Biopharmaceutics of mAbs: Challenges in Subcutaneous Bioavailability Prediction

3/21/2022 16:05 - 16:35

Reliable prediction of clinical subcutaneous bioavailability of monoclonal antibodies (mAbs) remains challenging. Only limited success was reported in use of preclinical-to-clinical translation, ex vivo methods, or in silico methods. This gap has a direct impact on human subcutaneous dose selection and cost of goods in development of a new drug product.

This presentation will review the biopharmaceutics of mAbs with special emphasis on the subcutaneous absorption process and hypotheses behind incomplete systemic absorption. These are related to formulation-related events (e.g. precipitation at the site of injection or strong nonionic interaction of mAbs with SC tissue) and physiological events (e.g. nonspecific metabolic degradation at the site of injection or during transit in the lymphatic system). A deeper understanding of these processes may facilitate developing better predictive tools, streamlined development, and cost savings.

Mikolaj Milewski, Principal Scientist, MSD