Diafiltration is a critical unit operation which is part of practically every downstream purification train of monoclonal antibody or bio therapeutic modality production. It is typically employed to provide an efficient and robust method for exchanging buffer matrix for the therapeutic modality and offers simultaneous clearance of small molecule and elemental impurities.<br/>Continuous manufacturing and process intensification approaches has been an area of keen interest and various technologies are being investigated to make biotherapeutic manufacturing process more efficient in terms of facility utilization and capital cost reduction by reducing reliance on large scale facilities. Technologies like multi-column cycling, inline viral inactivation and single pass tangential flow filtration (SPTFF) for protein concentration have been developed in past few years, offering significant improvement over their existing batch equivalents. Ability to develop a similar technology for diafiltration suitable for GMP manufacturing has remain rather elusive.<br/>Our approach here is based on a shift in perspective wherein the process design is based on membrane utilization and system footprint as opposed to flux and process time in a typical batch diafiltration process. This rather flexible technology offers 6-8-fold increased membrane utilization, up to 3-fold reduction in pump passes and system footprint can be substantially decreased. Buffer usage, extent of buffer exchange, and product yield are consistent with a constant volume diafiltration process.<br/>In this presentation, we will present a system design for this concept and a 24-hour experimental data demonstrating operational robustness. Implementation into a fully continuous, or intensified process train and flexibility of the system to accommodate complex diafiltation schemes for challenging molecules will also be discussed.

Tank cycling approach for continuous diafiltration process

2019 Spring National Meeting

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