Considerations for Scaling-up Depth Filtration of Harvested Cell Culture Fluid - Data on the performance and variability of different formats. - BioPharm International
Figure 2. Experimental design: there were 27 separate depth-filter tests
Test operating conditions were the same for each filter device and size to minimize operating condition variability. Each
filter was flushed with 50 L/m2 of water for injection (WFI) at a flux of 100 LMH (liters per m2 per hour). This was lowered from the recommended 600 LMH because of pump limitations. HCCF centrate was pumped at a constant
flux of 111 LMH, representative of manufacturing-scale operation. Feed pressure and liters filtered were recorded using a
data acquisition system during processing for small-area devices and recorded manually for large-scale devices. Filtrate quality
was assessed by measuring turbidity every 40 L/m2. The run was stopped when the feed pressure reached 25 psid, past the 15 psid design limit. Pooled depth filter filtrates
from each test were also filtered through a 0.2 μm sterile filter. These sterile filter tests were run at a constant 10 psi
feed pressure and the filtered volume recorded over time. All depth filter formats were tested simultaneously and three replicates
of the test plan were completed sequentially. Replicate testing was used to determine variability in results. There were 27
separate depth-filter tests as summarized in Figure 2.
RESULTS
Figure 3. Depth filter resistance profiles
The pressure drop across each filter was calculated by subtracting the measured filtrate pressure from the feed pressure at
each time point. This pressure drop was then divided by the constant filtrate flux of 111 LMH to calculate a hydraulic resistance
as psid/LMH. Figure 3 shows the increase in filter resistance with loading for the 27 tests.
The filter resistance profiles showed a consistent shape for most filters, starting at around 0.025 psid/LMH and remaining
fairly flat, then rising fairly rapidly. The initial variability is attributed to some air locking which disappears after
a 0.05 psi/LMH resistance once the membrane intrusion pressure has been reached. The Mini capsule filters (Mini), however,
tended to show increasing resistances at higher loading compared with other filters that tended to lie together.
Figure 4. Depth filtrate turbidity profiles
Figure 4 shows the filtrate turbidity profiles for the 27 tests. These values are much lower than the average HCCF feed turbidity
of 91 NTU showing that particles are being removed by the filters. The turbidity profiles for most filtrates showed the typical
shape, a slow initial rise followed by a steady value. Contributing to the lower initial values is dilution by held-up WFI
used for flushing at about 10 L/m2. Run 3 for the 0.45 m2 Stack was an outlier with higher turbidities from the outset.
