Upstream Single-Use Technologies

Demonstrated Performance of a Disposable Bioreactor with an Anchorage-Dependent Cell Line

    Increased adoption of disposable storage vessels and mixing systems for biopharmaceutical manufacturing operations has provided economic and efficiency benefits to a number of life-science companies. Single-use technologies have reduced validation requirements, shortened turnaround times, eliminated cleaning regimes, increased the speed of set-up procedures, and facilitated the development of flexible manufacturing platforms. Many biomanufacturers have sought to extend those benefits into the field of cell culture by using disposable bioreactors. Here we describe work undertaken to develop and demonstrate…

Using Disposables in Cell-Culture–Based Vaccine Production

    A recent private grant of US$10 billion for human vaccine applications illustrates the revival of interest in vaccine science (1). The 2009 response by vaccine manufacturers to the H1N1 pandemic revealed the convergence of three technological developments. First is a revolution in technology: Vaccines are being developed for diverse and unprecedented applications through a number of entirely new approaches. Second is the recent adoption of cultured cell-based production for a growing number of vaccines, such as influenza. And…

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”…

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…

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…

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 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…

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…

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…