Fouling of virus filtration membranes by monoclonal antibody feeds with low aggregate content

Abstract

Membrane fouling by monoclonal antibodies (mAbs) is one of the main challenges in virus‐filtration processes. Previous publications attributed membrane fouling to the presence of mAb aggregates in the solution, which block the membrane pores. This fouling mechanism can be solved by a prefilter; however, it was shown that there are mAbs that severely foul the membranes (reduce permeability by 90% and more) even after prefiltering the aggregates, while other mAbs foul the membrane weakly (reduce permeability by ~10% and less). Unfortunately, the differences between the fouling‐ and the nonfouling mAbs have never been convincingly explained. To get a deeper insight on these differences, we measured the fouling of chemically modified Isoprene‐Styrene‐4‐vinylpyridine (ISV) membranes (TeraPore Technologies) by 8 mAbs exhibiting different hydrophobicity and charge. The results show that mAb solutions with low concentration of aggregates foul ISV membranes via an adsorptive mechanism, and the adsorption is driven mainly by hydrophobic forces between the mAb and the membrane. The charge of the mAbs plays a secondary role in fouling. We want to emphasize that the conclusions pertain to ISV membranes; the insights presented in this paper can potentially be used to engineer new surface chemistries to mitigate fouling of other virus‐filtration and/or ultrafiltration membranes.

Special Issue on “Recovery of Biological Products: Past, Present, Future”

“…The issue reflects on presentations and discussions covering state‐of‐the‐art technologies for harvesting and purifying proteins such as monoclonal antibodies (mAbs) and non‐protein modalities, such as viral vectors. Topics include: future facility designs that embrace modular (Bertran & Babi, 2024) and continuous concepts (Konoike et al, 2024; Minervini et al, 2024), novel purification technologies from fluidized bed systems and 3D‐printed monoliths (Herlevi et al, 2024; Pei et al, 2024; Saballus et al, 2024) through to new membrane and chromatography devices (Lavoie et al, 2024; Platteau et al, 2024), bioprocess development acceleration tools that embrace high throughput tools with novel sensors, data analytics, modeling, and control strategies (Andersson et al, 2024; Banerjee et al, 2024; Dürauer et al, 2024; Hahn et al, 2024; Kaufman et al, 2024; Keulen et al, 2024; Lorek et al, 2024; Sebastian et al, 2024), separation science and solutions for non‐mAb proteins (Rodriguez et al, 2024; Roush et al, 2024) and emerging viral products (Kish et al, 2024; Konstantinidis et al, 2024; Lyle et al, 2024; Perry et al, 2024; Soni et al, 2024), perspectives on the current status and future outlook for downstream processing of biological products drawn from the conference roundtable discussions (Jungbauer et al, 2024). …”

“…bioprocess development acceleration tools that embrace high throughput tools with novel sensors, data analytics, modeling, and control strategies (Andersson et al, 2024; Banerjee et al, 2024; Dürauer et al, 2024; Hahn et al, 2024; Kaufman et al, 2024; Keulen et al, 2024; Lorek et al, 2024; Sebastian et al, 2024),…”