A Perspective on Model-Informed IVIVC for Development of Subcutaneous Injectables.

Subcutaneously administered drugs are growing in popularity for both large and small molecule drugs. However, development of these systems - particularly generics - is slowed due to a lack of formal guidance regarding preclinical testing and in vitro - in vivo correlations (IVIVC). Many of these methods, while appropriate for oral drugs, may not be optimized for the complex injection site physiologies, and release rate and absorption mechanisms of subcutaneous drugs. Current limitations for formulation design and IVIVC can be supported by implementing mechanistic, computational methods. These methods can help to inform drug development by identifying key drug and formulation attributes, and their effects on drug release rates. This perspective, therefore, addresses current guidelines in place for oral IVIVC development, how they may differ for subcutaneously administered compounds, and how modeling and simulation can be implemented to inform design of these products. As such, integration of modeling and simulation with current IVIVC systems can help in driving the development of subcutaneous injectables.