Editorial | Regulation | Oct 15, 2019

      Dr. Gilchrist on FDA Grand Rounds

      Appropriate for the protection of public health: Why the FDA authorized the Tobacco Heating System (THS) to be marketed in the U.S.


      By Dr. Moira Gilchrist, VP Strategic & Scientific Communications


      FDA authorized sale of THS in U.S. – but why?

      The U.S. FDA granted authorization for our Tobacco Heating System, THS to be marketed in the U.S. as IQOS on April 30, 2019 after a 2-year review of our Premarket Tobacco Product Application (PMTA). Learn more about our PMTA application. Last week, the FDA took the opportunity to explain their reasoning for granting that authorization.

      The webcast was hosted by Dr. Priscilla Callahan-Lyon, Deputy Director for the Division of Individual Health Science in the Office of Science, Center for Tobacco Products. Dr. Callahan-Lyon is a medical doctor (MD) with 20 years in private practice as a pulmonologist and 10 years with FDA (both on the drug and tobacco sides).  She served as the lead technical reviewer for the PMTAs. 

      As a start, Dr. Callahan-Lyon clarified a couple of important points with regards to the PMTA. “No tobacco product is safe. A tobacco product authorization does not use a safety and efficacy standard. It’s a completely different frame of reference. We do not approve a tobacco product; we authorize them for marketing…Also, there isn’t a specific regulatory definition for Appropriate for Protection of the Public Health (APPH). So, this is a standard that we have imposed if we determine the marketing of the product has the potential to result in decreasing morbidity and or mortality than we can find it to be appropriate for the protection of public health at this point in time. This standard may change depending upon the marketing environment of the future.”

      The U.S. Food and Drug Administration (FDA) hosted a webcast entitled “Why FDA authorized the marketing of the IQOS heated tobacco product as ‘appropriate for the protection of the public health’” on Thursday, October 10.  Dr. Moira Gilchrist, Vice President Strategic and Scientific Communications, gives us an overview of the key points mentioned during this webinar, as well as her take on some important factors.

      Moira Gilchrist

      Dr. Callahan-Lyon clearly outlined the framework of the FDA’s review process and emphasized the thoroughness of the assessment, including not only the review of our scientific studies, but performing independent testing on THS as well. One thing that came out loud and clear from the webcast was the degree of oversight that FDA has had—on the product, its ingredients, manufacturing and science—and will continue to have as THS (marketed as IQOS) is sold in the United States. The FDA have reviewed our science, inspected our facilities, and essentially evaluated the whole value chain associated with THS. They will be receiving marketing plans for review before they’re implemented — “If there’s a problem, we’ll see it,” said Dr. Callahan-Lyon.


      FDA approves sale of IQOS Tobacco Heating System via pre-market tobacco product pathway.

      THS heats tobacco rather than burning it

      Dr. Callahan-Lyon explained how the THS works, highlighting that the device heats specially-designed tobacco plugs at a specific temperature range to allow for generation of aerosol, without burning the tobacco. She highlighted that the device energy supply will actually cut off if it gets above a certain temperature where combustion may start. 

      It struck me that not everyone in the scientific and public health communities may know how THS works, or how the technology differs from e-cigarettes. Dr. Callahan-Lyon's explanation was useful in this regard, as is the diagram below.


      Infographic showing difference between heated tobacco products and e-cigarettes.

      Lower levels of harmful chemicals

      Dr. Callahan-Lyon mentioned that the toxicological data we provided indicated the potential for relative benefit compared to combustible cigarettes for adult smokers who switch completely to THS. Specifically, she mentioned reductions in exposure to carbon monoxide as well as acrolein and formadehyde.

      She also added that our data did indicate that the product's aerosols contained some possible carcinogens, and other chemicals that might be genotoxic, but that the levels were quite low. "And overall our toxicologist thought that although some of those chemicals maybe have toxic effects, they're present at very low levels and that the potential effects were outweighed by the substantial decrease in the number and levels of the HPHCs that are found in combusted cigarettes."

      Dr. Callahan-Lyon indicated that our short-term clinical studies showed an improvement in the biomarkers of exposure indicating reduced exposure to HPHCs, and that this improvement trend persisted in longer studies.


      Appealing to adult smokers and not to non-smokers

      Listeners heard during the webcast that FDA considers that use of the product by youth and former- or non-smokers is expected to be low based on available evidence. Dr. Callahan-Lyon reported that FDA did not see a very high percentage of never-smokers, including the young-adult never-smokers, with a particular interest in the product. Even among former smokers, interest in the product was not very high. At the same time, she also reported that the levels of nicotine and resulting satisfaction from the product were considered to be enough to satisfy a current smoker. Dr. Callahan-Lyon was clear that THS is addictive, but poses no more addiction risk than cigarettes.

      In a section of the webcast where Dr. Callahan-Lyon was discussing adult smoker switching rates, I was struck by the importance of our continued use of guided trials of THS to encourage complete switching. It makes a big difference when knowledgeable, friendly representatives can guide the adult smoker through the use of the product, making it easier for them to make a full switch as quickly as possible. After all, as the tobacco harm reduction equation indicates – the science supporting a product makes no difference to public health unless smokers switch to it.


      No worrisome adverse events related to THS

      Dr. Callahan-Lyon stated that PMI has already provided two annual safety update reports from counties outside of the U.S. She reiterated that FDA did not find any worrisome adverse events specifically related to THS from data in other countries. She also noted that FDA is not aware of any cases of lung injury similar to those seen recently in the U.S.


      THS creates a new standard for heated tobacco products

      Ultimately, this webcast highlighted the U.S. approach for authorizing alternative products: recognition of the continuum of risk, an inclusive and transparent process, and rigorous science-based decision making. Concerns related to product quality, aerosol characterization, potential health effects, non-smoker appeal (including former smokers and youth), and flavors are all considered as part of FDA’s review process.

      During the Q&A, FDA was asked whether future heated tobacco products would be compared with combustible cigarettes or THS when deciding whether the new product is beneficial for public health. Dr. Callahan-Lyon said "If it's another heated tobacco product, we [FDA] would compare internally with this heated tobacco product [IQOS] and the information that we know about it." At PMI, we are proud that our product and our data has set a new benchmark.