On December 7,2020, FDA issued a marketing order authorizing Philip Morris Products to sell its IQOS 3 heated tobacco product, an updated version of the IQOS 2.4 system FDA had previously authorized for sale in April 2019. Based on FDA’s streamlined review of Philip Morris’ “supplementary application” comparing IQOS 3 to IQOS 2.4, FDA determined that permitting the marketing of IQOS 3 is “appropriate for the protection of the public health” because Philip Morris did not identify any new exposures or risks from IQOS, present any evidence of increased risk of youth initiation and use for IQOS 3 compared to IQOS 2.4, FDA found “no reason to believe” the IQOS 3 device would result in different nicotine exposure, use patterns, user populations, or abuse liability, and the proposed labeling is not false or misleading.
FDA characterized the changes in the newer IQOS model as “minor design differences,” including how the holder inserts into the charger, changes to the charging connectors and LED indicator lights, a new touch feedback feature, a “new haptic feature,” and an option to reduce the perceived heat from the tobacco aerosol inhaled by users.”
However, because premarket tobacco product applications (PMTAs) are not made available to the public for comment and because FDA chose not to have it reviewed by its Tobacco Products Scientific Advisory Committee (TPSAC) – which would have made at least a redacted version of the application available for public comment – neither Philip Morris nor the FDA made meaningful information public about the new features of the IQOS 3.
In addition, the FDA redacted significant portions of its scientific review of the IQOS 3 PMTA (the “Technical Project Lead (TPL) Review of PMTA”), including sections that discuss the Harmful and Potential Harmful Constituent (HPHC) yields, the product design and composition, the product test data, and the environmental impacts.
The FDA provided insufficient evidence that Philip Morris’s supplemental PMTA demonstrated that the IQOS 3 is appropriate for the protection of the public health
The FDA describes the design modifications as “mainly aesthetic.” However, without having access to the actual application materials, we cannot determine whether the “new touch feedback feature” was designed to positively reinforce increased nicotine intake or to give Philip Morris enhanced information about user puff patterns through IQOS’s Bluetooth function that PM could use to “tune” the device to make it more addictive. We also cannot determine why PM added the new “option to reduce the perceived heat the tobacco aerosol inhaled by users,” including whether it was designed to make inhalation easier for non-users, including youth, and former users, thereby giving the IQOS 3 the potential to attract non-users to initiate tobacco use with IQOS, and for former users to reinitiate and halt their attempts to quit smoking.
Of additional concern, the TPL points out at section 3.4 that the PMTA for IQOS 3 did not include new data related to product use or user populations in the US and acknowledges that the “marketing and use patterns for IQOS 3 in other countries does not necessarily reflect or predict initiation or user behavior in the US.” And while the TPL notes that “users report switching completely to IQOS (as opposed to dual use with cigarettes),” it acknowledges that “the data are quite limited.” In other words, we do not know the actual level of dual use with cigarettes or other tobacco products.
The TPL also admitted that because youth and young adults under age 24 were grouped together, it was “impossible to determine the rate of youth interest and initiation/product purchase,” a tremendously important contributor to determining IQOS 3’s public health impact.
FDA’s reliance on its April 2019 marketing order for IQOS 2.4 is misplaced
As we showed in our paper on FDA’s marketing authorization for IQOS 2.4, FDA failed to address significant concerns found in published literature about the health impacts of IQOS and did not make a good case that IQOS is safer than a conventional cigarette. A December 21, 2020 paper demonstrated that short-term inhalation of IQOS aerosols generates damage and proinflammatory changes in the lung that are similar to cigarette smoke exposure and warned that long-term inhalation of IQOS aerosols could cause severe alterations in the lung epithelial cells and immune impairment.
FDA’s assessment of the IQOS 3 provided the agency with an opportunity to consider these important issues. It did not do so.
A November 2020 study of young adult perceptions of PM’s packaging and marketing claims found that IQOS’s “no smoke” claims and design similarities to high-end electronics appeal to young adult tobacco users and leads to perceptions that smoking IQOS is safer than smoking cigarettes, suggesting that packaging and implicit claims may be false or misleading. FDA did not address this important issue.
Instead of relying on its April 2019 marketing order for IQOS 2.4 to authorize a new version of IQOS, FDA should have considered the growing scientific evidence that IQOS does not protect the public health.
The streamlined PMTA process protects the industry, not the public health
The IQOS 3 authorization was based on the first “supplemental” PMTA received by FDA through which Philip Morris sought authorization to modify its tobacco product based on the previously obtained marketing order through the more rigorous PMTA process. Under the streamlined “supplemental PMTA” process (which was introduced in FDA’s in September 2019 proposed rule on PMTA requirements, but was never finalized by FDA), applicants may cross-reference content from a previously authorized PMTA and provide new information related to the product modifications. As FDA explains in the proposed rule, the supplemental PMTA process was designed to “reduce the burden of submitting and reviewing a standard PMTA,” but the precedent that FDA established in its handling of the IQOS 3 application suggests that the FDA is going to allow manufacturers to avoid conducting and submitting population-wide data for new products. This shortcut is especially disconcerting considering that thousands of tobacco products could use this system in the future to sidestep rigorous review of modifications that are presented as “minor modifications,” but in fact have potential major health impacts.
Postmarket reports are not a substitute for premarket review
The fact that the IQOS 3 marketing authorization requires postmarket reporting does not cure the deficiencies in FDA’s scientific review and marketing order. The rigorous premarket review process envisioned by the Tobacco Control Act was designed to ensure that no new tobacco products would be marketed in the US unless the manufacturers demonstrate on the basis of significant scientific evidence that the proposed product will protect the public health. We have seen with the explosive growth of Juul and other e-cigarette products that closing the barn door after the horses have escaped is not effective.
Lauren Lempert prepared the first draft of this blog post.