Validation of sterility testing of radiopharmaceuticals by membrane filtration for reduction of the radiation dose

USP/BP/EP/IP recommended sterility testing is performed by majority of the radiopharmacy centres, by membrane filtration or direct inoculation method depending upon the volume of radiopharmaceuticals. Since, direct inoculation method subject the analyst to high radiation exposure, present study was planned for standardization and validation of a low cost sterility testing of different radiopharmaceuticals by membrane filtration method. The membrane filtration method was initially validated by performing growth promotion test with Staphylococcus aureus, Bacillus subtilis and Candida albicans at different cell concentrations ranging from 0 to 100 CFU and by serial dilution and spread plate method. The cell concentrations were also confirmed spectrophotometrically by taking OD at 560 nm. Radiopharmaceuticals like (¹⁸F)FDG, (¹⁸F)NaF, (¹⁸F)FLT, (¹⁸F)FMISO, (¹⁷⁷Lu)DOTANOC and (⁹⁹m Tc)TcO₄− (1.5 ml) at concentrations of 3, 1 and 0.5 mci/ml, were aspirated in syringe and passed through 0.22 μm sterile syringe filter (polyether sulfone/mixed cellulose ester -membrane). This was followed by aspiration of 20 ml growth medium through the same filter into sterile syringe and incubation of syringe in vertical position at appropriate temperature for 14 days. For comparison, sterility testing (positive and negative cultures) was also performed for the same samples of radiopharmaceuticals by direct inoculation using 20 ml of growth medium. Results: Luxuriant growth same as the positive control, was observed in the all the radiopharmaceuticals and at various concentrations for all the micro-organisms used. This was confirmed by CFU using spread plate method. Positive and negative controls used in both the methods exhibited expected results of presence and absence of growth respectively. When sterility testing of (F-18) radiopharmaceuticals was performed by present method, analyst received dose of 40-300 μsv/h compared to the dose of 0.8-4.5 msv/h in the direct inoculation. Further, for (^177Lu)DOTANOC and (^99mTc)TcO₄− for present method, 8-50 μsv/h dose was received by analyst compared to dose of 100-800 μsv/h in direct inoculation. All the doses were without any lead shielding. Conclusions: Sterility testing by present method was successfully validated for different radiopharmaceuticals and it decreased the radiation dose received by the analyst by 16-20 fold as compared to direct inoculation method. (author)