The disastrous trial in the UK in March clearly illustrated one thing: the tests we rely on to predict how a drug will behave in people are outdated. Scientists in Europe are developing new tests to help get a better picture.

In the UK trial, six men suffered severe immune reactions to an experimental leukemia drug. Tests in animals revealed nothing extraordinary, and the investigators ruled out any possibility of contamination in the drug.

There are many unresolved questions about that trial (Nature 440, 856; 2006), but the human body’s response to the drug, based on a monoclonal antibody, proved particularly unpredictable.

Up to 30% of experimental drugs fail in clinical trials. Because of differences in immune makeup, animal models are likely to be even poorer at predicting the toxicity of protein-based therapies.

“These types of drugs make up more than 50% of new drug applications,” notes Thomas Hartung, head of the European Centre for the Validation of Alternative Methods (EVCAM). “We can’t use toxicology that is 60 years old.”

In March, EVCAM approved six new toxicology screens based on cultures of human cells. Five of the tests detect pyrogenic contaminants in drugs—for instance, bacteria that can infiltrate injectable or intravenous drugs during manufacture and cause lethal immune reactions. The tests rely on cultured human white blood cells, and might replace two expensive current methods—the Limulus assay and testing on rabbits.

The new techniques improve on both methods. The Limulus assay picks up only a subset of bacteria, but these methods detect most bacteria, viruses and fungi.

Drugs not suitable for the Limulus test, such as monoclonal antibodies and other biological compounds, are typically tested in rabbits. But the tests only provide a simple yes or no for contamination and cannot quantify the amount of toxin. Because of species differences, the immune reaction in a rabbit may also not match the response in humans.