Potency Assay Development for Gene Therapy Products – Approaches and Points to Consider in Data Processing

Purpose

Gene therapies – including AAVs, engineered viruses and polymer formulated oligonucleotides/plasmids – are among the highest growth area in biopharmaceuticals. They provide great promise as therapeutics but present many development challenges owing to their complex mechanisms of action (MOA). Potency assays play a pivotal role in the development of nearly every biologic and are an expectation of global regulatory agencies. These assays take many forms depending on the MOA of the biologic and include analysis of cell activity using ELISAs, Flow Cytometry, and ddPCR/qPCR. The cells and the readout are critical but so is the appropriate processing of the data to derive a relative potency. Here case studies for representative gene therapies have been provided as examples of the challenges encountered in acquiring and processing data. Different data modelling is applied to achieve robust outcomes that meet the requirements of a GMP Relative Potency assay. We include discussion of phase appropriateness and the risks and benefits of differing approaches. The modalities include a plasmid gene therapeutic as well as AAVs. Dilution series, ranges and other aspects of the assay execution are optimized to better fit the best processing paradigm