Tolerability of High-Volume Subcutaneous Injections of a Viscous Placebo Buffer: A Randomized, Crossover Study in Healthy Subjects
Open accessAbstract
Monoclonal antibody biotherapeutics are often administered by subcutaneous (SC) injection. Due to dose requirements and formulation limitations, SC injections >1 mL are often required. We used a viscous placebo buffer (5 cP), characteristic of a high-concentration antibody formulation, to investigate the effect of dose volume and injection rate on the tolerability of higher-volume SC injections. In this randomized, crossover, single-center study, 48 healthy adults received one 1.2-mL bolus injection over 5 s and three 3.5-mL injections over 1, 4, and 10 min in different abdominal quadrants, with each injection separated by approximately 2 h. The primary objective was to compare pain scores associated with the injections, immediately after administration and 1 h later, using a 100-mm visual analog scale (VAS). Secondary objectives included assessment of adverse events, including injection site reactions and swelling. Mean age was 38.4 (11.6) years and 20 subjects (42%) were female. Lowest mean VAS score was for the 10-min (6.83 mm) and highest for the 1-min injection (19.13 mm). One hour after administration, mean VAS scores were <3.5 mm for all injections. Swelling was similar among the three 3.5-mL injections. After needle removal, leakage occurred following 14 (29%) 1.2-mL injections, eight (17%) 4-min injections, five (10%) 1-min injections, and four (8%) 10-min injections. Fifteen subjects (31%) experienced an adverse event, none of which was serious, fatal, or led to study discontinuation. All injection durations were well tolerated, suggesting a single large-volume SC injection of a biotherapeutic agent could be used instead of multiple injections.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Significant research is being conducted with a focus on further facilitating subcutaneous injections, such as enhancements in infusion-rate-dependent tolerability, improvements in infusion pump technology, and novel drug-delivery devices.
“Inspired by the benefits of subcutaneous dosing to patients and the overall healthcare system, significant research is being conducted with a focus on further facilitating subcutaneous injections, such as enhancements in infusion-rate-dependent tolerability, improvements in infusion pump technology, and novel drug-delivery devices [67–69].”
From Subcutaneous Administration of Biotherapeutics: An Overview of Current Challenges and Opportunities (2018) · cites this paper as [67]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Osterberg, L., & Blaschke, T. (2005) · New England Journal of Medicine · doi:10.1056/nejmra050100 · Cited by 7,974 · see citing works
Kirk, J. M. W., MacDonald, A., Lavender, P., Dean, J. M., & Rubin, G. (2017) · Biomedicine Hub · doi:10.1159/000480347 · Cited by 3,901 · see citing works
Long-term persistence in use of statin therapy in elderly patients
Benner, J. S. (2002) · JAMA · doi:10.1001/jama.288.4.455 · Cited by 1,232 · see citing works
Keystone, E. C., Kavanaugh, A. F., Sharp, J. T., Tannenbaum, H., Hua, Y., Teoh, L. S., Fischkoff, S. A., & Chartash, E. (2004) · Arthritis & Rheumatism · doi:10.1002/art.20217 · Cited by 1,174 · see citing works
Clinical Significance of Reported Changes in Pain Severity☆☆☆★
Todd, K. H., Funk, K. G., Funk, J. P., & Bonacci, R. P. (1996) · Annals of Emergency Medicine · doi:10.1016/s0196-0644(96)70238-x · Cited by 1,110 · see citing works
Adherence with statin therapy in elderly patients with and without acute coronary syndromes
Jackevicius, C. A. (2002) · JAMA · doi:10.1001/jama.288.4.462 · Cited by 1,077 · see citing works
Gallagher, E. J., Liebman, M., & Bijur, P. E. (2001) · Annals of Emergency Medicine · doi:10.1067/mem.2001.118863 · Cited by 1,021 · see citing works
Monoclonal Antibody Pharmacokinetics and Pharmacodynamics
Wang, W., Wang, E., & Balthasar, J. (2008) · Clinical Pharmacology & Therapeutics · doi:10.1038/clpt.2008.170 · Cited by 978 · see citing works
Pharmaceutical Dosage Forms and Drug Delivery Systems
Ansel, H. C., Allen, L. V., & Popovich, N. G. (1990) · Cited by 694 · see citing works
Reliability and validity of a visual analog scale for acute abdominal pain in the ED
Gallagher, E. J., Bijur, P. E., Latimer, C. T., & Silver, W. G. (2002) · The American Journal of Emergency Medicine · doi:10.1053/ajem.2002.33778 · Cited by 454 · see citing works
Diamant, M., Van Gaal, L., Stranks, S., Northrup, J., Cao, D., Taylor, K., & Trautmann, M. (2010) · The Lancet · doi:10.1016/s0140-6736(10)60406-0 · Cited by 434 · see citing works
Giugliano, R. P., Desai, N. R., Kohli, P., Rogers, W. J., Somaratne, R. M., Huang, F., Liu, T., Mohanavelu, S., Hoffman, E. B., McDonald, S. T., et al. (2012) · The Lancet · doi:10.1016/s0140-6736(12)61770-x · Cited by 425 · see citing works
Blaschke, T. F., Osterberg, L. G., Vrijens, B., & Urquhart, J. (2011) · The Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev-pharmtox-011711-113247 · Cited by 420 · see citing works
Ismael, G., Hegg, R., Muehlbauer, S., Heinzmann, D., Lum, B., Kim, S.-B., Pienkowski, T., Lichinitser, M., Semiglazov, V., Melichar, B., et al. (2012) · The Lancet Oncology · doi:10.1016/s1470-2045(12)70329-7 · Cited by 351 · see citing works
Frost, G. I. (2007) · Expert Opinion on Drug Delivery · doi:10.1517/17425247.4.4.427 · Cited by 323 · see citing works
Pivot, X., Gligorov, J., Müller, V., Barrett-Lee, P., Verma, S., Knoop, A., Curigliano, G., Semiglazov, V., López-Vivanco, G., Jenkins, V., et al. (2013) · The Lancet Oncology · doi:10.1016/s1470-2045(13)70383-8 · Cited by 230 · see citing works
Subcutaneous immunoglobulin replacement in primary immunodeficiencies
Berger, M. (2004) · Clinical Immunology · doi:10.1016/j.clim.2004.02.002 · Cited by 193 · see citing works
Basch, E., Reeve, B. B., Cleeland, C. S., Sloan, J., Schrag, D., Atkinson, T., Mendoza, T. R., Hay, J., Abernethy, A. P., Minasian, L. M., et al. (2010) · Value in Health · doi:10.1016/s1098-3015(11)72017-4 · Cited by 163 · see citing works
Diabetes management in the new millennium using insulin pump therapy
Bode, B. W., Sabbah, H. T., Gross, T. M., Fredrickson, L. P., & Davidson, P. C. (2002) · Diabetes/Metabolism Research and Reviews · doi:10.1002/dmrr.205 · Cited by 155 · see citing works
Deodhar, A. A., Braun, J., Inman, R. D., van der Heijde, D. M. F. M., Zhou, Y., Xu, S., Han, C., & Hsu, B. L. (2014) · Annals of the Rheumatic Diseases · doi:10.1136/annrheumdis-2014-205862 · Cited by 146 · see citing works
Wynne, C., Harvey, V. J., Schwabe, C., Waaka, D., McIntyre, C., & Bittner, B. (2012) · The Journal of Clinical Pharmacology · doi:10.1177/0091270012436560 · Cited by 125 · see citing works
Assessment of Visual Analog versus Categorical Scale for Measurement of Osteoarthritis Pain
Averbuch, M., & Katzper, M. (2004) · The Journal of Clinical Pharmacology · doi:10.1177/0091270004263995 · Cited by 109 · see citing works
Braun, J., Deodhar, A. A., Inman, R. D., van der Heijde, D. M. F. M., Mack, M., Xu, S., & Hsu, B. L. (2011) · Annals of the Rheumatic Diseases · doi:10.1136/ard.2011.154799 · Cited by 105 · see citing works
Once-Weekly Exenatide Versus Once- or Twice-Daily Insulin Detemir
Davies, M., Heller, S., Sreenan, S., Sapin, H., Adetunji, O., Tahbaz, A., & Vora, J. (2013) · Diabetes Care · doi:10.2337/dc12-1333 · Cited by 83 · see citing works
Shapiro, R. (2010) · Journal of Clinical Immunology · doi:10.1007/s10875-009-9352-2 · Cited by 75 · see citing works
Express Subcutaneous IgG Infusions: Decreased Time of Delivery with Maintained Safety
Hansen, S., Gustafson, R., Smith, C. I. E., & Gardulf, A. (2002) · Clinical Immunology · doi:10.1006/clim.2002.5215 · Cited by 54 · see citing works
Oldfield, V., & Plosker, G. L. (2009) · BioDrugs · doi:10.2165/00063030-200923020-00005 · Cited by 40 · see citing works
Dumond, P., Franck, P., Morisset, M., Sainte‐Laudy, J., Kanny, G., & Moneret‐Vautrin, D. A. (2009) · PubMed · Cited by 27 · see citing works
Porcine model to evaluate local tissue tolerability associated with subcutaneous delivery of protein
Kang, D. W., Oh, D. A., Fu, G., Anderson, J. M., & Zepeda, M. L. (2013) · Journal of Pharmacological and Toxicological Methods · doi:10.1016/j.vascn.2013.01.011 · Cited by 26 · see citing works
Anderson, G. H., Meyer, D., Herrman, C., Sheppard, C. R. C., Murray, R., Fox, E., Mathena, J., Conner, J. B., & Buck, P. O. (2010) · Journal of Neurology · doi:10.1007/s00415-010-5779-x · Cited by 26 · see citing works
Allergic contact dermatitis due to sodium carboxymethyl cellulose
Hamada, T., & Horiguchi, S. (1978) · Contact Dermatitis · doi:10.1111/j.1600-0536.1978.tb03809.x · Cited by 19 · see citing works
Black, D. M., Bilezikian, J. P., Greenspan, S. L., Wüster, C., Muñoz‐Torres, M., Bone, H. G., Rosen, C. J., Andersen, H. S., & Hanley, D. A. (2012) · Osteoporosis International · doi:10.1007/s00198-012-2098-3 · Cited by 16 · see citing works
Jones, C. A., Rojavin, M. A., & Baggish, J. S. (2011) · Journal of Pharmaceutical Health Services Research · doi:10.1111/j.1759-8893.2011.00076.x · Cited by 14 · see citing works
Ng, P., Incekol, D., Lee, R., Paisley, E., Dara, C., Brandle, I., Kaufman, M., Chen, C. I., Trudel, S., Tiedemann, R. E., et al. (2014) · Journal of Oncology Pharmacy Practice · doi:10.1177/1078155214533367 · Cited by 11 · see citing works
Flagged first, then by citations
Research works printed but not linked: 1
- Williams EJ. Environmental designs balanced for the estimation of residual effects of treatments. Aust J Sci Res. 1949;2(2):149-68.
Cited by
Sorted by citations
Subcutaneous Administration of Biotherapeutics: An Overview of Current Challenges and Opportunities
Bittner, B., Richter, W., & Schmidt, J. (2018) · BioDrugs · doi:10.1007/s40259-018-0295-0 · Cited by 447 · see citing works
Subcutaneous Injection Volume of Biopharmaceuticals—Pushing the Boundaries
Mathaes, R., Koulov, A. V., Joerg, S., & Mahler, H. (2016) · Journal of Pharmaceutical Sciences · doi:10.1016/j.xphs.2016.05.029 · Cited by 173 · see citing works
Schwarzenbach, F., Berteau, C., Santos, O. F., Wang, T., Rojas, H., & Granger, C. (2015) · Medical Devices Evidence and Research · doi:10.2147/mder.s91019 · Cited by 137 · see citing works
Badkar, A. V., Gandhi, R. B., Davis, S. P., & LaBarre, M. J. (2021) · Drug Design Development and Therapy · doi:10.2147/dddt.s287323 · Cited by 129 · see citing works
Jones, A. S. C., Prignano, F., Gonçalves, J., Paul, M., & Sewerin, P. (2020) · Rheumatology and Therapy · doi:10.1007/s40744-020-00245-0 · Cited by 124 · see citing works
Collins, D. S., Sánchez-Félix, M., Badkar, A. V., & Mrsny, R. J. (2020) · Journal of Controlled Release · doi:10.1016/j.jconrel.2020.02.036 · Cited by 113 · see citing works
Challenges and Opportunities in the Delivery of Cancer Therapeutics: Update on Recent Progress
Lorscheider, M., Gaudin, A., Nakhlé, J., Veiman, K.-L., Richard, J., & Chassaing, C. (2020) · Therapeutic Delivery · doi:10.4155/tde-2020-0079 · Cited by 113 · see citing works
Röthlisberger, D., Mahler, H., Altenburger, U., & Pappenberger, A. (2016) · Journal of Pharmaceutical Sciences · doi:10.1016/j.xphs.2016.09.034 · Cited by 92 · see citing works
Desai, M. G., Kundu, A., Hageman, M., Lou, H., & Boisvert, D. (2023) · mAbs · doi:10.1080/19420862.2023.2285277 · Cited by 92 · see citing works
Pharmacokinetics, Pharmacodynamics, Safety, and Tolerability of Dupilumab in Healthy Adult Subjects
Li, Z., Radin, A. R., Li, M., Hamilton, J. D., Kajiwara, M., Davis, J. D., Takahashi, Y., Hasegawa, S., Ming, J. E., DiCioccio, A. T., et al. (2020) · Clinical Pharmacology in Drug Development · doi:10.1002/cpdd.798 · Cited by 76 · see citing works
Collins, D. S., Kourtis, L. C., Thyagarajapuram, N. R., Sirkar, R., Kapur, S., Harrison, M. W., Bryan, D. J., Jones, G. B., & Wright, J. M. (2017) · Pharmaceutical Research · doi:10.1007/s11095-017-2229-9 · Cited by 74 · see citing works
Woodley, W. D., Morel, D. R., Sutter, D. E., Pettis, R. J., & Bolick, N. G. (2021) · Clinical and Translational Science · doi:10.1111/cts.13109 · Cited by 49 · see citing works
Portron, A., Jordan, P., Draper, K., Muenzer, C., Dickerson, D., van Iersel, T. M., & Hofmann, C. (2019) · Clinical Therapeutics · doi:10.1016/j.clinthera.2019.11.015 · Cited by 43 · see citing works
Mathias, N. R., Huille, S., Picci, M., Mahoney, R. P., Pettis, R. J., Case, B. C., Helk, B., Kang, D. W., Shah, R., Ma, J., et al. (2024) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2024.115301 · Cited by 42 · see citing works
Schneider, A., Mueller, P., Jordi, C., Richard, P., Sneeringer, P., Nayyar, R., Yovanoff, M., & Lange, J. (2019) · Expert Opinion on Drug Delivery · doi:10.1080/17425247.2020.1704730 · Cited by 41 · see citing works
Deb, V. K., & Jain, U. (2024) · Drug Delivery and Translational Research · doi:10.1007/s13346-024-01572-3 · Cited by 37 · see citing works
Schneider, A., Jost, R., Jordi, C., & Lange, J. (2023) · Expert Opinion on Drug Delivery · doi:10.1080/17425247.2023.2219891 · Cited by 34 · see citing works
Bruin, G. J. M., Hockey, H., Stella, P. L., Sigurgeirsson, B., Fu, R., Patekar, M., Charef, P., Woessner, R., & Boutouyrie‐Dumont, B. (2019) · British Journal of Clinical Pharmacology · doi:10.1111/bcp.14155 · Cited by 34 · see citing works
Broadly neutralizing antibodies for HIV prevention: a comprehensive review and future perspectives
Mahomed, S. (2024) · Clinical Microbiology Reviews · doi:10.1128/cmr.00152-22 · Cited by 33 · see citing works
Deokar, V., Sharma, A. K., Mody, R., & Subrahmanyam, V. M. (2020) · Journal of Pharmaceutical Sciences · doi:10.1016/j.xphs.2020.09.014 · Cited by 31 · see citing works
Hou, P., Zheng, F., Corpstein, C. D., Xing, L., & Li, T. (2021) · Pharmaceutical Research · doi:10.1007/s11095-021-03062-4 · Cited by 29 · see citing works
Dolton, M. J., Chesterman, A., Moein, A., Sink, K. M., Waitz, A., Blondeau, K., Kerchner, G. A., Hu, N., Brooks, L., Wetzel-Smith, M. K., et al. (2021) · Clinical Pharmacology & Therapeutics · doi:10.1002/cpt.2385 · Cited by 27 · see citing works
Stevenson, J., Poker, R., Schoss, J., Campbell, M., Everitt, C., Holly, B., Stones, N., Pettis, R. J., & Sánchez-Félix, M. (2024) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2024.115322 · Cited by 25 · see citing works
Dang, X., Shih, H., Sharma, R. K., Angwin-Kaerner, D. T., Lin, K., Kapur, S., Thyagarajapuram, N. R., Shi, G. H., & Collins, D. S. (2024) · Pharmaceutical Research · doi:10.1007/s11095-024-03683-5 · Cited by 20 · see citing works
Poly(trehalose methacrylate) as an Excipient for Insulin Stabilization: Mechanism and Safety
Gelb, M. B., Messina, K. M. M., Vinciguerra, D., Ko, J. H., Collins, J., Tamboline, M., Xu, S., Ibarrondo, F. J., & Maynard, H. D. (2022) · ACS Applied Materials & Interfaces · doi:10.1021/acsami.2c09301 · Cited by 20 · see citing works
Clinical Evaluation of an Investigational 5 mL Wearable Injector in Healthy Human Subjects
Woodley, W. D., Wen, Y., Morel, D. R., Lainesse, A., Pettis, R. J., & Bolick, N. G. (2020) · Clinical and Translational Science · doi:10.1111/cts.12946 · Cited by 20 · see citing works
Sigurgeirsson, B., Schäkel, K., Hong, C.-H., Effendy, I., Placek, W. J., Rich, P. A., Keefe, D. L., Bruin, G. J. M., Charef, P., Fu, R., et al. (2021) · Journal of Dermatological Treatment · doi:10.1080/09546634.2021.1902925 · Cited by 19 · see citing works
Enabling faster subcutaneous delivery of larger volume, high viscosity fluids
Rini, C. J., Roberts, B. C., Vaidyanathan, A., Li, A., Klug, R., Sherman, D. B., & Pettis, R. J. (2022) · Expert Opinion on Drug Delivery · doi:10.1080/17425247.2022.2116425 · Cited by 19 · see citing works
Lyophilization of High-Concentration Protein Formulations
Garidel, P., & Presser, I. (2018) · Methods in pharmacology and toxicology · doi:10.1007/978-1-4939-8928-7_12 · Cited by 19 · see citing works
Jain, M., Doughty, D. V., Clawson, C., Li, X., White, N., Agoram, B. M., & van der Merwe, R. (2017) · International Journal of Clinical Pharmacology and Therapeutics · doi:10.5414/cp203023 · Cited by 18 · see citing works
Formative Study on the Wearability and Usability of a Large-Volume Patch Injector
Lange, J., Schneider, A., Jordi, C., Lau, M., & Disher, T. C. (2021) · Medical Devices Evidence and Research · doi:10.2147/mder.s337670 · Cited by 17 · see citing works
Taghizadeh, B., Jaafari, M. R., & Zarghami, N. (2022) · Frontiers in Endocrinology · doi:10.3389/fendo.2022.963336 · Cited by 17 · see citing works
An Innovative Needle-free Injection System: Comparison to 1 ml Standard Subcutaneous Injection
Kojić, N., Goyal, P., Lou, C. H., & Corwin, M. J. (2017) · AAPS PharmSciTech · doi:10.1208/s12249-017-0779-0 · Cited by 17 · see citing works
Imaging of large volume subcutaneous deposition using MRI: exploratory clinical study results
Pettis, R. J., Woodley, W. D., Ossege, K. C., Blum, A., Bolick, N. G., & Rini, C. J. (2023) · Drug Delivery and Translational Research · doi:10.1007/s13346-023-01318-7 · Cited by 14 · see citing works
Nanolipoprotein Particles as a Delivery Platform for Fab Based Therapeutics
Darwish, M., Shatz-Binder, W., Leonard, B. C., Loyet, K. M., Barrett, K., Wong, J. L., Li, H., Abraham, R., Lin, M. H., Franke, Y., et al. (2020) · Bioconjugate Chemistry · doi:10.1021/acs.bioconjchem.0c00349 · Cited by 13 · see citing works
Practical Considerations for High Concentration Protein Formulations
Piedmonte, D. M., Gu, J. H., Brych, S. R., & Goss, M. (2018) · AAPS advances in the pharmaceutical sciences series · doi:10.1007/978-3-319-90603-4_7 · Cited by 12 · see citing works
Rathore, A. S., Metya, S., Sharma, R., & Nitika, N. (2026) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2026.115812 · Cited by 11 · see citing works
Kang, D. W., Connor, R., Nekoroski, T., Bitsura, J. A. M., Kindig, S. K., Knowles, S. P., & LaBarre, M. J. (2025) · Drug Delivery and Translational Research · doi:10.1007/s13346-025-01883-z · Cited by 9 · see citing works
Dorati, R., Cosco, D., Battaglia, L., Cirri, M., Conti, B., Borghi, T., Gabriele, M., Bruno, G. M., Rocco, P., Selmin, F., et al. (2025) · Drug Discovery Today · doi:10.1016/j.drudis.2025.104441 · Cited by 8 · see citing works
Gelb, M. B., & Maynard, H. D. (2021) · Macromolecular Materials and Engineering · doi:10.1002/mame.202100197 · Cited by 8 · see citing works
Purcell, M. L., Babaee, S., Galluppi, M., Cline, J., Hu, G., Petrescu, I., Hughes, J., Allen, M., Messina, E. J., Persak, S. C., et al. (2023) · Frontiers in Drug Delivery · doi:10.3389/fddev.2023.1223177 · Cited by 8 · see citing works
Connor, R., Nekoroski, T., & Kang, D. W. (2025) · AAPS PharmSciTech · doi:10.1208/s12249-025-03116-5 · Cited by 7 · see citing works
Subcutaneous Administration: Evolution, Challenges, and the Role of Hyaluronidase
Eisenberg, S. (2021) · Clinical journal of oncology nursing · doi:10.1188/21.cjon.663-671 · Cited by 7 · see citing works
Sotatercept for Pulmonary Arterial Hypertension in the Inpatient Setting
Torbic, H., & Tonelli, A. R. (2024) · Journal of Cardiovascular Pharmacology and Therapeutics · doi:10.1177/10742484231225310 · Cited by 7 · see citing works
Hu, Q., Jiang, B., Liu, D., Tang, X. C., Daly, T. J., & Shameem, M. (2020) · AAPS advances in the pharmaceutical sciences series · doi:10.1007/978-3-030-31415-6_14 · Cited by 7 · see citing works
Novel cannula design improves large volume auto-injection rates for high viscosity solutions
Roberts, B. C., Rini, C. J., Klug, R., Sherman, D. B., Morel, D. R., & Pettis, R. J. (2021) · Drug Delivery · doi:10.1080/10717544.2021.2018069 · Cited by 6 · see citing works
Monoclonal Antibodies: From Structure to Therapeutic Application
Deng, R., Li, J., Boswell, C. A., Joshi, A., & Li, C. (2024) · Springer eBooks · doi:10.1007/978-3-031-30023-3_8 · Cited by 5 · see citing works
In-line warming reduces in-line pressure of subcutaneous infusion of concentrated immunoglobulins
Leidenmuehler, P., Höfinghoff, J., Haider, N., Brachtl, G., Weiller, M., Bilić, I., & Gangadharan, B. (2023) · Drug Delivery and Translational Research · doi:10.1007/s13346-023-01321-y · Cited by 5 · see citing works
Akinseye, C., Fiorini, A., Jarvis, E., Fry, M., Raza, A., Soleman, S., Igwe, S., & Palmer, M. (2024) · Medical Devices Evidence and Research · doi:10.2147/mder.s479507 · Cited by 4 · see citing works
High concentration subcutaneous biological drug products: challenges and advancements
Hu, G., Milewski, M., Krishnamachari, Y., Procopio, A. T., Wuelfing, W. P., Zhu, L., Mittal, S., Cheung, J. K., Givand, J. C., Burlage, R., et al. (2026) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2026.115793 · Cited by 4 · see citing works
Matching placebo development for injectable biologics—a practical tutorial
Xin, L., Zhang, Z., Shah, K., Hashemi, V., Li, X. D., Qin, G., Ren, S., Chen, W. Q., & Li, Y. (2025) · Antibody Therapeutics · doi:10.1093/abt/tbaf009 · Cited by 3 · see citing works
Monoclonal Antibodies: From Structure to Therapeutic Application
Deng, R., Boswell, C. A., Putnam, W. S., Tang, M. T., Garg, A., Li, C., Chung, S., & Girish, S. (2019) · Springer eBooks · doi:10.1007/978-3-030-00710-2_8 · Cited by 3 · see citing works
Moschetti, V., Buschke, S., Bertulis, J., Hohl, K., & McCabe, D. (2024) · Expert Opinion on Biological Therapy · doi:10.1080/14712598.2024.2354902 · Cited by 2 · see citing works
Majem, M., Chewaskulyong, B., Zvirbule, Z., Lee, K. H., Korbenfeld, E. P., Kołb-Sielecki, J., Sanchez, A. Y. C., Bustillos, A., Herráez-Baranda, L. A., Liu, X., et al. (2025) · Oncology and Therapy · doi:10.1007/s40487-025-00402-x · Cited by 1 · see citing works
REMOVED: Challenging the myths of subcutaneous delivery: An industry expert perspective
Bittner, B., Buist, N., Bruin, G. J. M., Harris, K., Huille, S., Mittal, S., Printz, M. A., Sánchez-Félix, M., Shih, H., Venczel, M., et al. (2026) · Journal of Controlled Release · doi:10.1016/j.jconrel.2026.114800 · Cited by 1 · see citing works
RetractedDesai, K. G. H. (2025) · Molecular Pharmaceutics · doi:10.1021/acs.molpharmaceut.4c01166 · Cited by 1 · see citing works
Gläser, D., Liniger, J., & Peter, D. E. M. V. (2018) · AAPS advances in the pharmaceutical sciences series · doi:10.1007/978-3-319-90603-4_11 · Cited by 1 · see citing works
TRENDS IN FORMULATION AND DRUG DELIVERY FOR ANTIBODIES
Mahler, H., & Mathäs, R. (2017) · Wiley eBooks · doi:10.1002/9781119126942.ch31
Laurusonis, L., Cleathero, I., & Jensen, H. J. (2020) · AAPS advances in the pharmaceutical sciences series · doi:10.1007/978-3-030-31415-6_33
Challenging the myths of subcutaneous delivery: An industry expert perspective
Bittner, B., Buist, N., Bruin, G. J. M., Harris, K., Huille, S., Mittal, S., Printz, M. A., Sánchez-Félix, M., Shih, H., Venczel, M., et al. (2026) · Journal of Controlled Release · doi:10.1016/j.jconrel.2026.114902
Fluid mechanics signature and jet characteristics in needle-free injection systems
Nikkhoo, A., Mousavi, S. P., Hassanzadeh, H., Larachi, F., Pouliot, R., Berthod, F., Rouabhia, M., Ohl, C., Witzel, B., & Taghavi, S. M. (2026) · International Journal of Heat and Fluid Flow · doi:10.1016/j.ijheatfluidflow.2026.110552
Peet, M. M., Agrahari, V., Singh, P., Nguyen, L. L. H., Ouattara, L. A., Yang, E. S., Herrera, C., Pegu, A., Pierson, T. C., Nguyen, T. D., et al. (2026) · Molecular Pharmaceutics · doi:10.1021/acs.molpharmaceut.5c01650
Pettis, R. J. (2026) · Expert Opinion on Drug Delivery · doi:10.1080/17425247.2026.2725755
- Authors
- Dias, C., Abosaleem, B., Crispino, C., Gao, B., & Shaywitz, A.
- Affiliations
- Amgen (United States) (US)
- Corresponding author
- Dias, Clapton
- Venue
- AAPS PharmSciTech
- Published
- 2015-02-19
- Volume
- 16
- Issue
- 5
- Pages
- 1101-1107
- ISSN
- 1530-9932 (ISSN-L)
- PMC
- PMC4666247
- OpenAlex
- W2032424691
- Cited by
- 63
- References
- 34
- Citations by year
- 2026: 7 · 2025: 6 · 2024: 9 · 2023: 5 · 2022: 3 · 2021: 9 · 2020: 9 · 2019: 4 · 2018: 4 · 2017: 4 · 2016: 2 · 2015: 1
- FWCI
- 3.56
- Type
- journal article
- Language
- en
- Update notices
- correction (2015-04-23)
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- AAPS PharmSciTech (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Amgen
- Topics
- Health Sciences › Medicine › Emergency Medicine › Intramuscular injections and effects
- Life Sciences › Immunology and Microbiology › Immunology › Biosimilars and Bioanalytical Methods
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Monoclonal and Polyclonal Antibodies Research
- Keywords
- subcutaneous injection, injection pain, injection rate, dose volume, injection site reactions, swelling, leakage, tolerability, adverse events
- MeSH terms
- Adult, Antibodies, Monoclonal, Buffers, California, Drug Compounding, Female, Humans, Injections, Subcutaneous, Male, Middle Aged, Pain, Pain Measurement, Time Factors, Pharmaceutical Vehicles, Viscosity, Cross-Over Studies, Infusions, Subcutaneous, Healthy Volunteers
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
