{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T04:21:58Z","timestamp":1777868518009,"version":"3.51.4"},"reference-count":47,"publisher":"Springer Science and Business Media LLC","license":[{"start":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T00:00:00Z","timestamp":1777507200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T00:00:00Z","timestamp":1777507200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Halozyme Therapeutics, Inc."}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Drug Deliv. and Transl. Res."],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Miniature pigs are an established preclinical model for subcutaneous (SC) drug administration; however, research on the direct translatability of this model is limited. This post hoc analysis of preclinical and clinical data assessed the translatability of performance characteristics of a high-volume auto-injector (HVAI) and SC injection site outcomes from the miniature pig model to humans. An HVAI was developed to subcutaneously administer 10\u00a0mL of an antibody solution at a targeted delivery time of\u2009~\u200930\u00a0s. These rapid, high-volume injections were facilitated by co-administration with recombinant human hyaluronidase PH20. The HVAI was assessed in previous preclinical studies in miniature pigs and in a Phase I clinical trial using the same devices (syringe pump and HVAI), test solution, and injection hardware, facilitating direct comparison between injection outcomes. Injection duration and injection site outcomes (swelling, induration, erythema, back-leakage) were measured in all studies. Injection force measurements with the syringe pump in pigs versus humans allowed for the calculation of a scaling factor to model injection duration in humans (90.8%) which was used to estimate an injection time of 27.5\u00a0s with this specific HVAI configuration. Observed injection duration between the two species were similar and not statistically different (30.0\u00a0s vs 27.9\u00a0s;\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.17). Swelling and induration were more significant in pigs than in humans (p\u2009&lt;\u20090.01), while erythema scores tended to be higher in humans than in pigs (p\u2009&lt;\u20090.05). Collectively, the miniature pig is a translatable model for subcutaneous injection that can generate useful predictions of injection times in human studies and de-risk clinical trials.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Graphical abstract<\/jats:bold>\n                  <\/jats:p>","DOI":"10.1007\/s13346-026-02126-5","type":"journal-article","created":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T12:03:16Z","timestamp":1777550596000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Translatability of a miniature pig model to predict subcutaneous clinical injection times with a high-volume auto-injector and recombinant human hyaluronidase"],"prefix":"10.1007","author":[{"given":"Robert J.","family":"Connor","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tara","family":"Nekoroski","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David W.","family":"Kang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2026,4,30]]},"reference":[{"issue":"1","key":"2126_CR1","doi-asserted-by":"publisher","DOI":"10.1038\/s41408-023-00801-1","volume":"13","author":"KT Maples","year":"2023","unstructured":"Maples KT, Hall KH, Joseph NS, Hofmeister CC, Gupta V, Dhodapkar MV, et al. Eliminating the monitoring period with subcutaneous daratumumab: a single-center experience. Blood Cancer J. 2023;13(1):29. https:\/\/doi.org\/10.1038\/s41408-023-00801-1.","journal-title":"Blood Cancer J"},{"issue":"5","key":"2126_CR2","doi-asserted-by":"publisher","first-page":"1172","DOI":"10.1177\/10781552221103551","volume":"29","author":"MV Mateos","year":"2023","unstructured":"Mateos MV, Rigaudeau S, Basu S, Spicka I, Schots R, Wrobel T, et al. Switching to daratumumab SC from IV is safe and preferred by patients with multiple myeloma. J Oncol Pharm Pract. 2023;29(5):1172\u20137. https:\/\/doi.org\/10.1177\/10781552221103551.","journal-title":"J Oncol Pharm Pract"},{"issue":"10","key":"2126_CR3","doi-asserted-by":"publisher","first-page":"1979","DOI":"10.1093\/annonc\/mdu364","volume":"25","author":"X Pivot","year":"2014","unstructured":"Pivot X, Gligorov J, Muller V, Curigliano G, Knoop A, Verma S, et al. Patients\u2019 preferences for subcutaneous trastuzumab versus conventional intravenous infusion for the adjuvant treatment of HER2-positive early breast cancer: final analysis of 488 patients in the international, randomized, two-cohort PrefHer study. Ann Oncol. 2014;25(10):1979\u201387. https:\/\/doi.org\/10.1093\/annonc\/mdu364.","journal-title":"Ann Oncol"},{"issue":"4","key":"2126_CR4","doi-asserted-by":"publisher","first-page":"836","DOI":"10.1093\/annonc\/mdw685","volume":"28","author":"M Rummel","year":"2017","unstructured":"Rummel M, Kim TM, Aversa F, Brugger W, Capochiani E, Plenteda C, et al. Preference for subcutaneous or intravenous administration of rituximab among patients with untreated CD20+ diffuse large B-cell lymphoma or follicular lymphoma: results from a prospective, randomized, open-label, crossover study (PrefMab). Ann Oncol. 2017;28(4):836\u201342. https:\/\/doi.org\/10.1093\/annonc\/mdw685.","journal-title":"Ann Oncol"},{"key":"2126_CR5","doi-asserted-by":"publisher","first-page":"223","DOI":"10.1016\/j.ejca.2021.03.047","volume":"152","author":"J O'Shaughnessy","year":"2021","unstructured":"O\u2019Shaughnessy J, Sousa S, Cruz J, Fallowfield L, Auvinen P, Pulido C, et al. Preference for the fixed-dose combination of pertuzumab and trastuzumab for subcutaneous injection in patients with HER2-positive early breast cancer (PHranceSCa): a randomised, open-label phase II study. Eur J Cancer. 2021;152:223\u201332. https:\/\/doi.org\/10.1016\/j.ejca.2021.03.047.","journal-title":"Eur J Cancer"},{"issue":"5","key":"2126_CR6","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. https:\/\/doi.org\/10.1007\/s40259-018-0295-0.","journal-title":"BioDrugs"},{"issue":"3","key":"2126_CR7","doi-asserted-by":"publisher","first-page":"154","DOI":"10.1097\/NAN.0b013e31824d2271","volume":"35","author":"SS Dychter","year":"2012","unstructured":"Dychter SS, Gold DA, Haller MF. Subcutaneous drug delivery: a route to increased safety, patient satisfaction, and reduced costs. J Infus Nurs. 2012;35(3):154\u201360. https:\/\/doi.org\/10.1097\/NAN.0b013e31824d2271.","journal-title":"J Infus Nurs"},{"issue":"4","key":"2126_CR8","doi-asserted-by":"publisher","first-page":"936","DOI":"10.1016\/j.jaci.2004.06.053","volume":"114","author":"A Gardulf","year":"2004","unstructured":"Gardulf A, Nicolay U, Math D, Asensio O, Bernatowska E, Bock A, et al. Children and adults with primary antibody deficiencies gain quality of life by subcutaneous IgG self-infusions at home. J Allergy Clin Immunol. 2004;114(4):936\u201342. https:\/\/doi.org\/10.1016\/j.jaci.2004.06.053.","journal-title":"J Allergy Clin Immunol"},{"issue":"1","key":"2126_CR9","doi-asserted-by":"publisher","first-page":"384","DOI":"10.1080\/10717544.2019.1587043","volume":"26","author":"BJF van den Bemt","year":"2019","unstructured":"van den Bemt BJF, Gettings L, Domanska B, Bruggraber R, Mountian I, Kristensen LE. A portfolio of biologic self-injection devices in rheumatology: how patient involvement in device design can improve treatment experience. Drug Deliv. 2019;26(1):384\u201392. https:\/\/doi.org\/10.1080\/10717544.2019.1587043.","journal-title":"Drug Deliv"},{"issue":"4","key":"2126_CR10","doi-asserted-by":"publisher","first-page":"427","DOI":"10.1517\/17425247.4.4.427","volume":"4","author":"GI Frost","year":"2007","unstructured":"Frost GI. Recombinant human hyaluronidase (rHuPH20): an enabling platform for subcutaneous drug and fluid administration. Expert Opin Drug Deliv. 2007;4(4):427\u201340. https:\/\/doi.org\/10.1517\/17425247.4.4.427.","journal-title":"Expert Opin Drug Deliv"},{"issue":"6","key":"2126_CR11","doi-asserted-by":"publisher","first-page":"815","DOI":"10.1080\/17425247.2023.2219891","volume":"20","author":"A Schneider","year":"2023","unstructured":"Schneider A, Jost R, Jordi C, Lange J. Autoinjectors for large-volume subcutaneous drug delivery: a review of current research and future directions. Expert Opin Drug Deliv. 2023;20(6):815\u201330. https:\/\/doi.org\/10.1080\/17425247.2023.2219891.","journal-title":"Expert Opin Drug Deliv"},{"issue":"1","key":"2126_CR12","doi-asserted-by":"publisher","first-page":"98","DOI":"10.1080\/10717544.2018.1551442","volume":"26","author":"KW Locke","year":"2019","unstructured":"Locke KW, Maneval DC, LaBarre MJ. ENHANZE\u00ae drug delivery technology: a novel approach to subcutaneous administration using recombinant human hyaluronidase PH20. Drug Deliv. 2019;26(1):98\u2013106. https:\/\/doi.org\/10.1080\/10717544.2018.1551442.","journal-title":"Drug Deliv"},{"issue":"9","key":"2126_CR13","doi-asserted-by":"publisher","first-page":"2106","DOI":"10.1016\/j.bpj.2016.03.040","volume":"110","author":"CC DuFort","year":"2016","unstructured":"DuFort CC, DelGiorno KE, Carlson MA, Osgood RJ, Zhao C, Huang Z, et al. Interstitial pressure in pancreatic ductal adenocarcinoma is dominated by a gel-fluid phase. Biophys J. 2016;110(9):2106\u201319. https:\/\/doi.org\/10.1016\/j.bpj.2016.03.040.","journal-title":"Biophys J"},{"key":"2126_CR14","doi-asserted-by":"publisher","unstructured":"Laurent TC. The ultrastructure and physical-chemical properties of interstitial connective tissue. Pfl\u00fcgers Arch. 1972:S21-S42. https:\/\/doi.org\/10.1007\/bf00586226.","DOI":"10.1007\/bf00586226"},{"issue":"4","key":"2126_CR15","doi-asserted-by":"publisher","first-page":"461","DOI":"10.1007\/s40259-018-0295-0","volume":"12","author":"TA McDonald","year":"2010","unstructured":"McDonald TA, Zepeda ML, Tomlinson MJ, Bee WH, Ivens IA. Subcutaneous administration of biotherapeutics: current experience in animal models. Curr Opin Mol Ther. 2010;12(4):461\u201370. https:\/\/doi.org\/10.1007\/s40259-018-0295-0.","journal-title":"Curr Opin Mol Ther"},{"issue":"21","key":"2126_CR16","doi-asserted-by":"publisher","first-page":"41","DOI":"10.7748\/ns2008.01.22.21.41.c6418","volume":"22","author":"J Hunter","year":"2008","unstructured":"Hunter J. Subcutaneous injection technique. Nurs Stand. 2008;22(21):41\u20134. https:\/\/doi.org\/10.7748\/ns2008.01.22.21.41.c6418.","journal-title":"Nurs Stand"},{"key":"2126_CR17","unstructured":"US Food and Drug Administration: REPATHA prescribing information. 2021. https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2021\/125522orig2s000lbl.pdf. Accessed September 18, 2024."},{"issue":"2","key":"2126_CR18","doi-asserted-by":"publisher","first-page":"230","DOI":"10.1016\/j.jconrel.2006.05.027","volume":"114","author":"LH Bookbinder","year":"2006","unstructured":"Bookbinder LH, Hofer A, Haller MF, Zepeda ML, Keller GA, Lim JE, et al. A recombinant human enzyme for enhanced interstitial transport of therapeutics. J Control Release. 2006;114(2):230\u201341. https:\/\/doi.org\/10.1016\/j.jconrel.2006.05.027.","journal-title":"J Control Release"},{"issue":"4","key":"2126_CR19","doi-asserted-by":"publisher","first-page":"254","DOI":"10.1007\/s13346-012-0065-3","volume":"2","author":"DW Kang","year":"2012","unstructured":"Kang DW, Jadin L, Nekoroski T, Drake FH, Zepeda ML. Recombinant human hyaluronidase PH20 (rHuPH20) facilitates subcutaneous infusions of large volumes of immunoglobulin in a swine model. Drug Deliv Transl Res. 2012;2(4):254\u201364. https:\/\/doi.org\/10.1007\/s13346-012-0065-3.","journal-title":"Drug Deliv Transl Res"},{"key":"2126_CR20","unstructured":"US Food and Drug Administration. Prescribing information. HERCEPTIN HYLECTA\u2122 [trastuzumab and hyaluronidase-oysk] injection, for subcutaneous use. 2019. https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2019\/761106s000lbl.pdf. Accessed 24\u00a0Oct 2024."},{"key":"2126_CR21","unstructured":"US Food and Drug Administration. DARZALEX FASPRO\u2122 (daratumumab and hyaluronidase-fihj) injection, for subcutaneous use. 2020. https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2020\/761145s000lbl.pdf. Accessed 24\u00a0Oct 2024."},{"key":"2126_CR22","unstructured":"US Food and Drug Administration. PHESGO [pertuzumab, trastuzumab, and hyaluronidase-zzxf] injection, for subcutaneous use. 2020. https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2020\/761170s000lbl.pdf. Accessed 24\u00a0Oct 2024."},{"key":"2126_CR23","unstructured":"US Food and Drug Administration. VYVGART\u00ae HYTRULO (efgartigimod alfa and hyaluronidase-qvfc) injection, for subcutaneous use. 2023. https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2023\/761304s000lbl.pdf. Accessed 24\u00a0Oct 2024."},{"key":"2126_CR24","unstructured":"US Food and Drug Administration. TECENTRIQ HYBREZA\u2122 (atezolizumab and hyaluronidase-tqjs) injection, for subcutaneous use. 2024. https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2024\/761347s000lbl.pdf. Accessed 24\u00a0Oct 2024."},{"key":"2126_CR25","unstructured":"US Food and Drug Administration. Prescribing information RITUXAN HYCELA\u2122 (rituximab and hyaluronidase human) injection, for subcutaneous use. 2018. https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2017\/761064s000lbl.pdf. Accessed 24\u00a0Oct 2024."},{"key":"2126_CR26","unstructured":"US Food and Drug Administration. OCREVUS ZUNOVO\u2122 (ocrelizumab and hyaluronidase-ocsq) injection, for subcutaneous use. 2024. https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2024\/761371s000lbl.pdf. Accessed 24\u00a0Oct 2024."},{"key":"2126_CR27","unstructured":"US Food and Drug Administration. Prescribing information. OPDIVO QVANTIG\u2122 [nivolumab and hyaluronidase-nvhy] injection, for subcutaneous use. 2024. https:\/\/packageinserts.bms.com\/pi\/pi_opdivo-qvantig.pdf. Accessed 13\u00a0Jan 2025."},{"key":"2126_CR28","unstructured":"Johnson & Johnson. European commission approves subcutaneous RYBREVANT\u00ae\u25bc (amivantamab) for the treatment of patients with advanced EGFR-mutated non-small cell lung cancer. 2025. https:\/\/www.jnj.com\/media-center\/press-releases\/european-commission-approves-subcutaneous-rybrevant-amivantamab-for-the-treatment-of-patients-with-advanced-egfr-mutated-non-small-cell-lung-cancer. Accessed 24\u00a0Jul 2025."},{"key":"2126_CR29","unstructured":"US Food and Drug Administration. HYQVIA [Immune Globulin Infusion 10% (Human) with Recombinant Human Hyaluronidase] Solution, for subcutaneous administration. 2014. https:\/\/www.fda.gov\/media\/89844\/download?attachment. Accessed 24\u00a0Oct 2024."},{"issue":"10","key":"2126_CR30","doi-asserted-by":"publisher","first-page":"1205","DOI":"10.1016\/j.jsps.2021.09.004","volume":"29","author":"A Roy","year":"2021","unstructured":"Roy A, Geetha RV, Magesh A, Vijayaraghavan R, Ravichandran V. Autoinjector \u2013 a smart device for emergency cum personal therapy. Saudi Pharm J. 2021;29(10):1205\u201315. https:\/\/doi.org\/10.1016\/j.jsps.2021.09.004.","journal-title":"Saudi Pharm J"},{"issue":"1","key":"2126_CR31","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1007\/s13346-025-01883-z","volume":"16","author":"DW Kang","year":"2026","unstructured":"Kang DW, Connor RJ, Nekoroski T, Bitsura JAM, Kindig SK, Knowles SP, et al. A phase I clinical study to evaluate rapid, high-volume, subcutaneous auto-injector tolerability with recombinant human hyaluronidase. Drug Deliv Transl Res. 2026;16(1):95\u2013107. https:\/\/doi.org\/10.1007\/s13346-025-01883-z.","journal-title":"Drug Deliv Transl Res"},{"issue":"5","key":"2126_CR32","doi-asserted-by":"publisher","DOI":"10.1208\/s12249-025-03116-5","volume":"26","author":"RJ Connor","year":"2025","unstructured":"Connor RJ, Nekoroski T, Kang DW. Development and preclinical testing of a rapid, high-volume, auto-injector for subcutaneous administration with recombinant human hyaluronidase. AAPS PharmSciTech. 2025;26(5):141. https:\/\/doi.org\/10.1208\/s12249-025-03116-5.","journal-title":"AAPS PharmSciTech"},{"key":"2126_CR33","doi-asserted-by":"publisher","first-page":"341","DOI":"10.1016\/j.etp.2006.03.004","volume":"57","author":"JA Mahl","year":"2006","unstructured":"Mahl JA, Vogel BE, Court M, Kolopp M, Roman D, Nogues V. The minipig in dermatotoxicology: methods and challenges. Exp Toxicol Pathol. 2006;57:341\u20135. https:\/\/doi.org\/10.1016\/j.etp.2006.03.004.","journal-title":"Exp Toxicol Pathol"},{"issue":"3","key":"2126_CR34","doi-asserted-by":"publisher","first-page":"140","DOI":"10.1016\/j.vascn.2013.01.011","volume":"67","author":"DW Kang","year":"2013","unstructured":"Kang DW, Oh DA, Fu GY, Anderson JM, Zepeda ML. Porcine model to evaluate local tissue tolerability associated with subcutaneous delivery of protein. J Pharmacol Toxicol Methods. 2013;67(3):140\u20137. https:\/\/doi.org\/10.1016\/j.vascn.2013.01.011.","journal-title":"J Pharmacol Toxicol Methods"},{"issue":"1","key":"2126_CR35","doi-asserted-by":"publisher","DOI":"10.1080\/10717544.2023.2252999","volume":"30","author":"RJ Connor","year":"2023","unstructured":"Connor RJ, Clift R, Kang DW. Identifying a predictive relationship between maximal flow rate and viscosity for subcutaneous administration of macromolecules with recombinant human hyaluronidase PH20 in a miniature pig model. Drug Deliv. 2023;30(1):2252999. https:\/\/doi.org\/10.1080\/10717544.2023.2252999.","journal-title":"Drug Deliv"},{"issue":"1","key":"2126_CR36","doi-asserted-by":"publisher","DOI":"10.1208\/s12249-020-01880-0","volume":"22","author":"GH Shi","year":"2021","unstructured":"Shi GH, Connor RJ, Collins DS, Kang DW. Subcutaneous injection performance in yucatan miniature pigs with and without human hyaluronidase and auto-injector tolerability in humans. AAPS PharmSciTech. 2021;22(1):39. https:\/\/doi.org\/10.1208\/s12249-020-01880-0.","journal-title":"AAPS PharmSciTech"},{"key":"2126_CR37","doi-asserted-by":"publisher","DOI":"10.1016\/j.curtheres.2020.100604","volume":"93","author":"MA Printz","year":"2020","unstructured":"Printz MA, Dychter SS, DeNoia EP, Harrigan R, Sugarman BJ, Zepeda M, et al. A phase I study to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of recombinant human hyaluronidase PH20 administered intravenously in healthy volunteers. Curr Ther Res Clin Exp. 2020;93:100604. https:\/\/doi.org\/10.1016\/j.curtheres.2020.100604.","journal-title":"Curr Ther Res Clin Exp"},{"issue":"6","key":"2126_CR38","doi-asserted-by":"publisher","DOI":"10.1208\/s12248-022-00757-3","volume":"24","author":"MA Printz","year":"2022","unstructured":"Printz MA, Sugarman BJ, Paladini RD, Jorge MC, Wang Y, Kang DW, et al. Risk factors, hyaluronidase expression, and clinical immunogenicity of recombinant human hyaluronidase PH20, an enzyme enabling subcutaneous drug administration. AAPS J. 2022;24(6):110. https:\/\/doi.org\/10.1208\/s12248-022-00757-3.","journal-title":"AAPS J"},{"key":"2126_CR39","doi-asserted-by":"publisher","first-page":"369","DOI":"10.1016\/j.jconrel.2024.07.062","volume":"374","author":"RP Nolan","year":"2024","unstructured":"Nolan RP, Kang DW, Maneval DC, Knowles SP, LaBarre MJ, Printz MA. The safety of recombinant human hyaluronidase PH20 in nonclinical models: an overview of toxicology, pharmacology, and impact of anti-PH20 antibodies. J Control Release. 2024;374:369\u201383. https:\/\/doi.org\/10.1016\/j.jconrel.2024.07.062.","journal-title":"J Control Release"},{"key":"2126_CR40","volume-title":"ENHANZE\u00ae Drug Delivery Technology","author":"B Bittner","year":"2022","unstructured":"Bittner B, Locke KW, Maneval DC, Flamion B, Connor RJ, LaBarre MJ. ENHANZE\u00ae\u00a0drug delivery technology. Oxford, UK: S. Karger Publishers Ltd; 2022."},{"issue":"7_Suppl_1","key":"2126_CR41","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000210572","volume":"104","author":"T Hargraves","year":"2025","unstructured":"Hargraves T, Allosery K, Borgions F, De Muynck C, Noukens J. Investigating the pharmacodynamics, injection speed, and usability of subcutaneous efgartigimod PH20 administration using a prefilled syringe (P9-11.026). Neurology. 2025;104(7_Suppl_1):2768. https:\/\/doi.org\/10.1212\/WNL.0000000000210572.","journal-title":"Neurology"},{"issue":"6","key":"2126_CR42","doi-asserted-by":"publisher","DOI":"10.1007\/s00432-025-06228-4","volume":"151","author":"C Wynne","year":"2025","unstructured":"Wynne C, Wang B, Deng R, Li J, Eiger D, Bene Tchaleu F, et al. Pharmacokinetic bioequivalence of the fixed-dose combination of pertuzumab and trastuzumab administered subcutaneously using a handheld syringe or an on-body delivery system. J Cancer Res Clin Oncol. 2025;151(6):188. https:\/\/doi.org\/10.1007\/s00432-025-06228-4.","journal-title":"J Cancer Res Clin Oncol"},{"issue":"10","key":"2126_CR43","doi-asserted-by":"publisher","first-page":"754","DOI":"10.3390\/ani9100754","volume":"9","author":"RC Hubrecht","year":"2019","unstructured":"Hubrecht RC, Carter E. The 3Rs and humane experimental technique: implementing change. Animals (Basel). 2019;9(10):754. https:\/\/doi.org\/10.3390\/ani9100754.","journal-title":"Animals"},{"issue":"15","key":"2126_CR44","doi-asserted-by":"publisher","first-page":"1236","DOI":"10.1093\/ajhp\/zxac058","volume":"79","author":"BL Erstad","year":"2022","unstructured":"Erstad BL, Barletta JF. Implications of obesity for drug administration and absorption from subcutaneous and intramuscular injections: a primer. Am J Health-Syst Pharm. 2022;79(15):1236\u201344. https:\/\/doi.org\/10.1093\/ajhp\/zxac058.","journal-title":"Am J Health-Syst Pharm"},{"key":"2126_CR45","doi-asserted-by":"publisher","first-page":"475","DOI":"10.1016\/j.jconrel.2020.02.036","volume":"321","author":"DS Collins","year":"2020","unstructured":"Collins DS, S\u00e1nchez-F\u00e9lix M, Badkar AV, Mrsny R. Accelerating the development of novel technologies and tools for the subcutaneous delivery of biotherapeutics. J Control Release. 2020;321:475\u201382. https:\/\/doi.org\/10.1016\/j.jconrel.2020.02.036.","journal-title":"J Control Release"},{"key":"2126_CR46","doi-asserted-by":"publisher","first-page":"363","DOI":"10.2147\/mder.S337670","volume":"14","author":"J Lange","year":"2021","unstructured":"Lange J, Schneider A, Jordi C, Lau M, Disher T. Formative study on the wearability and usability of a large-volume patch injector. Med Dev (Auckland, NZ). 2021;14:363\u201377. https:\/\/doi.org\/10.2147\/mder.S337670.","journal-title":"Med Dev (Auckland, NZ)"},{"issue":"10, Suppl","key":"2126_CR47","doi-asserted-by":"publisher","DOI":"10.1016\/j.cardfail.2020.09.199","volume":"26","author":"AD Andre","year":"2020","unstructured":"Andre AD, Mohr J, Cornelius B, Goodwin MM, Whitaker C, Patel B, et al. Successful validation of a wearable, on-body infusor for subcutaneous administration of Furoscix\u00ae in heart failure patients, caregivers, and health care practitioners. J Card Fail. 2020;26(10, Suppl):S68. https:\/\/doi.org\/10.1016\/j.cardfail.2020.09.199","journal-title":"J Card Fail"}],"container-title":["Drug Delivery and Translational Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s13346-026-02126-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s13346-026-02126-5","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s13346-026-02126-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T12:03:24Z","timestamp":1777550604000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s13346-026-02126-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,30]]},"references-count":47,"alternative-id":["2126"],"URL":"https:\/\/doi.org\/10.1007\/s13346-026-02126-5","relation":{},"ISSN":["2190-393X","2190-3948"],"issn-type":[{"value":"2190-393X","type":"print"},{"value":"2190-3948","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,30]]},"assertion":[{"value":"27 November 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 April 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 April 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":"All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2000 (5). The protocol approved by the US FDA and an institutional review board (Advarra, Columbia, MD, USA). Informed consent was obtained from all subjects for being included in the study and all subjects were compensated for their participation.All institutional and national guidelines for the care and use of laboratory animals were followed under approved Institutional Animal Care and Use Committee (IACUC) protocols (IACUC protocol: Calmi 076.1) following United States Department of Agriculture guidelines and regulations for research.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval"}},{"value":"RJC, TN, and DWK are employees of Halozyme Therapeutics, Inc., and hold shares in the company.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}