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Virus filtration is used to ensure the high level of virus clearance required in the manufacture of biopharmaceutical products such as monoclonal antibodies. Flux decline during virus filtration can occur due to the formation of reversible aggregates consisting of self-assembled monomeric monoclonal antibody molecules, particularly at high antibody concentrations. While size exclusion chromatography is generally unable to detect these reversible aggregates, dynamic light scattering may be used to determine their presence. Flux decline during virus filtration may be minimized by pretreating the feed using a membrane adsorber in order to disrupt the reversible aggregates that are present. The formation of reversible aggregates is highly dependent on the monoclonal antibody and the feed conditions. For the pH values investigated here, pretreatment of the feed using a hydrophobic interaction membrane adsorber was the most effective in minimizing flux decline during virus filtration. Ion exchange membranes may also be effective if the monoclonal antibody and membrane are oppositely charged. Consequently, the effectiveness of ion exchange membrane adsorbers is much more dependent on solution pH when compared to hydrophobic interaction membrane adsorbers. Size based prefiltration was found to be ineffective at disrupting these reversible aggregates. These results can help guide the development of more effective virus filtration processes for monoclonal antibody production.
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This content will become publicly available on March 1, 2026
Characterization, Performance, and Toxicological Assessment of Polysulfone-Sulfonated Polyether Ether Ketone Membranes for Water Separation Applications
The removal of small molecular weight charged compounds from aqueous solutions using membrane remains a challenge. In this study, polysulfone (PSf)- and sulfonated polyether ether ketone (SPEEK)-based membranes were fabricated via non-solvent induced phase separation process (NIPS) using N-Methyl-2-Pyrrolidone (NMP) as solvent and water as non-solvent. Membranes were characterized structurally and morphologically, followed by toxicity assessment conducted before and after filtration, both with and without annealing at various pH values to evaluate potential leaching of trapped solvent from the membrane pores. Additionally, membrane performance was characterized using binary mixtures of cationic and anionic dyes. The results demonstrated selective filtration behavior, with cationic dyes being preferentially rejected due to size exclusion and electrostatic interactions. Additionally, a key focus of this work was the investigation of solvent leaching, framed within a Safe(r)-by-Design (SbD) approach aimed at enhancing functional performance while minimizing environmental toxicity. Toxicity assessments using a model organism, a nematode Caenorhabditis elegans, revealed that annealing reduced solvent leaching and thus permeate toxicity, particularly at neutral pH values, by facilitating trapped solvent release prior to membrane use. These findings provide insights for the importance of including an SbD approach during membrane casting to fabricate membranes with desirable properties while minimizing toxicity.
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- PAR ID:
- 10656051
- Publisher / Repository:
- mdpi
- Date Published:
- Journal Name:
- Membranes
- Volume:
- 15
- Issue:
- 3
- ISSN:
- 2077-0375
- Page Range / eLocation ID:
- 87
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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