Use of pressure-hold test for sterilizing filter membrane integrity in radiopharmaceutical manufacturing

Nucl Med Biol. 2009 Nov;36(8):955-9. doi: 10.1016/j.nucmedbio.2009.07.008.

Abstract

The bubble point test is the de facto standard for postproduction filter membrane integrity test in the radiopharmaceutical community. However, the bubble point test depends on a subjective visual assessment of bubbling rate that can be obscured by significant diffusive gas flows below the manufacturer's prescribed bubble point. To provide a more objective means to assess filter membrane integrity, this study evaluates the pressure-hold test as an alternative to the bubble point test. In our application of the pressure-hold test, the nonsterile side of the sterilizing filter is pressurized to 85% of the predetermined bubble point with nitrogen, the filter system is closed off from the pressurizing gas and the pressure is monitored over a prescribed time interval. The drop in pressure, which has a known relationship with diffusive gas flow, is used as a quantitative measure of membrane integrity. Characterization of the gas flow vs. pressure relationship of each filter/solution combination provides an objective and quantitative means for defining a critical value of pressure drop over which the membrane is indicated to be nonintegral. The method is applied to sterilizing filter integrity testing associated with the commonly produced radiopharmaceuticals, [(18)F]FDG and [(11)C]PIB. The method is shown to be robust, practical and amenable to automation in radiopharmaceutical manufacturing environments (e.g., hot cells).

Publication types

  • Evaluation Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Equipment Design
  • Equipment Failure Analysis
  • Filtration / instrumentation*
  • Filtration / methods
  • Isotope Labeling / instrumentation*
  • Isotope Labeling / methods
  • Membranes, Artificial
  • Pressure
  • Radiopharmaceuticals / chemical synthesis*
  • Sterilization / methods*

Substances

  • Membranes, Artificial
  • Radiopharmaceuticals