Sunday, February 1, 2009 Daily Archives

The Maturation of the Biomanufacturing Industry

    In my opening editorial, I referred to an industry in transition. This is being driven by challenges that are by no means unique to biotech: all other industry sectors are experiencing similar pressures. We are seeing the impact in terms of factory design, manufacturing technologies, validation and business processes; these are all themes that have been addressed in this supplement. The big innovation in terms of manufacturing systems has been the wholesale acceptance of disposable manufacturing technologies during…

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.…

Purifying a Recalcitrant Therapeutic Recombinant Protein with a Mixed-Mode Chromatography Sorbent

Mixed-mode chromatography sorbents can save time and money by reducing the number of steps required to purify recombinant proteins. They also have the potential to purify proteins that single-mode sorbents cannot. As the term mixed mode suggests, these sorbents contain ligands that offer multiple modes of interaction. Although mixed-mode sorbents are used extensively in solid-phase extraction for high-pressure liquid chromatography (HPLC) sample preparation — and to a more limited extent in analytical HPLC — these resins are generally unsuitable for…

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…

Rapid Purification of Lys-C from Cultures

Endoproteases specific for cleavage of peptidyl bonds on the C-terminal side of lysine residues (e.g., Lys-C) are produced from a number of bacterial species, including Achromobacter lyticus (1), Pseudomonas aeruginosa (2), and Lysobacter enzymogenes (3). The Achromobacter protease 1 (API) protein has been substantially characterized (4,5,6) and shown to be a resilient enzyme that can specifically cleave after lysine residues under a wide range of buffer conditions, including high concentrations of denaturing agents such as urea and sodium dodecyl sulphate…

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…

Environmental Impact of Single-Use and Reusable Bioprocess Systems

    Bioprocess manufacturing systems have incorporated single-use/disposable components for more than 50 years and have demonstrated well-defined process benefits from their use (1,2,3,4,5,6). The environmental impact of single-use technologies, however, has been a major focus of attention only in recent years. This evolving interest has been driven by many factors including concerns over environmental change, emissions, and energy supplies; rapidly increasing costs and restrictions on waste disposal; greater recognition of the role of disposables in bioprocessing; and availability of…

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…

Of Mice and Men…

Few US industries demonstrate preeminent creative and financial world leadership year in and year out, but we can think of two that look forward to continuing blockbusters that will provide mountains of new cash followed by consistent follow-on revenues. In both arenas, an idea is calculated to be something that people everywhere will want, so it is launched with a huge bolus of cash and a cash burn that almost takes its company to the brink. Both industries capitalize on…

An Industry in Transition

As an industry, biopharmaceutical manufacturing is in transition and is facing challenges borne out of success. It was in the early 1980s that the first products were commercialized, namely the replacement hormones insulin and human growth hormone. The industry initially grew rapidly in the early ‘80s against a background of an immature supply industry: there were no large-scale columns (>10 cm diameter), column controllers, limited resin supplies and no established ultrafiltration technology. The position today is that the industry has…