February 2009 Supplement

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…

Biopharmaceutical Processes: A Glance into the 21st Century

    Biopharmaceutical drug products are not only well established but also contribute to a large degree to new drug entity filings. Currently approved biopharmaceuticals and proteins are now widely used to treat diseases as diverse as cancer, autoimmune disorders, myocardial infarction and various growth factor deficiencies. The unmet medical need can be so essential, such as a novel approach to cancer treatment, that biotech companies will choose to defer the optimal design of the production process to reduce the…

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 Factory or Tailor Made Integration of Single-Use Systems?

    The use of disposables in biopharmaceutical manufacturing has increased significantly during the last few years and is expected to grow substantially in the near future. Bioplan Associates report in their 2007 “Report and Survey of Biopharmaceutical Manufacturing Capacity and Production” that the main drivers for this ongoing trend continue to be the elimination of cleaning followed by the reduction of capital investment in facilities and the required equipment. However, with the further penetration of disposables into larger volumes…

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…

Extractables and Leachables from Single-Use Disposables

Evaluating single-use systems for extractables and leachables is new territory for many end-users. This paper presents a risk-based approach for evaluating extractables and leachables from single-use systems. Approaches are described that have been accepted by various regulatory agencies utilizing risk assessments and sound scientific principles. Biopharmaceutical processing materials must be evaluated to determine whether they impact the final drug product with regard to safety and efficacy. For single-use and reusable systems, this usually leads to evaluations that demonstrate compatibility with…

Implementing Cost Reduction Strategies for HuMab Manufacturing Processes

    The combination of innovative and traditional process technologies has resulted in major advancements in the antibody industry, such as accelerated process development and time-to-market. In addition, this paper examines the avenues that have opened as a result of exploring established process technologies for new applications, as in the case of perfusion cell cultures to amplify dhfr-based expression cell lines by incrementally increasing selection markers in the perfusion medium for the faster generation of stable and high-productivity clones. Furthermore,…

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…

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…

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.…