title: Model-based process development for the purification of a modified human growth hormone using multimodal chromatography.
abstract: This study demonstrates how the multimodal Capto adhere resin can be used in concert with calcium chloride or arginine hydrochloride as mobile phase modifiers to create a highly selective purification process for a modified human growth hormone. Importantly, these processes are shown to result in significant clearance of product related aggregates and host cell proteins. Furthermore, the steric mass action model is shown to be capable of accurately describing the chromatographic process and the aggregate removal. Finally, justification of the selected operating ranges is evaluated using the model together with Latin hypercube sampling. The results in this article establish the utility of multimodal chromatography when used with appropriate mobile phase modifiers for the downstream bioprocessing of a modified human growth hormone and offer new approaches for bioprocess verification.
authors.affiliation: Dept. of Chemical and Biological Engineering, Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Inst, 110 8th Street, Troy, NY, 12180; Research and Development, Novo Nordisk A/S, Denmark.
authors.forename: Lars
authors.initials: L
authors.lastname: Sejergaard
authors.forename: Hanne Sophie
authors.initials: HS
authors.lastname: Karkov
authors.forename: Janus Kristian
authors.initials: JK
authors.lastname: Krarup
authors.forename: Anne Birgitte Bagge
authors.initials: AB
authors.lastname: Hagel
authors.forename: Steven M
authors.initials: SM
authors.lastname: Cramer
mesh_terms: D000818:Animals; D001120:Arginine; D002122:Calcium Chloride; D002853:Chromatography, Liquid / Q000379:methods*; D029968:Escherichia coli Proteins / Q000737:chemistry; D019382:Human Growth Hormone / Q000737:chemistry / Q000302:isolation & purification*; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008956:Models, Chemical; D015233:Models, Statistical; D066329:Protein Aggregates; D011817:Rabbits; D055672:Static Electricity
chemical_list: D029968:Escherichia coli Proteins; D066329:Protein Aggregates; D019382:Human Growth Hormone; D001120:Arginine; D002122:Calcium Chloride
keywords: Latin hypercube sampling; SMA model; arginine hydrochloride; calcium chloride; multimodal chromatography