title: Model-based design and integration of a two-step biopharmaceutical production process.
abstract: This paper presents the design of a two-step process in which the first step is PEGylation of a protein, and the second step is chromatographic purification of the target mono-PEGylated protein from the unreacted and the di-PEGylated impurities. The difference between optimizing each process step separately and optimizing them simultaneously is studied. It was found that by optimizing the steps simultaneously up to a 100 % increase in productivity could be obtained without reduction in yield. Optimizing both steps at the same time makes it possible for the optimization method to take into account that the di-PEGylated protein is much easier to separate than the non-PEGylated protein. The easier separation makes it possible to get a higher yield and productivity at the same time. The effect of recycling was also studied and the yield could be increased by 30 % by recycling the unreacted protein. However, if maximum productivity is required, batch mode is preferable.
authors.affiliation: Department of Chemical Engineering, Lund University, Box 124, 221 00, Lund, Sweden.
authors.forename: Bruno
authors.initials: B
authors.lastname: Otero
authors.forename: Marcus
authors.initials: M
authors.lastname: Degerman
authors.forename: Thomas Budde
authors.initials: TB
authors.lastname: Hansen
authors.forename: Ernst Broberg
authors.initials: EB
authors.lastname: Hansen
authors.forename: Bernt
authors.initials: B
authors.lastname: Nilsson
mesh_terms: D001702:Biopharmaceutics; D008962:Models, Theoretical