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).
To verify the product stability and establish a product shelf life, we follow international standards, in particular ICHand FDA.
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 I||22ºC ± 2ºC||60 ± 5% RH||12 months|
|2: Hot and very humid climate Zone IVb||30ºC ± 2ºC||75 ± 5% RH||12 months|
|3: Hot and dry climate Zone III||30ºC ± 2ºC||35 ± 5% RH||12 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.
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)
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.
The predictive distribution model of HPHC's v the Nicotine yield which represent a range of puffing intensities
 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.
Read more on the ICH Harmonised Tripartite Guideline, Stability Testing of New Drug Substances and Products Q1A(R2)
International Conference On Harmonisation Of Technical Requirements For Registration Of Pharmaceuticals For Human Use Stability testing of new drug substances and products Q1A(R2) Current Step 4 version, dated 6 February 2003
Read more on the ICH Harmonised Tripartite Guideline, Bracketing and Matrixing Designs for Stability Testing of New Drug Substances and Products Q1D
International Conference On Harmonisation Of Technical Requirements For Registration Of Pharmaceuticals For Human Use Bracketing and Matrixing Designs for Stability Testing of New Drug Substances and Products Current Step 4 version, dated 7 February 2002
Read more on Evaluation for Stability Data Q1E, ICH Harmonised Tripartite Guideline
International Conference On Harmonisation Of Technical Requirements For Registration Of Pharmaceuticals For Human Use Evaluation for Stability Data Q1E Current Step 4 version, dated 6 February 2003
See the US Food and Drug Administration (FDA), 21 CFR 211.166 Stability Testing