{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T22:03:47Z","timestamp":1792015427117,"version":"4.4.0"},"reference-count":46,"publisher":"Wiley","issue":"3","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":["aiche.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Biotechnology Progress"],"published-print":{"date-parts":[[2025,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>As the industry continues to explore the benefits of continuous and intensified manufacturing, it is important to assure that the cell line development (CLD) workflows in practice today are well suited to generate clones that meet the unique challenges associated with these processes. Most cell lines used in intensified processes are currently developed using traditional fed\u2010batch CLD workflows followed by adaptation of these cell lines to perfusion processes. This method maybe suboptimal as fed\u2010batch CLD workflows select clones which produce high volumetric titers irrespective of cell growth rate and specific productivity (qP). Although sufficient for fed\u2010batch processes, performance of cells derived from this traditional CLD workflow may not be maintained in perfusion processes, where an intricate balance of performance parameters is needed. Until now, a thorough investigation into the effect of the CLD workflow on top clone performance in perfusion processes has not been conducted. Here, we show how the CLD workflow impacts cell performance in both fed\u2010batch and perfusion processes, emphasizing the advantages of adopting a perfusion\u2010specific CLD workflow which includes the use of medium specially designed for expansion and production in a perfusion setting, scale\u2010down models which more accurately simulate perfusion process, and the adoption of perfusion\u2010specific cell line selection criteria. Together, this results in the development of more efficient cell lines, fit for continuous and intensified processing.<\/jats:p>","DOI":"10.1002\/btpr.70003","type":"journal-article","created":{"date-parts":[[2025,2,19]],"date-time":"2025-02-19T04:54:36Z","timestamp":1739940876000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Improving outcomes in intensified processing via optimization of the cell line development workflow"],"prefix":"10.1002","volume":"41","author":[{"given":"Vincent","family":"Balassi","sequence":"first","affiliation":[{"name":"Expression Systems and Novel Biopharmaceutical Materials, MilliporeSigma  Saint Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary","family":"Otto","sequence":"additional","affiliation":[{"name":"Expression Systems and Novel Biopharmaceutical Materials, MilliporeSigma  Saint Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Corey","family":"Kretzmer","sequence":"additional","affiliation":[{"name":"Expression Systems and Novel Biopharmaceutical Materials, MilliporeSigma  Saint Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amber","family":"Petersen","sequence":"additional","affiliation":[{"name":"Expression Systems and Novel Biopharmaceutical Materials, MilliporeSigma  Saint Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Channing","family":"McLaurin","sequence":"additional","affiliation":[{"name":"Cell Culture Media and Process Development, MilliporeSigma  Saint Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jana","family":"Mahadevan","sequence":"additional","affiliation":[{"name":"Cell Culture Media and Process Development, MilliporeSigma  Saint Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason","family":"Gustin","sequence":"additional","affiliation":[{"name":"Expression Systems and Novel Biopharmaceutical Materials, MilliporeSigma  Saint Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Trissa","family":"Borgschulte","sequence":"additional","affiliation":[{"name":"Expression Systems and Novel Biopharmaceutical Materials, MilliporeSigma  Saint Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6292-0169","authenticated-orcid":false,"given":"David","family":"Razafsky","sequence":"additional","affiliation":[{"name":"Expression Systems and Novel Biopharmaceutical Materials, MilliporeSigma  Saint Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,2,19]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.4161\/mabs.1.5.9448"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.coche.2018.10.006"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/bit.28226"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells12222661"},{"key":"e_1_2_11_6_1","first-page":"1","article-title":"Biopharmaceutical proteins: opportunities and challenges","volume":"308","author":"Birch JR","year":"2005","journal-title":"Methods Mol Biol"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1385\/1592599222"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/btm2.10061"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4939-7312-5_12"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/elsc.202100062"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/biot.201700733"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00253-022-12342-x"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbiotec.2019.04.005"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/bit.26278"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbiotec.2011.11.009"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1080\/19420862.2016.1268307"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1080\/07388551.2021.1998821"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/bit.24608"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/btpr.2973"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biotechadv.2021.107831"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbiotec.2005.10.013"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1021\/bp049807b"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/biot.201700721"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00253-016-7380-4"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/btpr.3449"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0277620"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-13867-y"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1002\/bit.27690"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1002\/biot.201700686"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.4161\/mabs.2.6.13333"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11095-023-03628-4"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.3390\/antib11040073"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1002\/bit.26904"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tibtech.2016.02.013"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1002\/bit.28682"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1002\/biot.201900306"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.164.3879.555"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF02618284"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.3389\/fbioe.2023.1160223"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.1002\/btpr.3399"},{"issue":"1","key":"e_1_2_11_41_1","first-page":"1","article-title":"Evaluation of two transposases for improving expression of recombinant proteins in Chinese hamster ovary cell stable pools by co\u2010transfection and supertransfection approaches","volume":"17","author":"Lenser M","year":"2024","journal-title":"Biotechnol Prog"},{"key":"e_1_2_11_42_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-0716-3878-1_9"},{"issue":"1","key":"e_1_2_11_43_1","first-page":"1","article-title":"The new frontier in CHO cell line development: From random to targeted transgene integration technologies","volume":"108402","author":"Zeh N","year":"2024","journal-title":"Biotechnol Adv"},{"key":"e_1_2_11_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymben.2022.03.015"},{"key":"e_1_2_11_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymben.2023.09.006"},{"key":"e_1_2_11_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymben.2021.03.017"},{"key":"e_1_2_11_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.crmeth.2021.100062"}],"container-title":["Biotechnology Progress"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/aiche.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/btpr.70003","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T12:11:04Z","timestamp":1761653464000},"score":1,"resource":{"primary":{"URL":"https:\/\/aiche.onlinelibrary.wiley.com\/doi\/10.1002\/btpr.70003"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2,19]]},"references-count":46,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2025,5]]}},"alternative-id":["10.1002\/btpr.70003"],"URL":"https:\/\/doi.org\/10.1002\/btpr.70003","archive":["Portico"],"relation":{},"ISSN":["8756-7938","1520-6033"],"issn-type":[{"value":"8756-7938","type":"print"},{"value":"1520-6033","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,2,19]]},"assertion":[{"value":"2024-07-22","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-01-29","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-02-19","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70003"}}