title: Large-scale monoclonal antibody purification by continuous chromatography, from process design to scale-up.
abstract: The development and optimization of a purification process of monoclonal antibodies based on two continuous chromatography steps for capture and intermediate purification are presented. The two chromatography steps were individually optimized using either batch chromatography or sequential multicolumn chromatography (SMCC). Proprietary simulation software was used to optimize SMCC and to evaluate the potential gains compared with batch chromatography. The SMCC recipes provided by the simulation software were evaluated experimentally. A good correlation was found between the simulated results and experimental observations. Significant gains were observed on the productivity, buffer consumption and the volume of resin required for SMCC over batch chromatography. Based on these results, a chained process from the capture to polishing steps was implemented. This chained process demonstrated significantly better performance compared with the batch equivalent while satisfying the specifications. The expected positive impact provided by implementing continuous chromatography is also discussed.
authors.affiliation: Novasep Belgium, 16 rue Clément Ader, 6041 Gosselies, Belgium. Electronic address: Valerie.girard@novasep.com.
authors.forename: Valérie
authors.initials: V
authors.lastname: Girard
authors.affiliation: Novasep Process SAS, 82 Boulevard de la Moselle, Site Eiffel - BP50, 54340 Pompey, France. Electronic address: Nicolas-julian.hilbold@novasep.com.
authors.forename: Nicolas-Julian
authors.initials: NJ
authors.lastname: Hilbold
authors.affiliation: Novasep Inc., 23 Creek Circle - Boothwyn, PA 19061, USA. Electronic address: candy.ng@novasep.com.
authors.forename: Candy K S
authors.initials: CK
authors.lastname: Ng
authors.affiliation: Novasep Process SAS, 82 Boulevard de la Moselle, Site Eiffel - BP50, 54340 Pompey, France. Electronic address: Laurence.pegon@novasep.com.
authors.forename: Laurence
authors.initials: L
authors.lastname: Pegon
authors.affiliation: Novasep Belgium, 16 rue Clément Ader, 6041 Gosselies, Belgium. Electronic address: Wael.chahim@novasep.com.
authors.forename: Wael
authors.initials: W
authors.lastname: Chahim
authors.affiliation: Novasep Process SAS, 82 Boulevard de la Moselle, Site Eiffel - BP50, 54340 Pompey, France. Electronic address: Fabien.rousset@novasep.com.
authors.forename: Fabien
authors.initials: F
authors.lastname: Rousset
authors.affiliation: Novasep Process SAS, 82 Boulevard de la Moselle, Site Eiffel - BP50, 54340 Pompey, France. Electronic address: Vincent.monchois@novasep.com.
authors.forename: Vincent
authors.initials: V
authors.lastname: Monchois
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000302:isolation & purification*; D019149:Bioreactors; D016466:CHO Cells; D002852:Chromatography, Ion Exchange / Q000379:methods; D006224:Cricetinae; D003412:Cricetulus; D007074:Immunoglobulin G / Q000276:immunology*; D013205:Staphylococcal Protein A / Q000737:chemistry
chemical_list: D000911:Antibodies, Monoclonal; D007074:Immunoglobulin G; D013205:Staphylococcal Protein A
keywords: Antibody purification; Continuous biomanufacturing; Continuous bioprocessing; Continuous chromatography; Downstream processing; Monoclonal antibody