Organ-on-a-chip adoption: The roadmap to broader use

Paving the way for Organ-on-a-chip adoption

Drug discovery is becoming more complex as we move from a small molecule world to large molecules and new modality drugs. This shift brings new challenges, particularly in pre-clinical toxicology testing, where traditional animal models often fall short because of differences in genetics, metabolism or immunological response that make animal models unsuitable.

Pharmaceutical companies face increasing pressure to improve the efficiency of their drug discovery pipeline by reducing attrition rates. A significant portion of drug failures, up to 30% (Giri et al., 2015), are due to toxicity issues that were not predicted during pre-clinical testing. This high attrition rate highlights the need for more reliable and predictive toxicology testing methods that can narrow the current gap between pre-clinical and clinical outcomes.

The FDA Modernization Act 2.0 supports the increased use of alternative approaches to in vivo testing, by expanding the range of tools available to drug developers. Ultimately the FDA aims to ensure that companies are using the best tools available as well as the right combination of tools to avoid any adverse effects during clinical trials. The key to successfully including Organ-on-a-chip (also known as Microphysiological Systems) data in regulatory submissions lies in establishing a clear context of use. By positioning these tools often before in vivo studies, it is possible to be more confident that the right dose of a molecule will hit its intended target, delivering maximal efficacy without inducing toxicity. A more human-centric approach to toxicology testing may prevent potentially successful molecules from being lost in the clinic or before.

PhysioMimix Organ-on-a-chip adoption into toxicology workflows

Technologies, such as CN Bio’s PhysioMimix®  OOC, offer a reliable, reproducible and higher throughput (see our new Multi-Chip Liver-48 plate) option to accurately assess the same biomarkers in preclinical testing as the clinic. These more sophisticated in vitro models, which incorporate immune components, can detect highly specific and human-translatable endpoints compared to in vivo animal models.

One significant application of OOC technology is in pre-clinical toxicology testing. A recent survey by CN Bio and CiteLine showed that more than half of drug developers are using or planning to use OOCs for safety toxicology testing. Since in vivo safety tox studies are often the most complex and costly part of preclinical development, it makes sense to start here.

What are the benefits of Organ-on-a-chip adoption within toxicology workflows?

These technologies have a crucial role to play in reducing the riskiness of developing new drugs by providing:

• detailed assessments of acute and chronic exposure to gain deep mechanistic insights into a compound’s toxicological profile to guide the selection of the most appropriate animal species. More detailed and relevant data upfront will help improve in vivo study design, reducing the number of animals needed and lowering associated costs.
• improved translatability of pre-clinical data to clinical outcomes will ensure that drug developers can confidently take fewer, safer drugs forward.
• data for better patient study design; based on more clinically-relevant data, and data from different populations (e.g. the highly prevalent liver disorder MASLD and its more advanced form MASH) before drugs enter first-in-human (phase I) clinical trials reducing clinical risk.

Organ-on-a-chip versus animal models: reduce, refine or replace?

OOCs provide cost effective alternatives that complement animal studies to deliver human-translatable results faster. There is a clear advantage to using OOCs before starting in vivo animal testing. However, human OOCs are not attempting to be comparable to animal models especially where animal models are poor predictors of clinical outcomes. Their purpose is to catch what animal models might miss, or falsely flag as toxic due to interspecies differences. Additionally, for human-specific new modality drugs, OOCs offer a viable path forward where animal species are less suited to reduce unnecessary animal use.

Recent experiments by CN Bio using animal-on-a-chip models (or animal MPS) that utilize primary rat, or dog cells show that animal OOC data closely matches published animal testing results. These data demonstrate the system’s ability to recapitulate in vivo physiology, building confidence and trust to facilitate accelerated Organ-on-a-chip adoption. Additional data, guidance on broader context of animal OOC use, and its potential to inform species selection and safeguard research animal will be available in 2025.

By improving the translatability of data between the laboratory and the clinic, OOCs can make more accurate predictions of human responses in the pre-clinical phase, decreasing the risk of unexpected results in clinical trials. This can help to improve the efficiency of the drug development process. More accurate, human-relevant data not only addresses the limitations of traditional animal models and enhances the predictability of clinical outcomes, but also enables more effective drugs to reach the market faster.

---

References

1. Giri S., Bader A. (2015). A low-cost, high-quality new drug discovery process using patient-derived induced pluripotent stem cells. Drug Discov. Today 20, 37–49. 10.1016/j.drudis.2014.10.011