Optimizing capacity utilization by large scale 3000 L perfusion in seed train bioreactors

TLDR

Increasing capacity utilization and lowering manufacturing costs are critical for pharmaceutical companies, and next‑generation cell lines, improved media, mature technologies, and innovative operational strategies have been deployed to enhance yields and capacity utilization. The study presents a large‑scale perfusion strategy for the N‑1 seed‑train bioreactor aimed at achieving higher inoculation cell densities in production culture. The approach uses a 3,000‑L perfusion bioreactor with an inclined settler cell‑retention device operating at 2,950 L day⁻¹ perfusion rates to sustain high cell densities. The 3,000‑L perfusion at 2,950 L day⁻¹ with >85 % retention achieved cell densities up to 1.58 × 10⁷ cells mL⁻¹, increased inoculation densities, reduced cultivation times by ~20 %, and improved capacity utilization and cost in a large‑scale cGMP CHO antibody process.

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.