Developing an ultra-intensified fed-batch cell culture process with greatly improved performance and productivity

Area of Science:

• Biotechnology
• Bioprocess Engineering
• Cell Culture Technology

Background:

• Intensified fed-batch (IFB) is a common strategy for improving cell culture productivity.
• However, IFB can lead to increased apoptosis and unsustainable productivity.
• There is a need for improved cell culture processes that enhance productivity while maintaining cell viability.

Purpose of the Study:

• To develop and evaluate a novel intermittent-perfusion fed-batch (IPFB) process.
• To investigate the potential of ultra-intensified IPFB (UI-IPFB) for further productivity gains.
• To assess the feasibility, scalability, and cost-effectiveness of these novel processes.

Main Methods:

• Developed IPFB by incorporating intermittent perfusion cycles into IFB.
• Designed UI-IPFB with significantly higher seeding densities using alternating tangential flow (ATF) filtration.
• Evaluated IPFB and UI-IPFB in multiple recombinant Chinese hamster ovary (CHO) cell lines and products.

Main Results:

• IPFB demonstrated an average titer increase of approximately 45% compared to IFB across eight CHO cell lines.
• UI-IPFB achieved up to 6-fold higher productivity than traditional fed-batch and 3-fold higher than IFB.
• Both processes showed broad feasibility, cost reduction, and scalability.

Conclusions:

• IPFB offers a viable strategy for sustained cellular and metabolic behavior, leading to improved productivity.
• UI-IPFB represents a significant advancement in cell culture intensification, achieving unprecedented yields.
• These novel processes are effective, scalable, and reduce the cost of goods for biopharmaceutical manufacturing.