Improving Tangential Flow Filtration Yield - How to maximize product yield and membrane lifetime to enhance a tangential flow filtration process. - BioPharm International

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Improving Tangential Flow Filtration Yield
How to maximize product yield and membrane lifetime to enhance a tangential flow filtration process.


BioPharm International
Volume 21, Issue 7

During the initial phase of laboratory-scale process development, three types of membranes were tested to screen out the two with the lowest performance potential. The following membrane devices were tested: a PES-based 8 kD device (current); a PES-based 5 kD (new); and a regenerated cellulose–based 5 kD device (new).


Figure 1
Flux (JF) is the permeate flow rate per unit surface area (in this case, in L/min.h or simply, LMH). To assess process optimization performance in regard to crossflow rates, TMPs, and their associated permeate flow rates, JF-versus-TMP curves were constructed for each membrane. Crossflow rates and TMP ranges were selected according to commercial process capabilities. To ensure performance assessments over the entire process range, the JF-versus-TMP curves were developed at both the initial and final protein concentration levels. Figures 1 and 2 show the JF-versus-TMP relationships for the three membranes types at the approximate initial and final concentration levels, respectively.


Figure 2
As shown in Figures 1 and 2, the PES-based 8 kDa membranes exhibited the highest permeabilities across the crossflow rates and TMP ranges studied. Both 5 kDa membranes had lower flux profiles, with the regenerated cellulose device showing the least permeability. Flux profiles are a good predictor of process cycle times. Flux profiles should be evaluated for decreasing trends, which could signal fouling or excessive polarization across the membrane surface. In this case, when comparing both PES-based devices, researchers noted lower permeabilities with the higher concentration profiles shown in Figure 2. This fact translates into a flux decrease during the concentration process, as a result of membrane polarization or fouling. Although the regenerated cellulose membranes led to slower cycles times because of their lower permeabilities, they exhibited more stable flux profiles than did the PES-based membranes. The flux profiles were essentially the same for all evaluated crossflow rates and protein concentration levels. This fact shows that the regenerated cellulose membranes are less susceptible to membrane polarization or fouling with the protein of interest. In addition, because the PES-based 8 kDa membrane pore size is the largest of the three membranes tested, its flux is the most dependent on crossflow rates; hence, the PES-based 8 kDa membrane showed a greater variability in performance.


Figure 3
Higher permeabilities could also lead to product losses through the membrane. Transmissibility refers to the permeability, or transmission, of the product component through the membrane layers. Figures 3 and 4 show the transmissibility profiles according to permeate absorbance measurements taken during the JF-versus-TMP trials. The absorbance measurements are given in milli-absorbance units (mAU).


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