Cell cycle and apoptosis in PER.C6® cultures

Mercier, Sarah M.; Diepenbroek, Bas; Martens, Dirk E.; Wijffels, René H.; Streefland, Mathieu

doi:10.1186/1753-6561-7-s6-p48

Cited by 2 publications

(2 citation statements)

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“…Real-time process control using statistically designed experiments requires multivariate analysis tools to analyze data from multidimensional databases (Mercier, Diepenbroek, Wijffels, & Streefland, 2014). To develop a predictive model using multivariate analysis, establishing an interrelationship between process and product is essential (Sokolov et al, 2017).…”

Section: Introductionmentioning

confidence: 99%

Online/at‐line measurement, analysis and control of product titer and critical product quality attributes (CQAs) during process development

Chemmalil¹,

Prabhakar

Kuang³

et al. 2020

Biotech & Bioengineering

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Process analytical technology (PAT) has been defined by the Food and Drug Administration as a system for designing, analyzing, and controlling manufacturing through timely measurements to ensure final product quality. Based on quality-by-design (QbD) principles, real-time or near-real-time data monitoring is essential for timely control of critical quality attributes (CQAs) to keep the process in a state of control. To facilitate nextgeneration continuous bioprocessing, deployment of PAT tools for real-time monitoring is integral for process understanding and control. Real-time monitoring and control of CQAs are essential to keep the process within the design space and align with the guiding principles of QbD. The contents of this manuscript are pertinent to the online/at-line monitoring of upstream titer and downstream product quality with timely process control. We demonstrated that an ultra-performance liquid chromatography (UPLC) system interfaced with a UPLC-process sample manager (UPLC-PSM) can be utilized to measure titer and CQAs directly from bioreactors and downstream unit operations, respectively. We established online titer measurements from fed-batch and perfusion-based alternating tangential flow bioreactors as well as product quality assessments of downstream operations for real-time peak collection. This integrated, fully automated system for online data monitoring with feedback control is designed to achieve desired product quality.

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Section: Introductionmentioning

confidence: 99%

Online/at‐line measurement, analysis and control of product titer and critical product quality attributes (CQAs) during process development

Chemmalil¹,

Prabhakar

Kuang³

et al. 2020

Biotech & Bioengineering

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“…Mid-IR spectroscopy and MVDA approach includes initial construction of a chemometric model for a given attribute with the use of training set data (Mercier, Diepenbroek, Wijffels, & Streefland, 2014;Tobyn, Ferreira, Morris, & Menezes, 2018). Upon construction and optimization of the model, it is possible to use it for the prediction of the attribute based on the spectroscopic measurements (Mercier et al, 2014;Tobyn et al, 2018). The specificity of Mid-IR spectroscopic signal corresponds to the unique bond vibrations in the molecule of interest.…”

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confidence: 99%

Real‐time monitoring of quality attributes by in‐line Fourier transform infrared spectroscopic sensors at ultrafiltration and diafiltration of bioprocess

Wasalathanthri

Feroz

Puri

et al. 2020

Biotech & Bioengineering

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Technologies capable of monitoring product quality attributes and process parameters in real time are becoming popular due to the endorsement of regulatory agencies and also to support the agile development of biotherapeutic pipelines. The utility of vibrational spectroscopic techniques such as Fourier transform midinfrared (Mid-IR) and multivariate data analysis (MVDA) models allows the prediction of multiple critical attributes simultaneously in real time. This study reports the use of Mid-IR and MVDA model sensors for monitoring of multiple attributes (excipients and protein concentrations) in real time (measurement frequency of every 40 s) at ultrafiltration and diafiltration (UF/DF) unit operation of biologics manufacturing. The platform features integration of fiber optic Mid-IR probe sensors to UF/DF set up at the bulk solution and through a flow cell at the retentate line followed by automated Mid-IR data piping into a process monitoring software platform with pre-loaded partial least square regression (PLS) chemometric models. Data visualization infrastructure is also built-in to the platform so that upon automated PLS prediction of excipients and protein concentrations, the results were projected in a graphical or numerical format in real time. The Mid-IR predicted concentrations of excipients and protein show excellent correlation with the offline measurements by traditional analytical methods. Absolute percent difference values between Mid-IR predicted results and offline reference assay results were ≤5% across all the excipients and the protein of interest; which shows a great promise as a reliable process analytical technology tool.

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Cell cycle and apoptosis in PER.C6® cultures

Cited by 2 publications

References 0 publications

Online/at‐line measurement, analysis and control of product titer and critical product quality attributes (CQAs) during process development

Online/at‐line measurement, analysis and control of product titer and critical product quality attributes (CQAs) during process development

Real‐time monitoring of quality attributes by in‐line Fourier transform infrared spectroscopic sensors at ultrafiltration and diafiltration of bioprocess

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