The speakers all cited either throughput or cost as barriers to the use of complex cell assays for routine screening. As Dr. Ludbrook noted, “At GSK we like cost-effective, fast assays. Some of the more complex cell-based assays using techniques such as flow cytometry are just too low throughput.
“We use flow cytometry in a kinase program to support lead optimization but can only characterize a fraction of the number of compounds we need to. This is why we’re investigating using the HyperCyt® technology for flow cytometry, as this will take us into real-world screening throughput because it reduces plate read time from 120 minutes to 14 minutes for a typical assay, and therefore gives us the potential to screen thousands of compounds in a disease relevant assay."
“Primary cell assays are expensive,” added Dr. Bays. “With whole blood, you can only get so much blood to work with from one draw and it requires special handling conditions. We use instruments like the Labcyte ECHO to reduce volumes as much as possible, but it still currently costs us about $900 per run for antibodies alone.
“We have not yet reached our goal of spending less than $1 per well. However, we have reduced costs significantly and are not spending anywhere near the $23 per well cost we incurred when we were first developing these assays and had to rely on standard reagent sizes.”
According to Dr. Barry, qPCR is too expensive at the moment for the PLA “but as qPCR and microfluidics are on the point of explosion, it may get to the cost point where we may in the future be able to use this technology for transcriptional screening.”
Dr. Ludbrook identified a wider scientific gap in the understanding of toxicity readouts compared to efficacy readouts.
“The battery of assays used in understanding toxic characteristics of compounds should lead to a reduction in attrition at this stage of drug discovery,” he said.
“However, there is less understanding of translational complex cellular assays that are truly representative of disease. The risk is we could be taking a larger number of safer candidates into expensive and time-consuming Phase II/III trials.
“But if we fail to improve our predictions of efficacy, then we will be failing later and more expensively. We need to focus on this to enable us to bring more medicines to patients at a lower cost of development.”