Integrated continuous biomanufacturing platform with ATF perfusion and one column chromatography operation for optimum resin utilization and productivity

• Published in: Preparative biochemistry & biotechnology Vol. 48; no. 5; pp. 383 - 390
• Main Authors: Kamga, Mark-Henry, Cattaneo, Maurizio, Yoon, Seongkyu
• Format: Journal Article
• Language: English
• Published: England Taylor & Francis Ltd 28-05-2018
• Subjects: Antibodies; Biotechnology; Chromatography; Column chromatography; Continuous production; Immunoglobulins; Perfusion; Productivity; Proteins; Upstream; antibody production; protein A; integrated continuous biomanufacturing; dynamic binding capacity; continuous chromatography
• ISSN: 1082-6068; 1532-2297
• DOI: 10.1080/10826068.2018.1446151

A new integrated continuous biomanufacturing platform for continuous production of antibodies at fixed cell volumes and cell concentrations for extended periods with immediate capture is presented. Upstream antibody production has reached technological maturity, however, the bottleneck for continuous biomanufacturing remains the efficient and cost effective capture of therapeutic antibodies in an initial chromatography step. In this study, the first successful attempt at using one-column continuous chromatography (OCC) for the continuous capture of therapeutic antibodies produced through alternating tangential flow (ATF) perfusion is presented. By performing upstream media optimizations, the upstream perfusion rate was reduced to one vessel volume per day (vv/d), increasing antibody titer and reducing the volume of perfusate. In addition, process improvements were performed to increase productivity by 80% over previously reported values. In addition, a real-time method for evaluating column performance in order to make column switching decisions was developed. This improved productivity coupled with the use of a single column improved process monitoring and control in OCC compared to multi-column systems. This approach is the first report on using a single column for the implementation of an integrated continuous biomanufacturing platform and offers a cost effective and flexible platform process for the manufacture of therapeutic proteins.