HTS to become key drug discovery tool?
in Europe has singled out high throughput screening (HTS) as an
approach that will provide mechanistic insights and new drug leads
with improved efficiency whilst reducing cost.
According to market researchers Frost & Sullivan, the constant pressure to discover and develop new therapeutics at a lesser cost and within shorter timeframes has led to many pharmaceutical and biotechnology companies actively seeking out alternative yet equally effective approaches that justify the mammoth costs involved with bringing a drug onto the market.
High content screening, an advanced form of HTS using cell-based assays, offers the potential to address and ease the bottlenecks currently encountered in the drug discovery process.
HTS is the process in which batches of compounds are tested for binding activity or biological activity against target molecules. Test compounds act as inhibitors of target enzymes, as competitors for binding of a natural ligand to its receptor, as agonists or antagonists for receptor-mediated intracellular processes, and so forth.
Dr Amarpreet Dhiman, a research analyst with Frost & Sullivan said: "By shortening the drug discovery cycle, HTS offers the opportunity to capture maximum market share and optimise revenue generation within the first year of entry."
"It is also likely to increase the chances of clearing clinical trials by addressing issues related to pharmacokinetics, animal toxicity and side-effects."
The race to be the first to market a new drug has never been more intense with a fine line between success and failure always apparent. As of 2003, the European HTS market was worth $483 million (€377m) and is projected to be valued at $925 million in 2010. Germany is the largest market for HTS in Europe, with revenues greater than $120 million of the market value.
Globally, the HTS market is on the increase as the number of both drug candidates for evaluation and targets has ensured continued investment this technology by drug discovery companies. At present, the US remains the single largest market for HTS due to the geographical location of the major pharmaceutical and biotechnology companies. The US generated revenues approaching $3.1 billion in 2003, with the market growing substantially since 2000. This includes all aspects from instrumentation, supplies and to consumables.
The benefit of being the first to market a new drug can be as much as $1bn revenue in the first year, with a large percentage of the market share for the lifetime of the drug. With investments regularly exceeding $500 million and nine out of ten candidates failing to get drug approval, the chances of failure and the rewards for success have never been greater.
Today, many competing companies are screening 100,000-300,000 or more compounds per screen to produce approximately 100-300 hits. On average, one or two of these become lead compound series. Larger screens of up to 2-3,000,000 compounds (involving UHTS - Ultra High Throughput Screening) may be required to generate something closer to 7-10 leads.
To bring down costs, an emerging trend of outsourcing HTS has provided access to additional drug entities and innovative technology, significantly raising the chances of success. According to the market researchers, outsourcing is expected to form 57 per cent of total drug development expenditure in 2010.
Bioinformatics has become increasingly popular with multinationals, speeding up the drug discovery process by predicting the biological properties of a particular lead compound and its viability as a potential drug candidate. When used in conjunction with bioinformatics, HTS can rely on quality lead compounds to generate considerable time and cost savings.
Other approaches have been tried in an attempt to shorten the discovery cycle. Integration of robotics with HTS has played a key role in achieving higher screening rates and avoiding expensive manual interventions.
Dhiman commented: "Insights from information-rich assays are likely to assist in the discovery of effective drugs and could also reduce the need for secondary screens in the future."
Indeed, over the past 10 years, it has been the development of additional technologies that has complemented HTS and heightened its success.
Major advances in combinatorial chemistry, molecular and cellular biology, genetics, genomics and proteomics has resulted in new classes of therapeutic molecules to be developed due to the success of genomics and proteomics in providing an expanding list of cellular targets.
The report concludes the need to develop data handling techniques in which the diversity of information gathered needs to be interpreted. In addition, data interpretation and analysis also remain crucial for evaluating future drug candidates.
Dhiman explained that the lack of validated statistical methods to ensure the validity of the data obtained during the screening becomes challenging for most companies involved in drug discovery.
"In this regard, it is absolutely critical to improve statistical procedures for efficiently analysing the data generated during the HTS process."
