Water-Intrusion Test Integration - Pharmaceutical Technology

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Water-Intrusion Test Integration
The authors describe the operational qualification of test accuracy with regard to temperature drift using a thermal-compensation algorithm on several freeze dryers.


Pharmaceutical Technology
pp. 64-70

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.

Conclusion

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 testing.

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,
. 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.

References

1. European Commission, EudraLex Vol. 4: Good Manufacturing Practice (GMP) Guidelines, Annex 1: Manufacture of Sterile Medicinal Products (2009).

2. T. H. Meltzer, M. Jornitz, and P. J. Waibel, Pharm. Technol. 18 (9) 76–84 (1994).


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