{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T15:43:24Z","timestamp":1788018204942,"version":"build-2784847793"},"reference-count":43,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2025,5,1]],"date-time":"2025-05-01T00:00:00Z","timestamp":1746057600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2025,5,1]],"date-time":"2025-05-01T00:00:00Z","timestamp":1746057600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2025,2,19]],"date-time":"2025-02-19T00:00:00Z","timestamp":1739923200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Journal of Biotechnology"],"published-print":{"date-parts":[[2025,5]]},"DOI":"10.1016\/j.jbiotec.2025.02.007","type":"journal-article","created":{"date-parts":[[2025,2,18]],"date-time":"2025-02-18T16:31:29Z","timestamp":1739896289000},"page":"11-20","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":8,"special_numbering":"C","title":["A robust scale-down model development and process characterization for monoclonal antibody biomanufacturing using multivariate data analysis"],"prefix":"10.1016","volume":"401","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-4914-8075","authenticated-orcid":false,"given":"Sung-Hyuk","family":"Han","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6140-412X","authenticated-orcid":false,"given":"Seo-Young","family":"Park","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyun-Myoung","family":"Cha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kwang-Bae","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin-Hyuk","family":"Lim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0901-708X","authenticated-orcid":false,"given":"Dong-Yup","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.jbiotec.2025.02.007_bib1","doi-asserted-by":"crossref","DOI":"10.1002\/biot.201100052","article-title":"Towards dynamic metabolic flux analysis in CHO cell cultures","author":"Ahn","year":"2012","journal-title":"Biotechnol. J."},{"key":"10.1016\/j.jbiotec.2025.02.007_bib2","doi-asserted-by":"crossref","first-page":"392","DOI":"10.1198\/004017004000000491","article-title":"Two projection methods for use in the analysis of multivariate process data with an illustration in petrochemical production","volume":"46","author":"Badcock","year":"2004","journal-title":"Technometrics"},{"key":"10.1016\/j.jbiotec.2025.02.007_bib3","doi-asserted-by":"crossref","first-page":"1337","DOI":"10.1002\/bit.27282","article-title":"Reduced scale model qualification of 5-L and 250-ml bioreactors using multivariant visualization and Bayesian inferential methods","volume":"117","author":"Banton","year":"2020","journal-title":"Biotechnol. Bioeng."},{"key":"10.1016\/j.jbiotec.2025.02.007_bib4","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1002\/btpr.678","article-title":"Chemometrics applications in biotech processes: assessing process comparability","volume":"28","author":"Bhushan","year":"2012","journal-title":"Biotechnol. Prog."},{"key":"10.1016\/j.jbiotec.2025.02.007_bib5","doi-asserted-by":"crossref","DOI":"10.1016\/j.ijpharm.2020.120164","article-title":"From cell line development to the formulated drug product: The art of manufacturing therapeutic monoclonal antibodies","author":"Carrara","year":"2021","journal-title":"Int. J. Pharm."},{"key":"10.1016\/j.jbiotec.2025.02.007_bib6","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/j.enzmictec.2017.04.010","article-title":"Co-overexpression of Mgat1 and Mgat4 in CHO cells for production of highly sialylated albumin-erythropoietin","volume":"103","author":"Cha","year":"2017","journal-title":"Enzym. Microb. Technol."},{"key":"10.1016\/j.jbiotec.2025.02.007_bib7","doi-asserted-by":"crossref","DOI":"10.1016\/j.freeradbiomed.2014.08.027","article-title":"The Warburg effect: Evolving interpretations of an established concept","author":"Chen","year":"2015","journal-title":"Free Radic. Biol. Med."},{"key":"10.1016\/j.jbiotec.2025.02.007_bib8","article-title":"Multi- and megavariate data analysis","volume":"45","author":"Eriksson","year":"2013","journal-title":"Technometrics"},{"key":"10.1016\/j.jbiotec.2025.02.007_bib9","doi-asserted-by":"crossref","DOI":"10.1002\/biot.201800684","article-title":"Multivariate data analysis methodology to solve data challenges related to scale-up model validation and missing data on a micro-bioreactor system","volume":"15","author":"Goldrick","year":"2020","journal-title":"Biotechnol. J."},{"key":"10.1016\/j.jbiotec.2025.02.007_bib10","doi-asserted-by":"crossref","DOI":"10.1016\/j.ejpb.2019.12.007","article-title":"Quality by design in pharmaceutical manufacturing: a systematic review of current status, challenges and future perspectives","author":"Grangeia","year":"2020","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"10.1016\/j.jbiotec.2025.02.007_bib11","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1002\/jctb.4481","article-title":"Multivariate analysis of the effect of operating conditions on hybridoma cell metabolism and glycosylation of produced antibody","volume":"90","author":"Green","year":"2015","journal-title":"J. Chem. Technol. Biotechnol."},{"key":"10.1016\/j.jbiotec.2025.02.007_bib12","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.bej.2018.01.031","article-title":"Intracellular response of CHO cells to oxidative stress and its influence on metabolism and antibody production","volume":"133","author":"Handlogten","year":"2018","journal-title":"Biochem. Eng. J."},{"key":"10.1016\/j.jbiotec.2025.02.007_bib13","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1186\/1753-6561-5-S8-P70","article-title":"Development and fine-tuning of a scale down model for process characterization studies of a monoclonal antibody upstream production process","volume":"5","author":"Harmsen","year":"2011","journal-title":"BMC Proc."},{"key":"10.1016\/j.jbiotec.2025.02.007_bib14","doi-asserted-by":"crossref","DOI":"10.1002\/bit.28785","article-title":"Development and qualification of 3\u2009L scale-down model for large scale vaccine process on Vero cell culture using microcarriers","author":"Huang","year":"2024","journal-title":"Biotechnol. Bioeng."},{"key":"10.1016\/j.jbiotec.2025.02.007_bib15","doi-asserted-by":"crossref","first-page":"2300053","DOI":"10.1002\/biot.202300053","article-title":"Scale-down of CHO cell cultivation from shake flasks based on oxygen mass transfer allows application of parallelized, non-invasive, and time-resolved monitoring of the oxygen transfer rate in 48-well microtiter plates","volume":"18","author":"Ihling","year":"2023","journal-title":"Biotechnol. J."},{"key":"10.1016\/j.jbiotec.2025.02.007_bib16","doi-asserted-by":"crossref","first-page":"1623","DOI":"10.1002\/btpr.2162","article-title":"Application of high-throughput mini-bioreactor system for systematic scale-down modeling, process characterization, and control strategy development","volume":"31","author":"Janakiraman","year":"2015","journal-title":"Biotechnol. Prog."},{"key":"10.1016\/j.jbiotec.2025.02.007_bib17","doi-asserted-by":"crossref","DOI":"10.1080\/19420862.2020.1860476","article-title":"Antibodies to watch in 2021","volume":"13","author":"Kaplon","year":"2021","journal-title":"MAbs"},{"key":"10.1016\/j.jbiotec.2025.02.007_bib18","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1016\/j.biologicals.2016.06.003","article-title":"Establishing a control system using QbD principles","volume":"44","author":"Kepert","year":"2016","journal-title":"Biologicals"},{"key":"10.1016\/j.jbiotec.2025.02.007_bib19","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1002\/9783527811410.ch16","article-title":"Development and qualification of a cell culture scale-down model","author":"Khattak","year":"2019","journal-title":": Cell Cult. Eng."},{"key":"10.1016\/j.jbiotec.2025.02.007_bib20","doi-asserted-by":"crossref","first-page":"720","DOI":"10.1021\/bp0704384","article-title":"Application of multivariate data analysis for identification and successful resolution of a root cause for a bioprocessing application","volume":"24","author":"Kirdar","year":"2008","journal-title":"Biotechnol. Prog."},{"key":"10.1016\/j.jbiotec.2025.02.007_bib21","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/j.xphs.2019.08.009","article-title":"Physicochemical stability of monoclonal antibodies: a review","volume":"109","author":"Le Basle","year":"2020","journal-title":"J. Pharm. Sci."},{"key":"10.1016\/j.jbiotec.2025.02.007_bib22","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1016\/j.jbiotec.2012.08.021","article-title":"Multivariate analysis of cell culture bioprocess data\u2014lactate consumption as process indicator","volume":"162","author":"Le","year":"2012","journal-title":"J. Biotechnol."},{"key":"10.1016\/j.jbiotec.2025.02.007_bib23","doi-asserted-by":"crossref","first-page":"696","DOI":"10.1021\/bp0504041","article-title":"A systematic approach for scale-down model development and characterization of commercial cell culture processes","volume":"22","author":"Li","year":"2006","journal-title":"Biotechnol. Prog."},{"key":"10.1016\/j.jbiotec.2025.02.007_bib24","doi-asserted-by":"crossref","DOI":"10.1186\/s12929-019-0592-z","article-title":"Development of therapeutic antibodies for the treatment of diseases","author":"Lu","year":"2020","journal-title":"J. Biomed. Sci."},{"key":"10.1016\/j.jbiotec.2025.02.007_bib25","doi-asserted-by":"crossref","DOI":"10.1002\/btpr.2959","article-title":"Effective temperature shift strategy development and scale confirmation for simultaneous optimization of protein productivity and quality in Chinese hamster ovary cells","volume":"36","author":"McHugh","year":"2020","journal-title":"Biotechnol. Prog."},{"key":"10.1016\/j.jbiotec.2025.02.007_bib26","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1208\/s12249-019-1451-7","article-title":"Development and qualification of a scale-down mammalian cell culture model and application in design space development by definitive screening design","volume":"20","author":"Nie","year":"2019","journal-title":"AAPS PharmSciTech"},{"key":"10.1016\/j.jbiotec.2025.02.007_bib27","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1208\/s12249-019-1451-7","article-title":"Development and qualification of a scale-down mammalian cell culture model and application in design space development by definitive screening design","volume":"20","author":"Nie","year":"2019","journal-title":"AAPS PharmSciTech"},{"key":"10.1016\/j.jbiotec.2025.02.007_bib28","doi-asserted-by":"crossref","DOI":"10.1038\/nbt0109-26","article-title":"Quality by design for biopharmaceuticals","author":"Rathore","year":"2009","journal-title":"Nat. Biotechnol."},{"key":"10.1016\/j.jbiotec.2025.02.007_bib29","doi-asserted-by":"crossref","first-page":"1173","DOI":"10.1002\/bit.26534","article-title":"Identification of process conditions influencing protein aggregation in Chinese hamster ovary cell culture","volume":"115","author":"Paul","year":"2018","journal-title":"Biotechnol. Bioeng."},{"key":"10.1016\/j.jbiotec.2025.02.007_bib30","doi-asserted-by":"crossref","first-page":"1311","DOI":"10.1002\/jctb.4428","article-title":"Chemometrics application in biotech processes: assessing comparability across processes and scales","volume":"89","author":"Rathore","year":"2014","journal-title":"J. Chem. Technol. Biotechnol."},{"key":"10.1016\/j.jbiotec.2025.02.007_bib31","doi-asserted-by":"crossref","DOI":"10.1002\/biot.201700766","article-title":"Scale-down model development in ambr systems: an industrial perspective","author":"Sandner","year":"2019","journal-title":"Biotechnol. J."},{"key":"10.1016\/j.jbiotec.2025.02.007_bib32","doi-asserted-by":"crossref","first-page":"1171","DOI":"10.1016\/j.cjche.2018.10.009","article-title":"Chemometric identification of canonical metabolites linking critical process parameters to monoclonal antibody production during bioprocess development","volume":"27","author":"Shen","year":"2019","journal-title":"Chin. J. Chem. Eng."},{"key":"10.1016\/j.jbiotec.2025.02.007_bib33","doi-asserted-by":"crossref","first-page":"1381","DOI":"10.1007\/s10616-015-9899-0","article-title":"Equipment characterization to mitigate risks during transfers of cell culture manufacturing processes","volume":"68","author":"Sieblist","year":"2016","journal-title":"Cytotechnology"},{"key":"10.1016\/j.jbiotec.2025.02.007_bib34","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1159\/000505379","article-title":"Late-stage failures of monoclonal antibody drugs: a retrospective case study analysis","volume":"105","author":"Sun","year":"2020","journal-title":"Pharmacology"},{"key":"10.1016\/j.jbiotec.2025.02.007_bib35","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1002\/btpr.1819","article-title":"Development of a scale down cell culture model using multivariate analysis as a qualification tool","volume":"30","author":"Tsang","year":"2014","journal-title":"Biotechnol. Prog."},{"key":"10.1016\/j.jbiotec.2025.02.007_bib36","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1016\/j.jbiotec.2005.05.016","article-title":"Monitoring Chinese hamster ovary cell culture by the analysis of glucose and lactate metabolism","volume":"118","author":"Tsao","year":"2005","journal-title":"J. Biotechnol."},{"key":"10.1016\/j.jbiotec.2025.02.007_bib37","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0093865","article-title":"Differential effect of culture temperature and specific growth rate on CHO cell behavior in chemostat culture","volume":"9","author":"Vergara","year":"2014","journal-title":"PLoS One"},{"key":"10.1016\/j.jbiotec.2025.02.007_bib38","doi-asserted-by":"crossref","DOI":"10.1002\/biot.201700733","article-title":"Perfusion cell culture decreases process and product heterogeneity in a head-to-head comparison with fed-batch","volume":"14","author":"Walther","year":"2019","journal-title":"Biotechnol. J."},{"key":"10.1016\/j.jbiotec.2025.02.007_bib39","doi-asserted-by":"crossref","first-page":"1201","DOI":"10.1007\/s10529-018-2586-4","article-title":"Ultra-low carbon dioxide partial pressure improves the galactosylation of a monoclonal antibody produced in Chinese hamster ovary cells in a bioreactor","volume":"40","author":"Wang","year":"2018","journal-title":"Biotechnol. Lett."},{"key":"10.1016\/j.jbiotec.2025.02.007_bib40","doi-asserted-by":"crossref","DOI":"10.1002\/bit.27461","article-title":"Technology outlook for real-time quality attribute and process parameter monitoring in biopharmaceutical development\u2014A review","author":"Wasalathanthri","year":"2020","journal-title":"Biotechnol. Bioeng."},{"key":"10.1016\/j.jbiotec.2025.02.007_bib41","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1002\/bit.22287","article-title":"Scale-up analysis for a CHO cell culture process in large-scale bioreactors","volume":"103","author":"Xing","year":"2009","journal-title":"Biotechnol. Bioeng."},{"key":"10.1016\/j.jbiotec.2025.02.007_bib42","doi-asserted-by":"crossref","first-page":"478","DOI":"10.1002\/btpr.2417","article-title":"Characterization of TAP Ambr 250 disposable bioreactors, as a reliable scale-down model for biologics process development","volume":"33","author":"Xu","year":"2017","journal-title":"Biotechnol. Prog."},{"key":"10.1016\/j.jbiotec.2025.02.007_bib43","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1007\/s12247-010-9085-z","article-title":"Application of multivariate tools in pharmaceutical product development to bridge risk assessment to continuous verification in a quality by design environment","volume":"5","author":"Zomer","year":"2010","journal-title":"J. Pharm. Innov."}],"container-title":["Journal of Biotechnology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0168165625000410?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0168165625000410?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,3,12]],"date-time":"2025-03-12T17:41:52Z","timestamp":1741801312000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0168165625000410"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5]]},"references-count":43,"alternative-id":["S0168165625000410"],"URL":"https:\/\/doi.org\/10.1016\/j.jbiotec.2025.02.007","relation":{},"ISSN":["0168-1656"],"issn-type":[{"value":"0168-1656","type":"print"}],"subject":[],"published":{"date-parts":[[2025,5]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"A robust scale-down model development and process characterization for monoclonal antibody biomanufacturing using multivariate data analysis","name":"articletitle","label":"Article Title"},{"value":"Journal of Biotechnology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.jbiotec.2025.02.007","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2025 The Authors. Published by Elsevier B.V.","name":"copyright","label":"Copyright"}]}}