{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T21:27:30Z","timestamp":1793827650422,"version":"4.6.1"},"reference-count":61,"publisher":"Springer Science and Business Media LLC","issue":"10","license":[{"start":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T00:00:00Z","timestamp":1789603200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T00:00:00Z","timestamp":1789603200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"funder":[{"name":"Stevanato Group","award":["PRJ00186"],"award-info":[{"award-number":["PRJ00186"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Pharm Res"],"published-print":{"date-parts":[[2026,10]]},"DOI":"10.1007\/s11095-026-04168-3","type":"journal-article","created":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T19:56:57Z","timestamp":1789675017000},"page":"3835-3848","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Effects of Siliconization Techniques, Headspace, Mechanical and Thermal Stress on Particle Generation in an Antibody Formulation"],"prefix":"10.1007","volume":"43","author":[{"given":"Alexandra","family":"Lucas","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deepak Kumar","family":"Tripathi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angelina","family":"Bespalova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara","family":"Callegari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vaibhav","family":"Upadhyay","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Myles","family":"Chetcuti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Odra","family":"Pinato","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew A.","family":"Monte","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David L.","family":"Bain","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony","family":"Vico","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8308-5318","authenticated-orcid":false,"given":"Krishna M. G.","family":"Mallela","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,9,17]]},"reference":[{"issue":"9","key":"4168_CR1","doi-asserted-by":"publisher","first-page":"655","DOI":"10.1038\/nrd4363","volume":"13","author":"S Mitragotri","year":"2014","unstructured":"Mitragotri S, Burke PA, Langer R. Overcoming the challenges in administering biopharmaceuticals: formulation and delivery strategies. Nat Rev Drug Discov. 2014;13(9):655\u201372.","journal-title":"Nat Rev Drug Discov"},{"issue":"1","key":"4168_CR2","doi-asserted-by":"publisher","first-page":"2411","DOI":"10.1038\/s41467-023-38039-x","volume":"14","author":"SB Ebrahimi","year":"2023","unstructured":"Ebrahimi SB, Samanta D. Engineering protein-based therapeutics through structural and chemical design. Nat Commun. 2023;14(1):2411.","journal-title":"Nat Commun"},{"key":"4168_CR3","doi-asserted-by":"crossref","unstructured":"Crescioli S, Kaplon H, Chenoweth A, Wang L, Visweswaraiah J, Reichert JM. Antibodies to watch in 2024. In.MAbs: Taylor & Francis; 2024. p. 2297450.","DOI":"10.1080\/19420862.2023.2297450"},{"issue":"4","key":"4168_CR4","doi-asserted-by":"publisher","first-page":"1440","DOI":"10.1002\/jps.24357","volume":"104","author":"V Saller","year":"2015","unstructured":"Saller V, Matilainen J, Grauschopf U, Bechtold-Peters K, Mahler HC, Friess W. Particle shedding from peristaltic pump tubing in biopharmaceutical drug product manufacturing. J Pharm Sci. 2015;104(4):1440\u201350.","journal-title":"J Pharm Sci"},{"issue":"1","key":"4168_CR5","doi-asserted-by":"publisher","first-page":"6","DOI":"10.3109\/10837450903511178","volume":"15","author":"GA Sacha","year":"2010","unstructured":"Sacha GA, Saffell-Clemmer W, Abram K, Akers MJ. Practical fundamentals of glass, rubber, and plastic sterile packaging systems. Pharm Dev Technol. 2010;15(1):6\u201334.","journal-title":"Pharm Dev Technol"},{"key":"4168_CR6","doi-asserted-by":"publisher","first-page":"467","DOI":"10.1002\/9781118971147.ch17","volume-title":"ICH quality guidelines: an implementation guide","author":"SR Rudge","year":"2017","unstructured":"Rudge SR, Nims RW. ICH Q6B specifications: test procedures and acceptance criteria for biotechnological\/biological products. In: ICH quality guidelines: an implementation guide. 2017. p. 467\u201386."},{"issue":"1","key":"4168_CR7","doi-asserted-by":"publisher","first-page":"640","DOI":"10.1016\/j.xphs.2019.10.066","volume":"109","author":"N Jiao","year":"2020","unstructured":"Jiao N, Barnett GV, Christian TR, Narhi LO, Joh NH, Joubert MK, et al. Characterization of subvisible particles in biotherapeutic prefilled syringes: the role of polysorbate and protein on the formation of silicone oil and protein subvisible particles after drop shock. J Pharm Sci. 2020;109(1):640\u20135.","journal-title":"J Pharm Sci"},{"issue":"11","key":"4168_CR8","doi-asserted-by":"publisher","DOI":"10.1007\/s11095-020-02936-3","volume":"37","author":"R Fish","year":"2020","unstructured":"Fish R, Lin J, Doshi N. Impact of silicone oil on free fatty acid particle formation due to polysorbate 20 degradation. Pharm Res. 2020;37(11):216.","journal-title":"Pharm Res"},{"issue":"2","key":"4168_CR9","doi-asserted-by":"publisher","first-page":"721","DOI":"10.1002\/jps.22290","volume":"100","author":"RS Kishore","year":"2011","unstructured":"Kishore RS, Pappenberger A, Dauphin IB, Ross A, Buergi B, Staempfli A, et al. Degradation of polysorbates 20 and 80: studies on thermal autoxidation and hydrolysis. J Pharm Sci. 2011;100(2):721\u201331.","journal-title":"J Pharm Sci"},{"issue":"4","key":"4168_CR10","doi-asserted-by":"publisher","first-page":"1004","DOI":"10.1039\/D1CB00067E","volume":"2","author":"MLE Lundahl","year":"2021","unstructured":"Lundahl MLE, Fogli S, Colavita PE, Scanlan EM. Aggregation of protein therapeutics enhances their immunogenicity: causes and mitigation strategies. RSC Chem Biol. 2021;2(4):1004\u201320.","journal-title":"RSC Chem Biol"},{"issue":"51","key":"4168_CR11","doi-asserted-by":"publisher","first-page":"35947","DOI":"10.1039\/D3RA06476J","volume":"13","author":"M Rahban","year":"2023","unstructured":"Rahban M, Ahmad F, Piatyszek MA, Haertle T, Saso L, Saboury AA. Stabilization challenges and aggregation in protein-based therapeutics in the pharmaceutical industry. RSC Adv. 2023;13(51):35947\u201363.","journal-title":"RSC Adv"},{"issue":"8","key":"4168_CR12","doi-asserted-by":"publisher","first-page":"2013","DOI":"10.1016\/j.xphs.2018.04.005","volume":"107","author":"MR Nejadnik","year":"2018","unstructured":"Nejadnik MR, Randolph TW, Volkin DB, Schoneich C, Carpenter JF, Crommelin DJA, et al. Postproduction handling and administration of protein pharmaceuticals and potential instability issues. J Pharm Sci. 2018;107(8):2013\u20139.","journal-title":"J Pharm Sci"},{"issue":"9","key":"4168_CR13","doi-asserted-by":"publisher","first-page":"2909","DOI":"10.1002\/jps.21566","volume":"98","author":"HC Mahler","year":"2009","unstructured":"Mahler HC, Friess W, Grauschopf U, Kiese S. Protein aggregation: pathways, induction factors and analysis. J Pharm Sci. 2009;98(9):2909\u201334.","journal-title":"J Pharm Sci"},{"issue":"6","key":"4168_CR14","doi-asserted-by":"publisher","DOI":"10.1208\/s12249-025-03189-2","volume":"26","author":"S Rojekar","year":"2025","unstructured":"Rojekar S, Gholap AD, Jadhav K, Shevalkar G, Sugandhi VV, Pai R, et al. Exploring protein aggregation in biological products: from mechanistic understanding to practical solutions. AAPS PharmSciTech. 2025;26(6):189.","journal-title":"AAPS PharmSciTech"},{"issue":"2","key":"4168_CR15","doi-asserted-by":"publisher","first-page":"119","DOI":"10.1111\/anae.16181","volume":"79","author":"D Whitaker","year":"2024","unstructured":"Whitaker D, Lomas J. Time for prefilled syringes-everywhere. Anaesthesia. 2024;79(2):119\u201322.","journal-title":"Anaesthesia"},{"issue":"12","key":"4168_CR16","doi-asserted-by":"publisher","first-page":"1199","DOI":"10.1080\/17425247.2018.1546692","volume":"15","author":"AR Kafal","year":"2018","unstructured":"Kafal AR, Vinh DC, Langelier MJ. Prefilled syringes for immunoglobulin G (IgG) replacement therapy: clinical experience from other disease settings. Expert Opin Drug Deliv. 2018;15(12):1199\u2013209.","journal-title":"Expert Opin Drug Deliv"},{"issue":"9","key":"4168_CR17","doi-asserted-by":"publisher","first-page":"1391","DOI":"10.1517\/17425247.2014.923400","volume":"11","author":"RG Ingle","year":"2014","unstructured":"Ingle RG, Agarwal AS. Pre-filled syringe - a ready-to-use drug delivery system: a review. Expert Opin Drug Deliv. 2014;11(9):1391\u20139.","journal-title":"Expert Opin Drug Deliv"},{"issue":"4","key":"4168_CR18","doi-asserted-by":"publisher","first-page":"459","DOI":"10.1080\/17425247.2021.1853699","volume":"18","author":"S Yoneda","year":"2021","unstructured":"Yoneda S, Torisu T, Uchiyama S. Development of syringes and vials for delivery of biologics: current challenges and innovative solutions. Expert Opin Drug Deliv. 2021;18(4):459\u201370.","journal-title":"Expert Opin Drug Deliv"},{"issue":"6","key":"4168_CR19","doi-asserted-by":"publisher","first-page":"1601","DOI":"10.1002\/jps.23973","volume":"103","author":"A Gerhardt","year":"2014","unstructured":"Gerhardt A, McGraw NR, Schwartz DK, Bee JS, Carpenter JF, Randolph TW. Protein aggregation and particle formation in prefilled glass syringes. J Pharm Sci. 2014;103(6):1601\u201312.","journal-title":"J Pharm Sci"},{"issue":"8","key":"4168_CR20","doi-asserted-by":"publisher","DOI":"10.1016\/j.xphs.2025.103848","volume":"114","author":"V Upadhyay","year":"2025","unstructured":"Upadhyay V, Panja S, Krishnamachari Y, Mittal SN, Xi H, Xu W, et al. Effect of silicone oil on the structure, stability, and aggregation of a therapeutic antibody. J Pharm Sci. 2025;114(8):103848.","journal-title":"J Pharm Sci"},{"issue":"6","key":"4168_CR21","doi-asserted-by":"publisher","first-page":"1946","DOI":"10.1002\/jps.24429","volume":"104","author":"T Perevozchikova","year":"2015","unstructured":"Perevozchikova T, Nanda H, Nesta DP, Roberts CJ. Protein adsorption, desorption, and aggregation mediated by solid-liquid interfaces. J Pharm Sci. 2015;104(6):1946\u201359.","journal-title":"J Pharm Sci"},{"issue":"4","key":"4168_CR22","doi-asserted-by":"publisher","first-page":"918","DOI":"10.1002\/jps.20321","volume":"94","author":"LS Jones","year":"2005","unstructured":"Jones LS, Kaufmann A, Middaugh CR. Silicone oil induced aggregation of proteins. J Pharm Sci. 2005;94(4):918\u201327.","journal-title":"J Pharm Sci"},{"issue":"7","key":"4168_CR23","doi-asserted-by":"publisher","first-page":"1852","DOI":"10.1016\/j.xphs.2018.03.016","volume":"107","author":"NN Pardeshi","year":"2018","unstructured":"Pardeshi NN, Zhou C, Randolph TW, Carpenter JF. Protein nanoparticles promote microparticle formation in intravenous immunoglobulin solutions during freeze-thawing and agitation stresses. J Pharm Sci. 2018;107(7):1852\u20137.","journal-title":"J Pharm Sci"},{"issue":"9","key":"4168_CR24","doi-asserted-by":"publisher","first-page":"3167","DOI":"10.1002\/jps.21719","volume":"98","author":"R Thirumangalathu","year":"2009","unstructured":"Thirumangalathu R, Krishnan S, Ricci MS, Brems DN, Randolph TW, Carpenter JF. Silicone oil- and agitation-induced aggregation of a monoclonal antibody in aqueous solution. J Pharm Sci. 2009;98(9):3167\u201381.","journal-title":"J Pharm Sci"},{"key":"4168_CR25","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2026.115926","author":"DK Tripathi","year":"2026","unstructured":"Tripathi DK, Lucas A, Upadhyay V, Fukuhara PS, Bespalova A, Callegari C, et al. Silicone oil in protein drug products and its implications for formulation stability. Adv Drug Deliv Rev. 2026. https:\/\/doi.org\/10.1016\/j.addr.2026.115926.","journal-title":"Adv Drug Deliv Rev"},{"issue":"5","key":"4168_CR26","doi-asserted-by":"publisher","first-page":"1601","DOI":"10.1002\/jps.24387","volume":"104","author":"A Gerhardt","year":"2015","unstructured":"Gerhardt A, Nguyen BH, Lewus R, Carpenter JF, Randolph TW. Effect of the siliconization method on particle generation in a monoclonal antibody formulation in pre-filled syringes. J Pharm Sci. 2015;104(5):1601\u20139.","journal-title":"J Pharm Sci"},{"issue":"1","key":"4168_CR27","doi-asserted-by":"publisher","first-page":"50","DOI":"10.1016\/j.xphs.2015.10.012","volume":"105","author":"S Bai","year":"2016","unstructured":"Bai S, Landsman P, Spencer A, DeCollibus D, Vega F, Temel DB, et al. Evaluation of incremental siliconization levels on soluble aggregates, submicron and subvisible particles in a prefilled syringe product. J Pharm Sci. 2016;105(1):50\u201363.","journal-title":"J Pharm Sci"},{"issue":"2","key":"4168_CR28","doi-asserted-by":"publisher","first-page":"136","DOI":"10.5731\/pdajpst.2012.00856","volume":"66","author":"E Chan","year":"2012","unstructured":"Chan E, Hubbard A, Sane S, Maa YF. Syringe siliconization process investigation and optimization. PDA J Pharm Sci Technol. 2012;66(2):136\u201350.","journal-title":"PDA J Pharm Sci Technol"},{"issue":"8","key":"4168_CR29","doi-asserted-by":"publisher","first-page":"2203","DOI":"10.1016\/j.xphs.2023.05.017","volume":"112","author":"K Gentile","year":"2023","unstructured":"Gentile K, Huang C, Liu X, Whitty-Leveille L, Hamzaoui H, Cristofolli E, et al. Variables impacting silicone oil migration and biologics in prefilled syringes. J Pharm Sci. 2023;112(8):2203\u201311.","journal-title":"J Pharm Sci"},{"key":"4168_CR30","doi-asserted-by":"publisher","first-page":"304","DOI":"10.1016\/j.ejpb.2015.08.009","volume":"96","author":"S Funke","year":"2015","unstructured":"Funke S, Matilainen J, Nalenz H, Bechtold-Peters K, Mahler HC, Friess W. Analysis of thin baked-on silicone layers by FTIR and 3D-laser scanning microscopy. Eur J Pharm Biopharm. 2015;96:304\u201313.","journal-title":"Eur J Pharm Biopharm"},{"issue":"12","key":"4168_CR31","doi-asserted-by":"publisher","first-page":"3520","DOI":"10.1016\/j.xphs.2016.08.031","volume":"105","author":"S Funke","year":"2016","unstructured":"Funke S, Matilainen J, Nalenz H, Bechtold-Peters K, Mahler HC, Friess W. Silicone migration from baked-on silicone layers. Particle characterization in placebo and protein solutions. J Pharm Sci. 2016;105(12):3520\u201331.","journal-title":"J Pharm Sci"},{"issue":"5","key":"4168_CR32","doi-asserted-by":"publisher","first-page":"1384","DOI":"10.1002\/jps.23947","volume":"103","author":"RA Depaz","year":"2014","unstructured":"Depaz RA, Chevolleau T, Jouffray S, Narwal R, Dimitrova MN. Cross-linked silicone coating: a novel prefilled syringe technology that reduces subvisible particles and maintains compatibility with biologics. J Pharm Sci. 2014;103(5):1384\u201393.","journal-title":"J Pharm Sci"},{"issue":"6","key":"4168_CR33","doi-asserted-by":"publisher","first-page":"1521","DOI":"10.1016\/j.xphs.2018.01.021","volume":"107","author":"T Maruno","year":"2018","unstructured":"Maruno T, Watanabe H, Yoneda S, Uchihashi T, Adachi S, Arai K, et al. Sweeping of adsorbed therapeutic protein on prefillable syringes promotes micron aggregate generation. J Pharm Sci. 2018;107(6):1521\u20139.","journal-title":"J Pharm Sci"},{"issue":"14","key":"4168_CR34","doi-asserted-by":"publisher","first-page":"2349","DOI":"10.1039\/C9TB00168A","volume":"7","author":"SJ Attwood","year":"2019","unstructured":"Attwood SJ, Kershaw R, Uddin S, Bishop SM, Welland ME. Understanding how charge and hydrophobicity influence globular protein adsorption to alkanethiol and material surfaces. J Mater Chem B. 2019;7(14):2349\u201361.","journal-title":"J Mater Chem B"},{"issue":"12","key":"4168_CR35","doi-asserted-by":"publisher","DOI":"10.1016\/j.xphs.2025.104032","volume":"114","author":"A Lucas","year":"2025","unstructured":"Lucas A, Bespalova A, Upadhyay V, Monroe L, Chetcuti M, Callegari C, et al. Synergistic effect of plunger insertion and siliconization methods on particle formation of an antibody formulation. J Pharm Sci. 2025;114(12):104032.","journal-title":"J Pharm Sci"},{"issue":"7","key":"4168_CR36","doi-asserted-by":"publisher","first-page":"2105","DOI":"10.1016\/j.xphs.2016.04.009","volume":"105","author":"DV Doughty","year":"2016","unstructured":"Doughty DV, Clawson CZ, Lambert W, Subramony JA. Understanding subcutaneous tissue pressure for engineering injection devices for large-volume protein delivery. J Pharm Sci. 2016;105(7):2105\u201313.","journal-title":"J Pharm Sci"},{"key":"4168_CR37","volume-title":"USP-NF","author":"Pharmacopeia US","year":"2021","unstructured":"Pharmacopeia US. \u2329787\u232a Subvisible particulate matter in therapeutic protein injections. In: USP-NF. Rockville, MD: United States Pharmacopeia; 2021."},{"issue":"2","key":"4168_CR38","doi-asserted-by":"publisher","first-page":"536","DOI":"10.1002\/jps.24156","volume":"104","author":"C Kalonia","year":"2015","unstructured":"Kalonia C, Kumru OS, Prajapati I, Mathaes R, Engert J, Zhou S, et al. Calculating the mass of subvisible protein particles with improved accuracy using microflow imaging data. J Pharm Sci. 2015;104(2):536\u201347.","journal-title":"J Pharm Sci"},{"issue":"10","key":"4168_CR39","doi-asserted-by":"publisher","first-page":"2745","DOI":"10.1016\/j.xphs.2022.07.006","volume":"111","author":"H Shibata","year":"2022","unstructured":"Shibata H, Terabe M, Shibano Y, Saitoh S, Takasugi T, Hayashi Y, et al. A collaborative study on the classification of silicone oil droplets and protein particles using flow imaging method. J Pharm Sci. 2022;111(10):2745\u201357.","journal-title":"J Pharm Sci"},{"issue":"2","key":"4168_CR40","doi-asserted-by":"publisher","first-page":"832","DOI":"10.1016\/j.xphs.2018.08.006","volume":"108","author":"M Kiyoshi","year":"2019","unstructured":"Kiyoshi M, Shibata H, Harazono A, Torisu T, Maruno T, Akimaru M, et al. Collaborative study for analysis of subvisible particles using flow imaging and light obscuration: experiences in Japanese biopharmaceutical consortium. J Pharm Sci. 2019;108(2):832\u201341.","journal-title":"J Pharm Sci"},{"key":"4168_CR41","doi-asserted-by":"crossref","unstructured":"Shah DD, Singh SM, Mallela KM. Effect of chemical oxidation on the higher order structure, stability, aggregation, and biological function of interferon alpha-2a: role of local structural changes detected by 2D NMR: Shah, Singh and Mallela. Pharm Res. 2018;35(12):232.","DOI":"10.1007\/s11095-018-2518-y"},{"key":"4168_CR42","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpharm.2022.122210","volume":"627","author":"J Eshraghi","year":"2022","unstructured":"Eshraghi J, Dou Z, Veilleux JC, Shi G, Collins D, Ardekani AM, et al. The air entrainment and hydrodynamic shear of the liquid slosh in syringes. Int J Pharm. 2022;627:122210.","journal-title":"Int J Pharm"},{"key":"4168_CR43","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpharm.2024.124735","volume":"666","author":"S Sreenivasan","year":"2024","unstructured":"Sreenivasan S, Schoneich C, Rathore AS. Aggregation of therapeutic monoclonal antibodies due to thermal and air\/liquid interfacial agitation stress: occurrence, stability assessment strategies, aggregation mechanism, influencing factors, and ways to enhance stability. Int J Pharm. 2024;666:124735.","journal-title":"Int J Pharm"},{"key":"4168_CR44","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1016\/j.ejpb.2021.08.010","volume":"168","author":"S Sreenivasan","year":"2021","unstructured":"Sreenivasan S, Jiskoot W, Rathore AS. Rapid aggregation of therapeutic monoclonal antibodies by bubbling induced air\/liquid interfacial and agitation stress at different conditions. Eur J Pharm Biopharm. 2021;168:97\u2013109.","journal-title":"Eur J Pharm Biopharm"},{"issue":"2","key":"4168_CR45","doi-asserted-by":"publisher","first-page":"377","DOI":"10.1016\/j.xphs.2022.10.009","volume":"112","author":"MRG Kopp","year":"2023","unstructured":"Kopp MRG, Grigolato F, Zurcher D, Das TK, Chou D, Wuchner K, et al. Surface-induced protein aggregation and particle formation in biologics: current understanding of mechanisms, detection and mitigation strategies. J Pharm Sci. 2023;112(2):377\u201385.","journal-title":"J Pharm Sci"},{"issue":"2","key":"4168_CR46","doi-asserted-by":"publisher","first-page":"72","DOI":"10.1208\/s12249-018-1281-z","volume":"20","author":"A Hauptmann","year":"2019","unstructured":"Hauptmann A, Hoelzl G, Loerting T. Distribution of protein content and number of aggregates in monoclonal antibody formulation after large-scale freezing. AAPS PharmSciTech. 2019;20(2):72.","journal-title":"AAPS PharmSciTech"},{"key":"4168_CR47","doi-asserted-by":"publisher","first-page":"108","DOI":"10.1016\/j.btre.2015.03.004","volume":"6","author":"U Roessl","year":"2015","unstructured":"Roessl U, Leitgeb S, Nidetzky B. Protein freeze concentration and micro-segregation analysed in a temperature-controlled freeze container. Biotechnol Rep. 2015;6:108\u201311.","journal-title":"Biotechnol Rep"},{"key":"4168_CR48","volume":"4","author":"O Bluemel","year":"2022","unstructured":"Bluemel O, Buecheler JW, Hauptmann A, Hoelzl G, Bechtold-Peters K, Friess W. The effect of mAb and excipient cryoconcentration on long-term frozen storage stability - part 2: Aggregate formation and oxidation. Int J Pharm X. 2022;4:100109.","journal-title":"Int J Pharm X"},{"issue":"5","key":"4168_CR49","doi-asserted-by":"publisher","first-page":"505","DOI":"10.1080\/10837450701481157","volume":"12","author":"BS Bhatnagar","year":"2007","unstructured":"Bhatnagar BS, Bogner RH, Pikal MJ. Protein stability during freezing: separation of stresses and mechanisms of protein stabilization. Pharm Dev Technol. 2007;12(5):505\u201323.","journal-title":"Pharm Dev Technol"},{"issue":"12","key":"4168_CR50","doi-asserted-by":"publisher","first-page":"1325","DOI":"10.1021\/js960080y","volume":"85","author":"BS Chang","year":"1996","unstructured":"Chang BS, Kendrick BS, Carpenter JF. Surface-induced denaturation of proteins during freezing and its inhibition by surfactants. J Pharm Sci. 1996;85(12):1325\u201330.","journal-title":"J Pharm Sci"},{"issue":"12","key":"4168_CR51","doi-asserted-by":"publisher","first-page":"4569","DOI":"10.1002\/jps.23328","volume":"101","author":"F Felsovalyi","year":"2012","unstructured":"Felsovalyi F, Janvier S, Jouffray S, Soukiassian H, Mangiagalli P. Silicone-oil-based subvisible particles: their detection, interactions, and regulation in prefilled container closure systems for biopharmaceuticals. J Pharm Sci. 2012;101(12):4569\u201383.","journal-title":"J Pharm Sci"},{"issue":"4","key":"4168_CR52","doi-asserted-by":"publisher","first-page":"1656","DOI":"10.1021\/acs.molpharmaceut.0c01113","volume":"18","author":"A Kannan","year":"2021","unstructured":"Kannan A, Shieh IC, Negulescu PG, Chandran Suja V, Fuller GG. Adsorption and aggregation of monoclonal antibodies at silicone oil-water interfaces. Mol Pharm. 2021;18(4):1656\u201365.","journal-title":"Mol Pharm"},{"issue":"4","key":"4168_CR53","doi-asserted-by":"publisher","first-page":"1282","DOI":"10.1002\/jps.24358","volume":"104","author":"SB Mehta","year":"2015","unstructured":"Mehta SB, Lewus R, Bee JS, Randolph TW, Carpenter JF. Gelation of a monoclonal antibody at the silicone oil-water interface and subsequent rupture of the interfacial gel results in aggregation and particle formation. J Pharm Sci. 2015;104(4):1282\u201390.","journal-title":"J Pharm Sci"},{"issue":"11","key":"4168_CR54","doi-asserted-by":"publisher","first-page":"4758","DOI":"10.1007\/s12325-023-02671-2","volume":"40","author":"A Antalfy","year":"2023","unstructured":"Antalfy A, Berman K, Everitt C, Alten R, Latymer M, Godfrey CM. The adherence and outcomes benefits of using a connected, reusable auto-injector for self-injecting biologics: a narrative review. Adv Ther. 2023;40(11):4758\u201376.","journal-title":"Adv Ther"},{"issue":"11","key":"4168_CR55","doi-asserted-by":"publisher","first-page":"3568","DOI":"10.1016\/j.xphs.2021.07.007","volume":"110","author":"S Yoneda","year":"2021","unstructured":"Yoneda S, Maruno T, Mori A, Hioki A, Nishiumi H, Okada R, et al. Influence of protein adsorption on aggregation in prefilled syringes. J Pharm Sci. 2021;110(11):3568\u201379.","journal-title":"J Pharm Sci"},{"issue":"4","key":"4168_CR56","doi-asserted-by":"publisher","first-page":"1116","DOI":"10.1208\/s12249-012-9843-y","volume":"13","author":"N Dixit","year":"2012","unstructured":"Dixit N, Maloney KM, Kalonia DS. Effect of processing parameters on the physical stability of silicone coatings. AAPS PharmSciTech. 2012;13(4):1116\u20139.","journal-title":"AAPS PharmSciTech"},{"issue":"11","key":"4168_CR57","doi-asserted-by":"publisher","first-page":"3681","DOI":"10.1002\/jps.24573","volume":"104","author":"CF Chisholm","year":"2015","unstructured":"Chisholm CF, Nguyen BH, Soucie KR, Torres RM, Carpenter JF, Randolph TW. In vivo analysis of the potency of silicone oil microdroplets as immunological adjuvants in protein formulations. J Pharm Sci. 2015;104(11):3681\u201390.","journal-title":"J Pharm Sci"},{"issue":"5","key":"4168_CR58","doi-asserted-by":"publisher","first-page":"1623","DOI":"10.1016\/j.xphs.2016.02.019","volume":"105","author":"CF Chisholm","year":"2016","unstructured":"Chisholm CF, Baker AE, Soucie KR, Torres RM, Carpenter JF, Randolph TW. Silicone oil microdroplets can induce antibody responses against recombinant murine growth hormone in mice. J Pharm Sci. 2016;105(5):1623\u201332.","journal-title":"J Pharm Sci"},{"issue":"7","key":"4168_CR59","doi-asserted-by":"publisher","first-page":"2278","DOI":"10.1016\/j.xphs.2019.02.002","volume":"108","author":"E Krayukhina","year":"2019","unstructured":"Krayukhina E, Yokoyama M, Hayashihara KK, Maruno T, Noda M, Watanabe H, et al. An assessment of the ability of submicron- and micron-size silicone oil droplets in dropped prefillable syringes to invoke early- and late-stage immune responses. J Pharm Sci. 2019;108(7):2278\u201387.","journal-title":"J Pharm Sci"},{"issue":"3","key":"4168_CR60","doi-asserted-by":"publisher","first-page":"946","DOI":"10.1002\/jps.23018","volume":"101","author":"W Jiskoot","year":"2012","unstructured":"Jiskoot W, Randolph TW, Volkin DB, Middaugh CR, Schoneich C, Winter G, et al. Protein instability and immunogenicity: roadblocks to clinical application of injectable protein delivery systems for sustained release. J Pharm Sci. 2012;101(3):946\u201354.","journal-title":"J Pharm Sci"},{"issue":"4","key":"4168_CR61","doi-asserted-by":"publisher","first-page":"651","DOI":"10.1007\/s11095-024-03678-2","volume":"41","author":"JR Cohen","year":"2024","unstructured":"Cohen JR, Brych SR, Prabhu S, Bi V, Elbaradei A, Tokuda JM, et al. A High Threshold of Biotherapeutic Aggregate Numbers is Needed to Induce an Immunogenic Response In Vitro, In Vivo, and in the Clinic. Pharm Res. 2024;41(4):651\u201372.","journal-title":"Pharm Res"}],"container-title":["Pharmaceutical Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s11095-026-04168-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s11095-026-04168-3","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s11095-026-04168-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T21:04:02Z","timestamp":1793826242000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s11095-026-04168-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,17]]},"references-count":61,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2026,10]]}},"alternative-id":["4168"],"URL":"https:\/\/doi.org\/10.1007\/s11095-026-04168-3","relation":{},"ISSN":["0724-8741","1573-904X"],"issn-type":[{"value":"0724-8741","type":"print"},{"value":"1573-904X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,17]]},"assertion":[{"value":"19 May 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"25 July 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"17 September 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"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.","order":1,"name":"Ethics","label":"Conflict of interest","group":{"name":"EthicsHeading","label":"Declarations"}}]}}