title: Optimizing capacity utilization by large scale 3000 L perfusion in seed train bioreactors.
abstract: Increasing capacity utilization and lowering manufacturing costs are critical for pharmaceutical companies to improve their competitiveness in a challenging environment. Development of next generation cell lines, improved media formulations, application of mature technologies and innovative operational strategies have been deployed to improve yields and capacity utilization. This article describes a large-scale perfusion strategy for the N-1 seed train bioreactor that was successfully applied to achieve higher inoculation cell densities in the production culture. The N-1 perfusion at 3,000-L scale, utilizing a inclined settler, achieved cell densities of up to 158 × 10(5) cell mL(-1) at perfusion rates of 2950 L day(-1) and a retention efficiency of >85%. This approach increased inoculation cell densities and decreased cultivation times by ~20% in a CHO-based, fed-batch antibody manufacturing process while providing comparable culture performance, productivity, and product quality. The strategy therefore yielded significant increase in capacity utilization and concomitant cost improvement in a large scale cGMP facility. Details of the strategy, the cell retention device, and the cell culture performance are described in this article.
authors.affiliation: Pharmaceutical Biotech Production and Development, Roche Diagnostics GmbH, Penzberg, Germany. pohlscheidt.michael@gene.com
authors.forename: Michael
authors.initials: M
authors.lastname: Pohlscheidt
authors.forename: Melanie
authors.initials: M
authors.lastname: Jacobs
authors.forename: Stefan
authors.initials: S
authors.lastname: Wolf
authors.forename: Joerg
authors.initials: J
authors.lastname: Thiele
authors.forename: Alexander
authors.initials: A
authors.lastname: Jockwer
authors.forename: Josef
authors.initials: J
authors.lastname: Gabelsberger
authors.forename: Marco
authors.initials: M
authors.lastname: Jenzsch
authors.forename: Hermann
authors.initials: H
authors.lastname: Tebbe
authors.forename: Josef
authors.initials: J
authors.lastname: Burg
mesh_terms: D000818:Animals; D019149:Bioreactors; D016466:CHO Cells; D002452:Cell Count; D018929:Cell Culture Techniques; D006224:Cricetinae; D003412:Cricetulus; D004867:Equipment Design