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Monoclonal Antibody Process Development Using Medium Concentrates
Author(s) -
Bibila Theodora A.,
Ranucci Colette S.,
Glazomitsky Konstantin,
Buckland Barry C.,
Aunins John G.
Publication year - 1994
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/bp00025a011
Subject(s) - monoclonal antibody , process development , titer , fed batch culture , cell culture , osmotic concentration , chemically defined medium , antibody , process (computing) , biology , chemistry , microbiology and biotechnology , chromatography , process engineering , computer science , biochemistry , fermentation , in vitro , immunology , genetics , engineering , operating system
A fed‐batch process using concentrated medium was evaluated for its ability to improve cell culture longevity and final monoclonal antibody (MAb) titers for two monoclonal antibody producing cell lines. It was found to result in up to 7‐fold increases in final antibody titers compared to batch culture controls. Although the development of cell line specific fed‐batch protocols is critical to the development of cost‐efficient largescale production processes, the use of complete medium concentrates provided us with a quick and simple method for producing large quantities of antibodies in the early stages of process development, thus accelerating early work on purification process development, analytical development, biochemical characterization, and safety studies. Insights gained from the concentrated medium fed‐batch approach were valuable for the development of refined, cell line specific feeding strategies yielding final MAb titers on the order of 1–2 g/L. Process development data on the effects of inhibitory growth byproducts, medium osmolarity, and the mode of nutrient feed addition on culture longevity and MAb production and information on culture metabolic behavior were successfully incorporated in the development of the optimized fed‐batch protocols.