(228ai) Nanofiltration for Mitigation of Upstream Viral Contamination Risks from Cell Culture Media and Feed

Adventitious viral contamination of production cells of commercial drugs can cause severe economic consequences due to losses of drug product batches and market share, costs associated with decontamination, and fines for regulatory non-compliance. A number of measures have been implemented in manufacturing processes to mitigate the risk of viral contamination of biopharmaceutics, which include testing of production cell lines, raw materials, process intermediates and final products, and inclusion of downstream process steps capable of reducing, removing, and inactivating viruses. Nonetheless, virus entry into the process through the cell culture medium preparation remains a possibility. Technology for upstream processing such as high temperature short time (HTST) processing for prevention of viral infection in cell culture is practiced by a small number of biotech companies. Retentive viral filtration (nanofiltration) of cell culture media and feeds is another key viral contamination risk mitigation technology, which has been implemented in GMP Manufacturing by a number of biopharma companies. In this study, small-scale nanofilters from three nanofilter vendors were evaluated for BI production and feed media, and the results with four CHO cell lines show no significant negative impact on cell culture performance. The nanofilter from one of the vendors demonstrated promising potential for implementation at 12K manufacturing scale and is being evaluated at pilot scale.