Upstream cell culture process characterization and in-process control strategy development at pandemic speed

Area of Science:

• Biopharmaceutical Manufacturing
• Process Development
• COVID-19 Therapeutics

Background:

• The COVID-19 pandemic created an urgent need for rapid development of effective treatments.
• Neutralizing monoclonal antibodies (mAbs) emerged as a key therapeutic strategy.
• Chemistry, Manufacturing, and Controls (CMC) process development must keep pace with urgent clinical needs.

Purpose of the Study:

• To present a case study on accelerating late-stage cell culture process development for mAb production.
• To demonstrate the feasibility of achieving pandemic-speed development for biotherapeutics.
• To ensure consistent product quality and manufacturing yield for combination therapies.

Main Methods:

• Implemented late-stage cell culture process characterization (PC) within an accelerated timeline.
• Utilized strategies including pre-PC risk assessment and scale-down model qualification.
• Developed robust in-process control strategies for manufacturing process performance qualification (PPQ).

Main Results:

• Completed late-stage PC for two mAbs (mAb1 and mAb2) in approximately 4 months, significantly faster than the standard 1-year timeline.
• Successfully initiated the PPQ campaign without compromising product quality.
• Demonstrated the effectiveness of the accelerated strategies in a real-world pandemic scenario.

Conclusions:

• Accelerated late-stage cell culture process development is achievable at pandemic speed.
• The presented strategies can expedite biopharmaceutical development for urgent patient needs.
• This approach can be applied to other biologics to reduce overall development timelines.