A high-yielding, generic fed-batch cell culture process for production of recombinant antibodies

Abstract

A fed‐batch cell culture process was developed that has general applicability to all evaluated Sp2/0 (n = 8) and NS0 (n = 1) antibody‐producing cell lines. The two key elements of this generic process were a protein‐free concentrated feed medium, and a robust, metabolically responsive feeding strategy based on the off‐line measurement of glucose. The fed‐batch process was shown to perform equivalently at the 15 L development scale and 750 L manufacturing scale. Compared to batch cultures, the fed‐batch process yielded a 4.3 fold increase in the average integral of viable cell concentration and a 1.7 fold increase in average specific antibody production rate, equivalent to a 7.6 fold increase in average final antibody concentration. The highest producing cell line reached a peak viable cell concentration of 1.0 × 107 cell mL−1 and a final antibody concentration of 750 mg L−1 in a 10 day process. For all lines evaluated, reducing bioreactor pH set point from 7.2 to 7.0 resulted in an additional 2.4 fold increase in average final antibody concentration. The optimized fed‐batch process consistently yielded a volumetric productivity exceeding 50 mg L−1 day−1. This generic, high‐yielding fed‐batch process significantly decreased development time, and increased manufacturing efficiency, thereby facilitating the clinical evaluation of numerous recombinant antibodies. © 2000 John Wiley & Sons, Inc. Biotechnol Bioeng 67: 585–597, 2000.

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