scholarly journals Online Monitoring and Control of Upstream Cell Culture Process Using 1D & 2D-LC with SegFlow Interface

2021 ◽  
Author(s):  
Letha Chemmalil ◽  
Dhanuka Wasalthanthri ◽  
Xin Zhang ◽  
June Kuang ◽  
Chun Shao ◽  
...  
Keyword(s):  
Cell Culture ◽  
Capital Investment ◽  
Quality By Design ◽  
Integrated System ◽  
Cell Culture Process ◽  
Next Generation ◽  
Monitoring And Control ◽  
Batch Mode ◽  
Knowledge Based ◽  
Online Measurements

The biopharmaceutical industry is transitioning from currently deployed batch-mode bioprocessing to a highly efficient and agile next generation bioprocessing with the adaptation of continuous bioprocessing, which reduces the capital investment and operational costs. Continuous bioprocessing, aligned with FDA’s quality-by-design (QbD) platform, is designed to develop robust processes to deliver safe and effective drugs. With the deployment of knowledge based operations, product quality can be built into the process to achieve desired critical quality attributes (CQAs) with reduced variability. To facilitate next generation continuous bio-processing, it is essential to embrace a fundamental shift-in-paradigm from “quality-by-testing” to “quality-by-design”, which requires the deployment of process analytical technologies (PAT). With the adaptation of PAT, a systematic approach of process and product understanding and timely process control are feasible. Deployment of PAT tools for real-time monitoring of CQAs and feedback control is critical for continuous bioprocessing. Given the current deficiency in PAT tools to support continuous bioprocessing, we have integrated Agilent 2D-LC with a post-flow-splitter in conjunction with the SegFlow automated sampler to the bioreactors. With this integrated system, we have established a platform for online measurements of titer and CQAs of monoclonal antibodies (mAbs) as well as amino acid concentrations of bioreactor cell culture.

scholarly journals The way to a design space for an animal cell culture process according to Quality by Design (QbD)

2011 ◽  
Vol 5 (S8) ◽  
Author(s):  
Robert Puskeiler ◽  
Jan Kreuzmann ◽  
Caroline Schuster ◽  
Katharina Didzus ◽  
Nicole Bartsch ◽  
...  
Keyword(s):  
Cell Culture ◽  
Quality By Design ◽  
Design Space ◽  
Animal Cell ◽  
Animal Cell Culture ◽  
Cell Culture Process ◽  
Culture Process ◽  
The Way

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.

Online Monitoring and Control of Upstream Cell Culture Process Using 1D & 2D‐LC with SegFlow Interface

2021 ◽  
Author(s):  
Letha Chemmalil ◽  
Dhanuka P. Wasalathanthri ◽  
Xin Zhang ◽  
June Kuang ◽  
Chun Shao ◽  
...  
Keyword(s):  
Cell Culture ◽  
Online Monitoring ◽  
Cell Culture Process ◽  
Monitoring And Control ◽  
Culture Process ◽  
And Control

Application of Quality by Design to the characterization of the cell culture process of an Fc-Fusion protein

2012 ◽  
Vol 81 (2) ◽  
pp. 426-437 ◽  
Author(s):  
Yolande Rouiller ◽  
Thomas Solacroup ◽  
Véronique Deparis ◽  
Marco Barbafieri ◽  
Ralf Gleixner ◽  
...  
Keyword(s):  
Cell Culture ◽  
Fusion Protein ◽  
Quality By Design ◽  
Cell Culture Process ◽  
Fc Fusion Protein ◽  
Culture Process

APPLICATION OF AMBR15 MINIBIOREACTORS IN CHARACTERIZATION OF SUSPENSION MONOCLONAL ANTIBODY CHO-PRODUCER CELL CULTURE PROCESS BASED ON QBD PRINCIPLES

2021 ◽  
Vol 1 (19) ◽  
pp. 180-181
Author(s):  
A.N. Morozov ◽  
I.R. Yakhin
Keyword(s):  
Cell Culture ◽  
Monoclonal Antibody ◽  
Monoclonal Antibodies ◽  
Quality By Design ◽  
Systematic Approach ◽  
Cell Culture Process ◽  
Culture Process ◽  
Producer Cell

A systematic approach to characterizing the cell culture process of CHO-producers of monoclonal antibodies within the framework of the concept "Quality by design" (QbD) with the use of ambr15 mini-bioreactors (TAP Biosystems) is shown.

Applying the Quality by Design to Robust Optimization and Design Space Define for Erythropoietin Cell Culture Process

2019 ◽  
Vol 40 (10) ◽  
pp. 1002-1012 ◽  
Author(s):  
Tae Kyu Kim ◽  
Kwang‐Seok Seo ◽  
Sang‐Oh Kwon ◽  
Hee‐Sung Kim ◽  
Jun‐Hee Kim ◽  
...  
Keyword(s):  
Cell Culture ◽  
Robust Optimization ◽  
Quality By Design ◽  
Design Space ◽  
Cell Culture Process ◽  
Culture Process

Miniature Bioreactors for Rapid Bioprocess Development of Mammalian Cell Culture

2012 ◽  
Vol 59 (1) ◽  
Author(s):  
Mohd Helmi Sani ◽  
Frank Baganz
Keyword(s):  
Cell Culture ◽  
Mammalian Cell ◽  
Process Development ◽  
Mammalian Cell Culture ◽  
Small Scale ◽  
Cell Culture Process ◽  
Deep Wells ◽  
Working Volume ◽  
Culture Process ◽  
And Control

At present, there are a number of commercial small scale shaken systems available on the market with instrumented controllable microbioreactors such as Micro–24 Microreactor System (Pall Corporation, Port Washington, NY) and M2P Biolector, (M2P Labs GmbH, Aachen, Germany). The Micro–24 system is basically an orbital shaken 24–well plate that operates at working volume 3 – 7 mL with 24 independent reactors (deep wells, shaken and sparged) running simultaneously. Each reactor is designed as single use reactor that has the ability to continuously monitor and control the pH, DO and temperature. The reactor aeration is supplied by sparging air from gas feeds that can be controlled individually. Furthermore, pH can be controlled by gas sparging using either dilute ammonia or carbon dioxide directly into the culture medium through a membrane at the bottom of each reactor. Chen et al., (2009) evaluated the Micro–24 system for the mammalian cell culture process development and found the Micro–24 system is suitable as scaledown tool for cell culture application. The result showed that intra-well reproducibility, cell growth, metabolites profiles and protein titres were scalable with 2 L bioreactors.

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