MAY 20259LIFE SCIENCES REVIEWDare to Innovate Overcome the main manufacturing challenges One must integrate an advanced manufacturing platform approach to significantly enhance viral vector overall yield leading to AAV and lentivirus (LV) process cost reduction and therefore, affordable virus based therapeutic drug. To meet the high vector demand, the market is moving into suspension cells or producer cell line, even though their current specific productivity is lower, the process can be scalable. To enhance the vector yield for the suspension cells it is critical to integrate a better fit perfusion system into the vector production bioreactor enabling both higher growth and continuous harvest during production. The perfusion system, such as the tangential flow depth filtration (TFDF) is a great fit to vector production since it does both. This perfusion system currently benefits mostly envelope viruses that are secreted outside the cells like lentivirus, retrovirus, VSV and many current AAV serotypes that are secreted outside the cells. Higher recovery yield of the functional vector and process performance consistency, at all manufacturing scales and during each of the downstream step, can be achieved by using systems that were designed by having the needs for advanced therapy medicinal products (ATMP) in mind. The main design features of concentration and purification systems should have over-molded tubing connections, compact XO valve designs, combining filter and bubble trap, and advanced gradient control enabling consistent and better separation of AAV during the polishing step functions primarily to separate capsid lacking DNA (empty) from capsid containing DNA (full). Systems that have those features such as RS TFF system and KRM chromatography system enable increased process efficiency and overall process step yield, protect potency and product integrity, reduce the overall risk of deviations through design, and enhance user experience.Another major challenge in the vector production process is the lack of on-line rapid and accurate analytical tools. The implementation of the FlowVPX System technology with variable pathlength technology (VPT) can offer a quick and direct total viral vector analysis during development to enhance throughput and improve decision-making. Willing to build an agnostic single use and closed automated platform by adopting advance technologies that are better fit to large fragile viruses, should enhance vector yield through process efficiency as well as protecting vector potency and integrity, reduce deviation risks through process control and meet vector demand at affordable cost. Advanced technologies are needed to meet the vector demand and provide the required reliability and robustness for manufacturing, enabling gene therapies to meet their full potential
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