Bioreactors

Monitoring Live Biomass in Disposable Bioreactors

Often simply referred to as capacitance, radio-frequency (RF) impedance has been used for over two decades to measure online biomass. It is generally regarded as the most robust and reliable method to monitor live-cell concentrations in mammalian cell culture (1). Many biopharmaceutical companies have now made the transition from conventional glass or stainless steel multiuse (MU) vessels to single-use (SU) bioreactors. Disposables are rapidly becoming the preferred platform for new processes requiring current good manufacturing practice (CGMP) compliance. At the…

Using Optical Sensors for Bioprocess Monitoring: A Measurement Technique for Bioprocessors

Over the past decade, the application of chemical optical sensors for bioprocess monitoring has gradually taken roots. Constant further development of this measurement technology and the possibility to manufacture such sensors in various designs (even for single-use applications) have led to new state-of-the-art devices for the biotechnology sector. Chemical optical sensors enable in situ, real-time monitoring of important culture parameters without sampling and therefore without disturbing a culture. Implementing this technology can decrease workloads and deepen knowledge about bioprocesses. In…

Development, Qualification, and Application of a Bioreactor Scale-Down Process: Modeling Large-Scale Microcarrier Perfusion Cell Culture

Qualified scale-down models of large-scale cell culture processes are essential to conducting studies for applications such as investigating manufacturing deviations, enhancing process understanding, and improving process robustness. For example, scale-down models can be used for raw material investigations as well as evaluation and qualification of new good manufacturing practice (GMP) cell banks for manufacturing implementation. Process characterization studies are performed also with qualified scale-down models to improve process consistency (1, 2). Often it is impractical to conduct investigational studies at…

Experiences with a Benchtop-Scale Glass Bioreactor: Engineering Data and Cultivation Results

Animal cell lines (the dominant expression systems in biopharmaceutical production processes) are mostly cultivated in stirred bioreactors (1). Although such bioreactors are widely accepted and applicable over a wide range of scales, engineering data for these systems are still lacking. Nevertheless, studies have shown that the correct choice of key parameters (e.g., power input, tip speed, mixing time, and oxygen mass transfer) can influence the growth of animal cell cultures (2). Therefore, detailed characterization is essential. It enables reliable scaling…

Bioreactor Design for Adherent Cell Culture: The Bolt-On Bioreactor Project, Part 4 — Process Economics

The Bolt-on Bioreactor (BoB) project is an independent initiative developing and commercializing a bioreactor for efficient, automated culture of adherent cells for biopharmaceutical applications (1). After conducting thorough research on available culture systems for adherent cells, the BoB team believes that a successful alternative to existing devices must solve four major challenges: volumetric productivity (2), process automation (3), containment and sterility (4), and process economics. This month concludes a four-part series addressing each of those challenges while describing design features…

Fluid Dynamics of a Single-Use, Stirred-Tank Bioreactor for Mammalian Cell Culture

The benefits of single-use technologies in both upstream and downstream operations are now widely acknowledged by the biopharmaceutical industry, and have led to radical changes in the design and operation of many bioprocesses. Those changes typically provide more robust processes and increased production flexibility. For mammalian cell culture, cleanable multiuse glass or stainless steel stirred-tank reactors (STRs) have been used successfully for growth of suspension-adapted cell lines in both small- and large-scale systems. However, achieving the same or better performance…

Bioreactor Design for Adherent Cell Culture — The Bolt-On Bioreactor Project, Part 3: Containment, Sterility

The Bolt-on Bioreactor (BoB) project is an independent initiative aimed at developing and commercializing a bioreactor for the automated and efficient culture of adherent cells, especially for application in the production of therapeutic cells and other biopharmaceuticals (1). After conducting thorough research on available culture systems for adherent cells, the BoB team believes that a successful alternative to existing devices must answer four major challenges. Addressed in the first article of this series (2), the first challenge has to do…

Bioreactor Design for Adherent Cell Culture: The Bolt-On Bioreactor Project, Part 2 — Process Automation

  The Bolt-on Bioreactor (BoB) project is an independent initiative to develop and commercialize a bioreactor for automated and efficient culture of adherent cells, especially in production of therapeutic cells and other biopharmaceuticals (1). After conducting thorough research on available culture systems for adherent cells, the BoB team believes that a successful alternative to existing devices must solve four major challenges. Addressed in the first installment of this series (2), the first challenge concerns volumetric productivity. The second challenge is…

30 Years of Upstream Productivity Improvements

We recently completed an analysis of the past 30 years of industry progress in commercial-scale expression titers and bioprocessing yields. These basic measures of biopharmaceutical manufacturing efficiency also benchmark the technological progress made in bioprocessing over recent decades. Titer and yield improvements generally indicate related bioprocessing cost savings, something most commercial-scale manufacturers work to improve. This focus on efficiency and productivity has led to constant bioprocessing improvements even for long-approved and -marketed products. Our findings indicate that although upstream titers…

Perfusion’s Role in Maintenance of High-Density T-Cell Cultures

T-cell therapy is a rapidly growing field of personalized medicine, attracting the interest of venture capitalists and pharmaceutical companies alike. Such therapies exploit T cells’ innate abilities to protect against pathogens as well as to seek and destroy cancerous cells. Although many different forms of T-cell therapies are currently in clinical trials, they all follow a common protocol: T cells are isolated from a patient, modified and expanded in a laboratory setting, and then infused back into the same patient…