Evaluation of single-use optical and electrochemical pH sensors in upstream bioprocessing
Erica J. Fratz-Berilla,
Casey Kohnhorst,
Nicholas Trunfio,
Xin Bush,
Aron Gyorgypal,
Cyrus Agarabi
Affiliations
Erica J. Fratz-Berilla
U.S. Food and Drug Administration, Center for Drug Evaluation and Research, Office of Pharmaceutical Quality, Office of Biotechnology Products, Division of Biotechnology Review and Research II, Silver Spring, MD, USA; Corresponding author.
Casey Kohnhorst
U.S. Food and Drug Administration, Center for Drug Evaluation and Research, Office of Pharmaceutical Quality, Office of Biotechnology Products, Division of Biotechnology Review and Research II, Silver Spring, MD, USA
Nicholas Trunfio
U.S. Food and Drug Administration, Center for Drug Evaluation and Research, Office of Pharmaceutical Quality, Office of Biotechnology Products, Division of Biotechnology Review and Research II, Silver Spring, MD, USA
Xin Bush
U.S. Food and Drug Administration, Center for Drug Evaluation and Research, Office of Pharmaceutical Quality, Office of Biotechnology Products, Division of Biotechnology Review and Research II, Silver Spring, MD, USA; Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, University of Rhode Island, Kingston, RI, USA
Aron Gyorgypal
Department of Chemical and Biochemical Engineering, School of Engineering, Rutgers the State University of New Jersey, Piscataway, NJ, 08854, USA
Cyrus Agarabi
U.S. Food and Drug Administration, Center for Drug Evaluation and Research, Office of Pharmaceutical Quality, Office of Biotechnology Products, Division of Biotechnology Review and Research II, Silver Spring, MD, USA
Culture pH is a critical process parameter during CHO cell bioreactor operations that is key for proper cell growth, protein production, and maintaining the critical quality attributes of a monoclonal antibody drug substance. The traditional means of measuring pH in bioreactors is with an electrochemical probe that can withstand and maintain accuracy through repeated sterilization cycles. An alternative technique for measuring pH is an optical sensor composed of a fluorescent dye that is sensitive to the hydrogen ion concentration. In this work we explore single-use electrochemical and single-use optical pH sensors in stirred-tank and rocking bioreactors, respectively, to understand how their overall performance compares to traditional electrochemical probes in benchtop glass stirred tank bioreactors. We found that the single-use optical pH sensors were generally less accurate than the electrochemical probes, especially in detecting large pH drifts from the setpoint. The single-use electrochemical probes were increasingly accurate as pH was increased from <7.0 to 7.5 but tended to decrease in accuracy as the batch age increased. In conclusion, single-use pH sensors offer a convenient means to measure pH during an upstream bioprocess, but the limitations of these sensors should be built into process control such that deviations in process pH, and consequently potential fluctuations in product quality, can be avoided.
