{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T06:50:52Z","timestamp":1791960652998,"version":"4.3.4"},"reference-count":23,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T00:00:00Z","timestamp":1791849600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T00:00:00Z","timestamp":1791849600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Biotech &amp;amp; Bioengineering"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Process consistency in biomanufacturing, particularly for commercial products, is critical for achieving consistent yield and product quality. The N\u20101 seed bioreactor stage, where cells grow before the transfer to a production bioreactor, often faces variability in final viable cell density (VCD), which leads to variable seeding densities in the production bioreactor and subsequent variability in total protein output per batch. In this study, we address the challenge of precise batch transfer by developing an upstream, stage\u2010specific, level\u20102 digital twin (digital shadow). Here we show that a cell growth process model predicts growth accurately and updates forecasts using off\u2010line and in\u2010line measurements, enabling precise determination of the final sample time. Deployment of this seed transfer digital twin led to all N\u20101 to production transfers falling within acceptable limits and resulted in statistically significant increases in harvest yield relative to historical batches. This improvement is attributed to significantly higher on\u2010target accuracy of final N\u20101 VCDs and significantly higher working volumes in the production bioreactors. Our findings demonstrate that such digital twins ensure consistent cell density during transfer, improve overall upstream process consistency, and lay a foundation for more advanced process control strategies.<\/jats:p>","DOI":"10.1002\/bit.70400","type":"journal-article","created":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T06:42:07Z","timestamp":1791960127000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Biomanufacturing Digital Twin for Consistent N\u20101 Seed Bioreactor Transfers for Commercial Monoclonal Antibody Production"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1379-6373","authenticated-orcid":false,"given":"Yu","family":"Luo","sequence":"first","affiliation":[{"name":"GSK, Predictive Sciences Upper Merion Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sumit","family":"Pareek","sequence":"additional","affiliation":[{"name":"GSK, Global Supply Chain Digital and Technology Upper Merion Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolyn","family":"Zhang","sequence":"additional","affiliation":[{"name":"GSK, Enterprise AI Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelly","family":"Sarnese","sequence":"additional","affiliation":[{"name":"GSK, MSAT Upper Merion Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diana","family":"Ritz","sequence":"additional","affiliation":[{"name":"GSK, Biopharmaceutical Drug Substance Development Upper Merion Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7670-0439","authenticated-orcid":false,"given":"Sameer","family":"Talwar","sequence":"additional","affiliation":[{"name":"GSK, Predictive Sciences Upper Merion Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,13]]},"reference":[{"issue":"1","key":"e_1_2_9_2_1","doi-asserted-by":"crossref","DOI":"10.1002\/btpr.3503","article-title":"Hybrid Modeling for in Silico Optimization of a Dynamic Perfusion Cell Culture Process","volume":"41","author":"Agarwal P.","year":"2025","journal-title":"Biotechnology Progress"},{"key":"e_1_2_9_3_1","doi-asserted-by":"crossref","DOI":"10.3389\/fbioe.2021.740215","article-title":"Model Transferability and Reduced Experimental Burden in Cell Culture Process Development Facilitated by Hybrid Modeling and Intensified Design of Experiments","volume":"9","author":"Bayer 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Y.Luo andZ.Hatzenbeller. Towards \u201cTighter\u201d Titer: Model Predictive Control in Fed\u2010batch Bioreactors. in 2025 American Control Conference (ACC).2025.","DOI":"10.23919\/ACC63710.2025.11107677"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/btpr.3410"},{"issue":"9","key":"e_1_2_9_16_1","doi-asserted-by":"crossref","first-page":"2494","DOI":"10.1002\/bit.28405","article-title":"Data\u2010Driven Prediction Models for Forecasting Multistep Ahead Profiles of Mammalian Cell Culture Toward Bioprocess Digital Twins","volume":"120","author":"Park S. Y.","year":"2023","journal-title":"Biotechnology and Bioengineering"},{"key":"e_1_2_9_17_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.coche.2021.100702","article-title":"Bioprocess Digital Twins of Mammalian Cell Culture for Advanced Biomanufacturing","volume":"33","author":"Park S.\u2010Y.","year":"2021","journal-title":"Current Opinion in Chemical Engineering"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.3389\/fbioe.2023.1237963"},{"issue":"1","key":"e_1_2_9_19_1","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1002\/btpr.1672","article-title":"Optimizing Capacity Utilization by Large Scale 3000 L Perfusion in Seed Train Bioreactors","volume":"29","author":"Pohlscheidt M.","year":"2013","journal-title":"Biotechnology Progress"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.3389\/fbioe.2022.948905"},{"issue":"4","key":"e_1_2_9_21_1","doi-asserted-by":"crossref","first-page":"128","DOI":"10.3390\/bioengineering9040128","article-title":"N\u20101 Perfusion Platform Development Using a Capacitance Probe for Biomanufacturing","volume":"9","author":"Rittershaus E. 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