Gene therapy potency strategy roadmap

Developing robust potency strategies for in vivo gene therapies remains one of the most complex challenges in the advanced therapy medicinal products (ATMP) sector. Regulatory expectations vary globally, and the scientific and operational hurdles in implementing phase-appropriate potency assays add further complexity. To address these issues, BioPhorum convened a cross-industry workstream to create a consensus-driven roadmap for recombinant adeno-associated virus (rAAV) gene therapy products. This roadmap provides practical guidance for designing potency strategies that integrate product understanding, analytical methodology, and regulatory considerations. It emphasizes: - A phase-appropriate approach to potency assay implementation, evolving from mechanism-focused assays in early development to functional assays aligned with clinical outcomes. - An integrated framework linking Quality Target Product Profile (QTPP), Critical Quality Attributes (CQAs), and Analytical Target Profile (ATP) to ensure potency reflects the product’s mechanism of action. - Strategic recommendations on cell line selection, including justification for non-representative cell lines, and critical evaluation of traditional methods such as TCID50 to avoid redundancy and improve clinical relevance. - A matrix approach for potency testing when a single assay cannot capture all relevant attributes. By following this roadmap, developers can create scientifically sound, regulatorily acceptable potency strategies that support consistent product quality and accelerate patient access to life-changing gene therapies. The document serves as both a practical guide and a foundation for continued industry alignment.