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

Abstract

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.

Emissions, puffing topography, mouth level exposure and consumption among Japanese users of tobacco heated products

“…4 A recent in vitro study on the feasibility of bridging also found comparable chemical reductions (94-97%) among glo TM type 1 and five variants. 21 Notably, the variants in that study had minor changes in aesthetics and tobacco flavour in contrast to the major changes between glo TM type 1 and glo TM type 3 in the present study, indicating that fairly substantial adaptations may be made to the device while maintaining equivalence.…”

“…20 An initial study comparing the original THP and variant THPs has demonstrated the equivalence of the products in terms of emissions and cytotoxicity, thereby supporting the feasibility of a bridging approach. 17,21 Puffing topography and MLE studies play a key part in determining whether consumers use the product in a manner that reduces their individual exposure or health risk when compared to a conventional cigarette. 22,23 These studies provide a key insight into how consumers use the product, such as number of puffs taken, puff volume, puff duration, inter-puff interval, MLE to nicotine-free dry particulate matter (NFDPM) and nicotine and ADC, and therefore, will be a component in the dataset provided to bridge different variants of a given THP.…”

Evaluation of behavioural, chemical, toxicological and clinical studies of a tobacco heated product glo™ and the potential for bridging from a foundational dataset to new product iterations

“…In a study by Jaunky et al [59] , six variants of the glo™ THP Type 1, original, (including the original THP 1.0 T) and THS2.2 were evaluated against a scientific reference cigarette using analytical chemical measurement of toxicants and in vitro toxicology. The variants included changes in flavour ingredients, nicotine content and emissions, aesthetics and the addition of a foil wrap for the tobacco consumable.…”

The Product Science of Electrically Heated Tobacco Products: An Updated Narrative Review of the Scientific Literature

“…When directly comparing these in vitro experimental approaches, there is an apparent inverse association between practicability and biological relevance. The necessity of standardized dosimetry approaches to facilitate direct comparisons between studies has also been highlighted [60], and the use of a 'bridging' approach to achieve a comparison between new HTP variants and previously characterized ones without the need for repetitive and expensive data generation for each new variant is appropriate [61][62][63].…”