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Effect of protein fouling on filtrate flux and virus breakthrough behaviors during virus filtration process
Authors:Dongwoo Suh  Hoeun Jin  Hosik Park  Changha Lee  Young Hoon Cho  Youngbin Baek
Institution:1. School of Chemical and Biological Engineering, Seoul National University (SNU), Seoul, Republic of Korea

Contribution: Conceptualization, ?Investigation, Data curation, Writing - original draft, Writing - review & editing;2. Department of Biological Engineering, Inha University, Incheon, Republic of Korea

Contribution: ?Investigation, Data curation, Writing - review & editing;3. Green Carbon Research Center, Korea Research Institute of Chemical Technology (KRICT), Daejeon, Republic of Korea

Department of Advanced Materials and Chemical Engineering, University of Science & Technology (UST), Daejeon, Yuseong-gu, Republic of Korea

Contribution: ?Investigation, Data curation, Writing - review & editing;4. School of Chemical and Biological Engineering, Seoul National University (SNU), Seoul, Republic of Korea;5. Green Carbon Research Center, Korea Research Institute of Chemical Technology (KRICT), Daejeon, Republic of Korea;6. Department of Biological Engineering, Inha University, Incheon, Republic of Korea

Abstract:Virus filtration process is used to ensure viral safety in the biopharmaceutical downstream processes with high virus removal capacity (i.e., >4 log10). However, it is still constrained by protein fouling, which results in reduced filtration capacity and possible virus breakthrough. This study investigated the effects of protein fouling on filtrate flux and virus breakthrough using commercial membranes that had different symmetricity, nominal pore size, and pore size gradients. Flux decay tendency due to protein fouling was influenced by hydrodynamic drag force and protein concentration. As the results of prediction with the classical fouling model, standard blocking was suitable for most virus filters. Undesired virus breakthrough was observed in the membranes having relatively a large pore diameter of the retentive region. The study found that elevated levels of protein solution reduced virus removal performance. However, the impact of prefouled membranes was minimal. These findings shed light on the factors that influence protein fouling during the virus filtration process of biopharmaceutical production.
Keywords:biopharmaceutical downstream process  filtrate flux  protein fouling  virus breakthrough  virus filtration membrane
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