FDA sets exceptionally low bar when authorizing IQOS, a new tobacco products

FDA’s April 2019 decision authorizing Philip Morris to market its IQOS heated tobacco product in the United States set a new low bar for establishing that a new tobacco product protects the public health.

Lauren Lempert and I have read the FDA’s 122 page decision document and prepared a detailed analysis of the FDA’s decision (the “Technical Project Lead Review”) for the IQOS PMTA.  This analysis raises serious questions over how the FDA assessed the risks and public health impact of IQOS that raise serious questions about how the FDA will handle premarket applications in the future. 

Before marketing any new tobacco product in the United States, a manufacturer must submit a premarket tobacco application (PMTA) to FDA. In May 2017, Philip Morris submitted a PMTA seeking an order permitting it to sell its IQOS heated tobacco product in the U.S.

The law places the burden on applicants to meet a rigorous public health standard: applicants must demonstrate that their products are “appropriate for the protection of the public health,” and requires FDA to deny a PMTA and issue an order that the product may not be marketed if public health benefits are not shown.

In determining whether the applicant has met this burden, the FDA is required to look at the risks and benefits to the population as a whole, including users and nonusers (including youth and former users), and consider the increased or decreased likelihood that current tobacco product users will quit, and the increased or decreased likelihood that nonusers will initiate using or return to using.

The FDA’s decision to allow IQOS to be sold in the United State, the FDA turned this standard on its head.  Rather than applying the public health standard clearly spelled out in the law the FDA instead established a de facto standard: a new product will be approved if it is not more dangerous than cigarettes.

Even more troubling, FDA appears to have turned the law on its head by requiring that the FDA has to demonstrate that the it does not have evidence to reject a PMTA rather than enforcing an affirmative obligation on the applicant (in this case PMI) to make an affirmative case that allowing the product on the market would improve public health.

In addition to ignoring the law, FDA ignored the science.  FDA ignored the recommendations of its own scientists, and ignored peer-reviewed literature showing that IQOS presents serious risks to users including potential cytotoxicity, genotoxicity, hepatotoxicity, and cardiovascular risks.  Philip Morris’ PMTA did not report the full range of HPHCs, and FDA ignored evidence in the PMTA showing that IQOS produces higher levels of some toxins than cigarettes.  Impacts on clinical measures are the most important thing for assessing whether a new product is “appropriate for the protection of public health” and Philip Morris’ own data did not show any difference in clinical markers of disease risk between IQOS and conventional cigarettes.

While FDA acknowledged this fact (and rejected PMI’s obscure statistical attempt to argue otherwise), but instead focused on the fact that IQOS delivers less of some toxins.  Measuring toxin exposure is important, but actual biological effects are more important since many effects are nonlinear, which big effects occurring at low exposures.

Despite information available in the literature, concerns raised by its own scientists, and data provided by the applicant itself showing that IQOS does not meet the public health standard, FDA decided to issue a marketing order because “the exposure levels appear low.”  This is especially disconcerting consider FDA is currently considering Philip Morris’ MRTP application for IQOS that includes reduced exposure as well as reduced risk claims, and the literature shows that the public will misconstrue reduced exposure claims as reduced risk claims.

In applying its “not worse than cigarettes” standard, FDA did not consider other products on the market, such as e-cigarettes that may deliver lower levels of toxins than IQOS. And despite the law’s mandate and recommendations in FDA’s guidances, FDA failed to properly consider dual use, the predominant use pattern.

Taken altogether, FDA’s low bar for authorizing the marketing of a new tobacco product with demonstrated harms shows that it prioritizes the tobacco industry’s interests over the public’s health.

Lauren and my detailed analysis that describes these and other problems in greater detail, and includes citations to published literature is here.  The FDA’s decision is here.