How Industry Embraces Organ-on-Chips: A 2024 Status Report

The pharmaceutical industry faces a significant challenge with high drug attrition rates. Traditionally, animal models have served as the gold standard for pre-clinical testing. However, it is now widely acknowledged that these models do not fully predict human toxicities and efficacies. Particularly concerning is their limited success in predicting liver toxicities. Ethical concerns, especially regarding the use of non-human primates (NHPs), have spurred the development of complex in vitro models derived from human cells. These models, validated for various Contexts of Use (CoUs), offer promising insights in drug discovery.

Organ-on-chips are 3D complex in vitro models that generally incorporate 3D microenvironment, spatially arranged human-derived cells of an organ, and various mechanical cues consisting of organ relevant flow and motion. For instance, lung-on-a-chip may simulate breathing motion and systemic blood flow, featuring human-derived lung epithelium and endothelial cells separated by a membrane or hydrogel.

The last decade witnessed extensive validation of organ-on-chips (OoC) by the academia and OoC makers, setting the stage for broader industry adoption in the current decade. A significant milestone was the passing of the FDA Modernization Act 2.0 law in the United States, signaling a shift toward embracing non-animal methods in drug discovery. The recently introduced legislation, FDA modernization act 3.0, underscores this commitment by outlining detailed guidelines related to the qualification process under which the applicant can request for the eligibility of the non-clinical method.

Recognizing that industry validation is crucial for gauging the translatability of OoC models, collaborative efforts between industry and OoC innovators are underway. Several major pharmaceutical companies have initiated exploratory studies, marking a pivotal moment in OoC adoption. This report outlines these collaborative endeavors and provides insights into the translatability of OoC models.

Figure 1 illustrates a consistent growth in collaborative studies over the years, with a total of 70 publications in the last 10 years. Notably, the past four years have seen a twofold increase in industrial validation across various fields and organ models, peaking in 2022 and 2020. This positive change is partly due to the strong backing from the regulatory agencies and various government initiatives that resulted into promotion of MPS (microphysiological systems) usage in drug discovery. Further, this rigorous industrial testing trend indicates that the next 3-5 years present a favorable investment opportunity in such models.