The production of clinical-grade AAV involves many steps to ensure the quality and safety of the final product. The first stage of any campaign is process development
, in which various parameters involving the source plasmids, producer cell lines, and purification methods are optimized. Following this step, procedures must be adapted to the larger scales necessary to generate the increased amounts of material required for clinical trials. Next, an engineering run is performed to confirm that all of the processes and procedures yield the expected amount of virus at the larger scale. After the engineering run, a CGMP run that fully complies with FDA and EMA guidelines is performed. This is the run that produces the actual material for clinical use. However, before this material can be used in patients, quality control testing must be conducted in order to confirm the final product’s identity and purity. Finally, release testing must also be completed before the final product is deemed ready for use in patients. The release testing confirms sterility and stability of the final product. Altogether, it can take 10-15 months to complete a CGMP project.