Analytical

eBook: Addressing Quality in Cell-Line Development — Direct Analysis of Bioreactor Harvest for Clone Selection and Process Optimization

Using Direct Analysis of Bioreactor Harvest for Clone Selection and Process Optimization Therapeutic monoclonal antibodies (MAbs) mostly are manufactured using bioengineered mammalian cells cultured in a bioreactor for two to three weeks. High temperatures and an altered redox environment may compromise the quality of MAbs produced (e.g., fragmentation, truncation), as can the presence of proteases, reductases, and other chemicals released from dead cells. Thus, it would be valuable to establish analytical methods that can help cell culture groups monitor immunoglobulin…

An Approach to Generating Better Biosimilars: Considerations in Controlling Glycosylation Variability in Protein Therapeutics

The global market for biotherapeutics has expanded extensively over the past decade and is projected to account for more than a quarter of the pharmaceutical market by 2020, with sales exceeding US$290 billion (1). Continued expansion of the biosimilar marketplace has led to many commercial opportunities and technical challenges. The biological systems used to manufacture such drug products are inherently variable — a feature that has important consequences for the reproducibility, safety, and efficacy of the resulting products. Therefore, a…

eBook: Of Microbrews and Medicines — Understanding Their Similarities and Differences in Bioprocessing Can Help Improve Yields and Quality While Reducing Cost

Meeting a biopharmaceutical scientist or engineer who proclaims a love for brewing is not surprising. Perhaps it’s because of the challenge of mixing raw ingredients together and waiting patiently for the final product, maybe it’s the hands-on nature of the equipment or the data analytics entertainment, or it just might be the simple joy of creating something. Whatever attracts a scientist or engineer to making medicines and/or craft brews, a surprising number of principles hold true for both bioprocesses despite…

eBook: Bioinks for Bioprinting — Three-Dimensional Printing in Research and Medicine

Three-dimensional (3D) printing is one method of digital biomanufacturing for both basic biological research and translational, clinical applications. The medical field has used it to create such constructions as 3D surgical models for preoperative planning, to assist surgeons in their procedure preparations, which improves postsurgical outcomes. Examples here include generation of cleft-palate models (1), orthopedic applications (2), and cardiovascular surgical planning (3). Other forms of 3D printing for biological applications — such as 3D bioprinting — go beyond such surgical…

Implementation of the BPOG Extractables Testing Protocols: Working with Multiple Single-Use Components

Single-use technologies offer significant advantages over traditional stainless-steel solutions for biopharmaceutical manufacturing. Reductions in setup times, cleaning and cleaning-validation costs, elimination of cross-contamination risks, and smaller footprints are just some of the benefits they provide. Although adoption of single-use systems (SUS) for commercial manufacturing is expanding, concerns persist that extractable and leachable (E&L) compounds from plastic SUS components potentially can leach into final drug products and compromise efficacy and safety. Those concerns are magnified amid the growing number of SUS…

Simplify Upstream Process Development and Scale-Up: Single-Use 5:1 Turndown-Ratio Bioreactor Technology

Single-use technologies (SUTs) have been adopted widely in the biopharmaceutical industry for product development as well as clinical- and commercial-scale manufacturing. Over the years, suppliers of such equipment have addressed concerns about waste management, extractables and leachables, and reliability of supply — and as a result, end users have gained confidence in SUTs. Recognizing potential benefits that can be realized for both clinical and commercial operations, biomanufacturers increasingly are implementing SU solutions at larger scales in both upstream production and…

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…