Upstream Processing

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…

Bridging the Gap from Reusable to Single-Use Manufacturing with Stirred, Single-Use Bioreactors

    During the past few years, use of disposable bioreactors in development and manufacturing processes has become widely accepted. Particularly, low–oxygen-demanding cell types such as human and insect cells have proven to be perfectly suitable for cultivation in single-use bag chambers. These bioreactors have significant advantages over their reusable counterparts (1). They transform a single-purpose process using stainless steel reactors into a multipurpose facility in which switching from one application to another is both easy and cost effective. Reusable…

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…

Medium and Process Optimization for High Yield, High Density Suspension Cultures: From Low Throughput Spinner Flasks to High Throughput Millilitre Reactors

    The most important contributions to high-yield manufacturing processes for the production of recombinant proteins from cultivated mammalian cells have come from the identification of highly enriched and well-balanced media formulations, and fine tuning the process conditions that support high cell culture densities with high specific productivity. The industry standard yield for immunoglobulins or similar molecules derived from suspension-cultivated mammalian cells in bioreactors has risen during the past 20 years from the tens of mg/L to g/L. The more…

Disposable Bioreactors in Cell Culture-Based Upstream Processing

    During the last 10 years, cost pressures and the changing requirements for bioreactors in the modern pharmaceutical industry have resulted in the increased use of disposable bioreactors in both R&D and manufacturing. Numerous studies have demonstrated their efficiency in cell culture-based upstream processing at small- and middle-volume scales. As shown in Figure 1, disposable bioreactors with culture volumes between 10 mL and 2 m3 are most widely used for cell proliferation, screening experiments, the production of therapeutic agents…

Non-Invasive Sensors as Enablers of “Smart” Disposables

    Disposable bioprocessing has come of age. Economic and regulatory conditions are driving the widespread adoption of disposable equipment at all stages of bioprocessing. This review considers the entire bioprocess chain and assesses the status of disposables. In particular, we focus on the current availability and need for additional sensors that will enable the disposable process to be integrated — in compliance — with the latest Process Analytical Technologies. Traditional bioprocessing is highly compartmentalized into upstream and downstream operations.…

Better Positioned Than Ever

    In June 2007, Sartorius AG acquired the French company, Stedim S.A., and a global solution provider for the biopharmaceutical industry was created. Since then, the new company — Sartorius Stedim Biotech (SSB) — has entered into collaborations with a number of other key industry players, including Metroglas, Bayer Technology Services GmbH and the recently acquired Wave Biotech AG to bring technologies such as single-use bioreactors, UVC irradiation and the first disposable–integrated electrochemical pH sensor into its rapidly expanding…