Manufacturing recombinant adeno-associated viral vectors from producer cell clones.

A commercial rAAV manufacturing process needs to provide a safe product at high yield, be easily scalable, regulatory-compliant, and have reasonable cost of goods. Considerations for process development include not only product quantity and quality, but also ease of obtaining equipment, performing validation, and demonstrating control. In these regards, it is usually efficient to make use of proven technologies for more established areas of manufacturing, such as cell culture and purification methods used by the recombinant protein/monoclonal antibody industry.

Characterizing clearance of helper adenovirus by a clinical rAAV1 manufacturing process.

Recombinant adeno-associated viral vectors (rAAV) are being developed as gene therapy delivery vehicles and as genetic vaccines, and some of the most scaleable manufacturing methods for rAAV use live adenovirus to induce production. One aspect of establishing safety of rAAV products is therefore demonstrating adequate and reliable clearance of this helper virus by the vector purification process. The ICH Q5A regulatory guidance on viral safety provides recommendations for process design and characterization of viral clearance for recombinant proteins, and these principles were adapted to a rAAV serotype 1 purification process for clinical vectors.