{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T07:55:06Z","timestamp":1790582106169,"version":"4.1.0"},"reference-count":31,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T00:00:00Z","timestamp":1790467200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T00:00:00Z","timestamp":1790467200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Biotech &amp; Bioengineering"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Perfusion cell culture is increasingly adopted to improve productivity, reduce footprint, and enable integrated continuous bioprocessing. The high\u2010intensity, low\u2010volume perfusion (HILVOP) process for antibody production was implemented at both 100\u2009L pilot and 500\u2009L manufacturing scales for early clinical supply, and development work was completed in tandem to create a next\u2010generation HILVOP platform. The HILVOP process employs a dynamic two\u2011stage strategy, using cell\u2011controlled perfusion during the growth phase followed by product removal during the intensified production phase via tangential flow filtration (TFF). Scale\u2011up performance was evaluated across multiple CHO cell lines with a focus on membrane robustness, product recovery, and space\u2011time yield. Early manufacturing runs identified membrane fouling as a key risk, particularly with challenging cell lines. Systematic optimization of TFF operating conditions (reduced membrane wall shear rate, larger pore size, alternative filter membrane, and refinement of perfusion rate profiles) improved membrane performance, delayed transmembrane pressure (TMP) rise, and increased cumulative product recovery while reducing media consumption. Additional productivity gains were achieved through high\u2011density seeding and extension of the productive perfusion phase, resulting in increased permeate space\u2011time yield. These results demonstrate the robustness and scalability of the HILVOP platform and highlight key design considerations enabling reliable manufacturing\u2011scale perfusion operation.<\/jats:p>","DOI":"10.1002\/bit.70389","type":"journal-article","created":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T06:55:58Z","timestamp":1790578558000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Implementing an Intensified Dynamic Perfusion Process for Biologics Manufacturing at Scale and Continued Development"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-6706-2294","authenticated-orcid":false,"given":"Jennifer","family":"Nguyen","sequence":"first","affiliation":[{"name":"Bioprocess Research and Development, Pfizer Inc Andover Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-9904-7424","authenticated-orcid":false,"given":"Alaina","family":"Anand","sequence":"additional","affiliation":[{"name":"Bioprocess Research and Development, Pfizer Inc Andover Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meghan","family":"Sullivan","sequence":"additional","affiliation":[{"name":"Bioprocess Research and Development, Pfizer Inc Andover Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenge","family":"Wang","sequence":"additional","affiliation":[{"name":"Bioprocess Research and Development, Pfizer Inc Andover Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-0706-2224","authenticated-orcid":false,"given":"Spencer","family":"Barr","sequence":"additional","affiliation":[{"name":"Bioprocess Research and Development, Pfizer Inc Andover Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9","family":"Gomes","sequence":"additional","affiliation":[{"name":"Bioprocess Research and Development, Pfizer Inc Andover Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandra","family":"Molinaro","sequence":"additional","affiliation":[{"name":"Bioprocess Research and Development, Pfizer Inc Andover Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Greg","family":"Porter","sequence":"additional","affiliation":[{"name":"Bioprocess Research and Development, Pfizer Inc Andover Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0386-0562","authenticated-orcid":false,"given":"Matthew","family":"Gagnon","sequence":"additional","affiliation":[{"name":"Bioprocess Research and Development, Pfizer Inc Andover Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aravindan","family":"Rajendran","sequence":"additional","affiliation":[{"name":"Bioprocess Research and Development, Pfizer Inc Andover Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,27]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biotechadv.2018.04.011"},{"key":"e_1_2_9_3_1","volume-title":"Technologies in Cell Culture \u2010 A Journey From Basics to Advanced Applications","author":"Chemmalil L.","year":"2023"},{"key":"e_1_2_9_4_1","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1007\/978-3-031-45669-5_4","volume-title":"Biopharmaceutical Manufacturing: Progress, Trends and Challenges","author":"Chotteau V.","year":"2023"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/bit.70184"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/btpr.3378"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/bit.23072"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/btpr.2723"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbiotec.2016.12.005"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bej.2018.01.031"},{"key":"e_1_2_9_11_1","unstructured":"Hiller G. 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