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

Qualification of test accuracy

The important considerations for the qualification of this system include the following:

  • Filling the water tank with test water
  • Controlling the temperature of the test water
  • Controlling the water filling speed of the filter housing
  • Cooling the filter housing after steaming
  • WIT accuracy
  • Temperature compensation algorithm
  • Draining the filter housing after WIT
  • Drying the filter after draining.

All individual steps were qualified after delivery of the complete system to the end user.

The main concerns of the end user were the test accuracy, its capacity to detect a nonconforming filter, and its capacity to compensate for temperature drift. The accuracy was expected to be 5% or better.

For accuracy qualification, a test-cartridge dummy is used, which allows a small quantity of water to be removed during the measurement phase (typically 3–4 g/10 min/10 in. cartridge) and thereby simulate the water intrusion phenomenon. A high precision balance with a minimum accuracy of 0.005 g is used for weighing the water, and a temperature sensor is used to define water density.

The correlation between water weight and the water-intrusion reference value is shown in the following equation:

where WIT ref is the water intrusion reference value in ml/test time (10 min), W scale is weight on the balance in grams. P abs is the actual absolute test pressure at the beginning of the test in mbar (approximately 3500 mbar), δwater is water density in g/mL, 1000 is the reference pressure of 1000 mbar, which is different from the atmospheric pressure.

During the qualification, three different values were generated under stable temperature conditions, and WIT values of the freeze dryer were compared with the calculated reference values.

A forth value corresponding to a nonconformity test (3.9 g/10 min/10 in.) was generated and gave a nonconformity test result with the same accuracy ( 5% or better). Note that 3.9 g/10 min corresponds to a WIT value of 13.8 mL/10 min. The maximum WIT value for a Sartofluor 0.2 m 10 in. cartridge is 13 mL/10 min.

Qualification of temperature-drift compensation

Figure 5: Set-up for qualification of temperature drift compensation using electro-heating ribbon (heating resistance).
As the stainless steel part containing the compacted gas net volume was insulated, it was decided that the most appropriate way to simulate a temperature drift was to use a electro heating ribbon in direct contact with the insulation, thus representing a clear worst case because of a higher heat transfer than ambient air. The accuracy measurements were performed using the same method as for the stable temperature qualification but with the addition of heating the insulation (see Figure 5).

Results of accuracy and temperature qualification

Table I: Recorded test parameters and resulting test values.
The recorded test parameters and the resulting test values are shown in Table 1, where Atm is atmospheric pressure (mbar absolute), W is weight (g) of water removed on the scale during the measurement phase, T 0 is the gas temperature in the net volume before compaction, T 1 is the gas temperature in the compacted net volume in the beginning of the measurement phase, T 2 is the gas temperature in the compacted net volume at the end of the measurement phase before draining, "Deviation with T corr " is the deviation of the integrated measurement using the temperature correction algorithm versus the reference measurement, and "Calculation without T corr " is manual calculation of the deviations that would have been existed without temperature correction.


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