Evaluation of various membranes at different fluxes to enable large‐volume single‐use perfusion bioreactors

Citations Over Time

Abstract

The growing demand for biological therapeutics has increased interest in large-volume perfusion bioreactors, but the operation and scalability of perfusion membranes remain a challenge. This study evaluates perfusion cell culture performance and monoclonal antibody (mAb) productivity at various membrane fluxes (1.5-5 LMH), utilizing polyvinylidene difluoride (PVDF), polyethersulfone (PES), or polysulfone (PS) membranes in tangential flow filtration mode. At low flux, culture with PVDF membrane maintained higher cell culture growth, permeate titer (1.06-1.34 g/L) and sieving coefficients (≥83%) but showed lower permeate volumetric throughput and higher transmembrane pressure (TMP) (>1.50 psi) in the later part of the run compared to cultures with PES and PS membrane. However, as permeate flux increased, the total mass of product decreased by around 30% for cultures with PVDF membrane, while it remained consistent with PES and PS membrane, and at the highest flux studied, PES membrane generated 12% more product than PVDF membrane. This highlights that membrane selection for large-volume perfusion bioreactors depends on the productivity and permeate flux required. Since operating large-volume perfusion bioreactors at low flux would require several cell retention devices and a complex setup, PVDF membranes are suitable for low-volume operations at low fluxes whereas PES membranes can be a desirable alternative for large-volume higher demand products at higher fluxes.

Related Papers

• → Living With Heterogeneities in Bioreactors: Understanding the Effects of Environmental Gradients on Cells(2006)384 cited
• → Stirred Bioreactors(2016)23 cited
• → Development, Engineering and Biological Characterization of Stirred Tank Bioreactors(2018)16 cited
• → Bioreactor for biopharmaceutical production: Simple controlled environment design(2018)1 cited
• → Scale-Up Production of Bioactive Compounds Using Bioreactors(2022)1 cited