A “>” preceding the logarithmic reduction factor (R)
combined with a “no” result for the parameter “virus breakthrough”
indicates removal below the limit of detection for all of the filtrate
fractions.
If minimal virus infectivity was found in a minority of the filtrate
fractions (i.e., the titers were at the limit of detection) then the
result for virus-breakthrough is “minimal”.
In the meanwhile, new filters are continuously being developed – some
of which focus on increasing throughput whilst maintaining virus
clearance capacity. These improved 2nd generation
filters reduce the filter area demand for large volume virus filtration,
and thus reduce facility floor footprint for large-volume filtration, as
well as filter cost.
All investigated filters showed a significantly higher initial feed flow
rate than the until then commercially available filters (see Table 4).
This led to higher initial throughput, but filter fouling occurred
relatively early for all filters.
For filter SG IV this is probably the reason for the termination of the
process due to significant flow decay within 1 to 2 days after up to
3,900 L/m² had been filtered. For this filter virus reduction was
effective – with mean R values of 4.4 and 3.7 log10 but
virus breakthrough was observed in most filtrate fractions. Nonetheless,
this filter is a significant improvement to filter FG III from the same
manufacturer, with which only 2.6 log10 MMV reduction
was achieved. This filter could be suitable for batch filtration prior
to the actual fermenter process.
Filter SG V showed an increased initial flow rate when compared to
filter SG I of the same manufacturer, but all other parameters such as
throughput and duration were not as good. Furthermore, although virus
reduction was effective (mean R value: 4.4 log10) it was
significantly lower than what was achieved for filter SG I (5.0 to
>6.5 log10).
Filter SG III shows a significant improvement of the filter
characteristics with respect to high volume long duration filtration
when compared to filters FG I and FG II from the same vendor. The same
can be said about developmental filter SG VI when compared to filter
FG IV of the same manufacturer (however, when compared to filter SG II
– which is an early 2nd generation filter from the
same vendor – no significant improvements can be seen).