Upstream Development

A Bioreactor System Based on a Novel Oxygen Transfer Method

Bioreactor technologies for mammalian cell culture may seem quite sophisticated (1). In fact, efficient mammalian cell culture is simple and requires just two major elements: mixing and oxygen (O2) transfer. Traditional methods for mixing use an impellor, and the classical O2 transfer method features a sparging stone that expels air bubbles to increase the O2 transfer surface area in contact with a culture medium. Mammalian cells are sensitive to shear forces and also to the toxicity of pure or enriched…

A Review of Therapeutic Protein Expression By Mammalian Cells

During the past five years, many biopharmaceuticals have found their way into clinical trials and commercial production (1–4). So far, about 60 million patients worldwide have benefited from these new drugs. The market for biopharmaceuticals was estimated at US$33 billion in 2004 and projected to reach US$70 billion by the end of the decade. During the period 2003–2006, regulators in Europe and the United States approved 32 biopharmaceuticals for human use, including hormones and growth factors, therapeutic enzymes, vaccines, and…

An Emerging Star for Therapeutic and Catalytic Protein Production

Since the 1980s launch of the first recombinant-DNA–sourced protein insulin, the 1990s introduction of interferons and interleukins, and the first commercial approval of MAbs around the turn of the century, the therapeutic protein market has shown a very healthy growth of 15–19% (Figure 1). Between 1980 and 2004, about 300 antibodies and 400 other recombinant proteins entered clinical trials, totaling about 750 products (1). Figure 1: () A survey of biopharmaceutical production technologies in 2005 shows that Chinese hamster ovary…

Automated Closed-Loop Solution for Bioreactors and Fermentors

Today, there is much discussion regarding the promise of improved insight into bioprocess industry processes. Look to the pages of industry publications such as this one, and you’ll see that industry leaders in process measurement and control have begun to discuss openly the potential for simulating and modeling bioprocesses. “Important opportunities such as the application of mass spectrometers, dissolved carbon dioxide probes, and inferential measurements of metabolic processes have come to fruition today opening the door to more advanced process…

Moving On in Cell Culture

Record-breaking titer outputs in mammalian cell culture systems in the past few years have pushed the industry to a new crisis of sorts: resolving the downstream bottleneck. However, the cell culture and fermentation groups at biopharmaceutical companies aren’t yet ready to sit back and rest on their laurels. Instead, they are moving forward, tackling the downstream issue with upstream modifications and continuing their drive for more cost-efficient processing. The Cell Culture and Upstream Processing track will focus on cell culture…

Cutting Down Process Time and Costs

Because the biopharmaceutical industry operates as an industry rather than a nonprofit, the bottom line is an important consideration in every aspect of product design. From laboratory automation methods that speed discovery to streamlined manufacturing processes that incorporate the themes of operational excellence, Lean manufacturing, and quality by design, the industry is undeniably focused on minimizing cost and maximizing revenue. At the BioProcess International European Conference and Exhibition, the Scale-Up and Manufacturing track will focus on economic strategy and technology…

High-Throughput Process Development

Increasing pipelines, shorter timelines, talent scarcity, reduced budgets — all these are issues faced by companies working in today’s biotechnology environment. The ultimate goal of a process development team is to stay off the “critical path” to drug approval. But how do they complete the necessary work to create a robust manufacturing process in light of such pressures? To increase the effectiveness of development, many companies are turning to high-throughput technologies within their development platforms. Such technologies promise that scientists…

The Biopharmaceutical Industry’s New Operating Paradigm

Currently the biopharmaceutical industry is transitioning to a new business model of production efficiency through implementing operational excellence (Op Ex). Borrowing from such principles as “lean manufacturing” and “Six Sigma” (6σ), and incorporating quality by design (QbD) (1), Op Ex is being applied through the implementation of such advanced enabling concepts and technologies as quality risk management (QRM) (2), process analytical technology (PAT) (3), and systems biology (SB) (4). Some people see a conflict here: This paradigm shift is occurring…

Automated Closed-Loop Solution for Bioreactors and Fermentors

Today, there is much discussion regarding the promise of improved insight into bioprocess industry processes. Look to the pages of industry publications such as this one, and you’ll see that industry leaders in process measurement and control have begun to discuss openly the potential for simulating and modeling bioprocesses. “Important opportunities such as the application of mass spectrometers, dissolved carbon dioxide probes, and inferential measurements of metabolic processes have come to fruition today opening the door to more advanced process…

PAT Tools for Accelerated Process Development and Improvement

Broadley-James Corporation, Emerson Process Management, and the University of Texas at Austin are working together to examine and quantify the potential for faster optimization of batch operating points, process design, and cycle times. We’re also looking for more reproducible and predictable batch endpoints. The objective of this effort is to show that the impact of PAT can be maximized through the integration of dynamic simulation and multivariate analytics in a laboratory-optimized control system during product development. Data from bench-top and…