Abstract
There is an upsurge of interest in continuous bioprocessing, but currently continuous downstream bioprocessing has not been implemented to generate clinical material. This review focusses on the current state of the art of continuous downstream processing, highlighting the key advantages over traditional batch manufacturing. This allows the identification of scenarios where continuous downstream processing may be critical for commercial manufacturing success.
Similar content being viewed by others
References
Alsaab H, Sau S, Alzhrani R et al (2017) PD-1 and PD-L1 checkpoint signaling inhibition for cancer immunotherapy: mechanism, combinations, and clinical outcome. Front Pharmacol 8:561
Association Alzheimer’s (2016) Alzheimer’s disease facts and figures. Alzheimers Dement 12(4):459–509
Bell D, Dunnill P, Esser K, Flaschel E, Hoare M, Holló J, Kula M-R, Lang-Hinrichs C, Nyeste L, Pécs M, Sevella B (2013) Downstream processing. Springer, New York
Biopharm International, Outsourcing resources 2017
BioPlan White Paper (2015) Continuous bioprocessing: industry demanding more data to make decisions. BioPlan Associates Inc, Rockville
Bisschops M, Brower M (2013) The impact of continuous multicolumn chromatography on biomanufacturing efficiency. Pharm Bioprocess 1(4):361–372
Bisschops M, Frick L, Fulton S, Ransohoff T (2009) Single-use, continuous-countercurrent, multicolumn chromatography. BioProcess Int 7:S18–S23
Boedeker B (2001) Production processes of licensed recombinant factor VIII preparations. Semin Thromb Hemost 27(4):385–394
Boedeker B, Magnus J (2017) Opportunities and limitations of continuous processing and use of disposables. Am Pharm Rev 20(1)
Brower M, Pollard D, Hung F (2015) Protein Refinery Operations Lab (PRO Lab): a sandbox for continuous protein production & advanced process control. Proceedings of integrated continuous biomanufacturing II. http://dc.engconfintl.org/biomanufact_ii/82/
Clapperton R (2001) Practical use of continuous processing in developing and scaling up. Org Process Res Dev 5(6):613–621
Dörner T, Kay J (2015) Biosimilars in rheumatology: current perspectives and lessons learnt. Nat Rev Rheumatol 11(12):713–724
Fletcher H (2010) Turn batch to continuous processing. Manuf Chem 24–26. https://www.manufacturingchemist.com/news/article_page/Turn_batch_to_continuous_processing/54954
Godawat R, Konstantinov K, Rohani M, Warikoo V (2015) End-to-end integrated fully continuous production of mAbs. J Biotechnol 213:13–19
Goudar C, Domach M (2017) Special section on continuous bioprocessing and welcome professor Liu to the editorial board. Biotechnol Progr 33:853
Hammerschmidt N, Tscheliessnig A, Sommer R, Helk B, Jungbauer A (2014) Economics of recombinant antibody production processes at various scales: industry-standard compared to continuous precipitation. Biotechnol J 9:766–775
Hernandez R (2017) Unifying continuous biomanufacturing operations. BioPharm Int 30(6):14–19
Hummel J, Pagkaliwangan M, Gjoka X, Davidovits T, Stock R, Ransohoff T, Gantier R, Schofield M (2018) Modeling the downstream processing of monoclonal antibodies reveals cost advantages for continuous methods for a broad range of manufacturing scales. Biotechnol J. https://doi.org/10.1002/biot.201700665
James F, Leslie W, Heather S, Kate L, Alvydas M, John O, Jeff S (2016) First-inhuman, double-blind, placebo-controlled, single-dose escalation study of aducanumab (BIIB037) in mild-to-moderate Alzheimer’s disease. Alzheimers Dement 2:169–176
Kelley B (2009) Industrialization of mAb production technology. The bioprocessing industry at a crossroads. mAbs 1(5):443–452
Klutz S, Magnus J, Lobedann M, Schwan P, Maiser B, Niklas J, Temming M, Schembecker G (2015) Developing the biofacility of the future based on continuous processing and single-use technology. J Biotechnol 213:120–130
Konstantinov K, Cooney C (2015) White paper on continuous bioprocessing. J Pharm Sci 104(3):813–820
Laird T (2007) Continuous processes in small-scale manufacture. Org Process Res Dev 11(6):927
Lansing SD (1920) The paper machine—its history and future development. Pap Mak J 20:17–21
Levine H, Stock R, Lilja J, Gaasvik A, Hummel H, Ransohoff T, Jones SD (2013) Single-use technology and modular construction. Biopharm International 11(4):40–45
Okazaki T, Honjo T (2006) The PD-1-PD-L pathway in immunological tolerance. Trends Immunol 27:195–201
Ozturk S (2014) Opportunities and challenges for the implementation of continuous processing in biomanufacturing. Wiley, New York
Pearson S (2006) Multiproduct manufacturing facilities: despite contamination and compliance concerns, flexibility remains the key driver. Genet Eng News 26:42–43
Piachaud B (2002) Outsourcing in the pharmaceutical manufacturing process: an examination of the CRO experience. Technovation 22(2):81–90
Poggioli G, Laureti S, Campieri M et al (2007) Infliximab in the treatment of Crohn’s disease. Ther Clin Risk Manag 3(2):301–308
Pollard D, Brower M, Abe Y, Lopes A, Sinclair A (2017) Standardized economic cost modeling for next-generation MAb production. Bioprocess Int 14(8):14–23
Pollard D, Brower M, Richardson D (2018) Progress toward automated single-use continuous monoclonal antibody manufacturing via the protein refinery operations lab. Continuous biomanufacturing—innovative technologies and methods: innovative technologies and methods. Wiley-VCH Verlag GmbH & Co, Weinheim
Pollock J, Coffman J, Ho SV, Farid SS (2017) Integrated continuous bioprocessing: economic, operational, and environmental feasibility for clinical and commercial antibody manufacture. Biotechnol Prog 33(4):854–866
Reay D, Ramshaw C, Harvey A (2008) Process intensification: engineering for efficiency, sustainability and flexibility. Butterworth-Heinemann, Oxford
Steiner R, Jornitz M (2017) Continuous processing in the pharmaceutical industry: status and perspective. Wiley, New York
Thomas H (2008) Batch-to-continuous—coming out of age. Chem Eng 805:38–45
Walther J, Godawat R, Hwang C, Abe Y, Sinclair A, Konstantinov K (2015) The business impact of an integrated continuous biomanufacturing platform for recombinant protein production. J Biotechnol 213:3–12
Warikoo V, Godawat R, Brower K, Jain S, Cummings D, Simons E, Johnson T, Walther J, Yu M, Wright B, McLarty J, Karey K, Hwang C, Zhou W, Riske F, Konstantinov K (2012) Integrated continuous production of recombinant therapeutic proteins. Biotechnol Bioeng 109:3018–3029
Biogen International. https://www.biogen-international.com/en/about-biogen/biogen-international/Solothurn-Biologics-Manufacturing-Facility.html
Zhu M, Mollet M, Hubert R (2012) Industrial production of therapeutic proteins: cell lines, cell culture, and purification. In: Kent J (ed) Handbook of industrial chemistry and biotechnology. Springer, Boston
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Schofield, M. Current state of the art in continuous bioprocessing. Biotechnol Lett 40, 1303–1309 (2018). https://doi.org/10.1007/s10529-018-2593-5
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10529-018-2593-5