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  • Virus removal filtration of chemically defined Chinese Hamster Ovary cells medium with nanocellulose-based size exclusion filter.

Virus removal filtration of chemically defined Chinese Hamster Ovary cells medium with nanocellulose-based size exclusion filter.

Biologicals : journal of the International Association of Biological Standardization (2019-03-16)
Levon Manukyan, Justine Padova, Albert Mihranyan
ABSTRACT

Sterility of bioreactors in biotherapeutic processing remains a significant challenge. Virus removal size-exclusion filtration is a robust and highly efficient approach to remove viruses. This article investigates the virus removal capacity of nanocellulose-based filter for upstream bioprocessing of chemically defined Chinese hamster ovary (CHO) cells medium containing Pluronic F-68 (PowerCHO™, Lonza) and supplemented with insulin-transferrin-selenium (ITS) at varying process parameters. Virus retention was assessed by spiking ITS-supplemented PowerCHO™ medium with small-size ΦX174 phage (28 nm) as a surrogate for mammalian parvoviruses. The nanocellulose-based size exclusion filter showed high virus retention capacity (over 4 log10) and high flow rates (around 180 L m-2 h-1). The filter had no impact on ITS supplements during filtration. It was further shown that the filtered PowerCHO™ medium supported cell culture growth with no impact on cell viability, morphology, and confluence. The results of this work show new opportunities in developing cost-efficient virus removal filters for upstream bioprocessing.