The first of the five steps of our systems toxicology strategy for Reduced-Risk Product (RRP) assessment is focused on the production of high-quality, systems-wide experimental data, which we generate through a combination of in vitro, in vivo and clinical systems. We use whole smoke / aerosol exposure techniques for our in vitro models.
In Vitro Systems
In 2007, the US National Research Council published a new strategic plan for toxicological assessment in order to update and advance our knowledge of the toxicity and mode of action of environmental agents1. To generate better data on the potential risks to humans, the strategy recommends the use of computational toxicology and systems biology in combination with human-relevant in vitro models that allow multiple dose testing.
For details and references, please read below.
In Vivo Systems
In vivo models (usually rodents) are used to assess the systemic toxicological impact of compounds and products. We are applying the in vivo testing guidelines defined by the Organization for Economic Co-operation and Development (OECD) and are committed to efforts to “Replace, Reduce, Refine” in vivo testing1, as evidenced by our significant investment into the advancement in vitro methods. In the assessment of Reduced-Risk Products (RRPs), we use in vivo disease models that respond to cigarette smoke2,3,4,5,6.
For details and references, please read below.
Clinical Systems
The aim of clinical systems biology at PMI is to conduct observational, non-interventional clinical research studies to generate human systems biology data for our systems biology assessment of Reduced-Risk Products (RRPs). Samples are collected as part of our clinical assessment work, allowing us to conduct systems analysis as exploratory endpoints.
For details and references, please read below.
Whole Smoke/Aerosol Exposure
There are a variety of whole smoke exposure systems available for the generation, dilution and delivery of cigarette smoke or Reduced-Risk Product (RRP) aerosols in vitro, all of which aim to ensure that there are limited changes between generation and exposure7.
For details and references, please read below.
In Vitro Systems
Human 2D models and High Content Screening
Human 3D models
In Vivo Systems
To
In Vivo Disease Models
Cardiovascular disease
Chronic obstructive pulmonary disease (COPD)
Lung cancer
OECD+
Testing a prototypic RRP in an in vivo model of COPD

Clinical Systems
The aim of clinical systems biology at PMI is to conduct observational, non-interventional clinical research studies to generate human systems biology data for our systems biology assessment of Reduced-Risk Products (RRPs). Samples are collected as part of our clinical assessment work, allowing us to conduct systems analysis as exploratory endpoints.
Biomarkers of Disease Onset
Identifying Biomarkers of Disease Onset for COPD

Whole Smoke Exposure
There are a variety of whole smoke exposure systems available for the generation, dilution and delivery of cigarette smoke or Reduced-Risk Product (RRP) aerosols in vitro, all of which aim to ensure that there are limited changes between generation and exposure1.
Smoke/aerosol fractions and in vitro exposure
In vitro whole smoke/aerosol exposure
