A novel approach to residence time distribution characterization in a mAb continuous process

Area of Science:

• Biopharmaceutical Manufacturing
• Process Engineering
• Chemical Engineering

Background:

• Continuous bioprocessing offers advantages for monoclonal antibody (mAb) production.
• Understanding unit operation dynamics is crucial for process robustness and product quality.
• Residence time distribution (RTD) modeling is a key tool for characterizing dynamic processes.

Purpose of the Study:

• To model and characterize an integrated perfusion continuous bioprocess using RTD analysis.
• To elucidate the impact of process excursions, such as filter fouling and changes in packed cell volume, on mAb production.
• To investigate protein quality modulation, specifically glycosylation, within the continuous process.

Main Methods:

• Modeled unit operations as continuous-stirred tank reactors (CSTRs).
• Utilized a glycosylation inhibitor as a tracer to study its RTD and impact on glycosylation.
• Employed a fluorescently labeled antibody as a tracer molecule to assess process dynamics.

Main Results:

• Characterized the RTD of a small molecule glycan inhibitor and its effect on glycosylation.
• Confirmed the influence of packed cell volume and filter fouling on process dynamics using a labeled antibody tracer.
• Demonstrated the applicability of RTD modeling for analyzing continuous bioprocesses.

Conclusions:

• RTD modeling provides valuable insights into continuous bioprocessing.
• This approach can identify and mitigate factors affecting mAb production, ensuring process robustness.
• Understanding process dynamics is essential for maintaining consistent product quality in biologics manufacturing.