In a previous post I described the drivers for, and, benefits from, the trend towards the continuousproduction of biopharmaceutical drugs in which I referenced the article of Veena Warikoo from Genzyme, a Sanofi company, and co-workers published in 2012 on the “Integrated Continuous Production of RecombinantTherapeutic Proteins” (Biotech Bioeng, 2012;109: 3018-3029). Amongst Veena’s contributing authors is Konstantin Konstantinov a key contributor to the literature on continuous bioprocessing and Keynote speaker at the Bioprocess International 2015 Conference with a presentation entitled “What is the Future of Continuous Processing – What is the Time Frame for Implementing Fully Continuous Processing in Commercial Production?"Extending continuous processing downstream to include the capture step
A key concept that the team from Genzyme developed is the integration of continuous chromatography with a perfusion bioreactor for the production of both high volume and stable monoclonal antibodies and low volume, less stable recombinant human enzymes. A 12 L bioreactor was operated for up to 70 days by utilizing the Alternating Tangential Flow (ATF) cell retention technology. The ATF permeate that was harvest was loaded directly onto a periodic counter current (PCC) chromatography system. Systems such as these are now available from a variety of suppliers including GE Healthcare, Pall, Semba and NovaSep. Genzyme were able to operate the PCC system in a fully closed and sterile state for a prolonged period of time.
The benefits of integrating continuous culture with continuous captureAdopting this approach can lead to significant benefits because of the high cell densities and volumetric productivities that can be achieved. This allows significantly smaller bioreactors to be used thereby reducing facility size and capital costs. The ATF system eliminated the need for a more complex harvesting system, however, integration with PCC eliminated the need for large hold tanks, a non-value adding operation, and allowed the capture column to be reduced by a minimum of two-fold.
Improved product quality of less stable proteins
Integration of upstream and downstream operations in this way allows for the continuous flow of product from the bioreactor, through the capture step and into the chromatography eluate and mitigates the risk of product degradation of less stable proteins.
Though the issue of stability may be less of a concern for monoclonal antibodies, the team have created a platform capable of delivering a range of biopharmaceuticals from within a single facility.
What is the Time Frame for Implementing Fully Continuous Processing in Commercial Production?
How would you answer this question? Do you think the industry will see this within 5 years? 10 years? 20 years? Or more?
Dr Nick Hutchinson
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Dr Nick Hutchinson has a Masters and Doctorate in Biochemical Engineering from University College London, UK where he focused on laboratory tools for rapid bioprocess development and characterization. He then worked at Lonza Biologics in an R&D function investigating novel methods for large-scale antibody purification before moving to an operational role scaling-up and transferring manufacturing processes between Lonza sites in the UK, Spain and USA. Nick now works in Market Development at Parker domnick hunter where his focus is in bringing Parker's strengths in Motion & Control to Bioprocessing. This will enable customers to improve the quality and deliverability of existing and future biopharmaceuticals.
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