{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T04:51:05Z","timestamp":1782190265538,"version":"3.54.5"},"reference-count":23,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2023,1,24]],"date-time":"2023-01-24T00:00:00Z","timestamp":1674518400000},"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":[[2023,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>A single\u2010stage clarification was developed using a single\u2010use chromatographic clarification device (CCD) to recover a recombinant protein from Chinese Hamster Ovary (CHO) harvest cell culture fluid (HCCF). Clarification of a CHO HCCF is a complex and costly process, involving multiple stages of centrifugation and\/or depth filtration to remove cells and debris and to reduce process\u2010related impurities such as host cell protein (HCP), nucleic acids, and lipids. When using depth filtration, the filter train consists of multiple filters of varying ratios, layers, pore sizes, and adsorptive properties. The depth filters, in combination with a 0.2\u2010micron membrane filter, clarify the HCCF based on size\u2010exclusion, adsorptive, and charge\u2010based mechanisms, and provide robust bioburden control. Each stage of the clarification process requires time, labor, and utilities, with product loss at each step. Here, use of the 3M\u2122 Harvest RC Chromatographic Clarifier, a single\u2010stage CCD, is identified as an alternative strategy to a three\u2010stage filtration train. The CCD results in less overall filter area, less volume for flushing, and higher yield. Using bioprocess cost modeling, the single\u2010stage clarification process was compared to a three\u2010stage filtration process. By compressing the CHO HCCF clarification to a single chromatographic stage, the overall cost of the clarification process was reduced by 17%\u201330%, depending on bioreactor scale. The main drivers for the cost reduction were reduced total filtration area, labor, time, and utilities. The benefits of the single\u2010stage harvest process extended throughout the downstream process, resulting in a 25% relative increase in cumulative yield with comparable impurity clearance.<\/jats:p>","DOI":"10.1002\/btpr.3323","type":"journal-article","created":{"date-parts":[[2023,1,4]],"date-time":"2023-01-04T06:35:15Z","timestamp":1672814115000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Single\u2010stage chromatographic clarification of Chinese Hamster Ovary cell harvest reduces cost of protein production"],"prefix":"10.1002","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2145-5659","authenticated-orcid":false,"given":"Brian","family":"O'Mara","sequence":"first","affiliation":[{"name":"Process Development Ambrx, Inc.  La Jolla California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9440-9266","authenticated-orcid":false,"given":"Naveen Kumar","family":"Singh","sequence":"additional","affiliation":[{"name":"Process Development Ambrx, Inc.  La Jolla California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alicia","family":"Menendez","sequence":"additional","affiliation":[{"name":"Process Development Ambrx, Inc.  La Jolla California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Tipton","sequence":"additional","affiliation":[{"name":"Process Development Ambrx, Inc.  La Jolla California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Vail","sequence":"additional","affiliation":[{"name":"Separation and Purification Sciences 3M  St. Paul Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexei","family":"Voloshin","sequence":"additional","affiliation":[{"name":"Separation and Purification Sciences 3M  St. Paul Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Buechler","sequence":"additional","affiliation":[{"name":"Process Development Ambrx, Inc.  La Jolla California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0365-2552","authenticated-orcid":false,"given":"Sean M.","family":"Anderson","sequence":"additional","affiliation":[{"name":"Separation and Purification Sciences 3M  St. Paul Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,1,24]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0290(20000705)69:1<74::AID-BIT9>3.0.CO;2-K"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/9783527800599.ch14"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/bit.260440609"},{"issue":"4","key":"e_1_2_9_5_1","first-page":"30","article-title":"Fed\u2010batch mammalian cell culture in bioproduction","volume":"4","author":"Whitford WG","year":"2006","journal-title":"Bio Proc 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