Considerations for Scaling-up Depth Filtration of Harvested Cell Culture Fluid - Data on the performance and variability of different formats. - BioPharm International

ADVERTISEMENT

Considerations for Scaling-up Depth Filtration of Harvested Cell Culture Fluid
Data on the performance and variability of different formats.


BioPharm International
Volume 22, Issue 3


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.


blog comments powered by Disqus

ADVERTISEMENT

ADVERTISEMENT

FDA Approves Pfizer's Trumenba for the Prevention of Meningitis B
October 30, 2014
EMA: Extrapolation Across Indications for Biosimilars a Possibility
October 30, 2014
Bristol-Myers Squibb Announces Agreement to Acquire HER2-Targeted Cancer Treatment
October 29, 2014
Contract Research and Manufacturing Organization Paragon Bioservices Raises $13 Million
October 28, 2014
Yale and Gilead Extend Sequencing Initiative
October 28, 2014
Author Guidelines
Source: BioPharm International,
Click here