Adeno-associated virus (AAV) vectors have emerged as a leading delivery system for gene therapy. Poloxamer 188 (P188), a non-ionic surfactant, is increasingly utilized in viral vector purification and formulation to enhance AAV particle stability and prevent aggregation during the final tangential flow filtration (TFF) process. TFF employs ultrafiltration and diafiltration to exchange the buffer and concentrate the vector into the drug substance. However, the amphiphilic nature of P188 leads to micelle formation at high concentrations, and it could also have complex interactions with both the product and filtration membranes. These properties necessitate careful monitoring and control to prevent P188 co-concentration with the viral vector during processing, which could impact the final product consistency. Our study sought to understand and investigate P188 control during the TFF process. Through systematic scaled-down studies, we identified multiple factors significantly influencing P188 retention, including membrane material (type, chemistry, charge, etc.), TFF format (e.g., hollow fiber and flat sheet cassette), pore size, and operating conditions. These insights help to minimize P188 co-concentration and improve overall product quality, thus addressing a critical challenge in AAV vector purification. The learnings from this research can be applied to the general excipient control in biopharmaceutical processing.
