title: Model based adaptive control of a continuous capture process for monoclonal antibodies production.
abstract: A two-column capture process for continuous processing of cell-culture supernatant is presented. Similar to other multicolumn processes, this process uses sequential countercurrent loading of the target compound in order maximize resin utilization and productivity for a given product yield. The process was designed using a novel mechanistic model for affinity capture, which takes both specific adsorption as well as transport through the resin beads into account. Simulations as well as experimental results for the capture of an IgG antibody are discussed. The model was able to predict the process performance in terms of yield, productivity and capacity utilization. Compared to continuous capture with two columns operated batch wise in parallel, a 2.5-fold higher capacity utilization was obtained for the same productivity and yield. This results in an equal improvement in product concentration and reduction of buffer consumption. The developed model was used not only for the process design and optimization but also for its online control. In particular, the unit operating conditions are changed in order to maintain high product yield while optimizing the process performance in terms of capacity utilization and buffer consumption also in the presence of changing upstream conditions and resin aging.
authors.affiliation: Institute for Chemical and Bioengineering, Department of Chemistry and Applied Biosciences, ETH Zurich, 8093 Zurich, Switzerland.
authors.forename: Fabian
authors.initials: F
authors.lastname: Steinebach
authors.affiliation: Institute for Chemical and Bioengineering, Department of Chemistry and Applied Biosciences, ETH Zurich, 8093 Zurich, Switzerland.
authors.forename: Monica
authors.initials: M
authors.lastname: Angarita
authors.affiliation: Institute for Chemical and Bioengineering, Department of Chemistry and Applied Biosciences, ETH Zurich, 8093 Zurich, Switzerland.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Karst
authors.affiliation: Institute for Chemical and Bioengineering, Department of Chemistry and Applied Biosciences, ETH Zurich, 8093 Zurich, Switzerland; ChromaCon AG, Zurich, Switzerland.
authors.forename: Thomas
authors.initials: T
authors.lastname: Müller-Späth
authors.affiliation: Institute for Chemical and Bioengineering, Department of Chemistry and Applied Biosciences, ETH Zurich, 8093 Zurich, Switzerland. Electronic address: massimo.morbidelli@chem.ethz.ch.
authors.forename: Massimo
authors.initials: M
authors.lastname: Morbidelli
mesh_terms: D000327:Adsorption; D000911:Antibodies, Monoclonal / Q000302:isolation & purification*; D001709:Biotechnology / Q000295:instrumentation / Q000379:methods*; D002021:Buffers; D018929:Cell Culture Techniques; D003377:Countercurrent Distribution; D007074:Immunoglobulin G / Q000302:isolation & purification; D008954:Models, Biological; D012117:Resins, Synthetic / Q000737:chemistry
chemical_list: D000911:Antibodies, Monoclonal; D002021:Buffers; D007074:Immunoglobulin G; D012117:Resins, Synthetic
keywords: Antibody purification; Continuous bioprocessing; Continuous chromatography; Process control; Protein A affinity chromatography