Sequence identity confirmation for genetically modified products is a regulatory expectation to demonstrate that the product contains the intended sequence. This is relevant to products such as virus-based vaccines, virus seeds, and viral vectors used in gene therapy applications, as well as nucleic acid based therapeutic products such as plasmids or RNA. Identity testing is usually established early in the development process and performed on starting materials such as plasmids or virus seed stocks. Following production, sequencing can also be used to establish vector identity and production consistency.
Identity testing can be performed using a variety of molecular-based methods ranging from restriction enzyme analysis and product-specific PCR methods to sequencing. The strategy for establishing identity using one of these methods may differ depending on the product and stage of product development. However, sequencing techniques play a crucial role in establishing the quality attributes of a variety of therapeutic products.
Regulators set high expectations on drug manufacturers to establish the sequence identity and stability of viral and non-viral vectors used for gene delivery. Next generation sequencing (NGS), also known as high-throughput sequencing, has emerged as a useful state-of-the-art method to establish product quality through sequence identity.