Multi‐Attribute PAT for UF/DF of Proteins—Monitoring Concentration, Particle Sizes, and Buffer Exchange
Abstract
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, and a liquid density sensor (microLDS). Based on the measured signals, the protein concentration, buffer exchange, apparent molecular weight, and hydrodynamic radius were monitored. The setup was tested in three case studies. First, lysozyme was used in an UF/DF run to show the comparability of on-line and off-line measurements. The corresponding correlation coefficients exceeded 0.97. Next, urea-induced changes in protein size of glucose oxidase (GOx) were monitored during two DF steps. Here, correlation coefficients were ≥ 0.92 for static light scattering (SLS) and dynamic light scattering (DLS). The correlation coefficient for the protein concentration was 0.82, possibly due to time-dependent protein precipitation. Finally, a case study was conducted with a monoclonal antibody (mAb) to show the full potential of this setup. Again, off-line and on-line measurements were in good agreement with all correlation coefficients exceeding 0.92. The protein concentration could be monitored i…
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A variable pathlength UV-Vis spectrometer has been utilized for the in-line monitoring of protein concentration during UFDF on a lab scale.
“A variable pathlength UV‐Vis spectrometer has already been utilized for the in‐line monitoring of protein concentration during the UFDF on a lab scale [82].”
From Current PAT Landscape in the Downstream Processing of Biopharmaceuticals (2025) · cites this paper as [82]
Cites
A critical review of methods for size characterization of non-particulate protein aggregates
Philo, J. (2009) · Current Pharmaceutical Biotechnology · doi:10.2174/138920109788488815 · Cited by 196 · see citing works
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Wasalathanthri, D. P., Rehmann, M. S., Song, Y., Gu, Y., Mi, L., Shao, C., Chemmalil, L., Lee, J., Ghose, S., Borys, M. C., et al. (2020) · Biotechnology and Bioengineering · doi:10.1002/bit.27461 · Cited by 177 · see citing works
Goldrick, S., Umprecht, A., Tang, A., Zakrzewski, R., Cheeks, M., Turner, R., Charles, A., Les, K., Hulley, M., Spencer, C., et al. (2020) · Processes · doi:10.3390/pr8091179 · Cited by 48 · see citing works
Current PAT Landscape in the Downstream Processing of Biopharmaceuticals
Sathiyapriyan, P., Mukherjee, S., Vogel, T., Essen, L., Boerema, D., Vey, M., & Kalina, U. (2025) · Analytical Science Advances · doi:10.1002/ansa.70013 · Cited by 45 · see citing works
Continuous integrated manufacturing for biopharmaceuticals: A new paradigm or an empty promise?
Rathore, A. S., Thakur, G., & Kateja, N. (2023) · Biotechnology and Bioengineering · doi:10.1002/bit.28235 · Cited by 41 · see citing works
- Authors
- Rolinger, L., Rüdt, M., Diehm, J., Chow-Hubbertz, J., Heitmann, M., Schleper, S., & Hubbuch, J.
- Venue
- Analytical and Bioanalytical Chemistry
- Published
- 2020-02-18
- Volume
- 412
- Issue
- 9
- Pages
- 2123-2136
- ISSN
- 1618-2642
- 1618-2650
- Cited by
- 45
- References
- 1
- Language
- en
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