Process Monitoring and Controls

Model Predictive Control for Bioprocess Forecasting and Optimization

Automation hierarchy in bioprocess manufacturing consists of a regulatory layer, process analytics technology (PAT), and (potentially) a top-level model-predictive or supervisory layer. The regulatory layer is responsible for keeping typical process measurements such as temperature, pressure, flows, and pH on target. In some cases, spectral instrumentation in combination with multivariate analysis (MVA) can be configured to measure parameters such as glucose concentration. A cascade control structure can be set up when the nutrient flow setpoint is adjusted to maintain the…

CO2, O2, and Biomass Monitoring in Escherichia coli Shake Flask Culture: Following Glucose–Glycerin Diauxie Online

Carbon dioxide (CO2) is an important parameter in microbial cultures because it can inhibit or stimulate growth under certain conditions. In our experiment, we monitored Escherichia coli diauxie growth phases online and focused on dissolved CO2 (dCO2) and oxygen readings. We assessed diauxic growth in medium containing glycerin and glucose online with the SFR vario system (from PreSens), which optically measures oxygen, pH, and biomass in an Erlenmeyer flask. The shake flask contained an oxygen sensor spot and an optical…

Regulating Quality in Continuous Processing

Regardless of the industry and product being manufactured, continuous processing has demonstrated numerous benefits. In addition to smaller manufacturing footprints, reduced material consumption and waste generation, increased efficiencies, and lower capital and operating costs continuous manufacturing typically leads to more consistent processes and product quality. In the pharmaceutical industry, the latter two attributes align perfectly with FDA’s Quality by Design (QbD) and process analytical technology (PAT) initiatives. The challenge is determining how to apply these concepts in practice. Applying the…

NIR Spectroscopy for Process Monitoring and Control in Mammalian Cell Cultivation

The quality by design (QbD) and process analytical technology (PAT) approaches have shown significant benefit in the classical pharmaceutical industry and are now strongly influencing bioprocessing. Monitoring critical process parameters (CPPs) during biotechnological cell cultivations is essential to maintaining high efficiencies and quality. Commercial sensor systems for real-time inline monitoring are available for some parameters, such as pH or the concentration of dissolved oxygen (DO). For others such as glucose concentration, total cell count (TCC), and viability no robust online…