Biopharmaceutics Risk Assessment-Connecting Critical Bioavailability Attributes with In Vitro, In Vivo Properties and...

Area of Science:

• Pharmaceutical Sciences
• Drug Development
• Regulatory Science

Background:

• Quality risk assessment (QRA) based on ICH Q9 principles is crucial for drug efficacy and safety.
• Current QRA primarily focuses on manufacturing aspects, not in vivo performance.
• Extending QRA to biopharmaceutics, identifying critical bioavailability attributes (CBA), is an emerging regulatory trend.

Purpose of the Study:

• To provide a harmonized biopharmaceutics risk assessment framework for generic regulatory submissions.
• To establish a workflow for identifying, evaluating, and controlling CBAs.
• To guide generic product development and regulatory strategies.

Main Methods:

• Development of a detailed biopharmaceutics risk assessment workflow.
• Identification of initial CBAs (iCBAs) and their confirmatory evaluation.
• Application of tools such as bio-discriminatory dissolution methods and physiologically based biopharmaceutics modeling (PBBM).
• Case study demonstrating CBA evaluation using PBBM for an extended-release product.

Main Results:

• A practical workflow for biopharmaceutics risk assessment in generics was proposed.
• Physiologically based biopharmaceutics modeling (PBBM) demonstrated utility in CBA evaluation.
• A case study validated the workflow for an extended-release product, supporting regulatory submission.

Conclusions:

• The proposed framework facilitates biopharmaceutics risk assessment for generic submissions.
• Integration of CBA evaluation and risk assessment with initiatives like KASA is recommended.
• Standardized risk assessment templates and enhanced industry-academia collaboration are needed.