Strategic framework for education and training in Quality by Design (QbD) and process analytical technology (PAT)

2016 ◽  
Vol 90 ◽  
pp. 2-7 ◽  
Author(s):  
Marcel de Matas ◽  
Thomas De Beer ◽  
Staffan Folestad ◽  
Jarkko Ketolainen ◽  
Hans Lindén ◽  
...  
Keyword(s):  
Quality By Design ◽  
Process Analytical Technology ◽  
Education And Training ◽  
Strategic Framework ◽  
Analytical Technology ◽  
And Training

Process Analytical Technology and Quality by Design for Animal Cell Culture

2019 ◽  
pp. 365-390
Author(s):  
Hae‐Woo Lee ◽  
Hemlata Bhatia ◽  
Seo‐Young Park ◽  
Mark‐Henry Kamga ◽  
Thomas Reimonn ◽  
...  
Keyword(s):  
Cell Culture ◽  
Quality By Design ◽  
Process Analytical Technology ◽  
Animal Cell ◽  
Animal Cell Culture ◽  
Analytical Technology

scholarly journals Advances in monitoring and control of refolding kinetics combining PAT and modeling

2021 ◽  
Vol 105 (6) ◽  
pp. 2243-2260
Author(s):  
Jan Niklas Pauk ◽  
Janani Raju Palanisamy ◽  
Julian Kager ◽  
Krisztina Koczka ◽  
Gerald Berghammer ◽  
...  
Keyword(s):  
Real Time ◽  
Quality By Design ◽  
Process Analytical Technology ◽  
Waste Product ◽  
High Yield ◽  
Monitoring And Control ◽  
Batch Mode ◽  
And Control ◽  
Analytical Technology ◽  
Refolding Kinetics

Abstract Overexpression of recombinant proteins in Escherichia coli results in misfolded and non-active protein aggregates in the cytoplasm, so-called inclusion bodies (IB). In recent years, a change in the mindset regarding IBs could be observed: IBs are no longer considered an unwanted waste product, but a valid alternative to produce a product with high yield, purity, and stability in short process times. However, solubilization of IBs and subsequent refolding is necessary to obtain a correctly folded and active product. This protein refolding process is a crucial downstream unit operation—commonly done as a dilution in batch or fed-batch mode. Drawbacks of the state-of-the-art include the following: the large volume of buffers and capacities of refolding tanks, issues with uniform mixing, challenging analytics at low protein concentrations, reaction kinetics in non-usable aggregates, and generally low re-folding yields. There is no generic platform procedure available and a lack of robust control strategies. The introduction of Quality by Design (QbD) is the method-of-choice to provide a controlled and reproducible refolding environment. However, reliable online monitoring techniques to describe the refolding kinetics in real-time are scarce. In our view, only monitoring and control of re-folding kinetics can ensure a productive, scalable, and versatile platform technology for re-folding processes. For this review, we screened the current literature for a combination of online process analytical technology (PAT) and modeling techniques to ensure a controlled refolding process. Based on our research, we propose an integrated approach based on the idea that all aspects that cannot be monitored directly are estimated via digital twins and used in real-time for process control. Key points • Monitoring and a thorough understanding of refolding kinetics are essential for model-based control of refolding processes. • The introduction of Quality by Design combining Process Analytical Technology and modeling ensures a robust platform for inclusion body refolding.

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