A review published in Discover Pharmaceutical Sciences examines the current capabilities and future prospects of large-volume subcutaneous (LVSC) drug delivery. The paper, authored by Alyssa Wu, Brent Rutland, Carleton Southworth, Jasmin Bosshard, and Devin Wall, focuses on how administering larger volumes of medication under the skin can transform pharmaceutical manufacturing and drug delivery device development. The authors identify subcutaneous immunoglobulin (SCIg) therapy as a leading example of this approach, highlighting its role in shifting treatment from intravenous (IV) to subcutaneous (SC) routes for patients with immunodeficiency disorders.
LVSC drug delivery is defined in the review as the administration of medication in volumes ranging from 2 to 50 mL. The authors note that volumes exceeding 50 mL are sometimes referred to as ultra-large volume subcutaneous delivery, although this term is not formally established in published literature. This method represents a significant transition from traditional IV administration, offering advantages in patient experience, treatment outcomes, and cost-effectiveness. The review emphasizes that pharmaceutical manufacturers play a crucial role in this transformation by developing specialized devices, optimizing drug formulations, and exploring new therapeutic areas for LVSC delivery.
The success of SCIg therapy serves as the primary case study for the review. SCIg involves administering immunoglobulin therapy subcutaneously in volumes of 5 to 30 mL per site, delivering concentrated doses of antibodies to patients with impaired immune systems. The authors state that numerous studies have demonstrated the efficacy of SCIg in maintaining protective antibody levels, preventing infections, and improving overall health outcomes in patients with primary immunodeficiencies. SCIg has been shown to be equally effective and safe as IVIg therapy, making it a suitable alternative for patients who prefer or require subcutaneous administration.
One of the key advantages of SCIg therapy is its positive impact on patient quality of life. Compared to IVIg, SCIg offers greater flexibility and convenience, allowing patients to self-administer the treatment at home. This reduces the need for frequent visits to healthcare facilities and enhances treatment adherence. The review cites a recent study concluding that only 3.3% of patients reported lower adherence after switching from IV to SC immune globulin, while 37.4% reported improved or substantially improved adherence. Additionally, SCIg has a favorable safety profile, with gradual absorption and release of immunoglobulin reducing systemic side effects and adverse events compared to IVIg.
The review provides specific data on the volumes administered during SCIg infusions, sourced from pharmaceutical manufacturers and specialty pharmacies. For example, Hizentra, a commonly used SCIg product, has a mean dose volume of 66.25 mL. Other products include Cuvitru (80.60 mL), HyQvia (340.20 mL), GammGARD (130.0 mL), Xembify (81.25 mL), CutaQUIG (72 mL), and GammuNEX-C (60 mL). The authors note that across all SCIg drugs in the dataset, 78.04% of patients received a dose per infusion exceeding 50 mL. This data underscores the practical reality of large-volume administration in clinical settings and highlights the necessity for robust delivery systems.
From an economic standpoint, the review highlights the potential cost-effectiveness of LVSC drug delivery. Shifting from healthcare center administration to home-based self-administration can significantly reduce healthcare resource utilization, including decreased hospital visits and nursing staff requirements. The authors cite a 2022 economic analysis in Canada that found self-administered subcutaneous immune globulin was $5,386 less costly per patient-year compared to clinic-administered intravenous immune globulin. This cost savings, combined with the reduced burden on healthcare facilities, contributes to overall healthcare system efficiency and allows providers to focus on patients with more complex needs.
The review also discusses the technical challenges and safety considerations associated with LVSC delivery. Mitigating injection site reactions, such as pain, swelling, and erythema, is a critical aspect of patient safety. Strategies to minimize these reactions include proper site rotation, administering medications at room temperature, and using smaller gauge needles or subcutaneous cannulas. Patient education on proper injection techniques and site care is also emphasized as crucial for ensuring compliance and minimizing adverse events. Regular follow-up visits and monitoring of injection sites are essential to evaluate the safety and efficacy of the therapy and to detect any signs of infections or systemic reactions promptly.
Medical devices play a pivotal role in facilitating LVSC drug delivery. The authors compare various technologies, including mechanical pumps, wearable devices, and programmable pumps. Conventional mechanical pumps are described as well-established, portable, and cost-effective, though they offer limited control over infusion rates. Wearable devices provide portability and programmability but are often single-use and can be costly, with limitations in handling very large volumes. Programmable electronic pumps offer precise flow rates and dosing schedules but require reliable electricity and involve higher costs for maintenance and technical expertise. The authors argue that while wearable and programmable pumps offer advanced features, their higher costs may limit widespread adoption compared to non-programmable alternatives with equal clinical efficacy.
The review explores the potential for expanding LVSC delivery to other therapeutic areas beyond immunoglobulin therapy. Factors such as drug molecular weight, solubility, and stability under subcutaneous conditions are critical considerations for selecting suitable drugs. Advancements in formulation technologies and the use of excipients can help improve drug solubility and enable LVSC administration. The authors mention that drugs in development for autoimmune diseases, hematological disorders, and certain cancers, such as Crovalimab, Daratumumab, and Relatlimab and nivolumab, represent potential candidates for LVSC delivery. This expansion could revolutionize treatment approaches for chronic diseases and improve patient outcomes by enabling sustained and controlled release of medications.
The authors emphasize the importance of collaboration between pharmaceutical manufacturers, device developers, and healthcare providers to drive innovation in LVSC drug delivery. This collaboration can foster the development of more advanced and user-friendly devices, facilitate the exchange of knowledge and expertise, and identify optimal drug candidates and formulation strategies. The review concludes that LVSC drug delivery holds great promise for the future of healthcare, offering improved patient care, optimized treatment outcomes, and reduced healthcare costs. By embracing this approach, manufacturers can offer innovative solutions that empower healthcare providers and patients, marking a shift towards more patient-centric and efficient therapeutic options in the healthcare industry.
The authors’ device evaluation framework detailed in the review illustrates how clinical efficacy and operational expenditure interact when healthcare payors select delivery hardware. To structure this comparison, the review presents an illustrative four-category matrix mapping cost against clinical performance, though the authors note this conceptual diagram is not derived from an existing published theory or external empirical dataset. Non-powered, non-programmable mechanical pumps occupy the favorable low-cost and high-efficacy quadrant. These systems deliver reliable, controlled subcutaneous infusions without requiring battery power or advanced circuitry, keeping initial procurement costs modest and restricting ongoing operational expenses primarily to standard auxiliary supplies.
In contrast, both wearable pumps and non-wearable programmable electronic pumps are categorized as high-cost technologies offering high clinical efficacy. Programmable electronic pumps provide programmable dosing schedules, automated volume measurements, and fine control over flow rates, but they depend on consistent electrical supplies and impose heavy financial burdens related to technical expertise, device maintenance, and user training. Wearable pumps face additional economic constraints because their single-use disposable construction generates substantial ongoing costs, particularly for regimens that require patients to use multiple units each week. Furthermore, wearable devices require specialized dosing syringes and complex setup. The authors note that pairing larger-volume prefilled syringes with conventional non-programmable mechanical pumps presents a substantially more cost-competitive option, as it administers higher medication volumes using fewer separate dosing syringes.
Because advanced wearable and programmable pumps carry substantial auxiliary and maintenance expenses without demonstrating clinical efficacy superior to simpler options, the authors suggest these higher-cost platforms may remain confined to a niche market. Patients, healthcare providers, and payors may hesitate to absorb the extra financial investments and technical complexities of programming and maintenance when lower-cost mechanical alternatives deliver equivalent therapeutic outcomes. In addition, the review points out that large-volume autoinjectors were intentionally excluded from the paper’s formal device comparison table because current understanding and published scientific literature concerning their practical performance in large-volume applications remain exceptionally sparse.
Selecting and reformulating intravenous pharmaceuticals for subcutaneous delivery also requires overcoming delicate biochemical and biomechanical obstacles. Unlike direct intravenous access, the subcutaneous environment introduces physiological variables such as tissue pH, local temperature, and endogenous enzymatic activity, all of which can compromise formulation stability by accelerating drug degradation or inducing molecular aggregation. Simultaneously, physical characteristics such as fluid viscosity and delivery flow rates must align with device capabilities to prevent tissue trauma. When successfully formulated into subcutaneous depots, however, medications achieve sustained and controlled release profiles that prolong therapeutic activity, stabilize circulating drug concentrations, and reduce dosing intervals for patients managing chronic ailments or hormonal imbalances. This decentralization of routine care reduces institutional burdens, enabling healthcare facilities to shorten wait times and reallocate specialized clinical staff to individuals requiring acute hospital management.
Regulatory compliance represents another decisive dimension in advancing these specialized delivery platforms from engineering concepts to widespread therapeutic use. Regulatory agencies provide formal guidelines and recommendations governing the development, approval, and safe clinical use of subcutaneous drug delivery systems. For pharmaceutical manufacturers, navigating these regulatory frameworks requires demonstrating thorough validation of both the therapeutic formulation and the accompanying medical hardware. Ensuring rigorous compliance with regulatory standards not only protects patient safety during prolonged home administration, but also facilitates timely regulatory review, formal market approval, and subsequent clinical adoption by healthcare systems seeking dependable alternatives to conventional intravenous therapy.
Subject of Research: Large-volume subcutaneous drug delivery capabilities and prospects
Article Title: The transformative potential of large-volume subcutaneous drug delivery: a discussion of current capabilities and future prospects for pharmaceutical manufacturers
Article References: Wu, A., Rutland, B., Southworth, C., Bosshard, J., & Wall, D. (2025). The transformative potential of large-volume subcutaneous drug delivery: a discussion of current capabilities and future prospects for pharmaceutical manufacturers. Discover Pharmaceutical Sciences, 1(1), Article 11. https://doi.org/10.1007/s44395-025-00012-6
Image Credits: AI Generated
DOI: 10.1007/s44395-025-00012-6
Keywords: subcutaneous delivery, pharmaceutical manufacturing, drug delivery devices, immunoglobulin therapy, patient adherence, healthcare costs, medical pumps, drug formulation, transformative, potential, large-volume, subcutaneous
News Source: Ophelia Keating. (November 10, 2026). Large-Volume Subcutaneous Delivery Expands Drug Administration Options. Scienmag.
