Former U.S. Food and Drug Administration Commissioner Robert Califf is expected to return to the regulatory agency after President Joe Biden nominated the cardiologist for the position. According to the Washington Post, if confirmed by the Senate, Califf would take over an agency poised to make key decisions on the vaping industry, as well as coronavirus vaccines and treatments while facing criticism of recent controversial drug approvals and widespread burnout due to the ongoing pandemic.
Robert Califf/ Credit: Duke University
Califf previously served as commissioner for nearly a year in Obama’s second administration after an overwhelming vote in his favor. The White House has not finalized its decision, and the people with knowledge cautioned the situation could still change. But nine months into its search for a permanent FDA chief, Califf is now viewed as the leading candidate for the job.
Despite the agency’s prominent role in the nation’s coronavirus response, it has been without a permanent leader since Biden took office in January. Califf would replace acting Commissioner Janet Woodcock, the agency’s longtime drug chief, who has helmed the agency for nine months. Califf returned to cardiology after his tenure at FDA and currently works for the Duke Clinical Research Institute, but also took a position leading health policy at Google’s parent company Alphabet in 2019.
While he garnered support from many senators in his 2016 confirmation process, Sen. Bernie Sanders (I-Vt.) voiced concerns about his industry ties and said he could oppose the vote. Califf at the time had written papers with pharmaceutical industry executives and consulted for drug and device makers.
The U.S. Food and Drug Administration announced today it has authorized the marketing approval of three new vapor products to the RJ Reynolds (RJR) Vapor Company for its Vuse device and two tobacco-flavored pods It marks the first set of electronic nicotine-delivery system (ENDS) products ever to be authorized by the FDA through the premarket tobacco product application (PMTA) pathway. It also denied Vuse PMTAs for flavored products other than tobacco.
The FDA issued marketing granted orders for RJR’s Vuse Solo closed ENDS device and accompanying tobacco-flavored e-liquid pods, specifically, Vuse Solo Power Unit, Vuse Replacement Cartridge Original 4.8% G1, and Vuse Replacement Cartridge Original 4.8% G2.
The agency suggests the data submitted to the FDA by RJR demonstrated that marketing of these products is appropriate for the protection of public health. The authorization allows these products to be legally sold in the U.S.
“Today’s authorizations are an important step toward ensuring all new tobacco products undergo the FDA’s robust, scientific premarket evaluation. The manufacturer’s data demonstrates its tobacco-flavored products could benefit addicted adult smokers who switch to these products – either completely or with a significant reduction in cigarette consumption – by reducing their exposure to harmful chemicals,” said Mitch Zeller, director of the FDA’s Center for Tobacco Products. “We must remain vigilant with this authorization and we will monitor the marketing of the products, including whether the company fails to comply with any regulatory requirements or if credible evidence emerges of significant use by individuals who did not previously use a tobacco product, including youth. We will take action as appropriate, including withdrawing the authorization.”
Under the PMTA pathway, manufacturers must demonstrate to the agency that, among other things, marketing of the new tobacco product would be appropriate for the protection of the public health. These products were found to meet this standard because, among several key considerations, the agency determined that study participants who used only the authorized products were exposed to fewer harmful and potentially harmful constituents (HPHCs) from aerosols compared to users of combusted cigarettes, according to a release.
“The toxicological assessment also found the authorized products’ aerosols are significantly less toxic than combusted cigarettes based on available data comparisons and results of nonclinical studies. Additionally, the FDA considered the risks and benefits to the population as a whole, including users and non-users of tobacco products, and importantly, youth,” the release states. “This included review of available data on the likelihood of use of the product by young people. For these products, the FDA determined that the potential benefit to smokers who switch completely or significantly reduce their cigarette use, would outweigh the risk to youth, provided the applicant follows post-marketing requirements aimed at reducing youth exposure and access to the products.
The FDA also issued 10 marketing denial orders (MDOs) for flavored ENDS products submitted under the Vuse Solo brand by RJR. Due to potential confidential commercial information issues, the FDA is not publicly disclosing the specific flavored products.
These products subject to an MDO for a premarket application may not be introduced or delivered for introduction into interstate commerce. Should any of them already be on the market, they must be removed from the market or risk enforcement. Retailers should contact RJR with any questions about products in their inventory. The agency is still evaluating the company’s application for menthol-flavored products under the Vuse Solo brand.
“Additionally, today’s authorization imposes strict marketing restrictions on the company, including digital advertising restrictions as well as radio and television advertising restrictions, to greatly reduce the potential for youth exposure to tobacco advertising for these products,” the release states. “RJR Vapor Company is also required to report regularly to the FDA with information regarding the products on the market, including, but not limited to, ongoing and completed consumer research studies, advertising, marketing plans, sales data, information on current and new users, manufacturing changes and adverse experiences.
The FDA may suspend or withdraw a marketing order issued under the PMTA pathway for a variety of reasons if the agency determines the continued marketing of a product is no longer “appropriate for the protection of the public health,” such as if there is a significant increase in youth initiation. While today’s action permits the products to be sold in the U.S., it does not mean these products are safe or “FDA approved.”
The agency will continue to issue decisions on applications, as appropriate, and is committed to working to transition the current marketplace to one in which all ENDS products available for sale have demonstrated that marketing of the product is “appropriate for the protection of the public
Triton Distribution filed a motion to stay the U.S. Food and Drug Administration’s decision to issue the company marketing denial orders (MDOs) for its premarket tobacco product applications (PMTAs). The company requested a decision from the judge by Oct. 15.
“Black-letter rules of administrative law prevent an agency from retroactively changing legal requirements and from doing so without accounting for reliance interests. FDA failed to satisfy these requirements when it executed an about-face on the evidence it required to support a premarket tobacco product application (“PMTA”) for a marketing order for flavored electronic nicotine delivery system (“ENDS”) products almost a year after such applications were due,” the motion states. “FDA also acted arbitrarily and capriciously by ignoring relevant evidence found in Petitioner Wages and White Lion Investments, LLC d/b/a Triton Distributions (“Triton”) PMTA and applying a double standard to its consideration of that evidence when it issued Triton a marketing denial order (“MDO”). Further, by imposing a new, across-the-board requirement that flavored ENDS products be demonstrably more effective at promoting smoking cessation than otherwise identical tobacco-flavored products, FDA acted contrary to its authority under Section 910 of the Food, Drug and Cosmetic Act (“FDCA), 21 U.S.C. § 387j, and not in accordance with law.”
Triton states that it has been irreparably harmed as a result of the FDA’s actions and faces an imminent shutdown of its business in approximately two weeks. This is why Triton entered an emergency stay of the “FDA’s MDO for Triton’s products by October 15, 2021, and order expedited merits briefing. Respondent FDA consents to the proposed expedited merits briefing schedule but opposes a stay.”
At least six companies have filed lawsuits challenging the agency’s decision to make the companies remove their products from the market. Last week, the FDA rescinded the MDO issued to Turning Point Brands (TPB) and the company will be allowed to continue marketing its vapor products while the FDA re-reviews the company’s premarket tobacco product application (PMTA).
The FDA admitted it made an error in TPB’s PMTA review and TPB did in fact submit studies that the agency decided during the PMTA process were needed, after saying for years the studies were not required. “Upon further review of the administrative record, FDA found relevant information that was not adequately assessed,” reads the FDA letter to TPB. “Specifically your applications did contain randomized controlled trials comparing tobacco-flavored ENDS to flavored ENDS as well as several cross-sectional surveys evaluating patterns of use, likelihood of use, and perceptions in current smokers, current ENDS users, former tobacco users, and never users, which require further review.”
Turning Point Brands (TPB) has had its marketing denial orders (MDOs) rescinded by the U.S. Food and Drug Administration. The company will be allowed to continue marketing its vapor products while the FDA re-reviews the company’s premarket tobacco product application (PMTA).
“We are encouraged by the FDA’s decision to reconsider our product applications and look forward to engaging the agency as our PMTAs are reviewed,” said Larry Wexler, president and CEO, Turning Point Brands. “It is important that the PMTA process is transparent, purposeful, and evidence-based. Our organization dedicated significant time and resources in filing our applications in accordance with agency guidance. We remain hopeful that the depth and range of our studies and data will persuade the FDA that the continued marketing of our vapor products is appropriate for the protection of the public health and that the agency will ultimately preserve a diverse vapor market for the more than 30 million American adult smokers who may wish to transition from combustible cigarettes to lower risk alternatives.”
Credit: Momius
The FDA admitted it made an error in TPB’s PMTA review and TPB did in fact submit studies that the agency decided during the PMTA process were needed, after saying for years the studies were not required. “Upon further review of the administrative record, FDA found relevant information that was not adequately assessed,” reads the FDA letter to TPB. “Specifically your applications did contain randomized controlled trials comparing tobacco-flavored ENDS to flavored ENDS as well as several cross-sectional surveys evaluating patterns of use, likelihood of use, and perceptions in current smokers, current ENDS users, former tobacco users, and never users, which require further review.”
The letter comes after TPB filed a petition with the court that forced the FDA to provide an administrative record for its decisions on PMTAs. TPB sells various flavored e-liquids marketed under the Solace, VaporFi and Vapor Shark brands. TPB then filed a stay motion asking the the court to review the FDA order “on the grounds that it is arbitrary and capricious, an abuse of discretion, contrary to the Federal Food, Drug, and Cosmetic Act, as amended by the Family Smoking Prevention and Tobacco Control Act of 2009, and otherwise not in accordance with law.”
Avail Vapor and several other companies that received MDOs have also now filed petitions for information related to their PMTA reviews. After the FDA rescinded TPB’s MDOs, the company dropped its lawsuit against the regulatory agency.
“In light of the unusual circumstances,” the FDA’s Center for Tobacco Products (CTP) Director Matt Holman stated in the letter. “FDA has no intention of initiating an enforcement action” against TPB’s products that had previously received an MDO.
The U.S Food and Drug Administration today issued warning letters to 20 companies for unlawfully continuing to market electronic nicotine-delivery system (ENDS) products that are the subject of marketing denial orders (MDOs).
These are the first warning letters issued for the marketing of products subject to MDO determinations on their premarket tobacco product applications (PMTAs), according to an FDA statement. The FDA has also issued warning letters for the unlawful marketing of tobacco products to one company that received Refuse to File (RTF) determinations on their PMTA, one company that received both RTF and MDO determinations on their PMTA, and six companies that did not submit any premarket applications.
“Collectively, these 28 companies have listed a combined total of more than 600,000 products with the FDA. All new tobacco products sold, distributed, or imported in the United States without FDA authorization are marketed unlawfully and risk FDA enforcement,” the statement reads. “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.”
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.
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.
The U.S. Food and Drug Administration has issued two final rules for the premarket review of new tobacco products. These foundational rules provide additional information on the requirements for the content, format and review of premarket tobacco product applications (PMTAs) and substantial equivalence (SE) reports—two of the most commonly used pathways through which a manufacturer can seek marketing authorization for a new tobacco product from the FDA.
According to the agency, the finalization of these rules helps ensure that all future submissions contain the basic information needed to determine whether the new tobacco products meet the relevant premarket requirements to efficiently and effectively implement the Family Smoking Prevention and Tobacco Control Act. It also formalizes the general procedures the FDA follows when evaluating PMTAs, including application acceptance, application filing and inspections.
It also outlines, among other things, requirements for submitting application amendments, the time for review, withdrawal of applications, postmarket reporting requirements for applicants that receive marketing granted orders, the FDA’s communications with an applicant and the FDA’s disclosure procedures and electronic submission requirements. It also allows for a supplemental PMTA as opposed to a new submission in cases such as authorization for a modified version of a tobacco product for which they have already received a PMTA marketing granted order.
“These final rules are important components of the FDA’s comprehensive approach to tobacco product regulation, which includes premarket application review, science-based use of the product standard authority and prioritized compliance and enforcement actions,” said acting FDA Commissioner Janet Woodcock, in a statement. “The FDA is committed to protecting Americans from tobacco-related disease and death by ensuring that new tobacco products undergo appropriate regulatory review to determine if they meet the public health standards set by law. If new tobacco products do not meet the standards for these pathways, they cannot be marketed or sold in the United States.”
“Conducting review of new tobacco products before they can be legally marketed is a critical responsibility of the FDA,” said Mitch Zeller, director of the FDA’s Center for Tobacco Products. “These final rules will provide greater clarity and efficiency in review of new tobacco products by describing information that any company must provide if they seek to market a new tobacco product in this country.”
On Jan. 19, 2021, the PMTA and SE final rules were displayed in the Federal Register but did not publish. On Jan. 20, 2021, a memo from the White House Chief of Staff ordered the withdrawal of any rules that did not publish in the Federal Register by noon on that day. Therefore, these final rules were withdrawn at that time. The rules displaying today reflect clarifying changes made from the previous versions, but no significant substantive changes. Both final rules will publish on Oct. 5 and are effective Nov. 4. Beginning on the effective date, applications submitted through these pathways must meet the requirements described in these final rules.
At least three suits stemming from marketing denial orders (MDOs) issued by the U.S. Food and Drug Administration in response to premarket tobacco product applications (PMTAs) have been filed in the 2nd, 6th and 11th circuits courts of appeals (possibly more) against the FDA. Turning Point Brands (TPB) filed first a petition for review (a statutory review) with the United States Court of Appeals for the Sixth Circuit. TPB then filed an emergency motion to stay the FDAs order to remove TPB’s products from the market. Bidi Vapor and at least one other company have filed similar suits.
Credit: Vitalii Vodolazskyi
The TPB petition forced the FDA to provide an administrative record for its decisions on PMTAs. TPB sells various flavored e-liquids marketed under the Solace, VaporFi and Vapor Shark brands. TPB is now asking the court to review the FDA order “on the grounds that it is arbitrary and capricious, an abuse of discretion, contrary to the Federal Food, Drug, and Cosmetic Act, as amended by the Family Smoking Prevention and Tobacco Control Act of 2009, and otherwise not in accordance with law.” The company requests the court “vacate or modify” the FDA order and asks that TPB be allowed to “continue to market the products subject to the challenged order.”
In an explanation for its actions, the FDA’s director for its Center for Tobacco Products (CTP), Mitch Zeller, stated in a release that many of the accepted applications ultimately received an RTF letter at the filing stage of the review process because the application did not include required information. “For example, companies received RTF letters for not including required content such as ingredient listings, labels for each product to be marketed, or adequate environmental assessments,” he wrote.
In a joint news release with Zeller and acting FDA commissioner Janet Woodcock, the FDA explained that the applications from many MDO recipients “lacked sufficient evidence that they have a benefit to adult smokers sufficient to overcome the public health threat posed by the levels of youth use” of electronic nicotine-delivery systems (ENDS) products.
The PMTAs submitted by TPB and denied by MDO included an in-depth toxicological review, a clinical study, and studies on patterns and likelihood of use, according to the motion to stay filed by TPB on Sept. 30. The stay contained responses from the FDA’s response to TPB’s petition for review. “TPB’s studies demonstrated that TPB’s products help adult smokers transition away from riskier traditional cigarettes. Those studies confirmed that youth users do not currently purchase TPB products and there is virtually zero likelihood that they will in the future,” the motion states.
TPB accuses the FDA of moving the goalposts for data needed to receive a marketing order based on what the agency “learned” from the “review [of] PMTAs for flavored ENDS so far,” according to the stay. TPB noted that the “North Star of administrative law” is that agencies cannot induce regulated parties to rely on “agency representations about regulatory requirements,” then penalize them using the previously unannounced criteria after-the-fact.
“But that is precisely what FDA did here,” the stay motion states. “[The] FDA reasoned that TPB failed to conduct ‘a randomized controlled trial and/or longitudinal cohort study’ or other studies performed ‘over time’ to show that TPB’s specific flavored products help adult users stop smoking more than tobacco-flavored products do. Yet FDA previously deemed these studies unnecessary.”
Seven leading public health, medical and parent organizations are urging the U.S. Food and Drug Administration to expedite decisions on remaining marketing applications for e-cigarettes and promptly deny applications for all flavored e-cigarettes, including menthol-flavored products.
The organizations say they are concerned about these products’ appeal to youth and adverse impact on public health.
In a letter to Acting FDA Commissioner Janet Woodcock, the groups also urged the FDA to prioritize enforcement against unauthorized flavored e-cigarettes with the largest market shares and products with the highest prevalence of youth use.
The groups sending the letter are the American Academy of Pediatrics, American Cancer Society Cancer Action Network, American Heart Association, American Lung Association, Campaign for Tobacco-Free Kids, Parents Against Vaping e-cigarettes and Truth Initiative.
Since Sept. 9, the FDA has denied marketing applications for more than 1,167,000 products, but it has yet to issue decisions on e-cigarette brands with the highest market shares, such as Juul, Vuse, NJOY and Blu, which make up over 78 percent of the market, according to Nielsen data.
The health groups expressed particular concern that the FDA is still considering whether to authorize any menthol-flavored e-cigarettes and urged the FDA not to do so given the clear evidence that menthol is a flavor that appeals to and is widely used by kids.
“Contrary to the FDA’s August 26 statement that menthol e-cigarette products raise ‘unique considerations’ for purposes of FDA review, we do not believe there is anything ‘unique’ about menthol flavoring that would justify issuance of a marketing order,” the groups wrote in their letter. “Indeed, there is no question that when FDA decided to prioritize enforcement against cartridge-based e-cigarettes in flavors other than menthol and tobacco, youth shifted to using menthol-flavored products.”
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.
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.
As of Sept. 17, the U.S. Food and Drug Administration has issued 295 marketing denial orders (MDOs) for more than 1,089,000 flavored e-liquid products. The move has sent shockwaves through the industry and crippled many vapor industry businesses ranging from prominent players to small business owners. All of the MDOs were for flavored e-liquids that were not either tobacco or menthol.
Credit: Elnur
Many of the most surprising denials were from company’s that many believed had the funds and experience to submit extensive and detailed premarket tobacco product applications (PMTAs). Turning Point Brands (TPB) International, Humble Juice Co., Beard Vape Co. and Avail Vapor were a few of the long-standing vapor industry companies whose flavored other-than-tobacco products were denied marketing approval.
The letters are straightforward, according to James Xu, founder of Avail Vapor. “It just says you failed to demonstrate in your application for a flavored [electronic nicotine delivery system] ENDS product [that the benefits] outweigh the known risks of youth appeal,” Xu said, speaking only with Vapor Voice. “Then it goes on to say that it can be corrected with some form of a randomized controlled trial or longitudinal cohort studies that the FDA had previously stated weren’t required.”
Many industry experts believe the FDA will only approve some tobacco and menthol flavors, most expected to be in closed-system formats. The FDA has yet to make a decision on any major tobacco company’s PMTA submissions for brands such as Juul, Logic, Vuse and Blu. The agency has not denied any synthetic product, although it’s difficult to know for sure since only brand names have been released and not actual flavor profiles.
Many companies are moving towards using synthetic nicotine in their products in hopes to avoid current FDA regulations. The agency has stated that a synthetic product “may” be outside the agency’s jurisdiction.
Eric Lindblom, a senior scholar at Georgetown’s O’Neill Institute for National and Global Health Law and a former director of the FDA’s Center for Tobacco Products Office of Policy, said that, in response to such moves by vapor companies, the FDA could either assert jurisdiction over synthetic nicotine as tobacco product or push for synthetic nicotine to be regulated like any other drug.
The lawsuits are coming. At least two companies have already filed lawsuits against the FDA, although Vapor Voice could not confirm what companies had filed suit. The FDAs public list of companies released on Sept. 17 only includes 241 brands, the remaining 54 MDOs are believed to for brands that had not yet been on the market.
“If smoking rates go up in 2022 and beyond, do not blame the tobacco industry. This predictable result will entirely be the fault of elected officials and regulators who have utterly failed to protect public health,” said Gregory Conley, president of the American Vaping Association. “The FDA’s opaque review process was intentionally designed to eliminate all but the largest players from the market. We look forward to lending our support to future court challenges.”
