JUUL LABS PUBLISHES ITS 10.75 APPEAL, DETAILING THE SUBSTANTIVE AND PROCEDURAL ERRORS IN FDA’S MARKETING DENIAL ORDER FOR JUUL PRODUCTS AND BASIS FOR RESCISSION

Company News

October 21, 2022

Today, Juul Labs, Inc. (JLI) posted its administrative appeal of the marketing denial order (MDO) issued by the Food and Drug Administration (FDA), which explains the company’s position, based on science and evidence, that the MDO was substantively and procedurally flawed. This appeal, referred to as a 10.75 appeal, is currently under review by FDA. 

In its press release for the MDO, FDA stated that JLI’s premarket tobacco product applications (PMTAs) “lacked sufficient evidence regarding the toxicological profile of the products” and that some of the “study findings raised concerns due to insufficient and conflicting data.” As presented in its appeal, JLI believes that each of the deficiencies in the MDO is based on an incorrect and incomplete assessment of the data and, when the data are appropriately evaluated within the PMTAs, FDA can properly assess the toxicological profile of JUUL products and relative to other tobacco products including combustible cigarettes. The appeal also shows that all perceived limitations could have been resolved by clarifications through the usual, iterative process that FDA has followed for prior applications. 

Through its 10.75 appeal, JLI requests that the MDO be rescinded and its PMTAs be placed back into substantive review so that FDA can complete a full and fair review to determine whether the JUUL System is appropriate for the protection of public health. We believe that once FDA does a complete review of all of the science and evidence presented in the applications, without political interference, as required by law, we should receive marketing authorization for our products.  

Below is a summary of the MDO’s four deficiencies and JLI’s responses, as well as links to JLI’s full 10.75 appeal, the MDO, and FDA’s Technical Project Lead memorandum that provides additional analysis for its decision.

From the Executive Summary of JLI’s 10.75 appeal: “The MDO incorrectly and incompletely concluded that, based on a limited and narrow toxicology review, [Center for Tobacco Products Office of Science] was precluded from determining that the marketing of the JUUL System is APPH. For each alleged deficiency, the MDO erred by overlooking key information, incorrectly analyzing the information it did consider, and inequitably holding the PMTAs to a new and different standard compared to similarly-situated applicants. The alleged deficiencies, if anything, were limitations that warranted additional engagement and review and could have been reconciled with information already provided in the PMTAs. Far from justifying a denial, the marketing decision reflected an analysis that failed to conduct a complete, holistic, and fair review of the body of science and evidence in JLI’s PMTAs.”

For context, in July 2020, JLI submitted PMTAs to FDA for its currently marketed products and a new device with age-verification technology. The PMTAs included over 125,000 pages of data, information, and analysis from over 110 scientific studies across nonclinical (75+ studies), clinical (14 studies), and behavioral (21 studies) research programs to support the marketing of JUUL products. JLI also assessed its products relative to combustible cigarettes, an FDA-authorized heated tobacco product (IQOS), and other marketed vapor products.

Despite this science and evidence, on June 23, 2022, FDA issued a MDO for JLI’s PMTAs. On July 5, FDA stayed the MDO, announcing, on its own, that it would review the decision after determining “there are scientific issues unique to this application that warrant additional review.” 

Separately, on July 29, JLI submitted its own 10.75 appeal and presents two fundamental points that warrant rescinding the MDO: It was substantively and procedurally flawed.

The MDO was substantively flawed.

The conclusions and supporting findings in the MDO are inconsistent with the information, data, and analysis provided in JLI’s PMTAs. Each deficiency rests on an incorrect or incomplete assessment of the data.

Deficiency 1: The MDO asserted that JLI identified certain leachable constituents of potential toxicological concern in simulated e-liquid studies but did not evaluate the mainstream aerosol yields of those constituents to determine whether and at what levels users could be exposed. 

Response: The deficiency is premised on a finding that overlooked critical and dispositive data. Through non-targeted analysis of the JUUL System aerosol, the PMTAs showed that the leachables in question were not detected in the aerosol and thus would not be exposed to the user. For the data and analysis as provided in the 10.75 appeal, see pages 30-48.

Deficiencies 2 and 3: The MDO asserted that JLI did not provide reliable and valid data to assess the genotoxic potential of JUUL products and as compared to combustible cigarettes and other vapor products.

Response: These deficiencies are premised on an incomplete and inadequate assessment. The MDO focused on limited methodological differences in select in vitro and in vivo studies, from which JLI did provide sufficient and reliable information to inform on the genotoxic potential of JUUL products. Critically, the MDO did not account for the additional science and evidence in which a signal of potential genotoxicity from an in vitro study was further assessed by subsequent studies and incorporated into whole product risk assessments to characterize potential exposures and associated health risk from the use of the JUUL System. For the data and analysis as provided in the 10.75 appeal, see pages 48-70.

Deficiency 4: The MDO asserted that JLI provided data showing its Menthol 5.0% product is potentially mutagenic.

Response: The deficiency is premised on an arbitrary deviation from the study protocol and OECD guideline and an incorrect application of the testing criteria. Applying the study protocol, OECD guideline, and testing criteria correctly, the in vitro assay confirmed that the product did not induce a mutagenic response. Rather, FDA used the wrong control data and applied the testing criteria incorrectly in reaching its conclusion. For the data and analysis as provided in the 10.75 appeal, see pages 71-83.

In short, the MDO was based on alleged deficiencies that failed to consider the data, considered the data inadequately, misinterpreted the data, and applied the data incorrectly.

The MDO was procedurally flawed.

Amid a backdrop of immense political pressure, the marketing decision applied a new and different standard to the data, which appears to have been created for, and applied only to, JLI’s PMTAs. The MDO’s limited and narrow approach tied to toxicology is inconsistent with the requirement for a complete and holistic review of PMTAs under Section 910 of the Family Smoking Prevention and Tobacco Control Act and a departure from FDA precedent and established scientific principles.

Lack of Iterative Review: During the nearly two-year review period for its PMTAs, JLI received just one substantive request for additional information, which it addressed by providing additional information, data, and analysis to support FDA’s review in June 2021. From June 2021 until the MDO in June 2022, FDA did not raise any other questions or otherwise engage substantively with JLI.

This limited engagement is in direct contrast to FDA’s usual, iterative process that defines a full and complete review of product applications generally and how it has managed other PMTAs specifically, particularly those that it has authorized. For other PMTAs:

• Philip Morris International’s IQOS had 2 meetings, 4 information requests, and 12 amendments; 
• JTI’s Logic vapor products had 4 information requests and 10 amendments; 
• Swedish Match’s General Snus products had 3 meetings, 2 information requests, and 11 amendments; and  
• 22nd Century’s Moonlight Very-Low-Nicotine Cigarettes had 6 meetings and 14 amendments.

All perceived limitations identified by the MDO could have been resolved by clarifications through an iterative process that FDA has previously developed and followed for prior PMTAs and that is necessary to assure that its product-specific decisions serve its public-health objectives.

Different Standard: By law, FDA is required to undertake a complete and holistic review of the totality of the evidence in a PMTA to determine whether the marketing of the product is appropriate for the protection of public health – weighing the benefits to adult smokers against the risks to nonusers including those underage. FDA has done just that for other PMTAs that it has authorized, including those that raised toxicological concerns. For IQOS, FDA found that “some of the chemicals are genotoxic or cytotoxic” but that “these chemicals are present in very low levels and potential effects are outweighed by the substantial decrease in the number and levels of HPHCs found in [combustible cigarettes].” For Moonlight Very-Low-Nicotine Cigarettes, FDA found that the product’s toxicological profile was “likely similar to” combustible cigarettes. But here, FDA applied a different standard and the outcome for JLI’s PMTAs and the JUUL System was quite different.

Political Pressure: Since JLI submitted its PMTAs, FDA has been under immense and unprecedented political pressure to reach a very specific decision – deny the applications and remove JUUL products from the market. As detailed in the 10.75 appeal, the record of statements and testimony from certain members of Congress is notable. For example, the day before the MDO, one member of Congress asserted that FDA’s Commissioner should either deny JLI’s PMTAs or “step aside.” The day after the MDO, another member of Congress publicly admitted to having had a “long conversation with the FDA Commissioner” about JUUL products and suggested that this had motivated FDA to “finally . . . stop JUUL.”

These and other issues discussed in the 10.75 appeal make the MDO inconsistent with the data provided in JLI’s PMTAs, inconsistent with the principles of sound scientific assessment, inconsistent with established FDA policies, procedures, and processes, and inconsistent with statutory authorities that required FDA to give JLI’s PMTAs a fair and complete review.

JLI initiated a company-wide reset to combat underage usage of JUUL products. As part of our reset, we halted all broadcast, print and digital product advertising in the U.S., suspended distribution of all flavored products other than tobacco and menthol in the U.S., and restructured our company to focus resources on the development of technologies aimed at combating underage use, such as the introduction of Enhanced Access Controls (EAC) at retail, which prevents access to potential underage buyers and limits anyone from buying in bulk.

Since that time, according to National Youth Tobacco Surveys, use of JUUL as “usual brand” fell from 57.9% of past 30-day vapor product underage users in 2019, to 6.8% in 2021, and in 2022, JUUL was not on the list of most often reported usual brands. While the recent NYTS data demonstrates that underage use of vapor products overall remains high, even factoring in the changes to the NYTS due to COVID-19, the numbers on JUUL use represent real progress in Juul Labs’ ability to advance harm reduction for adult smokers while using data-driven measures to keep our products away from underage users. To continue that progress, the company must combat underage use and resolve issues from its past.

To see the full materials and additional information go to the Juul Labs Science website here.

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