consumers clearly distinguish products made or derived from tobacco that are intended for tobacco cessation from those intended for other uses.’
The US Food and Drug Administration has issued a final rule regarding the refuse-to-accept procedures for premarket tobacco submissions.
Under this rule, the agency says, it will refuse to accept tobacco product submissions or applications that are not in English, do not pertain to a tobacco product, do not include contact information, or do not meet other requirements as listed in the rule.
At the same time, the FDA has issued its Submission of Warning Plans for Cigars, a guide to assist industry players that are required to submit warning plans related to statements on cigar packaging and advertising.
Those concerned are required to submit a proposed warning plan to the FDA no later than May 10, 2017, or 12 months prior to advertising or commercially marketing the cigar, whichever is later.
Meanwhile, the FDA has published its final guidance entitled Listing of Ingredients in Tobacco Products.
‘This guidance is intended to assist manufacturers and importers making tobacco product ingredient submissions to the FDA, as required by the Tobacco Control Act,’ said the FDA. ‘Revisions to this guidance include minor clarifying and editorial changes to promote consistency throughout the FDA’s guidances and updated submission compliance dates.
‘The guidance also explains the statutory requirement to submit a list of all ingredients in tobacco products, who submits ingredient information, what information is included in the submissions, how and when to submit the information, the FDA’s compliance policies, and definitions.
‘Under the policies outlined in the guidance, the FDA does not intend to enforce the submission requirement for newly deemed tobacco products that were on the market as of August 8, 2016, until August 8, 2017, or February 8, 2018 for small-scale manufacturers. Tobacco products entering the market after August 8, 2016, must submit the ingredient information at least 90 days before the product is introduced into interstate commerce.
‘FDA is currently accepting ingredient listings for tobacco products and encourages manufacturers to start the processes as early as possible.’
Jason Rock is the chief technology officer and co-founder of GlobalSubmit.
Rock has been integral in the FDA’s efforts to harmonize regulatory submission standards for the tobacco industry, as he was when the FDA first implemented similar standards for life sciences.
He served as the project lead for the first-ever MRTP application accepted for review by the CTP and the first-ever approved PMTA.
During the April 9–10, 2015, Tobacco Products Scientific Advisory Committee (TPSAC) meeting to discuss MRTP applications submitted by Swedish Match, Rock was the only non-FDA, non-tobacco industry participant to address the audience.
Best practices for filing FDA tobacco product applications
By Jason Rock
The final deeming regulation extending the U.S. Food and Drug Administration’s (FDA) authority to additional products has, to put it mildly, captured the attention of the entire tobacco industry. A predicate—or “grandfather”—date of Feb. 15, 2007, will force the majority, if not all, of e-cigarette or electronic nicotine-delivery system manufacturers into the premarket tobacco product application (PMTA) pathway—the costliest and most complex avenue from a regulatory standpoint.
In this article, I’ll give you an idea of what to expect when filing a large application to the FDA and provide general guidelines for formulating a successful approach.
Similarities between pharma and tobacco
A few years ago, I read an account from a major tobacco company executive predicting that tobacco companies would one day be regarded in the same vein as pharmaceuticals. The comparison is especially apt when considering the size and content of applications. Typically, a large New Drug Application (NDA) submitted to the FDA contains 20–25 studies and ranges anywhere from 100,000–300,000 pages. There are always exceptions, and I’ve seen applications with as few as five studies while others have broken the 100-study barrier.
In all likelihood, PMTAs are comparable in scope, if not equivalent, to these large marketing applications. Modified-risk tobacco products (MRTPs) are much larger, as they require the submission of case report forms. Swedish Match, the first company to receive marketing authorization from the FDA under the PMTA pathway, submitted a 130,000-page MRTP application for eight products.
Timing and project management
If you’re committed to the PMTA pathway, the date marked on your calendar is Aug. 8, 2018. A missed filing deadline could trigger FDA enforcement action for your products currently on the market. Work on large pharmaceutical applications typically precedes the filing date by at least 12 months. It’s not unusual for applicants to begin work 18–24 months prior to the filing deadline set for an NDA.
A winning timing strategy for PMTAs is to start early and set an internal submission target for six months prior to the statutory deadline (Feb. 8, 2018). The natural instinct is to start the submission process once your summary documents are in progress. Don’t wait! Start early to lower your risk. Any studies already completed should be published as soon as possible, whereas other parts of the application can be completed on a rolling basis. Plan for late document delivery and work ahead. We believe it’s better to have 20 percent of the documents 100 percent complete versus 100 percent of the documents 20 percent complete.
In terms of project management, you’ll want to appoint an internal resource to manage the document production process or find an expert with experience. A custom tracking tool is the most plausible solution for tracking the delivery date and submission readiness for each document.
You’ll want to schedule a pre-submission meeting with the FDA to review your strategy. The probability of project success goes up if you can achieve agency buy-in up front.
Submission publishing standards
In preparing electronic applications for drug products, pharmaceutical companies have to adhere to internationally harmonized standards for documents and folder structures or face technical rejection. These standards have been in place for over a decade. And while regulatory requirements around PDF versions, bookmarks and hyperlinks, fonts, and headings and hierarchy might sound unduly burdensome, the formatting standards are integral to streamlined document review and timely approval.
Without the luxury of documented standards as are in place for pharmaceutical companies, tobacco applicants should strive to meet as many existing standards as possible. The men and women who will ultimately review your tobacco applications are descendants of the Center for Drug Evaluation and Research and the Center for Biologics Evaluation and Research. The reviewers are familiar with pharmaceutical standards and prefer tobacco submissions to resemble what they are used to receiving.
Your strategy should center on setting up a pre-submission meeting with the FDA Center for Tobacco Products and proposing use of existing standards such as CDISC (Clinical Data Interchange Standards Consortium ) or CDISC-like datasets for clinical and nonclinical study data, International Conference on Harmonization E3 guidelines for clinical study reports, pre-eCTD PDF publishing specifications, and best practices for laboratory testing and manufacturing.
Cost
How much does it cost to prepare a PMTA?
The answer depends on who you ask. In the final deeming regulation, the FDA estimated an effort of more than 1,700 hours to prepare a PMTA, which adds up to roughly $1 million per product. Independent tobacco industry figures project a high-end cost of up to $10 million per PMTA, if not higher.
Submission publishing, project management and quality review of documents fit into the administrative portion of the estimate. As is true in the pharmaceutical industry, these activities are the least expensive part of a very expensive process. Standard rates for submission publishing and related activities are set per page. For a quick ballpark estimation, you can use a $5 per page rate inclusive of publishing, management and other tasks.
Learn from experience
Prior to the successful MRTP and PMTA submission filed by Swedish Match, a number of applicants were rejected by the FDA for failure to adhere to the aforementioned standards and failure to adequately articulate a submission strategy.
In the early preparatory stages of its filing, Swedish Match was challenged about the mechanics of filing an MRTP application. In the end, three key discoveries emerged: (1) the true scope of the project, (2) the FDA’s expectations for document formatting and (3) the role of correspondence with the FDA CTP during the project.
Successfully filing a PMTA requires drawing on the considerable experience of the pharmaceutical industry, starting the process early and securing the proper expert resources, adhering to existing and agreed upon standards, and following the lead of others who have achieved the desired outcomes.
The US Food and Drug Administration’s Center for Tobacco Products is due to explain the processes it uses in the review of tobacco product applications.
