{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T16:32:57Z","timestamp":1790785977935,"version":"4.1.0"},"reference-count":23,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,10,25]],"date-time":"2025-10-25T00:00:00Z","timestamp":1761350400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Biotech &amp;amp; Bioengineering"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Sterile filtration is an essential step in the production of lipid nanoparticles (LNPs) used in mRNA vaccines and therapeutics. The overlap between the particle size of the LNPs (typically 50\u2013200\u2009nm) and the pore size of the sterilizing\u2010grade membranes (rated at 0.2\u2009\u00b5m) complicates the design and operation of the sterile filtration process. The objective of this study was to characterize the pore size distribution, fouling behavior, and capacity of different sterilizing\u2010grade membranes and prefilters for LNP filtration. Mercury intrusion porosimetry revealed significant variability in pore size distributions across several sterilizing\u2010grade membranes despite their consistent 0.2\u2009\u00b5m rating, with LNP filtration capacity strongly correlated with the experimentally observed mean pore size. Dual\u2010layer membranes, including the 0.8\/0.2\u2009\u00b5m Sartopore 2 XLG, significantly enhanced LNP filtration capacity and reduced fouling due to their integrated prefilter layer. Prefilter membranes with pore sizes in the 400\u2013800\u2009nm range provided the greatest enhancement in LNP filtration capacity. These findings highlight that for a given LNP formulation, the filtration capacity is strongly influenced by sterilizing\u2010grade filter selection and specifically by the membrane pore size distribution and morphology, which are generally not published by filter manufacturers.<\/jats:p>","DOI":"10.1002\/bit.70089","type":"journal-article","created":{"date-parts":[[2025,10,25]],"date-time":"2025-10-25T08:01:28Z","timestamp":1761379288000},"page":"164-173","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Characterization of Sterilizing\u2010Grade Membranes\/Prefilters and Application to mRNA\u2010LNP Process Development"],"prefix":"10.1002","volume":"123","author":[{"given":"Kevork Oliver","family":"Messerian","sequence":"first","affiliation":[{"name":"Department of Chemical Engineering The Pennsylvania State University, University Park  Pennsylvania USA"},{"name":"Moderna Inc. Cambridge Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anton","family":"Zverev","sequence":"additional","affiliation":[{"name":"Moderna Inc. Cambridge Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jack F.","family":"Kramarczyk","sequence":"additional","affiliation":[{"name":"Moderna Inc. 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R.Wilkins andC.Carbrello \u201cSterile Filtration: Principles Best Practices and New Developments \u201d2013 [Online].https:\/\/api.semanticscholar.org\/CorpusID:107944252.","DOI":"10.1007\/978-1-4614-7978-9_16"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.18609\/vac\/2023.64"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/bit.28200"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.memsci.2023.121896"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.memsci.2024.122965"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.3390\/membranes12050524"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.3390\/polym11071160"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.memsci.2020.118750"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.memsci.2021.119436"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpharm.2025.125520"}],"container-title":["Biotechnology and Bioengineering"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/bit.70089","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,12]],"date-time":"2025-12-12T05:24:46Z","timestamp":1765517086000},"score":1,"resource":{"primary":{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/10.1002\/bit.70089"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,25]]},"references-count":23,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026,1]]}},"alternative-id":["10.1002\/bit.70089"],"URL":"https:\/\/doi.org\/10.1002\/bit.70089","archive":["Portico"],"relation":{},"ISSN":["0006-3592","1097-0290"],"issn-type":[{"value":"0006-3592","type":"print"},{"value":"1097-0290","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,25]]},"assertion":[{"value":"2025-07-31","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-10-15","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-10-25","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}