Upstream Processing

Disposable pH Sensors

    This paper describes the design, development and validation procedure for a novel, single-use gamma-stable electrochemical pH probe jointly developed by Sartorius Stedim Biotech SA and Metroglas. This new, single-use pH sensor offers a range of pH measurements (from 0 to 11 with ±0.1 precision) and features a one-point calibration process in its storage solution that provides a fast and easy pre- and post-use sensor performance check. Also described is a specific encapsulation device designed to integrate the pH…

Implementing Gamma-Stable RFID Tags in Single-Use Fluid Management Systems

    This paper describes how RFID (Radio Frequency Identification) technologies can be implemented into single-use systems to generate electronic records for both bag manufacturers and bag end-users. RFID technology will enable the user to both read and write all relevant product and process information directly onto the single-use bag, providing instantaneous data recall. The tag can also provide the user with immediate access to the bag’s original part number, lot number, date of manufacture, expiration date and other critical…

A Readily Available Source of BSA Consistently Supports Cultivation and Differential Gene Expression

    Lyme disease caused by the spirochete Borrelia burgdorferi is the leading vector-borne illness in the United States (1). The natural infectious lifecycle of B. burgdorferi is complex in that it is necessary for the bacteria to colonize both an arthropod vector (the Ixodes scapularis tick, pictured right) and a mammalian host (2). As the bacteria transitions between those two diverse niches, it alters the expression of its major outer surface proteins (Osps) such that expression of those that…

Many Considerations in Selecting Bioproduction Culture Media

    Not long ago, the ability to support efficient large-scale culture of cells was the main factor in choice and development of production media. However, a number of new performance demands have been imposed on production media (as listed in the “Key Factors” box). These new criteria arise from such sources as the demand for increased efficiency in a number of production operations, goals invoked by new quality initiatives, and a more science-based approach to process development. Not only…

Many Considerations in Selecting Bioproduction Culture Media

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.

Considering Cell Culture Automation in Upstream Bioprocess Development

Cell culture automation has become more common in drug discovery and research applications, thereby freeing bench scientists from repetitive work as well as improving the consistency of their cell culture processes (1). Mammalian cell culture is used in the production of biopharmaceuticals, where developing a production cell line requires a large amount of repetitive manual work for bench scientists. With the increasing importance of biologics in today’s pharmaceutical market, throughput and efficiency are crucial in developing a production cell line.…

Applying Good Engineering Practices to the Design of Single-Use Systems

Significant changes are being incorporated into biopharmaceutical manufacturing processes as a result of drivers such as increasingly strict regulatory demands, reduction of manufacturing costs, and outsourcing to contract manufacturing organizations (CMOs). Historically, many biopharmaceutical processes were designed and built based on cleanable, reusable stainless steel systems and unit operations. Today several industry drivers are shifting some unit operations toward single-use technologies, namely lowered cross-contamination, reduced capital investments, and desired further reduction in manufacturing costs and shortened drug development times (1,2,3).…

Monitoring ATP Status in the Metabolism of Production Cell Lines

Development of industrial cell culture processes for production of recombinant proteins seeks high efficiency, reproducibility, and predictability. Usually the time allowed for process development is short, during which culture conditions and scale-up protocols must be defined so as to maximize cell productivity and yield while minimizing process scope and overall costs (1). Although scientific literature describes various methods that increase productivity of a cell culture by reducing and arresting cell growth or weakening cell physiology (2), the cells must be…

Achieving High-Efficiency Production with Microbial Technology in a Single-Use Bioreactor Platform

Major efforts are under way to develop new, high-efficiency, cell-based expression systems and flexible low-cost biomanufacturing platforms for biotherapeutics and vaccines to drastically reduce development and manufacturing times. The industry’s enormous growth is driving many of these efforts. The global market for biotherapeutics now stands at $80 billion. Resurgent interest in vaccines is coupled with recent failures in current vaccine manufacturing technologies and the advent of cell-based vaccine manufacturing. The emerging class of follow-on biologics will create additional demand for…

Comparing Mammalian Expression Systems

Almost every pharmaceutical and biopharmaceutical company in the world depends on the use of recombinant stable cell lines to enable drug discovery, development, and often manufacturing of biologics. It normally falls on multidisciplinary upstream development teams to attain this goal, requiring a wide variety of technologies and skill sets such as laboratory robotics, optical analyzers, molecular biology, and data processing. The large capital investment required to procure the equipment and expertise necessary to develop biologics can be cost prohibitive, which…