Applications of Clinically Relevant Dissolution Testing: Workshop Summary Report.

Area of Science:

• Pharmaceutical Sciences
• Drug Development
• Regulatory Science

Background:

• Current drug product development for solid oral dosage forms faces challenges in establishing clinical relevance.
• Industry and regulatory agencies grapple with setting clinically relevant drug product specifications (CRDPS).

Purpose of the Study:

• To summarize strategies for building clinical relevance into drug product development.
• To discuss challenges in setting clinically relevant drug product specifications.
• To explore the role of dissolution and translational modeling in patient-centric drug development.

Main Methods:

• Understanding the relationship between critical quality attributes (CQAs) and clinical outcomes.
• Introducing variations in critical material attributes (CMAs) and critical process parameters (CPPs) to link in vitro dissolution to in vivo performance.
• Utilizing in silico methods like in vitro-in vivo correlation (IVIVC) and physiologically based pharmacokinetic (PBPK) modeling and simulation (M&S).

Main Results:

• Dissolution testing, enhanced by modeling, can establish safe boundaries for drug product batches.
• In silico approaches improve development efficiency by potentially reducing the need for in vivo studies.
• Established relationships between in vitro dissolution and in vivo PK performance serve as surrogates for clinical outcomes.

Conclusions:

• Integrating dissolution and translational modeling enhances patient-centric drug product development.
• These strategies facilitate regulatory flexibility throughout the drug product lifecycle.
• Achieving clinical relevance in dissolution testing is a multidisciplinary effort.