The drive for high product titer mammalian cell culture of recombinant proteins, especially monoclonal antibodies, has increased cell density and process-related impurity levels. These high productivity cultures are therefore placing a larger burden on traditional downstream clarification and purification operations. Controlled flocculation and precipitation of mammalian cell culture suspensions by acidification has been employed to both enhance clarification throughput and aid removal of process related impurities such as host cell protein and DNA. However, acid precipitation can complicate downstream processing at production-scale. For example, it may necessitate harvest pool neutralization before affinity chromatography. Therefore a modification of the traditional acid precipitation technique is presented whereby the cell culture is acidified, held, and neutralized before clarification. The two techniques are compared in terms of impurity removal, filter throughput, and downstream processing convenience for clarification via dead end depth filtration both with and without prior disk stack centrifugation.

Comparison of acid precipitation with acid shock treatment for clarification of high cell density mammalian cell cultures

247th National Meeting (2014)

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