title: High-throughput methods for miniaturization and automation of monoclonal antibody purification processes.
abstract: In the last decade, high-throughput downstream process development techniques have entered the biopharmaceutical industry. As chromatography is the standard downstream purification method, several high-throughput chromatographic methods have been developed and applied including miniaturized chromatographic columns for utilization on liquid handling stations. These columns were used to setup a complete downstream process on a liquid handling station for the first time. In this article, a monoclonal antibody process was established in lab-scale and miniaturized afterwards. The scale-down methodology is presented and discussed. Liquid handling in miniaturized single and multicolumn processes was improved and applicability was demonstrated by volume balances. The challenges of absorption measurement are discussed and strategies were shown to improve volume balances and mass balances in 96-well microtiter plates. The feasibility of miniaturizing a complete downstream process was shown. In the future, analytical bottlenecks should be addressed to gain the full benefit from miniaturized complete process development.
authors.affiliation: Section IV: Biomolecular Separation Engineering, Institute of Engineering in Life Sciences, Karlsruhe Institute of Technology, Engler-Bunte-Ring 1, Karlsruhe 76131, Germany.
authors.forename: Katrin
authors.initials: K
authors.lastname: Treier
authors.forename: Sigrid
authors.initials: S
authors.lastname: Hansen
authors.forename: Carolin
authors.initials: C
authors.lastname: Richter
authors.forename: Patrick
authors.initials: P
authors.lastname: Diederich
authors.forename: Jürgen
authors.initials: J
authors.lastname: Hubbuch
authors.forename: Philip
authors.initials: P
authors.lastname: Lester
mesh_terms: D000042:Absorption; D000837:Anion Exchange Resins; D000911:Antibodies, Monoclonal / Q000302:isolation & purification*; D001331:Automation; D002411:Cation Exchange Resins; D002852:Chromatography, Ion Exchange / Q000379:methods*; D008904:Miniaturization
chemical_list: D000837:Anion Exchange Resins; D000911:Antibodies, Monoclonal; D002411:Cation Exchange Resins