Upstream Processing

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…

Cell-line/Process Development – BPI Theater @ BIO 2015

Ray Price (senior director of business development, DiscoveRx) 3:30–3:55 pm Advances in Research Tools to Accelerate Drug Development Price introduced the BioSeek drug-discovery platform with examples. The technology is built on three pillars: primary human cells; models that use growth factors or cytokines to model a disease environment and then predict how drugs change biomarker responses in those systems; and comparisons of generated profiles with a reference database of more than 4,000 compounds. DiscoveRx uses that database and informatics tools…

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…

BioProcess Theater: Cell-Line and Process Development

Process development forms the core of BioProcess International’s coverage and interests. From cell-line engineering through seed-train and production cultures, the results of which are harvested and purified to yield a bulk drug substance, every biologic therapy and vaccine begins its life at small scale in a research and development laboratory.Cell lines may be mammalian, insect, microbial, or even plant-sourced (1). They all require different types of culture media and supplements. And purification options are many and diverse. Process intermediates are…

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…

Single-Use Processing for Microbial Fermentations

During the past decade, single‑use bioprocessing has emerged as a standard platform for current good manufacturing practice (CGMP) mammalian cell culture. Biomanufacturers have come to appreciate the benefits of lower capital and operating costs, reduced contamination risk, continuity from early development through manufacturing, flexibility, and sustainability (1). Disposable cell‑culture vessels have gained wide acceptance because their performance duplicates that of stainless‑steel, fixed‑tank bioreactors, with which manufacturers have extensive experience. This is no accident: Single‑use bioreactors use stainless–steel engineering principles, particularly…

Culture Media and Protein Expression From Conversations with William G. Whitford

As part of BPI’s “Ask the Expert” series, editorial advisor William G. Whitford (senior technical market manager for GE Healthcare Life Sciences) spoke with editor-in-chief Anne Montgomery and marketing and digital content strategist Leah Rosin on two separate occasions about issues related to culture media and expression titers. Sourcing Serum-Free Media Anne discussed cell culture media and process fluids with Bill in March 2014. Whitford: Things are advancing, and the industry is changing significantly. In general, we are using more…

A Novel Seed-Train Process: Using High-Density Cell Banking, a Disposable Bioreactor, and Perfusion Technologies

A typical cell culture process begins with thawing of a cryopreserved cell-bank vial, followed by successive expansions into larger culture vessels such as shake flasks, spinners, Wave bags, and stirred bioreactors (1). When culture volume and cell density meet predetermined criteria, the culture is transferred to a production bioreactor in which cells continue to grow and express product. This approach presents several challenges. Shake flasks or spinners used in the initial stages require manual manipulations inside a laminar flow hood,…

Culturing a Duck ES-Derived Cell Line in Single-Use Bioreactors: A Rapid, Efficient, and Cost-Effective Vaccine Manufacturing System Based on Suspension Culture

Cell substrates managed in controlled culture environments have become, over the past few decades, the subject of intensive technological developments for the biomanufacturing of viral vaccines. The driving force of such work is an expanding demand for safety, high production capacities, cost savings, and flexibility. Egg, tissue, and primary-cell–based manufacturing methods of limited capacity are now considered to be outdated technologies. In the influenza vaccine field, for example, time delays in vaccine delivery (especially during pandemic responses) have increased concerns…

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…