Process performance and product quality in an integrated continuous antibody production process.

Area of Science:

• Biopharmaceutical Manufacturing
• Biotechnology
• Chemical Engineering

Background:

• Continuous manufacturing offers potential benefits for therapeutic protein production, including improved cost and quality.
• Integrating bioreactor perfusion culture with downstream continuous affinity capture is a key challenge.

Purpose of the Study:

• To demonstrate the stable integration of continuous perfusion culture with continuous affinity capture for monoclonal antibody production.
• To optimize process control for enhanced productivity and product quality.

Main Methods:

• Utilized a Chinese hamster ovary (CHO) cell line in perfusion mode connected to a continuous affinity capture step.
• Implemented control loops for volumetric flow and capture process adaptation.
• Combined at-line HPLC with a mechanistic model for real-time monitoring and control.

Main Results:

• Achieved stable operation at multiple viable cell densities (20–60 × 10^6 cells/mL) with yields consistently above 99%.
• Maintained consistent product quality (aggregates, fragments, charge isoforms, N-linked glycosylation) across different steady states.
• Demonstrated significant reduction of host cell DNA and proteins (HCP) by the capture step.

Conclusions:

• Integrated continuous manufacturing enhances product quality control and modulation.
• This integrated system provides a robust platform for efficient and high-quality biopharmaceutical production.
• The study highlights the potential of continuous processing for the biopharmaceutical industry.