The lung is a highly complex organ, comprised of more than 40 cell types that are responsible for various important functions, the lung’s complexity contributes to the subsequent challenges with developing complex in vitro co-culture models (also called micro-physiological systems or (MPS) or organs-on-ships). In vivo pharmacology naturally fulfills an important role in drug discovery, enabling benchmarking and selection of lead compounds against a particular target and understanding of PK/PD relationships to enable clinical dose prediction and calculation of safety margins amongst other roles.
Although there are a myriad of considerations and limitations in the development and qualification of such in vitro systems, MPS exhibit great promise in the fields of pharmacology and toxicology. Successful development and implementation of MPS may enable assessment of human translation of mechanistic responses observed in non-clinical species, potentially increasing the clinical relevance of efficacy or safety endpoints, while decreasing overall animal use. This article summarizes, from the pharmaceutical industry perspective, essential elements in the development and qualification of lung MPS that MPS developers and manufacturers can adapt to facilitate the rapid implementation of these models for safety evaluation during the drug development process.
1. What role can ex vivo models and ‘lung-on a-chip’ model play in respiratory drug discovery?
2. A look into the future: considerations for design and utility of the next generation micro-physiological systems for respiratory drug discovery