Navigating large-volume subcutaneous injections of biopharmaceuticals: a systematic review of clinical pipelines and approved products

Subcutaneous (SC) administration is transforming the delivery of biopharmaceuticals, facilitating care in a variety of healthcare settings, including home self-treatment. Large-volume single SC doses have gained attention for their potential to expand therapeutic applications and improve long-term, patient-centric dosing regimens, often at a reduced SC injection frequency. However, a systematic understanding of dose volumes and frequencies for large-volume (>2.0 mL) SC biopharmaceuticals (LVSCs) is lacking. Accordingly, this study systematically reviewed clinical-stage and approved intravenous (IV) and SC biopharmaceuticals, identifying 182 LVSCs - predominantly monoclonal or bispecific antibodies - which correspond to approximately 15% of all IV and SC biopharmaceuticals. These LVSCs are designed to target cancer and a range of non-cancer chronic disease states, including autoimmune, neurological, and cardiovascular diseases. Results show that anti-cancer LVSCs (n = 75) typically require 5.0 to 20.0 mL doses every three weeks and are administered by healthcare professionals. In contrast, non-cancer LVSCs (n = 107), which are typically self-administered monthly, show more significant dosing variability, with