Potency is one of the critical attributes of biological medicinal products and therefore a robust potency assay is critical for successful development of cell and gene therapy products. It should reflect the mechanism of action of the product and ideally the results should correlate with the clinical response. Robust potency assays are fundamental also for comparability studies, process validation and stability testing.
An NDA team specialized on ATMPs together with Prof. Steffen Thirstrup from EMA published on 5th of May 2023 an article titled: “Potency testing of cell and gene therapy products” in Frontiers in Medicine, Regulatory Science. The article highlights the importance and complexity of potency assay development for cell and gene therapy products. Understanding regulatory expectations for potency assay along with the limitation and challenges related to the development of such assays is key for successful transition of innovative products from the clinic to patients.
Regulatory expectations for potency testing
- Legal requirement for development of potency assays along with specific scientific guidelines available in EU and US may vary depending on the phase of development.
- Guidelines recommend evaluating multiple potency assays for ATMPs during early development.
- US FDA requirement of having a functional potency assay for release of ATMPs can cause challenges if considered late.
- EU guidance provides some flexibility in consideration of release testing using validated surrogate assays in case a functional assay is available for characterization and the results of the assays correlate with each other.
Limitations and challenges of potency assays
- The biological activity of ATMPs can be mediated by numerous factors meaning one single marker or assay may not fully reflect the functionality of the product.
- Functional potency assays can be difficult to validate due to the cellular components and inherent variability related to the material and manufacturing process.
- Limited number of cells available in autologous therapies and needs for rapid patient administration (fresh products) may restrict potency testing possibilities at release
Key takeaways
Focus on:
- A thorough characterisation of the product, especially for potency, using multiple analytical tools
- Robust correlation of potency with clinical efficacy
- Early engagement with regulatory authorities to discuss potency testing
