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SC administration offers multiple benefits, including potential for at-home administration, enhanced patient compliance, reduced hospital congestion, lowered health care costs, and improved sustainability by reducing drug wastage and minimizing environmental impact. However, for many biologics, the shift to SC administration requires the development of high-concentration monoclonal antibody products (HCmAP) due to the need for large dose volumes. Here we explore the impact of the COVID-19 pandemic on immunotherapy administration and the imperative of adopting SC administration. We discuss challenges encountered throughout the manufacturing, shipping, storage, and delivery of HCmAP. A central hurdle identified involves the biophysical instability and the large increase in viscosity of these biologics due to increased antibody concentration. Further complications can arise from \u201cnon-ideality\u201d effects through molecular crowding or co-exclusion effects (macromolecules blocking the free movement in solution of other macromolecules) and elevated macromolecular interactions. For reducing the viscosity for a given concentration of antibody, the main excipients reported are salts and amino acids, with Arg-HCl demonstrating particularly improved formulation viscosity in an HCmAP. However, excipients with viscosity-lowering effects can also impact protein stability. The journey to discover suitable excipient strategies remains ongoing, combined with emerging approaches such as molecular engineering and computational techniques, with the ultimate aim of facilitating the successful integration of SC administration for economic savings, environmental sustainability, and social equity.<\/jats:p>","DOI":"10.1007\/s12551-025-01346-2","type":"journal-article","created":{"date-parts":[[2025,8,2]],"date-time":"2025-08-02T14:18:59Z","timestamp":1754144339000},"page":"1013-1031","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Developing high-concentration monoclonal antibody formulations for subcutaneous administration to improve patient treatment"],"prefix":"10.1007","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-9252-9102","authenticated-orcid":false,"given":"Laura R. 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