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The drug discovery process has changed dramatically over the past decade and continues to evolve in response to new discoveries and technologies. There is also increasing demand to produce more drug candidates and decrease attrition during drug development.

Recent advances in cell culture robotic technology have grown out of the need to maximise efficiency and minimise the possibility of errors, contamination and failure associated with high-throughput cell culture.

In addition, the trends towards assay miniaturisation and multiplexing for high-throughput and ultrahigh-throughput have been triggered by the necessity to reduce development and operational costs. Despite advances in cell based assay technology, numerous bottlenecks still need to be addressed in drug discovery for the identification of novel drug candidates.

New analysis from global growth consulting company Frost & Sullivan finds that the market for cell based assay kits earned revenues of US$66.2 million in 2007 and estimates this to reach US$220.1 in 2014.

According to 'European cell based assays markets', as pharmaceutical companies strive to improve the cost effectiveness of their drug discovery programmes, it is becoming apparent that considerable amounts of money are lost on com pounds that fail late in the drug discovery process because of their toxicity.

"Over the past decade, various initiatives have been taken to improve the science of predicting toxicity and improving extrapolation to humans, including the use of cell based assays to enhance predictions," noted Frost & Sullivan research analyst Laleh Safinia. "The revolution in the drug discovery process has recently demonstrated emerging lab disciplines and technology platforms in the area of cell based assay screening, holding great promise for the discovery of new drug targets.

Sparking biotech interest

Drug targets derived from genomics and proteomics projects have sparked the interest of biotechnology, pharmaceutical and drug discovery companies in screening large numbers of com pounds using cell based assays in an ultrahigh-throughput format.

Progress and advances in a number of technologies have made the utilisation of live cells in high-throughput screening and high-content screening assays an attractive option in the drug discovery process.

Partnerships and alliances between active participants within this industry will allow the acquisition of new molecules, increase profitability and offer a pipeline of other drugs in development as well as remove some of the bottlenecks within drug discovery.

Cell based assays are an important aspect of the drug discovery process. However, there is a growing need for reliable and robust assay kits to enable the effective standardisation of assays and a reduction in variability. For researchers using automated screening systems, the stability and compatibility of reagents with robotic components is often a concern, resulting in high cost of operation.

"The assay reagent must be stable at ambient temperature; signal generated by the assay should be stable for an adequate period of time to be able to monitor cells over a period of time," said Safinia. "Thus, HTS requires the optimisation of HTS assays and protocols. Approximately US$200 million could be saved through more productive discovery programs or cell based assay screens that boost clinical success rates."

With the increase in demand for new drugs, the degree of competition among the drug discovery companies is also intensifying. The initial investment is considerable; however, the scope for new drug target and profit margins is also high.

"There is, therefore, a heightened need for target validation technology to verify the correct target through advances in assay protocols, novel technologies and reliable data analyses," commented. Safinia. "Identifying the correct drug target through the use of genomics, proteomics and chemical libraries for drug discovery is a critical bottleneck in the pharmaceutical and biotechnology industries."

There have been tremendous efforts by the pharmaceutical industry to improve cell based screening platforms to expedite target validation as well as for use in preclinical trials. In order to understand the complexity of biological systems and accelerate the hit-to-lead process, recent advances in microfluidic technologies and automation have attracted a lot of attention with promising applications in cell based biosensors and drug screening.

In addition, said the report, considerable efforts are being made to improve the science of predicting the toxicology of emerging clinical candidates to reduce the ADME/Tox failure of drug candidates.

Functional proteomics, speedier discovery

This latest report builds on another Frost & Sullivan carried out recently. In Functional proteomics, the company points out that nearly every major biotech and pharmaceuticals firm has implemented a proteomics programme.

Functional proteomics, the study of protein function and identification of protein interactions, is playing a major role in drug discovery, biomarkers, molecular diagnostics, and antibody therapies. A primary goal of biomedical research is discovering how cells respond to genetic instructions by creating thousands of protein variations and observing their reactions.

"Functional proteomics is developing at a rapid pace to address a critical need in the discovery of drug targets, with the development of a single drug costing an average of US$500 million , and only 30 per cent of approved drugs recovering these costs," said research analyst Katherine Austin. "To address this need, pharmaceuticals companies need to find out methods to collect large amounts of data to dissect the complex, disease-causing interactions between proteins within the cell, and between proteins in the extra-cellular environment."

Functional proteomic technologies enable identification of functions for uncharacterised human proteins, the discovery of other proteins with which they interact, and an understanding of their involvement in important disease pathways. Understanding cell-signaling pathways and the manner in which cells communicate will provide greater understanding of disease mechanisms, revealing potential drug targets that are more likely to succeed. After the development of drugs, pathway knowledge is critical in understanding the downstream effects of drug treatment. Enhanced knowledge of pathways will reduce side affects.

Unfortunately, proteins are far more complicated than DNA. Technical problems have plagued functional proteomic R&D on every front. Problems associated with functional proteomic technologies, such as protein arrays are also numerous.

"The development of various proteomic kits and targeted solutions is fraught with pitfalls, many of which deal with the vast range of chemical and physical properties of different proteins," explained Austin. "Some of these include the complexity of the protein-interaction map, a lack of standardisation, which makes it difficult to compare or validate results from different laboratories, and a lack of protein-specific capture agents such as antibodies."

The report concluded that before accepting functional proteomics as a standard, high throughput approach, technology developers need to address a number of challenges.

There is a need for new tools and research strategies on all fronts, for protein expression, purification, screening, and measuring protein interactions. In addition, assay sensitivity- the ability to detect low-abundance proteins-need to be more, by following standard techniques that provide reliable and acceptable results for pharmaceuticals applications