Regulatory Perspective for Biologics License Application of Recombinant Adeno-Associated Virus Products in China.

Recombinant adeno-associated virus (rAAV) vectors have emerged as a leading viral vector for in vivo gene therapy because they offer significant advantages over other viral vectors, such as stable physicochemical properties, low pathogenicity, low integration risk, and long-term expression of the transgene. In recent years, the number of rAAV products that have received approval for commercial marketing and clinical trials has grown rapidly, bringing hope for the treatment of refractory and rare diseases. However, rAAV products are highly innovative and complex, and the manufacturing processes to produce them are diverse and rapidly improving. Concurrently, the quality control methodologies and technologies are rapidly advancing and evolving. As biotechnology rapidly advances, there is a heightened need for communication between regulatory authorities and entities applying for rAAV products to be used for in-human trials or commercial marketing. Here, we focus on the discussion of chemistry, manufacturing, and control issues such as the control of adventitious viruses in different manufacturing processes and quality control during the biologics license application of rAAV products. It is expected to provide references and suggestions for the manufacturing and quality control of rAAV vectors, thereby accelerating the high-quality development of gene therapy products.