Our products are designed to reduce exposure to a ranges of HPHCs and before biological testing we verify the performance of the products by measuring the smoke chemistry under standardized smoking conditions. We are, however, also verifying that the product performance is maintained with time or usage under a range of real life situations (such as climatic conditions and smoking pattern).

 

Product stability

To verify the product stability and establish a product shelf life, we follow international standards, in particular ICH[1][2][3]and FDA[4].

Multiple batches are stored under predefined conditions, covering the WHO climatic zones defined in ICH guidelines (Q1):

Test Condition n° and Zones Temperature  (ºC)Relative Humidity (%)Storage Time
1: Temperate climate Zone I22ºC ± 2ºC60 ± 5% RH12 months
2: Hot and very humid climate Zone IVb30ºC ± 2ºC75 ± 5% RH12 months
3: Hot and dry climate Zone III30ºC ± 2ºC35 ± 5% RH12 months

Different time points are defined, where selected batches will be tested for a range of HPHCs in the aerosol, physical characteristic of the product, sensory property and visual inspection.

For quantitative data, all values measured are then aggregated together to build a regression model for the time evolution and the confidence limit for every parameter followed in the course of the aging study. The confidence level is then compared to a pre-established spec to define the shelf life of the product.


1.1.3.4-linegraph_0_ProductStabilityRobustness

UMCL – Upper 95% confidence interval for the regression

LMCL – Lower 95% confidence interval for the regression

USL – Upper shelf life specification limit

LSL – Lower shelf life specification limit

 

Product robustness under various climatic conditions

Our products will be used in different regions therefore we need data to demonstrate that the products performance will be maintained in various climatic conditions.

To do that, we have a climatic smoking machine enabling testing the products under defined humidity and temperatures. We use the temperature and humidity ranges covering the WHO climatic zones defined in ICH guidelines (Q1), also used for aging studies.

Two distinct scenario are simulated: the product is stored under different conditions and used under normal (ISO) conditions, or the product is stored and used under different conditions. The focus is then on analysing the aerosol content, deliveries and HPHCs, and the levels are compared to those obtained under standard conditions.

 

Product robustness under different puffing regimes

People smoke differently therefore we need to evaluate product performance under different puffing regimes that we have developed, for example as described by de La Bourdonnaye et al. (2015)[5]

Using this range of puffing regimes, HPHCs are measured and then plotted vs. nicotine deliveries, to verify that their levels are kept in proportion to nicotine, with the ratio of nicotine to HPHCs either constant or decreasing. This product behavior ensures that the reduced exposure compared to cigarette use will be maintained, regardless of the puffing patterns.

1.1.3.4-graph_ProductStabilityRobustness

The predictive distribution model of HPHC's v the Nicotine yield which represent a range of puffing intensities

References:

[1] Stability Testing of New Drug Substances and Products Q1A(R2), ICH Harmonised Tripartite Guideline

[2] Read Bracketing and Matrixing Designs for Stability Testing of New Drug Substances and Products Q1D, ICH Harmonised Tripartite Guideline

[3] Evaluation for Stability Data Q1E, ICH Harmonised Tripartite Guideline

[4] US Food and Drug Administration (FDA), 21 CFR 211.166 Stability Testing

[5] Investigation on puffing topography parameters and product evaluation recorded during five days of use of the tobacco heating system 2.2: A comparison with continued combustible cigarette use. Society for Research on Nicotine and Tobacco Annual Meeting 2015. , de La Bourdonnaye G et al.