Biomanufacturing evolution from conventional to intensified processes for productivity improvement: a case study.

Area of Science:

• Biotechnology
• Biopharmaceutical Manufacturing
• Chemical Engineering

Background:

• Biomanufacturing traditionally faces challenges with productivity and cost-effectiveness.
• Process intensification offers a promising strategy to overcome these limitations.
• Conventional methods require optimization for large-scale therapeutic protein production.

Purpose of the Study:

• To evolve a conventional monoclonal antibody (mAb) production process to intensified schemes.
• To evaluate the impact of intensified upstream and downstream processing on titers and quality.
• To assess the cost-effectiveness of intensified biomanufacturing strategies.

Main Methods:

• Implemented intensified seed culture (enriched medium or perfusion) for higher cell densities.
• Utilized fed-batch mode in production bioreactors with higher inoculation densities.
• Adopted high-capacity resins, multi-column chromatography, and integrated pool-less polishing steps for downstream processing.
• Performed cost-of-goods analysis comparing conventional and intensified processes.

Main Results:

• Achieved 4-fold and 8-fold titer increases from Process A to B and C, respectively.
• Maintained comparable final product quality across all processes.
• Reduced resin requirements, buffer consumption, and processing times significantly.
• Demonstrated 6.7 to 10.1-fold cost reduction in consumables for intensified Process C.

Conclusions:

• Hybrid process intensification is effective for increasing mAb production titers and efficiency.
• Intensified upstream and downstream processing can be readily implemented in biomanufacturing.
• This approach provides a foundation for future fully continuous manufacturing processes.