Streamlining viral safety in AAV manufacturing: Simultaneous cell lysis and viral inactivation using biodegradable detergents

Abstract

Ensuring viral safety in biopharmaceutical production is vital for global regulatory standards adherence and safeguarding patients. This study evaluates the efficacy of newly developed biodegradable detergent formulations, designed to comply with regulatory requirements, for inactivating enveloped viruses during the cell lysis step of adeno-associated virus (AAV) production. Virus clearance (VC) studies showed robust inactivation kinetics against Xenotropic Murine Leukemia Virus (XMuLV), achieving a log reduction value (LRV) of ≥5.34 within 30 to 120 min. Comparative testing in crude cell lysate and PBS buffer showed consistent viral inactivation across different matrices, highlighting the versatility of the detergent formulations. Importantly, the detergent composition preserved AAV capsid integrity, and subsequent purification steps, including affinity and ion-exchange chromatography, effectively removed residual detergent. Overall, this study demonstrates the potential of biodegradable detergents to simultaneously facilitate cell lysis and viral inactivation in AAV manufacturing, offering a sustainable alternative that aligns with industry standards.

Keywords: AAV manufacturing; Biodegradable detergent; Cell lysis and; Log reduction value (LRV); Regulatory-compliant; Viral inactivation.