title: 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 x 10(7) 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.
authors.affiliation: Cell Culture Development, Protein Design Labs, 34801 Campus Drive, Fremont, California 94555, USA. psauer@pdl.com
authors.forename: P W
authors.initials: PW
authors.lastname: Sauer
authors.forename: J E
authors.initials: JE
authors.lastname: Burky
authors.forename: M C
authors.initials: MC
authors.lastname: Wesson
authors.forename: H D
authors.initials: HD
authors.lastname: Sternard
authors.forename: L
authors.initials: L
authors.lastname: Qu
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000235:genetics* / Q000276:immunology*; D018929:Cell Culture Techniques / Q000379:methods*; D002460:Cell Line / Q000276:immunology*; D006801:Humans; D051379:Mice; D015202:Protein Engineering; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D011994:Recombinant Proteins