Draining the housing and drying the filter
After WIT, the filter housing is drained. Drying the hydrophobic filter after WIT is particularly important with regard to
freeze dryers because the exposure of a wetted filter to high vacuum levels would lead to ice crystal formation in the membrane
and damage the filter cartridge.
The standard method of drying, which involves dry air or nitrogen flow over the filter (without going through the membrane),
together with heating the upstream gas flow, has been shown to be inefficient within an acceptable period of time. The drying
procedure used for the freeze dryer in this article uses a water ring vacuum pump. The residual moisture in the filter was
then dried under a low vacuum and exhausted by the induced gas flow through the filter.
The drying-procedure parameters for one filter manufacturer are not necessarily transferable to another manufacturer as filter
construction has a strong influence; a single layer construction is easier to dry than a double layer construction when humidity
is trapped between the two membranes.
- Optimal drying conditions include the following:
- High flow rate through the membrane
- High temperature (e.g., 80 °C)
- Low pressure (e.g., 500 mbar absolute).
At high temperatures, it is preferable to use nitrogen gas to avoid oxidization of the polypropylene fleeces in the cartridge.
Qualification of drying
The qualification of the drying is based on the weight of the cartridge. The cartridge is weighed out of its box, and its
value is recorded. After WIT, the cartridge is weighed again, and its value is recorded. The drying cycle is then launched
and interrupted on a regular basis (e.g., every 10 min) and the weight of the cartridge is recorded again. The cartridge must
return to its original weight within ± 0.5 g/10 inch.
Integrating WIT within SCADA and the freeze dryer control system (or any other type of equipment) gives straight forward test
results without imposing additional downtime and without imposing operator influence. It therefore answers the request for
increased process security in accordance with regulatory requirements.
The operational qualification described in this paper demonstrates an accuracy of ± 5% or better. The qualification of the
temperature drift compensation had to be conducted under extreme conditions because of the insulation. Despite the electro
heating ribbon being in direct contact with the insulation, the low temperature drift (max 0.7 °C) shows that this kind of
insulation is sufficient for preventing temperature drift caused by environmental conditions. Nevertheless, it is clear that
from a process safety point of view, temperature compensation gives undeniable evidence for test result accuracy.
The large difference between the reference WIT value and the calculated WIT value when no temperature compensation was used
shows the great influence of temperature variation on the test value and the risk of getting false conformity or false nonconformity
test results. Environmental conditions must therefore always be taken into account in the risk analysis for filter integrity
The deviation of –4.7% when heating 0.7 °C (read from the temperature probe), compared with a deviation of around +2% under
stable conditions, most probably comes from the fact that the heating was unevenly done and therefore generated temperature
gradients within the gas net volume. Also, the temperature probe did not cover the full length of the gas volume. This point
could be improved upon from an engineering perspective. Nevertheless, the test accuracy was within the defined limit. This
comprehensive qualification of the test process responded to the expectation of quality assurance in a pharmaceutical environment
and gave a traceable guarantee for the integrity of the cartridge when performed within the limits of the defined parameters.
Magnus Stering* is head of application specialists for filtration technology southern Europe at Sartorius Stedim Biotech, firstname.lastname@example.org
. Nicolas Debruyne is senior engineer, global technical services at GSK Biologicals, and Gianfranco Castiglioni is senior field service and qualification expert at IMA Life.
*To whom all correspondence should be addressed.
Submitted: Aug. 22, 2011. Accepted: Sep. 26, 2011.
1. European Commission, EudraLex Vol. 4: Good Manufacturing Practice (GMP) Guidelines, Annex 1: Manufacture of Sterile Medicinal
2. T. H. Meltzer, M. Jornitz, and P. J. Waibel, Pharm. Technol.
(9) 76–84 (1994).