{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T04:25:48Z","timestamp":1786940748218,"version":"build-2736575974"},"reference-count":28,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,8,16]],"date-time":"2026-08-16T00:00:00Z","timestamp":1786838400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,8,16]],"date-time":"2026-08-16T00:00:00Z","timestamp":1786838400000},"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"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Low\u2010pH viral inactivation (LPVI) is a widely used, validated unit operation for enveloped virus clearance in antibody manufacturing. However, acid exposure during Protein A (ProA) elution and subsequent low\u2010pH holds can destabilize some antibodies and Fc\u2010containing modalities, increasing aggregation risk and product loss\u2014a challenge that is particularly acute for multi\u2010specific antibody formats and other pH\u2010labile Fc\u2010containing modalities. Mild\u2010pH ProA capture strategies protect such molecules, but the resulting higher\u2010pH eluates often require re\u2010acidification to meet conventional LPVI setpoints, reintroducing low\u2010pH stress. Here we evaluate a dual\u2010mechanism strategy in which mild acidity is combined with low concentrations of non\u2010ionic detergent to accelerate inactivation without prolonged exposure to strongly acidic conditions. Using xenotropic murine leukemia virus (X\u2010MuLV) spiked into ProA eluates, 0.10% N\u2010methylglucamide (Mega\u201010) at pH\u20093.91 reduced infectivity to below the assay limit of detection within 2.5\u2009min (log10 reduction factor [LRF]\u2009\u2265\u20095.40), whereas low pH alone or detergent alone produced substantially lower reductions over the same interval. Similarly, 0.15% Mega\u201010 at pH\u20094.05 achieved nondetectable infectivity within 10\u2009min (LRF \u2265\u20095.81). Comparable time compression was observed with Tween 80 or Tween 20 at pH ~3.97, reducing time\u2010to\u2010nondetectable infectivity from 120\u2009min (low pH alone) to 5\u2009min. The operating window was tunable through paired adjustment of detergent concentration and pH, and feasibility was demonstrated at pH\u20094.56 with low detergent levels, offering a practical solution for pH\u2010labile products and higher\u2010pH eluates.<\/jats:p>","DOI":"10.1002\/btpr.88549","type":"journal-article","created":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T04:07:38Z","timestamp":1786939658000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Synergistic viral inactivation platform: Rapid enveloped virus inactivation at mildly acidic\n                    <scp>pH<\/scp>\n                    using low non\u2010ionic detergent in Protein A eluates"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-1010-6473","authenticated-orcid":false,"given":"June X.","family":"Zou","sequence":"first","affiliation":[{"name":"Pathogen Safety, Biologics Development Bayer Healthcare LLC  Berkeley California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-2885-5912","authenticated-orcid":false,"given":"Janice H.","family":"Lee","sequence":"additional","affiliation":[{"name":"Pathogen Safety, Biologics Development Bayer Healthcare LLC  Berkeley California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shengjiang\u00a0\u201cShawn\u201d","family":"Liu","sequence":"additional","affiliation":[{"name":"Pathogen Safety, Biologics Development Bayer Healthcare LLC  Berkeley California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-6447-7786","authenticated-orcid":false,"given":"Hendri","family":"Tjandra","sequence":"additional","affiliation":[{"name":"Isolation &amp; Purification, Biologics Development Bayer Healthcare LLC  Berkeley California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,16]]},"reference":[{"key":"e_1_2_10_2_1","unstructured":"International Council for Harmonisation (ICH).ICH Harmonised Guideline: Viral Safety Evaluation of Biotechnology Products Derived from Cell Lines of Human or Animal Origin Q5A(R2). Final version adopted 1 Nov 2023."},{"issue":"3","key":"e_1_2_10_3_1","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1002\/bit.10574","article-title":"Bracketed generic inactivation of rodent retroviruses by low pH treatment for monoclonal antibodies and recombinant proteins","volume":"82","author":"Brorson K","year":"2003","journal-title":"Biotechnol Bioeng"},{"issue":"8","key":"e_1_2_10_4_1","doi-asserted-by":"crossref","first-page":"1479","DOI":"10.1080\/19420862.2019.1658493","article-title":"Protein aggregation and mitigation strategy in low pH viral inactivation for monoclonal antibody purification","volume":"11","author":"Jin W","year":"2019","journal-title":"mAbs"},{"key":"e_1_2_10_5_1","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/j.chroma.2015.08.068","article-title":"Protein A chromatography increases monoclonal antibody aggregation rate during subsequent low pH virus inactivation hold","volume":"1415","author":"Mazzer AR","year":"2015","journal-title":"J Chromatogr A"},{"key":"e_1_2_10_6_1","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.chroma.2007.09.040","article-title":"Protein aggregation kinetics during Protein A chromatography: case study for an Fc fusion protein","volume":"1171","author":"Shukla AA","year":"2007","journal-title":"J Chromatogr A"},{"key":"e_1_2_10_7_1","doi-asserted-by":"crossref","first-page":"4201","DOI":"10.1039\/D5AN00664C","article-title":"Assessment of IgG stability in a low pH elution buffer using ATR\u2010FTIR spectroscopic imaging and microfluidics","volume":"150","author":"Haaren C","year":"2025","journal-title":"Analyst"},{"key":"e_1_2_10_8_1","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1016\/j.xphs.2015.11.002","article-title":"Immunogenicity of therapeutic protein aggregates","volume":"105","author":"Moussa EM","year":"2016","journal-title":"J Pharm 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