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Downstream Processing Technologies/Capturing and Final Purification

Opportunities for Innovation, Change, and Improvement. A Review of Downstream Processing Developments in Protein Purification

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Book cover New Bioprocessing Strategies: Development and Manufacturing of Recombinant Antibodies and Proteins

Part of the book series: Advances in Biochemical Engineering/Biotechnology ((ABE,volume 165))

Abstract

Increased pressure on upstream processes to maximize productivity has been crowned with great success, although at the cost of shifting the bottleneck to purification. As drivers were economical, focus is on now on debottlenecking downstream processes as the main drivers of high manufacturing cost. Devising a holistically efficient and economical process remains a key challenge. Traditional and emerging protein purification strategies with particular emphasis on methodologies implemented for the production of recombinant proteins of biopharmaceutical importance are reviewed. The breadth of innovation is addressed, as well as the challenges the industry faces today, with an eye to remaining impartial, fair, and balanced. In addition, the scope encompasses both chromatographic and non-chromatographic separations directed at the purification of proteins, with a strong emphasis on antibodies. Complete solutions such as integrated USP/DSP strategies (i.e., continuous processing) are discussed as well as gains in data quantity and quality arising from automation and high-throughput screening (HTS). Best practices and advantages through design of experiments (DOE) to access a complex design space such as multi-modal chromatography are reviewed with an outlook on potential future trends. A discussion of single-use technology, its impact and opportunities for further growth, and the exciting developments in modeling and simulation of DSP rounds out the overview. Lastly, emerging trends such as 3D printing and nanotechnology are covered.

Workflow of high-throughput screening, design of experiments, and high-throughput analytics to understand design space and design space boundaries quickly. (Reproduced with permission from Gregory Barker, Process Development, Bristol-Myers Squibb)

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Acknowledgments

The authors would like to thank Yan Yao, Ph.D., Associate Director, Bristol-Myers Squibb, and Gregory Barker, Ph.D., Senior Engineer, Bristol-Myers Squibb for their critical review and feedback. The authors would also like to thank Professor Giorgio Carta, Ph.D., School of Engineering and Applied Sciences, University of Virginia, Arch Creasy, graduate student at the School of Engineering and Applied Sciences, University of Virginia, and aforementioned colleagues Gregory Barker and Yan Yao for the generous permission to reproduce Fig. 6, and Gregory Barker for the generous provision of Fig. 4.

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  1. Bristol-Myers Squibb, Global Manufacturing and Supply, Devens, MA, 01434, USA

    Nripen Singh

  2. Bristol-Myers Squibb, Global Manufacturing and Supply, Hopewell, NJ, 01434, USA

    Sibylle Herzer

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Correspondence to Nripen Singh .

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  1. Sutro Biopharma Inc., San Francisco, CA, USA

    Bob Kiss

  2. Lonza, Basel, Switzerland

    Uwe Gottschalk

  3. Solothurn Manufacturing Facility, Biogen International GmbH, Luterbach, Switzerland

    Michael Pohlscheidt

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Singh, N., Herzer, S. (2017). Downstream Processing Technologies/Capturing and Final Purification. In: Kiss, B., Gottschalk, U., Pohlscheidt, M. (eds) New Bioprocessing Strategies: Development and Manufacturing of Recombinant Antibodies and Proteins. Advances in Biochemical Engineering/Biotechnology, vol 165. Springer, Cham. https://doi.org/10.1007/10_2017_12

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