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In‐Line Monitoring of Protein Concentration With MIR Spectroscopy During UFDF

Milewska, Adrianna, Baekelandt, Géraldine, Boutaieb, Sarra, Mozin, Vitalii, Falconbridge, Andrew·2023·Engineering in Life Sciences
DOI 10.1002/elsc.202200050PMC PMC9893749
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Abstract

Rapid increase of product titers in upstream processes has presented challenges for downstream processing, where purification costs increase linearly with the increase of the product yield. Hence, innovative solutions are becoming increasingly popular. Process Analytical Technology (PAT) tools, such as spectroscopic techniques, are on the rise due to their capacity to provide real‐time, precise analytics. This ensures consistent product quality and increased process understanding, as well as process control. Mid‐infrared spectroscopy (MIR) has emerged as a highly promising technique within recent years, owing to its ability to monitor several critical process parameters at the same time and unchallenging spectral analysis and data interpretation. For in‐line monitoring, Attenuated Total Reflectance—Fourier Transform Infrared Spectroscopy (ATR‐FTIR) is a method of choice, as it enables reliable measurements in a liquid environment, even though water absorption bands are present in the region of interest. Here, we present MIR spectroscopy as a monitoring tool of critical process parameters in ultrafiltration/diafiltration (UFDF). MIR spectrometer was integrated in the UFDF process in an in‐line fashion through a single‐use flow cell containing a single bounce silicon ATR crystal. The results indicate that the one‐point calibration algorithm applied to the MIR spectra, predicts highly accurate protein concentrations, as compared with validated offline analytical methods.

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  • ATR-FTIR has been implemented in-line during the UFDF step to monitor protein concentration with a simple one-point calibration algorithm or both protein and various excipient concentrations with a multivariate data analysis model.

    “Recently, ATR‐FTIR has also been implemented in‐line during the UFDF step, to monitor the protein concentration with a simple one‐point calibration algorithm [55] or both protein and various excipient concentrations, with a multi‐variate data analysis (MVDA) model [56].”

    From Current PAT Landscape in the Downstream Processing of Biopharmaceuticals (2025) · cites this paper as [55]

  • In ATR-FTIR monitoring during UFDF, rapid measurements in seconds and accurate concentration predictions were achieved.

    “In both cases, rapid measurements in seconds and accurate concentration predictions were achieved.”

    From Current PAT Landscape in the Downstream Processing of Biopharmaceuticals (2025) · cites this paper as [55]

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Cited by

Sorted by citations

Authors
Milewska, A., Baekelandt, G., Boutaieb, S., Mozin, V., & Falconbridge, A.
Affiliations
  • Alvotech Reykjavík Iceland
  • IRUBIS GmbH München Germany
Venue
Engineering in Life Sciences
Publisher
Wiley
Published
2022-12-23
Volume
23
Issue
2
ISSN
  • 1618-0240
  • 1618-2863
DOI
10.1002/elsc.202200050
PMC
PMC9893749
Cited by
17
References
1
Language
en
Licence
creativecommons.org/licenses/by/4.0/ (vor)

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