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


Table 1. Summary of laboratory scale developmental runs for PES 8 kDa, PES 5 kDa, and regenerated cellulose 5 kDa systems
Based on the performance observed during bench-scale experimentation, the regenerated cellulose 5 kDa devices offer the best qualities and risk-benefit profile. Quality testing showed no detrimental effect on the purity and identity of the product. The regenerated cellulose membranes at the 5 kDa MWCO specification offered the best product recovery and cleaning and reuse potential; therefore, development and scale-up activities continued with a pilot-plant trial.

PILOT-PLANT STUDIES

Regenerated cellulose cassettes with 2.5 m2 membrane area were used for the pilot-plant runs. The protein load target was set at 34 g/m2. To process the available material at this product load, 10 m2 of filtration area were required. To prepare the system, four membrane devices were assembled, flushed, integrity tested, sanitized, reflushed, and buffer equilibrated. The pilot system was manually constructed with flexible hoses, a recirculation pump, cassette housing, and line elements, such as flow meters, pressure transmitters, manual valves, and temperature elements. A 100-L vessel served as the retentate tank, and a 750-L portable tank contained the diluted bulk protein product.


Table 2. Pilot plant run summary for regenerated cellulose 5 kDa
During the membrane preparation activities, an initial NCWP measurement was taken before equilibration to provide a baseline NCWP. The baseline NCWP was measured at 0.975 LMH/psig. On completion of preparation and equilibration activities, the concentration–diafiltration process was carried out. Crossflow rate and TMP parameters were set at 2.0 LPM/m2 and 25 psig respectively, because bench-work development had demonstrated satisfactory performance at these values. Table 2 provides a summary of the performance highlights noted with the pilot-plant run.

Two buffer flushes equal to 1.2 system hold-up volumes were performed after the initial product transfer out, each with 15-minute circulation periods. A crossflow rate of 0.5 LPM/m2 was used during the circulations to rid the membrane of any remaining traces of product. In the end, a final recovery of 98.9% was achieved. Ultraviolet analyses on permeate samples found no detectable product losses.

Process flux was at a steady 13.8 LMH during the concentration phase, before drifting slightly to 12.6 LMH at the end of diafiltration. These values are in line with benchtop data and further support the low protein-binding qualities of the regenerated cellulose membranes toward the molecule in question. Given the minimal membrane soiling experienced at the pilot scale, post-use cleaning was performed with a simple caustic solution of 0.2 N NaOH. Room temperature conditions were used, and cleaning crossflow rates and TMPs were similar to the ones used during product processing.

The NCWP increase or decrease over time is measured in terms of NCWP recovery. NCWP recovery is defined as:




On cleaning and flushing the membranes to the required neutrality conditions, a final NCWP measurement was taken and measured at 0.99 LMH/psig. This signified a 101.5% NCWP recovery, which met the acceptable criteria for reuse, and which was much better than previous results with PES-based 8 kDa devices.


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