BPI White Papers

Single-Use, Continuous-Countercurrent, Multicolumn Chromatography

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Over the past decade, improvements in the biopharmaceutical manufacturing industry have resulted in a dramatic rise in the expression levels from animal cell cultures – some mAb titers have increased 30-fold over the last 15 years. However, increased titers have led to an increase in downstream bottlenecks. To address this challenge, some manufacturers are turning to multicolumn chromatography.

The principles of simulated moving-bed technology can be applied to create a continuous-countercurrent process. The first column in a loading train is allowed to break through, and material coming off it is captured on a second column. Binding capacity can thus be exploited beyond dynamic binding capacity. These processes often significantly improve media use – and hence significantly reduce consumption of media and buffers.

June 1, 2009

A Presanitized, Purpose-Designed, Single-Use TFF Strategy

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As downstream processing accounts for about 70% of the total biomanufacturing cost, it is easy to see why improvements in product recovery and purification are urgently needed. One possible response to this need is the implementation of a single-use TFF process strategy.

Sius “single-use†cassettes provide a unique solution for a cost-effective downstream processing, with measurable cost-in-use savings, while eliminating a significant amount of time performing burdensome clean-in-place (CIP) procedures. This case study outlines the experimental design, development studies, and proposed single-use commercial TFF process based on work performed by Mike LaBreck at Groupe NovaSep.

June 1, 2009

Case Study: Evaluation and Implementation of a Single-Stage Multimedia Harvest Depth Filter for a Large-Scale Antibody Process

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While in the process of transferring to a new manufacturing facility, scientists and engineers at Genentech, Inc. performed small-scale studies to evaluate several candidates for a single-stage depth filter train to accommodate existing equipment at the new facility.

After testing several dual-layer, single-stage filter media, the team chose a robust filter and implemented it at commercial scale. By replacing the traditional two-stage filtration train, they were able to provide significant cost savings relative to piping reconfiguration, new equipment purchase, and new equipment validation. To learn more about the testing methods and results of this study, download the PDF linked below.

June 1, 2009

FlexFactory from Xcellerex – A Proven Biomanufacturing Platform Enabled by Disposables

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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.

May 1, 2009

Development of a High-Capacity MAb Capture Step Based on Cation-Exchange Chromatography

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With new advances in expression vectors, the bioprocessing industry has seen a significant increase in antibody expression levels. To meet the demands of these increased titers, protein A chromatography columns need to be further scaled up in size and/or run in multiple cycles — with a consequent increase in buffer consumption, preparation, and storage. One way to address this problem is to develop other capture steps with high-capacity resins that can replace the protein A step.

This article outlines the methods and materials used to develop a high-capacity capture step using cation-exchange (CEX) chromatography to replace the existing protein A chromatography – making it possible to use existing chromatography hardware and eliminate increases in the buffer volume and holding tank size at existing manufacturing plants. Download the full article as a PDF below.

May 1, 2009

Follow-on Biologics

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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.

May 1, 2009

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

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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.

May 1, 2009

Implementing Cost Reduction Strategies for HuMab Manufacturing Processes

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To keep up with increasing clinical demand, antibody manufacturers are forced to adapt their methods to increase production without increasing costs. In this informative paper, Dr. Arunakumari Alahari, Senior Director of Process Development at Medarex, Inc., discusses several processes that can be implemented to reduce costs of manufacturing, including:

• Perfusion Process for Cell Line Amplification
• Perfusion Process for Cell Bank Preparation
• CHO Production Using In-House Medium
• High Capacity Non-Protein A Purification Processes

Read the full article to discover how innovative technologies and effective regulatory strategies can accelerate process development and reduce time-to-market.

February 1, 2009

Many Considerations in Selecting Bioproduction Culture Media

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Until recently, the ability to support efficient large-scale culture of cells was the main factor in choice and development of production media. But lately the industry has seen a number of new performance demands imposed on production media, such as:

• Support higher growth rates and culture densities
• Promote culture longevity and suppress apoptosis
• Support clone stability in continued passage
• Promote high product yield
• And many more.

Not only is the overall number of criteria growing, but in fact there are users who must consider many different features in specifying their production media. Read this informative paper to learn more about the many functions now desired from production media.

January 1, 2009

Monitoring ATP Status in the Metabolism of Production Cell Lines

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Because the development of industrial cell culture processes for production of recombinant proteins seeks high efficiency, reproducibility and predictability, it is important to have access accurate analytical tools. Although established analytical methods deliver useful data, they are incomplete because they only partially address the cellular metabolic state and also because no predictions can be made.

This paper discusses the process used to establish and evaluate an assay for rapid and reliable online measurement of intracellular ATP (adenoside-5′-triphosphate) to monitor the physiological state of cells in combination with other parameters (cell number, viability, and glucose consumption).

December 1, 2008