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Metabolic-sensing characteristics of absorption-photometry for mammalian cell cultures in biopharmaceutical processes

Andrew Bawn, Hae Woo Lee, Andrew Downey, Jin Xu, Jason A Starkey and Seongkyu Yoon

In mammalian cell culture processes, metabolite concentrations have to be routinely monitored to ensure the consistency of both process operation and product quality. The absorption photometric-based technology (APBT) has been introduced recently as a new option for characterizing metabolic profiles of the cell-culture processes. In order to understand the measurement technology, the benchmarking study was conducted under various conditions, including known standard samples and untreated cell-culture samples. Results: The standard samples, with known concentrations of the metabolites, were analyzed using APBT, and its repeatability, as well as its accuracy was compared with the other two common technologies used in the industry: membrane-based technology, and supplementary HPLC. The three technologies were further validated using the supernatant collected from batch cellcultures from two different Chinese hamster ovary cell lines with extended culture duration, covering a broad range of experimental conditions. A statistical analysis was conducted to evaluate the different technologies, and it revealed that the APBT exhibited the best accuracy, while both APBT and membrane-based technology provided good reproducibility. On the other hand, HPLC was highly susceptible to instability when under sub-optimal conditions, especially to the untreated cell culture samples with high complexity and interference. At the same time, the investigation of correlations among the different technologies indicated that APBT was highly compatible with other two technologies. Conclusion: Both good accuracy and high precision of the metabolite analysis achievable with APBT suggest that it might be another viable option for analyzing the metabolites in mammalian cell cultures.