{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T18:01:19Z","timestamp":1780509679551,"version":"3.54.1"},"reference-count":76,"publisher":"Springer Science and Business Media LLC","issue":"4","license":[{"start":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T00:00:00Z","timestamp":1778025600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T00:00:00Z","timestamp":1778025600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["AAPS PharmSciTech"],"DOI":"10.1208\/s12249-026-03436-0","type":"journal-article","created":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T17:09:48Z","timestamp":1778087388000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Impact of Amino Acid Excipients on icIEF Method Development in Protein Therapeutics: A Formulation-Aware Analytical Framework"],"prefix":"10.1208","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6377-7381","authenticated-orcid":false,"given":"Pragya","family":"Manandhar","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole","family":"Payung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siddharth","family":"Sapa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-2607-5433","authenticated-orcid":false,"given":"Matthew","family":"Myers","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-2454-022X","authenticated-orcid":false,"given":"Zaneta","family":"Maijorovaite","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-2748-0026","authenticated-orcid":false,"given":"Haichen","family":"Nie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,5,6]]},"reference":[{"issue":"2","key":"3436_CR1","doi-asserted-by":"publisher","first-page":"771","DOI":"10.1016\/j.xphs.2020.09.048","volume":"110","author":"MN Ruesch","year":"2021","unstructured":"Ruesch MN, Benetti L, Berkay E, Cirelli DJ, Frantz N, Gastens MH, et al. Strategies for setting patient-centric commercial specifications for biotherapeutic products. J Pharm Sci. 2021;110(2):771\u201384.","journal-title":"J Pharm Sci"},{"issue":"1","key":"3436_CR2","doi-asserted-by":"publisher","first-page":"76","DOI":"10.1007\/s12247-018-9366-5","volume":"14","author":"J Bercu","year":"2019","unstructured":"Bercu J, Berlam SC, Berridge J, Cherney B, Cowley D, Laughton HW, et al. Establishing Patient Centric Specifications for Drug Substance and Drug Product Impurities. J Pharm Innov. 2019;14(1):76\u201389.","journal-title":"J Pharm Innov"},{"issue":"2","key":"3436_CR3","doi-asserted-by":"publisher","first-page":"219","DOI":"10.1111\/cts.12717","volume":"13","author":"V Shakhnovich","year":"2020","unstructured":"Shakhnovich V, Meibohm B, Rosenberg A, Kierzek AM, Hasenkamp R, Funk RS, et al. Immunogenicity in Clinical Practice and Drug Development: When is it Significant? Clin Transl Sci. 2020;13(2):219\u201323.","journal-title":"Clin Transl Sci"},{"issue":"3","key":"3436_CR4","doi-asserted-by":"publisher","DOI":"10.1208\/aapsj080359","volume":"8","author":"AS Rosenberg","year":"2006","unstructured":"Rosenberg AS. Effects of protein aggregates: an immunologic perspective. AAPS J. 2006;8(3):E501-7.","journal-title":"AAPS J"},{"issue":"8","key":"3436_CR5","doi-asserted-by":"publisher","first-page":"2067","DOI":"10.1007\/s00216-017-0844-2","volume":"410","author":"JE Schiel","year":"2018","unstructured":"Schiel JE, Turner A. The NISTmAb reference material 8671 lifecycle management and quality plan. Anal Bioanal Chem. 2018;410(8):2067\u201378.","journal-title":"Anal Bioanal Chem"},{"key":"3436_CR6","doi-asserted-by":"publisher","DOI":"10.1208\/s12249-026-03364-z","author":"R Dachineni","year":"2026","unstructured":"Dachineni R, Naseer N, Myers M, Maijorovaite Z, Nie H. Evaluating dextrose-derived interference in low-concentration monoclonal antibody quantification for clinical in-use studies. AAPS PharmSciTech. 2026.","journal-title":"AAPS PharmSciTech"},{"issue":"1","key":"3436_CR7","doi-asserted-by":"publisher","DOI":"10.1080\/19420862.2020.1743053","volume":"12","author":"M Bailly","year":"2020","unstructured":"Bailly M, Mieczkowski C, Juan V, Metwally E, Tomazela D, Baker J, et al. Predicting antibody developability profiles through early stage discovery screening. MAbs. 2020;12(1):1743053.","journal-title":"MAbs"},{"issue":"9-10","key":"3436_CR8","doi-asserted-by":"publisher","first-page":"1050","DOI":"10.1002\/elps.202100348","volume":"43","author":"S Madren","year":"2022","unstructured":"Madren S, McElroy W, Schultz-Kuszak K, Boumajny B, Shu Y, Sautter S, et al. Global intercompany assessment of ICIEF platform comparability for the characterization of therapeutic proteins. Electrophoresis. 2022;43(9\u201310):1050\u20138.","journal-title":"Electrophoresis"},{"issue":"1-2","key":"3436_CR9","doi-asserted-by":"publisher","first-page":"491","DOI":"10.1016\/j.chroma.2003.11.025","volume":"1037","author":"PG Righetti","year":"2004","unstructured":"Righetti PG. Determination of the isoelectric point of proteins by capillary isoelectric focusing. J Chromatogr A. 2004;1037(1\u20132):491\u20139.","journal-title":"J Chromatogr A"},{"key":"3436_CR10","doi-asserted-by":"publisher","DOI":"10.3389\/fchem.2025.1536222","volume":"13","author":"V Ghizzani","year":"2025","unstructured":"Ghizzani V, Ascione A, Gonnella F, Massolini G, Luciani F. Exploring imaged capillary isoelectric focusing parameters for enhanced charge variants quality control. Front Chem. 2025;13:1536222.","journal-title":"Front Chem"},{"key":"3436_CR11","unstructured":"International council of harmonisation. Specifications: Test procedures and acceptance criteria for biotechnological\/biological products; Q6B ICH Harmonised Tripartite Guideline [Internet]. 1999. Available from: https:\/\/www.ich.org\/page\/quality-guidelines. Accessed 16 Jan 2026."},{"key":"3436_CR12","unstructured":"International Council of Harmonisation. Harmonised guideline. Validation of Analytical Procedures Q2(R2) [Internet]. Available from: https:\/\/database.ich.org\/sites\/default\/files\/ICH_Q2%28R2%29_Guideline_2023_1130.pdf. Accessed 16 Jan 2026."},{"issue":"17","key":"3436_CR13","doi-asserted-by":"publisher","first-page":"9084","DOI":"10.1021\/acs.analchem.5b02385","volume":"87","author":"G Ponniah","year":"2015","unstructured":"Ponniah G, Kita A, Nowak C, Neill A, Kori Y, Rajendran S, et al. Characterization of the acidic species of a monoclonal antibody using weak cation exchange chromatography and LC-MS. Anal Chem. 2015;87(17):9084\u201392.","journal-title":"Anal Chem"},{"issue":"1","key":"3436_CR14","doi-asserted-by":"publisher","first-page":"209","DOI":"10.1007\/s11095-011-0536-0","volume":"29","author":"S Gandhi","year":"2012","unstructured":"Gandhi S, Ren D, Xiao G, Bondarenko P, Sloey C, Ricci MS, et al. Elucidation of degradants in acidic peak of cation exchange chromatography in an IgG1 monoclonal antibody formed on long-term storage in a liquid formulation. Pharm Res. 2012;29(1):209\u201324.","journal-title":"Pharm Res"},{"key":"3436_CR15","doi-asserted-by":"publisher","first-page":"96","DOI":"10.1016\/j.jchromb.2018.03.049","volume":"1085","author":"C King","year":"2018","unstructured":"King C, Patel R, Ponniah G, Nowak C, Neill A, Gu Z, et al. Characterization of recombinant monoclonal antibody variants detected by hydrophobic interaction chromatography and imaged capillary isoelectric focusing electrophoresis. J Chromatogr B. 2018;1085:96\u2013103.","journal-title":"J Chromatogr B"},{"key":"3436_CR16","doi-asserted-by":"crossref","unstructured":"Khawli LA, Goswami S, Hutchinson R, Kwong ZW, Yang J, Wang X, et al. Charge variants in IgG1: Isolation, characterization, in vitro binding properties. mAbs. 2010;2(6):613\u201324.","DOI":"10.4161\/mabs.2.6.13333"},{"issue":"2","key":"3436_CR17","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1016\/j.ab.2007.09.027","volume":"373","author":"C Quan","year":"2008","unstructured":"Quan C, Alcala E, Petkovska I, Matthews D, Canova-Davis E, Taticek R, et al. A study in glycation of a therapeutic recombinant humanized monoclonal antibody: where it is, how it got there, and how it affects charge-based behavior. Anal Biochem. 2008;373(2):179\u201391.","journal-title":"Anal Biochem"},{"issue":"1","key":"3436_CR18","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1016\/j.ab.2011.07.033","volume":"419","author":"M Alvarez","year":"2011","unstructured":"Alvarez M, Tremintin G, Wang J, Eng M, Kao Y-H, Jeong J, et al. On-line characterization of monoclonal antibody variants by liquid chromatography\u2013mass spectrometry operating in a two-dimensional format. Anal Biochem. 2011;419(1):17\u201325.","journal-title":"Anal Biochem"},{"issue":"7","key":"3436_CR19","doi-asserted-by":"publisher","first-page":"2426","DOI":"10.1002\/jps.21180","volume":"97","author":"H Liu","year":"2008","unstructured":"Liu H, Gaza-Bulseco G, Faldu D, Chumsae C, Sun J. Heterogeneity of monoclonal antibodies. J Pharm Sci. 2008;97(7):2426\u201347.","journal-title":"J Pharm Sci"},{"issue":"1","key":"3436_CR20","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1016\/j.jchromb.2007.12.001","volume":"862","author":"G Gaza-Bulseco","year":"2008","unstructured":"Gaza-Bulseco G, Bulseco A, Chumsae C, Liu H. Characterization of the glycosylation state of a recombinant monoclonal antibody using weak cation exchange chromatography and mass spectrometry. J Chromatogr B. 2008;862(1):155\u201360.","journal-title":"J Chromatogr B"},{"issue":"1","key":"3436_CR21","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1007\/s11095-011-0534-2","volume":"29","author":"A Sreedhara","year":"2012","unstructured":"Sreedhara A, Cordoba A, Zhu Q, Kwong J, Liu J. Characterization of the isomerization products of aspartate residues at two different sites in a monoclonal antibody. Pharm Res. 2012;29(1):187\u201397.","journal-title":"Pharm Res"},{"issue":"10","key":"3436_CR22","doi-asserted-by":"publisher","first-page":"3194","DOI":"10.1016\/j.xphs.2019.05.023","volume":"108","author":"Z Liu","year":"2019","unstructured":"Liu Z, Valente J, Lin S, Chennamsetty N, Qiu D, Bolgar M. Cyclization of N-terminal glutamic acid to pyro-glutamic acid impacts monoclonal antibody charge heterogeneity despite its appearance as a neutral transformation. J Pharm Sci. 2019;108(10):3194\u2013200.","journal-title":"J Pharm Sci"},{"issue":"1","key":"3436_CR23","doi-asserted-by":"publisher","first-page":"285","DOI":"10.1016\/j.jchromb.2006.11.050","volume":"850","author":"C Chumsae","year":"2007","unstructured":"Chumsae C, Gaza-Bulseco G, Sun J, Liu H. Comparison of methionine oxidation in thermal stability and chemically stressed samples of a fully human monoclonal antibody. J Chromatogr B. 2007;850(1):285\u201394.","journal-title":"J Chromatogr B"},{"issue":"16","key":"3436_CR24","doi-asserted-by":"publisher","first-page":"7112","DOI":"10.1021\/ac301426h","volume":"84","author":"T Zhang","year":"2012","unstructured":"Zhang T, Zhang J, Hewitt D, Tran B, Gao X, Qiu ZJ, et al. Identification and characterization of buried unpaired cysteines in a recombinant monoclonal IgG1 antibody. Anal Chem. 2012;84(16):7112\u201323.","journal-title":"Anal Chem"},{"issue":"1","key":"3436_CR25","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1016\/j.ab.2009.09.027","volume":"397","author":"D Ouellette","year":"2010","unstructured":"Ouellette D, Alessandri L, Chin A, Grinnell C, Tarcsa E, Radziejewski C, et al. Studies in serum support rapid formation of disulfide bond between unpaired cysteine residues in the VH domain of an immunoglobulin G1 molecule. Anal Biochem. 2010;397(1):37\u201347.","journal-title":"Anal Biochem"},{"issue":"1","key":"3436_CR26","doi-asserted-by":"publisher","DOI":"10.1080\/19420862.2024.2313737","volume":"16","author":"A Ascione","year":"2024","unstructured":"Ascione A, Belfiore M, Vesterinen J, Buda M, Holtkamp W, Luciani F. Charge heterogeneity of therapeutic monoclonal antibodies by different cIEF systems: views on the current situation. MAbs. 2024;16(1):2313737.","journal-title":"MAbs"},{"key":"3436_CR27","unstructured":"Food & Drug Administration, GRAS Substances (SCOGS) Database, FDA [Internet]. Available from: https:\/\/www.fda.gov\/food\/generally-recognized-safe-gras\/gras-substances-scogs-database. Accessed 04 Feb 2025."},{"issue":"4","key":"3436_CR28","doi-asserted-by":"publisher","first-page":"587","DOI":"10.1007\/s00726-007-0506-3","volume":"33","author":"T Arakawa","year":"2007","unstructured":"Arakawa T, Tsumoto K, Kita Y, Chang B, Ejima D. Biotechnology applications of amino acids in protein purification and formulations. Amino Acids. 2007;33(4):587\u2013605.","journal-title":"Amino Acids"},{"key":"3436_CR29","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpharm.2025.126498","volume":"689","author":"R Dachineni","year":"2026","unstructured":"Dachineni R, Nie H. Navigating the use of 2-hydroxypropyl-beta-cyclodextrin in liquid formulations: a systematic study of physical properties and surfactant compatibility. Int J Pharm. 2026;689:126498.","journal-title":"Int J Pharm"},{"issue":"13","key":"3436_CR30","doi-asserted-by":"publisher","first-page":"1074","DOI":"10.1016\/j.addr.2011.06.014","volume":"63","author":"D Shukla","year":"2011","unstructured":"Shukla D, Schneider CP, Trout BL. Molecular level insight into intra-solvent interaction effects on protein stability and aggregation. Adv Drug Deliv Rev. 2011;63(13):1074\u201385.","journal-title":"Adv Drug Deliv Rev"},{"issue":"7","key":"3436_CR31","doi-asserted-by":"publisher","DOI":"10.1002\/biot.201700523","volume":"13","author":"K Kemter","year":"2018","unstructured":"Kemter K, Altrichter J, Derwand R, Kriehuber T, Reinauer E, Scholz M. Amino acid-based advanced liquid formulation development for highly concentrated therapeutic antibodies balances physical and chemical stability and low viscosity. Biotechnol J. 2018;13(7):e1700523.","journal-title":"Biotechnol J"},{"issue":"12","key":"3436_CR32","doi-asserted-by":"publisher","first-page":"4478","DOI":"10.1021\/acs.molpharmaceut.5b00643","volume":"12","author":"S Wang","year":"2015","unstructured":"Wang S, Zhang N, Hu T, Dai W, Feng X, Zhang X, et al. Viscosity-lowering effect of amino acids and salts on highly concentrated solutions of two IgG1 monoclonal antibodies. Mol Pharm. 2015;12(12):4478\u201387.","journal-title":"Mol Pharm"},{"issue":"7","key":"3436_CR33","doi-asserted-by":"publisher","first-page":"2590","DOI":"10.1016\/j.xphs.2021.03.017","volume":"110","author":"RG Strickley","year":"2021","unstructured":"Strickley RG, Lambert WJ. A review of formulations of commercially available antibodies. J Pharm Sci. 2021;110(7):2590-608.e56.","journal-title":"J Pharm Sci"},{"issue":"13","key":"3436_CR34","doi-asserted-by":"publisher","first-page":"1118","DOI":"10.1016\/j.addr.2011.07.006","volume":"63","author":"TJ Kamerzell","year":"2011","unstructured":"Kamerzell TJ, Esfandiary R, Joshi SB, Middaugh CR, Volkin DB. Protein-excipient interactions: mechanisms and biophysical characterization applied to protein formulation development. Adv Drug Deliv Rev. 2011;63(13):1118\u201359.","journal-title":"Adv Drug Deliv Rev"},{"key":"3436_CR35","unstructured":"Inc. A. BLINCYTO\u00ae\u00a0(blinatumomab) for injection, for intravenous use. Thousand Oaks, California. Available from: https:\/\/nctr-crs.fda.gov\/fdalabel\/services\/spl\/set-ids\/38b482a8-960b-4591-9857-5031ecb830aa\/spl-doc?hl=BLINCYTO. Accessed 27 Mar 2026."},{"issue":"1","key":"3436_CR36","doi-asserted-by":"publisher","DOI":"10.1080\/19420862.2023.2205540","volume":"15","author":"I Ghosh","year":"2023","unstructured":"Ghosh I, Gutka H, Krause ME, Clemens R, Kashi RS. A systematic review of commercial high concentration antibody drug products approved in the US: formulation composition, dosage form design and primary packaging considerations. MAbs. 2023;15(1):2205540.","journal-title":"MAbs"},{"key":"3436_CR37","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpharm.2021.121375","volume":"613","author":"A Bongioanni","year":"2022","unstructured":"Bongioanni A, Bueno MS, Mezzano BA, Longhi MR, Garnero C. Amino acids and its pharmaceutical applications: a mini review. Int J Pharm. 2022;613:121375.","journal-title":"Int J Pharm"},{"issue":"18-19","key":"3436_CR38","doi-asserted-by":"publisher","first-page":"2382","DOI":"10.1002\/elps.201900162","volume":"40","author":"J Kahle","year":"2019","unstructured":"Kahle J, Stein M, W\u00e4tzig H. Design of experiments as a valuable tool for biopharmaceutical analysis with (imaged) capillary isoelectric focusing. Electrophoresis. 2019;40(18\u201319):2382\u20139.","journal-title":"Electrophoresis"},{"issue":"4","key":"3436_CR39","doi-asserted-by":"publisher","first-page":"408","DOI":"10.2174\/138920109788488851","volume":"10","author":"C Lange","year":"2009","unstructured":"Lange C, Rudolph R. Suppression of protein aggregation by L-arginine. Curr Pharm Biotechnol. 2009;10(4):408\u201314.","journal-title":"Curr Pharm Biotechnol"},{"issue":"5","key":"3436_CR40","doi-asserted-by":"publisher","first-page":"539","DOI":"10.1016\/j.jbiosc.2013.10.016","volume":"117","author":"N Inoue","year":"2014","unstructured":"Inoue N, Takai E, Arakawa T, Shiraki K. Arginine and lysine reduce the high viscosity of serum albumin solutions for pharmaceutical injection. J Biosci Bioeng. 2014;117(5):539\u201343.","journal-title":"J Biosci Bioeng"},{"issue":"22","key":"3436_CR41","doi-asserted-by":"publisher","first-page":"7447","DOI":"10.1021\/jp111920y","volume":"115","author":"CP Schneider","year":"2011","unstructured":"Schneider CP, Shukla D, Trout BL. Arginine and the Hofmeister series: the role of ion-ion interactions in protein aggregation suppression. J Phys Chem B. 2011;115(22):7447\u201358.","journal-title":"J Phys Chem B"},{"issue":"2","key":"3436_CR42","doi-asserted-by":"publisher","first-page":"216","DOI":"10.1080\/19420862.2015.1128606","volume":"8","author":"DS Tomar","year":"2016","unstructured":"Tomar DS, Kumar S, Singh SK, Goswami S, Li L. Molecular basis of high viscosity in concentrated antibody solutions: strategies for high concentration drug product development. MAbs. 2016;8(2):216\u201328.","journal-title":"MAbs"},{"key":"3436_CR43","unstructured":"Inc. MP. HULIO\u00ae (adalimumab-fkjp) injection, for subcutaneous use. Silver Spring, MD08\/2023. Available from: https:\/\/nctr-crs.fda.gov\/fdalabel\/services\/spl\/set-ids\/661ad70b-c313-2899-8a7e-7a67bd897ca9\/spl-doc?hl=hulio. Accessed 27 Mar 2026."},{"key":"3436_CR44","unstructured":"CSL Behring Canada I. STREPTASE\u00ae (Streptokinase Injection)- Fibrinolytic Agent. Ottawa, Ontario; 2007. Available from: https:\/\/pdf.hres.ca\/dpd_pm\/00003639.PDF. Accessed 27 Mar 2026."},{"key":"3436_CR45","unstructured":"Valeant Pharmaceuticals International I. SILIQ\u2122 (brodalumab) injection, for subcutaneous use. Available from: https:\/\/nctr-crs.fda.gov\/fdalabel\/services\/spl\/set-ids\/1a550c33-456a-4833-814e-8591aea7c688\/spl-doc?hl=SILIQ. Accessed on 27 March 2026."},{"issue":"1-2","key":"3436_CR46","doi-asserted-by":"publisher","first-page":"126","DOI":"10.1016\/j.ijpharm.2014.06.053","volume":"473","author":"P Kheddo","year":"2014","unstructured":"Kheddo P, Tracka M, Armer J, Dearman RJ, Uddin S, van der Walle CF, et al. The effect of arginine glutamate on the stability of monoclonal antibodies in solution. Int J Pharm. 2014;473(1\u20132):126\u201333.","journal-title":"Int J Pharm"},{"issue":"8","key":"3436_CR47","doi-asserted-by":"publisher","first-page":"2517","DOI":"10.1016\/j.xphs.2019.03.008","volume":"108","author":"BJ Dear","year":"2019","unstructured":"Dear BJ, Hung JJ, Laber JR, Wilks LR, Sharma A, Truskett TM, et al. Enhancing stability and reducing viscosity of a monoclonal antibody with cosolutes by weakening protein-protein interactions. J Pharm Sci. 2019;108(8):2517\u201326.","journal-title":"J Pharm Sci"},{"issue":"17","key":"3436_CR48","doi-asserted-by":"publisher","first-page":"E1705","DOI":"10.1073\/pnas.1400577111","volume":"111","author":"AL Hansen","year":"2014","unstructured":"Hansen AL, Kay LE. Measurement of histidine pKa values and tautomer populations in invisible protein states. Proc Natl Acad Sci U S A. 2014;111(17):E1705-12.","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"9","key":"3436_CR49","doi-asserted-by":"publisher","first-page":"3288","DOI":"10.1021\/acs.molpharmaceut.2c00453","volume":"19","author":"S Saurabh","year":"2022","unstructured":"Saurabh S, Kalonia C, Li Z, Hollowell P, Waigh T, Li P, et al. Understanding the Stabilizing Effect of Histidine on mAb Aggregation: A Molecular Dynamics Study. Mol Pharm. 2022;19(9):3288\u2013303.","journal-title":"Mol Pharm"},{"issue":"3","key":"3436_CR50","doi-asserted-by":"publisher","first-page":"713","DOI":"10.1016\/j.xphs.2016.11.014","volume":"106","author":"TJ Zbacnik","year":"2017","unstructured":"Zbacnik TJ, Holcomb RE, Katayama DS, Murphy BM, Payne RW, Coccaro RC, et al. Role of buffers in protein formulations. J Pharm Sci. 2017;106(3):713\u201333.","journal-title":"J Pharm Sci"},{"key":"3436_CR51","doi-asserted-by":"publisher","first-page":"119","DOI":"10.1016\/j.jchromb.2017.09.033","volume":"1065-1066","author":"A Goyon","year":"2017","unstructured":"Goyon A, Excoffier M, Janin-Bussat MC, Bobaly B, Fekete S, Guillarme D, et al. Determination of isoelectric points and relative charge variants of 23 therapeutic monoclonal antibodies. J Chromatogr B Analyt Technol Biomed Life Sci. 2017;1065\u20131066:119\u201328.","journal-title":"J Chromatogr B Analyt Technol Biomed Life Sci"},{"key":"3436_CR52","unstructured":"Kyowa Kirin I. POTELIGEO\u00ae (mogamulizumab-kpkc) injection, for intravenous use. 2018. Available from: https:\/\/nctr-crs.fda.gov\/fdalabel\/services\/spl\/set-ids\/e53960ab-42a1-40d1-9c7d-eb013fe7f18f\/spl-doc?hl=poteligeo. Accessed 08 Apr 2026."},{"key":"3436_CR53","unstructured":"Pharmaceuticals A. LUMOXITI\u2122 (moxetumomab pasudotox-tdfk) for injection, for intravenous use 2018. Available from: https:\/\/nctr-crs.fda.gov\/fdalabel\/services\/spl\/set-ids\/8ddffb08-aab1-41f5-bbc6-09457e4e80ca\/spl-doc?hl=lumoxiti. Accessed on 08 April 2026."},{"key":"3436_CR54","unstructured":"iCE System Suitability Kit for FC-coated Cartridges Part#102093 [Internet]. bio-techne; protein simple. Available from: https:\/\/www.bio-techne.com\/pdf-download-arena-document\/product-insert\/d-0000300-00."},{"issue":"9","key":"3436_CR55","doi-asserted-by":"publisher","first-page":"735","DOI":"10.1002\/elps.201900406","volume":"41","author":"X Zhang","year":"2020","unstructured":"Zhang X, Chemmalil L, Ding J, Li Z. A novel approach enables imaged capillary isoelectric focusing analysis of PEGylated proteins. Electrophoresis. 2020;41(9):735\u201342.","journal-title":"Electrophoresis"},{"issue":"11","key":"3436_CR56","doi-asserted-by":"publisher","first-page":"1893","DOI":"10.1007\/s11095-025-03949-6","volume":"42","author":"P Sharma","year":"2025","unstructured":"Sharma P, Nie H. Spotlight on clinical in-use parameters for intravenous infusion of therapeutic antibodies: a systematic review. Pharm Res. 2025;42(11):1893\u2013916.","journal-title":"Pharm Res"},{"issue":"6","key":"3436_CR57","doi-asserted-by":"publisher","first-page":"1390","DOI":"10.1002\/jps.20079","volume":"93","author":"SJ Shire","year":"2004","unstructured":"Shire SJ, Shahrokh Z, Liu J. Challenges in the development of high protein concentration formulations. J Pharm Sci. 2004;93(6):1390\u2013402.","journal-title":"J Pharm Sci"},{"issue":"1","key":"3436_CR58","doi-asserted-by":"publisher","DOI":"10.1080\/19420862.2023.2285277","volume":"15","author":"M Desai","year":"2023","unstructured":"Desai M, Kundu A, Hageman M, Lou H, Boisvert D. Monoclonal antibody and protein therapeutic formulations for subcutaneous delivery: high-concentration, low-volume vs. low-concentration, high-volume. MAbs. 2023;15(1):2285277.","journal-title":"MAbs"},{"key":"3436_CR59","unstructured":"LLC G. BENLYSTA (belimumab) for injection, for intravenous use 2024. Available from: https:\/\/nctr-crs.fda.gov\/fdalabel\/services\/spl\/set-ids\/2fa3c528-1777-4628-8a55-a69dae2381a3\/spl-doc?hl=BENLYSTA. Accessed on 27 March 2026."},{"key":"3436_CR60","unstructured":"UCB I. CIMZIA (certolizumab pegol) for injection, for subcutaneous use. 2024. Available from: https:\/\/nctr-crs.fda.gov\/fdalabel\/services\/spl\/set-ids\/b4c2c9dc-a0bb-4d64-a667-a67ebe88392d\/spl-doc?hl=cimzia. Accessed on 27 March 2026."},{"key":"3436_CR61","unstructured":"Behring C. HIZENTRA\u00ae, Immune Globulin Subcutaneous (Human), 20% Liquid. 2023. Available from: https:\/\/nctr-crs.fda.gov\/fdalabel\/services\/spl\/set-ids\/7b58f5ff-0316-49a3-b585-1f6003ddb953\/spl-doc?hl=HIZENTRA. Accessed 27 Mar 2026."},{"issue":"5","key":"3436_CR62","doi-asserted-by":"publisher","first-page":"425","DOI":"10.1007\/s40259-018-0295-0","volume":"32","author":"B Bittner","year":"2018","unstructured":"Bittner B, Richter W, Schmidt J. Subcutaneous administration of biotherapeutics: an overview of current challenges and opportunities. BioDrugs. 2018;32(5):425\u201340.","journal-title":"BioDrugs"},{"issue":"8082","key":"3436_CR63","doi-asserted-by":"publisher","first-page":"915","DOI":"10.1038\/s41586-025-09506-w","volume":"645","author":"T Mao","year":"2025","unstructured":"Mao T, Xu X, Winkler PM, Siri C, Poliukhina E, Silva PJ, et al. Stabilizing effect of amino acids on protein and colloidal dispersions. Nature. 2025;645(8082):915\u201321.","journal-title":"Nature"},{"key":"3436_CR64","doi-asserted-by":"publisher","first-page":"353","DOI":"10.1016\/j.ejpb.2017.06.029","volume":"119","author":"P Garidel","year":"2017","unstructured":"Garidel P, Kuhn AB, Schafer LV, Karow-Zwick AR, Blech M. High-concentration protein formulations: how high is high? Eur J Pharm Biopharm. 2017;119:353\u201360.","journal-title":"Eur J Pharm Biopharm"},{"issue":"7","key":"3436_CR65","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1007\/s11095-018-2398-1","volume":"35","author":"JJ Hung","year":"2018","unstructured":"Hung JJ, Dear BJ, Dinin AK, Borwankar AU, Mehta SK, Truskett TT, et al. Improving viscosity and stability of a highly concentrated monoclonal antibody solution with concentrated proline. Pharm Res. 2018;35(7):133.","journal-title":"Pharm Res"},{"issue":"4","key":"3436_CR66","first-page":"265","volume":"6","author":"S Ren","year":"2023","unstructured":"Ren S. Effects of arginine in therapeutic protein formulations: a decade review and perspectives. Antib Ther. 2023;6(4):265\u201376.","journal-title":"Antib Ther"},{"issue":"22","key":"3436_CR67","doi-asserted-by":"publisher","first-page":"3124","DOI":"10.1002\/jssc.201200633","volume":"35","author":"O Salas-Solano","year":"2012","unstructured":"Salas-Solano O, Kennel B, Park SS, Roby K, Sosic Z, Boumajny B, et al. Robustness of iCIEF methodology for the analysis of monoclonal antibodies: an interlaboratory study. J Sep Sci. 2012;35(22):3124\u20139.","journal-title":"J Sep Sci"},{"key":"3436_CR68","unstructured":"Genentech I. TNKase\u00ae (tenecteplase) for injection, for intravenous use. 02\/2025. Available from: https:\/\/nctr-crs.fda.gov\/fdalabel\/services\/spl\/set-ids\/e647640d-c395-4b4b-a0be-1162f9c21d84\/spl-doc?hl=tnkase. Accessed 08 Apr 2026."},{"key":"3436_CR69","unstructured":"Genentech I. ENSPRYNG\u00ae (satralizumab-mwge) injection, for subcutaneous use. 2020. Available from: https:\/\/nctr-crs.fda.gov\/fdalabel\/services\/spl\/set-ids\/64c156a4-9bad-4d45-a294-0733c141f47b\/spl-doc?hl=enspryng. Accessed 08 Apr 2026."},{"key":"3436_CR70","unstructured":"Genentech I. HEMLIBRA\u00ae (emicizumab-kxwh) injection, for subcutaneous use. 2017. Available from: https:\/\/nctr-crs.fda.gov\/fdalabel\/services\/spl\/set-ids\/2483adba-fab6-4d1b-96c5-c195577ed071\/spl-doc?hl=hemlibra. Accessed 08 Apr 2026."},{"key":"3436_CR71","unstructured":"Novartis AG and Genentech USA I. XOLAIR\u00ae (omalizumab) for injection, for subcutaneous use. 2003. Available from: https:\/\/nctr-crs.fda.gov\/fdalabel\/services\/spl\/set-ids\/7f6a2191-adfb-48b9-9bfa-0d9920479f0d\/spl-doc?hl=xolair%20pfs. Accessed 08 Apr 2026."},{"key":"3436_CR72","unstructured":"Genentech I. PERJETA\u00ae (pertuzumab) injection, for intravenous use. 2012. Available from: https:\/\/nctr-crs.fda.gov\/fdalabel\/services\/spl\/set-ids\/17f85d17-ab71-4f5b-9fe3-0b8c822f69ff\/spl-doc?hl=perjeta. Accessed 08 Apr 2026."},{"key":"3436_CR73","unstructured":"Corporation NP. KESIMPTA\u00ae (ofatumumab) injection, for subcutaneous use. 2024. Available from: https:\/\/nctr-crs.fda.gov\/fdalabel\/services\/spl\/set-ids\/6a8a3f53-2062-48ff-9dbe-b939df133ca3\/spl-doc?hl=kesimpta. Accessed 08 Apr 2026."},{"issue":"1","key":"3436_CR74","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-024-79108-5","volume":"14","author":"M Belfiore","year":"2024","unstructured":"Belfiore M, Ascione A, Ghizzani V, Di Meo S, Luciani F. A new paradigm for optimized experimental design in cIEF platforms aimed at an accurate robust and reliable mAbs charge-variant assessment. Sci Rep. 2024;14(1):28087.","journal-title":"Sci Rep"},{"key":"3436_CR75","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1016\/j.aca.2012.04.026","volume":"750","author":"G Zhu","year":"2012","unstructured":"Zhu G, Sun L, Yang P, Dovichi NJ. On-line amino acid-based capillary isoelectric focusing-ESI-MS\/MS for protein digests analysis. Anal Chim Acta. 2012;750:207\u201311.","journal-title":"Anal Chim Acta"},{"issue":"5-6","key":"3436_CR76","doi-asserted-by":"publisher","first-page":"540","DOI":"10.1002\/elps.202200170","volume":"44","author":"J Schlecht","year":"2023","unstructured":"Schlecht J, Moritz B, Kiessig S, Neususs C. Characterization of therapeutic mAb charge heterogeneity by iCIEF coupled to mass spectrometry (iCIEF-MS). Electrophoresis. 2023;44(5\u20136):540\u20138.","journal-title":"Electrophoresis"}],"container-title":["AAPS PharmSciTech"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1208\/s12249-026-03436-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1208\/s12249-026-03436-0","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1208\/s12249-026-03436-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T17:02:25Z","timestamp":1780506145000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1208\/s12249-026-03436-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,6]]},"references-count":76,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2026,5]]}},"alternative-id":["3436"],"URL":"https:\/\/doi.org\/10.1208\/s12249-026-03436-0","relation":{},"ISSN":["1530-9932"],"issn-type":[{"value":"1530-9932","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,6]]},"assertion":[{"value":"19 February 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"13 April 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 May 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. All authors are employees of Teva Branded Pharmaceutical Products R&D LLC, West Chester, PA.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of Interest"}}],"article-number":"201"}}