{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T13:24:15Z","timestamp":1790774655568,"version":"4.1.0"},"reference-count":111,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2026,5,25]],"date-time":"2026-05-25T00:00:00Z","timestamp":1779667200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Advanced Drug Delivery Reviews"],"published-print":{"date-parts":[[2026,8]]},"DOI":"10.1016\/j.addr.2026.115885","type":"journal-article","created":{"date-parts":[[2026,5,10]],"date-time":"2026-05-10T22:17:06Z","timestamp":1778451426000},"page":"115885","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":3,"special_numbering":"C","title":["High-Dose Subcutaneous Administration of Biologics: Overcoming Barriers Through Formulation and Device Innovation"],"prefix":"10.1016","volume":"235","author":[{"given":"Tarik A.","family":"Khan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deep","family":"Bhattacharya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Twinkle R.","family":"Christian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa","family":"Holstein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoqing","family":"Hua","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roshan","family":"James","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bowen","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Josowitz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danielle","family":"Laiacona","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shrenik","family":"Mehta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Apurva","family":"More","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edel","family":"Mullen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Myers","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brendon","family":"Ricart","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timon","family":"Rickenbacher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongchao","family":"Su","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naveen Kumar Reddy","family":"Yaragudi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.addr.2026.115885_bb0005","doi-asserted-by":"crossref","first-page":"745","DOI":"10.1038\/s41577-025-01207-9","article-title":"Fifty years of monoclonals: the past, present and future of antibody therapeutics","volume":"25","author":"Chan","year":"2025","journal-title":"Nat. Rev. Immunol."},{"key":"10.1016\/j.addr.2026.115885_bb0010","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1007\/s40259-023-00626-1","article-title":"Advancing subcutaneous dosing regimens for Biotherapeutics: clinical strategies for expedited market access","volume":"38","author":"Bittner","year":"2024","journal-title":"BioDrugs"},{"key":"10.1016\/j.addr.2026.115885_bb0015","doi-asserted-by":"crossref","DOI":"10.1016\/j.esmoop.2020.100007","article-title":"Flexible care in breast cancer","volume":"6","author":"Wardley","year":"2021","journal-title":"ESMO Open"},{"key":"10.1016\/j.addr.2026.115885_bb0020","doi-asserted-by":"crossref","DOI":"10.1016\/j.clon.2024.103671","article-title":"Switching to a fixed-dose combined Pertuzumab and Trastuzumab with recombinant human hyaluronidase subcutaneous injection to treat human epidermal growth factor receptor 2-positive breast Cancer in real-world UK clinical practice","volume":"37","author":"Harding","year":"2025","journal-title":"Clin. Oncol."},{"key":"10.1016\/j.addr.2026.115885_bb0025","doi-asserted-by":"crossref","DOI":"10.1016\/j.jconrel.2025.114156","article-title":"An industry perspective on clinical development and regulatory strategies for subcutaneously administered high-dose biologics","volume":"386","author":"Bruin","year":"2025","journal-title":"J. Control. Release"},{"key":"10.1016\/j.addr.2026.115885_bb0030","doi-asserted-by":"crossref","DOI":"10.1080\/19420862.2023.2211185","article-title":"High concentration formulation developability approaches and considerations","volume":"15","author":"Zarzar","year":"2023","journal-title":"mAbs"},{"key":"10.1016\/j.addr.2026.115885_bb0045","doi-asserted-by":"crossref","first-page":"914","DOI":"10.1177\/1932296815626723","article-title":"Injection technique and pen needle design affect leakage from skin after subcutaneous injections","volume":"10","author":"Pr\u00e6stmark","year":"2016","journal-title":"J. Diabetes Sci. Technol."},{"key":"10.1016\/j.addr.2026.115885_bb0050","doi-asserted-by":"crossref","first-page":"1107","DOI":"10.1016\/j.addr.2011.09.008","article-title":"Viscosity of concentrated therapeutic protein compositions","volume":"63","author":"Jezek","year":"2011","journal-title":"Adv. Drug Deliv. Rev."},{"key":"10.1016\/j.addr.2026.115885_bb0055","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1080\/19420862.2015.1128606","article-title":"Molecular basis of high viscosity in concentrated antibody solutions: strategies for high concentration drug product development","volume":"8","author":"Tomar","year":"2016","journal-title":"mAbs"},{"key":"10.1016\/j.addr.2026.115885_bb0060","doi-asserted-by":"crossref","first-page":"2968","DOI":"10.1016\/j.xphs.2022.08.036","article-title":"Advanced formulations\/drug delivery Systems for Subcutaneous Delivery of protein-based Biotherapeutics","volume":"111","author":"Lou","year":"2022","journal-title":"J. Pharm. Sci."},{"key":"10.1016\/j.addr.2026.115885_bb0065","doi-asserted-by":"crossref","first-page":"2517","DOI":"10.1016\/j.xphs.2019.03.008","article-title":"Enhancing stability and reducing viscosity of a monoclonal antibody with Cosolutes by weakening protein-protein interactions","volume":"108","author":"Dear","year":"2019","journal-title":"J. Pharm. Sci."},{"key":"10.1016\/j.addr.2026.115885_bb0070","doi-asserted-by":"crossref","first-page":"1077","DOI":"10.1016\/j.xphs.2020.12.016","article-title":"Product-specific impact of viscosity modulating formulation excipients during ultra-high concentration Biotherapeutics drug product development","volume":"110","author":"Rodrigues","year":"2021","journal-title":"J. Pharm. Sci."},{"key":"10.1016\/j.addr.2026.115885_bb0075","first-page":"1","article-title":"S.C. Delivery of ultra-high concentration (up to 500 mg\/mL) protein microparticle suspensions: pharmacokinetics, efficacy, biodistribution, and immunogenicity","author":"Shadbar","year":"2025","journal-title":"Drug Deliv. Transl. Res."},{"key":"10.1016\/j.addr.2026.115885_bb0080","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1016\/j.ejpb.2017.06.029","article-title":"High-concentration protein formulations: how high is high?","volume":"119","author":"Garidel","year":"2017","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"10.1016\/j.addr.2026.115885_bb0085","doi-asserted-by":"crossref","first-page":"922","DOI":"10.1016\/j.xphs.2023.01.029","article-title":"Patient-centric product development: a summary of select regulatory CMC and device considerations","volume":"112","author":"Algorri","year":"2023","journal-title":"J. Pharm. Sci."},{"key":"10.1016\/j.addr.2026.115885_bb0090","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1146\/annurev-pharmtox-052120-093517","article-title":"Patient centricity driving formulation innovation: improvements in patient care facilitated by novel therapeutics and drug delivery technologies","volume":"62","author":"Page","year":"2022","journal-title":"Annu. Rev. Pharmacol."},{"key":"10.1016\/j.addr.2026.115885_bb0095","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1016\/j.xphs.2021.11.008","article-title":"Ongoing challenges to develop high concentration monoclonal antibody-based formulations for subcutaneous administration: quo Vadis?","volume":"111","author":"Jiskoot","year":"2022","journal-title":"J. Pharm. Sci."},{"key":"10.1016\/j.addr.2026.115885_bb0040","doi-asserted-by":"crossref","DOI":"10.1080\/19420862.2024.2402713","article-title":"Navigating large-volume subcutaneous injections of biopharmaceuticals: a systematic review of clinical pipelines and approved products","volume":"16","author":"Green","year":"2024","journal-title":"mAbs"},{"key":"10.1016\/j.addr.2026.115885_bb0100","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1186\/s41120-022-00064-3","article-title":"Formulation mitigations for particle formation induced by enzymatic hydrolysis of polysorbate 20 in protein-based drug products: insights from a full-factorial longitudinal study","volume":"8","author":"Yuk","year":"2022","journal-title":"AAPS Open"},{"key":"10.1016\/j.addr.2026.115885_bb0105","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1007\/s41669-022-00361-3","article-title":"A systematic review of time and resource use costs of subcutaneous versus intravenous Administration of Oncology Biologics in a hospital setting","volume":"7","author":"McCloskey","year":"2023","journal-title":"PharmacoEconomics - Open"},{"key":"10.1016\/j.addr.2026.115885_bb0110","doi-asserted-by":"crossref","first-page":"833","DOI":"10.1007\/s12325-021-01996-0","article-title":"White paper on the value of time Savings for Patients and Healthcare Providers of breast Cancer therapy: the fixed-dose combination of Pertuzumab and Trastuzumab for subcutaneous injection as an example","volume":"39","author":"Jackisch","year":"2022","journal-title":"Adv. Ther."},{"key":"10.1016\/j.addr.2026.115885_bb0115","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0295730","article-title":"Cost minimization analysis of treatments for metastatic HER2-positive breast cancer in Peru: fixed-dose combination of pertuzumab and trastuzumab for subcutaneous injections","volume":"19","author":"Figallo","year":"2024","journal-title":"PLoS One"},{"key":"10.1016\/j.addr.2026.115885_bb0120","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1007\/s12282-025-01803-6","article-title":"Multidimensional impact of fixed-dose subcutaneous trastuzumab-pertuzumab on oncology workflow and patient time burden in a real-world study","volume":"33","author":"Oshi","year":"2026","journal-title":"Breast Cancer"},{"key":"10.1016\/j.addr.2026.115885_bb0125","doi-asserted-by":"crossref","first-page":"1213","DOI":"10.1122\/1.551021","article-title":"Curvilinear flows of noncolloidal suspensions: the role of normal stresses","volume":"43","author":"Morris","year":"1999","journal-title":"J. Rheol."},{"key":"10.1016\/j.addr.2026.115885_bb0130","doi-asserted-by":"crossref","DOI":"10.1103\/PhysRevLett.117.108001","article-title":"Shear thinning of noncolloidal suspensions","volume":"117","author":"V\u00e1zquez-Quesada","year":"2016","journal-title":"Phys. Rev. Lett."},{"key":"10.1016\/j.addr.2026.115885_bb0135","doi-asserted-by":"crossref","DOI":"10.1016\/j.jnnfm.2020.104298","article-title":"On the shear thinning of non-Brownian suspensions: friction or adhesion?","volume":"281","author":"Papadopoulou","year":"2020","journal-title":"J. Non-Newton. Fluid Mech."},{"key":"10.1016\/j.addr.2026.115885_bb0140","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1039\/D4PM00290C","article-title":"Injectable sustained-release hydrogel for high-concentration antibody delivery","volume":"2","author":"Zheng","year":"2024","journal-title":"RSC Pharm."},{"key":"10.1016\/j.addr.2026.115885_bb0145","doi-asserted-by":"crossref","first-page":"1520","DOI":"10.1208\/s12249-018-0963-x","article-title":"Delivery considerations of highly viscous polymeric fluids mimicking concentrated biopharmaceuticals: assessment of injectability via measurement of total work done \u201cWT,\u201d","volume":"19","author":"Zhang","year":"2018","journal-title":"AAPS PharmSciTech"},{"key":"10.1016\/j.addr.2026.115885_bb0150","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1007\/s40820-021-00712-5","article-title":"Nanoengineered shear-thinning hydrogel barrier for preventing postoperative abdominal adhesions","volume":"13","author":"Ruiz-Esparza","year":"2021","journal-title":"Nano-Micro Lett."},{"key":"10.1016\/j.addr.2026.115885_bb0155","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1007\/s00397-017-1002-7","article-title":"A review on wall slip in high solid dispersions","volume":"56","author":"Cloitre","year":"2017","journal-title":"Rheol. Acta"},{"key":"10.1016\/j.addr.2026.115885_bb0160","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1007\/12_2010_90","article-title":"High solid dispersions","author":"Bonnecaze","year":"2010","journal-title":"Adv. Polym. Sci."},{"key":"10.1016\/j.addr.2026.115885_bb0165","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1007\/s00397-021-01281-5","article-title":"Quantification of shear viscosity and wall slip velocity of highly concentrated suspensions with non-Newtonian matrices in pressure driven flows","volume":"60","author":"Wilms","year":"2021","journal-title":"Rheol. Acta"},{"key":"10.1016\/j.addr.2026.115885_bb0170","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1007\/s00348-016-2241-6","article-title":"Direct measurement of wall slip and slip layer thickness of non-Brownian hard-sphere suspensions in rectangular channel flows","volume":"57","author":"Jesinghausen","year":"2016","journal-title":"Exp. Fluids"},{"key":"10.1016\/j.addr.2026.115885_bb0175","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1016\/j.cej.2016.09.013","article-title":"A factorial approach to understanding the effect of inner geometry of baffled meso-scale tubes on solids suspension and axial dispersion in continuous, oscillatory liquid\u2013solid plug flows","volume":"308","author":"Ejim","year":"2017","journal-title":"Chem. Eng. J."},{"key":"10.1016\/j.addr.2026.115885_bb0180","doi-asserted-by":"crossref","first-page":"1357","DOI":"10.1021\/nn204166z","article-title":"Concentrated Dispersions of equilibrium protein nanoclusters that reversibly dissociate into active monomers","volume":"6","author":"Johnston","year":"2012","journal-title":"ACS Nano"},{"key":"10.1016\/j.addr.2026.115885_bb0185","doi-asserted-by":"crossref","DOI":"10.1002\/adma.202511918","article-title":"High concentration antibody formulations enabled via thermostable ionic liquids","volume":"38","author":"Erdi","year":"2026","journal-title":"Adv. Mater."},{"key":"10.1016\/j.addr.2026.115885_bb0190","doi-asserted-by":"crossref","DOI":"10.1002\/adma.202516429","article-title":"High-concentration antibody formulation via solvent-based dehydration","volume":"38","author":"Zheng","year":"2026","journal-title":"Adv. Mater."},{"key":"10.1016\/j.addr.2026.115885_bb0195","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/j.ejpb.2021.04.023","article-title":"Preparation of high concentration protein powder suspensions by milling of lyophilizates","volume":"166","author":"Marschall","year":"2021","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"10.1016\/j.addr.2026.115885_bb0200","doi-asserted-by":"crossref","first-page":"1605","DOI":"10.1016\/j.xphs.2025.01.028","article-title":"Developing ultra-high concentration formulations of human immune globulins for subcutaneous injectables","volume":"114","author":"Yadav","year":"2025","journal-title":"J. Pharm. Sci."},{"key":"10.1016\/j.addr.2026.115885_bb0205","doi-asserted-by":"crossref","first-page":"59","DOI":"10.5731\/pdajpst.2015.01003","article-title":"Manufacturing of high-concentration monoclonal antibody formulations via spray drying--the road to manufacturing scale","volume":"69","author":"Gikanga","year":"2015","journal-title":"PDA J. Pharm. Sci. Technol."},{"key":"10.1016\/j.addr.2026.115885_bb0210","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1021\/js980321x","article-title":"Stability and surface activity of lactate dehydrogenase in spray-dried trehalose","volume":"88","author":"Adler","year":"1999","journal-title":"J. Pharm. Sci."},{"key":"10.1016\/j.addr.2026.115885_bb0215","doi-asserted-by":"crossref","DOI":"10.1016\/j.ijpharm.2025.125422","article-title":"The value of spray drying as stabilization process for proteins","volume":"674","author":"Kopp","year":"2025","journal-title":"Int. J. Pharm."},{"key":"10.1016\/j.addr.2026.115885_bb0220","article-title":"How spray drying processing and solution composition can affect the mAbs stability in reconstituted solutions for subcutaneous injections. Part I: contribution of processing stresses against composition","volume":"655","author":"Barcel\u00f3-Chong","year":"2024","journal-title":"Int. J. Pharm."},{"key":"10.1016\/j.addr.2026.115885_bb0225","article-title":"How spray drying processing and solution composition can affect the mAbs stability in reconstituted solutions for subcutaneous injections. Part II: exploring each protein stabilizer effect","volume":"655","author":"Barcelo-Chong","year":"2024","journal-title":"Int. J. Pharm."},{"key":"10.1016\/j.addr.2026.115885_bb0230","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1016\/j.ejps.2018.10.026","article-title":"Spray drying of pharmaceuticals and biopharmaceuticals: critical parameters and experimental process optimization approaches","volume":"127","author":"Ziaee","year":"2019","journal-title":"Eur. J. Pharm. Sci."},{"key":"10.1016\/j.addr.2026.115885_bb0235","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1515\/ijfe-2014-0267","article-title":"Optimization of spray drying process parameters for sweet corn Enzymolysis liquid","volume":"11","author":"Jiang","year":"2015","journal-title":"Int. J. Food Eng."},{"key":"10.1016\/j.addr.2026.115885_bb0240","doi-asserted-by":"crossref","first-page":"eadv6427","DOI":"10.1126\/scitranslmed.adv6427","article-title":"Ultrahigh-concentration biologic therapeutics enabled by spray drying with a glassy surfactant excipient","volume":"17","author":"Jons","year":"2025","journal-title":"Sci. Transl. Med."},{"key":"10.1016\/j.addr.2026.115885_bb0245","doi-asserted-by":"crossref","first-page":"2291","DOI":"10.1007\/s11095-022-03331-w","article-title":"Spray-dried and spray-freeze-dried powder formulations of an anti-interleukin-4R\u03b1 antibody for pulmonary delivery","volume":"39","author":"Pan","year":"2022","journal-title":"Pharm. Res."},{"key":"10.1016\/j.addr.2026.115885_bb0250","doi-asserted-by":"crossref","DOI":"10.1016\/j.ijpharm.2024.123892","article-title":"Intranasal delivery of thin-film freeze-dried monoclonal antibodies using a powder nasal spray system","volume":"653","author":"Yu","year":"2024","journal-title":"Int. J. Pharm."},{"key":"10.1016\/j.addr.2026.115885_bb0255","doi-asserted-by":"crossref","first-page":"3763","DOI":"10.1002\/jps.23256","article-title":"Antibody nanoparticle dispersions formed with mixtures of crowding molecules retain activity and in vivo bioavailability","volume":"101","author":"Miller","year":"2012","journal-title":"J. Pharm. Sci."},{"key":"10.1016\/j.addr.2026.115885_bb0260","doi-asserted-by":"crossref","DOI":"10.1016\/j.ijpharm.2025.125825","article-title":"Recent advances in dry powder inhalation formulations prepared by co-spray drying technology: a comprehensive review","volume":"681","author":"Chen","year":"2025","journal-title":"Int. J. Pharm."},{"key":"10.1016\/j.addr.2026.115885_bb0265","doi-asserted-by":"crossref","first-page":"640","DOI":"10.1002\/jps.24279","article-title":"Enzyme dehydration using Microglassification\u2122 preserves the protein's structure and function","volume":"104","author":"Aniket","year":"2015","journal-title":"J. Pharm. Sci."},{"key":"10.1016\/j.addr.2026.115885_bb0270","doi-asserted-by":"crossref","first-page":"810","DOI":"10.1002\/jps.23847","article-title":"MicroglassificationTM: a novel technique for protein dehydration","volume":"103","author":"Aniket","year":"2014","journal-title":"J. Pharm. Sci."},{"key":"10.1016\/j.addr.2026.115885_bb0275","series-title":"Compositions Comprising Solid Particles","author":"Bitterfield","year":"2023"},{"key":"10.1016\/j.addr.2026.115885_bb0280","series-title":"Chemical Dehydration and Suspension Delivery of Protein Drug Products","author":"Elbaum","year":"2025"},{"key":"10.1016\/j.addr.2026.115885_bb0285","doi-asserted-by":"crossref","first-page":"935","DOI":"10.1016\/j.ijbiomac.2021.07.012","article-title":"Protein microbeadification to achieve highly concentrated protein formulation with reversible properties and in vivo pharmacokinetics after reconstitution","volume":"185","author":"Kim","year":"2021","journal-title":"Int. J. Biol. Macromol."},{"key":"10.1016\/j.addr.2026.115885_bb0290","doi-asserted-by":"crossref","first-page":"53","DOI":"10.3109\/02652049609006803","article-title":"Microencapsulation reactor scale-up by dimensional analysis","volume":"13","author":"Maa","year":"1996","journal-title":"J. Microencapsul."},{"key":"10.1016\/j.addr.2026.115885_bb0295","doi-asserted-by":"crossref","first-page":"419","DOI":"10.3109\/02652049609026028","article-title":"Liquid-liquid emulsification by static mixers for use in microencapsulation","volume":"13","author":"Maa","year":"1996","journal-title":"J. Microencapsul."},{"key":"10.1016\/j.addr.2026.115885_bb0300","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1016\/0168-3659(95)00123-9","article-title":"Liquid-liquid emulsification by rotor\/stator homogenization","volume":"38","author":"Maa","year":"1996","journal-title":"J. Control. Release"},{"key":"10.1016\/j.addr.2026.115885_bb0305","doi-asserted-by":"crossref","first-page":"e81","DOI":"10.1016\/j.ddtec.2008.11.001","article-title":"Drying methods for protein pharmaceuticals","volume":"5","author":"Maltesen","year":"2008","journal-title":"Drug Discov. Today Technol."},{"key":"10.1016\/j.addr.2026.115885_bb0310","doi-asserted-by":"crossref","first-page":"1054","DOI":"10.1016\/j.xphs.2023.10.021","article-title":"Stability comparison between Microglassification and Lyophilization using a monoclonal antibody","volume":"113","author":"Chandrababu","year":"2024","journal-title":"J. Pharm. Sci."},{"key":"10.1016\/j.addr.2026.115885_bb0315","doi-asserted-by":"crossref","first-page":"1390","DOI":"10.1002\/jps.20079","article-title":"Challenges in the development of high protein concentration formulations","volume":"93","author":"Shire","year":"2004","journal-title":"J. Pharm. Sci."},{"key":"10.1016\/j.addr.2026.115885_bb0320","doi-asserted-by":"crossref","DOI":"10.1016\/j.ijpharm.2021.120942","article-title":"Electrostatic spray drying for monoclonal antibody formulation","volume":"607","author":"Mutukuri","year":"2021","journal-title":"Int. J. Pharm."},{"key":"10.1016\/j.addr.2026.115885_bb0325","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/j.xphs.2022.06.016","article-title":"Drug product characterization of high concentration non-aqueous protein powder suspensions","volume":"112","author":"Marschall","year":"2023","journal-title":"J. Pharm. Sci."},{"key":"10.1016\/j.addr.2026.115885_bb0330","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.ejpb.2021.01.014","article-title":"Powder suspensions in non-aqueous vehicles for delivery of therapeutic proteins","volume":"161","author":"Marschall","year":"2021","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"10.1016\/j.addr.2026.115885_bb0335","doi-asserted-by":"crossref","first-page":"4433","DOI":"10.1002\/jps.23324","article-title":"Investigating high-concentration monoclonal antibody powder suspension in nonaqueous suspension vehicles for subcutaneous injection","volume":"101","author":"Bowen","year":"2012","journal-title":"J. Pharm. Sci."},{"key":"10.1016\/j.addr.2026.115885_bb0340","author":"U.S.F. and D. Administration"},{"key":"10.1016\/j.addr.2026.115885_bb0345","doi-asserted-by":"crossref","first-page":"1109","DOI":"10.1016\/S0161-6420(87)33328-7","article-title":"Silicone oil in the treatment of complicated retinal detachments","volume":"94","author":"Yeo","year":"1987","journal-title":"Ophthalmology"},{"key":"10.1016\/j.addr.2026.115885_bb0350","doi-asserted-by":"crossref","first-page":"165","DOI":"10.2174\/1389201003378942","article-title":"Characterization of protein and peptide stability and solubility in non-aqueous solvents","volume":"1","author":"Stevenson","year":"2000","journal-title":"Curr. Pharm. Biotechnol."},{"key":"10.1016\/j.addr.2026.115885_bb0355","doi-asserted-by":"crossref","DOI":"10.3389\/fnut.2021.734620","article-title":"Fabrication of bacterial cellulose nanofibers\/soy protein isolate colloidal particles for the stabilization of high internal phase Pickering emulsions by anti-solvent precipitation and their application in the delivery of curcumin","volume":"8","author":"Shen","year":"2021","journal-title":"Front. Nutr."},{"key":"10.1016\/j.addr.2026.115885_bb0360","doi-asserted-by":"crossref","DOI":"10.1016\/j.jddst.2022.103526","article-title":"Lipid based nanocarriers: Production techniques, concepts, and commercialization aspect","volume":"74","author":"Kumar","year":"2022","journal-title":"J. Drug Delivery Sci. Technol."},{"key":"10.1016\/j.addr.2026.115885_bb0365","doi-asserted-by":"crossref","first-page":"1148","DOI":"10.3390\/vaccines12101148","article-title":"Recent advances in lipid nanoparticles and their safety concerns for mRNA delivery","volume":"12","author":"Wang","year":"2024","journal-title":"Vaccines"},{"key":"10.1016\/j.addr.2026.115885_bb0370","doi-asserted-by":"crossref","first-page":"6934","DOI":"10.1073\/pnas.1131899100","article-title":"Crystalline monoclonal antibodies for subcutaneous delivery","volume":"100","author":"Yang","year":"2003","journal-title":"Proc. Natl. Acad. Sci."},{"key":"10.1016\/j.addr.2026.115885_bb0375","doi-asserted-by":"crossref","first-page":"4024","DOI":"10.1021\/acs.molpharmaceut.4c00418","article-title":"Small-angle X-ray scattering as a powerful tool for phase and crystallinity assessment of monoclonal antibody crystallites in support of batch crystallization","volume":"21","author":"Larpent","year":"2024","journal-title":"Mol. Pharm."},{"key":"10.1016\/j.addr.2026.115885_bb0380","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1038\/s41526-019-0090-3","article-title":"Pembrolizumab microgravity crystallization experimentation","volume":"5","author":"Reichert","year":"2019","journal-title":"Npj Microgravity"},{"key":"10.1016\/j.addr.2026.115885_bb0385","doi-asserted-by":"crossref","first-page":"936","DOI":"10.1021\/acs.molpharmaceut.1c00915","article-title":"Investigating crystalline protein suspension formulations of Pembrolizumab from MAS NMR spectroscopy","volume":"19","author":"Li","year":"2022","journal-title":"Mol. Pharm."},{"key":"10.1016\/j.addr.2026.115885_bb0390","doi-asserted-by":"crossref","DOI":"10.1002\/adhm.202202370","article-title":"Crystalline antibody-laden alginate particles: a platform for enabling high concentration subcutaneous delivery of antibodies","volume":"12","author":"Erfani","year":"2023","journal-title":"Adv. Healthc. Mater."},{"key":"10.1016\/j.addr.2026.115885_bb0395","doi-asserted-by":"crossref","DOI":"10.1080\/19420862.2024.2304624","article-title":"In-situ biophysical characterization of high-concentration protein formulations using wNMR","volume":"16","author":"Song","year":"2024","journal-title":"mAbs"},{"key":"10.1016\/j.addr.2026.115885_bb0400","doi-asserted-by":"crossref","first-page":"963","DOI":"10.1023\/A:1015888520352","article-title":"Physical characterization of pharmaceutical solids","volume":"8","author":"Brittain","year":"1991","journal-title":"Pharm. Res."},{"key":"10.1016\/j.addr.2026.115885_bb0405","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/j.biosystemseng.2004.09.001","article-title":"Indirect methods to estimate suspended sediment concentration: reliability and relationship of turbidity and Settleable solids","volume":"90","author":"Pavanelli","year":"2005","journal-title":"Biosyst. Eng."},{"key":"10.1016\/j.addr.2026.115885_bb0410","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1016\/j.powtec.2016.12.034","article-title":"Analysis of suspension sedimentation in fluids with rheological shear-thinning properties and thixotropic effects","volume":"308","author":"Moreira","year":"2017","journal-title":"Powder Technol."},{"key":"10.1016\/j.addr.2026.115885_bb0415","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1081\/DIS-120015373","article-title":"Dispersion stability and particle characterization by sedimentation kinetics in a centrifugal field","volume":"23","author":"Lerche","year":"2002","journal-title":"J. Dispers. Sci. Technol."},{"key":"10.1016\/j.addr.2026.115885_bb0420","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1016\/j.colsurfb.2017.08.015","article-title":"Assessing differences between Ostwald ripening and coalescence by rheology, laser diffraction and multiple light scattering","volume":"159","author":"Santos","year":"2017","journal-title":"Colloids Surf. B: Biointerfaces"},{"key":"10.1016\/j.addr.2026.115885_bb0425","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1016\/S0939-6411(96)00037-9","article-title":"Residual solvents in pharmaceutical products: acceptable limits, influences on physicochemical properties, analytical methods and documented values","volume":"43","author":"Witschi","year":"1997","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"10.1016\/j.addr.2026.115885_bb0430","series-title":"Encyclopedia of Pharmaceutical Science and Technology","first-page":"2222","year":"2013"},{"key":"10.1016\/j.addr.2026.115885_bb0435","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1007\/s11095-024-03673-7","article-title":"Unraveling pre-filled syringe needle clogging: exploring a fresh outlook through innovative techniques","volume":"41","author":"Hu","year":"2024","journal-title":"Pharm. Res."},{"key":"10.1016\/j.addr.2026.115885_bb0440","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1208\/s12249-025-03167-8","article-title":"Alternative syringe and needle Design for Clog-free Delivery of high-concentration suspensions","volume":"26","author":"Kowsari","year":"2025","journal-title":"AAPS PharmSciTech"},{"key":"10.1016\/j.addr.2026.115885_bb0445","doi-asserted-by":"crossref","first-page":"24241","DOI":"10.1021\/acs.langmuir.4c01547","article-title":"Effect of liquid properties on the non-Newtonian rheology of concentrated silica suspensions: discontinuous shear thickening, shear jamming, and shock absorbance","volume":"40","author":"Samitsu","year":"2024","journal-title":"Langmuir"},{"key":"10.1016\/j.addr.2026.115885_bb0450","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1007\/s11095-024-03683-5","article-title":"Clinical investigation of large volume subcutaneous delivery up to 25 mL for lean and non-lean subjects","volume":"41","author":"Dang","year":"2024","journal-title":"Pharm. Res."},{"key":"10.1016\/j.addr.2026.115885_bb0455","doi-asserted-by":"crossref","first-page":"2229","DOI":"10.1007\/s11095-014-1611-0","article-title":"Measuring tissue Back-pressure - in vivo injection forces during subcutaneous injection","volume":"32","author":"Allmendinger","year":"2015","journal-title":"Pharm. Res."},{"key":"10.1016\/j.addr.2026.115885_bb0460","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1007\/s11095-020-02906-9","article-title":"Tissue resistance during large-volume injections in subcutaneous tissue of Minipigs","volume":"37","author":"Allmendinger","year":"2020","journal-title":"Pharm. Res."},{"key":"10.1016\/j.addr.2026.115885_bb0465","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1111\/cts.13109","article-title":"Clinical evaluation of large volume subcutaneous injection tissue effects, pain, and acceptability in healthy adults","volume":"15","author":"Woodley","year":"2022","journal-title":"Clin. Transl. Sci."},{"key":"10.1016\/j.addr.2026.115885_bb0470","doi-asserted-by":"crossref","first-page":"2195","DOI":"10.1007\/s11095-023-03567-0","article-title":"SubQ-Sim: a subcutaneous physiologically based biopharmaceutics model. Part 1: the injection and system parameters","volume":"40","author":"Pepin","year":"2023","journal-title":"Pharm. Res."},{"key":"10.1016\/j.addr.2026.115885_bb0475","doi-asserted-by":"crossref","DOI":"10.1080\/19420862.2023.2285277","article-title":"Monoclonal antibody and protein therapeutic formulations for subcutaneous delivery: High-concentration, low-volume vs. low-concentration, high-volume","volume":"15","author":"Desai","year":"2023","journal-title":"mAbs"},{"key":"10.1016\/j.addr.2026.115885_bb0480","doi-asserted-by":"crossref","DOI":"10.1016\/j.xphs.2025.103877","article-title":"Current and emerging strategies for subcutaneous delivery of high-concentration and high-dose antibody therapeutics","volume":"114","author":"Ren","year":"2025","journal-title":"J. Pharm. Sci."},{"key":"10.1016\/j.addr.2026.115885_bb0485","doi-asserted-by":"crossref","first-page":"1337","DOI":"10.1002\/cpt.2385","article-title":"Safety, tolerability, and pharmacokinetics of high-volume subcutaneous Crenezumab, with and without recombinant human hyaluronidase in healthy volunteers","volume":"110","author":"Dolton","year":"2021","journal-title":"Clin. Pharmacol. Ther."},{"key":"10.1016\/j.addr.2026.115885_bb0540","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1208\/s12249-025-03116-5","article-title":"Development and preclinical testing of a rapid, high-volume, auto-injector for subcutaneous administration with recombinant human hyaluronidase","volume":"26","author":"Connor","year":"2025","journal-title":"AAPS PharmSciTech"},{"key":"10.1016\/j.addr.2026.115885_bb0545","doi-asserted-by":"crossref","first-page":"1194","DOI":"10.1001\/jamadermatol.2015.2232","article-title":"Effect of needle size on pain perception in patients treated with botulinum toxin type a injections: a randomized clinical trial","volume":"151","author":"Alam","year":"2015","journal-title":"JAMA Dermatol."},{"key":"10.1016\/j.addr.2026.115885_bb0550","doi-asserted-by":"crossref","DOI":"10.1016\/j.parkreldis.2023.105950","article-title":"Does needle size matter? Effects of micro-hypodermic needle injections of botulinum toxin type a in patients with hemifacial spasm","volume":"118","author":"Maytharakcheep","year":"2024","journal-title":"Parkinsonism Relat. Disord."},{"key":"10.1016\/j.addr.2026.115885_bb0555","doi-asserted-by":"crossref","first-page":"115","DOI":"10.3109\/2000656X.2015.1111223","article-title":"The importance of needle gauge for pain during injection of lidocaine","volume":"50","author":"W\u00e5g\u00f8","year":"2016","journal-title":"J. Plast. Surg. Hand Surg."},{"key":"10.1016\/j.addr.2026.115885_bb0560","first-page":"1","article-title":"A phase I clinical study to evaluate rapid, high-volume, subcutaneous auto-injector tolerability with recombinant human hyaluronidase","author":"Kang","year":"2025","journal-title":"Drug Deliv. Transl. Res."},{"key":"10.1016\/j.addr.2026.115885_bb0565","doi-asserted-by":"crossref","first-page":"474","DOI":"10.5731\/pdajpst.2021.012670","article-title":"Advances in large volume subcutaneous injections: a pilot tolerability study of an innovative needle-free injection platform","volume":"76","author":"Kelley","year":"2022","journal-title":"PDA J. Pharm. Sci. Technol."},{"key":"10.1016\/j.addr.2026.115885_bb0570","first-page":"473","article-title":"Evaluation of the impact of viscosity, injection volume, and injection flow rate on subcutaneous injection tolerance","volume":"8","author":"Berteau","year":"2015","journal-title":"M\u00e9d. Devices: \u00c9vid. Res."},{"key":"10.1016\/j.addr.2026.115885_bb0575","doi-asserted-by":"crossref","first-page":"7","DOI":"10.3109\/2000656X.2015.1058269","article-title":"The influence of injection speed on pain during injection of local anaesthetic","volume":"50","author":"Tangen","year":"2016","journal-title":"J. Plast. Surg. Hand Surg."},{"key":"10.1016\/j.addr.2026.115885_bb0585","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1080\/17425247.2020.1704730","article-title":"Hold the device against the skin: the impact of injection duration on user's force for handheld autoinjectors","volume":"17","author":"Schneider","year":"2020","journal-title":"Expert Opin. Drug Deliv."},{"key":"10.1016\/j.addr.2026.115885_bb0590","doi-asserted-by":"crossref","first-page":"981","DOI":"10.3389\/fimmu.2020.00981","article-title":"Facilitated subcutaneous immunoglobulin replacement therapy in clinical practice: a two center, long-term retrospective observation in adults with primary Immunodeficiencies","volume":"11","author":"Wiesik-Szewczyk","year":"2020","journal-title":"Front. Immunol."},{"key":"10.1016\/j.addr.2026.115885_bb0600","doi-asserted-by":"crossref","first-page":"159","DOI":"10.2147\/DDDT.S287323","article-title":"Subcutaneous delivery of high-dose\/volume biologics: current status and prospect for future advancements","volume":"15","author":"Badkar","year":"2021","journal-title":"Drug Des. Dev. Ther."},{"key":"10.1016\/j.addr.2026.115885_bb0605","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1002\/cpt.3150","article-title":"Subcutaneous Administration of Monoclonal Antibodies: pharmacology, delivery, immunogenicity, and learnings from applications to clinical development","volume":"115","author":"Davis","year":"2024","journal-title":"Clin. Pharmacol. Ther."},{"key":"10.1016\/j.addr.2026.115885_bb0610","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1016\/j.jconrel.2025.02.022","article-title":"Predicting human subcutaneous bioavailability of monoclonal antibodies using an integrated in-vitro\/in-silico approach","volume":"380","author":"Hanafy","year":"2025","journal-title":"J. Control. Release"},{"key":"10.1016\/j.addr.2026.115885_bb0615","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1007\/s40259-025-00755-9","article-title":"Clinical qualification of subcutaneous injection devices for monoclonal antibodies","volume":"40","author":"Bittner","year":"2026","journal-title":"BioDrugs"},{"key":"10.1016\/j.addr.2026.115885_bib616","unstructured":"C. for M.P. for H.U. (CHMP), Qualification opinion for Molecule-independent device bridging approach (MIDBA). 2026 https:\/\/www.ema.europa.eu\/en\/documents\/other\/qualification-opinion-molecule-independent-device-bridging-approach-midba_en.pdf accessed March 20, 2026."}],"container-title":["Advanced Drug Delivery Reviews"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0169409X26001195?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0169409X26001195?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,6,7]],"date-time":"2026-06-07T08:53:58Z","timestamp":1780822438000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0169409X26001195"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8]]},"references-count":111,"alternative-id":["S0169409X26001195"],"URL":"https:\/\/doi.org\/10.1016\/j.addr.2026.115885","relation":{},"ISSN":["0169-409X"],"issn-type":[{"value":"0169-409X","type":"print"}],"subject":[],"published":{"date-parts":[[2026,8]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"High-Dose Subcutaneous Administration of Biologics: Overcoming Barriers Through Formulation and Device Innovation","name":"articletitle","label":"Article Title"},{"value":"Advanced Drug Delivery Reviews","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.addr.2026.115885","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2026 The Authors. Published by Elsevier B.V.","name":"copyright","label":"Copyright"}],"article-number":"115885"}}