Advancing Potency Assay Development for Advanced Therapy Medicinal Products: A Comprehensive Approach and Regulatory...

Area of Science:

• Biotechnology and Pharmaceutical Sciences
• Regulatory Science
• Assay Development

Background:

• Advanced Therapy Medicinal Products (ATMPs) present unique potency assay development challenges due to inherent variability and complex mechanisms.
• Current assay methodologies often struggle to accommodate product-specific needs and evolving global regulatory standards.

Purpose of the Study:

• To address the critical question of how to design robust and reliable potency assays for ATMPs.
• To propose a product-specific framework for potency assay design, development, and validation.
• To identify innovative solutions and emerging technologies for ATMP potency testing.

Main Methods:

• A mixed-methods approach was employed, integrating systematic literature reviews (2018-2024), industry report analysis, and global regulatory guideline comparisons.
• Analysis of a database of potency assays for approved, rejected, and withdrawn Cellular and Gene Therapy Products (CGTs/ATMPs) to identify challenges.
• Synthesis of data to propose a product-specific framework and highlight emerging technologies.

Main Results:

• A product-specific framework for designing, developing, and validating ATMP potency assays was proposed, considering technical and regulatory constraints.
• Emerging technologies like droplet digital PCR and reporter gene assays were identified as promising for enhancing assay precision and reliability.
• The analysis highlighted the need for flexible, risk-based strategies that adapt throughout product development.

Conclusions:

• Robust potency assay development for ATMPs necessitates adaptable, product-specific, and risk-based strategies.
• Standardization, definition of acceptable variability, and correlation of in vitro data with clinical outcomes are crucial for future advancements.
• Adoption of innovative technologies can significantly improve the reliability and precision of ATMP potency testing.