Overcoming manufacturing challenges for advanced therapies

Filmed live at Advanced Therapies Week 2025, this AT-TV episode features Rachel Legmann, Senior Director of Technology at Repligen, discussing the critical obstacles in viral vector manufacturing and how the industry can address them to improve outcomes in advanced therapies.

Legmann identifies several interconnected challenges: the high cost of goods, process complexity, low cell density yields, inefficient transient transfection at scale, and difficult downstream purification due to intracellular vector localization. She also emphasizes the need for risk mitigation strategies, including single-use systems, closed processing, and automation to reduce human error and batch variability.

Central to the discussion is the integration of Process Analytical Technologies (PAT). Repligen is advancing real-time monitoring tools that provide direct measurements of product quality attributes—such as full-to-empty capsid ratios in AAV manufacturing. These innovations help optimize processes, improve product consistency, and facilitate faster, more informed decision-making on the manufacturing floor.

While AAV and lentiviral vectors remain dominant, Legmann sees potential in emerging non-viral delivery methods, such as mRNA-based therapies, though she is realistic about timelines. She stresses the importance of continuously improving existing viral vector platforms while cautiously advancing alternative modalities.

Legmann’s holistic approach advocates for purpose-built technologies that ensure molecule integrity throughout production, paired with better analytical tools to unlock efficiency and scalability in biomanufacturing.