» BIOTECHNOLOGY
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on increased cell culture growth, the physical characterization of bioreactors regarding mass transfer (especially CO2), mixing, and shear forces becomes more important [33-36]. A renewed focus on traditional engineering principles will be necessary. This will also be important to minimize risks for technology transfers and troubleshoot during technology transfers and process scale-up projects [37]. Expertise in modeling unit operations by Computational Fluid Dynamics and M3C (modeling, monitoring, measurement, and control) of bioprocesses via advanced approaches such as Artificial Neural Networks and Statistical Online Control will be relevant to supporting the next stage of process robustness and reliability [38-40].
Continuous processing trends should be noted. However, to date, only molecules requiring small residence time due to impact on product quality (e.g., Factor VIII, Epoitin, Factor VII, etc.) and specific expression systems have been established in commercial manufacturing processes. Recently, perfusion application in seed train for intermediate storage of large volume starter cultures and increase inoculation cell densities in production scale bioreactors to shorten operation time (subsequently leading to higher facility outputs) have been reported [41-43].
Much progress has been made in establishing reliable supply chains capable of delivering biopharmaceuticals for increasing applications that include numerous oncology and rheumatologic indications. The industry has matured significantly. While much has been achieved, unanswered questions remain. Pressures on the industry, such as the need for new molecular formats in the pipeline, evolving regulatory requirements driven by a desire to benefit from Quality by Design approaches and –most importantly – the need for global access to high quality bio-therapeutics addressing unmet medical needs at competitive costs, will drive the next decade’s achievements.
Author Biographies
Dr. Michael Pohlscheidt is Director of Manufacturing Operations at Genentech, Inc., Oceanside, CA. He received his degree in bioengineering in 2001 from the University of Applied Sciences in Aachen, Germany. His Ph.D. thesis was performed at Bayer HealthCare AG and Bayer Technology Services and guided by the University of Magdeburg, Germany (2005). From 2005 to 2010, he worked in different positions at Pharma Biotech Production & Development, Roche Diagnostics GmbH, Penzberg, Germany.
Dr. Robert Kiss is a Distinguished Engineer and the Director of Late Stage Cell Culture at Genentech, South San Francisco. He has worked in the process development and technical support of cell culture and fermentation processes for more than twenty years in the biopharmaceutical industry. He is a Fellow of the American Institute of Medical & Biological Engineers, and is a licensed professional engineer.
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