Monoclonal antibody and protein therapeutic formulations for subcutaneous delivery: high-concentration, low-volume vs. low-concentration, high-volume

Abstract

Biologic drugs are used to treat a variety of cancers and chronic diseases. While most of these treatments are administered intravenously by trained healthcare professionals, a noticeable trend has emerged favoring subcutaneous (SC) administration. SC administration of biologics poses several challenges. Biologic drugs often require higher doses for optimal efficacy, surpassing the low volume capacity of traditional SC delivery methods like autoinjectors. Consequently, high concentrations of active ingredients are needed, creating time-consuming formulation obstacles. Alternatives to traditional SC delivery systems are therefore needed to support higher-volume biologic formulations and to reduce development time and other risks associated with high-concentration biologic formulations. Here, we outline key considerations for SC biologic drug formulations and delivery and explore a paradigm shift: the flexibility afforded by low-to-moderate-concentration drugs in high-volume formulations as an alternative to the traditionally difficult approach of high-concentration, low-volume SC formulation delivery.

Monoclonal Antibodies from Space: Improved Crystallization Under Microgravity During Manufacturing in Orbit

“…Nonetheless, designing a typical therapeutic mAb dose, which often falls in the 150-200 mg range, for SC injection, remains a significant challenge. 9 Reports in the literature over the last three decades indicate that the microgravity environment can be used to create novel protein crystalline polymorphs with physicochemical properties significantly different from protein crystals grown on Earth at 1g (one g is the force per unit mass due to gravity at the Earth's surface; this standard gravity is defined as 9.8 meters per second squared), thus enabling the production of low-viscosity, highly concentrated colloidal protein crystal suspensions. [10][11][12] These physiochemical characteristics are essential for developing therapeutic mAb and ADC formulations that are suitable for simple SC injection.…”