Understand the human health impact of your products.
The purpose of clinical data is to demonstrate the likely benefit for smokers who choose to use the NGP product. Whilst pre-clinical data can show that an NGP produces less harmful chemicals than a combustible cigarette and that the NGP demonstrates less toxicological concern, it is important to note that these observations are gleaned from laboratory conditions where the puffing of a cigarette and an NGP are conducted by specialized smoking machines designed to puff in a defined way (puff volume, puff duration, and inter-puff timeframe). It is well known, that when humans smoke, they alter their smoking behavior considerably which means that the characteristics of the inhaled aerosol can be very different to the characteristics of the aerosol generated by machine puffing. Clinical studies are critical to show that when a person uses the NGP with a behavior that may be very different to a puffing machine, the generation of harmful chemicals and the resultant toxicological burden remains similar to that found in the laboratory and is still significantly beneficial compared to smoking combustible cigarettes.
In general there are four types of clinical studies that Broughton design, conduct and analyze for your regulatory applications:
Topography studies are designed to understand the puffing use behavior when subjects use the NGP. Parameters such as puff volume, puff duration, peak air flow and inter-puff intervals are measured to understand if the product is used differently from the standards used to generate aerosol on puffing machines in the laboratory. The data from these studies can also be directly used in desk-based toxicological assessments as a more accurate “dose” can be determined to calculate the toxicological risk.
PK/PD studies are important datapoints in regulatory applications. They provide information that indicates how much nicotine is delivered by the NGP by assessing the levels of nicotine in the blood of users compared to the levels detectable after smoking a combustible cigarette. There are a number of PK parameters considered for assessment of the data and product. However, the two most important parameters are the Maximum concentration of nicotine reached in the blood (Cmax) and time it takes to reach maximum concentrations (Tmax). If the Cmax is not high enough, the product is unlikely to provide sufficient satisfaction for current smokers and therefore it might be more difficult for smokers to off-ramp onto the NGP. If the Cmax is too high (higher than what a combustible cigarette delivers) then the potential for abuse liability increases (the NGP may be more addictive than a combustible cigarette). Similarly, if the Tmax is longer than a combustible cigarette, the craving relief a smoker feels may be too delayed with the NGP and therefore not an acceptable alternative. If the Tmax is shorter than that provided by combustible cigarettes, it may make the NGP more addictive. A PK profile that lies somewhere in between a combustible cigarette and medicinally approved nicotine replacement therapy (e.g. a nicotine patch) is ideal for an NGP.
Pharmacodynamic data relies on regulatory approved satisfaction questionnaires, whereby the NGP should demonstrate levels of satisfaction similar to a combustible cigarette to ensure that smokers can achieve off-ramping.
Biomarkers studies look at changes in blood, urine and physiology to understand the efficacy of an NGP. Biomarkers of Exposure are generally metabolic products of the Harmful and Potentially Harmful Constituents (HPHCs) found in cigarette smoke. Since the laboratory analysis is likely to have shown a reduction or elimination of the HPHCs compared to combustible cigarettes, biomarkers of exposure are the clinical confirmation that even with modified puffing behaviours of users, the levels of these HPHCs are far reduced after using the NGP. This data is the definitive proof that the NGP results in a reduced exposure to these harmful chemicals. Biomarker of exposure studies can either be conducted over a short duration (5 days) when subjects stay in a clinic and their exposures to other sources of the HPHCs are controlled, or be longer ambulatory studies (up to 6 months) where subjects use the product in the real world. The most robust applications use a combination of both approaches to show the reductions in both controlled and uncontrolled environments.
BoPH are associated with smoking-related disease endpoints e.g. lung function, blood pressure, inflammation. These studies are designed to show that prolonged use of the NGP, instead of combustible cigarettes, results in positive changes in these biomarkers demonstrating a reduction in risk of disease development. BoPH studies are normally much longer-term, 12-18 months, as these biomarkers need a longer time period to demonstrate change as a result of off-ramping. These types of studies are normally reserved for MRTP applications.
As part of our strategy definition phase for your project, depending on the regulatory pathway you selected for your product, our consultants help you decide which studies work best for your application and help you design and conduct the appropriate studies.
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