Risk Assessment in Pet Radiopharmaceuticals Production: Planning the Implementation of a Production Line Compliant With GMP Regulation

The production of radiopharmaceuticals (RP) is a very complex process, which must comply with numerous regulatory requirements. The short half-life of the radionuclide, the large number of batches produced per day, the administration before the completion of all quality controls are some of the critical factors characterizing the production of these compounds. The aim of this paper is to provide some indications for carrying out the risk assessment for the activation of a production line of a radiopharmaceutical containing a positrons emitter radionuclide. As "referring" radiopharmaceutical, a RP containing Fluoride-18 was chosen since its multistep production allows discussing the topic in more detail. The risk analysis was performed by following the ICH Q10 guideline and ISO 9001:2015 standards and by using the risk-based thinking approach applied to the entire product lifecycle, from the early design stages till the release of the final product. The identification of risks was not limited to technical risks but it was extended also to organizational, sustainability, and programmatic risks related to the availability of resources. The overall analysis has shown that hard and soft skills of the expert group are key factors of success both in technical and radiopharmaceuticals-related preparations as well as in risk management methodologies.