Improving Productivity in Today’s Drug Discovery Labs

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 are seeing a larger portion of revenues coming from older products that will soon lose patent protection
• The 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

New advances in separations science help pharmaceutical companies respond to these challenges. This article explores improving productivity and quality of results in two ways – high purity flash chromatography and ultra high-pressure liquid chromatography (UHPLC). These techniques can help lab managers improve productivity without sacrificing quality.

Flash chromatography: accelerating the drug discovery pipeline

Medicinal chemists synthesize thousands of compounds each day and provide pure compounds to High Throughput Screening (HTS) labs, where they are tested in search of a positive effect or “hit”. Because it takes such a large number of candidates to generate a few hits, the medicinal chemist has two primary goals:

• Quantity: pass along as many samples as possible in the course of a day
• Quality: ensure that the samples passed along will be pure enough to generate meaningful results in the HTS lab

While flash chromatography has been available for some time, its adoption continues to increase in drug discovery labs. As flash technologies continue to improve, the medicinal chemist can purify increasingly complex mixtures themselves without having to pass samples along to a preparative HPLC lab, helping reduce the time and expense of screening libraries.

The productivity advantages in using new high resolution flash chromatography cartridges are:

• Higher purity samples submitted to HTS minimizes the chance for false negatives/positives from contaminants
• Allows medicinal chemists to quickly and easily purify complex mixtures rather than waiting for them to be purified by a preparative LC group
• Less expensive than preparative chromatography
• Faster technique compared to alternatives of preparative LC and crystallization.

Previous 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 deliver highly pure compounds, and also effectively separate even the most complicated samples. Newer cartridge technologies not only provide better purity, they also help medicinal chemistry labs reduce consumption of cartridges and solvents, lowering costs and improving productivity.

Grace Davison Discovery Sciences, a company that provides a full range of chromatography and separations tools to pharmaceutical and life sciences companies, has been a key player in developing improved flash technology. A division of W.R. Grace and Company, Grace Davison was the first company to sell silica gel commercially in 1921. Grace also launched its industry-leading Davisil® Chromatographic Silica Gel, which has been used extensively in flash chromatography, in 1981.

Combining its silica expertise with other chromatography capabilities, Grace recently launched a new line of flash products. GraceResolv™ High Resolution Flash Cartridges have up to twice the loading capacity of conventional cartridges, so you can process more samples on a single cartridge or downgrade your cartridge size to save time and solvents. These cartridges, using proprietary Grace silica and bonding chemistries, also show improved resolution relative to competitive products, so you can collect higher quantities of higher purity compounds.

For scientists who need to get more done, be more confident in their results, and have cost and time constraints, GraceResolv™ Flash Cartridges are another step in the evolution of flash chromatography.

Small particles and high pressures are the key to speed

High-performance liquid chromatography (HPLC) is a technique used throughout the drug discovery process. This technique uses a column packed with silica or another adsorbent operated under high pressures with a system that detects compounds as they migrate through the column.

Silica with an average particle size of less than 2 μ m has been around for a decade, but recent advances in instrumentation have combined small particles with high pressures for unprecedented speed and resolution.

The Pressure Effect . Typically, conventional HPLC systems cannot exceed 5000psi. At these pressures you can use sub-2 μ m particles in short, large diameter columns to shorten analysis times.

If even greater speed is desired, or if these large ID columns are not suitable for your MS system, then you need to make the jump to the new ultra-high pressure technologies (12,000psi or higher). These new high performance columns and systems offer higher pressure limitations (to overcome backpressure) with reduced system volumes so smaller bore columns can be used effectively.

With an ultra-high pressure system, use sub-2 μ m particles in long, narrow diameter columns specifically designed to withstand high pressures.

Growth of Sub-2 μ m Applications . The installed base of ultra-high pressure instrument systems is increasing rapidly, but many researchers are waiting for a larger selection of ultra-high pressure columns before they convert critical methods, since security of supply of columns for this new technology is critical.

There are now several sources of HPLC columns with sub-2 μ m silica particles, both for conventional pressures and ultra-high pressures. Along with sub-2 μ m columns for conventional HPLC systems, Grace Davison Discovery Sciences also offers VisionHT™ Columns for ultra-high pressure systems. These columns use 1.5 μ m particles in new high-pressure column hardware that withstands up to 12,000psi with constant efficiencies and retention times for more than 17,000 column volumes.

Through our expertise in silica chemistry combined with specialized column hardware technologies, Grace Davison Discovery Sciences is an industry expert in HPLC column manufacturing. Grace is one of the few HPLC column suppliers with primary manufacturing capabilities for the raw 1.5 μ m silica, a variety of bonded phases, and column hardware design and packing methods that meet the stringent requirements of traditional as well as new instrument technologies.

Small Particles are the Key To Speed . Although the new ultra-high pressure columns and systems have significant speed and resolution advantages over conventional columns and systems, the key is the sub-2μm particle size silica. Using small particle sizes even at conventional pressures demonstrates significant speed and resolution benefits. So whether or not you decide to invest in new ultra-high pressure technologies, you can immediately improve productivity by switching to HPLC columns with sub-2μm particle size silica.