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A lot\u2010to\u2010lot approach to manufacturability is adopted where each biologic batch is assessed for manufacturability as a bulk, unfractionated pool. Manufacturers may explore a more granular approach, independently enriching and evaluating the filterability of antibody variants within each lot, especially within the confines of relative hydrophobicity and surface charge. This study examined the use of bind\u2010and\u2010elute chromatography to alter the proportions of monoclonal antibody (mAb) proteoforms in eluate sub\u2010pools from a mixed\u2010mode chromatography resin\u2010packed column. Filterability of each sub\u2010pool through a virus\u2010retaining filter was subsequently examined. Circular dichroism and Fourier transform infrared spectroscopy were performed for each sub\u2010pool to probe for higher\u2010order structure differences between mAb variants enriched therein. Bioanalytical techniques were also used to assess colloidal stability, surface hydrophobicity, surface charge, and size differences. Results showed that basic charge variants, high\u2010mannose glycovariants, high relative hydrophobicity proteoforms, and high\u2010molecular\u2010weight species were enriched in the last\u2010eluting (terminal) sub\u2010pools. The first sub\u2010pool and the final sub\u2010pool showed the most fouling propensity on VPro virus filters. Circular dichroism showed that enriched proteoforms in the last sub\u2010pool possessed a higher percentage of bends. Most secondary structures did not vary significantly between sub\u2010pools. Diffusion interaction parameter was highly negative across all sub\u2010pools and the bulk unfractionated pool. These results provide a design space for identifying and depleting problematic mAb variants before the crucial virus filtration step.<\/jats:p>","DOI":"10.1002\/btpr.70101","type":"journal-article","created":{"date-parts":[[2026,1,19]],"date-time":"2026-01-19T09:41:27Z","timestamp":1768815687000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A case study showing the role of hydrophobicity variants and other enriched\n                    <scp>mAb<\/scp>\n                    proteoforms on filterability through a virus filter with productivity improvement measures"],"prefix":"10.1002","volume":"42","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8106-1467","authenticated-orcid":false,"given":"Solomon","family":"Isu","sequence":"first","affiliation":[{"name":"Technical and Scientific Solutions MilliporeSigma  Burlington Massachusetts 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