Minute-by-minute metabolic control in cell therapy manufacturing: evidence from two real-world case studies

Continuous, real-time metabolic monitoring offers significant advantages over manual sampling in advanced therapy medicinal product manufacturing, including improved process control, reduced contamination risk, and lower operator burden. Two case studies are presented: on-line glucose and lactate monitoring in a cell expansion process, where real-time measurements showed strong correlation across three runs and with off-line reference data; and integration of real-time monitoring into a functionally closed custom bioreactor for the manufacture of personalized tissue-engineered arteries, where glucose was maintained at a physiological set point of 5.5 mmol/L. Key takeaways include the need for optimized controller settings, frequent auto-calibrations to manage sensor drift, and appropriate membrane selection to limit protease interference.

What you will learn

01

How continuous, real-time glucose and lactate monitoring outperforms manual sampling in ATMP manufacturing, cutting operator burden and contamination risk

02

How a PID-controlled feed strategy held glucose at a 5.5 mmol/L physiological set point in a functionally closed bioreactor for personalized tissue-engineered arteries

03

Key lessons for stable control: optimized controller tuning, frequent auto-calibration, and membrane selection to limit protease interference and sensor drift

Key interests

Real-time metabolic monitoring Glucose & lactate control PID feedback control Closed-system bioreactors Tissue-engineered arteries Sensor drift & calibration ATMP manufacturing GMP scale-up

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