The two partners will develop a highly innovative integrated human aerosol test platform that emulates the entire human respiratory tract with regard to dimension and architecture. PMI has established a platform that perfectly matches the architecture and characteristics of the human respiratory tract (InHALES). TissUse has established the widely used HUMIMIC Multi-Organ-Chip (MOC) platform, which enables functional human tissue response in vitro. A plug&play interface between the two technologies will allow physiologically relevant exposure to complex aerosols in the background of an in vivo-like organization and breathing performance of the human lungs. The novel integrated HUMIMIC–InHALES test platform will allow acute and subchronic tests on lung models in combination with miniaturized human liver equivalents, enabling assessment of local effects on the biological barrier of lung epithelia, penetration of substances into blood circulation, and eventual systemic effects. Altogethe r, HUMIMIC–InHALES will provide a highly predictive model for assessing respiratory toxicity and systemic human effects of inhaled aerosols and their constituents, such as environmental toxins, smoke particles, airborne pathogens, and inhalable medications.

“The agreement meets PMI’s ambitions to extend its competence in aerosol applications to the development of new methods for exploratory research and translational sciences, which will not only help advance the research & development of PMI products but also broadly support biomedical research beyond PMI’s core business.” explains Dr. Julia Hoeng, Global Head Discovery, Philip Morris International.

“This agreement synergizes the complementary ideas, know-how and experience of both companies. We are very much looking forward to enhancing TissUse’s highly innovative product and assay portfolio through this collaboration.” explains Dr. Reyk Horland, CEO of TissUse.
Technical and financial details of the collaboration were not disclosed.

About the Multi-Organ-Chip (MOC) technology
TissUse’s proprietary commercial MOC technology platform is a microfluidic microphysiological system capable of maintaining and culturing miniaturized organ equivalents that can emulate the biological function of their respective full-size counterparts over long periods. The system incorporates major features of living biology, such as pulsatile fluid flow, mechanical and electrical coupling, and physiological tissue-to-fluid and tissue-to-tissue ratios. This supports the development of a large variety of substance assays, ranging from acute and repeated dose toxicity assays to long-term disease treatment (efficacy assays). The technology allows flexible and customized combination of different tissue constructs or organ equivalents on a disposable chip-based microphysiological system. The number of organ equivalents supported by the platform ranges from a single organ culture up to an organ number that can support the study of complex organ interactions. The first commercially availa ble platforms support single-, two-, three-, and four-organ cultures. Examples of organ models available at TissUse include the liver, intestine, skin, vasculature, neuronal tissue, cardiac tissue, cartilage, pancreas, kidney, thyroid, hair follicle, lung tissue, fatty tissue, tumor models, and bone marrow. Further organ models are being developed. The platform further comprises HUMIMIC Starter devices that operate up to four MOCs simultaneously. These units provide the flexibility needed for controlling and monitoring any on-chip organ arrangement.

About the InHALES technology
PMI’s proprietary InHALES technology refers to an aerosol exposure device that closely resembles the human respiratory tract with regard to its dimension, structure, and function. It allows the study of deposition and adsorption of inhaled aerosols using a human-like lung model and thus renders the data for in vitro human respiratory toxicity more accurate and predictive. Current in vitro aerosol exposure systems do not commonly simulate these properties, which may result in the delivery of non-realistic, non-human-relevant doses of inhalable test substances to in vitro biological test systems. The new-generation in vitro aerosol exposure device—InHALES—developed by PMI can actively breathe, operate medical inhalers, or take puffs from tobacco products. In addition, it can be populated with three-dimensional epithelia isolated from various regions of the human respiratory tract. A proof of concept has recently been demonstrated with respect to aerosol delivery and compatibility of th e system with oral, bronchial, and alveolar cell cultures (Steiner et al. 2020)

InHALES follows a new strategy for aligning in vitro to in vivo dosimetry; instead of determining in vivo-delivered doses (which we define as the aerosol mass or the mass of a given aerosol constituent deposited on an exposed cell culture) and applying them to test systems, InHALES generates physiological conditions under which test atmospheres are likely to behave in the way they would in the respiratory tract of a living person. This inverse approach has the advantage that it eliminates the need for costly, time-consuming, and scientifically challenging efforts for determining in vivo delivered doses and is, by default, applicable to any test atmosphere and any test atmosphere constituent. Furthermore, by functionally and structurally mimicking the human respiratory tract, the system eliminates the need for repeated exposure when addressing different regions of the respiratory tract, because a single system covers and allows simultaneous exposure of all compartments and enables tes ting of any relevant breathing pattern or behavior. Because the system is capable of generating or sampling test aerosols on its own and in a way that is highly comparable to how the human respiratory tract does the same, the risk of introducing experimental artifacts during external test atmosphere generation or sampling is eliminated. Finally, the physiologically relevant dosing inside the system can be quantified with relative ease because the system allows complete accessibility for sampling and probes; the applicability of the system is, therefore, not limited to in vitro exposure; rather, the system is also a valuable tool for dosimetry applications.

About Philip Morris International
Philip Morris International (PMI) is leading a transformation in the tobacco industry to create a smoke-free future and ultimately replace cigarettes with smoke-free products to the benefit of adults who would otherwise continue to smoke, society, the company, its shareholders, and its other stakeholders. PMI is a leading international tobacco company engaged in the manufacture and sale of cigarettes, as well as smoke-free products, associated electronic devices and accessories, and other nicotine-containing products in markets outside the U.S. In addition, PMI ships versions of its IQOS Platform 1 device and consumables to Altria Group, Inc. for sale under license in the U.S., where these products have received marketing authorizations from the U.S. Food and Drug Administration (FDA) under the premarket tobacco product application (PMTA) pathway; the FDA has also authorized the marketing of a version of IQOS and its consumables as a Modified Risk Tobacco Product (M RTP), finding that an exposure modification order for these products is appropriate to promote the public health. PMI is building a future on a new category of smoke-free products that, while not risk-free, are a much better choice than continuing to smoke. Through multidisciplinary capabilities in product development, state-of-the-art facilities, and scientific substantiation, PMI aims to ensure that its smoke-free products meet adult consumer preferences and rigorous regulatory requirements. PMI’s smoke-free product portfolio includes heat-not-burn and nicotine-containing vapor products. As of March 31, 2021, PMI’s smoke-free products are available for sale in 66 markets in key cities or nationwide, and PMI estimates that approximately 14.0 million adults around the world have already switched to IQOS and stopped smoking. For more information, please visit www.pmi.com and www.pmiscience.com.