Bioanalysis of adeno-associated virus gene therapy therapeutics: regulatory expectations

The number of gene therapy (GTx) modality therapies in development has grown significantly in the last few years. Adeno-associated virus (AAV)-based delivery approach has become most prevalent among other virus-based GTx vectors. Several regulatory guidelines provide the industry with general considerations related to AAV GTx development including discussion and recommendations related to highly diverse bioanalytical support of the AAV-based therapeutics. This includes assessment of pre- and post-treatment immunity, evaluation of post-treatment viral shedding and infectivity, as well as detection of transgene protein expression. An overview of the current regulatory recommendations as found in currently active and published draft US FDA and EMA guidance or guideline documents is presented herein.