Karwath Pascal, Sartor Johannes, Gries Wolfgang, Wodarski Christine, Dittmar Claus, Biersack Hans J, Guhlke Stefan
Department of Nuclear Medicine, University of Bonn, Sigmund-Freud-Strasse 25, 53127 Bonn, Germany.
Appl Radiat Isot. 2005 Apr;62(4):577-86. doi: 10.1016/j.apradiso.2004.08.003.
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.
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.
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.
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.
为了将最终容器中2-[18F]FDG（氟代脱氧葡萄糖，FDG）的蒸汽灭菌应用于常规生产，我们验证并建立了一个全自动分装和灭菌系统，从而显著降低了人员的辐射负担。
该商用系统将在小型层流单元下无菌分装产品溶液与随后的蒸汽灭菌相结合，蒸汽灭菌通过分装单元中包含的高压灭菌器对最终容器中的产品进行加热来实现，从而纳入了当前用于生产注射用放射性药物的药品生产标准。针对各种pH配方，研究了所用灭菌周期的效率、灭菌条件下FDG的稳定性以及最终产品对辐射分解的稳定性。
该系统被发现完全适用于在A级层流（美国100级）环境中灌装小瓶以及对最终容器中的FDG进行灭菌。灭菌FDG溶液的pH必须略呈酸性以避免分解。pH为5.5似乎是最佳的，可得到放射化学纯度非常高（约99%）的FDG。此外，在高活性浓度溶液中，pH为5.5时FDG的辐射分解明显低于中性pH时。
终端灭菌使得即使在C级或D级（美国10000级或100000级）实验室中也能够完全符合GMP规定生产FDG。
