Clogging model analysis for aggregate-spiked mAb
Evaluation of the filtration behavior for the reference, control,
mixed-mode AEX1 output and normal AEX output for aggregate-spiked mAb
solutions in Figure 1 with each of the four clogging models is shown in
Figure 4. The reference solution (no aggregate spike) and the output
from mixed-mode AEX1 (complete removal of larger aggregate species)
showed good agreement between experimental and calculated values, with
plots for all four models being almost entirely identical and
overlapping with the plot of experimental results (Figure 4a and 4c). In
contrast, the control (aggregate-spiked mAb) and output from normal AEX
(minimal aggregate removal) had different plots for each clogging model,
and in both of these cases, the standard blocking model plot overlapped
the most with experimental values (Figure 4b and 4d).
The calculated k for output from mixed-mode AEX1 and mixed-mode AEX2 was
smallest, at around 0.001, followed by reference (no aggregate spike) at
around 0.002 (Figure 5a). For these solutions with low proportions of
aggregate, k was almost the same for all four clogging models, and all
of the clogging models show good agreement with experimental values. On
the other hand, the control, output from normal AEX and output from
nylon prefilter (all three solutions having relatively high proportions
of larger aggregate content) had markedly higher k than column output
from mixed-mode AEX (low proportion of aggregate), and the higher the
aggregate content, the larger the k. Further, for all three solutions
with larger aggregates, the k decreased in the order of cake filtration,
intermediate blocking, standard blocking and complete blocking models.
The differences between experimental and calculated values for each
solution with all four clogging models in Figure 5b show that for
solutions with high aggregate content and high k filtered on a virus
filter at constant pressure, the standard blocking model is the best
fit. On the other hand, for solutions with low aggregate proportion and
small k, there was practically no difference between experimental and
calculated values for all four clogging models, and it is suggested that
the clogging model results are indistinguishable from each other for
solutions with stable filtration behavior without clear clogging for the
throughput tested.