Demonstrating Comparability of AAV Gene Therapy Products During Clinical Development: Managing the Link Between the Product and the Process

Abstract

While the ideal path during product development would be to avoid process changes, especially during later phases of clinical development, manufacturing changes are common in gene therapy products for many reasons. Development of a comparability strategy should be incorporated during product development to minimize risks to future approvals. This comparability strategy may include non-clinical and/or clinical bridging studies to support the claim for comparability, as part of a stepwise approach, but an increased understanding of the physicochemical attributes of the Adeno-Associated Virus (AAV)-based product and understanding the structure-function relationships for the product may pre-empt the need for such bridging studies. To meet this objective, the results of the comparability assessment should demonstrate that there has been no change in the structure-function relationship of the product and that there is no ambiguity in the results. In this article, the authors suggest key points for consideration when planning and executing the comparability assessment.