719. Stability Could Be a Weak Point for Gene Therapy Sponsors

Abstract

So far, no gene therapy product has been approved by the Food and Drug Administration (FDA). One gene therapy for an extremely rare disease was approved in Europe in 2012, but questions about its effectiveness remain. Gene therapy refers to products that introduce genetic material into a person's DNA to replace faulty or missing genetic material, thus treating a disease or abnormal medical condition. There have been hundreds of trials of gene therapy in humans since 1990, and few gene therapies have reached advanced stages of development and have been submitted for authorization. Therefore, regulators have not yet worked out how best to assess gene therapy. While the same requirements as other medicinal products generally apply to the clinical development of gene therapies, regulators recognize that there might be cases where the principles might not apply and have issued guidance specific to gene therapy in order to facilitate product development and marketing approval. The shelf lives of gene therapy products may vary widely, depending on the nature of the product and its storage conditions. The design of stability testing should be based on a comprehensive understanding of the final product and its intended use. Testing should be based on real-time, real-temperature studies and should include a measure of product integrity, sterility, identity, purity, quality and other applicable assays. Additionally, potency assays should measure a relevant biological functionality either in vitro or in vivo. Interaction with the FDA however indicates that, beyond what is provided in the current guidelines, the regulators will likely scrutinize the results from the stability program for gene therapy during submission for marketing approval. Therefore, establishing shelf life and storage conditions of gene therapy products would most likely be a weak point for gene therapy sponsors. Even if the stability protocols follow the current guidelines, because the gene therapy territory is new and innovative, it is difficult to gauge whether an unexpected impact on product quality can occur years after stability has been completed. Based on this feedback, the recommendation is that the stability protocol should be established conservatively, maximizing time points, lot testing and with a careful evaluation of quality parameters and critical product attribute. In conclusion, the regulatory environment for gene therapy is still being established and commonly accepted principles guiding current product development should be thoroughly evaluated and most likely reassessed. Because of the biological complexities of these products, a conservative approach should be followed with regards to the stability program.