Manufacturing

Advanced Control Strategies at Biotech Week Boston

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…

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

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…

Accelerating Process Development Through Flexible Automated Workflows

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…

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…

Data Analysis and Visualization to Improve Biopharmaceutical Operations Part 1: What Are You Trying To Measure?

This begins a five-article series of “how-to” guides for tackling the most common obstacles in assessing, measuring, analyzing, and improving the performance of global biopharmaceutical manufacturing operations. Each installment covers a component of proper collection, analysis, and use of data for the best possible performance outcomes. When taken as a whole, the series should provide imperative best practices for handling business-performance data. First, consider what you want to know about your bioprocesses. How can you more appropriately measure those data…

Antibody–Drug Conjugates: Fast-Track Development from Gene to Product

In the fight against cancer, antibody–drug conjugates (ADCs) represent an increasingly important therapeutic approach. These biopharmaceuticals are designed to maximize the therapeutic index of cytotoxic small-molecule drugs through their selective delivery to tumor cells while leaving normal, healthy cells untouched. Structurally, an ADC is a monoclonal antibody (MAb) conjugated by a chemical linker to a potent cytotoxic drug. Conceptually, the MAb serves as the delivery component, targeting a specific tumor antigen that ideally is not expressed (or is expressed at…

Particulate Contamination in Single-Use Systems: Challenges of Detection, Measurement, and Continuous Improvement

Patients receiving particulate contamination through parenteral delivery of biopharmaceuticals presents a significant potential health risk. However, the severity of that risk often is unclear. It depends on the route of administration, dosage volume administered, particle properties and amount received, and the ultimate fate of particles within a patient’s body (1). The appearance of particulate contamination also can be a visible indicator of product quality. Consequently, when such contamination is discovered within biopharmaceutical manufacturing operations, often it triggers costly investigations and…

Viral Vector Particle Integrity and Purity Analyses in Early Process Development

Gene therapy is the transfer of genetic material to a patient’s cells to achieve a therapeutic effect. Therapeutic DNA typically is delivered using a viral vector system, and adenoviruses have been used for this purpose for over 20 years (1–3). Within the past 10 years or so, lentiviruses have shown promise in clinical trials (1–3), and adenoassociated viruses (AAVs) have been used in the first approved gene therapies in the Western world (4). The number of gene therapy applications based…

The 2017 World Biological Forum: Successes and Future Trends in Continuous Biomanufacturing

Continuous biomanufacturing was a central topic at the fourth annual World Biological Forum in Oxford, UK, on 26–28 June 2017. A well-rounded lineup of presenters appeared at this forum held in Oxford University’s Lady Margaret Hall, an eclectic location that well captured the historic charm of the university. Delegates were well supported throughout the meeting with generous meals, refreshments, and assistance provided by helpful staff. Papers were presented in Talbot Hall in the center of the college. The stately main…