{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T01:53:49Z","timestamp":1760061229449,"version":"build-2065373602"},"reference-count":38,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2024,7,11]],"date-time":"2024-07-11T00:00:00Z","timestamp":1720656000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Biotech &amp; Bioengineering"],"published-print":{"date-parts":[[2024,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Scale\u2010down models (SDM) are pivotal tools for process understanding and improvement to accelerate the development of vaccines from laboratory research to global commercialization. In this study, a 3\u2009L SDM representing a 50\u2009L scale Vero cell culture process of a live\u2010attenuated virus vaccine using microcarriers was developed and qualified based on the constant impeller power per volume principle. Both multivariate data analysis (MVDA) and the traditional univariate data analysis showed comparable and equivalent cell growth, metabolic activity, and product quality results across scales. Computational fluid dynamics simulation further confirmed similar hydrodynamic stress between the two scales.<\/jats:p>","DOI":"10.1002\/bit.28785","type":"journal-article","created":{"date-parts":[[2024,7,12]],"date-time":"2024-07-12T02:45:40Z","timestamp":1720752340000},"page":"3402-3414","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Development and qualification of 3\u2009L scale\u2010down model for large scale vaccine process on Vero cell culture using microcarriers"],"prefix":"10.1002","volume":"121","author":[{"given":"Renjing","family":"Huang","sequence":"first","affiliation":[{"name":"Bioprocess Drug Substance Commercialization, Merck &amp; Co., Inc. West Point Pennsylvania USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kai","family":"Wang","sequence":"additional","affiliation":[{"name":"Bioprocess Drug Substance Commercialization, Merck &amp; Co., Inc. West Point Pennsylvania USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthew H.","family":"Flamm","sequence":"additional","affiliation":[{"name":"Applied Mathematics and Modeling, Merck &amp; Co., Inc. West Point Pennsylvania USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jorge","family":"Vazquez","sequence":"additional","affiliation":[{"name":"Center of Mathematical Sciences, Merck &amp; Co., Inc. West Point Pennsylvania USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chris","family":"Gercke","sequence":"additional","affiliation":[{"name":"Bioprocess Drug Substance Commercialization, Merck &amp; Co., Inc. West Point Pennsylvania USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christopher","family":"Ton","sequence":"additional","affiliation":[{"name":"Vaccine Process Development, Merck &amp; Co., Inc. West Point Pennsylvania USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Travis","family":"Whitmer","sequence":"additional","affiliation":[{"name":"Bioprocess Drug Substance Commercialization, Merck &amp; Co., Inc. West Point Pennsylvania USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pamela K.","family":"Mathis","sequence":"additional","affiliation":[{"name":"Global Quality Large Molecule Analytical Sciences, Merck &amp; Co., Inc. West Point Pennsylvania USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kristin J. M.","family":"Ploeger","sequence":"additional","affiliation":[{"name":"Bioprocess Drug Substance Commercialization, Merck &amp; Co., Inc. West Point Pennsylvania USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-6176-6301","authenticated-orcid":false,"given":"Shahid","family":"Rameez","sequence":"additional","affiliation":[{"name":"Bioprocess Drug Substance Commercialization, Merck &amp; Co., Inc. West Point Pennsylvania USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,7,11]]},"reference":[{"doi-asserted-by":"publisher","key":"e_1_2_9_2_1","DOI":"10.1016\/B978-012387582-2\/50038-1"},{"doi-asserted-by":"publisher","key":"e_1_2_9_3_1","DOI":"10.1016\/j.bej.2020.107870"},{"doi-asserted-by":"publisher","key":"e_1_2_9_4_1","DOI":"10.1586\/erv.09.19"},{"doi-asserted-by":"publisher","key":"e_1_2_9_5_1","DOI":"10.1002\/BIOT.201600633"},{"doi-asserted-by":"publisher","key":"e_1_2_9_6_1","DOI":"10.1002\/bit.260320808"},{"doi-asserted-by":"publisher","key":"e_1_2_9_7_1","DOI":"10.1002\/bit.260290117"},{"key":"e_1_2_9_8_1","first-page":"1","article-title":"Development, qualification, and application of a bioreactor scale\u2010down process: Modeling large\u2010scale microcarrier perfusion cell culture","volume":"14","author":"DiCesare C.","year":"2016","journal-title":"BioProcess International"},{"doi-asserted-by":"publisher","key":"e_1_2_9_9_1","DOI":"10.1038\/s41591-021-01301-0"},{"doi-asserted-by":"publisher","key":"e_1_2_9_10_1","DOI":"10.3389\/fbioe.2022.921755"},{"doi-asserted-by":"publisher","key":"e_1_2_9_11_1","DOI":"10.1016\/J.CES.2022.118172"},{"doi-asserted-by":"publisher","key":"e_1_2_9_12_1","DOI":"10.1002\/bit.28647"},{"doi-asserted-by":"publisher","key":"e_1_2_9_13_1","DOI":"10.1002\/BTPR.646"},{"doi-asserted-by":"publisher","key":"e_1_2_9_14_1","DOI":"10.1002\/(SICI)1097-0290(20000720)69:2<171::AID-BIT6>3.0.CO;2-C"},{"doi-asserted-by":"publisher","key":"e_1_2_9_15_1","DOI":"10.1007\/s10616-011-9368-3"},{"doi-asserted-by":"publisher","key":"e_1_2_9_16_1","DOI":"10.1002\/BTPR.3277"},{"doi-asserted-by":"publisher","key":"e_1_2_9_17_1","DOI":"10.1016\/J.PROCBIO.2019.03.010"},{"doi-asserted-by":"publisher","key":"e_1_2_9_18_1","DOI":"10.1016\/j.biotechadv.2020.107608"},{"doi-asserted-by":"publisher","key":"e_1_2_9_19_1","DOI":"10.1016\/J.CES.2020.115912"},{"doi-asserted-by":"publisher","key":"e_1_2_9_20_1","DOI":"10.1002\/bit.22474"},{"doi-asserted-by":"publisher","key":"e_1_2_9_21_1","DOI":"10.4161\/mabs.2.5.12720"},{"doi-asserted-by":"publisher","key":"e_1_2_9_22_1","DOI":"10.1002\/BTPR.2870"},{"doi-asserted-by":"publisher","key":"e_1_2_9_23_1","DOI":"10.1023\/A:1020598031275"},{"doi-asserted-by":"publisher","key":"e_1_2_9_24_1","DOI":"10.1586\/erv.10.115"},{"issue":"8","key":"e_1_2_9_25_1","article-title":"A Rational, Step\u2010Wise Approach to Process Characterization","volume":"16","author":"Seely J.","year":"2003","journal-title":"BioPharm International"},{"key":"e_1_2_9_26_1","first-page":"e40","volume-title":"Clinical and Translational Discovery","author":"S\u00e8ne M. A.","year":"2022"},{"doi-asserted-by":"publisher","key":"e_1_2_9_27_1","DOI":"10.1002\/bit.28190"},{"doi-asserted-by":"publisher","key":"e_1_2_9_28_1","DOI":"10.3390\/life12091318"},{"doi-asserted-by":"publisher","key":"e_1_2_9_29_1","DOI":"10.21105\/JOSS.01450"},{"doi-asserted-by":"publisher","key":"e_1_2_9_30_1","DOI":"10.1002\/bit.24798"},{"doi-asserted-by":"publisher","key":"e_1_2_9_31_1","DOI":"10.1016\/j.btre.2023.e00782"},{"doi-asserted-by":"publisher","key":"e_1_2_9_32_1","DOI":"10.1002\/btpr.1819"},{"unstructured":"Vaccines and immunization. (n.d.). Retrieved December 28 2023 fromhttps:\/\/www.who.int\/health-topics\/vaccines-and-immunization#tab=tab_1","key":"e_1_2_9_33_1"},{"doi-asserted-by":"publisher","key":"e_1_2_9_34_1","DOI":"10.1007\/BF00353928"},{"doi-asserted-by":"publisher","key":"e_1_2_9_35_1","DOI":"10.1002\/bit.10310"},{"unstructured":"World Health Organization. (2023).COVID\u201019 cases | WHO COVID\u201019 dashboard.https:\/\/data.who.int\/dashboards\/covid19\/cases?n=c","key":"e_1_2_9_36_1"},{"doi-asserted-by":"publisher","key":"e_1_2_9_37_1","DOI":"10.1002\/bit.22287"},{"doi-asserted-by":"publisher","key":"e_1_2_9_38_1","DOI":"10.3390\/vaccines10111787"},{"doi-asserted-by":"publisher","key":"e_1_2_9_39_1","DOI":"10.1007\/s10616-006-9030-7"}],"container-title":["Biotechnology and Bioengineering"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/bit.28785","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T21:23:08Z","timestamp":1760044988000},"score":1,"resource":{"primary":{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/10.1002\/bit.28785"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,7,11]]},"references-count":38,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2024,11]]}},"alternative-id":["10.1002\/bit.28785"],"URL":"https:\/\/doi.org\/10.1002\/bit.28785","archive":["Portico"],"relation":{},"ISSN":["0006-3592","1097-0290"],"issn-type":[{"type":"print","value":"0006-3592"},{"type":"electronic","value":"1097-0290"}],"subject":[],"published":{"date-parts":[[2024,7,11]]},"assertion":[{"value":"2024-03-01","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-06-15","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-07-11","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}