A new flow cell and chemometric protocol for implementing in-line Raman spectroscopy in chromatography.
PAT
Raman spectroscopy
chromatography
downstream processing
flow cell
Journal
Biotechnology progress
ISSN: 1520-6033
Titre abrégé: Biotechnol Prog
Pays: United States
ID NLM: 8506292
Informations de publication
Date de publication:
09 2019
09 2019
Historique:
received:
19
03
2019
revised:
08
05
2019
accepted:
15
05
2019
pubmed:
18
5
2019
medline:
25
6
2020
entrez:
18
5
2019
Statut:
ppublish
Résumé
On-line monitoring tools for downstream chromatographic processing (DSP) of biotherapeutics can enable fast actions to correct for disturbances in the upstream, gain process understanding, and eventually lead to process optimization. While UV/Vis spectroscopy is mostly assessing the protein's amino acid composition and the application of Fourier transform infrared spectroscopy is limited due to strong water interactions, Raman spectroscopy is able to assess the secondary and tertiary protein structure without significant water interactions. The aim of this work is to implement the Raman technology in DSP, by designing an in-line flow cell with a reduced dead volume of 80 μL and a reflector to increase the signal intensity as well as developing a chemometric modeling path. In this context, measurement settings were adjusted and spectra were taken from different chromatographic breakthrough curves of IgG1 in harvest. The resulting models show a small average RMSEP of 0.12 mg/mL, on a broad calibration range from 0 to 2.82 mg/mL IgG1. This work highlights the benefits of model assisted Raman spectroscopy in chromatography with complex backgrounds, lays the fundamentals for in-line monitoring of IgG1, and enables advanced control strategies. Moreover, the approach might be extended to further critical quality attributes like aggregates or could be transferred to other process steps.
Substances chimiques
Recombinant Proteins
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e2847Informations de copyright
© 2019 American Institute of Chemical Engineers.
Références
Rathore AS, Bhambure R, Ghare V. Process analytical technology (PAT) for biopharmaceutical products. Anal Bioanal Chem. 2010;398(1):137-154. https://doi.org/10.1007/s00216-010-3781-x.
Simon LL, Pataki H, Marosi G, et al. Assessment of recent process analytical technology (PAT) trends: a multiauthor review. Org Process Res Dev. 2015;19(1):3-62. https://doi.org/10.1021/op500261y.
Rathore AS, Kapoor G. Application of process analytical technology for downstream purification of biotherapeutics. J Chem Technol Biotechnol. 2015;90(2):228-236. https://doi.org/10.1002/jctb.4447.
Roch P, Mandenius CF. On-line monitoring of downstream bioprocesses. Curr Opin Chem Eng. 2016;14:112-120. https://doi.org/10.1016/j.coche.2016.09.007.
Rüdt M, Briskot T, Hubbuch J. Advances in downstream processing of biologics-spectroscopy: an emerging process analytical technology. J Chromatogr A. 2017;1490:2-9.
Mendhe R, Thukkaram M, Patil N, Rathore AS. Comparison of PAT based approaches for making real-time pooling decisions for process chromatography-use of feed forward control. J Chem Technol Biotechnol. 2015;90(2):341-348. https://doi.org/10.1002/jctb.4448.
Fahrner RL, Lester PM, Blank GS, Reifsnyder DH. Real-time control of purified product collection during chromatography of recombinant human insulin-like growth factor-I using an on-line assay. J Chromatogr A. 1998;827(1):37-43. https://doi.org/10.1016/S0021-9673(98)00778-X.
Steinebach F, Ulmer N, Wolf M, et al. Design and operation of a continuous integrated monoclonal antibody production process. Biotechnol Prog. 2017;33(5):1303-1313. https://doi.org/10.1002/btpr.2522.
Krättli M, Steinebach F, Morbidelli M. Online control of the twin-column countercurrent solvent gradient process for biochromatography. J Chromatogr A. 2013;1293:51-59. https://doi.org/10.1016/J.CHROMA.2013.03.069.
Wen ZQ. Raman spectroscopy of protein pharmaceuticals. J Pharm Sci. 2007;96(11):2861-2878. https://doi.org/10.1002/jps.20895.
Jiskoot W, Crommelin D. Methods for Structural Analysis of Protein Pharmaceuticals. American Association of Pharmaceutical Scientists; 2005.
Rüdt M, Brestrich N, Rolinger L, Hubbuch J. Real-time monitoring and control of the load phase of a protein A capture step. Biotechnol Bioeng. 2017;114(2):368-373. https://doi.org/10.1002/bit.26078.
Capito F, Skudas R, Kolmar H, Hunzinger C. Mid-infrared spectroscopy-based antibody aggregate quantification in cell culture fluids. Biotechnol J. 2013;8(8):912-917. https://doi.org/10.1002/biot.201300164.
Capito F, Skudas R, Kolmar H, Stanislawski B. Host cell protein quantification by fourier transform mid infrared spectroscopy (FT-MIR). Biotechnol Bioeng. 2013;110(1):252-259. https://doi.org/10.1002/bit.24611.
Capito F, Skudas R, Kolmar H, Hunzinger C. At-line mid infrared spectroscopy for monitoring downstream processing unit operations. Process Biochem. 2015;50(6):997-1005. https://doi.org/10.1016/j.procbio.2015.03.005.
Whelan J, Craven S, Glennon B. In situ Raman spectroscopy for simultaneous monitoring of multiple process parameters in mammalian cell culture bioreactors. Biotechnol Prog. 2012;28(5):1355-1362. https://doi.org/10.1002/btpr.1590.
Berry BN, Dobrowsky TM, Timson RC, Kshirsagar R, Ryll T, Wiltberger K. Quick generation of Raman spectroscopy based in-process glucose control to influence biopharmaceutical protein product quality during mammalian cell culture. Biotechnol Prog. 2016;32(1):224-234. https://doi.org/10.1002/btpr.2205.
Buckley K, Ryder AG. Applications of Raman spectroscopy in biopharmaceutical manufacturing: a short review. 2017;71(6):1085-1116. https://doi.org/10.1177/0003702817703270.
Karst DJ, Steinebach F, Soos M, Morbidelli M. Process performance and product quality in an integrated continuous antibody production process. Biotechnol Bioeng. 2016;114(2):298-307. https://doi.org/10.1002/bit.26069.
Hubert M, Vanden Branden K. Robust methods for partial least squares regression. J Chemometr. 2003;17(10):537-549. https://doi.org/10.1002/cem.822.
Savitzky A, Golay MJE. Smoothing and differentiation of data by simplified least squares procedures. Anal Chem. 1964;36(8):1627-1639. https://doi.org/10.1021/ac60214a047.
Barnes RJ, Dhanoa MS, Lister SJ. Standard normal variate transformation and de-trending of near-infrared diffuse reflectance spectra. Appl Spectrosc. 1989;43(5):772-777.
Van Den BRA, Hoefsloot HCJ, Westerhuis JA, Smilde AK, Van Der WMJ. Centering , scaling , and transformations: improving the biological information content of metabolomics data. BMC Genomics. 2006;15:1-15. https://doi.org/10.1186/1471-2164-7-142.
Andersen CM, Bro R. Variable selection in regression-a tutorial. J Chemometr. 2010;24(11-12):728-737. https://doi.org/10.1002/cem.1360.
Nørgaard L, Saudland A, Wagner J, Nielsen JP, Munck L, Engelsen SB. Interval partial least-squares regression (iPLS): a comparative chemometric study with an example from near-infrared spectroscopy. Appl Spectrosc. 2000;54(3):413-419. https://doi.org/10.1366/0003702001949500.
Wold S, Sjöström M, Eriksson L. PLS-regression: a basic tool of chemometrics. Chemom Intel Lab Syst. 2001;58(2):109-130. https://doi.org/10.1016/S0169-7439(01)00155-1.
Kohavi R. A study of cross-validation and bootstrap for accuracy estimation and model selection. Proceedings of the 14th IJCAI. San Fran-cisco, CA: Morgan Kaufmann Pubshers; 1995:1137-1143.
Sokolov M, Ritscher J, MacKinnon N, et al. Robust factor selection in early cell culture process development for the production of a biosimilar monoclonal antibody. Biotechnol Prog. 2017;33(1):181-191. https://doi.org/10.1002/btpr.2374.
Downey G. Vibrational Spectroscopy in Studies of Food Origin. Woodhead Publishing Limited; 2013.
Butler HJ, Ashton L, Bird B, et al. Using Raman spectroscopy to characterize biological materials. Nat Protoc. 2016;11(4):664-687. https://doi.org/10.1038/nprot.2016.036.
Gautam R, Vanga S, Ariese F, Umapathy S. Review of multidimensional data processing approaches for Raman and infrared spectroscopy. EPJ Tech Instrum. 2015;2(1):8. https://doi.org/10.1140/epjti/s40485-015-0018-6.
André S, Lagresle S, Hannas Z, Calvosa É, Duponchel L. Mammalian cell culture monitoring using in situ spectroscopy: is your method really optimised? Biotechnol Prog. 2017;33(2):308-316. https://doi.org/10.1002/btpr.2430.
Maronna RA, Martin RD, Yohai VJ. Robust Statistics. Chichester, England: John Wiley & Sons, Ltd; 2006.
Internation Conference on Harmonization. Guidance for industry: Q2B validation of analytical procedures: Methodology. 1996. Retrieved from https://www.fda.gov/media/71725/download