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Improvements in single-use bioreactor film material composition leads to robust and reliable Chinese hamster ovary cell performance

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dc.contributor.author Kelly, Paul S.
dc.contributor.author Dorival-García, Noemi
dc.contributor.author Paré, Samantha
dc.contributor.author Carillo, Sara
dc.contributor.author Ta, Christine
dc.contributor.author Alarcon Miguez, Antonio
dc.contributor.author Coleman, Orla
dc.contributor.author Harper, Emma
dc.contributor.author Shannon, Maeve
dc.contributor.author Henry, Michael
dc.contributor.author Connolly, Lisa
dc.contributor.author Harper, Emma
dc.contributor.author Shannon, Maeve
dc.contributor.author Henry, Michael
dc.contributor.author Connolly, Lisa
dc.contributor.author Clynes, Martin
dc.contributor.author Meleady, Paula
dc.contributor.author Bones, Jonathan
dc.contributor.author Barron, Niall
dc.date.accessioned 2019-09-25T08:20:36Z
dc.date.issued 2019
dc.identifier.uri http://hdl.handle.net/10344/8067
dc.description peer-reviewed en_US
dc.description.abstract Single‐use technologies, in particular disposable bioreactor bags, have become integral within the biopharmaceutical community. However, safety concerns arose upon the identification of toxic leachable compounds derived from the plastic materials. Although the leachable bis(2,4‐di‐tert‐butylphenyl)‐phosphate (bDtBPP) has been previously shown to inhibit CHO cell growth, it is critical to determine if other compounds like this are still present in subsequent generations of films for industrial application. This study compares the performance of CHO cells, CHO‐K1, and CHO‐DP12, cultured in media conditioned in an older single‐use bioreactor (SUB) film (F‐1) and a newer generation film (F‐2) from the same vendor. CHO cells cultured in media conditioned for 7 days in the F‐1 film demonstrated significantly reduced growth and antibody productivity profiles when compared to controls and media conditioned for the same time period in the newer F‐2 film. Proteomic profiling of CHO cells cultured in the F‐1 conditioned media identified differentially expressed proteins involved in oxidative stress response as well as compromised ATP synthesis. These potentially metabolically compromised cells exhibited reduced oxidative phosphorylation activity as well as lower glycolytic metabolism, characteristic of slower growing cells. Nonvolatile and metal leachables analysis of film extracts by LC–MS revealed a reduction in the abundance of the analyzed leachates from F‐2 films when compared to F‐1 films including bDtBPP, potentially explaining improved CHO cell growth in F‐2 conditioned media. Furthermore, in vitro endocrine disruptor testing of the known leachable revealed this molecule to possess the potential to act as an androgen antagonist. This study demonstrates an improvement in the materials composition used in modern generations of SUBs for safe application in the bioprocess. en_US
dc.language.iso eng en_US
dc.publisher Wiley and Sons Ltd en_US
dc.relation.ispartofseries Biotechnology Progress;35 (4), e2824
dc.relation.uri https://dx.doi.org/10.1002/btpr.2824
dc.rights This is the author accepted peer reviewed version of the following article:Improvements in single-use bioreactor film material composition leads to robust and reliable Chinese hamster ovary cell performance, Biotechnology Progress, 2019, 35 (4), e2824, https://dx.doi.org/10.1002/btpr.2824 which has been published in final form at [Link to final article using the DOI]. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving. http://olabout.wiley.com/WileyCDA/Section/id-828039.html#terms en_US
dc.subject single use technologies en_US
dc.title Improvements in single-use bioreactor film material composition leads to robust and reliable Chinese hamster ovary cell performance en_US
dc.type info:eu-repo/semantics/article en_US
dc.type.supercollection all_ul_research en_US
dc.type.supercollection ul_published_reviewed en_US
dc.identifier.doi 10.1002/btpr.2824
dc.contributor.sponsor SFI
dc.relation.projectid 16/RI/3701
dc.relation.projectid 13/SPSSPC/12893
dc.date.embargoEndDate 2020-04-24
dc.embargo.terms 2020-04-24 en_US
dc.rights.accessrights info:eu-repo/semantics/openAccess en_US


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