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

Area of Science:

• Pharmacokinetics and Drug Delivery
• Computational Modeling in Pharmaceuticals

Background:

• Subcutaneous drug administration is increasingly utilized for both small and large molecules.
• Generic development for subcutaneous injectables is hindered by a lack of specific preclinical testing and in vitro-in vivo correlation (IVIVC) guidelines.
• Existing IVIVC methods, often developed for oral drugs, may not adequately address subcutaneous injection site physiology and drug absorption.

Purpose of the Study:

• To review current IVIVC guidelines for oral drugs.
• To discuss the unique challenges of IVIVC for subcutaneous drug products.
• To highlight the potential of mechanistic, computational modeling to support subcutaneous injectable development.

Main Methods:

• Literature review of existing IVIVC guidelines for oral drug products.
• Analysis of physiological and pharmacokinetic differences between oral and subcutaneous routes.
• Exploration of mechanistic modeling and simulation approaches for formulation design and IVIVC.

Main Results:

• Current IVIVC frameworks for oral drugs are insufficient for subcutaneous injectables.
• Subcutaneous drug release and absorption are influenced by complex injection site factors.
• Mechanistic modeling can identify critical drug and formulation attributes affecting subcutaneous drug release.

Conclusions:

• Formalized preclinical testing and IVIVC guidance are crucial for advancing generic subcutaneous drug development.
• Computational modeling and simulation offer a powerful approach to overcome current limitations in formulation design and IVIVC for subcutaneous injectables.
• Integrating modeling and simulation into existing IVIVC strategies can accelerate the development of subcutaneous injectable products.