Originally published in Genetic Engineering & Biotechnology News on 5 September 2024.

Drug development has traditionally relied on animal in vivo models to assess safety and efficacy before human trials. However physiological, metabolic and immunological differences between animal species and humans often result in misleading data. This can lead to inaccurate classifications of drugs as safe or toxic for humans.

To overcome these challenges, microphysiological systems (MPS), also known as Organ‑on‑a‑chip (OOC) technologies, are gaining traction. These devices allows us to grow 3D human tissues cultures, with fluidic flow, that recapitulate organ-level functions in a controlled in vitro setting, offering a more predictive, human-relevant testing platform.

The article highlights two compelling case studies:

• Vitamin B12 analog cobinamide was found safe across mice, rats, rabbits, and pigs but toxic in dogs. Dr. Gerard Boss, from the University of California, leveraged CN Bio’s PhysioMimix Liver‑on‑a‑chip model to accurately predicted how the human liver would respond to the two formulations, guiding safer candidate selection.

Webinar on demand

Fighting Toxic Chemicals: Evaluating the Safety of Cobinamide as a Neutralizing Agent

Prof. Gerard R. Boss, MD, UCSD discusses how the CN Bio CRS team leveraged the PhysioMimix OOC to uncover and compare the hepatotoxicity potential of Vitamin B12 cobinamide compounds in humas and other animal species. Watch here

• Antisense oligonucleotides (ASOs) developed by AstraZeneca displayed inconsistent toxicity profiles in animal models. A follow-up study using human OOC revealed that one ASO was toxic and another safe in humans, information animal tests failed to clarify.

Webinar on demand

Advancing oligonucleotide therapies with Liver-on-a-chip models

Dr. Oliver Culley, examines the challenges of developing and delivering oligonucleotide therapeutics using OOC, and explores two real-world cases. Watch now

Moreover, integrating human and animal OOCs early in development can reduce reliance on in vivo animal testing, especially when translating complex or species-specific responses, lowering costs and improving safety.

Webinar on demand

Harnessing liver-on-a-chip models for drug safety

Dr. Tomasz Kostrzewski, Dr. Emily Richardson and Dr. Dr. Rhiannon Hardwick (Bristol Myers Squibb) explores the use of OOC to improve IVIVE
Watch here

In conclusion, looking at in vivo models vs NAMs, technologies such as Organ‑on‑a‑chip won’t immediately eliminate animal testing. However, their proactive use before in vivo studies can refine experimental design, reduce animal use, clarify toxicity potential of different compounds, and de-risk first-in-human trials, making drug development safer, more efficient, and more ethical.

Access the full article here.