Establishing the Bioequivalence Safe Space for Immediate-Release Oral Dosage Forms using Physiologically Based...

Area of Science:

• Pharmacokinetics and Drug Metabolism
• Pharmaceutical Sciences
• Computational Modeling

Background:

• In vitro dissolution is a key predictor of in vivo drug absorption for oral products.
• Establishing in vitro-in vivo correlations (IVIVC) is challenging with traditional methods.
• Physiologically based biopharmaceutics modeling (PBBM) offers a promising alternative for IVIVC.

Purpose of the Study:

• To demonstrate the application of PBBM in establishing a "safe space" for drug product quality.
• To explore the use of PBBM for BCS Class 2 and 4 drugs in industrial and regulatory settings.
• To reflect on practical considerations for developing and validating PBBM-based safe spaces.

Main Methods:

• Utilized five case studies applying PBBM to define safe spaces for specific drug classes.
• Incorporated in vitro dissolution data and pharmacokinetic parameters into PBBM.
• Evaluated methodologies for data integration, model validation, and application.

Main Results:

• Successfully applied PBBM to establish safe spaces for BCS Class 2 and 4 drugs across different companies.
• Identified practical challenges and ideal dataset requirements for safe space development.
• Demonstrated PBBM's utility in internal decision-making and regulatory submissions.

Conclusions:

• PBBM is a valuable tool for establishing safe spaces and ensuring oral drug product quality.
• Further development and examples are needed to refine best practices for PBBM in this context.
• The field of PBBM for safe space establishment is evolving and shows significant potential.