More accurate predictions for safer drugs
- Press release
Innovative liver models outperform animal testing
A workshop at the Royal Society in London focused on investigating liver toxicity in drug development. Experts emphasized that animal testing cannot reliably predict liver damage. In contrast, complex in vitro models (CIVMs), such as organoids or liver chips, provide significantly more accurate results. The recently published findings from the workshop reinforce the nationwide association Doctors Against Animal Experiments' call for the consistent use of animal-free methods. This approach not only eliminates animal testing but also enhances patient safety.
The liver can be damaged by medications, a condition known as drug-induced liver injury (DILI). This adverse effect can range from mild symptoms like nausea to life-threatening liver failure. Many medications, including painkillers like paracetamol or antibiotics, pose a risk for DILI. Furthermore, liver damage is one of the most common reasons why new drugs fail to gain approval or are later withdrawn from the market.
Traditionally, liver toxicity is assessed using animal experiments. However, the authors of the publication highlight that animal metabolism differs fundamentally from that of humans. As a result, findings from animal studies cannot be reliably translated to humans. Studies show that only 33% of substances toxic to the human liver also cause liver damage in rats, and only 27% in dogs, according to the publication.
The authors conclude that complex in vitro models, on the other hand, can more realistically replicate the human liver. These include 3D cell cultures, such as organoids, as well as organ-on-a-chip technologies that culture human liver cells in microfluidic systems. These liver chips simulate blood flow and oxygen supply, allowing drugs to be tested under realistic conditions. "Animal-free methods are clearly superior to animal testing. With their improved predictive power, they can help make drugs safer and prevent adverse effects," emphasizes Dr. Johanna Walter, scientific advisor at Doctors Against Animal Experiments.
The article cites comparative studies showing that complex in vitro models (CIVMs) have significantly better predictive power than animal testing. Particularly promising is the liver-chip technology from the US company Emulate, which has a sensitivity of 87% and a specificity of 100%. This means that 87% of actually liver-toxic substances were correctly identified as toxic—including those that were falsely classified as non-toxic in animal experiments. Conversely, non-toxic substances were reliably classified as safe.
In addition to better protecting human health, CIVMs also offer economic advantages, as outlined in the publication. By identifying liver-toxic drug candidates earlier in the development process, costly failures can be avoided.
"We are at a turning point in drug development. Animal-free methods give us the opportunity to develop safer drugs faster and more cost-effectively," says Walter. Doctors Against Animal Experiments calls for a shift in drug testing—away from unreliable animal experiments and towards human-relevant methods. To achieve this, greater support for animal-free methods and closer collaboration between regulatory authorities, industry, and academia are necessary.