TY - JOUR
T1 - Use of pressure-hold test for sterilizing filter membrane integrity in radiopharmaceutical manufacturing
AU - Belanger, Anthony P.
AU - Byrne, John F.
AU - Paolino, Justin M.
AU - DeGrado, Timothy R.
N1 - Funding Information:
The work was funded in part by the NIH (CA108620, CA114839).
PY - 2009/11
Y1 - 2009/11
N2 - 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).
AB - 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).
KW - Filter membrane integrity
KW - Pressure-hold test
KW - Radiopharmaceutical
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U2 - 10.1016/j.nucmedbio.2009.07.008
DO - 10.1016/j.nucmedbio.2009.07.008
M3 - Article
C2 - 19875052
AN - SCOPUS:70350234477
SN - 0969-8051
VL - 36
SP - 955
EP - 959
JO - Nuclear Medicine and Biology
JF - Nuclear Medicine and Biology
IS - 8
ER -