{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T15:55:39Z","timestamp":1768406139543,"version":"3.49.0"},"reference-count":33,"publisher":"Public Library of Science (PLoS)","issue":"10","license":[{"start":{"date-parts":[[2024,10,24]],"date-time":"2024-10-24T00:00:00Z","timestamp":1729728000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100017530","name":"Fresenius Kabi","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100017530","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Background<\/jats:title>\n<jats:p>Pegfilgrastim is a long-acting recombinant human granulocyte colony-stimulating factor biologic that is indicated to reduce the incidence of infections, manifested by febrile neutropenia, in patients receiving myelosuppressive anti-cancer drugs and to increase survival in patients acutely exposed to myelosuppressive doses of radiation. Due to the high cost of biologic therapy and the scarcity of biosimilar alternatives, there is an unmet medical need for targeted biologics.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Objective<\/jats:title>\n<jats:p>This comparative analytical investigation aimed to confirm the similarity of biosimilar Stimufend<jats:sup>\u00ae<\/jats:sup> (pegfilgrastim-fpgk) to reference product Neulasta<jats:sup>\u00ae<\/jats:sup> (pegfilgrastim).<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Methods<\/jats:title>\n<jats:p>The analysis was designed using state-of-the-art orthogonal techniques and side-by-side testing to compare the physicochemical and biological properties of these two products. The measured quality attributes included the primary structure and higher order structure of the molecule, purity\/impurity profiles, product variants, process-related impurities, composition, content, and biological activity. The statistical analysis was based on risk ranking of the critical quality attributes (very low, low, moderate, high, very high), and scientific considerations in combination with the characteristics of the assay (sensitivity, selectivity, and variability). In addition, non-quantitative parameters were compared using a descriptive assessment of the product profile. Analytical similarity was concluded by quality attributes falling within the defined range of the originator product.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Results<\/jats:title>\n<jats:p>The results of this study confirm that Stimufend<jats:sup>\u00ae<\/jats:sup> is biosimilar to Neulasta<jats:sup>\u00ae<\/jats:sup> for all measured quality attributes. There are no clinically significant differences between Stimufend<jats:sup>\u00ae<\/jats:sup> and Neulasta<jats:sup>\u00ae<\/jats:sup>, which was confirmed by the marketing approval for Stimufend<jats:sup>\u00ae<\/jats:sup> by the Food and Drug Administration and the European Medicines Agency.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec005\">\n<jats:title>Conclusion<\/jats:title>\n<jats:p>The findings of this study provide robust evidence supporting the structural and functional biosimilarity between Stimufend<jats:sup>\u00ae<\/jats:sup> and Neulasta<jats:sup>\u00ae<\/jats:sup>.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0309480","type":"journal-article","created":{"date-parts":[[2024,10,24]],"date-time":"2024-10-24T17:42:52Z","timestamp":1729791772000},"page":"e0309480","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":4,"title":["Demonstration of physicochemical and functional similarity between Stimufend (pegfilgrastim-fpgk) and Neulasta (pegfilgrastim): A comparative analytical assessment"],"prefix":"10.1371","volume":"19","author":[{"given":"Alison","family":"Sykes","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Louise","family":"Ingram","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ulrich","family":"Kronthaler","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-5802-7353","authenticated-orcid":true,"given":"Laurent","family":"Chevalet","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2024,10,24]]},"reference":[{"issue":"2","key":"pone.0309480.ref001","doi-asserted-by":"crossref","first-page":"209","DOI":"10.4161\/mabs.3.2.15005","article-title":"Worldwide experience with biosimilar development","volume":"3","author":"M Mccamish","year":"2011","journal-title":"mAbs"},{"key":"pone.0309480.ref002","author":"European Medicines Agency","year":"2023","journal-title":"Biosimilar Medicines Overview"},{"issue":"3","key":"pone.0309480.ref003","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1007\/s40259-020-00411-4","article-title":"Biosimilar Pegfilgrastim: Improving Access and Optimising Practice to Supportive Care that Enables Cure.","volume":"34","author":"P Cornes","year":"2020","journal-title":"BioDrugs"},{"issue":"1","key":"pone.0309480.ref004","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1080\/19420862.2016.1259046","article-title":"Demonstration of physicochemical and functional similarity between the proposed biosimilar adalimumab MSB11022 and Humira\u00ae.","volume":"9","author":"L Magnenat","year":"2017","journal-title":"mAbs"},{"issue":"3","key":"pone.0309480.ref005","doi-asserted-by":"crossref","first-page":"e0212622","DOI":"10.1371\/journal.pone.0212622","article-title":"Structural similarity, characterization of Polyethylene Glycol linkage and identification of product related variants in biosimilar pegfilgrastim.","volume":"14","author":"R Shekhawat","year":"2019","journal-title":"PLOS ONE"},{"issue":"832059","key":"pone.0309480.ref006","first-page":"1","article-title":"Analytical Similarity Assessment of Biosimilars: Global Regulatory Landscape, Recent Studies and Major Advancements in Orthogonal Platforms.","volume":"10","author":"N Nupur","year":"2022","journal-title":"Front Bioeng."},{"key":"pone.0309480.ref007","article-title":"Biosimilar medicines can be interchanged","author":"European Medicines Agency","year":"2022"},{"key":"pone.0309480.ref008","article-title":"Biosimilars Report: The U.S. Journey and Path Ahead","author":"Cardinal Health","year":"2022"},{"issue":"3","key":"pone.0309480.ref009","first-page":"177","volume":"18","author":"Z Nahleh","year":"2022","journal-title":"Use of Biosimilar Medications in Oncology. J Onc Pract"},{"key":"pone.0309480.ref010","article-title":"Biosimilars: Review and Approval","author":"Food and Drug Administration"},{"issue":"1","key":"pone.0309480.ref011","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1080\/13696998.2021.1922252","article-title":"Biosimilar pegfilgrastim may offer affordable treatment options for patients in France: A budget impact analysis on the basis of clinical trial and real-world data.","volume":"24","author":"J Yang","year":"2021","journal-title":"J Med Econ"},{"issue":"1","key":"pone.0309480.ref012","doi-asserted-by":"crossref","first-page":"598","DOI":"10.1080\/13696998.2021.1916863","article-title":"Conversion from pegfilgrastim with on-body injector to pegfilgrastim-jmdb: cost-efficiency analysis and budget-neutral expanded access to prophylaxis and treatment.","volume":"24","author":"A McBride","year":"2021","journal-title":"J of Med Econ"},{"key":"pone.0309480.ref013","article-title":"Guidance for Industry. 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