{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T22:36:56Z","timestamp":1793313416618,"version":"4.5.0"},"reference-count":27,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,1,9]],"date-time":"2025-01-09T00:00:00Z","timestamp":1736380800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,1,9]],"date-time":"2025-01-09T00:00:00Z","timestamp":1736380800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100000038","name":"U.S. Food and Drug Administration","doi-asserted-by":"publisher","award":["1R01FD006588"],"award-info":[{"award-number":["1R01FD006588"]}],"id":[{"id":"10.13039\/100000038","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000038","name":"U.S. Food and Drug Administration","doi-asserted-by":"publisher","award":["1R01FD006588"],"award-info":[{"award-number":["1R01FD006588"]}],"id":[{"id":"10.13039\/100000038","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000038","name":"U.S. Food and Drug Administration","doi-asserted-by":"publisher","award":["1R01FD006588"],"award-info":[{"award-number":["1R01FD006588"]}],"id":[{"id":"10.13039\/100000038","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000038","name":"U.S. Food and Drug Administration","doi-asserted-by":"publisher","award":["1R01FD006588"],"award-info":[{"award-number":["1R01FD006588"]}],"id":[{"id":"10.13039\/100000038","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000038","name":"U.S. Food and Drug Administration","doi-asserted-by":"publisher","award":["1R01FD006588"],"award-info":[{"award-number":["1R01FD006588"]}],"id":[{"id":"10.13039\/100000038","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Cytotechnology"],"published-print":{"date-parts":[[2025,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:p>The choice of media and feeds significantly influences the performance of Chinese Hamster Ovary (CHO) mammalian cell cultures in producing desired biologics like monoclonal antibodies (mAb). Sub-optimal nutrient feed\/media composition can severely impact cell proliferation and the quality of the final mAb product. For instance, proper protein glycosylation, crucial for mAb stability, safety, and efficacy, heavily relies on cell culture conditions. Currently, starter CHO culture media and daily supplemental feeds used in industrial manufacturing consist of proprietary composition of nutrients critical for mAb production. Standardized optimal media\/feed combinations necessary for different cell lines are often lacking, necessitating individualized optimization for each cell line and mAb product. Here, we focused on a CHO-K1 cell line engineered to produce a Trastuzumab biosimilar and evaluated the effects of fourteen commercially relevant basal media and seven feeds on cell culture parameters such as viable cell density, viability, nutrient consumption, metabolite production, mAb titer, and mAb N-glycosylation. Our findings demonstrate clearly that the compositions of the basal medium and feed play a pivotal role in enhancing cell growth and mAb production. This work offers valuable insights into strategies for optimizing feed\/media composition for glycosylated monoclonal antibody production using CHO cells.<\/jats:p>","DOI":"10.1007\/s10616-024-00690-7","type":"journal-article","created":{"date-parts":[[2025,1,9]],"date-time":"2025-01-09T18:27:44Z","timestamp":1736447264000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Evaluating the impact of media and feed combinations on CHO cell culture performance and monoclonal antibody (trastuzumab) production"],"prefix":"10.1007","volume":"77","author":[{"given":"Aron","family":"Gyorgypal","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antash","family":"Chaturvedi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Viki","family":"Chopda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haoran","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3677-6735","authenticated-orcid":false,"given":"Shishir P. S.","family":"Chundawat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,1,9]]},"reference":[{"key":"690_CR1","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1016\/j.biologicals.2016.06.005","volume":"44","author":"N Alt","year":"2016","unstructured":"Alt N, Zhang TY, Motchnik P, Taticek R, Quarmby V, Schlothauer T, Beck H, Emrich T, Harris RJ (2016) Determination of critical quality attributes for monoclonal antibodies using quality by design principles. Biologicals 44:291\u2013305. https:\/\/doi.org\/10.1016\/j.biologicals.2016.06.005","journal-title":"Biologicals"},{"key":"690_CR2","doi-asserted-by":"publisher","first-page":"58","DOI":"10.1016\/j.aca.2014.06.021","volume":"840","author":"A Calvet","year":"2014","unstructured":"Calvet A, Ryder AG (2014) Monitoring cell culture media degradation using surface enhanced Raman scattering (SERS) spectroscopy. Anal Chim Acta 840:58\u201367. https:\/\/doi.org\/10.1016\/j.aca.2014.06.021","journal-title":"Anal Chim Acta"},{"key":"690_CR3","doi-asserted-by":"publisher","first-page":"563","DOI":"10.1016\/j.nbt.2012.12.002","volume":"30","author":"AR Costa","year":"2013","unstructured":"Costa AR, Withers J, Rodrigues ME, McLoughlin N, Henriques M, Oliveira R, Rudd PM, Azeredo J (2013) The impact of cell adaptation to serum-free conditions on the glycosylation profile of a monoclonal antibody produced by Chinese hamster ovary cells. N Biotechnol 30:563\u2013572. https:\/\/doi.org\/10.1016\/j.nbt.2012.12.002","journal-title":"N Biotechnol"},{"key":"690_CR4","doi-asserted-by":"publisher","first-page":"9","DOI":"10.4161\/19420862.2015.989042","volume":"7","author":"DM Ecker","year":"2015","unstructured":"Ecker DM, Jones SD, Levine HL (2015) The therapeutic monoclonal antibody market. Mabs 7:9\u201314. https:\/\/doi.org\/10.4161\/19420862.2015.989042","journal-title":"Mabs"},{"key":"690_CR5","doi-asserted-by":"publisher","first-page":"1591","DOI":"10.1002\/bit.23075","volume":"108","author":"MJ Gramer","year":"2011","unstructured":"Gramer MJ, Eckblad JJ, Donahue R, Brown J, Shultz C, Vickerman K, Priem P, van den Bremer ETJ, Gerritsen J, van Berkel PHC (2011) Modulation of antibody galactosylation through feeding of uridine, manganese chloride, and galactose. Biotechnol Bioeng 108:1591\u20131602. https:\/\/doi.org\/10.1002\/bit.23075","journal-title":"Biotechnol Bioeng"},{"key":"690_CR6","doi-asserted-by":"publisher","first-page":"126","DOI":"10.1002\/bit.26460","volume":"115","author":"MW Handlogten","year":"2018","unstructured":"Handlogten MW, Lee-O\u2019Brien A, Roy G, Levitskaya SV, Venkat R, Singh S, Ahuja S (2018) Intracellular response to process optimization and impact on productivity and product aggregates for a high-titer CHO cell process. Biotechnol Bioeng 115:126\u2013138. https:\/\/doi.org\/10.1002\/bit.26460","journal-title":"Biotechnol Bioeng"},{"key":"690_CR7","doi-asserted-by":"publisher","first-page":"869","DOI":"10.1007\/s00253-010-2790-1","volume":"88","author":"JK Hong","year":"2010","unstructured":"Hong JK, Cho SM, Yoon SK (2010) Substitution of glutamine by glutamate enhances production and galactosylation of recombinant IgG in Chinese hamster ovary cells. Appl Microbiol Biotechnol 88:869\u2013876. https:\/\/doi.org\/10.1007\/s00253-010-2790-1","journal-title":"Appl Microbiol Biotechnol"},{"key":"690_CR8","doi-asserted-by":"publisher","first-page":"359","DOI":"10.1002\/bit.25715","volume":"113","author":"HF Kildegaard","year":"2016","unstructured":"Kildegaard HF, Fan Y, Sen JW, Larsen B, Andersen MR (2016) Glycoprofiling effects of media additives on IgG produced by CHO cells in fed-batch bioreactors. Biotechnol Bioeng 113:359\u2013366. https:\/\/doi.org\/10.1002\/bit.25715","journal-title":"Biotechnol Bioeng"},{"key":"690_CR9","doi-asserted-by":"publisher","first-page":"547","DOI":"10.1080\/19420862.2018.1440170","volume":"10","author":"J Lee","year":"2018","unstructured":"Lee J, Kang HA, Bae JS, Kim KD, Lee KH, Lim KJ, Choo MJ, Chang SJ (2018) Evaluation of analytical similarity between trastuzumab biosimilar CT-P6 and reference product using statistical analyses. Mabs 10:547\u2013571. https:\/\/doi.org\/10.1080\/19420862.2018.1440170","journal-title":"Mabs"},{"key":"690_CR10","doi-asserted-by":"publisher","first-page":"92","DOI":"10.1016\/j.jbiotec.2021.01.023","volume":"329","author":"SR Madabhushi","year":"2021","unstructured":"Madabhushi SR, Podtelezhnikov AA, Murgolo N, Xu S, Lin H (2021) Understanding the effect of increased cell specific productivity on galactosylation of monoclonal antibodies produced using Chinese hamster ovary cells. J Biotechnol 329:92\u2013103. https:\/\/doi.org\/10.1016\/j.jbiotec.2021.01.023","journal-title":"J Biotechnol"},{"key":"690_CR11","doi-asserted-by":"publisher","first-page":"138","DOI":"10.1016\/j.ymben.2011.12.006","volume":"14","author":"BC Mulukutla","year":"2012","unstructured":"Mulukutla BC, Gramer M, Hu WS (2012) On metabolic shift to lactate consumption in fed-batch culture of mammalian cells. Metab Eng 14:138\u2013149. https:\/\/doi.org\/10.1016\/j.ymben.2011.12.006","journal-title":"Metab Eng"},{"key":"690_CR12","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1007\/s10616-016-0036-5","volume":"69","author":"X Pan","year":"2017","unstructured":"Pan X, Streefland M, Dalm C, Wijffels RH, Martens DE (2017) Selection of chemically defined media for CHO cell fed-batch culture processes. Cytotechnology 69:39\u201356. https:\/\/doi.org\/10.1007\/s10616-016-0036-5","journal-title":"Cytotechnology"},{"key":"690_CR13","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1146\/annurev.biochem.69.1.69","volume":"69","author":"AJ Parodi","year":"2000","unstructured":"Parodi AJ (2000) Protein glucosylation and its role in protein folding. Annu Rev Biochem 69:69\u201393. https:\/\/doi.org\/10.1146\/annurev.biochem.69.1.69","journal-title":"Annu Rev Biochem"},{"key":"690_CR14","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1002\/biot.201700499","volume":"13","author":"S Pereira","year":"2018","unstructured":"Pereira S, Kildegaard HF, Andersen MR (2018) Impact of CHO metabolism on cell growth and protein production: an overview of toxic and inhibiting metabolites and nutrients. Biotechnol J 13:1\u201313. https:\/\/doi.org\/10.1002\/biot.201700499","journal-title":"Biotechnol J"},{"key":"690_CR15","doi-asserted-by":"publisher","first-page":"206","DOI":"10.1002\/bit.24608","volume":"110","author":"J Pollock","year":"2013","unstructured":"Pollock J, Ho SV, Farid SS (2013) Fed-batch and perfusion culture processes: economic, environmental, and operational feasibility under uncertainty. Biotechnol Bioeng 110:206\u2013219. https:\/\/doi.org\/10.1002\/bit.24608","journal-title":"Biotechnol Bioeng"},{"key":"690_CR16","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3390\/antib7010001","volume":"7","author":"D Radhakrishnan","year":"2017","unstructured":"Radhakrishnan D, Robinson A, Ogunnaike B (2017) Controlling the glycosylation profile in mAbs using time-dependent media supplementation. Antibodies 7:1. https:\/\/doi.org\/10.3390\/antib7010001","journal-title":"Antibodies"},{"key":"690_CR17","doi-asserted-by":"publisher","DOI":"10.1101\/584144","author":"M Rasoul","year":"2019","unstructured":"Rasoul M, Sepideh S, Amir A, Mehdi K, Arezou FT, Paria M, Jafari F, Sofla I, Maleknia S (2019) Implementation of design of experiments (DOE) for optimization of feeding strategy and glyco-engineering of trastuzumab biosimilar. bioRxiv. https:\/\/doi.org\/10.1101\/584144","journal-title":"bioRxiv"},{"key":"690_CR18","doi-asserted-by":"publisher","first-page":"4645","DOI":"10.1007\/s00253-015-6514-4","volume":"99","author":"D Reinhart","year":"2015","unstructured":"Reinhart D, Damjanovic L, Kaisermayer C, Kunert R (2015) Benchmarking of commercially available CHO cell culture media for antibody production. Appl Microbiol Biotechnol 99:4645\u20134657. https:\/\/doi.org\/10.1007\/s00253-015-6514-4","journal-title":"Appl Microbiol Biotechnol"},{"key":"690_CR19","doi-asserted-by":"publisher","first-page":"303","DOI":"10.1016\/j.ijpharm.2012.08.002","volume":"437","author":"ME Rodrigues","year":"2012","unstructured":"Rodrigues ME, Costa AR, Henriques M, Azeredo J, Oliveira R (2012) Comparison of commercial serum-free media for CHO-K1 cell growth and monoclonal antibody production. Int J Pharm 437:303\u2013305. https:\/\/doi.org\/10.1016\/j.ijpharm.2012.08.002","journal-title":"Int J Pharm"},{"key":"690_CR20","doi-asserted-by":"publisher","first-page":"1415","DOI":"10.1002\/bit.24445","volume":"109","author":"S Selvarasu","year":"2012","unstructured":"Selvarasu S, Ho YS, Chong WPK, Wong NSC, Yusufi FNK, Lee YY, Yap MGS, Lee DY (2012) Combined in silico modeling and metabolomics analysis to characterize fed-batch CHO cell culture. Biotechnol Bioeng 109:1415\u20131429. https:\/\/doi.org\/10.1002\/bit.24445","journal-title":"Biotechnol Bioeng"},{"key":"690_CR21","doi-asserted-by":"publisher","first-page":"58","DOI":"10.1002\/btm2.10061","volume":"2","author":"AA Shukla","year":"2017","unstructured":"Shukla AA, Wolfe LS, Mostafa SS, Norman C (2017) Evolving trends in mAb production processes. Bioeng Transl Med 2:58\u201369. https:\/\/doi.org\/10.1002\/btm2.10061","journal-title":"Bioeng Transl Med"},{"key":"690_CR22","doi-asserted-by":"publisher","first-page":"1957","DOI":"10.1002\/bit.25251","volume":"111","author":"MM St. Amand","year":"2014","unstructured":"St. Amand MM, Radhakrishnan D, Robinson AS, Ogunnaike BA (2014) Identification of manipulated variables for a glycosylation control strategy. Biotechnol Bioeng 111:1957\u20131970. https:\/\/doi.org\/10.1002\/bit.25251","journal-title":"Biotechnol Bioeng"},{"key":"690_CR23","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1023\/A:1014032701800","volume":"36","author":"M Sue Lee","year":"2001","unstructured":"Sue Lee M, Min LG (2001) Effect of hypoosmotic pressure on cell growth and antibody production in recombinant Chinese hamster ovary cell culture. Cytotechnology 36:61\u201369","journal-title":"Cytotechnology"},{"key":"690_CR24","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1002\/biot.201700733","volume":"14","author":"J Walther","year":"2019","unstructured":"Walther J, Lu J, Hollenbach M, Yu M, Hwang C, McLarty J, Brower K (2019) Perfusion cell culture decreases process and product heterogeneity in a head-to-head comparison with fed-batch. Biotechnol J 14:1\u201310. https:\/\/doi.org\/10.1002\/biot.201700733","journal-title":"Biotechnol J"},{"key":"690_CR25","doi-asserted-by":"publisher","first-page":"3310","DOI":"10.1002\/bit.27496","volume":"117","author":"E Wells","year":"2020","unstructured":"Wells E, Song L, Greer M, Luo Y, Kurian V, Ogunnaike B, Robinson AS (2020) Media supplementation for targeted manipulation of monoclonal antibody galactosylation and fucosylation. Biotechnol Bioeng 117:3310\u20133321. https:\/\/doi.org\/10.1002\/bit.27496","journal-title":"Biotechnol Bioeng"},{"key":"690_CR26","doi-asserted-by":"publisher","first-page":"675","DOI":"10.1021\/bp070466m","volume":"24","author":"Z Xing","year":"2008","unstructured":"Xing Z, Li Z, Chow V, Lee SS (2008) Identifying inhibitory threshold values of repressing metabolites in CHO cell culture using multivariate analysis methods. Biotechnol Prog 24:675\u2013683. https:\/\/doi.org\/10.1021\/bp070466m","journal-title":"Biotechnol Prog"},{"key":"690_CR27","doi-asserted-by":"publisher","first-page":"2600","DOI":"10.1002\/bit.23218","volume":"108","author":"IH Yuk","year":"2011","unstructured":"Yuk IH, Zhang B, Yang Y, Dutina G, Leach KD, Vijayasankaran N, Shen AY, Andersen DC, Snedecor BR, Joly JC (2011) Controlling glycation of recombinant antibody in fed-batch cell cultures. Biotechnol Bioeng 108:2600\u20132610. https:\/\/doi.org\/10.1002\/bit.23218","journal-title":"Biotechnol Bioeng"}],"container-title":["Cytotechnology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10616-024-00690-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s10616-024-00690-7\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10616-024-00690-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,6]],"date-time":"2025-03-06T02:29:11Z","timestamp":1741228151000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s10616-024-00690-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,9]]},"references-count":27,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2025,2]]}},"alternative-id":["690"],"URL":"https:\/\/doi.org\/10.1007\/s10616-024-00690-7","relation":{},"ISSN":["0920-9069","1573-0778"],"issn-type":[{"value":"0920-9069","type":"print"},{"value":"1573-0778","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,1,9]]},"assertion":[{"value":"3 October 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"17 December 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"9 January 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"40"}}