Virus reduction filtration in continuous bioprocessing: Critical flux concept for virus breakthrough
October 6-10, 2019
Virus reduction filtration is an integral component of virus clearance strategy in modern biologics production processes. Continuous bioprocessing and process intensification are the buzz words in biopharmaceutical industry due to benefits of cost savings from higher productivity, operational flexibility and better product quality. A typical batch process operates virus reduction filters at constant pressure to maximize the throughput within one shift of process time constraint. However, continuous bioprocessing would demand constant low flux virus reduction operation over extended duration to address the complications of frequent filter switching. Due to relaxation of process time constraint, continuous bioprocessing allows better utilization of filter capacity (L/m2). However, there is limited understanding around the virus breakthrough mechanism and associated critical process parameters. This poses an interesting question how to define end point for virus reduction filtration while utilizing most of the filter capacity for low fouling feed. What is the effect of flux, differential pressure and total viral particle load on virus clearance performance of commercially available viral filters? Is there a critical flux for viral reduction filters below which they are susceptible to significant virus breakthrough (LRV <4) and if yes, how sensitive it is to filter’s property and other process parameters? This study explores the effect of flux, differential pressure and total viral particle load on viral clearance performance of three commercially available filters. These filters are selected to cover the wide range of filter permeability and membrane material. The viral clearance study was performed both in the presence and absence of products.
Dharmesh Kanani, Mi Jin, Rong Fan, Fu Namila, Ranil Wickramasinghe, and Xianghong Qian, "Virus reduction filtration in continuous bioprocessing: Critical flux concept for virus breakthrough" in "Integrated Continuous Biomanufacturing IV", Veena Warikoo, Roche, USA Alois Jungbauer, BOKU, Austria Jon Coffman, Boehringer Ingelheim, USA Jason Walther, Sanofi, USA Eds, ECI Symposium Series, (2019). https://dc.engconfintl.org/biomanufact_iv/40