Process- and Product-Related Foulants in Virus Filtration

Abstract

Regulatory authorities place stringent guidelines on the removal of contaminants during the manufacture of biopharmaceutical products. Monoclonal antibodies, Fc-fusion proteins, and other mammalian cell-derived biotherapeutics are heterogeneous molecules that are validated based on the production process and not on molecular homogeneity. Validation of clearance of potential contamination by viruses is a major challenge during the downstream purification of these therapeutics. Virus filtration is a single-use, size-based separation process in which the contaminating virus particles are retained while the therapeutic molecules pass through the membrane pores. Virus filtration is routinely used as part of the overall virus clearance strategy. Compromised performance of virus filters due to membrane fouling, low throughput and reduced viral clearance, is of considerable industrial significance and is frequently a major challenge. This review shows how components generated during cell culture, contaminants, and product variants can affect virus filtration of mammalian cell-derived biologics. Cell culture-derived foulants include host cell proteins, proteases, and endotoxins. We also provide mitigation measures for each potential foulant.

A Review on Downstream Processing of Monoclonal Antibodies (mAbs)

“…Due to the fact that normal flow (dead end) mode is less difficult and only needs a single pump, virus filters are often operated in this mode as opposed to the tangential flow mode utilised for protein ultrafiltration. [85] High permeability, no reduction in protein production, and consistent performance across various media lots, device lots, and device scales are all characteristics of the Viresolve TM Prefilter. Filter capacity can be reduced by plugging brought on by the trapping of protein aggregates, denatured proteins, and other contaminants.…”

Integration of Planova filters in manufacturing processes of biologicals improve the virus safety effectively: A review of publicly available data

“…8,37 Data reviewed and summarized in this review demonstrate for intermediates of a wide range of plasmaand cell culture-derived products a reliable, robust and size-based removal of viruses; Table 8 shows the compilation of peer-reviewed data (publications and package inserts (FDA)). The data presented are based on manufacturing process conditions, optimized for yield and quality of the desired protein, and aspects of flux/flux decay and membrane fouling 38 were already solved during development of the manufacturing process. The data presented by Mattila et al 8 and Johnson et al 5 confirm the efficacy of virus filtration, including Planova filters manufactured from regenerated cellulose, for cell culture-derived proteins and for plasma-derived medicinal products by Roth et al 6 the parameter protein concentration to be not relevant is also confirmed in these publications.…”

A versatile fabrication route for screening block copolymer membranes for bioprocessing

“…3 Critical to all such processes are membrane-based unit operations such as ultrafiltration, virus and sterile filtration, however, many are challenged by low throughput associated with fouling and the demands of meeting the required clearance requirements. 4 Commercial polyethersulfone (PES) membranes are manufactured using the well-established non-solvent induced phase separation (NIPS) method, pioneered by Loeb and Sourirajan in 1963, 5 and renowned for its versatility and scalability. This characteristic renders them indispensable in various key bio-separation applications for the recovery and purification of monoclonal antibodies, viral vectors, and lipid nanoparticles.…”