Researchers from the UK’s National Institute for Biological Standards and Control (NIBSC) have developed the test, which effectively reproduces the devastating immunological reaction suffered by the Northwick Park volunteers in isolated human cells.
Dr Stephen Poole, speaking at the British Pharmacological Society's Winter Meeting in Brighton, said: “we are still investigating why the effect of this drug was so catastrophically different in the clinic than in preclinical testing.”
“[But] we have at least managed to develop new preclinical tests that should help us to avoid such outcomes in the future."
The Northwick Park trial in 2006 involved an immunotherapeutic called TGN1412, developed by German biotech company Tegenero, which was administered to patients at a clinical facility operated by contract research organisation (CRO) Parexel.
Standard preclinical in vitro tests on TGN1412 failed to predict the catastrophic reaction that occurred when the drug was administered to human subjects.
The disaster resulted in the UK Medicine and Healthcare products Regulatory Agency (MHRA) suspending all clinical trials of immunotherapy drugs and commissioning NIBSC, a government-funded institute, to investigate why preclinical tests had failed to predict the response to the drug.
The new measures laid out by the NISBC include ensuring that such drugs are not tested solely on white blood cells in isolation. The NIBSC group has shown that having a mixed human cell culture of white blood cells and endothelial cells – the cells that line blood vessels – is a much better indicator of how this type of drug will react in vivo.
The NIBSC group has also developed a technique that dries the drug onto a plastic surface, rather than testing it on cells as a solution in water, which has proven to be a far more reliable indicator of how the drug will react in the human body.