Initiation Of A Prospective Clinical Multicentre Trial With Local Production Of A Short-Lived PSMA-PET Radiopharmaceutical In The D-A-CH-Region: Chances And Experiences

Aim/Introduction: The development of innovative radiotracers targeting PSMA for non-invasive imaging of prostate cancer and successive treatment results in an increasing number of multicentre clinical trials using the most promising PSMA ligand candidates. For prospective studies with short-lived radiopharmaceuticals like [⁶⁸Ga]Ga-PSMA-11, a regulatory and country-specific structure has to be established before recruitment of patients is possible. This structure allows the decentralized manufacturing of the investigational medicinal product (IMP) according to Good Manufacturing (GMP) and subsequent implementation of the respective tracer compliant with Good Clinical Practice (GCP). Materials and Methods: For the multicenter clinical trial (phases-I/-II) ,,Ga-68-PSMA-11 in high-risk prostate cancer“ (NCT03362359) within DKTK a harmonized decentralized radiotracer production in multiple radiopharmacies has been set up for the very first time in the German speaking Radiopharmacy/Nuclear Medicine Community. In this prospective clinical study Nuclear Medicine physicians, radiopharmacists, urologists, pathologists and study related experts like lawyers and study nurses out of eleven study sites within the so-called D-A-CH region (Germany-Austria-Switzerland) have been involved. The basis for the accurately specified radioactive IMP manufacturing procedure was defined by EU-GMP requirements plus national standards (e.g. Medicinal Products Act and Radiation Protection Law). Results: For the recruiting study sites the required allowances, e.g. manufacturing authorization from local authorities as well as approval from ethics committees and national regulatory bodies such as BfS and BfArM in Germany, BASG in Austria as well as BAG and Swissmedic in Switzerland, have been obtained. The challenge of manufacturing a short-lived radiopharmaceutical at each of the participating geographically different sites with identical specification by adaption of production and quality control processes and parameters according to the IMP dossier (IMPD) during the starting phase of the clinical trial under a centralized quality assurance management has been achieved. Conclusion: The initiation and establishment of a multicentre clinical trial including the manufacturing of a short-lived radiopharmaceutical IMP across local study sites is very complex, but manageable. In view of the high European and national regulatory and legal burdens and the number of involved partners it is feasible in a defined time frame. Based on the achieved structures, the decentralized manufacture of novel short-lived radiopharmaceuticals can be established in the D-A-CH region and even on a European level for further investigator initiated multicentre clinical trials. We estimate our experiences important for the development of the field Nuclear Medicine at the national and international level taking into account the new EU regulation No 536/2014. References: None.