title: Use of pressure-hold test for sterilizing filter membrane integrity in radiopharmaceutical manufacturing.
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).
authors.affiliation: Brigham and Women's Hospital, Boston, MA 02115, USA.
authors.forename: Anthony P
authors.initials: AP
authors.lastname: Belanger
authors.forename: John F
authors.initials: JF
authors.lastname: Byrne
authors.forename: Justin M
authors.initials: JM
authors.lastname: Paolino
authors.forename: Timothy R
authors.initials: TR
authors.lastname: DeGrado
mesh_terms: D004867:Equipment Design; D019544:Equipment Failure Analysis; D005374:Filtration / Q000295:instrumentation* / Q000379:methods; D007553:Isotope Labeling / Q000295:instrumentation* / Q000379:methods; D008567:Membranes, Artificial; D011312:Pressure; D019275:Radiopharmaceuticals / Q000138:chemical synthesis*; D013242:Sterilization / Q000379:methods*
chemical_list: D008567:Membranes, Artificial; D019275:Radiopharmaceuticals