Drug discovery techniques focus on speed and cost reduction

Drug discovery relies on a huge range of techniques, from polymerase chain reaction analysis to clinical trial design. Here we highlight the latest innovations designed to cut costs and increase the speed of new drug discovery.

Increasing the speed of bringing important medicines from the research phase to patients who need them is a driving objective for today's global biopharmaceutical companies.

Covance, one of the world's largest and most comprehensive drug development companies, has launched Xcellerate, a novel, proprietary methodology designed to help optimise clinical trial performance in order to assist biopharmaceutical companies in improving quality, reducing waste, and decreasing trial timelines - ultimately increasing their return on clinical trial investment.[Page Break]

Clinical trial design

Specifically, the Xcellerate methodology enables Covance to make custom recommendations on site, investigator and geographic selections for every programme it manages, and to help enhance clinical trial design and execution. Xcellerate is not a stand-alone service offering, but is embedded in Covance's approach to clinical trial management.

"Biopharmaceutical companies have come under increasing pressure in recent years to reduce their R&D spending and re-invigorate their drug development pipelines," said Rick Cimino, group president, clinical development services, Covance. "We believe that Covance, through Xcellerate, can deliver high value to our clients by improving time-to-market speeds that ultimately should help them bring new medicines to patients faster."

Cancer studies

Typically in cancer clinical studies across the industry, the number of low and non-enrolling sites (defined as the enrolment of 0 or 1 patient per site) averages approximately 54 per cent, which can cost a biopharmaceutical company US$50000 per site.

In a cancer study using Xcellerate methodology and a robust dataset, Covance reduced the low and non-performing sites to under 14 per cent for this single portfolio, resulting in significant time and cost savings for the client.

Xcellerate also significantly contributed to the recent completion of a portfolio study seven months ahead of its recruitment target date.

Additionally, a long Phase III respiratory clinical study with a number of pharmaceutical companies vying for the same patients presented a unique set of challenges to Covance's client: recruiting patients and retaining investigator and patient interest in the study.

Through Xcellerate, Covance was able to help the client finish patient enrolment ahead of target and minimise disruption to investigator sites and their regular activities. This gave the trial a competitive edge in investigator uptake and site enrolment. As a single provider, Covance created synergy across multiple data streams from multiple vendors, helping keep this complex trial on track.[Page Break]

Fast reaction times

The latest offering from QIAGEN is the Multiplex PCR Plus Kit, designed for rapid and sensitive multiplex polymerase chain reaction (PCR) that allows researchers to amplify several targets in one PCR run. The kit provides fast reaction times and comes with a pre-optimised protocol, eliminating the need for optimisation and delivering reliable results on the first attempt (Fig.1).

The master mix included with the new kit contains the enzyme HotStarTaq Plus DNA Polymerase, as well as a balanced combination of salts and additives, which increases multiplex reaction specificity and ensures comparable efficiencies for all primers in the PCR reaction.

This proprietary technology allows straightforward assay development for many challenging applications, such as detection of mutations or microsatellites and microbial genotyping.

The kit also includes CoralLoad, a buffer that contains two dyes that improve pipetting visibility during reaction setup, gel loading, and visualisation of DNA migration. Therefore, it is no longer necessary to use other dyes for gel electrophoresis.

Downstream analysis of the multiplex PCR products can be performed with a variety of methods such as agarose gels, capillary sequencers, as well as multicapillary electrophoresis with the QIAxcel Advanced System.

Sub three-minute PCR?

The standard approach to PCR typically takes about an hour, which is a vast improvement over pre-PCR techniques that required days.

However, PCR for point-of-care, emergency-response or widespread monitoring applications needs to be faster still - of the order of a few minutes.

Now, thanks to work by Reginald Beer and his team of scientists and engineers at Lawrence Livermore National Laboratory (LLNL), sub-three-minute amplification of nucleic acids (DNA and RNA) via PCR is possible.

Beer set out to find out just how fast PCR could go. His goal was to develop a device where the limiting factor would be enzyme kinetics or thermodynamics, not mechanical considerations.

He also wanted to use "volumes that are easy to interact with", not microfluidic-scale, knowing that in a diagnostic setting multiple analyses are often needed and the ability to load samples by hand is vital (Fig.2).

As described in a recently published paper in the journal Analyst, Beer and his colleagues created such a device and demonstrated PCR times of less than three minutes. Their work was funded by the US Defense Advanced Research Projects Agency and internal LLNL money.

The researchers demonstrated their PCR device by amplifying genomic DNA from an Enterobacter bacterium and a portion of SARS DNA.

The first tested the device's ability to rapidly amplify a large DNA segment, and the second showed the device's utility in handling a public health threat virus. The device achieved 30-cycle (billion-fold) PCR amplification of the target DNA in as little as two minutes and 18 seconds.

Now that Beer and his team have demonstrated sub-three-minute PCR, they are working to develop a real-time-detection device. They envision a PCR instrument that can complete a test, from sample to results, in five to 10 minutes.[Page Break]


Sistemic, a global company with expertise in microRNA, has announced the release of its new Companion Biomarker programme. Extending the company's existing SistemRNA suite of drug discovery and development tools, the Companion Biomarker programme simplifies the benefits of miRNA analysis and profiling to support timely decision making within clinical research.

Drug discovery companies will be able to utilise new multiple miRNA biomarkers to determine the efficacy of targeted drugs, in major therapeutic areas and when developing companion biomarker strategies for future clinical development.

MicroRNA profiling has rapidly become an indispensable technology with a whole catalogue of applications and new opportunities. Companion biomarkers are the most recent extension of the technology and are set to provide valuable clinical data to guide both pre-clinical and clinical studies.

The system will use the robustness and specificity of miRNA to identify highly discriminatory biomarkers which, in turn, will guide patient prognosis, the selection of appropriate drug treatment, and monitoring of drug response.


For its part, AMSBIO has announced a suite of new products for investigating the protein-binding properties of Heparin, Heparan Sulphate (HS) and other glycosaminoglycans (GAGS).

Such investigations have traditionally been constrained by the need for chemical modification prior to attachment to inert or derivatised surfaces.

The AMSBIO Heparin/GAG Binding Plate offers a simple solution to this problem - the specially-prepared plate surface adsorbs GAGS without modification whilst maintaining their protein-binding characteristics.

The versatility of the Heparin/GAG Binding Plate will find many applications including elucidation of optimum GAG sequences and sulphation patterns for binding to proteins of interest, analyses of sulphotransferases and endosulphatases and detection of inhibitors or enhancers of protein-GAG recognition.

The new plate can also be used for studying receptor binding to growth factors or chemokines bound to surface-immobilised GAGS.

The ELISA-type format of the Heparin/GAG Binding Plate is economical on the use of valuable protein reagents and is compatible with automated laboratory systems. AMSBIO has also introduced new high performance arrays designed for use with the plate

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