Improving outcomes in intensified processing via optimization of the cell line development workflow.

Area of Science:

• Biotechnology
• Bioprocessing
• Cell Line Development

Background:

• Intensified manufacturing processes require robust cell lines.
• Current cell line development (CLD) often uses fed-batch methods, followed by adaptation to perfusion.
• This traditional approach may not yield optimal clones for perfusion performance.

Purpose of the Study:

• To investigate the impact of CLD workflows on cell line performance in fed-batch and perfusion processes.
• To highlight the advantages of a perfusion-specific CLD workflow.
• To develop more efficient cell lines for continuous and intensified manufacturing.

Main Methods:

• Comparison of traditional fed-batch CLD with a perfusion-specific CLD workflow.
• Utilized specialized media for perfusion expansion and production.
• Employed scale-down models simulating perfusion processes.
• Implemented perfusion-specific cell line selection criteria.

Main Results:

• Fed-batch CLD workflows select for high volumetric titers, potentially neglecting growth rate and specific productivity.
• Cell lines developed via traditional CLD may not maintain performance in perfusion.
• A perfusion-specific CLD workflow demonstrated improved cell line performance in perfusion processes.

Conclusions:

• The CLD workflow significantly impacts cell line performance in both fed-batch and perfusion processes.
• Adopting a perfusion-specific CLD workflow is advantageous for intensified manufacturing.
• This approach leads to the development of more efficient cell lines tailored for continuous processing.