Chemometrics in bioprocess engineering: process analytical technology (PAT) applications

Multifrequency permittivity measurements enable on‐line monitoring of changes in intracellular conductivity due to nutrient limitations during batch cultivations of CHO cells

“…This shift can be characterized by the move of quality control key aspects from laboratory-based to process-based locations, that is, off-line to at-line/on-line. 2,3 On-line monitoring is furthermore critical to build better process models and develop reliable, well-controlled processes in a shorter period of time. 4 One of the most important parameters to monitor in any cell culture process is the viable, that is, metabolically active biomass.…”

Real time phase detection based online monitoring of batch fermentation processes

“…While searching through the parameter space, the following values for these parameters have been considered regardless of the organism: d [0, 4,8,12,16], t [5,10,15,20] min, j [4,5,6,7,8] and h [2,3,4,5,6,7,8]. We first construct the receiver operating characteristic (ROC) curve for all possible models (i.e.…”

“…These measurements are expensive, labor intensive and time consuming, are obtained at low frequencies (e.g., every few hours) at pre-defined intervals and hence, may not always lead to timely information about the status of the batch. Further, in some processes, the product formation begins only towards the later parts of the batch and this leads to additional difficulty in adequately monitoring the process using these offline measurements [3]. Fermentors are typically equipped with several on-line sensors such as pH, temperature, concentrations of dissolved oxygen (DO) and carbon dioxide and partial pressure of oxygen and carbon dioxide in the exhaust gas.…”

Model-based computer-aided framework for design of process monitoring and analysis systems

“…Introduction 2 considered as a landmark in the acceptance of process systems engineering tools in modern pharmaceutical manufacturing and quality assurance of food and drug production processes. In terms of process monitoring, the use of PAT represents a paradigm shift in the sense that sophisticated quality control moves from laboratory-based to process-based (i.e., in-process) approaches (Lopes et al, 2004). The availability of real time monitoring tools and its efficient utilization are two prerequisites to shift from the traditional labcentric production approach to the PAT inspired approach.…”