Increasing Throughput in the Drug Discovery Process

Like many companies in today’s environment, pharmaceutical companies must improve their bottom line results in increasingly difficult circumstances. Among the challenges faced uniquely in the pharmaceuticals industry:

• Firms continue to increase investment in research and development, although the returns are lower as the number of new approvals is declining
• Pipelines for promising new therapies are in decline, with many companies seeing a larger portion of revenues coming from older products that will soon lose patent protection
• Cost to develop new drugs continues to increase, with some estimates placing the total cost of bringing a new therapy to market at USD 1.6 billion

Fortunately, recent advances in technology in flash and liquid chromatography, used in the synthesis and high-throughput screening (HTS) stages of drug discovery, are providing researchers with the means to increase their productivity and improve the likelihood of identifying breakthrough therapies.

Flash chromatography: advantages in drug discovery
Medicinal chemists synthesize thousands of compounds each day, but have to provide pure compounds to the HTS labs, where compounds are tested in search of a positive effect or ‘hit’. At this stage, it is important to:

• Pass along as many samples as possible in the course of a day to the HTS labs
• Ensure that the samples passed along will be pure enough that the scientists in the HTS labs can be confident of the results they are (or are not) getting

Flash chromatography involves loading a sample into a cartridge containing a silica adsorbent, using pressure to push the sample through the cartridge, and collecting the purified fractions.

While flash chromatography was introduced in 1978, its adoption continues to increase in drug discovery labs. Flash is an alternative to preparative liquid chromatography (prep LC), which is a more complicated and time-consuming process. A flash system is easy to operate, inexpensive, and fast compared to prep LC.

Recent improvements in flash technology are driving the increase in adoption. Past generations of flash products required scientists to pack their own columns; newer products are pre-packed cartridges that can be disposed after one use. New silica adsorbents are providing increased capability to deliver pure compounds, and also effectively separate even complicated samples, reducing the need for prep LC. Newer cartridges, which provide better purity than previous generations of flash cartridges, also help the medicinal chemistry labs to reduce consumption, and subsequently to lower costs and improve productivity.

Advances in liquid chromatography improve speed and quality
High-performance liquid chromatography (HPLC) is a technique used throughout the drug discovery process. This technique involves the use of a column packed with silica or another adsorbent (the stationary phase), operated under high pressures sometimes exceeding 1000 bar, with a system that detects compounds as they migrate through the column.

Recently, new HPLC systems have the ability to operate at ‘ultra-high’ pressures (UHPLC), sometimes at the 1000 bar level, versus conventional HPLC, which used pressures closer to 300 bar. The impact of higher pressure along with lower system volume and improved silica particle technology allows for drastically reduced run times, in some cases from 30 minutes to 2 minutes, without sacrificing resolution and purity.

A relatively recent development in HPLC involves the use of smaller silica particle, in many cases as small as 1.5 μm in diameter, to improve the efficiency of the column. This improvement enabled the use of higher pressures to provide better resolution and shorter run times, but it can also be used with conventional pressure HPLC systems to achieve run times that are close to UHPLC.

Each of these advances in chromatography technology enables the scientist to process more samples on a daily basis, and to be confident in the purity of their material along with its potential impact in treating a disease target. These benefits will ultimately improve the pharmaceutical industry’s ability to replenish its pipelines in a cost-effective manner.

About Russ Lorber
Russ Lorber is a Marketing Manager with Grace Davison Discovery Sciences, a business unit of W.R. Grace and Company. He has 12 years of experience across operations, finance, and marketing in the chemicals and life sciences industries.