Raman spectroscopy as a process analytical technology to investigate biopharmaceutical freeze concentration processes.
Raman spectroscopy
formulation
freeze concentration
monoclonal antibody
Journal
Biotechnology and bioengineering
ISSN: 1097-0290
Titre abrégé: Biotechnol Bioeng
Pays: United States
ID NLM: 7502021
Informations de publication
Date de publication:
12 2021
12 2021
Historique:
revised:
06
08
2021
received:
21
05
2021
accepted:
31
08
2021
pubmed:
9
9
2021
medline:
1
3
2022
entrez:
8
9
2021
Statut:
ppublish
Résumé
Freezing processes are a well-established unit operation in the biopharmaceutical industry to increase the shelf-life of protein-based drugs. While freezing reduces degradation reaction rates, it may also exert stresses such as freeze concentration. Macroscopic freeze concentration in large-scale freezing processes has been described thoroughly by examination of frozen bulk material, but the transient process leading to such freeze concentration profiles has not been monitored yet for biopharmaceutical solutions. In this study, Raman spectroscopy as a process analytical technology is demonstrated for model formulations containing monoclonal antibodies (mAbs) or bovine serum albumin (BSA) in varying concentrations of sucrose and buffer salts. Therefore, a Raman probe was immersed into a bulk volume at different heights, monitoring the freeze concentration in the liquid phase during the freezing processes. Partial least square regression models were used to quantitatively discriminate between the protein and excipients simultaneously. The freeze concentration profiles were dependend on freezing temperature and formulation with freeze concentrations up to 2.4-fold. Convection currents at the bottom of the freezing container were observed with a maximum height of 1 mm. Furthermore, freeze concentration was correlated with the sucrose concentration in a formulation. Analysis of the freeze concentration slope indicated diffusion from the bottom to the top of the container. In summary, Raman spectroscopy is a valuable tool for process validation of freeze concentration simulations and to overcome scale-dependent challenges.
Substances chimiques
Antibodies, Monoclonal
0
Biological Products
0
Serum Albumin, Bovine
27432CM55Q
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
4708-4719Informations de copyright
© 2021 The Authors. Biotechnology and Bioengineering Published by Wiley Periodicals LLC.
Références
Authelin, J. R., Rodrigues, M. A., Tchessalov, S., Singh, S. K., McCoy, T., Wang, S., & Shalaev, E. (2020). Freezing of biologicals revisited: Scale, stability, excipients, and degradation stresses. Journal of Pharmaceutical Sciences, 109, 44-61. https://doi.org/10.1016/j.xphs.2019.10.062
Bhatnagar, B. S., Bogner, R. H., & Pikal, M. J. (2007). Protein stability during freezing: Separation of stresses and mechanisms of protein stabilization. Pharmaceutical Development and Technology, 12(5), 505-523. https://doi.org/10.1080/10837450701481157
Butler, M. F. (2002). Freeze concentration of solutes at the ice/solution interface studied by optical interferometry. Crystal Growth and Design, 2(6), 541-548. https://doi.org/10.1021/cg025591e
Buyel, J. F., Twyman, R. M., & Fischer, R. (2017). Very-large-scale production of antibodies in plants: The biologization of manufacturing. Biotechnology Advances, 35(4), 458-465. https://doi.org/10.1016/j.biotechadv.2017.03.011
Connolly, B. D., Le, L., Patapoff, T. W., Cromwell, M. E. M., Moore, J. M. R., & Lam, P. (2015). Protein aggregation in frozen trehalose formulations: Effects of composition, cooling rate, and storage temperature. Journal of Pharmaceutical Sciences, 104(12), 4170-4184. https://doi.org/10.1002/jps.24646
Dong, J., Hubel, A., Bischof, J. C., & Aksan, A. (2009). Freezing-induced phase separation and spatial microheterogeneity in protein solutions. Journal of Physical Chemistry B, 113(30), 10081-10087. https://doi.org/10.1021/jp809710d
Ðuričković, I., Claverie, R., Bourson, P., Marchetti, M., Chassot, J. M., & Fontana, M. D. (2011). Water-ice phase transition probed by Raman spectroscopy. Journal of Raman Spectroscopy, 42(6), 1408-1412. https://doi.org/10.1002/jrs.2841
Fick, A. (1855). Über Diffusion [Translated: (1995) “On liquid diffusion”. Journal of Membrane Science]. Poggendorff's Annalen Der Physik Und Chemie, 94(1), 59-86.
Filik, J., & Stone, N. (2007). Drop coating deposition Raman spectroscopy of protein mixtures. Analyst, 132(6), 544-550. https://doi.org/10.1039/b701541k
Geraldes, V., Gomes, D. C., Rego, P., Fegley, D., & Rodrigues, M. A. (2020). A new perspective on scale-down strategies for freezing of biopharmaceutics by means of computational fluid dynamics. Journal of Pharmaceutical Sciences, 109(6), 1978-1989. https://doi.org/10.1016/j.xphs.2020.02.012
Großhans, S., Rüdt, M., Sanden, A., Brestrich, N., Morgenstern, J., Heissler, S., & Hubbuch, J. (2018). In-line Fourier-transform infrared spectroscopy as a versatile process analytical technology for preparative protein chromatography. Journal of Chromatography A, 1547, 37-44. https://doi.org/10.1016/j.chroma.2018.03.005
Guo, S., Bocklitz, T., & Popp, J. (2016). Optimization of Raman-spectrum baseline correction in biological application. Analyst, 141(8), 2396-2404. https://doi.org/10.1039/c6an00041j
Kolhe, P., & Badkar, A. (2011). Protein and solute distribution in drug substance containers during frozen storage and post-thawing: A tool to understand and define freezing-thawing parameters in biotechnology process development. Biotechnology Progress, 27(2), 494-504. https://doi.org/10.1002/btpr.530
Li, J. Q., & Fan, T. H. (2020). Phase-field modeling of macroscopic freezing dynamics in a cylindrical vessel. International Journal of Heat and Mass Transfer, 156, 119915. https://doi.org/10.1016/j.ijheatmasstransfer.2020.119915
Miller, M. A., Rodrigues, M. A., Glass, M. A., Singh, S. K., Johnston, K. P., & Johnston, K. P. M. (2013). Frozen-state storage stability of a monoclonal antibody: Aggregation is impacted by freezing rate and solute distribution. International Journal of Pharmaceutical Sciences, 102(4), 1194-1208. https://doi.org/10.1002/jps
Miyawaki, O., Liu, L., & Nakamura, K. (1998). Effective partition constant of solute between ice and liquid phases in progressive freeze-concentration. Journal of Food Science, 63(5), 756-758. https://doi.org/10.1111/j.1365-2621.1998.tb17893.x
Ockman, N. (1958). The infra-red and Raman spectra of ice. Advances in Physics, 7(26), 199-220. https://doi.org/10.1080/00018735800101227
Parachalil, D. R., Brankin, B., McIntyre, J., & Byrne, H. J. (2018). Raman spectroscopic analysis of high molecular weight proteins in solution-considerations for sample analysis and data pre-processing. Analyst, 143(24), 5987-5998. https://doi.org/10.1039/c8an01701h
Privalov, P. L. (1990). Cold denaturation of protein. Critical Reviews in Biochemistry and Molecular Biology, 25(4), 281-306. https://doi.org/10.3109/10409239009090612
Reinsch, H., Spadiut, O., Heidingsfelder, J., & Herwig, C. (2015). Examining the freezing process of an intermediate bulk containing an industrially relevant protein. Enzyme and Microbial Technology, 71, 13-19. https://doi.org/10.1016/j.enzmictec.2015.01.003
Rodrigues, M. A., Miller, M. A., Glass, M. A., Singh, S. K., & Johnston, K. P. (2011). Effect of freezing rate and dendritic ice formation on concentration profiles of proteins frozen in cylindrical vessels. Journal of Pharmaceutical Sciences, 100(4), 1316-1329. https://doi.org/10.1002/jps
Rodrigues, M. A., Miller, M. A., Glass, M. A., Singh, S. K., & Johnston, K. P. (2012). Comparison of freezing rate and dendritic ice formation on concentration profiles of proteins frozen in cylindrical vessels. Journal of Pharmaceutical Sciences, 101(1), 322-332. https://doi.org/10.1002/jps.22383
Roessl, U., Jajcevic, D., Leitgeb, S., Khinast, J. G., & Nidetzky, B. (2014). Characterization of a laboratory-scale container for freezing protein solutions with detailed evaluation of a freezing process simulation. Journal of Pharmaceutical Sciences, 103(2), 417-426. https://doi.org/10.1002/jps.23814
Rohleder, D. R., Kocherscheidt, G., Gerber, K., Kiefer, W., Köhler, W., Möcks, J., & Petrich, W. H. (2005). Comparison of mid-infrared and Raman spectroscopy in the quantitative analysis of serum. Journal of Biomedical Optics, 10(3), 031108. https://doi.org/10.1117/1.1911847
Savitzky, A., & Golay, M. J. E. (1964). Smoothing and differentiation of data by simplified least squares procedures. Analytical Chemistry, 36(8), 1627-1639. https://doi.org/10.1021/ac60214a047
Schmälzlin, E., Moralejo, B., Rutowska, M., Monreal-Ibero, A., Sandin, C., Tarcea, N., Popp, J., & Roth, M. M. (2014). Raman imaging with a fiber-coupled multichannel spectrograph. Sensors, 14, 21968-21980. https://doi.org/10.3390/s141121968
Shamlou, P. A., Breen, L. H., Bell, W. V., Pollo, M., & Thomas, B. A. (2007). A new scaleable freeze-thaw technology for bulk protein solutions. Biotechnology and Applied Biochemistry, 46(1), 13-26. https://doi.org/10.1042/BA20060075
Shevchenko, N., Roshchupkina, O., Sokolova, O., & Eckert, S. (2015). The effect of natural and forced melt convection on dendritic solidification in Ga-In alloys. Journal of Crystal Growth, 417, 1-8. https://doi.org/10.1016/j.jcrysgro.2014.11.043
Shukla, A. A., Wolfe, L. S., Mostafa, S. S., & Norman, C. (2017). Evolving trends in mAb production processes. Bioengineering & Translational Medicine, 2(1), 58-69. https://doi.org/10.1002/btm2.10061
Singh, S. K., & Nema, S. (2010). Freezing and thawing of protein solutions. In F. Jameel & S. Hershenson (Eds.), Formulation and process development strategies for manufacturing biopharmaceuticals (pp. 625-675). John Wiley & Sons, Inc. https://doi.org/10.1002/9780470595886.ch26
Torres, J. F., Komiya, A., Okajima, J., & Shigenao, M. (2012). Measurement of the molecular mass dependence of the mass diffusion coefficient in protein aqueous solutions. Defect and Diffusion Forum, 326-328, 452-458. https://doi.org/10.4028/www.scientific.net/DDF.326-328.452
Twomey, A., Kurata, K., Nagare, Y., Takamatsu, H., & Aksan, A. (2015). Microheterogeneity in frozen protein solutions. International Journal of Pharmaceutics, 487(1-2), 91-100. https://doi.org/10.1016/j.ijpharm.2015.04.032
Vankeirsbilck, T., Vercauteren, A., Baeyens, W., Van der Weken, G., Verpoort, F., Vergote, G., & Remon, J. P. (2002). Applications of Raman spectroscopy in pharmaceutical analysis. TrAC Trends in Analytical Chemistry, 21(12), 869-877. https://doi.org/10.1016/S0165-9936(02)01208-6
Vynnycky, M., & Kimura, S. (2007). An analytical and numerical study of coupled transient natural convection and solidification in a rectangular enclosure. International Journal of Heat and Mass Transfer, 50(25-26), 5204-5214. https://doi.org/10.1016/j.ijheatmasstransfer.2007.06.036
Wang, X., & Fautrelle, Y. (2009). An investigation of the influence of natural convection on tin solidification using a quasi two-dimensional experimental benchmark. International Journal of Heat and Mass Transfer, 52(23-24), 5624-5633. https://doi.org/10.1016/j.ijheatmasstransfer.2009.05.030
Weber, D., & Hubbuch, J. (2021). Temperature based process characterization of pharmaceutical freeze-thaw operations. Frontiers in Bioengineering and Biotechnology, 9, 617770. https://doi.org/10.3389/fbioe.2021.617770
Weber, D., Sittig, C., & Hubbuch, J. (2021). Impact of freeze-thaw processes on monoclonal antibody platform process development. Biotechnology and Bioengineering. 118(10), https://doi.org/10.1002/bit.27867
Wold, S., Sjöström, M., & Eriksson, L. (2001). PLS-regression: A basic tool of chemometrics. Chemometrics and Intelligent Laboratory Systems, 58(2), 109-130. https://doi.org/10.1016/S0169-7439(01)00155-1