Evaluation of the bubble point test of a 0.22-μm membrane filter used for the sterilizing filtration of PET radiopharmaceuticals
- 554 Downloads
We developed a bubble point test kit and investigated the bubble point test of a 0.22-μm membrane filter used for the sterilizing filtration of [18F]FDG, [11C]MET and [11C]PIB. The bubble point test of the Millex-GS vented filter was often difficult due to air leakage from the vented portion of this filter. Therefore, to close the vented portion of this filter simply and reliably, we investigated the use of various materials.
The bubble point test of the Millex-GS vented filter was performed by closing the vented portion of this filter with various materials, such as vinyl tape, plastic paraffin film (parafilm), urethane elastomer adhesive mat and polyethylene foam cushion tape. Gradually, the plunger inside a syringe filled with air was pushed down to increase the pressure on the pressure gauge and the bubble point test kit. Simultaneously, the pressure when a continuous stream of air bubbles that appeared out of the 0.22-μm membrane filter was measured as the product-wetted bubble point value. Then, the plunger inside a syringe filled with 10 mL of water was pushed down to wash the 0.22-μm membrane filter. As in the case in the above-mentioned method of measuring the product-wetted bubble point, the water-wetted bubble point value was measured.
The use of the polyethylene foam cushion tape and a double clip could easily and reliably prevent air leakage from the vented portion of the Millex-GS vented filter. In the bubble point test of [18F]FDG, [11C]MET and [11C]PIB, the product-wetted bubble point values were 382.7 ± 6.9 kPa, 385.4 ± 6.2 kPa and 351.6 ± 7.6 kPa, respectively. The bubble point ratio was used to determine the minimum product-wetted bubble point value. All results of the product-wetted bubble point test were beyond the minimum product-wetted bubble point value (334.4 kPa ([18F]FDG), 334.4 kPa ([11C]MET) and 310.3 kPa ([11C]PIB)). Then, the water-wetted bubble point values were 396.5 ± 8.3 kPa, 395.8 ± 8.3 kPa and 390.3 ± 7.6 kPa, respectively. All results of the water-wetted bubble point test were beyond the filter manufacturer’s minimum bubble point specification (344.8 kPa).
The bubble point test technique using the bubble point test kit was practical for routine quality control tests of PET radiopharmaceuticals.
KeywordsSterilizing filtration Integrity test Bubble point test PET radiopharmaceutical
The authors thank the staff assigned to quality control tests of PET radiopharmaceuticals at the Department of Pharmacy, Oita University Hospital.
- 3.United States Pharmacopeia; <823> Positron Emission Tomography Drugs for Compounding, Investigational, and Reseach Uses. USP 35-NF30; 2011.Google Scholar
- 4.Japanese Pharmacopeia; General Information terminal Sterilization and Sterilization Indicators. 16th edition (English version); 2011.Google Scholar
- 5.Emory SF. Principles of integrity-testing hydrophilic microporous membrane filters. Part I. Pharm Tech. 1989;13:68–77.Google Scholar
- 6.Millipore technical publications; Millex-Sterivex Integrity Tester (Cat. No. SLTEST000, Lit. No. P34324). 2006; Available at: http://www.millipore.com/userguides/tech1/p34324.
- 10.Kashino G., Kano F., Hayashi k., Douhara K., Ohashi K., Yano T., The sterility assurance of PET diagnostic agents in advanced molecular imaging center (AMIC) at Oita university. Pharm Tech Japan., 2013; 29: 61–65.Google Scholar
- 11.Desaulniers C, Fey T. The product bubble-point ratio and its use in filter integrity testing. Pharm Tech. 1990;14:42–52.Google Scholar
- 12.Haque ME., Das AR. and Moulik SP. Mixed Micelles of Sodium Deoxycholate and Polyoxyethylene Sorbitan Monooleate (Tween 80). J col interface sci.1999; 217: 1 − 7.Google Scholar