Compared to small molecule process analytical technology （PAT） applications, biotechnology product PAT applications have certain unique challenges and opportunities. Understanding process dynamics of bioreactor cell...Compared to small molecule process analytical technology （PAT） applications, biotechnology product PAT applications have certain unique challenges and opportunities. Understanding process dynamics of bioreactor cell culture process is essential to establish an appropriate process control strategy for biotechnology product PAT applications. Inline spectroscopic techniques for real time monitoring of bioreactor cell culture process have the distinct potential to develop PAT approaches in manufac- turing 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 was 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） was evaluated via a stepwise approach. The FTIR fingerprints of the key metabolites were identified. The multivariate partial least squares （PLS） calibration models were 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 2＇ld derivative pre-processing algorithm to the FTIR spectra helps to reduce the number of PLS latent variables needed significantly 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 and protein yield over the course of the bioreactor cell culture process. Therefore, this work demonstrated the technical feasibility of real time monitoring of the bioreactor cell culture process via FTIR spectroscopy. Its implications for enabling cell culture PAT were discussed.展开更多
SCADA (Supervisory Control and Data Acquisition) is concerned with gathering process information from industrial control processes found in utilities such as power grids, water networks, transportation, manufacturing,...SCADA (Supervisory Control and Data Acquisition) is concerned with gathering process information from industrial control processes found in utilities such as power grids, water networks, transportation, manufacturing, etc., to provide the human operators with the required real-time access to industrial processes to be monitored and controlled either locally (on-site)or remotely (i.e., through Internet). Conventional solutions such as custom SCADA packages, custom communication protocols, and centralized architectures are no longer appropriate for engineering this type of systems because of their highly distribution and their uncertain continuously changing working environments. Multi-agent systems (MAS) appeared as a new architectural style for engineering complex and highly dynamic applications such as SCADA systems. In this paper, we propose an approach for simply developing flexible and interoperable SCADA systems based on the integration of MAS and OPC process protocol. The proposed SCADA system has the following advantages: 1) simple (easier to be implemented);2) flexible (able to adapt to its environment dynamic changes);and 3) interoperable (relative to the underlying control systems, which belongs to diverse of vendors). The applicability of the proposed approach is demonstrated by a real case study example carried out in a paper mill.展开更多
文摘Compared to small molecule process analytical technology （PAT） applications, biotechnology product PAT applications have certain unique challenges and opportunities. Understanding process dynamics of bioreactor cell culture process is essential to establish an appropriate process control strategy for biotechnology product PAT applications. Inline spectroscopic techniques for real time monitoring of bioreactor cell culture process have the distinct potential to develop PAT approaches in manufac- turing 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 was 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） was evaluated via a stepwise approach. The FTIR fingerprints of the key metabolites were identified. The multivariate partial least squares （PLS） calibration models were 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 2＇ld derivative pre-processing algorithm to the FTIR spectra helps to reduce the number of PLS latent variables needed significantly 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 and protein yield over the course of the bioreactor cell culture process. Therefore, this work demonstrated the technical feasibility of real time monitoring of the bioreactor cell culture process via FTIR spectroscopy. Its implications for enabling cell culture PAT were discussed.
文摘SCADA (Supervisory Control and Data Acquisition) is concerned with gathering process information from industrial control processes found in utilities such as power grids, water networks, transportation, manufacturing, etc., to provide the human operators with the required real-time access to industrial processes to be monitored and controlled either locally (on-site)or remotely (i.e., through Internet). Conventional solutions such as custom SCADA packages, custom communication protocols, and centralized architectures are no longer appropriate for engineering this type of systems because of their highly distribution and their uncertain continuously changing working environments. Multi-agent systems (MAS) appeared as a new architectural style for engineering complex and highly dynamic applications such as SCADA systems. In this paper, we propose an approach for simply developing flexible and interoperable SCADA systems based on the integration of MAS and OPC process protocol. The proposed SCADA system has the following advantages: 1) simple (easier to be implemented);2) flexible (able to adapt to its environment dynamic changes);and 3) interoperable (relative to the underlying control systems, which belongs to diverse of vendors). The applicability of the proposed approach is demonstrated by a real case study example carried out in a paper mill.
