Improving the Drug Development Process with Organ-Chips

To predict whether new therapeutics will be safe and effective for humans, drug developers first test them in animal- and cell-based models as well as computational tools that are designed to approximate human biology. Unfortunately, these approaches often fall short, as 90% of drug candidates that enter clinical trials fail—mostly because they are ineffective or have unforeseen toxicity. Not only is this inefficient system time- and resource-intensive, but it can be costly in terms of human lives1. To improve the odds of clinical success, researchers need models that better reflect human biology.

Organ-Chips combine cell culture with microfluidics to emulate the biological forces of different organ tissues and disease states, such as peristalsis in the intestines, breathing in the lungs, and blood flow through the vasculature2. The chips are flexible, thumb-drive-sized devices with parallel upper and lower microfluidic channels, each seeded with organ-specific cells. The channels are separated by a thin, porous membrane coated with a tissue-specific extracellular matrix, which creates an interface for cell-cell communication (Figure 1). 

Organ-Chips are cultured in a microfluidic platform that automates fluid flow and cyclic mechanical strain to create and maintain physiologically relevant conditions in the chip’s microenvironment. This ensures that the cells behave like they were in their native organ—and react to drugs, chemicals, and other substances accordingly.

Researchers can collect real-time data with high-content microscopy imaging, effluent sampling, and various functional measurements3. They can also perform traditional endpoint analyses such as cytotoxicity assays and immunohistochemistry, as well as omics-based analysis to identify relevant disease pathways.

Organ-on-a-Chip Applications

Organ-on-a-Chip technology is used across various research areas, including toxicology, immunology, gene therapy, and cancer research. Within academia, Organ-Chips enable researchers to develop new models with closer-to-human gene expression and gain a better understanding of human physiology and disease mechanisms. Within the pharmaceutical industry, the technology is primarily used to help determine drug candidates’ efficacy and toxicity during the preclinical stage, helping to improve the quality of drugs that enter the clinic3.

With a higher predictive validity than conventional models4, Organ-on-a-Chip technology can identify drug candidates with a greater probability of success, improve patient safety, lower development costs, and shorten the timeline for bringing new drugs to market. They can open doors in medical research by allowing scientists to create new disease models and probe unexplored biological pathways. Organ-Chips could also greatly benefit personalized medicine, as scientists could use the technology to create an in vitro model of a specific patient using biopsied cells and determine the best treatment strategy.

Organ-Chip research and development are heading into the next decade with many exciting advancements and promising prospects. One example is the passage of the FDA Modernization Act 2.0, signed into law by President Biden in December 2022. This legislation removes the nearly 100-year-old requirement that animals must be used to investigate drug safety and efficacy. Now, researchers can use animal model alternatives, including Organ-Chips and other microphysiological systems, when submitting an Investigational New Drug (IND) filing to the FDA. The law also includes funding to help create new Organ-Chip systems and improve existing ones5. This will help accelerate the development and standardization of more Organ-on-a-Chip technologies, making it easier for pharmaceutical researchers to integrate them into their drug development pipelines.

In December 2022, a first-of-its-kind study was published in Communications Medicine, a part of Nature Portfolio, in which researchers showed that the Emulate human Liver-Chip meets the IQ MPS Affiliate’s qualification guidelines for use in predictive toxicology applications. When tested against a set of 27 toxic and non-toxic drugs, the Liver-Chip was found to have 87% sensitivity and 100% specificity4. Importantly, each toxic drug used in the study was falsely deemed safe by animal testing, meaning the Liver-Chip has the potential to reduce drug-induced liver injury by up to 87%. Economic modeling in that study also showed that incorporating Organ-on-a-Chip technology into drug development programs can improve productivity for the small-molecule pharmaceutical industry by $3B annually.

Organ-on-a-Chip technology is a powerful preclinical model that gives scientists better insights into human biology and disease mechanisms. By precisely replicating organ biology and function, Organ-Chips overcome many of the issues with traditional preclinical models, giving drug developers confidence when progressing drugs to human trials. Ultimately, this will help create more efficient drug development pipelines—and, most importantly, better, safer medicines for patients.

1.    Scannell, J. W. & Bosley, J. When Quality Beats Quantity: Decision Theory, Drug Discovery, and the Reproducibility Crisis. PLoS One 11, e0147215 (2016).
2.    Ingber, D. E. Human organs-on-chips for disease modelling, drug development and personalized medicine. Nat. Rev. Genet. (2022) doi:10.1038/s41576-022-00466-9.
3.    Leung, C. M. et al. A guide to the organ-on-a-chip. Nat. Rev. Methods Prim. 2022 21 2, 1–29 (2022).
4.    Ewart, L. et al. Performance assessment and economic analysis of a human Liver-Chip for predictive toxicology. Commun. Med. 2022 21 2, 1–16 (2022).

5.    Sen. Paul, R. [R-K. S.5002 – 117th Congress (2021-2022): FDA Modernization Act 2.0. (2022).