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

MEMBRANE REUSE STUDIES

Given the satisfactory pilot-plant and benchtop performance of the regenerated cellulose 5 kDa devices, cleaning and reuse studies at the bench-scale were conducted. The small-scale model design required at least 30 use cycles at processing conditions modeled with the commercial process conditions. Previous runs at 25 or 34 g/m2 of product load produced satisfactory outcomes; however, cycle times were longer than for the existing commercial operation. To mitigate the potential for long process cycle times during scale-up, other factors can be considered. The membrane area can be increased to further reduce the protein load and increase the permeate flow rate. In this case, the commercial operation needed to maintain process cycle times in a specific time frame, so the product load was decreased to 17 g/m2 for commercial implementation.

When designing cleaning and reuse small-scale models, it is important to conduct studies at the large-scale target load to ensure that membranes are exposed to the expected amount of product under similar processing conditions. Because of cycle time restrictions, an increase in the commercial-scale filtration area from 20 m2 to 30 m2 would provide higher permeate flow rates and total cycle times within process requirements. Along with the target product load of 17 g/m2, the concentration–diafiltration runs were performed at the same crossflow rate and TMP operating conditions as in the pilot-plant studies (2.0 LPM/m2 and 25 psig).

The preparation and cleaning phases of the membrane were designed and carried out according to the expected large-scale conditions and commercial-scale requirements. These phases included chemical storage of the membrane in the system, in which commercial system requirements could play a role. In this case, the commercial skid system was cleaned and stored in a 0.2 N NaOH solution. For the current application, the regenerated cellulose membranes were cleaned with a 0.2 N NaOH solution, but they had been stored at 0.1 N NaOH. To consolidate cleaning and storage of the membrane in the commercial skid system, storage at 0.2 N NaOH and its effects on long-term performance were investigated with the small-scale reuse studies.

The cleaning effectiveness and clearance of residual protein from the membrane was determined by execution of blank runs and by NCWP measurements. The blank runs were performed according to the product runs, with the only difference being that clean buffer was used as the process feed material. The blank runs were performed following a post-use cleaning procedure, with the goal of collecting samples for an enzyme-linked immunosorbent assay (ELISA) analysis specific to the protein of interest. The samples were verified for traces of protein and compared to acceptable criteria for post-use cleaning conditions. Four blank runs were assigned and spread throughout the 30 use cycle schedule with the intention of grouping blocks of consecutive process and cleaning cycles, thereby challenging the membrane sequential-use regimen, and thereby ensuring the uniformity and bracketing of data.


Figure 9
Figure 9 shows the NCWP recovery profile obtained for the 30 process runs and the additional 4 blank runs. NCWP measurements were taken before and after each run; therefore, 68 data points are shown. The chart shows a gradual rise in the NCWP trend, signaling potential membrane degradation over time as the membrane is subjected to the repeated cleaning and reuse cycles. However, the small rise is within the established specifications for the membrane. The final NCWP recovery obtained at the end of the cycles was 109.1%, which met the acceptance criteria for the application. The current acceptance criteria range is 70 to 130% of NCWP recovery. No impact on the performance of the membrane is expected because of the 109.1% increase in NCWP. This expectation is supported by the total average product yields for the process runs, which were at 100% with no protein losses detected through the permeate stream.


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