Raman based chemometric model development for glycation and glycosylation real time monitoring in a manufacturing scale CHO cell bioreactor process.
Raman spectroscopy
chemometrics
multivariate data analysis
Journal
Biotechnology progress
ISSN: 1520-6033
Titre abrégé: Biotechnol Prog
Pays: United States
ID NLM: 8506292
Informations de publication
Date de publication:
03 2022
03 2022
Historique:
revised:
07
10
2021
received:
18
08
2021
accepted:
02
11
2021
pubmed:
6
11
2021
medline:
23
4
2022
entrez:
5
11
2021
Statut:
ppublish
Résumé
The Quality by Design (QbD) approach to the production of therapeutic monoclonal antibodies (mAbs) emphasizes an understanding of the production process ensuring product quality is maintained throughout. Current methods for measuring critical quality attributes (CQAs) such as glycation and glycosylation are time and resource intensive, often, only tested offline once per batch process. Process analytical technology (PAT) tools such as Raman spectroscopy combined with chemometric modeling can provide real time measurements process variables and are aligned with the QbD approach. This study utilizes these tools to build partial least squares (PLS) regression models to provide real time monitoring of glycation and glycosylation profiles. In total, seven cell line specific chemometric PLS models; % mono-glycated, % non-glycated, % G0F-GlcNac, % G0, % G0F, % G1F, and % G2F were considered. PLS models were initially developed using small scale data to verify the capability of Raman to measure these CQAs effectively. Accurate PLS model predictions were observed at small scale (5 L). At manufacturing scale (2000 L) some glycosylation models showed higher error, indicating that scale may be a key consideration in glycosylation profile PLS model development. Model robustness was then considered by supplementing models with a single batch of manufacturing scale data. This data addition had a significant impact on the predictive capability of each model, with an improvement of 77.5% in the case of the G2F. The finalized models show the capability of Raman as a PAT tool to deliver real time monitoring of glycation and glycosylation profiles at manufacturing scale.
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e3223Informations de copyright
© 2021 American Institute of Chemical Engineers.
Références
Andersen DC, Krummen L. Recombinant protein expression for therapeutic applications. Curr Opin Biotechnol. 2002;13:117-123.
Davis GC. Protein stability: impact upon protein pharmaceuticals. Biologicals. 1993;21(2):105.
Wang W. Instability, stabilization, and formulation of liquid protein pharmaceuticals. Int J Pharm. 1999;185(2):129-188.
Wang T, Miller K, Robbins D, Springall J, Smelko J, Choo A, Swan H, Aich U, Shimuta T, Malmquist G, Ohrvik H, Vasi J, Adkins M, Arriola B, Haschke, Cuellar M, Tovey J, Beller J, Wilkes B, Patel B, Saucedo V, Wei B, Grimm C, Hsaio T, Lynch M, Green B User Requirement Specification - Glycosylation Profile - Biophorum (12 May 2020). Available at: https://www.biophorum.com/download/in-line-monitoring-real-time-release-testing-in-biopharmaceutical-processes-prioritization-and-cost-benefit-analysis/ (Accessed: 2 July 2020).
Wacker C, Berger C, Girard P, Meier R. (2011). Glycosylation profiles of therapeutic antibody pharmaceuticals, Eu J Pharm Biopharm 79. 503-7.
Manning MC, Chou DK, Murphy BM, Payne RW, Katayama DS. Stability of protein pharmaceuticals: an update. Pharm Res. 2010;27(4):544-575.
Brady LJ, Martinez T, Balland A. Characterization of nonenzymatic glycation on a monoclonal antibody. Anal Chem. 2007;79(24):9403-9413.
Zhang Q, Ames JM, Smith RD, Baynes JW, Metz TO. A perspective on the Maillard reaction and the analysis of protein glycation by mass spectrometry: probing the pathogenesis of chronic disease. J Proteome Res. 2009;8(2):754-769.
Jakas A, Horvat S. Study of degradation pathways of Amadori compounds obtained by glycation of opioid pentapeptide and related smaller fragments: stability, reactions, and spectroscopic properties. Biopolymers. 2003;69:421-431.
Ghaderi D, Zhang M, Hurtado-Ziola N, Varki A. Production platforms for biotherapeutic glycoproteins. Occurrence, impact, and challenges of non-human sialylation. Biotechnol Gen Eng Rev. 2012;28:147-176.
Patro SY, Freund E, Chang BS. Protein formulation and fill-finish operations. Biotechnol Ann Rev. 2002;8:55-84.
Krishnamurthy R, Manning M. The stability factor: importance in formulation development. Curr Pharm Biotechnol. 2005;3(4):361-371.
Wei B, Berning K, Quan C, Taylor Zhang Y. Glycation of antibodies: modification, methods and potential effects on biological functions. mAbs. 2017;9(4):586-594.
Rathore AS, Winkle H. Quality by design for biopharmaceuticals. Nat Biotechnol. 2009;27:26-34.
Abu-Absi NR, Kenty BM, Cuellar ME, et al. Real time monitoring of multiple parameters in mammalian cell culture bioreactors using an in-line Raman spectroscopy probe. Biotechnol Bioeng. 2011;108:1215-1221.
Capito F, Zimmer A, Skudas R. Mid-infrared spectroscopy-based analysis of mammalian cell culture parameters. Biotechnol Prog. 2015;31(2):578-584.
Buckley K, Ryder AG. Applications of Raman spectroscopy in biopharmaceutical manufacturing: a short review. Appl Spectrosc. 2017;71:1085-1116.
Smith E, Dent G. The theory of Raman spectroscopy. Modern Raman Spectroscopy - A Practical Approach. John Wiley & Sons, Ltd; 2005:71-92.
André S, Cristau LS, Gaillard S, Devos O, Calvosa É, Duponchel L. In-line and real-time prediction of recombinant antibody titer by in situ Raman spectroscopy. Anal Chim Acta. 2015;892:148-152.
Li M, Ebel B, Paris C, Chauchard F, Guedon E, Marc A. Real-time monitoring of antibody glycosylation site occupancy by in situ Raman spectroscopy during bioreactor CHO cell cultures. Biotechnol Prog. 2018;34:486-493.
Rafferty C, Johnson K, OMahony J, Burgoyne B, Rea R, Balss K. Analysis of chemometric models applied to Raman spectroscopy for monitoring key metabolites of cell culture. Biotechnol Prog. 2020;36:e2977.
Esmonde-White KA, Cuellar M, Uerpmann C, Lenain B, Lewis IR. Raman spectroscopy as a process analytical technology for pharmaceutical manufacturing and bioprocessing. Analyt Bioanalyt Chem. 2017;409:637-649.
Yu LX, Amidon G, Khan MA, et al. Understanding pharmaceutical quality by design. AAPS J. 2014;16(4):771-783.
Yu LX. Pharmaceutical quality by design: product and process development, understanding, and control. Pharm Res. 2008;25(4):781-791.
Brewster VL, Ashton L, Goodacre R. Monitoring the glycosylation status of proteins using raman spectroscopy. Anal Chem. 2011;83(15):6074-6081.
Dong J, Migliore N, Mehrman SJ, Cunningham J, Lewis MJ, Hu P. High-throughput, automated protein a purification platform with multiattribute LC-MS analysis for advanced cell culture process monitoring. Anal Chem. 2016;88(17):8673-8679.
EMEA, (2016) Guideline on development, production, characterisation and specification for monoclonal antibodies and related products. Available at: https://www.ema.europa.eu/en/documents/scientific-guideline/guideline-development-production-characterisation-specification-monoclonal-antibodies-related_en.pdf. (Accessed: 8 July 2020).
Rafferty C, O J, Burgoyne B, Rea R, Balss KM, Latshaw DC II. Raman spectroscopy as a method to replace off-line pH during mammalian cell culture processes. Biotechnol Bioeng. 2020;117(1):146-156.
Matthews TE, Smelko JP, Berry B, et al. Glucose monitoring and adaptive feeding of mammalian cell culture in the presence of strong autofluorescence by near infrared Raman spectroscopy. Biotechnol Prog. 2018;34(6):1574-1580.
DeGelder J, Gussem D, Vandenabeele K, Moens P. Reference database of Raman spectra of biological molecules. J Raman Spectrosc. 2007;38:1133-1147.
Wells HA, Atalla RH. An investigation of the vibrational spectra of glucose, galactose and mannose. J Mol Struct. 1990;224:385-424.
She CY, Dinh ND, Tu AT. Laser Raman scattering of glucosamine N-acetylglucosamine, and glucuronic acid general subjects. Biochim Biophys Acta. 1974;372:345-357.
PDA, Technical Report 56: Application of phase appropriate quality systems and cgmp to the development of therapeutic protein drug substance. Parenteral Drug Association: Bethesda, MD, 2012
Kozlowski S, Swann P. Current and future issues in the manufacturing and development of monoclonal antibodies. Adv Drug Deliv Rev. 2006;58(5-6):707-722.
Wei B, Berning K, Quan C, Zhang YT. Glycation of antibodies: modification, methods and potential effects on biological functions. mAbs. 2017;9(4):580-586.
Templeton N, Dean J, Reddy P, Young JD. Peak antibody production is associated with increased oxidative metabolism in an industrially relevant fed-batch CHO cell culture. Biotechnol Bioeng. 2013;110:2013-2024.
Batra J, Rathore AS. Glycosylation of monoclonal antibody products: current status and future prospects. Biotechnol Prog. 2016;32(5):1091-1102.
Xing P. Metabolic characterization of a CHO cell size increase phase in fed-batch cultures. Appl Microbiol Biotechnol. 2017;101(22):8101-8113.
Ast T, Mootha VK. Oxygen and mammalian cell culture: are we repeating the experiment of Dr. ox? Nat Metabol Nat Res. 2019;1:858-860.
Chevallier V, Andersen MR, Malphettes L. Oxidative stress-alleviating strategies to improve recombinant protein production in CHO cells. Biotechnol Bioeng. 2020;117(4):1172-1186.
Ramasubramanyan N, Krincek J, Pezzini J, Lu R. Smelko J, Swann P, Loladze V, Barnett J, Brophy L, Cuellar M, Strachan D, O'Riordan, Seiber K, Higgins J, Zillmann M, Valery E, Doyle J, Jeffers P, Dillon P, Slade P, Harris R, Aich U, Dekner M, Philips M, Tummala S, Varghese J, Grimm C, Bell P, Josephs J, Dakin J, Green B (2020) In-line monitoring/real-time release testing in biopharmaceutical processes - prioritization and cost benefit analysis - BioPhorum Available at: https://www.biophorum.com/download/in-line-monitoring-real-time-release-testing-in-biopharmaceutical-processes-prioritization-and-cost-benefit-analysis/ (Accessed: 2 July 2020).