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

Abstract

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.

Investigating the combination of single‐pass tangential flow filtration and anion exchange chromatography for intensified mAb polishing

“…Recent advances in single‐pass tangential flow filtration (SPTFF) technology enable flow through product concentration without sacrificing the concentration benefits of traditional recirculated batch TFF . The absence of recirculation tanks in an SPTFF process simplifies implementation and reduces footprint, making it an attractive option for connected processing, intensified processing, and debottlenecking applications . In this work, SPTFF was investigated for inline concentration of mAb feed prior to an AEX polishing step.…”

End-to-end integrated fully continuous production of recombinant monoclonal antibodies

“…The technologies amenable to continuous processing include continuous centrifugation, precipitation, crystallization, Aqueous Two Phase Separation (ATPS), multi-zone SMB systems, single pass tangential flow filtration, UVC viral inactivation and many more (Azevedo et al, 2009;Dizon-Maspat et al, 2011;Grabski and Mierendorf, 2009;Hammerschmidt et al, 2014;Lorenz et al, 2009;Rosa et al, 2013).…”

“…However, the past few years have seen maturation of separation technologies such as Simulated Moving Bed (SMB) (Grabski and Mierendorf, 2009), Aqueous Two Phase Systems (ATPS) (Azevedo et al, 2009;Oelmeier et al, 2010;Rosa et al, 2013), single pass TFF (Dizon-Maspat et al, 2011), high capacity membrane absorbers (Orr et al, 2013), and continuous viral inactivation (Caillet-Fauquet et al, 2004;Lorenz et al, 2009). At present, the confluence of these emerging technologies and the business need to innovate is catalyzing the development of continuous bioprocessing.…”

Perspectives on integrated continuous bioprocessing—opportunities and challenges

“…UF/DF processes are currently performed as batch operations. Continuous versions of these membrane processes could potentially be developed based on membrane cascades [35] and/or single pass tangential flow filtration [36], although additional work will be needed to demonstrate the effectiveness of these methods, particularly for highly concentrated monoclonal antibody formulations [16 ]. Alternatively, product formulation could be achieved using lyophilization or crystallization in continuous tubular reactor systems [37].…”