Upstream Processing

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…

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…

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…

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.

Follow-on Biologics

This webcast will describe the key steps in developing a CHO culture process for manufacturing a follow-on biologic. Analytical characterization of 14 lots of the commercial product provided information about the range in key product quality attributes of the marketed drug. The scientists at SP-Diosynth have developed a process that yields a product that is analytically comparable to the commercially available molecule. Product quality attributes investigated were aggregation, acidic and basic variants, galactose, sialic acid and fucose content, and complement dependent cytotoxicity activity.

Scalability of the process was demonstrated in 100L stainless steel bioreactors and a 50L single use bioreactor (SUB). The webcast shows SP-Dionsyth’s data indicated that the process generates high titer at scale consistently while achieving product quality similar to the commercial material.

With this on-demand webcast, you will gain valuable insight into aspects of SP-Disoyth’s process development, such as:

• Cell Line Characteristics
• Scalability
• Manufacturability
• Comparability
• Commercializability

The webcast features Sigma S. Mostafa, Ph.D.

Microbial Expression Technology: The New Standard For Protein Expression – Addressing Speed, Quality and Cost of Goods

A new paradigm of microbial strain development has been achieved that overcomes today’s slow, iterative and error-prone process through the use of a novel, streamlined, high throughput platform. The P. fluorescens expression platform, Pfēnex Expression Technology™, reliably delivers host strains expressing large amounts of high quality target protein within very short development times. In this webcast, Dr. Charles H. Squires, Head of Discovery R&D at Pfēnex Inc., discusses:

• An Overview of Pfēnex Expression Technology™
• How Pfēnex Inc. Practices the Technology
• Case Studies Highlighting the Power of the Technology
• Product Areas
• Further Uses of Pfēnex Expression Technology™in Development

Join Dr. Squires as he illustrates how the combination of technologies available through the Pfēnex Expression Technology™system make it the most complete, flexible and productive bacterial strain development and biopharmaceutical production platform available today.

Scaling Up a CHO-Produced Hormone–Protein Fusion Product

    Many biotechnology companies recognize the powerful benefits of increasing product titer early in product development as a strategy to minimize manufacturing costs, scale, and the duration necessary to produce clinical supplies and achieve product commercialization. Additional benefits include minimizing or completely avoiding significant regulatory delays to market that can be caused by major process technology changes (such as cell line and product quality changes). Recently, another significant benefit has been realized too: Smaller, more productive and efficient 2,000-L…

Assay Validation for Rapid Detection of Mycoplasma Contamination

Mycoplasmas and related bacteria in the class Mollicutes are parasitic organisms found not only on the external surfaces of a wide range of eukaryotic host cells, but also intracellularly. They are characterized by small size and lack of a rigid cell wall, which gives them resistance to β-lactam antibiotics and the ability to pass through 0.2-µm filters (1,2). Contamination by Mollicutes is a common problem for cell cultures that is not easily detected because it usually does not produce turbidity…