Commercial viral vector manufacturing: Current and future state, challenges and opportunities

With several recent FDA approvals and a strong drug pipeline, the gene therapy market is providing new hope for patients. As demand for these new therapies increases, a robust and scalable manufacturing process is critical. We will address how to mitigate the risk of contamination by adventitious agents to ensure viral vector safety used in biotherapeutics. One of the first steps in designing a process is whether to use adherent or suspension cell cultures.  Each modality has its advantages and disadvantages. This presentation will outline the key considerations in choosing the right technology and some of the pitfalls that must be overcome to ensure success at large scale will be discussed.

We will present three case studies which illustrate the strategies for viral vector manufacturing production. The first case study will demonstrate the production of lentivirus in a fixed bed bioreactor, resulting in a 1.62-fold increase in the average titer (TU/cm²). The second case study will show data regarding the development of AAV9 production in adherent HEK293 cells, utilizing the iCELLis® Nano Bioreactor. Based on conditions developed in this bench-top iCELLis Nano, we scaled production to the fully closed, single-use Xpansion® 200 Multiplate Bioreactor for seed train and the production-scale iCELLis 500 single use bioreactor. Following a production phase, >10¹⁶ vector genomes were isolated from crude harvest of the bioreactor.  The last case study will demonstrate scalability of AAV production in suspension HEK293 cells from the Allegro^TM STR 50 Bioreactor to the Allegro STR 500 Bioreactor, while achieving similar product yield and quality.