GMP-compliant (68)Ga radiolabelling in a conventional small-scale radiopharmacy: a feasible approach for routine clinical use.

BACKGROUND: The number of routine care patient examinations with (68)Ga radiopharmaceuticals is still relatively limited, probably caused by the presumed need for large investments in hot cells, automated synthesis modules, laboratory equipment and validation efforts. Our aim was to set up the preparation of (68)Ga-DOTA-NOC in compliance with all current European Union-Good Manufacturing Practices (EU-GMP), current Good Radiopharmacy Practice (cGRPP) and European Pharmacopoeia (Ph. Eur.) guidance but without the availability of a hot cell and gas chromatography (GC), high-performance liquid chromatography (HPLC) and atomic absorption spectrometry (AAS) equipment. METHODS: A risk-based approach was applied to align preparation conditions with applicable regulations, together with a validation of a thin-layer chromatography (ITLC) method to replace HPLC as modality for examining radiochemical purity. RESULTS: Using an internally shielded labelling module for manual operation, a (68)Ga-DOTA-NOC labelling procedure was set up that meets all applicable Ph. Eur. specifications. The applied ITLC method showed very good correlation with HPLC results (r = 0.961) and was able to detect relevant deviations in radiolabelling procedures. All identified quality assurance aspects were made compliant with EU-GMP and cGRPP guidance. CONCLUSIONS: We consider the described configuration and validation approach feasible for many conventional small-scale radiopharmacies, something that could help to increase the availability of (68)Ga radiopharmaceuticals to a large number of patients.