472690 Real Time PAT Monitoring of Bioreactor Mab IgG3 Cell Culture Process Dynamics Via Fourier Transform Infrared Spectroscopy: Implications and Challenges

Tuesday, November 15, 2016: 5:27 PM
Continental 5 (Hilton San Francisco Union Square)
Huiquan Wu, OPQ/OPF, FDA/CDER, Silver Spring, MD

Compared to small molecule Process Analytical Technology (PAT) applications, biotechnology product PAT applications have certain unique challenges and opportunities. Understanding the process dynamics of bioreactor cell culture processes is essential to establish an appropriate control strategy for biotechnology product PAT applications. Inline spectroscopic techniques for real time monitoring of bioreactor cell culture processes are highly amendable to PAT approaches to monitor the manufacturing of biotechnology drug products. However, the use of inline Fourier Transform Infrared (FTIR) spectroscopic techniques for bioreactor cell culture process monitoring has not been reported. In this work, real time inline FTIR Spectroscopy is applied to a lab scale bioreactor mAb IgG3 cell culture fluid biomolecular dynamic model. The technical feasibility of using FTIR Spectroscopy for real time tracking and monitoring four key cell culture metabolites (including glucose, glutamine, lactate, and ammonia) and protein yield at increasing levels of complexity (simple binary system, fully formulated media, actual bioreactor cell culture process) is evaluated via a stepwise approach. The FTIR fingerprints of the key metabolites are identified. The multivariate Partial Least Squares (PLS) calibration models have been established to correlate the process FTIR spectra with the concentrations of key metabolites and protein yield of in-process samples, either individually for each metabolite and protein or globally for all four metabolites simultaneously. Applying the 2nd derivative pre-processing algorithm to the FTIR spectra helps to significantly reduce the number of PLS latent variables needed and thus simplify the interpretation of the PLS models. The validated PLS models show promise in predicting the concentration profiles of glucose, glutamine, lactate, and ammonia as well as protein yield over the course of the bioreactor cell culture process. Therefore, the technical feasibility of real time monitoring of the bioreactor cell culture process via FTIR spectroscopy has been  demonstrated in this w

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