Considerations for Scaling-up Depth Filtration of Harvested Cell Culture Fluid - Data on the performance and variability of different formats. - BioPharm International
Figure 5. Sterile filter resistance ratio profiles
Filtrate quality was also assessed by running the pooled depth filter filtrate through a 0.2 μm sterilizing filter. Sterile
filter plugging is assessed by calculating the ratio of the sterile filter hydraulic resistance at each time point divided
by its initial hydraulic resistance for each test. This ratio is obtained by numerically differentiating the weight versus
time data. Figure 5 shows the calculated ratio for 21 tests. Run 3 for the 0.45 m2 Stack was an outlier with rapidly increasing resistances with loading. This mirrors the higher turbidity results. The remaining
resistance ratios show consistently low resistance increases. There are some sporadic spikes in the ratio attributed to accidental
bumping of the scales.
DISCUSSION
Turbidity Outlier
Figure 6. Lenticular stack seal failure
The housing was disassembled for the 0.45 m2 Stack that was an outlier on turbidity and sterile filter profiles. The top gasket seal had failed to contact the adjacent
seal as shown in Figure 6. The nonintegral seal is considered a source of feed bypass and the data from this run was not considered
in further variability analysis.
Plugging Model Analysis
Figure 7. Plugging model analysis
The resistance profiles for the different filter formats and sizes were fit to different plugging models (see Appendix for
details): gradual pore plugging, cake filtration, intermediate plugging, complete pore blockage, cake-complete combined model,
second-order polynomial, and third-order polynomial. Figure 7 shows an example of the model fits for one resistance profile.
The empirical polynomial models fit the data best using more adjustable parameters. Of the mechanistic models, the combined
cake-complete plugging model provided the best fit of the data. This is consistent for the multilayer filter used in this
study that has a cast membrane layer in series with the cellulose media.
Table 2. Plugging model analysis
Table 2 shows that the combined cake-complete plugging model provided a good fit for all devices, and the magnitudes of the
best-fit parameters were comparable between formats. This provides a more quantitative assessment that the resistance curves
are similar for all devices and suggests that all format types plugged by similar mechanisms with similar magnitudes of feed
and filter interactions.
