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

Anthony P. Belanger, John F. Byrne, Justin M. Paolino, Timothy R. DeGrado

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

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, [18F]FDG and [11C]PIB. The method is shown to be robust, practical and amenable to automation in radiopharmaceutical manufacturing environments (e.g., hot cells).

Original languageEnglish (US)
Pages (from-to)955-959
Number of pages5
JournalNuclear Medicine and Biology
Volume36
Issue number8
DOIs
StatePublished - Nov 1 2009

Keywords

  • Filter membrane integrity
  • Pressure-hold test
  • Radiopharmaceutical

ASJC Scopus subject areas

  • Molecular Medicine
  • Radiology Nuclear Medicine and imaging
  • Cancer Research

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