Process Development

AAV manufacturing process development is the stage in which early research processes are translated into a robust, scalable manufacturing process capable of producing clinical-grade gene therapy vectors. During this phase, scientists optimize upstream production and downstream purification conditions, define critical process parameters, and generate the data needed to support scalable cGMP AAV manufacturing. Effective AAV process development ensures consistent vector yield, product quality, and readiness for clinical manufacturing.

The right approach depends on your program’s specific goals, timeline, and vector characteristics. A well-designed AAV platform process, like Forge’s FUEL™ platform, is built to accommodate a range of serotypes, transgene designs, and plasmid constructs while already incorporating product-specific optimizations, so many programs can advance efficiently without standalone process development. For some programs, additional process development activities may complement the platform approach to address unique product requirements or specific manufacturing objectives. The best path forward is one that aligns with your program’s needs, and an experienced CDMO partner can help you evaluate which approach, or combination of approaches, sets your program up for success.

A Design of Experiments (DoE) is a structured statistical approach used in AAV process development to evaluate how multiple process variables affect manufacturing performance. Instead of testing one parameter at a time, DoE studies assess combinations of factors (such as transfection ratios, DNA concentration, cell density, or chromatography conditions) to identify the optimal settings. This approach accelerates process optimization and helps improve AAV yield, product quality, and reproducibility.

AAV process development establishes the process knowledge and control strategy required for successful cGMP manufacturing. Activities such as scale-down modeling, process characterization studies, engineering runs, and analytical method alignment help ensure the manufacturing process performs reliably at production scale. These studies also generate the documentation and data needed to support technology transfer, IND-enabling manufacturing, and future regulatory submissions.

Yes. Targeted AAV process development can significantly improve vector yield and full-to-empty capsid ratios by optimizing both upstream and downstream conditions. Upstream optimization (such as adjusting transfection conditions, plasmid ratios, and harvest timing) can increase genome packaging efficiency, while downstream purification strategies (such as chromatography optimization and capsid enrichment methods) can improve recovery of full capsids and overall product quality.