While truly groundbreaking innovations in chromatography equipment happen every blue moon, there have been noteworthy gradual improvements in the areas of chromatography media, column packing and on-line buffer blending, say Howard Levine (president) and Tom Ransohoff (consultant) of BioProcess Technology Consultants (Acton, Mass.).
The need to process large quantities of protein more efficiently, due to larger upstream cell culture titers, has strained downstream processing, and particularly chromatography, Levine and Ransohoff say. The trend has given rise to the need for better flow volumes, binding capacities and control of processes.
While process analytical technologies (PAT) are already being applied to monitor pH, UV and conductivity, the PAT initiative is causing manufacturers to question what more can be done. Can peak-shape analysis be used for batch acceptance or rejection? Can on-line monitoring inform operators about column separation performance? Yes, say Levine and Ransahoff, and in the future more manufacturers will look to PAT for decision-making as well as monitoring assistance. Installed equipment is easily retrofitted to incorporate some of the new elements of PAT, they say.
Membrane adsorbers are gaining traction as well, Levine and Ransahoff note. While they can’t match chromatography media on a cost-per-capacity basis, they have gained acceptance for the removal of contaminants such as nucleic acids, host-cell proteins and product-related impurities. It will take increased capacities before adsorbers make inroads into the capture chromatography market, the two say.
Finally, advances in simulated moving bed (SMB) have spurred interest in small-molecule chromatography, particularly for chiral separations. Chromatography will increasingly be seen as an alternative to crystallization as small molecules become more complex, say Levine and Ransahoff.
All of these trends are reflected in the latest developments among the leading manufacturers of process-scale chromatography systems:
|GE's ÄKTAprocess system.
GE Healthcare (Piscataway, N.J.) is continuously developing and expanding its media offerings. MabSelect SuRe, a genetically engineered protein A resin, was introduced late last year as a more durable alternative to protein A that can last 200 to 300 run cycles and cleanings, says Eric Grund, director of Fast Trak Services at GE. A platform process based on MabSelect can be validated and characterized for a range of monoclonal antibody products, says Grund.
The company has also just released Capto S, a cation exchange resin and the third in the high-productivity Capto platform, as well as MacroCap SP, a cation exchanger for handling PEGylated and other very large recombinant proteins.
On the hardware side, GE has just released ÄKTAprocess, a flexible, large-scale chromatography system running GE’s Unicorn software. ÄKTAprocess comes with full regulatory support and wetted parts that are USP class VI, Grund says.
Millipore (Billerica, Mass.) has just introduced a 630-mm version of its QuikScale high-throughput column — the line now runs from 70 to 630 mm in glass, acrylic and stainless steel.
The new, largest QuikScale operates up to 3 bar of pressure, allows the use of all media types, and accommodates a range of linear velocities with minimal pressure differential. Its swing-arm design pivots on a vertical axis for ease of maintenance and operation.
Millipore is now using hydraulics in process-scale columns as a standard to maintain movement and enhance cleanability. The use of hydraulics meets customer demands for more ergonomically friendly production-scale columns, says Stephanie Wilson, global group product manager. To move columns between packing and processing stations, Millipore offers a modified tow truck option.
|Novasep's Supersep 50, a smaller SFC system.
Novasep, Inc. (Boothwyn, Pa.) is near completion of an advanced control system designed to simplify and shorten development time, particularly for continuous chromatography processes such as simulated moving bed (SMB), which Novasep Process has pioneered for pharma, and Varicol, Novasep's own binary separator that combines cocurrent and countercurrent motion.
The company is also constructing its largest HPLC column to date, says Dan Paradis, sales and marketing manager. The column, expected to be in operation by the end of the year, has an internal diameter of 1600 mm and height of 1200 mm, with an operating pressure up to 70 bar (1015 psi). It has been designed for the purification of recombinant insulin.
Also to be introduced this year, Paradis notes, are production-scale (up to 200-mm-diameter) supercritical fluid chromatography (SFC) systems.
|Pall's Mustang adsorber.|