Update on PMTA MDO Legal Challenges, Rescissions and PMTA Authorizations; CTP Leadership Presents at FDLI Conference
Two months after the September 9, 2021 PMTA enforcement discretion deadline, FDA has taken action on well over 90% of timely submitted PMTAs, and has issued over 323 marketing denial orders (MDOs) for more than 1.2 million non-tobacco and non-menthol flavored ENDS products The basis for the denials was the same across the board – using a new “fatal flaw” PMTA review standard, CTP reviewers were able to conclude that all the MDO’d PMTAs were missing “key evidence” that the flavored ENDS products provide an “added benefit” to adult smokers (who use the flavored ENDS products to reduce or completely switch from combusted cigarettes) that outweighs the general, known risks to youth of flavored ENDS. According to the agency, this evidence was expected to be presented in the form of randomized controlled trials (RCTs) comparing tobacco-flavored ENDS to flavored ENDS and/or longitudinal cohort studies that, among other things, evaluate the actual use of the new products, demonstrate the relative effect of the flavored products as compared to a tobacco-flavored product, or include outcomes assessing switching or combusted cigarette reduction. See FDA’s sample MDO decision summary.
As summarized in this Vaping360 article, there have been numerous legal challenges to MDOs, arguing that the denials are arbitrary, capricious, an abuse of discretion, and otherwise not in accordance with the law. As described below, a few courts have issued either full or temporary stays (holds) of the MDOs. In addition to the lawsuits, based on FDA’s updated MDO spreadsheet as of November 3, 2021, four companies (Turning Point, Fumizer, ESC Global and Humble Juice Co.) have had their MDOs completely or partially rescinded by FDA, presumably because FDA has now realized that their PMTAs did, in fact, “contain” RCTs and/or longitudinal cohort studies addressing the added benefit of flavors for adults. Three companies (Bidi Vapor, My Vape Order, and Avail Vapor) have had their MDOs administratively stayed by FDA while the agency reviews their requests to have their MDOs rescinded (presumably because their applications also contain relevant product-specific data).
On the court-ordered side, Triton Distribution (and Vapetasia, which is manufactured by Triton) had their MDO stayed by the 5th Circuit Court of Appeals. In granting the stay and holding that Triton is likely to succeed on the merits of its case arguing that its MDO is unlawful, the Court held that FDA “changed its regulatory requirements” and that this “switcheroo” to now require a randomized controlled trial and/or a longitudinal cohort study – which the Agency previously stated on numerous occasions would not be required – was arbitrary and capricious under the Administrative Procedure Act (“APA”). Accordingly, the 5th Circuit held that Triton has shown a strong likelihood of success on the merits because FDA failed to “reasonably consider the relevant issues and reasonably explain” the MDO. The Court further noted that FDA failed to consider Triton’s marketing plan, surveys, and evidence of potential benefits of flavored e-cigarettes. FDA also failed to consider the company’s legitimate reliance interests, as Triton relied on FDA’s statements made in numerous public meetings, guidance documents and rulemakings that it did not expect applicants would need to conduct long-term studies to support their PMTAs. Even FDA’s recently finalized PMTA final rules continues to emphasize this.
In addition to Triton, the 7th Circuit granted a full stay for Gripum LLC on November 4, 2021. My Vape Order (which has an FDA administrative stay in place) had its request for a judicial stay denied by the 9th Circuit, and Breeze Smoke recently had its stay request denied by the 6th Circuit.
FDA Spreadsheet (Updated 11/8/21) – Summary of Rescinded and Stayed MDOs
|Bidi Vapor||9/7/2021||FDA is reviewing this MDO pursuant to 21 C.F.R. § 10.75. On October 22, 2021, the Agency issued a stay for this MDO pending its review.|
|Gripum LLC||9/8/2021||On November 4, 2021, the United States Court of Appeals for the Seventh Circuit issued a stay of Gripum’s MDO pending resolution of Gripum’s petition for review.|
|My Vape Order Inc.||9/8/2021||FDA is reviewing this MDO pursuant to 21 C.F.R. § 10.75. On October 18, 2021, the Agency issued a stay for this MDO pending its review.|
|Fumizer LLC||9/9/2021||On October 22, 2021, FDA partially rescinded this denial with respect to certain products.|
|ECS Global||9/10/2021||On October 26, 2021, FDA partially rescinded this denial with respect to certain products.|
|Turning Point Brands (TPB International LLC)||9/14/2021||This order was rescinded on October 7, 2021.|
|Wages & White Lion Investments dba Triton Distribution||9/14/2021||On October 26, 2021, the United States Court of Appeals for the Fifth Circuit issued a stay of Triton’s MDO pending resolution of Triton’s petition for review.|
|Humble Juice Co., LLC||9/15/2021||This order was rescinded on November 2, 2021.|
|Avail Vapor LLC||9/15/2021||FDA is reviewing this MDO pursuant to 21 C.F.R. § 10.75. On November 1, 2021, the Agency issued a stay for this MDO pending its review|
|Vapetasia LLC||9/16/2021||On October 26, 2021, the United States Court of Appeals for the Fifth Circuit issued a stay of Vapetasia’s MDO pending resolution of Vapetasia’s petition for review.|
Vuse and Verve PMTA Authorizations
In the middle of FDA’s flurry of MDOs last month, on October 12, the Agency authorized the first set of ENDS products through the PMTA pathway: R.J. Reynolds (RJR) Vuse Solo closed ENDS device and accompanying tobacco-flavored e-liquid pods. (At the same time, however, FDA also issued 10 MDOs for RJR’s non-tobacco flavored Vuse Solo ENDS products, so we are still facing an uphill battle for flavors.) One of the key factors influencing a positive appropriate for the protection of the public health (APPH) determination by FDA was that study findings showed subjects using Vuse Solo were exposed to fewer harmful and potentially harmful constituents (HPHCs) from aerosols compared to users of combusted cigarettes. The toxicological assessment concluded that the authorized products’ aerosols are significantly less toxic than combusted cigarettes based on available data comparisons and results of nonclinical studies. Despite 2021 National Youth Tobacco Survey (NYTS) data that found that approximately 10 percent of high school students who currently used e-cigarettes named Vuse as their usual brand, FDA found risks to youth mitigated based on its conclusion that tobacco-flavored products are less appealing to youth. Based on these and other data, FDA concluded that authorizing these products may be beneficial for adult combusted cigarette smokers who completely switch to ENDS or significantly reduce their cigarette consumption. As with other recent PMTA marketing orders, FDA stipulated a number of strict marketing restrictions and comprehensive postmarketing reporting requirements to R.J.R. to reduce the potential for youth exposure to tobacco advertising for these products and to provide information on ongoing and completed consumer research studies, advertising, marketing plans, sales data, information on current and new users, manufacturing changes and adverse experiences.
The following week, on October 19, FDA authorized the marketing of four Verve oral tobacco products (Verve Discs Blue Mint, Verve Discs Green Mint, Verve Chews Blue Mint, and Verve Chews Green Mint) manufactured by U.S. Smokeless Tobacco Company LLC, a subsidiary of Altria. The Verve products are oral tobacco discs and chews with tobacco-derived nicotine that are chewed and discarded after use. Key findings that influenced FDA’s decision include research showing a low likelihood that youth, nonsmokers, or former smokers would initiate or reinitiate tobacco use with the Verve products. As with Vuse, exposure to fewer HPHCs for the Verve products compared to cigarettes and other smokeless tobacco products factored heavily into FDA’s APPH determination. FDA again imposed strict marketing restrictions and wide-ranging postmarketing reporting requirements as a condition of continued marketing. The Ageny’s decision summary further describes the basis for issuing marketing orders for these four products.
FDLI Annual Tobacco Conference
The annual Food and Drug Law Institute (FDLI) Tobacco and Nicotine Products Regulation and Policy Conference was held last month, and included FDA programmatic and PMTA review updates by CTP Director Mitch Zeller and CTP Office of Science Director Matt Holman. We provide below some key points from the FDA presentations, along with a description of a potential, streamlined “resubmission” application option for ENDS products subject to MDOs, and what this could look like for companies looking to resubmit their PMTAs. We also provide below some key points from the discussions (their presentations are attached).
Director Zeller Presentation (see presentation slides here)
Director Zeller’s presentation opened with the latest data on youth e-cigarette use. In September 2021, FDA and the Centers for Disease Control and Prevention (CDC) released findings from the 2021 National Youth Tobacco Survey (NYTS). Zeller emphasized that youth e-cigarette use remains an ongoing concern as the 2021 NYTS found that more than 2 million U.S. middle school and high school e-cigarette users used e-cigarettes in 2021, and almost 85 percent of youths using e-cigarettes used flavored products. Disposables were found to be the most commonly used e-cigarette device type. Due to special methodological considerations owing in part to COVID-19 and the survey’s online administration, the 2021 National Youth Tobacco Survey (NYTS) on e-cigarette use among middle and high school results cannot be directly compared to findings from NYTS surveys from previous years. FDA plans to publish additional findings on youth use of all tobacco products within the next few months.
FDA has issued marketing granted orders for 3 new tobacco products and issued marketing denial orders (MDOs) for more than 1 million non-tobacco flavored ENDS products. As for current review of menthol-flavored ENDS products, Director Zeller stated that, while the same review standard applies to menthol products, CTP is taking additional time to ensure it “gets the science right.” Roughly 80K tobacco and menthol flavored ENDS products are still pending under PMTA scientific review.
Approximately 45 different lawsuits have been filed challenging the recent MDOs for non-tobacco flavored ENDS. This is in addition to the dozens of requests for supervisory review. When asked whether the litigation challenges can result in FDA having to overturn MDOs en masse, Director Zeller stated that each of the filed cases are fact-specific, but deferred to litigators to address this question.
CTPs “highest enforcement priority” includes products with no application (i.e., no pending PMTA or subject to an MDO). When asked about what companies should do with left-over inventory, Director Zeller stated that it is illegal to sell those products, and companies should discuss with wholesalers and retailers about what to do about those products. With respect to monitoring and surveillance, Director Zeller stated that while he cannot discuss CTP’s methods, the process involves FDA having its own monitoring and surveillance abilities. For instance, for companies selling product online, FDA has a process to monitor, and all of this is supplemented by physical inspections of vape shops that meet the definition of manufacturer and physical inspections of brick and mortar inspections, subject to COVID restrictions.
Two foundational rules (PMTA Final Rule and SE Rule) are effective November 4, 2021. FDA described these rules as “forward-looking” and will apply to applications made on or after November 4, 2021,.
Menthol ban: FDA is working on the proposed rule to ban menthol as a characterizing flavor in cigarettes and to ban all characterizing flavors in cigars. This is on track for April 2022 publication. See our article on this here.
Synthetic nicotine “challenge” – In the wake of the MDOs, FDA is aware that Puff Bar and a growing number of ENDS companies are using or claim to be using synthetic nicotine. FDA is in discussion with Congress regarding a potential legislative fix. In the meantime, Director Zeller stated that FDA would continue to review products on a case-by-case basis “based on the totality of the circumstances,” including testing results and the source of nicotine. FDA acknowledges, however, that it has become increasingly challenging to test and differentiate tobacco-derived nicotine from synthetic nicotine based on advanced formulations that blur the distinction between the two isomeric forms of nicotine (R- and S-nicotine) for synthetic and tobacco-derived nicotine. When specifically asked about the Agency asserting drug jurisdiction over synthetic nicotine, Director Zeller stated that this option remains under consideration. See here regarding recent action on synthetic nicotine from the House Oversight Committee and here regarding North Carolina attorney general investigation into Puff Bar.
FDA PMTA Update Presentation by Matthew Holman, Director, CTP Office of Science (see presentation slides here)
Dr. Holman restated CTP’s emphasis on youth initiation concerns and added that, in the marketing granted orders that CTP has issued so far, the Office of Science is not yet convinced about the effectiveness of current youth marketing and access restrictions.
Dr. Holman clarified that the PMTA Final Rule will apply to PMTAs received by FDA on or after November 4, 2021. The changes in filing requirements include requiring substantive information for key health risk topics, including health risks and comparative health risks; likelihood of initiation and other changes in tobacco product use behavior; product perceptions and use intentions; abuse liability; and human factors. Substantive information for each of these disciplines will be required for filing after November 4, 2021.
One key point was whether, after receiving an MDO, applicants can submit a streamlined “resubmission” that directly responds to the deficiencies, as opposed to requiring applicants to resubmit the entire application along with any “missing” information or information that corrects deficiencies. After Dr. Holman raised this as a viable pathway, questions from the audience expressed concern that this instruction appears to contradict with the language in the “template” MDOs, which states that applicants may not cross-reference any information submitted in the PMTAs that are subject to an MDO. Dr. Holman stated he was aware of this language but could not recall the purpose, but instructed applicants to contact their regulatory health project managers with any questions or concerns. Dr. Holman did seem to take the position, however, that applicants can submit streamlined PMTAs and cross-reference original PMTA submissions and amendments. Given the confusion and substantial difference in workload and resources, both for applicants and FDA, between a resubmission that cross-references existing filed applications and targets identified deficiencies, and a submission of an entirely new application, companies should consider reaching out to their CTP Regulatory Health Project Managers for clarity.