Premium
Integrated continuous production of recombinant therapeutic proteins
Author(s) -
Warikoo Veena,
Godawat Rahul,
Brower Kevin,
Jain Sujit,
Cummings Daniel,
Simons Elizabeth,
Johnson Timothy,
Walther Jason,
Yu Marcella,
Wright Benjamin,
McLarty Jean,
Karey Kenneth P.,
Hwang Chris,
Zhou Weichang,
Riske Frank,
Konstantinov Konstantin
Publication year - 2012
Publication title -
biotechnology and bioengineering
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.136
H-Index - 189
eISSN - 1097-0290
pISSN - 0006-3592
DOI - 10.1002/bit.24584
Subject(s) - biomanufacturing , bioprocess , bioreactor , process engineering , continuous production , process analytical technology , biochemical engineering , batch processing , computer science , process (computing) , chemistry , microbiology and biotechnology , biology , chemical engineering , engineering , organic chemistry , programming language , operating system
In the current environment of diverse product pipelines, rapidly fluctuating market demands and growing competition from biosimilars, biotechnology companies are increasingly driven to develop innovative solutions for highly flexible and cost‐effective manufacturing. To address these challenging demands, integrated continuous processing, comprised of high‐density perfusion cell culture and a directly coupled continuous capture step, can be used as a universal biomanufacturing platform. This study reports the first successful demonstration of the integration of a perfusion bioreactor and a four‐column periodic counter‐current chromatography (PCC) system for the continuous capture of candidate protein therapeutics. Two examples are presented: (1) a monoclonal antibody (model of a stable protein) and (2) a recombinant human enzyme (model of a highly complex, less stable protein). In both cases, high‐density perfusion CHO cell cultures were operated at a quasi‐steady state of 50–60 × 10 6 cells/mL for more than 60 days, achieving volumetric productivities much higher than current perfusion or fed‐batch processes. The directly integrated and automated PCC system ran uninterrupted for 30 days without indications of time‐based performance decline. The product quality observed for the continuous capture process was comparable to that for a batch‐column operation. Furthermore, the integration of perfusion cell culture and PCC led to a dramatic decrease in the equipment footprint and elimination of several non‐value‐added unit operations, such as clarification and intermediate hold steps. These findings demonstrate the potential of integrated continuous bioprocessing as a universal platform for the manufacture of various kinds of therapeutic proteins. Biotechnol. Bioeng. 2012; 109: 3018–3029. © 2012 Wiley Periodicals, Inc.