Process Monitoring and Controls

Single-Use Sensors and Control and Data Acquisition Tools to Streamline Bioprocess Development

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Process development and biomanufacturing in the biopharmaceutical industry have evolved extensively over the past 10 years. More tools are available to study process variables to enable more efficient and productive processes, speed development, and reduce costs. High powered microcontrollers are embedded in laboratory devices to carry out complex tasks. Recently, users have started working with microcontrollers such as Raspberry Pi for personal projects. As personal computer power has accelerated multiplefold,leading to high processing power and compact, high-capacity memory readily available…

October 4, 2018

Big Biotech Data: Implementing Large-Scale Data Processing and Analysis for Bioprocessing

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Managing large amounts of data presents biopharmaceutical companies of all sizes with the need to adopt more efficient ways to handle the ongoing influx of information. At KNect365’s September 2017 Cell and Gene Therapy conference in Boston, Lisa Graham (founder and chief executive officer of Alkemy Innovation, Inc. in Bend, OR) spoke about the need for data management, data analysis, and process monitoring systems to evolve. Although she was speaking at a cell therapy event, her points are applicable to…

September 15, 2018

In-Line Turbidity Sensors for Monitoring Process Streams in Continuous Countercurrent Tangential Chromatography (CCTC)

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A strong connection between turbidity and total suspended solids (TSS) has been linked in the past to measuring well defined particles in processes. Optical density probes have seen wide adoption in the biotechnology industry for monitoring cell growth within a bioreactor, whereas in-line turbidity sensors have been used to monitor filter performance. Turbidity measurements offer a rapid quantification of suspended solids but have not been used in the biotechnology industry for chromatographic resins. In this study, turbidity measured with equipment developed by PendoTECH was used with novel continuous chromatography technology developed by Chromatan…

September 15, 2018

Advanced Control Strategies at Biotech Week Boston

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Attendees at this year’s Biotech Week Boston (24–28 September) had the opportunity to participate in several preconference symposia on the first day, including one on advanced control strategies for bioprocessing and biomanufacturing. Chaired by William Whitford (GE Healthcare), the session included presentations from Dan Kopec (Sartorius Stedim Data Analytics), Markus Gershater (Synthace), Jonathan Bones (National Institute for Bioprocessing), Robert Thomas (Loughborough University), Chris McCready (Sartorius Stedim Data Analytics), and Victor Konakovsky (Newcastle University). BPI has collaborated with conference organizer KNect365…

November 17, 2017

Integrated PAT Automated Feedback Control of Critical Process Parameters Using Modern In Situ Analytics

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Simply put, the best way to control a critical process parameter (CPP) is to measure that specific parameter, integrate the live signal into your control system, and apply a smart feedback algorithm for an automated control loop. The challenge in doing this for bioprocesses has been due, in part, to the complex, highly dynamic, and variable nature of the process along with the lack of robust, scalable, and multiformat (single-use or multiuse) technologies that can monitor (in real time) such…

November 17, 2017

Accelerating Process Development Through Flexible Automated Workflows

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Synthace began as a bioprocess optimization company in 2011, spun out of University College, London. The company worked on multifactorial approaches with 15–30 factors simultaneously instead of seven or eight. The work investigated genetic strain engineering factors alongside process parameters, defining deep interactions between the way strains were designed and the way they were treated in bioprocesses. Those complex experiments gave unique insight into the complexities of biological processes, but they were exceptionally taxing to plan and carryout manually. Automation…

November 17, 2017

Model Predictive Control for Bioprocess Forecasting and Optimization

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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…

November 17, 2017

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

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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…

November 17, 2017

Regulating Quality in Continuous Processing

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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…

June 27, 2016

NIR Spectroscopy for Process Monitoring and Control in Mammalian Cell Cultivation

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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…

September 1, 2013