Pilot-scale demonstration of an end-to-end integrated and continuous biomanufacturing process

Area of Science:

• Biopharmaceutical Manufacturing
• Bioprocess Engineering
• Drug Development

Background:

• The biopharmaceutical industry is shifting towards integrated and continuous biomanufacturing from traditional batch processes.
• Continuous manufacturing promises improved efficiency and accessibility of biologics drugs.
• A commercial implementation of a continuous bioprocess has not yet been reported in the literature.

Purpose of the Study:

• To demonstrate a pilot-scale, end-to-end integrated continuous bioprocess for monoclonal antibody (mAb) production.
• To validate the feasibility of current technologies for continuous biomanufacturing.
• To assess product quality and operational requirements of a continuous bioprocess.

Main Methods:

• An end-to-end integrated continuous bioprocess was designed and implemented, including all key unit operations for mAb production.
• The process incorporated virus removal filtration, ultrafiltration, diafiltration, and formulation steps.
• A 100-L perfusion bioreactor was utilized for the continuous production of the drug substance.

Main Results:

• The integrated continuous bioprocess was successfully operated for 25 days.
• A total of 4.9 kg of drug substance was produced, achieving a productivity of 200 g/day (2 g/L/day).
• The process yielded acceptable product quality with minimal operator intervention.

Conclusions:

• This pilot-scale study provides a successful proof-of-concept for end-to-end integrated continuous bioprocessing.
• Current technologies are capable of supporting continuous biomanufacturing.
• This work represents a significant advancement towards the commercialization of continuous bioprocessing for biologics.