Radiopharmaceuticals Production PIs: Dr Frederic Mievis, PhD, Dr Fabrice Giacomelli, PhD and Dr Joël Aerts, PhDOne of the main activities at the CRC is the production of radiopharmaceutical preparations. The CRC has obtained authorisation n°1550 for the synthesis of registered and experimental drugs. A « Site Master File » outlines the organisation of these manufacturing processes, specifically the synthesis of 18F-FDG (GLUCOTRACE) and its non radioactive precursor (tetra-O-acetyl-mannose triflate), as described in the NDA (new drug application). This NDA has been submitted to the Federal Agency for Medicines and Health Products, along with the manufacturing of radiopharmaceuticals used in clinical trials (CT). The manufacturing processes realised in compliance with the European quality standards applied in the pharmaceutical industry, including the European Pharmacopoeia (PhEUR) and the EUDRALEX rules and regulations (cGMP and cGLP). The quality standards at the CRC comply with Good Manufacturing Practice (GMP) guidelines under the marketing authorisation application (MAA) and with the European guide EC guide to GMP. Three independent functions (Quality Assurance, Manufacturing and Quality Control) enable the production of these radiopharmaceuticals preparations in compliance with these different quality guidelines. 1) Quality Assurance (QA)The Qualified Person (QP), responsible industrial pharmacist, administers the QA unit by checking all the aspects with an impact on the quality of the products. This includes supply and use of raw materials, manufacturing and control of final and intermediate products. The Quality Assurance system is based on GMP policies and on a review of the events and corrective actions required to achieve continuous improvement. The direct involvement of the responsible pharmacist as QA manager ensures the engagement of the other staff to GMP policy. This involvement is based on complete documentation and on continuous learning. The QA schedules and realises the internal and external audits, carries out the review of the radiopharmaceutical batches produced and manages the possible modifications. The QA is also responsible for the release of the produced batches and tracks these through drug monitoring reports if necessary. 2) Manufacturing (synthesis platforms and clean room)The pharmaceutical production area at the Research Center of Cyclotron is made of 9 rooms (ZP 1 to ZP9). Their classification is established counting the particles presence in the air and is from A to D. Monitoring of the different areas (pressure, humidity, temperature, particles counting,…) is done all the time by calibrated probes (annually qualified). You can find 6 shielded cells in the principal room (ZP4, class C): 4 cells dedicated to the synthesis in depression for radioprotection reasons and 2 dispensing cells in overpressure for pharmaceutical reasons. MX Tracerlab and FASTlab from GE are located in each synthesis cells. The dispensing system, located in one of the two other cells, consist of one pump, one carriage, one claw and one ionization chamber. The solution (coming from the synthesis cells) is dispensed in sterile vials trough double filtration. A tunnel with automatic opening allows the vial to go directly into the lead container which will be shipped to the customers. All the material use for synthesis or dispensing (vials, kit, syringe,..) is single use. 3) Quality Control (QC)The QC unit is responsible for these different activities :
These analyses are performed on the basis of described procedures and processes. These are written according to the available monographs, and the acceptance criteria and specifications are referred to these documents. The QC laboratory has the following apparatus at its disposal:
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