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


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

Figure 5
Figure 5 shows resulting trends for a concentration process with a PES-based 8 kDa membrane system. The trends show a steady decline of the process flux while exhibiting a steady rise of the permeate UV curve. The rise is particularly distinctive during the latter stages of the concentration. The process was run at a product load of 51 g/m2; however, similar trends were obtained at 34 and 25 g/m2. The mass balance showed a 2.5% loss of product through the permeate stream and a total recovery of 96%. Product recoveries for the PES-based 8 kDa systems ranged from 91.2 to 96.0%, and permeate losses ranged from 2.5 to 6.2%. Given this data, PES-based 8 kDa devices clearly are not the best option to maximize yield for this application. With flux values from 80.1 to 53.3 LMH, for the PES-based 8 kDa systems the only benefit observed was the fast processing time. However, permeate losses and decreases in flux performance were the main factors considered to reject the devices. In addition, with simple caustic regimes it was impossible to clean the soiled membranes and restore their permeability to the acceptable criteria for further reuses.

Figure 6
Figure 6 shows the resulting trends for a PES-based 5 kDa concentration at a 34 g/m2 protein load. A steady flux decrease was also noted. However, the permeate absorbance profile did not show a trend indicative of product loss. The absorbance oscillated around values well below the ones observed for the PES-based 8 kDa device, indicating better retention for the PES-based 5 kDa membrane. Recoveries for this latter device ranged from 95.3 to 100%. The average flux values ranged from 34.6 to 24.2 LMH for this system, leading to slower process cycle times in comparison to the PES-based 8 kDa device; this was obviously related to the smaller pore size.

Figure 7
Figures 7 and 8 show trends for regenerated cellulose 5 kDa TFF small-scale processes. Figure 7 corresponds to a concentration run at 25 g/m2 load with a crossflow rate of 3.0 LPM/m2 and a TMP of 20 psig. Figure 8 shows a concentration–diafiltration run at a 34 g/m2 protein load. Crossflow rate and TMP were set at 2.0 LPM/m2 and 25 psig for this system. As the figures show, the flux profiles were very stable with minor flux degradation. Permeate absorbance trends were also very stable and were contained under values leading to nondetectable protein losses. The permeate flux values ranged from 13.0 LMH to 14.5 LMH for the regenerated cellulose 5 kDa systems, leading to the longest cycle times. The stable flux profiles were a result of the low binding nature of the membranes, which led to minimal fouling. This benefit, combined with the absence of permeate product losses, outweighed that of longer cycle times for commercial implementation of this application. Provided a satisfactory cleaning and reuse result, the longer cycle time was offset by the time savings of not needing to install new cassettes for every lot processed. Table 1 shows a performance comparison summary of the three membrane devices.

Figure 8

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