Comprehensive Chemical Characterization of the Aerosol Generated by a Heated Tobacco Product

Below is the transcript of the video:

Hello! I am Gerhard Lang and I work for Philip Morris International in their R&D facility based in Neuchatel, Switzerland. 

First of all, I would like to thank the organizers for giving me the opportunity to present this research, where I will describe results for the chemical characterization of aerosol generated by a heated tobacco product – our Tobacco Heating System (THS). 

When tobacco is heated instead of being burned, the aerosol generated contains fewer and lower levels of chemical constituents than cigarette smoke, which is widely understood to contain more than 6,000 chemical constituents, 100 of which are known to be linked to smoking-related disease.

Targeted analysis, which quantifies selected known chemicals, has demonstrated that the average levels of known harmful and potentially harmful constituents are around 90-95% lower in THS aerosol than in cigarette smoke. 

However, because there is the possibility that additional unknown harmful constituents could be present, untargeted analysis of the aerosol was also performed. 

Untargeted analysis aims to identify and semi-quantify all chemical constituents within a matrix. And in order to achieve this a set of complementary methods was used, which was developed to cover the large chemical space of cigarette smoke and heated tobacco aerosols. 

For untargeted screening a threshold of 100 ng/stick was used for the reporting of chemical constituents in smoke or aerosol. The term stick here refers to the HeatStick used with THS or a cigarette. With this threshold applied, we estimate there are 10-fold fewer compounds present in THS aerosol compared with 3R4F smoke. 

In addition, all 532 compounds present in the aerosol of THS above this threshold were also present in the smoke of the reference cigarette. 

Overall, more than 96% of the total mass characterized by untargeted screening, representing 80% of the total number of compounds identified, were confirmed with reference standards. 

The untargeted differential screening approach does not apply a threshold and focuses on identifying all compounds that are higher in abundance in the aerosol of THS compared with 3R4F smoke. 

Using this approach, we reported a combined number of 85 compounds as being more abundant in aerosol across the 3 HeatStick product variants authorized for use in the United States – and 9 of these 85 compounds were unique to THS aerosol. 

Information regarding these 85 compounds, including an in-house toxicological evaluation, was provided to the FDA, who concluded their presence was not of toxicological concern relative to cigarette smoke. 

The compounds uniquely present in THS aerosol are primarily attributable to tobacco blend differences and the presence of flavor compounds, since 3R4F is an unflavored product. 

If we focus on the results for the U.S. Regular HeatStick variant, which is non-mentholated, 54 compounds were identified as being more abundant in THS aerosol compared with 3R4F smoke, and 3 of these were unique in THS aerosol. 

Based on their review of our Premarket Tobacco Product Application for THS, their own testing, and the review of published literature the FDA concluded that “Although some of the chemicals are genotoxic or cytotoxic, 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 combusted cigarettes.” 

To conclude, using untargeted screening we have confirmed that the aerosol generated by THS is significantly less complex than that of cigarette smoke – with about 10 times fewer compounds above our reporting threshold than the smoke of a reference cigarette. 

By using reference standards, we also confirmed the chemical identity of more than 96% of the total THS aerosol mass. 

Using untargeted differential screening we were able to characterize which compounds are present at higher levels in THS aerosol relative to 3R4F smoke. For the three U.S.-authorized THS variants, a total of 85 such compounds were found, of which 9 were unique. These more abundant constituents were not considered to be of toxicological concern and were attributable to differences in tobacco blend and the presence of flavors. 

Overall, based on the outcome of our research, we can conclude that the aerosol generated by THS has been characterized to the fullest practicable extent. 

With that, I would like to thank you for your attention.