Single pass tangential flow filtration to debottleneck downstream processing for therapeutic antibody production

• Published in: Biotechnology and bioengineering Vol. 109; no. 4; pp. 962 - 970
• Main Authors: Dizon-Maspat, Jemelle, Bourret, Justin, D'Agostini, Anna, Li, Feng
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01.04.2012; Wiley Subscription Services, Inc
• Subjects: Animals; Antibodies, Monoclonal - biosynthesis; Antibodies, Monoclonal - genetics; Antibodies, Monoclonal - isolation & purification; antibody purification; Batch Cell Culture Techniques - instrumentation; Batch Cell Culture Techniques - methods; Bioreactors; Biotechnology; Bottlenecks; Cell culture; CHO Cells; Chromatography, High Pressure Liquid; concentration factor; Cricetinae; Cricetulus; Equipment Design; Filtration - methods; Monoclonal antibodies; Nephelometry and Turbidimetry; Osmolar Concentration; Pressure; process debottleneck; Proteins; Recombinant Fusion Proteins - biosynthesis; Recombinant Fusion Proteins - isolation & purification; Rheology; Single Pass TFF (SPTFF); Spectrophotometry, Ultraviolet; Tangential Flow Filtration (TFF); ultrafiltration
• ISSN: 0006-3592; 1097-0290
• DOI: 10.1002/bit.24377

As the therapeutic monoclonal antibody (mAb) market continues to grow, optimizing production processes is becoming more critical in improving efficiencies and reducing cost‐of‐goods in large‐scale production. With the recent trends of increasing cell culture titers from upstream process improvements, downstream capacity has become the bottleneck in many existing manufacturing facilities. Single Pass Tangential Flow Filtration (SPTFF) is an emerging technology, which is potentially useful in debottlenecking downstream capacity, especially when the pool tank size is a limiting factor. It can be integrated as part of an existing purification process, after a column chromatography step or a filtration step, without introducing a new unit operation. In this study, SPTFF technology was systematically evaluated for reducing process intermediate volumes from 2× to 10× with multiple mAbs and the impact of SPTFF on product quality, and process yield was analyzed. Finally, the potential fit into the typical 3‐column industry platform antibody purification process and its implementation in a commercial scale manufacturing facility were also evaluated. Our data indicate that using SPTFF to concentrate protein pools is a simple, flexible, and robust operation, which can be implemented at various scales to improve antibody purification process capacity. Biotechnol. Bioeng. 2012; 109:962–970. © 2011 Wiley Periodicals, Inc. Single Pass Tangential Flow Filtration (SPTFF) is an emerging technology, which is potentially useful in debottlenecking downstream capacity, especially when the pool tank size is a limiting factor. In this study, SPTFF technology was systematically evaluated for reducing process intermediate volumes from 2× to 10× with multiple mAbs and the impact of SPTFF on product quality, and process yield was analyzed.