[18F]FDG production facility at the Joint Research Centre Cyclotron (Ispra Site – Italy)

The JRC Cyclotron is a Scanditronix MC40 model with variable energy. It accelerates protons, deuterons, alphas and Helium-3 ion particles. For protons, the maximum energy is 40 MeV and the maximum extracted current is 60 A. The JRC Cyclotron is successfully used for routine [18F]FDG production in compliance with the Marketing Authorization under a commercial partnership between JRC and General Electric Healthcare (GE HC). The commercial production has been operational since April 2004 without any significant interruption. This radiopharmaceutical site has been the first producing centre authorised in Italy. About 18F production, the cyclotron is running every night for about 6 hours. The [18F]FDG radiopharmaceutical is distributed to hospitals and diagnostic centres in the north and central regions of Italy. The radiopharmaceutical is commercially recorded under the brand name SteriPET. This commercial activity does not interfere with other research projects that normally take place during daytime working hours. As regards to [18F]FDG commercial production, JRC is responsible for 18F supply and for radioprotection support while GE HC is responsible for the [18F]FDG synthesis and distribution to hospitals. The production facility is located inside the controlled area of the cyclotron building. It comprises the target for 18F-Fluoride production, two automated synthesis modules and an automated dispensing unit, installed in three separate hot-cells. The quality control of the produced [18F]FDG is carried out according to the SteriPET Marketing Authorization. GE HC, after the radiopharmaceutical site of Ispra, has developed other 3 production facilities around Italy in collaboration with national research centres or private companies. The complete [18F]FDG production facility, being located in the cyclotron controlled area (radioprotection regulations), is in depression with respect to the atmosphere. The Clean Room where the [18F]FDG is synthesised and sterilised is in over pressure with respect to other areas of the facility (pharmaceutical regulations). The two synthesis modules and the [18F]FDG dispenser unit are fully controlled and monitored by computers. In the area dedicated to QC all instruments and equipment are automated. A synthesis cycle is accomplished in about 35 min. The preparation of the synthesis module does not exceed 15 min. After synthesis, the radiopharmaceutical is transferred to the dispensing unit by helium pressure. The yield of [18F]FDG is around 75 % (decay-corrected). In the dispensing unit, a final sterilisation cycle is performed. Up to 17 vials of [18F]FDG can be dispensed and sterilised in a single production run. The dispensing process is based on dispensing under laminar flow and sterilisation in the final vials with steam at 135°C . The dispensing process lasts a maximum of 30 min depending on the number of vials. After sterilisation, vials are remotely inserted in lead containers inside the hot cell and then transferred through a pass through box into the shipment room. The software of the synthesis module, dispenser and QC equipment are also designed according to GMP guidelines and all relevant parameters are recorded and stored and can be reviewed at any time. Quality controls on the product are carried out according to the SteriPET Marketing Authorization where the specifications of the product as a radiopharmaceutical are presented. About 30 minutes are necessary for completion of those quality controls required for the release of the radiopharmaceutical. Radionuclide, chemical and radiochemical purity controls are carried out. The [18F]FDG can be released before completion of the biological analysis. As regards to the site production efficiency, the annual production plan for the period March 2011 – March 2012 was defined and approved. Over this period, more than 400 productions were carried out, in which 260 GBq/run of 18F have been produced.

ABBAS Kamel;  SIMONELLI Federica;  GIBSON Peter;  HOLZWARTH Uwe;  PECORALE Andrea;  BARBERIS NEGRA Federico; 

2014-11-14

Via Medica

JRC70516

1506-9680,   

http://czasopisma.viamedica.pl/nmr/article/view/28481,    https://publications.jrc.ec.europa.eu/repository/handle/JRC70516,   

10.5603/NMR.2012.0003,