Continuous counter‐current chromatography for capture and polishing steps in biopharmaceutical production

Abstract

The economic advantages of continuous processing of biopharmaceuticals, which include smaller equipment and faster, efficient processes, have increased interest in this technology over the past decade. Continuous processes can also improve quality assurance and enable greater controllability, consistent with the quality initiatives of the FDA. Here, we discuss different continuous multi-column chromatography processes. Differences in the capture and polishing steps result in two different types of continuous processes that employ counter-current column movement. Continuous-capture processes are associated with increased productivity per cycle and decreased buffer consumption, whereas the typical purity-yield trade-off of classical batch chromatography can be surmounted by continuous processes for polishing applications. In the context of continuous manufacturing, different but complementary chromatographic columns or devices are typically combined to improve overall process performance and avoid unnecessary product storage. In the following, these various processes, their performances compared with batch processing and resulting product quality are discussed based on a review of the literature. Based on various examples of applications, primarily monoclonal antibody production processes, conclusions are drawn about the future of these continuous-manufacturing technologies.

Microheterogeneity of therapeutic monoclonal antibodies is governed by changes in the surface charge of the protein

“…Correspondence: Prof. Alois Jungbauer, Department of Biotechnology, University of Natural Resources and Life Sciences, Vienna, Muthgasse 18, 1190 Vienna, Austria E-mail: alois.jungbauer@boku.ac.at Abbreviations: ADCC, antibody dependent cellular cytotoxicity; ApHGE, analytical ionexchange chromatography with pH gradient elution; CEX, Cation exchange chromatography; EGFR, epidermal growth factor receptor; mAb, monoclonal antibody; DSC, differential scanning calorimetry; SPR, surface plasmon resonance ants it is still difficult to decide, how precisely a product produced by different methods must match [14][15][16][17][18]. Cation exchange chromatography (CEX) with pH gradient elution has repeatedly been reported as a suitable method for high-resolution separation of antibody variants exhibiting different surface charge characteristics [19][20][21][22].…”

“…Either a batch process is directly converted into a continuous process or new unit operations are used in continuous manufacturing. Without knowing the biological significance of the different vari-ants it is still difficult to decide, how precisely a product produced by different methods must match [14][15][16][17][18].…”

Continuous Solvent/Detergent Virus Inactivation Using a Packed‐Bed Reactor

“…Continuous virus inactivation (VI) remains a major challenge while the biopharma industry is moving toward continuous processing due to economic benefits, the ability to control the quality of the product, and to automate processes. A compromise must be found between sufficient time for VI and product loss; therefore, reactors with narrow residence time distribution (RTD) must be used to avoid unnecessary long incubations during continuous operations.…”

Purification of common light chain IgG-like bispecific antibodies using highly linear pH gradients

“…25 Furthermore, the technique can also be combined with continuous purification procedures, 41 as well as purification schemes specifically designed for common LC BsAbs. 34 As such, the combination of IEX and linear pH gradient elution has the potential to become a state-of-the-art method for the purification and polishing of BsAbs in general.…”