For the purpose of implementing steam sterilization of 2-[18F]FDG (FDG) in the final container into routine production, we have validated and established a fully automated dispensing and sterilization system, thereby considerably reducing the radiation burden to the personnel.
Methods: The commercially available system combines aseptic dispensing of the product solution under a miniaturized laminar flow unit with subsequent steam sterilization, realized by heating of the product in the final containers by an autoclave included in the dispensing unit, thus incorporating current pharmaceutical manufacturing standards for the production of parental radiopharmaceuticals. The efficiency of the used sterilization cycle, the stability of FDG under the conditions of sterilization and the stability of the final product towards radiolysis was investigated with respect to various pH-formulations.
Results: The system was found to be fully valid for filling of vials in a laminar flow class A (US-class 100) environment and for sterilization of FDG in the final container. The pH for sterilizing FDG solutions must be slightly acidic to avoid decomposition. A pH of 5.5 appears to be optimal and gives FDG of very high radiochemical purity (approximately 99%). In addition, radiolysis of FDG in solutions of high activity concentration was significantly lower at pH 5.5 than at neutral pH.
Conclusion: Terminal sterilization enables the production of FDG in full compliance with GMP-regulations even in Class C or D (US class 10,000 or 100,000) laboratories.