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State‐of‐the‐art in downstream processing of monoclonal antibodies: Process trends in design and validation
Author(s) -
MarichalGallardo P. A.,
Álvarez M. M.
Publication year - 2012
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 - 10.1002/btpr.1567
Subject(s) - downstream processing , monoclonal antibody , ultrafiltration (renal) , biopharmaceutical , downstream (manufacturing) , bioreactor , centrifugation , process engineering , chromatography , chemistry , scale (ratio) , scale up , cell culture , microcarrier , process (computing) , biochemical engineering , computer science , microbiology and biotechnology , antibody , cell , biology , biochemistry , engineering , immunology , operations management , organic chemistry , classical mechanics , physics , genetics , quantum mechanics , operating system
Monoclonal antibodies (mAbs) are the most important family of biopharmaceutical compounds in terms of market share. At present, 30 mAbs have been approved and are now commercialized for therapeutic purposes. mAbs are typically produced by mammalian cell culture in bioreactors that range in scale of 1–20 m 3 . Regardless of scale, from laboratory to commercial settings, the recovery and purification of mAbs present important challenges. Depending on the scale, the particular product, and the type of production process (bioreactor operation, process time, complexity of the culture media, cell density, etc.), many possible downstream configurations are possible and have been used. In this contribution, we review each type of unit operation that forms a downstream train for mAb production. We provide information regarding typical operation settings and critical variables for centrifugation, ultrafiltration, affinity chromatography, ion exchange chromatography, and viral removal operations. In addition, we discuss some important considerations required for the formulation of drugs based on mAbs. © 2012 American Institute of Chemical Engineers Biotechnol. Prog., 28: 899–916, 2012