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Development and Qualification of a Novel Virus Removal Filter for Cell Culture Applications
Author(s) -
Liu Shengjiang,
Carroll Mark,
Iverson Raquel,
Valera Christine,
Vennari Joann,
Turco Kimberly,
Piper Robert,
Kiss Robert,
Lutz Herbert
Publication year - 2000
Publication title -
biotechnology progress
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.572
H-Index - 129
eISSN - 1520-6033
pISSN - 8756-7938
DOI - 10.1021/bp000027m
Subject(s) - bioreactor , filtration (mathematics) , microbiology and biotechnology , cell culture , virus , bacterial virus , bacteriophage , biology , chemistry , virology , biochemistry , escherichia coli , statistics , mathematics , gene , genetics , botany
Commercial bioreactors employing mammalian cell cultures to express biological or pharmaceutical products can become contaminated with adventitious viruses. The high expense of such a contamination can be reduced by passing all gases and fluids feeding the bioreactor through virus inactivation or removal steps, which act as viral barriers around the bioreactor. A novel virus barrier filter has been developed for removing viruses from serum‐free cell culture media. This filter removes the 20 nm minute virus of mice by >3 log reduction value (LRV), the 28 nm bacteriophage ΦX174 by >4.5 LRV, the mycoplasma Acholeplasma laidlawii by ≥8.8 LRV, and the bacteria Brevundimonas diminuta by ≥9.2 LRV. Robust removal occurs primarily by size exclusion as demonstrated over a wide range of feedstocks and operating conditions. The filtered media are indistinguishable from unfiltered media in growth of cells to high densities, maintenance of cell viability, and productivity in expressing protein product. Insulin and transferrin show high passage through the filter. The virus barrier filter can be autoclaved. The relatively high membrane permeability enables the use of a moderate filtration area.