Comparing the preclinical risk profile of inhalable candidate and potential candidate modified risk tobacco products: A bridging use case

Schlage, Walter K.; Titz, Bjoern; Iskandar, Anita; Poussin, Carine; Toorn, Marco van der; Wong, Ee Tsin; Pratte, Pascal; Maeder, Serge; Schaller, Jean‐Pierre; Pospíšil, Pavel; Boué, Stéphanie; Vuillaume, Gregory; Leroy, Patrice; Martin, Florian; Ivanov, Nikolai V.; Peitsch, Manuel C.; Hoeng, Julia

doi:10.1016/j.toxrep.2020.09.004

Cited by 9 publications

(7 citation statements)

References 80 publications

(110 reference statements)

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“…These conclusions are in agreement with those of a separate review published by PMI researchers, which concluded that "the experimental results [from systems biology and systems toxicology studies] demonstrate a reduced impact on apical and molecular endpoints, no novel effect not seen with cigarette smoke exposure, and an effect of switching from cigarettes to either MRTP [two heated tobacco products; one electrically heated and one with a carbon-heating design] that is comparable to that of complete smoking cessation" (Schlage et al, 2020). PMI researchers have also attempted to further validate their scientific approach to assessment of the THS2.2 heated tobacco product by providing their biological and clinical samples or data packages to external independent researchers (in a blinded fashion) to see whether or not they would reach the same conclusions as the original researchers (Poussin et al, 2017;Boué et al, 2019;Belcastro et al, 2020).…”

Section: Discussionsupporting

confidence: 87%

The product science of electrically heated tobacco products: a narrative review of the scientific literature

Malt

Thompson²,

Mason

et al. 2022

F1000Res

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Heated tobacco products represent a novel category of tobacco products in which a tobacco consumable is heated to a temperature that releases nicotine from the tobacco leaf but not to a temperature sufficient to cause combustion. Heated tobacco products may therefore have the potential to be a less harmful alternative for adult smokers that would otherwise continue to smoke conventional cigarettes. Given the rapid development of this product category, the aim of this review was to examine the available peer-reviewed scientific evidence related to heated tobacco products and highlight any research gaps. In recent years, manufacturers of heated tobacco products have published a number of studies on their respective heated tobacco products. Whilst there is limited research that is independent of commercial interests, the available scientific evidence indicates that heated tobacco products produce a much simpler aerosol than conventional cigarette smoke, with fewer and substantially lower levels of harmful toxicants. Toxicology assessments indicate these reductions in aerosol toxicants translate to reduced biological effects. Biomarker and clinical data from studies in which product use is controlled within a clinical setting, indicate changes in biomarker levels and clinical end-points similar to observations in cessation studies, indicating the potential for reduced harm. The scientific evidence also indicates that exposure of non-users to emissions from heated tobacco products in indoor environments is significantly reduced compared to exposure resulting from smoking conventional cigarettes. Overall, the available scientific evidence indicates that heated tobacco products hold promise as a less harmful alternative to conventional cigarettes, but more independent data is required to validate industry findings. As a growing product category, epidemiological studies and independent population modelling studies are outstanding, and empirical data on how dual tobacco product category use by consumers affects their risk profile is lacking.

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Section: Discussionsupporting

confidence: 87%

The product science of electrically heated tobacco products: a narrative review of the scientific literature

Malt

Thompson²,

Mason

et al. 2022

F1000Res

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“…For tobacco products, a "bridging" dataset of emissions and toxicological data on a new variant product might be similarly used to demonstrate equivalence to a base product, thereby easing the burden of testing and regulatory review. For equivalence, the variant product should have a similar emissions yield and exposure profile, should evoke the same type of physiological responses and be used in the same manner by the consumer (13). In this proof-of-concept study, we have conducted emissions and toxicological testing on six THPs: a THP_base (THP1.0_BT), on which an extensive chemistry, in vitro, and clinical foundational data set has been previously generated (6, 14-21) and five modified variants.…”

Section: Introductionmentioning

confidence: 99%

“…This would therefore avoid repetition of vast data generation and could ease authorisation requirements on newer iterations. Such bridging approaches to demonstrate THP-to-THP equivalence are currently being scientifically discussed with a view to establishing a regulatory compliant approach (13). In this case study we are comparing the chemistry as well as the biological activity across products tested, where we are trying to relate the two showing differences and similarities.…”

Section: Introductionmentioning

confidence: 99%

An Experimental Analytical and In Vitro Approach to Bridge Between Different Heated Tobacco Product Variants

Jaunky

Thorne

Baxter

et al. 2022

Contributions to Tobacco &Amp; Nicotine Research

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Summary Tobacco heating products (THPs) have reduced toxicant emissions relative to cigarettes. THPs are continually evolving, but safety and efficacy studies on each new variant involve considerable resources. As employed by the pharmaceutical industry, a “bridging” process could be used to demonstrate product equivalence. Therefore, we investigated the feasibility of a bridging approach by evaluating aerosol emissions and in vitro cytotoxicity of five variant THPs in relation to a base product. All products were compared to a reference cigarette and a commercial benchmark. Relative to smoke, chemical reductions in THP aerosols were comparable among the THPs at 94–97%. The aerosols showed similar cytotoxicity in human lung tissues exposed at the air-liquid interface (p = 0.8378) but were significantly less toxic than smoke (p = 0.04). Relative to the THP benchmark, variant THPs showed lower cytotoxicity (p = 0.0141). Emissions and cytotoxicity data demonstrated that the variant THPs were comparable to the base THP, irrespective of consumable format or flavour. This dataset demonstrates the feasibility of a bridging approach and can inform an evidence-based strategy in developing sufficient data to predict similarity against an already established dataset. Therefore, avoiding repetition of vast data generation could ease authorisation requirements of newer products. Finally, we propose that more work is required to understand chemical, biological (in vitro), human consumption, and clinical data before the equivalence of these products (and others) can be definitively demonstrated. Future studies maybe needed to assess additional chemical and biological outputs and all data will need to be contextualised against human consumption data in terms of a bridging framework.

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“…It is difficult to compare the present results on nicotine and HPHC yields in the waterpipe aerosols with those in other tobacco products [ 34 , 36 ]. While comparison of e-cigarette or heated tobacco product aerosols with mainstream cigarette smoke in terms of nicotine and HPHC yields has been widely practiced and is based on consumer behavior and daily consumption [ 37 , 38 ], such a comparison is less obvious in case of waterpipe tobacco products.…”

Section: Resultsmentioning

confidence: 99%

Analysis of waterpipe aerosol constituents in accordance with the ISO standard 22486

et al. 2020

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Comparing the preclinical risk profile of inhalable candidate and potential candidate modified risk tobacco products: A bridging use case

Abstract: Graphical abstract

Cited by 9 publications

References 80 publications

The product science of electrically heated tobacco products: a narrative review of the scientific literature

The product science of electrically heated tobacco products: a narrative review of the scientific literature

An Experimental Analytical and In Vitro Approach to Bridge Between Different Heated Tobacco Product Variants

Analysis of waterpipe aerosol constituents in accordance with the ISO standard 22486

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