Upstream Single-Use Technologies

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…

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…

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…

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…

Guide to Irradiation and Sterilization Validation of Single-Use Bioprocess Systems

Single-use bioprocess manufacturing systems increasingly are being implemented by the biopharmaceutical industry based on safety, time, and cost-reduction benefits. These disposable systems are used to process or contain fluids ranging from culture media, additives, and buffers, to bulk intermediates and final formulations. In many cases microbial control or sterility is required to ensure product purity and safety. Radiation sterilization is a common means of microbial control and sterilization applied to single-use systems. The standard methods for validating radiation sterilization are…

Comparing Shaker Flasks with a Single-Use Bioreactor for Growing Yeast Seed Cultures

Pichia pastoris is a species of methylotrophic yeast that is widely used for protein expression both in academia and the biotechnology industry. A number of properties make it suited for this task (1). Pichia has a high growth rate, and it can grow on simple, inexpensive media. It can also be grown in either shaker flasks or bioreactors, which makes it suitable for both small-and large-scale protein production. PRODUCT FOCUS: Yeast-expressed recombinant proteinsPROCESS FOCUS: ProductionWHO SHOULD READ: Manufacturing and process…

Recommendations for Extractables and Leachables Testing

Extractables and leachables from disposable manufacturing systems must be addressed as part of process validation. Extractables are compounds that can migrate from a material into a solvent under exaggerated conditions of time and temperature. Leachables are compounds that actually do migrate into a drug product formulation under normal processing conditions. All materials have extractables and potentially have leachables. When properly evaluated, both are easily addressed and rarely lead to disqualification of a disposable component. PRODUCT FOCUS: ALL BIOLOGICSPROCESS FOCUS: MANUFACTURINGWHO…