With increasing interest in advanced therapy medicinal products (ATMPs) in recent years, the biopharmaceutical industry has developed and adapted manufacturing strategies. In particular, adeno-associated virus (AAV) has emerged as a leading viral vector candidate, and these processes carry an added challenge of removing large viral contaminants related to the vector expression system in addition to the usual risks of viral contamination. The applicability of nanofiltration with Planova 35N filters to separate large viral contaminants while retaining small virus particles on the size order of AAVs was examined by co-spiking experiments. Filtration feed solution spiked with bacteriophage PP7 (22-26 nm) representing viral vector and bacteriophage PR772 (64-82 nm) representing larger viral contaminants resulted in complete clearance of the larger bacteriophage (PR772) without significant reduction of the smaller capsid (PP7). Additionally, the impacts of low pressure and process interruption were investigated to demonstrate the robustness of model contaminant removal by nanofiltration. This co-spike approach serves as proof-of-concept for removing contaminant virus from gene therapy products and provides a platform for exploring and developing manufacturing strategies for ATMPs.

Demonstrating size-selective separation of virus vector and large viral contaminants by nanofiltration using bacteriophages PP7 and PR772

ACS Fall 2021

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