{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T14:47:50Z","timestamp":1788446870093,"version":"build-2803163510"},"reference-count":12,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2023,4,20]],"date-time":"2023-04-20T00:00:00Z","timestamp":1681948800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Biotech &amp; Bioengineering"],"published-print":{"date-parts":[[2023,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>In the production of monoclonal antibodies (mAbs) intended for use in humans, it is a global regulatory requirement that the manufacturing process includes unit operations that are proven to inactivate or remove adventitious agents to ensure viral safety. Viral inactivation by low pH hold (LPH) is typically used to ensure this viral safety in the purification process of mAbs and other biotherapeutics derived from mammalian cell lines. To ascertain the effectiveness of the LPH step, viral clearance studies have evaluated LPH under worst\u2010case conditions of pH above the manufacturing set point and hold duration at or below the manufacturing minimum. Highly acidic conditions (i.e., pH\u2009&lt;\u20093.60) provide robust and effective enveloped virus inactivation but may lead to reduced product quality of the therapeutic protein. However, when viral inactivation is operated above pH 3.60 to ensure product stability, effective (&gt;4 log<jats:sub>10<\/jats:sub> reduction factor) viral inactivation may not be observed under these worst\u2010case pH conditions in viral clearance studies. A multivariate design of experiments was conducted to further characterize the operating space for low pH viral inactivation of a model retrovirus, xenotropic murine leukemia virus (X\u2010MuLV). The statistically designed experiment evaluated the effect of mAb isotype, pH, temperature, acid titrant, sodium chloride (NaCl) concentration, virus spike timing, and post\u2010spike filtration on X\u2010MuLV inactivation. Data from the characterization study were used to generate predictive models to identify conditions that reliably achieve effective viral inactivation at pH\u2009\u2265\u20093.60. Results of the study demonstrated that NaCl concentration has the greatest effect on virus inactivation in the range studied, and pH has a large effect when the load material has no additional NaCl. Overall, robust and effective inactivation of X\u2010MuLV at pH 3.65\u20133.80 can be achieved by manipulating either the pH or the NaCl concentration of the load material. This study contributes to the understanding of ionic strength as an influential parameter in low pH viral inactivation studies.<\/jats:p>","DOI":"10.1002\/bit.28379","type":"journal-article","created":{"date-parts":[[2023,3,16]],"date-time":"2023-03-16T02:49:10Z","timestamp":1678934950000},"page":"1605-1613","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Characterization of ionic strength for X\u2010MuLV inactivation by low pH treatment for monoclonal antibody purification"],"prefix":"10.1002","volume":"120","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4931-9210","authenticated-orcid":false,"given":"Jena","family":"Daya","sequence":"first","affiliation":[{"name":"Regeneron Pharmaceuticals, Inc.  Tarrytown New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valerie","family":"Cusick","sequence":"additional","affiliation":[{"name":"Regeneron Pharmaceuticals, Inc.  Tarrytown New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Mattila","sequence":"additional","affiliation":[{"name":"Regeneron Pharmaceuticals, Inc.  Tarrytown New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,4,20]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11095-012-0885-3"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1520\/E2888-12"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/bit.10574"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/btpr.2183"},{"key":"e_1_2_9_6_1","unstructured":"EMEA. (2008).Guideline on virus safety evaluation of biotechnology investigational medicinal products. European Medicines Agency."},{"key":"e_1_2_9_7_1","unstructured":"ICH. (1998). Guidance on viral safety evaluation of biotechnology products derived from cell lines of human or animal origin Q5A.International conference for harmonization of technical requirements for registration of pharmaceuticals for human use.Geneva Switzerland."},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/biot.201400052"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.5731\/pdajpst.2016.006478"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/bit.22662"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chroma.2007.09.040"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jchromb.2006.09.026"},{"key":"e_1_2_9_13_1","unstructured":"U.S. Food and Drug Administration (FDA). (1997). Points to consider in the manufacture and testing of monoclonal antibody products for human use.Docket No 94D\u20130259."}],"container-title":["Biotechnology and Bioengineering"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/bit.28379","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/bit.28379","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T20:13:05Z","timestamp":1760040785000},"score":1,"resource":{"primary":{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/10.1002\/bit.28379"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,4,20]]},"references-count":12,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2023,6]]}},"alternative-id":["10.1002\/bit.28379"],"URL":"https:\/\/doi.org\/10.1002\/bit.28379","archive":["Portico"],"relation":{},"ISSN":["0006-3592","1097-0290"],"issn-type":[{"value":"0006-3592","type":"print"},{"value":"1097-0290","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,4,20]]},"assertion":[{"value":"2023-02-07","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-03-13","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-04-20","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}