Single-Pass Tangential Flow Filtration (SPTFF) of Nanoparticles: Achieving Sustainable Operation with Dilute Colloidal Suspensions for Gene Therapy Applications

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Abstract

Recent approval of several viral-vector-based therapeutics has led to renewed interest in the development of more efficient bioprocessing strategies for gene therapy products. Single-Pass Tangential Flow Filtration (SPTFF) can potentially provide inline concentration and final formulation of viral vectors with enhanced product quality. In this study, SPTFF performance was evaluated using a suspension of 100 nm nanoparticles that mimics a typical lentivirus system. Data were obtained with flat-sheet cassettes having 300 kDa nominal molecular weight cutoff, either in full recirculation or single-pass mode. Flux-stepping experiments identified two critical fluxes, one based on boundary-layer particle accumulation (Jbl) and one based on membrane fouling (Jfoul). The critical fluxes were well-described using a modified concentration polarization model that captures the observed dependence on feed flow rate and feed concentration. Long-duration filtration experiments were conducted under stable SPTFF conditions, with the results suggesting that sustainable performance could potentially be achieved for as much as 6 weeks of continuous operation. These results provide important insights into the potential application of SPTFF for the concentration of viral vectors in the downstream processing of gene therapy agents.

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APA

Chaubal, A. S., & Zydney, A. L. (2023). Single-Pass Tangential Flow Filtration (SPTFF) of Nanoparticles: Achieving Sustainable Operation with Dilute Colloidal Suspensions for Gene Therapy Applications. Membranes, 13(4). https://doi.org/10.3390/membranes13040433

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