{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T11:11:56Z","timestamp":1788174716964,"version":"build-2803163510"},"reference-count":19,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T00:00:00Z","timestamp":1760313600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100017239","name":"BeiGene","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100017239","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Background\/Objectives: Monoclonal antibody (mAb) stability is critical not only during manufacturing but also at the point of clinical administration. For therapies like tislelizumab (Tevimbra), a programmed death-1 (PD-1) targeting IgG mAb, delays in dosing often result in prepared infusions being discarded, contributing to substantial drug waste despite being engineered for improved stability. Methods: To evaluate the physicochemical in-use stability of tislelizumab in a ready-to-administer format, we mapped degradation pathways, including post-translational modifications (PTMs); peptide alterations; pH and solution characteristics\u2014under 12-month storage (ultra-long), under 1-month storage (0, 7, 14, 21, 28 and 31 days), and under exposure-related forced degradation conditions including room temperature, elevated temperature, pH (acidic\/basic), oxidation and UV exposure. Structural analysis was contextualised to the known PD-1 binding site, making stability assessment relevant to tislelizumab\u2019s mechanism-of-action in blocking PD-1. To assess solution stability, a validated size-exclusion chromatography (SEC) assay was applied to all conditions. Results: Aggregation was identified as the primary degradation pathway during ultra-long-term storage. SEC and chemical assessment revealed no measurable changes in protein quantity, aggregation, peptide integrity, or PTM profile over 31 days at 2\u20138 \u00b0C in polyolefin intravenous bags (1.6 mg\/mL). Conclusions: These results support the structural and physicochemical stability of tislelizumab under refrigerated conditions.<\/jats:p>","DOI":"10.3390\/ph18101539","type":"journal-article","created":{"date-parts":[[2025,10,14]],"date-time":"2025-10-14T05:48:21Z","timestamp":1760420901000},"page":"1539","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Structure-Guided In-Use Stability Assessment of Monoclonal Antibody Tislelizumab"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3104-309X","authenticated-orcid":false,"given":"David Andre","family":"Rudd","sequence":"first","affiliation":[{"name":"Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, VIC 3052, Australia"},{"name":"Medicines Manufacturing Innovation Centre, Australian Synchrotron, Clayton, VIC 3168, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ghizal","family":"Siddiqui","sequence":"additional","affiliation":[{"name":"Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, VIC 3052, Australia"},{"name":"Drug Target Identification Platform, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, VIC 3052, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1001\/jamaoncol.2022.7826","article-title":"Estimates and Projections of the Global Economic Cost of 29 Cancers in 204 Countries and Territories From 2020 to 2050","volume":"9","author":"Chen","year":"2023","journal-title":"JAMA Oncol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"eaax0182","DOI":"10.1126\/science.aax0182","article-title":"Neoadjuvant checkpoint blockade for cancer immunotherapy","volume":"367","author":"Topalian","year":"2020","journal-title":"Science"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2106","DOI":"10.1002\/cam4.2888","article-title":"Economics of alternative dosing strategies for pembrolizumab and nivolumab at a single academic cancer center","volume":"9","author":"Hall","year":"2020","journal-title":"Cancer Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"946","DOI":"10.1377\/hlthaff.2023.00102","article-title":"Adopting Weight-Based Dosing with Pharmacy-Level Stewardship Strategies Could Reduce Cancer Drug Spending by Millions","volume":"42","author":"Bryant","year":"2023","journal-title":"Health Aff."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1177\/1078155213476723","article-title":"Dose rounding of ipilimumab in adult metastatic melanoma patients results in significant cost savings","volume":"20","author":"Jarkowski","year":"2014","journal-title":"J. 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