Design and Operation of Continuous Countercurrent Chromatography in Biotechnological Production

Abstract

Continuous countercurrent chromatography has been established in industrial operations for over six decades and in fine chemical and pharmaceutical industry since the 1990s. In biotechnological processing, the area where chromatography plays a criticaland often multipleroles, implementation is lacking for various reasons. Options are shown to correct this and make continuous countercurrent chromatography a technologically and economically viable option in GMP-regulated processing. Current approaches, with the exception of MCSGP (multicolumn countercurrent solvent gradient purification), just operate a manifold of 2–6 columns in a sequential but batchwise scheduling. Modifications were made to reduce equipment complexity in GMP-regulated manufacturing and to exploit benefits of countercurrent operation for adsorbent and buffer reduction. A solution with only one column and a minimum of valves, pumps, and buffer vessels was developed. The approach also describes integration of two or more chromatography steps in continuous production, both GMP- and biocompatible.

Alternatives to Cryogenic Distillation: Advanced Porous Materials in Adsorptive Light Olefin/Paraffin Separations

“…c) Schematic representation of the SMB process. Modified and reproduced with permission 56a. Copyright 2014, American Chemical Society.…”

“…Apart from PSA, VSA, TSA, and their combinatorial processes, simulated moving bed (SMB) technology is another adsorptive separation approach that can produce polymer‐grade olefins in a continuous manner. Different from conventional discontinuous batch chromatography and continuous true moving bed (TMB) technologies which are realized by the transportation of adsorbents in a direction opposite to the flow of eluent fluid, SMB simulates the bed movement by shifting the positions of the eluent inlet, feed inlet, extract outlet, and raffinate outlet in the same direction of eluent fluid (Figure b,c) . In this way, SMB inherits the merits of TMB, namely high utilization of adsorbent capacity, high productivity of high‐purity products, and reduced solvent consumption, while avoiding mechanical erosion of adsorbents, abrasion of the equipment, and realizing plug flow of gas in the solid phase 56b.…”

Buffer recycling in downstream processing of biologics

“…These techniques have not yet entered the field of bioseparations. Additional information can be found in various reviews [31].…”

“…Integrated continuous counter current chromatography (iCCC) [31] is a technique that combines peak shaving, recycling, and seamless loading. An ion-exchange column is loaded, washed, and then a gradient is applied for the elution.…”

Multicomponent Separations by Simulated Moving Bed (SMB)-Based Processes

“…Another alternative for ternary separations is the pseudo-SMB Japan Organo (JO) process, which is a two-step process used to separate a multicomponent mixture in three fractions . Besides the SMB-based processes, other multicolumn processes such as sequential multicolumn chromatography (SMCC) have shown good results in dealing with multicomponent complex mixtures (Zobel et al, 2014). Besides the SMB-based processes, other multicolumn processes such as sequential multicolumn chromatography (SMCC) have shown good results in dealing with multicomponent complex mixtures (Zobel et al, 2014).…”