Key Factors Impacting Viral Retention, Protein Passage & Flow Rates in Ultrafiltration

Viral filtration by ultrafiltration membranes is a critical step to ensure viral removal in many biomanufacturing process streams. However, the nature of the feed solution and the filtration parameters used can significantly affect filter performance, product quality, and safety. In this work, the impact of three different parameters on ultrafiltration performance was investigated: 1) feed concentration, 2) protein size, and 3) inlet pressure. Findings indicate that the protein concentration of the feed solution affects flow rates in a dose-dependent manner but did not significantly alter retention of ΦX174 bacteriophage particles at the concentrations tested. Results further demonstrated that flow rates and downstream recovery of low-MW BSA were significantly higher than high-MW HgG at the same feed concentration, indicating that the molecular weight of the protein solution significantly alters ultrafiltration performance and downstream product recovery. Finally, testing showed that increasing the inlet pressure increased flow rates and throughput but decreased downstream protein recovery. Therefore, increased pressure has benefits and drawbacks that must be carefully evaluated when developing ultrafiltration process parameters.