Design and validation of a semi-automated sodium[18F]fluoride formulation system

Abstract

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Objectives: It has been the aim of the present work to develop and validate a GMP compliant semi-automated formulation module to produce sodium[18F]fluoride for injection. Methods: A semi-automated formulation and purification system has been developed operated by a time triggered sequential control. During the production process raw sodium[18F]fluoride from the cyclotron “silver” target is trapped on an anion exchange cartridge, cleaned with sterile water and eluted with sterile saline 0.9 % solution. The production process is followed by a semi-automated cleaning sequence. The process validation of the system consisted of the validation of the purification and trapping efficacy as well as of the cleaning process. Results: A production module has been developed which represents a closed fully GMP- compliant production system. In course of the process validation it could be proofed that just 5.6 x 10-4 % of the trapped target radioactivity was left on the anion exchange cartridge after the final elution. Furthermore, the efficacy of the purification step has been evaluated by the determination of the amount long living isotopes of the raw target liquid, left on the cartridge, in the final product as well as in the waste liquid. The gamma spectroscopy of the final product showed that the concentration of long-living isotopes could be reduced by 97 % compared to the raw product with means of the applied purification process. An ICP-OES analysis of the final product could not detect any traces of silver based on a limit of detection of 0.1 ppm. The validation of the cleaning procedure of the synthesis module after the production showed that the time and the substance employed for cleaning are appropriate and leave no residue that could impair the following synthesis. The microbiological cleaning validation also neither showed any endotoxines nor any microbiological recount. Conclusions: A GMP compliant semi-automated formulation module for the production of sodium[18F]fluoride for injection has been developed. The process validation and evaluation of the system confirmed a high purification efficacy and suitability.