Upstream Processing

Maintaining Product Titer While Replacing Undefined Components in a CHO Culture System

    Proteins, hydrolysates, and lysates of plant or yeast origin are commonly used in cell culture media for large-scale manufacturing processes for human biotherapeutics. Lot-to-lot variability in the composition of such constituents is well established and can affect multiple biological performance indicators. Our goal was to replace an undefined, protein-containing medium with a chemically defined medium (meaning the chemical structure and concentration for each component in a formulation is known). Such a formulation should be free of protein and…

Rethinking Media Performance

    Fetal bovine serum (FBS) was — and in many cases still is — the supplement of choice to maintain the viability of mammalian cells in culture. However, there are considerable limitations to its use. In the early days of cell culture, the issues surrounding serum were mainly its variable performance and the potential to contaminate cultures with fungi, viruses, and bacteria. Early attempts to produce a serum-free medium (SFM) were academic exercises that usually relied on the use…

Single-Use Strategies in Bioprocessing

BioProcess International has followed, from the beginning, the ways in which single-use technologies have transformed the landscape of industrial bioprocessing. On 18 March 2009, we organized a panel session at the annual Interphex conference (Jacob Javitz Center, NYC) to drive discussion toward longer-term implications of single-use components and technologies on the future of bioprocessing. Is their use a cost-saving strategy overall? What economic factors are driving their adoption? The panelists were prepared to address such topics as economic considerations in…

Development and Qualification of a Generic IgG Quantification Assay Using Surface Plasmon Resonance

Fast, precise, and accurate quantification technologies are indispensable for efficient process development in applications such as IgG production in a GXP environment. Based on surface plasmon resonance (SPR) technology, the Biacore C system from GE Healthcare (www.biacore.com) is an alternative technology for IgG quantification that has benefits over traditional methods. Assay development is simplified and accelerated due to real-time detection. Assay hands-on time is reduced, and sample throughput can be increased using automation and efficient data evaluation with regulatory-compliant software.…

Development of a Turn-Key Harvest Solution for Small-Volume Bioreactors

Over the past 10 years, disposable bioreactors have grown from a niche tool servicing small-scale projects to a common and essential component in the CGMP production of human therapeutics (1). Recent advances in filter integration, aseptic connectors, and disposable sensing allow entire cell culture processes to be performed using only single-use components. However, harvest and clarification operations remain largely dependent on centrifugation, cross-flow filtration, and depth filtration (2), which are all techniques that have not been widely adapted to single-use…

A Single-Use, Scalable Perfusion Bioreactor System

We have previously described a patented nonsparging, nonbubbling oxygen transfer method (1). This method is based on interaction between the air-exposed smooth surface of a bioreactor vessel and culture medium repeatedly sweeping across it with a certain force, which seems to generate microscopic bubbles among the water molecules (2). We manufactured high–oxygen-transfer Current suspension bioreactors with working volumes of 5 L, 50 L, 150 L, and 300 L. Here we describe the use of these suspension bioreactors as “artificial lungs”…

Automated Liquid Handlers As Sources of Error

Use of automated liquid handling equipment for rapid testing and reproducible screening of thousands of molecules, cells, and compounds has become an essential component of life-science laboratories across the globe. Along with an increase in such use, transferred volumes have shrunk, as demands increase on transfer accuracy and precision when aspirating, diluting, dispensing, mixing, and washing. Automated liquid handlers are generally used to increase the productivity and repeatability of volume transfer, but as discussed here, they are still prone to…

Implementation of Single-Use Technology in Biopharmaceutical Manufacturing

Single-use filtration systems are increasingly replacing traditional stainless steel filter assemblies, piping, and tanks for purification and storage of bioprocess fluids in biopharmaceutical manufacturing. Unfamiliarity with polymeric materials and the need to ensure patient safety, however, have made extractables and leachables from these new components and systems a primary concern of process developers along with specialists in quality, validation, regulatory affairs, as well as agency reviewers. A general risk-based approach to determination of extractables and leachables from disposable bioprocess equipment…

Production of Recombinant Whole-Cell Vaccines with Disposable Manufacturing Systems

Live whole-cell bacterial products have been used as vaccines for many years, and there are currently three such products licensed on the market. Over recent years, however, interest has renewed in this type of product as a delivery system for novel recombinant therapies and vaccines. A number of different organisms have been proposed, such as Escherichia coli and Salmonella species, which might have applicability for such applications. Vaccine applications tend to relate to the potential for low-cost orally delivered products…

FlexFactory from Xcellerex – A Proven Biomanufacturing Platform Enabled by Disposables

FlexFactory from Xcellerex is a biomanufacturing platform that is transforming the way the biotechnology industry approaches drug production. Built almost exclusively around disposables technology, each unit operation within the FlexFactory is self-contained in its own controlled environment module (CEM), effectively shrinking the cleanroom around each operation.

In this on-demand webcast, Parrish Galliher, Founder & Chief Technical Officer of Xcellerex, demonstrates how the FlexFactory eliminates the need for expensive clean-room facilities and CIP/SIP infrastructure, resulting in:
• Reduction in Capital Investment by 50% or More
• 70% Reduction in Start-up Time
• 55% Reduction of Carbon Footprint
• Major reduction of Water Consumption
• Increased Flexibility

FlexFactory is the only biomanufacturing platform that delivers the speed and capital efficiency of the CMO approach with the control and long-term economics of company-controlled manufacturing. View this webcast to gain an in-depth understanding of the benefits of this innovative technology.