7,944
Views
15
CrossRef citations to date
0
Altmetric
Review

A systematic review of commercial high concentration antibody drug products approved in the US: formulation composition, dosage form design and primary packaging considerations

, , , &
Article: 2205540 | Received 11 Oct 2022, Accepted 18 Apr 2023, Published online: 27 May 2023

References

  • Strickley RG, Lambert WJ. A review of formulations of commercially available antibodies. J Pharm Sci. 2021;110(7):2590–20. doi:10.1016/j.xphs.2021.03.017.
  • Shawn Shouye Wang YY, Yan Y(, Ho K. US FDA-approved therapeutic antibodies with high-concentration formulation: summaries and perspectives. Antib Ther. 2021;4(4):262–73. doi:10.1093/abt/tbab027.
  • The Antibody Society, Inc. Therapeutic monoclonal antibodies approved or in regulatory review. [accessed 4 14 2023]. www.antibodysociety.org/antibody-therapeutics-product-data.
  • R-M L, Hwang Y-C, Liu I-J, Lee C-C, Tsai H-Z, Li H-J, Wu H-C. Development of therapeutic antibodies for the treatment of diseases. J Biomed Sci. 2020;27(1). http://www.ncbi.nlm.nih.gov/pubmed/31894001.
  • Thomas F. Rising to the challenge of biologic drug formulation. Pharm Technol Eur. 2019;31:24–26.
  • Wang W, Singh S, Zeng DL, King K, Nema S. Antibody structure, instability, and formulation. J Pharm Sci. 2006;96(1):1–26. doi:10.1002/jps.20727.
  • Le Basle Y, Chennell P, Tokhadze N, Astier A, Sautou V. Physicochemical stability of monoclonal antibodies: a review. J Pharm Sci. 2020;109(1):169–90. doi:10.1016/j.xphs.2019.08.009.
  • Manning MC, Patel K, Borchardt RT. Stability of protein pharmaceuticals. Pharm Res. 1989;6(11):903–18. doi:10.1023/A:1015929109894.
  • Manning M, Chou D, Murphy B, Payne R, Katayama D. Stability of Protein Pharmaceuticals: an Update. Pharm Res. 2010;27(4):544–75. doi:10.1007/s11095-009-0045-6.
  • Wang O, Ohtake S. Science and art of protein formulation development. Int J Pharm. 2019;568:568. doi:10.1016/j.ijpharm.2019.118505.
  • Wang W. Instability, stabilization, and formulation of liquid protein pharmaceuticals. Int J Pharm. 1999;185(2):129–88. doi:10.1016/S0378-5173(99)00152-0.
  • Wang W. Lyophilization and development of solid protein pharmaceuticals. Int J Pharm. 2000;203(1–2):1–60. doi:10.1016/S0378-5173(00)00423-3.
  • Messick S, Saggu M, Ríos Quiroz A. Chapter 1: monoclonal antibodies: structure, physicochemical stability, and protein engineering. In: Messick S, Saggu M Ríos Quiroz A. editors. Development of biopharmaceutical drug-device products;2020. p. 3. 10.1007/978-3-030-31415-6_1
  • Carpenter JF, Chang BS, Garzon-Rodriguez W, Randolph TW. Rational design of stable lyophilized protein formulations: theory and practice. Pharm Biotechnol. 2002;13:109–33. http://www.ncbi.nlm.nih.gov/pubmed/11987749.
  • Jameel F, Hershenson S. Formulation & process development strategies for manufacturing biopharmaceuticals. 2010. doi:10.1002/9780470595886.
  • Jameel F, Hershenson S, Khan MA, Martin-Moe S, editors. In: Quality by design for biopharmaceutical drug product development. New York: Springer; 2015. p. 1–710.
  • Shire SJ. Formulation and manufacturability of biologics. Curr Opin Biotechnol. 2009;20(6):708–14. doi:10.1016/j.copbio.2009.10.006.
  • Rathore N, Rajan RS. Current perspectives on stability of protein drug products during formulation, fill and finish operations. Biotechnol Prog. 2008;24(3):504–14. doi:10.1021/bp070462h.
  • Wang W, Roberts C. Non-Arrhenius protein aggregation. Aaps J. 2013;15(3):840–51. doi:10.1208/s12248-013-9485-3.
  • Roberts CJ. Non-native protein aggregation kinetics. Biotechnol Bioeng. 2007;98(5):927–38. doi:10.1002/bit.21627.
  • Weiss WF, Young TM, Roberts CJ. Principles, approaches, and challenges for predicting protein aggregation rates and shelf life. J Pharm Sci. 2009;98(4):1246–77. doi:10.1002/jps.21521.
  • Vázquez‐rey M, Lang DA. Aggregates in monoclonal antibody manufacturing processes. Biotechnol Bioeng. 2011;108(7):1494–508. doi:10.1002/bit.23155.
  • Roberts CJ, Wang W. Aggregation of therapeutic proteins. 2010.
  • Wang W. Protein aggregation and its inhibition in biopharmaceutics. Int J Pharm. 2005;289(1–2):1–30. doi:10.1016/j.ijpharm.2004.11.014.
  • Wang R, Roberts CJ. Protein aggregation – Mechanisms, detection, and control. Int J Pharm. 2018;550(1):251–68. doi:10.1016/j.ijpharm.2018.08.043.
  • Kingsbury JS, Saini A, Auclair SM, Fu L, Lantz MM, Halloran KT, Calero-Rubio C, Schwenger W, Airiau CY, Zhang J, et al. A single molecular descriptor to predict solution behavior of therapeutic antibodies. Sci Adv. 2020;6(32):EABB372. http://www.ncbi.nlm.nih.gov/pubmed/32923611.
  • Raut AS, Kalonia DS. Opalescence in monoclonal antibody solutions and its correlation with intermolecular interactions in dilute and concentrated solutions. J Pharm Sci. 2015;104(4):1263–74. doi:10.1002/jps.24326.
  • Raut AS, Kalonia DS. Pharmaceutical perspective on opalescence and liquid–liquid phase separation in protein solutions. Mol Pharm. 2016;13(5):1431–44. doi:10.1021/acs.molpharmaceut.5b00937.
  • Connolly BD, Petry C, Yadav S, et al. Weak interactions govern the viscosity of concentrated antibody solutions: high-throughput analysis using the diffusion interaction parameter. Biophys J. 2012;103(1):69–78. doi:10.1016/j.bpj.2012.04.047.
  • Salinas BA, Sathish HA, Bishop SM, Harn N, Carpenter JF, Randolph TW. Understanding and modulating opalescence and viscosity in a monoclonal antibody formulation. 2010;99:82–93. doi:10.1002/jps.21797.
  • Tomar D, Singh S, Li L, Broulidakis M, Kumar S. In Silico prediction of diffusion interaction parameter (kD), a key indicator of antibody solution behaviors. Pharm Res. 2018;35(10):1–20. doi:10.1007/s11095-018-2466-6.
  • Neergaard MS, Kalonia DS, Parshad H, Nielsen AD, Moller EH, van de Weert M. Viscosity of high concentration protein formulations of monoclonal antibodies of the IgG1 and IgG4 subclass - Prediction of viscosity through protein-protein interaction measurements. Eur J Pharm Sci. 2013;49(3):400–10. doi:10.1016/j.ejps.2013.04.019.
  • Jarasch A, Koll H, Regula JT, Bader M, Papadimitriou A, Kettenberger H. Developability assessment during the selection of novel therapeutic antibodies. J Pharm Sci. 2015;104(6):1885–98. doi:10.1002/jps.24430.
  • Yang X, Xu W, Dukleska S, et al. Developability studies before initiation of process development: improving manufacturability of monoclonal antibodies. MAbs. 2013;5(5):787–94. doi:10.4161/mabs.25269.
  • Xu Y, Wang D, Mason B, et al. Structure, heterogeneity and developability assessment of therapeutic antibodies. MAbs. 2019;11(2):239–64. doi: 10.1080/19420862.2018.1553476.
  • 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):154–60. doi:10.1097/NAN.0b013e31824d2271.
  • Stoner K, Harder H, Fallowfield L, Jenkins V. Intravenous versus subcutaneous drug administration. which do patients prefer? A systematic review. Patient. 2015;8(2):145–53. doi:10.1007/s40271-014-0075-y.
  • Reggia R. Switching from intravenous to subcutaneous formulation of abatacept: a single-center Italian experience on efficacy and safety. J Rheumatol. prepub;http://www.ncbi.nlm.nih.gov/pubmed/25512476
  • DuMond B, Patel V, Gross A, Fung A, Weber S. Fixed-dose combination of pertuzumab and trastuzumab for subcutaneous injection in patients with HER2-positive breast cancer: a multidisciplinary approach. J Oncol Pharm Pract. 2021;27(5):1214–21. doi:10.1177/1078155221999712.
  • Heo Y-A, Syed YY. Subcutaneous trastuzumab: a review in HER2-Positive Breast Cancer. Target Oncol. 2019;14(6):749–58. doi:10.1007/s11523-019-00684-y.
  • Sanford M. Subcutaneous trastuzumab: a review of its use in HER2-positive breast cancer. Target Oncol. 2014;9(1):85–94. doi:10.1007/s11523-014-0313-1.
  • Jagosky M, Tan AR. Combination of pertuzumab and trastuzumab in the treatment of HER2-positive early breast cancer: a review of the emerging clinical data. Breast Cancer (Dove Med Press). 2021;13:393–407. doi:10.2147/BCTT.S176514.
  • Van den Nest M, Glechner A, Gold M, Gartlehner G. The comparative efficacy and risk of harms of the intravenous and subcutaneous formulations of trastuzumab in patients with HER2-positive breast cancer: a rapid review. Syst Rev. 2019;8(1). http://www.ncbi.nlm.nih.gov/pubmed/31829250.
  • Soikes R. Moving from vials to prefilled syringes: a project manager’s perspective. Pharm Techno. 2009;33:12–16.
  • Falconer RJ. Advances in liquid formulations of parenteral therapeutic proteins. Biotechnol Adv. 2019;37(7):107412. doi:10.1016/j.biotechadv.2019.06.011.
  • Gervasi DA, Cullen M, Vucen C, McCoy T, Vucen S, Crean A. Parenteral protein formulations: an overview of approved products within the European Union. Eur J Pharm Biopharm. 2018;131:8–24. doi:10.1016/j.ejpb.2018.07.011.
  • Shire SJ, Liu J, Friess W, Jörg S, Mahler H-C. High-concentration antibody formulations. In: Jameel F Hershenson S. editors. Formulation & process development strategies for manufacturing biopharmaceuticals;2010. pp. 349–81. 10.1002/9780470595886.ch15
  • Shire SJ, Shahrokh Z, Liu J. Challenges in the development of high protein concentration formulations. J Pharm Sci. 2004;93(6):1390–402. doi:10.1002/jps.20079.
  • Shire SJ, Shahrokh Z, Liu J. Challenges in the development of high protein concentration formulations. InCurrent trends in monoclonal antibody development and manufacturing. Springer New York; 2010pp. 131–47. 10.1007/978-0-387-76643-09.
  • Sahin E, Deshmukh S. Challenges and considerations in development and manufacturing of high concentration biologics drug products. J Pharm Innov. 2020;15(2):255–67. doi:10.1007/s12247-019-09414-3.
  • Garidel P, Kuhn AB, Schäfer LV, Karow-Zwick AR, Blech M. High-concentration protein formulations: how high is high? Eur J Pharm Biopharm. 2017;119:353–60. doi:10.1016/j.ejpb.2017.06.029.
  • Usach I, Martinez R, Festini T, Peris J-E. Subcutaneous injection of drugs: literature review of factors influencing pain sensation at the injection site. Adv Ther. 2019;36(11):2986–96. doi:10.1007/s12325-019-01101-6.
  • Datta-Mannan A, Estwick S, Zhou C, et al. Influence of physiochemical properties on the subcutaneous absorption and bioavailability of monoclonal antibodies. MAbs. 2020;12(1):1770028. doi:10.1080/19420862.2020.1770028.
  • Bittner B, Richter W, Schmidt J. Subcutaneous administration of biotherapeutics: an overview of current challenges and opportunities. BioDrugs. 2018;32(5):425–40. doi:10.1007/s40259-018-0295-0.
  • Richter WF, Jacobsen B. Subcutaneous absorption of biotherapeutics: knowns and unknowns. Drug Metab Dispos. 2014;42(11):1881–89. doi:10.1124/dmd.114.059238.
  • Rodrigues D, Tanenbaum LM, Thirumangalathu R, Somani S, Zhang K, Kumar V, Amin K, Thakkar SV. Product-specific impact of viscosity modulating formulation excipients during ultra-high concentration biotherapeutics drug product development. J Pharm Sci. 2021;110(3):1077–82. doi:10.1016/j.xphs.2020.12.016.
  • Liu J, Nguyen MDH, Andya JD, Shire SJ. Reversible self‐association increases the viscosity of a concentrated monoclonal antibody in aqueous solution. J Pharm Sci. 2005;95(1):234–35. doi:10.1002/jps.20556.
  • Esfandiary R, Parupudi A, Casas‐finet J, Gadre D, Sathish H. Mechanism of reversible self‐association of a monoclonal antibody: role of electrostatic and hydrophobic interactions. J Pharm Sci. 2015;104(2):577–86. doi:10.1002/jps.24237.
  • Hu Y, Arora J, Joshi SB, Esfandiary R, Middaugh CR, Weis DD, Volkin DB. Characterization of excipient effects on reversible self-association, backbone flexibility, and solution properties of an IgG1 monoclonal antibody at high concentrations: part 1. J Pharm Sci. 2020;109(1):340–52. doi:10.1016/j.xphs.2019.06.005.
  • Arora J, Hu Y, Esfandiary R, et al. Charge-mediated Fab-Fc interactions in an IgG1 antibody induce reversible self-association, cluster formation, and elevated viscosity. MAbs. 2016;8(8):1561–74. doi:10.1080/19420862.2016.1222342.
  • Hu Y, Toth RT, Joshi SB, Esfandiary R, Middaugh CR, Volkin DB, Weis DD. Characterization of excipient effects on reversible self-association, backbone flexibility, and solution properties of an IgG1 monoclonal antibody at high concentrations: part 2. J Pharm Sci. 2020;109(1):353–63. doi:10.1016/j.xphs.2019.06.001.
  • Kolhe P, Amend E, Singh K. Impact of freezing on pH of buffered solutions and consequences for monoclonal antibody aggregation. Biotechnol Prog. 2010;26(3):727–33. doi:10.1002/btpr.377.
  • Connolly BD, Le L, Patapoff TW, Cromwell MEM, Moore JMR, Lam P. Protein aggregation in frozen trehalose formulations: effects of composition, cooling rate, and storage temperature. J Pharm Sci. 2015;104(12):4170–84. doi:10.1002/jps.24646.
  • Singh S, Kolhe P, Mehta A, Chico S, Lary A, Huang M. Frozen state storage instability of a monoclonal antibody: aggregation as a consequence of trehalose crystallization and protein unfolding. Pharm Res. 2011;28(4):873–85. doi:10.1007/s11095-010-0343-z.
  • Jena S, Suryanarayanan R, Aksan A. Mutual influence of mannitol and trehalose on crystallization behavior in frozen solutions. Pharm Res. 2016;33(6):1413–25. doi:10.1007/s11095-016-1883-7.
  • Jena S, Horn J, Suryanarayanan R, Friess W, Aksan A. Effects of excipient interactions on the state of the freeze-concentrate and protein stability. Pharm Res. 2017;34(2):462–78. doi:10.1007/s11095-016-2078-y.
  • Sundaramurthi P, Suryanarayanan R. Influence of crystallizing and non-crystallizing cosolutes on trehalose crystallization during freeze-drying. Pharm Res. 2010;27(11):2384–93. doi:10.1007/s11095-010-0221-8.
  • Hutchings R. Effect of antimicrobial preservatives on partial protein unfolding and aggregation. Abstracts of Papers. 2013;245:123.
  • Bis M, Mallela KMG. Antimicrobial preservatives induce aggregation of interferon alpha-2a: the order in which preservatives induce protein aggregation is independent of the protein. Int J Pharm. 2014;472(1):356–61. doi:10.1016/j.ijpharm.2014.06.044.
  • Arora J, Joshi SB, Middaugh CR, Weis DD, Volkin DB. Correlating the effects of antimicrobial preservatives on conformational stability, aggregation propensity, and backbone flexibility of an IgG1 mAb. J Pharm Sci. 2017;106(6):1508–18. doi:10.1016/j.xphs.2017.02.007.
  • Arakawa T, Ejima D, Tsumoto K, Obeyama N, Tanaka Y, Kita Y, Timasheff SN. Suppression of protein interactions by arginine: a proposed mechanism of the arginine effects. Biophys Chem. 2007;127(1–2):1–8. doi:10.1016/j.bpc.2006.12.007.
  • Nema S, Brendel RJ. Excipients and their role in approved injectable products: current usage and future directions. PDA J Pharm Sci Technol. 2011;65(3):287–332. doi:10.5731/pdajpst.2011.00634.
  • Nema S, Washkuhn RJ, Brendel RJ. Excipients and their use in injectable products. PDA J Pharm Sci Technol. 1997;51(4):166–71. http://www.ncbi.nlm.nih.gov/pubmed/9277127
  • Lee JC, Timasheff SN. The stabilization of proteins by sucrose. J Biol Chem. 1981;256(14):7193–201. doi:10.1016/S0021-9258(19)68947-7.
  • Arakawa T, Timasheff SN. Mechanism of stabilization of proteins by glycerol and sucrose. Seikagaku. 1982;54(11):1255–59. http://www.ncbi.nlm.nih.gov/pubmed/6762399
  • Wang B, Tchessalov S, Warne NW, Pikal MJ. Impact of sucrose level on storage stability of proteins in freeze‐dried solids: i. correlation of protein–sugar interaction with native structure preservation. J Pharm Sci. 2009;98(9):3131–44. doi:10.1002/jps.21621.
  • Wang B, Tchessalov S, Cicerone MT, Warne NW, Pikal MJ. Impact of sucrose level on storage stability of proteins in freeze‐dried solids: iI. Correlation of aggregation rate with protein structure and molecular mobility. J Pharm Sci. 2009;98(9):3145–66. doi:10.1002/jps.21622.
  • Kendrick BS, Chang BS, Arakawa T, Peterson B, Randolph TW, Manning MC, Carpenter JF. Preferential exclusion of sucrose from recombinant interleukin-1 receptor antagonist: role in restricted conformational mobility and compaction of native state. Proc Natl Acad Sci U S A. 1997;94(22):11917–22. doi:10.1073/pnas.94.22.11917.
  • Ajito S, Iwase H, Takata S, Hirai M. Sugar-mediated stabilization of protein against chemical or thermal denaturation. J Phys Chem B. 2018;122(37):8685–97. doi:10.1021/acs.jpcb.8b06572.
  • Jain NK, Roy I. Trehalose and protein stability. Curr Protoc Protein Sci. 2010;59(1). http://www.ncbi.nlm.nih.gov/pubmed/20155732.
  • Warne NW, Mahler H-C. Sucrose and trehalose in therapeutic protein formulations. In: Warne N Mahler H-C, editors. Challenges in protein product development. Springer;2018. p. 63. doi:10.1007/978-3-319-90603-4_3.
  • Piedmonte D, Summers C, McAuley A, Karamujic L, Ratnaswamy G. Sorbitol crystallization can lead to protein aggregation in frozen protein formulations. Pharm Res. 2007;24(1):136–46. doi:10.1007/s11095-006-9131-1.
  • Ohtake S, Wang YJ. Trehalose: current use and future applications. J Pharm Sci. 2011;100(6):2020–53. doi:10.1002/jps.22458.
  • Sundaramurthi P, Patapoff T, Suryanarayanan R. Crystallization of Trehalose in Frozen Solutions and its Phase Behavior during Drying. Pharm Res. 2010;27(11):2374–83. doi:10.1007/s11095-010-0243-2.
  • Viola M, Sequeira J, Seiça R, Veiga F, Serra J, Santos AC, Ribeiro AJ. Subcutaneous delivery of monoclonal antibodies: how do we get there? J Control Release. 2018;286:301–14. doi:10.1016/j.jconrel.2018.08.001.
  • Gokarn YR, Kras E, Nodgaard C, Dharmavaram V, Fesinmeyer RM, Hultgen H, Brych S, Remmele RL Jr, Brems DN, Hershenson S. Self‐buffering antibody formulations. J Pharm Sci. 2008;97(8):3051–66. doi:10.1002/jps.21232.
  • Karow AR, Bahrenburg S, Garidel P. Buffer capacity of biologics—from buffer salts to buffering by antibodies. Biotechnol Prog. 2013;29(2):480–92. doi:10.1002/btpr.1682.
  • Bahrenburg S, Karow AR, Garidel P. Buffer‐free therapeutic antibody preparations provide a viable alternative to conventionally buffered solutions: from protein buffer capacity prediction to bioprocess applications. Biotechnol J. 2015;10(4):610–22. doi:10.1002/biot.201400531.
  • Cologna SM, Williams BJ, Russell WK, Pai P-J, Vigh G, Russell DH. Studies of histidine as a suitable isoelectric buffer for tryptic digestion and isoelectric trapping fractionation followed by capillary electrophoresis–mass spectrometry for proteomic analysis. Anal Chem. 2011;83(21):8108–14. doi:10.1021/ac201237r.
  • Wang C, Yamniuk A, Dai J, Chen S, Stetsko P, Ditto N, Zhang Y. Investigation of a degradant in a biologics formulation buffer containing L-Histidine. Pharm Res. 2015;32(8):2625–35. doi:10.1007/s11095-015-1648-8.
  • Wang C, Brailsford Y, Tymiak Z, Yamniuk AP, Tymiak AA, Zhang Y. Characterization and quantification of histidine degradation in therapeutic protein formulations by size exclusion-hydrophilic interaction two dimensional-liquid chromatography with stable-isotope labeling mass spectrometry. J Chromatogr A. 2015;1426:133–39. doi:10.1016/j.chroma.2015.11.065.
  • Wakankar AA, Borchardt RT. Formulation considerations for proteins susceptible to asparagine deamidation and aspartate isomerization. J Pharm Sci. 2006;95(11):2321–36. doi:10.1002/jps.20740.
  • Wakankar AA, Borchardt RT, Eigenbrot C, et al. Aspartate isomerization in the complementarity-determining regions of two closely related monoclonal antibodies. Biochemistry. 2007;46(6):1534–44. 10.1021/bi061500t.
  • Kerwin BA. Polysorbates 20 and 80 used in the formulation of protein biotherapeutics: structure and degradation pathways. J Pharm Sci. 2008;97(8):2924–35. doi:10.1002/jps.21190.
  • Dwivedi B, Presser G, Presser I, Garidel P. Polysorbate degradation in biotherapeutic formulations: identification and discussion of current root causes. Int J Pharm. 2018;552(1):422–36. doi:10.1016/j.ijpharm.2018.10.008.
  • Kishore R, Kiese S, Fischer S, Pappenberger A, Grauschopf U, Mahler H-C. The degradation of polysorbates 20 and 80 and its potential impact on the stability of biotherapeutics. Pharm Res. 2011;28(5):1194–210. doi:10.1007/s11095-011-0385-x.
  • Martos A, Koch W, Jiskoot W, Wuchner K, Winter G, Friess W, Hawe A. Trends on analytical characterization of polysorbates and their degradation products in biopharmaceutical formulations. J Pharm Sci. 2017;106(7):1722–35. doi:10.1016/j.xphs.2017.03.001.
  • Jones M, Mahler H-C, Yadav S, Bindra D, Corvari V, Fesinmeyer RM, Gupta K, Harmon AM, Hinds KD, Koulov A, et al. Considerations for the use of polysorbates in biopharmaceuticals. Pharm Res. 2018;35(8):1–8.10.1007/s11095-018-2430-5.
  • Dasnoy S, Dezutter N, Lemoine D, Le Bras V, Préat V. High-throughput screening of excipients intended to prevent antigen aggregation at air-liquid interface. Pharm Res. 2011;28(7):1591–605. doi:10.1007/s11095-011-0393-x.
  • Grapentin C, Müller C, Kishore RSK, Adler M, ElBialy I, Friess W, Huwyler J, Khan TA. Protein-polydimethylsiloxane particles in liquid vial monoclonal antibody formulations containing poloxamer 188. J Pharm Sci. 2020;109(8):2393–404. doi:10.1016/j.xphs.2020.03.010.
  • Dear BJ, Hung JJ, Laber JR, Wilks LR, Sharma A, Truskett TM, Johnston KP. Enhancing Stability and Reducing Viscosity of a Monoclonal Antibody with Cosolutes by Weakening Protein-Protein Interactions. J Pharm Sci. 2019;108(8):2517–26. doi:10.1016/j.xphs.2019.03.008.
  • Yadav S, Liu J, Shire SJ, Kalonia DS. Specific interactions in high concentration antibody solutions resulting in high viscosity. J Pharm Sci. 2010;99(3):1152–68. doi:10.1002/jps.21898.
  • Yadav S, Shire SJ, Kalonia DS. Factors affecting the viscosity in high concentration solutions of different monoclonal antibodies. J Pharm Sci. 2010;99(12):4812–29. doi:10.1002/jps.22190.
  • Yadav S, Shire SJ, Kalonia DS. Viscosity behavior of high‐concentration monoclonal antibody solutions: correlation with interaction parameter and electroviscous effects. J Pharm Sci. 2012;101(3):998–1011. doi:10.1002/jps.22831.
  • Yadav S, Laue TM, Kalonia DS, Singh SN, Shire SJ. The influence of charge distribution on self-association and viscosity behavior of monoclonal antibody solutions. Mol Pharm. 2012;9(4):791–802. doi:10.1021/mp200566k.
  • Connolly BD, Petry C, Yadav S, Demeule B, Ciaccio N, Moore JR, Shire S, Gokarn Y. Weak interactions govern the viscosity of concentrated antibody solutions: high-throughput analysis using the diffusion interaction parameter. 2012;103:69–78. doi:10.1016/j.bpj.2012.04.047.
  • Lilyestrom WG, Yadav S, Shire SJ, Scherer TM. Monoclonal antibody self-association, cluster formation, and rheology at high concentrations. J Phys Chem B. 2013;117(21):6373–84. doi:10.1021/jp4008152.
  • Singh S, Yadav S, Shire S, Kalonia D. Dipole-dipole interaction in antibody solutions: correlation with viscosity behavior at high concentration. Pharm Res. 2014;31(9):2549–58. doi:10.1007/s11095-014-1352-0.
  • Pindrus M, Shire SJ, Kelley RF, Demeule B, Wong R, Xu Y, Yadav S. Solubility challenges in high concentration monoclonal antibody formulations: relationship with amino acid sequence and intermolecular interactions. Mol Pharm. 2015;12(11):3896–907. doi:10.1021/acs.molpharmaceut.5b00336.
  • Pindrus M, Shire S, Yadav S, Kalonia D. Challenges in determining intrinsic viscosity under low ionic strength solution conditions. Pharm Res. 2017;34(4):836–46. doi:10.1007/s11095-017-2112-8.
  • Wang S, Zhang N, Tao H, Dai W, Feng X, Zhang X, Qian F. Viscosity-lowering effect of amino acids and salts on highly concentrated solutions of two igg1 monoclonal antibodies. Mol Pharm. 2015;12. 10.1021/acs.molpharmaceut.5b00643
  • Inoue T, Arakawa S, Arakawa T, Shiraki K. Arginine and lysine reduce the high viscosity of serum albumin solutions for pharmaceutical injection. J Biosci Bioeng. 2014;117(5):539–43. doi:10.1016/j.jbiosc.2013.10.016.
  • Inoue N, Takai E, Arakawa T, Shiraki K. Specific decrease in solution viscosity of antibodies by arginine for therapeutic formulations. Mol Pharm. 2014;11(6):1889–96. doi:10.1021/mp5000218.
  • Hung J, Dear B, Dinin A, Borwankar AU, Mehta SK, Truskett TT, Johnston KP. Improving viscosity and stability of a highly concentrated monoclonal antibody solution with concentrated proline. Pharm Res. 2018;35(7):1–14. doi:10.1007/s11095-018-2398-1.
  • Byeong Seon Chang. Protein formulations containing amino acids. 2014-05-08.:US9364542B2.
  • Shenoy B. High concentration protein formulations with reduced viscosity. US10646569B2. 2018.
  • Yarbrough M, Hodge T, Menard D, Jerome R, Ryczek J, Moore D, Baldus P, Warne N, Ohtake S. Edetate disodium as a polysorbate degradation and monoclonal antibody oxidation stabilizer. J Pharm Sci. 2019;108(4):1631–35. doi:10.1016/j.xphs.2018.11.031.
  • Zhou S, Zhang B, Sturm E, Teagarden DL, Schöneich C, Kolhe P, Lewis LM, Muralidhara BK, Singh SK. Comparative evaluation of disodium edetate and diethylenetriaminepentaacetic acid as iron chelators to prevent metal‐catalyzed destabilization of a therapeutic monoclonal antibody. J Pharm Sci. 2010;99(10):4239–50. doi:10.1002/jps.22141.
  • Chu J-W, Brooks BR, Trout BL. Oxidation of methionine residues in aqueous solutions: free methionine and methionine in granulocyte colony-stimulating factor. J Am Chem Soc. 2004;126(50):16601–07. doi:10.1021/ja0467059.
  • Yin J, Chu J-W, Ricci MS, Brems DN, Wang DIC, Trout BL. Effects of excipients on the hydrogen peroxide-induced oxidation of methionine residues in granulocyte colony-stimulating factor. Pharm Res. 2005;22(1):141–47. doi:10.1007/s11095-004-9019-x.
  • Yin J, Chu J-W, Ricci MS, Brems DN, Wang DIC, Trout BL. Effects of antioxidants on the hydrogen peroxide-mediated oxidation of methionine residues in granulocyte colony-stimulating factor and human parathyroid hormone fragment 13-34. Pharm Res. 2004;21(12):2377–83. doi:10.1007/s11095-004-7692-4.
  • Badkar A, Wolf A, Bohack L, Kolhe P. Development of biotechnology products in pre-filled syringes: technical considerations and approaches. AAPS Pharm Sci Tech. 2011;12(2):564–72. doi:10.1208/s12249-011-9617-y.
  • Yoneda S, Torisu T, Uchiyama S. Development of syringes and vials for delivery of biologics: current challenges and innovative solutions. Expert Opin Drug Deliv. 2021;18(4):459–70. doi:10.1080/17425247.2021.1853699.
  • Jones LS, Kaufmann A, Middaugh CR. Silicone oil induced aggregation of proteins. J Pharm Sci. 2005;94(4):918–27. doi:10.1002/jps.20321.
  • Thirumangalathu R, Krishnan S, Ricci MS, Brems DN, Randolph TW, Carpenter JF. Silicone oil‐ and agitation‐induced aggregation of a monoclonal antibody in aqueous solution. J Pharm Sci. 2009;98(9):3167–81. doi:10.1002/jps.21719.
  • Basu P, Blake‐haskins AW, O’Berry KB, Randolph TW, Carpenter JF. Albinterferon α2b adsorption to silicone oil–water interfaces: effects on protein conformation, aggregation, and subvisible particle formation. J Pharm Sci. 2014;103(2):427–36. doi:10.1002/jps.23821.
  • Basu P, Krishnan S, Thirumangalathu R, Randolph TW, Carpenter JF. IgG1 aggregation and particle formation induced by silicone‐water interfaces on siliconized borosilicate glass beads: a model for siliconized primary containers. J Pharm Sci. 2013;102(3):852–65. doi:10.1002/jps.23434.
  • Bai S, Landsman P, Spencer A, DeCollibus D, Vega F, Temel DB, Houde D, Henderson O, Brader ML. Evaluation of incremental siliconization levels on soluble aggregates, submicron and subvisible particles in a prefilled syringe product. J Pharm Sci. 2016;105(1):50–63. doi:10.1016/j.xphs.2015.10.012.
  • Locke KW, Maneval DC, LaBarre MJ. ENHANZE® drug delivery technology: a novel approach to subcutaneous administration using recombinant human hyaluronidase PH20. Drug Deliv. 2019;26(1):98–106. doi:10.1080/10717544.2018.1551442.
  • Knowles SP, Printz MA, Kang DW, LaBarre MJ, Tannenbaum RP. Safety of recombinant human hyaluronidase PH20 for subcutaneous drug delivery. Expert Opin Drug Deliv. 2021;18(11):1673–85. doi:10.1080/17425247.2021.1981286.
  • Frost GI. Recombinant human hyaluronidase (rHuph20): an enabling platform for subcutaneous drug and fluid administration. Expert Opin Drug Deliv. 2007;4(4):427–40. doi:10.1517/17425247.4.4.427.