High-throughput screening has enabled pharmaceutical companies to run assays on more compounds than ever before, but there has been no appreciable increase in the number of final drugs approved for sale. Some technology developers feel that this is because screening has focused on quantity rather than quality.
The advent of high-throughput screening (HTS) technology revolutionised the process of compound assays, enabling researchers to rapidly collect huge amounts of data and explore compound libraries with unprecedented thoroughness. Investments in the technology by pharmaceutical companies were ultimately intended to achieve one thing - a greater number of final drug products that could be sold at market. However, there are signs that this has not been achieved.
"Ten years ago there was a vast increase in the number of compounds that could be screened and people were very excited," says Günther Knebel, head of R&D Department for Greiner Bio-One. "They turned to HTS to get more hits from their compound libraries and produce more drugs. But there are restrictions. The number of substances screened has risen, but not the number of approved drugs. FDA approvals are at the same level as they were ten years ago."
Greiner Bio-One was among the first suppliers to focus on high-density plate formats in the late 1990s. It specialises in developing solutions for the biotechnology, diagnostic, pharmaceutical and medical device sectors. Its BioScience division has focused its attention on this seeming paradox in HTS.
From his company's observations of HTS, Knebel feels the pharma industry needs to look at the benefits of screening campaigns to find out how to derive better content, with the focus firmly on the final output - a marketable drug.
Firms have made the investment in more robust, long life-cycle equipment and streamlined processes, incorporating their own detection technologies. To improve the number of 'hits' from a compound library, firms have previously sought to increase the density of their screening plates in order to achieve a further step up in the number of assays. This, Knebel believes, could prove futile.
Indeed, he notes that only 10 per cent of the market use 1536-well microplates, with such high densities the preserve of global pharma companies. He sees a trend towards using 384-well plates with industry-supported standards, especially among mid-sized companies.
"We focus on 384 formats, which achieve a good balance between investment and results," he says. "They offer high density, better cost performance and the technology is very robust. 1536 well plates demand high-end technology and large screening campaigns, though for global players the investment makes sense."
With miniaturisation reaching what Knebel believes is a physical limit at 1536, the question is how to derive better content from existing densities. The answer, he feels, is to tailor plates specifically to the needs of individual companies and allow them the flexibility to adapt plates to their own screening technologies.
"By focusing on quality rather than quantity we can get better results from existing libraries, improve efficiency and reduce the time to market for marketable drugs," he says.
Tailored HTS plates may help achieve this, along with a change in the targets for screening. "One focus will be cell-based assays, not just compounds. For this you need well-adapted surfaces, which is why we make plates with a biological coating. The process is well established, but with a biological product there are issues over stability and the interaction with cell-lines. So, we looked at whether we could develop a chemical coating, using a well-defined mix of back-traceable chemicals, which can promote the growth of cell-lines like today's bio-coatings."
Greiner Bio One has built up expertise in non-binding chemical surfaces for the storage of compound libraries, and is now focusing on developing chemical coatings that will perform as well as biological coatings for cell-based assays and compound HTS. Time will tell if it will lead its pharma clients on its quest for quality.
Greiner Bio-One GmbH specialises in labware for biotechnology, the diagnostic and pharmaceutical industries as well as in medical and in-vitro diagnostics.