Tag: U.S. Food and Drug Administration

  • FDA Urged to Act on Remaining Applications

    FDA Urged to Act on Remaining Applications

    Photo: New Africa

    Several anti-tobacco groups have sent a letter to the U.S. Food and Drug Administration urging the agency to act on the outstanding premarket tobacco product applications (PMTAs) and pushing for the denial of all flavored e-cigarette products.

    It’s been more than four months since the FDA was supposed to decide which e-cigarette products can remain on the market, but the agency still hasn’t completed some of the reviews, including some of the bestselling e-cigarettes.

    “We write to urge the U.S. Food and Drug Administration (FDA) to expedite decisions on the premarket tobacco product applications (PMTAs) still pending before the agency involving the flavored e-cigarette products, including those with menthol flavoring and, based on the best available scientific evidence, deny the pending applications for all nontobacco flavored e-cigarettes in order to protect the nation’s young people from the health harms of these products,” the letter said.

    The letter was signed by the American Academy of Pediatrics, the American Heart Association and the Campaign for Tobacco-Free Kids, among others.

    “Every day that FDA delays action, more of our kids remain at risk,” said Matthew Myers, president of the Campaign for Tobacco-Free Kids. “While the FDA has ruled on applications from a lot of small companies, it hasn’t ruled on the applications from the large companies whose products are being used by a majority of kids.”

    American Vaping Association President Gregory Conley pointed to data showing that youth vaping has been declining. According to the Centers for Disease Control and Prevention (CDC), use of e-cigarettes went down among middle school and high school students from 2019 to 2020.

    But even with the drop, the CDC said it “estimated that more than 2 million U.S. middle [school] and high school students reported currently using e-cigarettes in 2021.”

  • Modified-Risk Marketing Orders for 22nd Century

    Modified-Risk Marketing Orders for 22nd Century

    Photo: 22nd Century Group

    The U.S. Food and Drug Administration has authorized the marketing of 22nd Century Group VLN King and VLN Menthol King combusted, filtered cigarettes as modified risk tobacco products (MRTPs), which help reduce exposure to, and consumption of, nicotine for smokers who use them. These are the first combusted cigarettes to be authorized as MRTPs and the second tobacco products overall to receive “exposure modification” orders, which allows them to be marketed as having a reduced level of, or presenting a reduced exposure to, a substance.

    “Our mission is to find ways to stop tobacco-related disease and death. We know that three out of four adult smokers want to quit and the data on these products show they can help addicted adult smokers transition away from highly addictive combusted cigarettes,” said Mitch Zeller, director of the FDA’s Center for Tobacco Products, in a statement.

    “Having options like these products authorized today, which contain less nicotine and are reasonably likely to reduce nicotine dependence, may help adult smokers. If adult smokers were less addicted to combusted cigarettes, they would likely smoke less and may be exposed to fewer harmful chemicals that cause tobacco-related disease and death.”

    The exposure modification orders specifically authorize the manufacturer to market VLN King and VLN Menthol King with certain reduced exposure claims regarding nicotine, including:

    • 95 percent less nicotine
    • Helps reduce your nicotine consumption
    • Greatly reduces your nicotine consumption

    When using any of the reduced exposure claims in the product label, labeling or advertising, the company must include, “Helps you smoke less.” The FDA also recommends that the labeling and advertising include the statement, “Nicotine is addictive. Less nicotine does NOT mean safer. All cigarettes can cause disease and death.” The manufacturer is also required to label the packages with one of four warning statements for cigarettes as required by the Federal Cigarette Labeling and Advertising Act; for example, “Surgeon General’s Warning: Smoking Causes Lung Cancer, Heart Disease, Emphysema, And May Complicate Pregnancy.”

    Having options like these products authorized today, which contain less nicotine and are reasonably likely to reduce nicotine dependence, may help adult smokers.

    Mitch Zeller, director, FDA Center for Tobacco Products

    In the review of 22nd Century Group’s MRTP applications, the FDA evaluated data from both the company and FDA testing and found that nicotine levels in tobacco and mainstream smoke of VLN cigarettes are at least 96 percent lower than the majority of marketed and market-leading conventional cigarette brands.

    Furthermore, the FDA’s behavioral and clinical pharmacology review found that by exclusively smoking cigarettes with the same or similarly reduced nicotine content as VLN cigarettes, consumers could reduce their exposure to nicotine by approximately 95 percent. The data also showed it is reasonably likely that using these products reduces nicotine dependence, which is anticipated to lead to long-term reductions in exposure to the smoking-related toxicants associated with morbidity and mortality by reducing smoking.

    Published studies have shown that significantly reducing the number of cigarettes smoked per day is associated with lower risk of lung cancer and death, with greater reductions in cigarettes per day resulting in less risk. Additionally, as required for authorization, the FDA found that the applications supported consumer understanding of the claims that VLN cigarettes contain much lower levels of nicotine than other cigarettes. 

    The authorization for these products requires the company to conduct post-market surveillance and studies to determine whether the authorization criteria for these exposure modification orders continue to be met, including assessing use among youth.

    These products are also subject to the post-market requirements and restrictions previously imposed in their December 2019 premarket tobacco product marketing granted orders. In particular, to limit youth access to the products and to limit youth exposure to advertising and promotion, the marketing granted orders placed stringent restrictions on how the products are marketed–especially via websites and through social media platforms—by including requirements that advertising be targeted to adults of legal age to purchase tobacco products.

    The company must request and receive authorization from the FDA to continue marketing the products with the same modified exposure information after the initial exposure modification orders expire in five years. The FDA also may withdraw the initial, and any potential subsequent, exposure modification orders if the agency determines that, among other things, the orders are no longer expected to benefit the health of the population as a whole; for example, as a result of an uptake in use of the products by youth or former smokers, or a decrease in the number of current smokers who completely switch to the products.

    In reaching today’s determination, the FDA considered both the current legal status of menthol cigarettes and the available science demonstrating that these particular products could help addicted cigarette smokers reduce their nicotine consumption and the number of cigarettes they smoke per day. The FDA is committed to moving forward with the rulemaking process to ban menthol as a characterizing flavor in cigarettes and all characterizing flavors in cigars and remains on track to issue proposed rules in the spring of 2022.

    22nd Century Group welcomed the FDA decision. “Today’s decision to authorize VLN’s MRTP application places the FDA and 22nd Century together at the vanguard of transforming the tobacco industry,” said James A. Mish, chief executive officer at 22nd Century Group, in a statement.

    “With 60 percent of adult smokers in our U.S. market research telling us they are likely to try VLN, this is a complete game-changer for 22nd Century, the tobacco industry, public health, and adult smokers looking to change their relationship with nicotine–the addictive chemical found in all tobacco products.

    “This is the first, and most likely will be the only, combustible cigarette to ever carry the FDA’s MRTP designation. The FDA’s decision to require the additional headline claim ‘Helps You Smoke Less’ alongside our requested headline claim of ’95 percent Less Nicotine’ gives adult smokers a crystal-clear reason to replace their conventional and highly addictive cigarettes with VLN.”

  • FDA Releases Draft Guidance on Validation of Test Methods

    FDA Releases Draft Guidance on Validation of Test Methods

    Photo: PMI

    The U.S. Food and Drug Administration on Dec. 21 announced the availability of a draft guidance for the industry titled “Validation and Verification of Analytical Testing Methods Used for Tobacco Products” and is requesting comments, including scientific and other information, concerning the recommendations set forth in the draft guidance. The comment period will continue through Feb. 22, 2022.

    The draft guidance, when finalized, would provide information and recommendations related to the validation and verification of analytical test methods, including analytical testing of tobacco product constituents, ingredients and additives as well as stability testing of tobacco products. This draft guidance would help the industry produce more consistent and reliable analytical data used to support regulatory submissions for finished tobacco products.

  • FDA Nominee Vows to Close Synthetic Nicotine Loophole

    FDA Nominee Vows to Close Synthetic Nicotine Loophole

    Robert Califf

    Robert Califf vowed to close the synthetic nicotine loophole if appointed commissioner of the U.S. Food and Drug Administration, according to a report by Vaping360.

    During Califf’s nomination hearing on Dec. 14, Wisconsin Senator Tammy Baldwin expressed concern over reports that companies are switching to making flavored synthetic nicotine products in the wake of FDA marketing denial orders.

    “As FDA commissioner, how would you work to address the rise in youth use of synthetic nicotine, and will you commit to working with Congress to ensure that the FDA has the authorities and resources it needs to crack down on these products?” Baldwin asked.

    In response, Califf first noted that is crucial to appoint the right person to succeed Center for Products Director Mitch Zeller, who plans to retire in April 2022.

    “Secondly,” Califf continued, “this is not limited to children. I may have some family members using synthetic nicotine, I learned as I was going through the paces here. And what people don’t realize is that there are two enantiomers of nicotine—one of which is not occurring in nature—that are in this product, and its properties are not known.

    “So we’ve got to close this loophole,” Califf added, “so that we make sure that we understand the risks and benefits, and particularly deal with the issues in children.”

    The Senate Health, Education, Labor & Pensions Committee will vote soon on whether to recommend Califf’s nomination to the full Senate. If the committee approves him, the former commissioner can expect full Senate confirmation to be the new commissioner soon, probably in January.

  • Zeller to Retire from CTP in April

    Zeller to Retire from CTP in April

    Mitch Zeller (Photo: David Parker)

    Mitch Zeller, the director of the Food and Drug Administration’s Center for Tobacco Products, plans to retire in April 2022 after serving in the post since 2013, reports The Washington Post. In a letter to staff, acting FDA Commissioner Janet Woodcock praised his work as “invaluable and instrumental” to advancing “numerous historic public health milestones in tobacco regulation.”

    A graduate of Dartmouth College and the American University Washington College of Law, Zeller has been working on FDA issues for more than 30 years. He began his career as a public interest attorney in 1982 at the Center for Science in the Public Interest (CSPI). In 1988, Zeller left CSPI to become counsel to the human resources and intergovernmental relations subcommittee of the House of Representatives’ government operations committee, where he conducted oversight of enforcement of federal health and safety laws.

    In 1993, Zeller joined the staff of then FDA Commissioner David Kessler. What began as a two-week assignment by Kessler to examine the practices of the tobacco industry led to his serving as associate commissioner and director of the FDA’s first Office of Tobacco Programs. Instrumental in crafting the agency’s 1996 tobacco regulations, Zeller also represented the FDA before Congress, federal and state agencies. Zeller also served as an official U.S. delegate to the World Health Organization working group for the Framework Convention on Tobacco Control.

    In 2000, Zeller became executive vice president of the American Legacy Foundation. His responsibilities there included marketing, communications, strategic partnerships and, in 2002, creating the foundation’s first Office of Policy and Government Relations. That year, Zeller joined PinneyAssociates, where, as senior vice president, he provided strategic planning and communications advice. 

    He left PinneyAssociates in 2013 to begin his second stint at the FDA.

  • Final Guidance on Tobacco User Fees

    Final Guidance on Tobacco User Fees

    Photo: Stranislav Nyenahov

    The U.S. Food and Drug Administration has issued a final guidance relating to tobacco product user fees.

    Titled, “Tobacco Product User Fees: Responses to Frequently Asked Questions,” this document provides details about what information is needed to assess user fees owed by each domestic manufacturer or importer of tobacco products and how FDA determines whether a company owes user fees in each quarterly assessment.

    Among other topics, this guidance explains how the FDA determines which companies are included in the quarterly tobacco user fee assessments; whether water pipe tobacco is subject to user fee requirements; and how companies should submit their monthly report to the agency.

    The Federal Food, Drug and Cosmetic (FD&C) Act requires FDA to “assess user fees on, and collect such fees from, each manufacturer and importer of tobacco products subject to” the tobacco product provisions of the FD&C Act.

    The tobacco products that are subject to user fee assessments are cigarettes, snuff, chewing tobacco, roll-your-own tobacco, cigars, and pipe tobacco. ENDS products, such as e-cigarettes, are not subject to user fee assessments.

    The FD&C Act provides for the total quarterly assessment to be allocated among specified classes of tobacco products. The class allocation is based on each tobacco product class’s volume of tobacco products removed into commerce. Within each class of tobacco products, an individual domestic manufacturer or importer is assessed a user fee based on its market share for that tobacco product class.

  • Down to the Wire

    Down to the Wire

    Photo: kurgu128

    Uncertainty lingers about the future for vaping as the FDA decides the fate of the remaining marketing applications.

    By Stefanie Rossel

    Two months after the Sept. 9, 2021, deadline for the U.S. Food and Drug Administration to determine the fate of millions of premarket tobacco product applications (PMTAs), uncertainty continues to prevail, and the fate of e-liquids with flavors other than tobacco remains unclear. The agency’s approach to e-cigarette regulation to date, alternatingly labeled a “fiasco” or “bureaucratic chaos” by critics, suggests that the U.S. may be heading toward a de facto ban of all nontobacco flavors.

    The 2009 Tobacco Control Act (TCA) gave the FDA authority to regulate cigarettes, smokeless tobacco, cigarette tobacco and roll-your-own tobacco. The “deeming rule” of Aug. 8, 2016, extended the agency’s authority to electronic nicotine-delivery systems (ENDS), cigars, pipe tobacco, nicotine gels and hookah tobacco. As a result, deemed products are now subject to all TCA rules, including the requirement that any new tobacco product must receive premarket authorization from the FDA to be legally marketed.

    Following litigation by anti-tobacco groups, a court set the deadline for manufacturers to submit their applications by Sept. 9, 2020, and gave the agency one year to decide on them. The time frame presented a daunting challenge to the chronically understaffed agency. The FDA received more than 6.5 million marketing applications for newly deemed tobacco products alone. At press time, the agency had acted on more than 98 percent of these applications. Its actions included refuse-to-accept letters to more than 200,000 applications, a refuse to file order for approximately 4.5 million products submitted by a single company and marketing denial orders (MDOs) for more than 1 million nontobacco-flavored ENDS. Only three new tobacco products received marketing granted orders. The FDA still needs to rule on applications covering about 80,000 products, including those submitted by market leaders such as Juul and NJOY.

    David Sweanor

    Retroactive Change of Requirements

    Most of the MDOs were directed at vape products with flavors other than tobacco, including menthol. The manufacturers, the agency claimed in its MDO letters, had failed to provide sufficient evidence that their nontobacco-flavored products deliver a net public health benefit for adult smokers compared with the “threat posed by the well-documented, alarming levels of youth use” of flavored vapes through either a randomized controlled trial in which a specific group of people is examined through intervals of time, or a longitudinal cohort study, which tracks large groups of people over an extended period of time.

    “It appears that the FDA is planning to significantly hobble the vaping category and thus protect lethal cigarettes from what is perhaps the greatest threat that business has ever faced,” says David Sweanor, adjunct professor of law at the University of Ottawa. “But how far this succeeds depends on many factors, not least what the courts will say about the process.”

    The requirement is now part of the PMTA rules, which the agency finalized in October 2021, and which took effect in November. However, it had not been in the original guidance for PMTA applications, according to critics.

    For most smaller vape manufacturers, the FDA’s ruling has meant the end of their business activities. “Like most vape companies, we cannot remain financially viable with only two [tobacco-flavored] products, and we will most certainly be forced to close our business after eleven years,” California-based Kai’s Virgin Vapor states on its website.

    Paul Blair

    Temporary Stays Granted

    Others have taken legal action. Arguing that the FDA moved the goalpost by retroactively changing the PMTA requirements, MDO recipients filed more than 40 petitions for review and stay on the grounds that the FDA had acted in an “arbitrary and capricious manner.” At the time of writing, at least five companies had been granted a temporary stay either by the FDA or the courts, and their products were back under review.

    Among them was Turning Point Brands, which may now continue to market its vapor products while its PMTAs are being reassessed. “We’re encouraged that the agency has acknowledged the robust nature of our PMTAs for a wide range of tobacco, menthol and other flavored vapor products,” Paul Blair, vice president of government affairs at Turning Point Brands, told Tobacco Reporter. “These open system e-liquids, sold predominantly in vape shops across the U.S., play an important role in providing reduced-risk options to more than 30 million adult smokers who may be looking for alternatives to combustible cigarettes. It is our hope that at the end of the PMTA review process, the agency will preserve the important off-ramp from cigarettes to a wide range of vapor products used by adults. Preserving these options will ensure that the diverse vapor marketplace can help ultimately achieve a more significant reduction in smoking rates across the U.S.”

    “The cases look strong,” Sweanor states. “Administrative bodies, like referees in sporting competitions, are challenged when they seek to change the rules mid-game. This is supposed to be an example of transparent rule-making in a democratic society. There is also a history, in the U.S. and globally, of vaping companies using the courts to overturn laws and administrative rulings that have overly restricted their products and marketing.”

    However, a second review does not guarantee that the products will receive authorization. Critics fear that manufacturers who have received an MDO will continue to appeal the decisions to maximize the time to sell their products. THR advocates hope that legal challenges will force the FDA to make more careful decisions.

    Uncertain Future for Flavors

    There are many indications that the era of nontobacco vapor flavors is coming to an end in the U.S. After bombarding the vapor business with MDOs, the FDA on Oct. 12 approved R.J. Reynolds Vapor Co.’s Vuse Solo and accompanying tobacco-flavored e-liquid pods—the first-ever marketing granted order for an e-cigarette.

    Tobacco harm reduction advocates received the news with mixed feelings. While welcoming the agency’s acknowledgement that vape products can help adult smokers to quit cigarettes, they were disappointed that the order pertained to an outdated device with few users. Furthermore, while authorizing two Vuse tobacco-flavored e-liquid pods, the agency issued 10 MDOs for Vuse Solo nontobacco-flavored pods, claiming that Reynolds failed to demonstrate they were appropriate for the protection of public health.

    The agency is still evaluating Reynolds’ application for menthol-flavored products under the Vuse Solo brand. Menthol is another bone of contention: In late April, the FDA announced that it would initiate a notice and comment rule-making process to ban menthol-flavored cigarettes and all characterizing flavors in cigars and cigarillos within the next year. Vape manufacturers are hence unsure of whether their mentholated products will remain on the market.

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    Sloppy Assessment

    In its denial of providing marketing authorization to nontobacco-flavored e-liquids, the FDA referred to the most recent National Youth Tobacco Survey (NYTS), arguing the study had shown that among the estimated 2 million middle school and high school students that were using e-cigarettes in 2021, more than eight in 10 were using nontobacco-flavored vape products. It did not mention that, according to the same study, the use of e-cigarette among youths has more than halved over the past two years, from 27.5 percent in 2019 to 11.3 percent currently.

    Critics have accused the FDA of being “obsessed with youth vaping rates and flavors.” The online publication Filter revealed that, in order to cope with the unprecedented flood of PMTA submissions before the court-ordered deadline, the FDA relied on a database query to identify the top-12 manufacturers with the largest number of pending PMTAs for nontobacco-flavored e-liquid products not in the third of three FDA review phases.

    This approach allowed the agency to filter out 85 percent of all pending PMTA applications. It then introduced, apparently for the first time, a “fatal flaw” standard. The fatal flaw review is a simple review in which the reviewer examines the submission to identify whether or not it contains the necessary type of studies. “The fatal flaw review will be limited to determining presence or absence of such studies; it will not evaluate the merits of the studies,” according to an FDA Center for Tobacco Products Office of Science memorandum cited by Filter.

    With its attempt at speeding up matters, the agency has done itself no favors, say critics. The road to regulatory certainty in the U.S. vape market will likely become even longer. “At this point,” Sweanor suggests, “the solution could be to announce reasonable product standards aimed squarely at reducing harms—as is done with foods—rather than treat each subcategory of each product as if totally independent of other products.”

    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.
  • Biden Picks Robert Califf to Lead FDA

    Biden Picks Robert Califf to Lead FDA

    Robert Califf

    U.S. President Joe Biden today announced that he would nominate Robert M. Califf, a former commissioner of the Food and Drug Administration, to lead the agency again, reports The New York Times.

    A cardiologist and long-time consultant to drug companies, Califf ran the FDA during the last year of the Obama administration

    “Dr. Califf is one of the most experienced clinical trialists in the country, and has the experience and expertise to lead the Food and Drug Administration during a critical time in our nation’s fight to put an end to the coronavirus pandemic,” Biden said in a statement.

    Califf has been a forceful advocate for tobacco control; before he was the FDA commissioner, he was the agency’s deputy commissioner for medical products and tobacco. In an appearance with other former commissioners this year, he said, “I have never seen more capable or nastier lawyers than what I experienced in trying to deal with the tobacco industry. It was awesome and quite frightening for public health.”

    After stepping down as the vice chancellor for clinical and translational health at Duke University, Califf has worked as a senior adviser to Verily Life Sciences, a health technology firm, and its sister company Google Health. Califf, who remains an adjunct professor of medicine at both Duke and Stanford University, is on the corporate board of Cytokinetics, a biopharmaceutical company, according to its website.

    Califf said he was honored to be nominated for the position “at a critical time for our country,” adding, “There’s a lot of work to do, and if confirmed I look forward to rejoining the great team at the FDA to help in their inspiring mission to serve the public.”

    The FDA has had seven different commissioners, including Califf, since 2012, when Margaret Hamburg left the post.

  • FDA Rescinds Marketing Denial for Humble Juice

    FDA Rescinds Marketing Denial for Humble Juice

    Photo: AliFuat

    The U.S. Food and Drug Administration has rescinded the marketing denial order (MDO) issued Sept. 15, 2021, for Humble Juice Co.’s flavored e-liquid products, the company announced on Nov. 5.

     Humble had filed a petition in October with the U.S. Court of Appeals for the Ninth Circuit, challenging the FDA’s decision and seeking to have the MDO vacated. Following the receipt of the rescission letter, Humble withdrew its petition as FDA’s rescission of Humble’s MDO places the brand’s flavored e-liquids back into the PMTA review process and provides Humble with a pathway to market its products while its PMTAs are pending.

    FDA’s rescission letter states that upon further review it identified information contained in Humble’s PMTA that requires additional evaluation such as “randomized controlled trials comparing tobacco-flavored ENDS to flavored ENDS as well as several cross-sectional surveys evaluating intentions to use or likelihood of use in current smokers, current ENDS users, former tobacco users, and never users.”

    The agency also stated that due to the unusual circumstances, it “has no intention of initiating an enforcement action” against any of Humble’s flavored e-liquid products with pending PMTAs. Humble will continue to market its products while its application remains in the review process.

    “FDA’s decision to rescind the MDO re-instills our faith in this challenging but science-based regulatory process,” said Humble CEO Daniel Clark. “We remain confident in and proud of our extensive PMTA submission. We are committed to working with the FDA to obtain marketing orders for the products submitted in our initial PMTAs in order to provide Humble’s adult consumers with flavor-filled and affordable e-juice long into the future.”

  • Filter: Some PMTAs Not Evaluated on Merits

    Filter: Some PMTAs Not Evaluated on Merits

    Photo: Ronstix

    Confronted with an unexpected large volume of premarket tobacco applications, the U.S. Food and Drug Administration subjected some premarket tobacco product applications (PMTAs) to only a superficial review, according to documents obtained by Filter.

    The report follows the FDA’s denial of more than 1,167,000 marketing applications since Sept. 9, 2021.

    The PMTA review process comprises three phases: Phase I (Acceptance), which essentially means an application has been received; Phase II (Notification or Filing), which entails acknowledging a company had enough information for its applications to be formally filed; and Phase III (Review), which involves a substantive scientific evaluation, followed by a marketing granted order or marketing denial order (MDOs).

    Overwhelmed by the large number of PMTAs and facing a court-ordered deadline of Sept. 9, 2021, the FDA in effect opted for a shortcut, according to Filter.

    The publication cites a memorandum signed on July 9 by Matthew Holman, the director of FDA Center for Tobacco Products Office of Science (OS). “Considering the large number of applications that remain to be reviewed by the September 9, 2021, deadline, OS will conduct a Fatal Flaw review of PMTAs not in Phase III for non-tobacco-flavored ENDS products,” it reads.

    The Fatal Flaw review is a simple review in which the reviewer examines the submission to identify whether or not it contains the necessary type of studies. “The Fatal Flaw review will be limited to determining presence or absence of such studies; it will not evaluate the merits of the studies,” the memorandum states.

    Filter suggests that CTP reviewers created what’s probably a new method to get through a backlog of millions of PMTAs, searched those applications for longitudinal cohort studies and randomized clinical trials without evaluating any other evidence, and for applications lacking them, did not advance them beyond Phase II and just sent out templated MDOs.