Continuous chromatography, also referred to as Simulated Moving Bed (SMB), Multi-column Continuous Chromatography (MCC) and Periodic Counter Current (PCC) chromatography, is an automated or semi-automated process chromatography technique that involves using multiple (two or more) columns for implementing chromatographic separation and purification in a continuous manner. In contrast to conventional batch chromatography methods, a continuous chromatography approach provides increased productivity in terms of quantity of product purified as well as media requirements, and a higher yield of recovery and purity of the product.

Continuous chromatography systems function on the same fundamental principles of conventional batch chromatography, but differ in terms of design, operation and applications. Hence, SMB instruments are unable implement a separation or purification cycle that cannot be performed using simple column purification, but they can implement it with a higher degree of performance and cost effectiveness. Such systems generally operate at a higher flow rate (100–300 mL/min) and pressure (50–300 bar), and employ large column ID’s (Internal Diameter) (20–50 mm).

A typical continuous chromatography system is designed using multiple columns and operated similar to a “carousel” manner, where the columns move against the direction of feed flow, thereby lengthening the stationary phase. Due to the periodic nature of this column movement, it is also dubbed PCC.

The configuration of a system can vary based on the separation requirements and design, and primarily differs in terms of the number of columns utilized. Currently available multi-column chromatography systems employ anywhere between 2 to 16 columns. Generally, 2 loading columns are considered sufficient to achieve an effective continuous chromatography cycle. However, the addition of extra columns marginally improves the chromatography media–capacity utilization, while increasing the complexity of the system configuration in terms of pump requirements, valve arrangements and maintenance.

The unique design of a moving bed usually implemented in such systems provides several advantages, such as reducing the requirements of the amount of separation media, solvent and energy utilized. Consequently, such configurations increase the productivity (grams of product purified per liter of resin per hour) by several fold, reduce operating cost by about 40%–60%, enhance flexibility and standardization for production, allow easy scalability, and lower the equipment footprint. However, it also makes the design more complex and expensive, along with adding higher maintenance requirements.

Due to its productivity attributes, continuous chromatography is popular in the pharmaceutical and biotechnology industries for a wide range of applications. It is most prominently used for the purification and production of recombinant protein products, biologics and mAbs.

The market deman for laboratory-scale continuous chromatography is estimated to grow at a rate of 6.5% over the next five years. This market growth is mainly driven by the increasing popularity of single-use, multi-column purification systems in process development laboratories and high-throughput downstream processing applications in the biotech and pharmaceutical industries. The food and agricultural biotech industries have also been recently adopting continuous chromatography techniques for their separation and purification needs.

GE Healthcare leads the market with its ÄKTA pcc 75 chromatography system, which offers a three column configuration. Pall is another large manufacturer in the continuous processing market thanks to its Cadence series of BioSMB multi-column, benchtop chromatography systems. Among its several system and configuration offerings, the Cadence Acoustic Separator and the Cadence BioSMB PD systems are the most popular. Knauer, LEWA, Novasep and Semba Biosciences are some other significant manufacturers in this market.

Continuous Chromatography at a Glance

Leading Vendors:

• GE Healthcare
• Pall (Danaher)
• Novasep

Largest Markets:

• Pharmaceutical
• Biotech
• Clinical

Instrument Cost:

• $25,000–$65,000