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Process analytical technology implementation for protein refolding: GCSF as a case study
Author(s) -
Hebbi Vishwanath,
Thakur Garima,
Rathore Anurag S.
Publication year - 2019
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.26900
Subject(s) - process analytical technology , quality by design , process (computing) , biopharmaceutical , process engineering , computer science , consistency (knowledge bases) , quality (philosophy) , process control , product (mathematics) , statistical process control , process development , biochemical engineering , chemistry , engineering , bioprocess , microbiology and biotechnology , downstream (manufacturing) , mathematics , chemical engineering , artificial intelligence , philosophy , operations management , geometry , epistemology , biology , operating system
Abstract Process analytical technology is gaining interest in the biopharmaceutical industry as a means to enable consistency in processing and thereby in product quality via process control. Protein refolding is known to be significantly impacted by critical process parameters and feed material attributes including composition and pH of the solubilisation and refolding buffers. Hence, to achieve robust process control and product quality, these attributes and parameters need to be monitored. This paper presents an approach towards statistical process control and monitoring of protein refolding, from buffer preparation to refold quenching, during manufacturing of therapeutic proteins from Escherichia coli based systems. The proposed approach utilises measurements of online redox potential, temperature, and pH for development of a statistical model. The model has then been integrated with LabView to permit real‐time monitoring of the refolding process. The proposed system has been demonstrated to successfully identify process deviations and thereby enable process control for manufacturing product of consistent quality.