Multi-attribute PAT for UF/DF of Proteins—Monitoring Concentration, particle sizes, and Buffer Exchange

@article{Rolinger2020MultiattributePF,
  title={Multi-attribute PAT for UF/DF of Proteins—Monitoring Concentration, particle sizes, and Buffer Exchange},
  author={Laura Rolinger and Matthias R{\"u}dt and Juliane Diehm and Jessica Chow-Hubbertz and Martin Heitmann and S Schleper and J{\"u}rgen Hubbuch},
  journal={Analytical and Bioanalytical Chemistry},
  year={2020},
  volume={412},
  pages={2123-2136}
}
Ultrafiltration/diafiltration (UF/DF) plays an important role in the manufacturing of biopharmaceuticals. Monitoring critical process parameters and quality attributes by process analytical technology (PAT) during those steps can facilitate process development and assure consistent quality in production processes. In this study, a lab-scale cross-flow filtration (CFF) device was equipped with a variable pathlength (VP) ultraviolet and visible (UV/Vis) spectrometer, a light scattering photometer… 
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References

SHOWING 1-10 OF 51 REFERENCES
Process monitoring of virus‐like particle reassembly by diafiltration with UV/Vis spectroscopy and light scattering
TLDR
The proposed experimental setup provides a powerful platform for developing and monitoring VLP reassembly steps by CFF and showed that off‐line size‐exclusion chromatography does not provide a complete picture of the particle content.
Real‐time monitoring and control of the load phase of a protein A capture step
TLDR
Partial Least Squares Regression modeling on UV/Vis absorption spectra was applied to quantify mAb in the effluent of a Protein A capture step during the load phase, which might enhance the resin capacity utilization, eliminate time‐consuming offline analytics, and contribute to the realization of continuous processing.
Combined Dynamic Light Scattering and Raman Spectroscopy Approach for Characterizing the Aggregation of Therapeutic Proteins
TLDR
A new instrument is described that measures protein secondary and tertiary structure, as well as molecular size, over a range of concentrations and formulation conditions of low volume samples, and mechanistic insights for aggregation are obtained from the application of this technique to the characterization of lysozyme.
Application of process analytical technology for downstream purification of biotherapeutics
TLDR
This article presents a review of PAT applications for monitoring commonly used downstream biotech unit operations and focuses on recent advancements (last 5 years).
Advances in inline quantification of co‐eluting proteins in chromatography: Process‐data‐based model calibration and application towards real‐life separation issues
TLDR
The presented process‐data‐based PLS model calibration in combination with the tool for selective inline quantification has a great potential for the monitoring of future chromatography steps and may contribute to manage batch‐to‐batch variability by real‐time pooling decisions.
Ultrafiltration behavior of partially retained proteins and completely retained proteins using equally‐staged single pass tangential flow filtration membranes
TLDR
This work presents the first body of data for partially and completely retained solutes together in the SPTFF mode and provides a strategy to increase protein concentration at higher feed flow rates.
A tool for selective inline quantification of co‐eluting proteins in chromatography using spectral analysis and partial least squares regression
TLDR
A powerful integration of software and chromatography hardware will be introduced that enables the applicability of this methodology for a selective inline quantification of co‐eluting proteins in chromatography to make product purity‐based real‐time pooling decisions.
...
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