The ANOVA analysis confirms that the 23.5 cm2 Mini is a major source of capacity variability (Lutz, 2006). Excluding these devices causes the total capacity variance
to drop 6x, from 4,072 (L/m2)2 to 735 (L/m2)2. This corresponds to a RSV = 6.8% (relative standard deviation = standard deviation/average). Note that the variances were
assumed independent, so they are additive while the RSV are square roots of the variance and do not add. The variance distribution
is shown in Figure 10. The variance is dominated by location with a RSV = 5.1%, which includes operator, instrumentation and
experimental error. Sequence (capacity of first versus final runs) caused mean filter capacity to decrease approximately 10%
with a RSV = 3.3%. Size and format are negligible contributors, indicating that there are minimal differences in filter capacity
between the remaining laboratory-scale Pod filter (LSP), Pod, and Stack formats. Device variability with a RSV = 3.0%, is
associated with filter variation in a single lot.
Figure 10. Variance components (excluding Mini devices)
It was anticipated that size would affect variability more significantly. Consider a larger filter or filter assembly with
area A composed of n equal small filter elements of area A. If these small elements have a mean permeability μ and a standard
deviation σ, the assembly of n elements has the same mean permeability μ and a standard deviation of either σ if the elements
are perfectly correlated or σ/√n if the filter areas are statistically independent. The actual filter should lie between these
extremes and show a reduction in variability with surface area. This can be called an averaging effect. This data shows that
from the 270 cm2 LSP device upward, the variability is somewhat constant and any averaging effect is negligible compared with the other sources.
Excluding Mini devices, Figure 11 shows that the resistance profiles for all the remaining tests lie very close together.
The capacities at 0.15 psi/LMH are 400 L/m2 +/–10%. LSP devices with 270 cm2 are the smallest-scale devices that are comparable with large- scale filter assemblies. It also suggests that the Stack
and Pod formats have equivalent capacities and can be used interchangeably. The Mini is not a preferred scaling device.
Figure 11. Depth filter resistance profiles (excluding Mini devices)
Mini devices may perform differently as a result of having low area, in which the averaging effect has not yet reduced scale
variability. It also may perform differently because the peripheral seal region is a larger fraction of the total filter area
in the Mini compared with the other filter formats. The region near the seal may have different flow because of filter media
compression. It has been observed in other testing (data not shown here) that the Mini capacity can vary up to +/–30% among
devices or between the Mini and larger devices.
A review was done of 14 different 12,000-L manufacturing-scale runs of the same monoclonal antibody product. The way these
runs were performed allowed the resistance to increase to 0.15 psi/LMH and the capacity determined. The batch-to-batch RSV
was 10%. This includes batch-to-batch variability arising from feed, filter, and operating conditions. A comparison with the
format study RSV = 6.8% confirms expectations that additional variability in capacity arises from differences in feed and
filter media lots.
The manufacturing-scale capacities closely followed a normal distribution when graphed on a quartile plot. Using a safety
factor of 1.4 sizes a filter assembly at 1.4 times the mean capacity, four relative standard deviations above the mean capacity.
The chance of requiring a larger area is given by the area under the normal distribution as one in 10,000 batches.