{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,22]],"date-time":"2026-08-22T07:23:12Z","timestamp":1787383392858,"version":"build-2736575974"},"reference-count":14,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,4,3]],"date-time":"2026-04-03T00:00:00Z","timestamp":1775174400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,4,3]],"date-time":"2026-04-03T00:00:00Z","timestamp":1775174400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["aiche.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Biotechnology Progress"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>We investigated side\u2010by\u2010side clarification with a two\u2010stage depth filter system against a single\u2010stage charge chromatographic clarifier on a number of Chinese hamster ovary (CHO) cell cultures. We found that the one\u2010stage fibrous anion exchange (AEX) clarification met or exceeded the performance of the conventional two\u2010stage depth filtration systems in terms of product recovery, removal of process\u2010related impurities, and throughput. The one\u2010stage anion clarification approach had a smaller footprint, a shorter set\u2010up time, an easier setup, consumed less buffer flush volume, and operated at a lower differential pressure relative to those of conventional systems. In a comparability study at 200\u2009L scale, antibodies in cell culture fluid (CCF) clarified by depth filtration system exhibited product quality degradation due to disulfide bond reduction (DSBR), whereas antibodies clarified by AEX fiber method were not. We surmised that the lower operating differential pressure and electrostatic adsorption mechanism of the anion clarification system minimized the potential of product to undergo DSBR. We developed a bench\u2010scale process model that allowed us to assay DSBR and predict the process results. We then utilized it to demonstrate that the antibody was reduced when clarified with a two\u2010stage 3\u2009M\u2122 Zeta Plus\u2122 Depth Filter system but not with the anionic clarification system. This bench\u2010scale DSBR assay allowed us to rank the relative disulfide bond reduction potentials of various monoclonal antibodies (mAbs) and demonstrate the reduction\u2010mitigating impacts of the fibrous clarification approach on a reduction\u2010prone antibody culture at 2000\u2009L processing scale.<\/jats:p>","DOI":"10.1002\/btpr.88507","type":"journal-article","created":{"date-parts":[[2026,4,3]],"date-time":"2026-04-03T08:07:23Z","timestamp":1775203643000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Disulfide bond reduction of antibodies during clarification: A bench\u2010scale assay and a mitigation tool"],"prefix":"10.1002","volume":"42","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-6447-7786","authenticated-orcid":false,"given":"Hendri","family":"Tjandra","sequence":"first","affiliation":[{"name":"Biologics Pilot Lab PDM, Gilead Sciences  Foster City California USA"},{"name":"Biologics Development Isolation &amp; Purification, Bayer Healthcare LLC  Berkeley California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deepa","family":"Surendar","sequence":"additional","affiliation":[{"name":"Biologics Development Isolation &amp; Purification, Bayer Healthcare LLC  Berkeley California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isu","family":"Yoon","sequence":"additional","affiliation":[{"name":"Biologics Development Isolation &amp; Purification, Bayer Healthcare LLC  Berkeley California USA"},{"name":"Manufacturing Science and Technology \u2013 Purification Lonza  Vacaville California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florence","family":"Rusly","sequence":"additional","affiliation":[{"name":"Biologics Development Isolation &amp; Purification, Bayer Healthcare LLC  Berkeley California USA"},{"name":"Pre\u2010Pivotal Purification Development PDM, Gilead Sciences  Foster City California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Su","sequence":"additional","affiliation":[{"name":"Biologics Development Isolation &amp; Purification, Bayer Healthcare LLC  Berkeley California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vu","family":"Thai","sequence":"additional","affiliation":[{"name":"Biologics Development Isolation &amp; Purification, Bayer Healthcare LLC  Berkeley California USA"},{"name":"Process Development Ultragenyx Pharmaceutical Inc.  South San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Liu","sequence":"additional","affiliation":[{"name":"Biologics Development Isolation &amp; Purification, Bayer Healthcare LLC  Berkeley California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashley","family":"Hesslein","sequence":"additional","affiliation":[{"name":"Biologics Development Isolation &amp; Purification, Bayer Healthcare LLC  Berkeley California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,4,3]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978\u20100\u201008\u2010103019\u20106.00006\u20100"},{"issue":"5","key":"e_1_2_9_3_1","first-page":"34","article-title":"Harvest and recovery of monoclonal antibodies from large\u2010scale mammalian cell culture","volume":"21","author":"Shukla AA","year":"2008","journal-title":"BioPharm Int"},{"issue":"9","key":"e_1_2_9_4_1","first-page":"52","article-title":"Evaluating disposable depth filtration platforms for mAb harvest clarification","volume":"9","author":"Pegel A","year":"2011","journal-title":"BioProcess Int"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/btpr.2882"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/bit.27513"},{"issue":"9","key":"e_1_2_9_7_1","first-page":"32","article-title":"The secret life of protein a","volume":"13","author":"Gagnon P","year":"2015","journal-title":"BioProcess Int"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/btpr.3323"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/bit.25967"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/btpr.4"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/bit.26964"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/bit.24607"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/bit.27797"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/bit.22699"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/bit.22848"}],"container-title":["Biotechnology Progress"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/aiche.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/btpr.88507","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/aiche.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/btpr.88507","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/aiche.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/btpr.88507","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,22]],"date-time":"2026-08-22T06:33:13Z","timestamp":1787380393000},"score":1,"resource":{"primary":{"URL":"https:\/\/aiche.onlinelibrary.wiley.com\/doi\/10.1002\/btpr.88507"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,3]]},"references-count":14,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2026,7]]}},"alternative-id":["10.1002\/btpr.88507"],"URL":"https:\/\/doi.org\/10.1002\/btpr.88507","archive":["Portico"],"relation":{},"ISSN":["8756-7938","1520-6033"],"issn-type":[{"value":"8756-7938","type":"print"},{"value":"1520-6033","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,3]]},"assertion":[{"value":"2025-11-16","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-03-12","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-04-03","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e88507"}}