Development roadmap for subcutaneous delivery of high dose biologics - high concentration formulation, analytical comparability and patient preference considerations for large volume devices.

High dose biologic drug products (DPs) have become a common trend for the treatment of chronic diseases across a wide range of therapeutic areas. While the expectation is to deliver these DPs via subcutaneous (SC) self-administration due to patient and healthcare provider preference, there are unique challenges that make the product development highly complex. Critical aspects that need to be considered while designing the development roadmap include high concentration formulation development, drug-device combination product design to deliver large volumes, assessment of pharmacokinetic (PK) bridging risk, user preferences, patient tolerability, etc. Such challenges can be overcome by robust formulation development strategies, analytical characterization to ensure product comparability, and well-designed patient preference and human factors studies to identify appropriate patient friendly delivery device technology. This review discusses novel formulation and processing technologies associated with patient tolerability and in-vitro/-vivo studies to minimize the risk of clinical bridging. The review also presents multiple case studies to understand user and patient preferences for defining the quality target product profile (QTPP) for selecting an appropriate device approach, dosing frequency, and overall development road map from first-in-human (FIH) to product launch. The opinions summarized in this review can be used as guidance for the development of high-dose biologic DPs.