General routes of manufacturing radionuclides for use in radiopharmaceutical preparations include the following general routes: nuclear fission reactions, charged particle induced reactions, neutron induced reactions and radionuclide generator systems. To produce a given radionuclide, the desired nuclear reaction must be identified and its feasibility evaluated, which depends on the cross section for the reaction of interest, energy and nature of the incident particle, chemical purity and availability of the target materials and radionuclidic composition after irradiation, among other factors.
Independently of the mode of production, the quality framework of Good Manufacture Practice (GMP) might be needed to be introduced at certain steps of the manufacturing process of a medical radionuclide, but not in all of them. For the step involving the nuclear reaction itself, usually described as “irradiation”, it is acceptable the involvement of non-GMP processes. By contrast, the more or less complex radiochemical processing required to obtain the desired radiochemical precursor, with radionuclide and radiochemical purity compatible with clinical uses, should comply with GMP guidelines. Noteworthily, radionuclide purification by mass separation processes, applied to produce several radionuclides available at PRISMAP’s portfolio, might also be considered as a non-GMP step because it is technologically very similar to cyclotron irradiations.
All these aspects are covered and discussed in the documents and sources provided below, which comprise information on the nuclear reactions and purification processes involved in the production of PRISMAP’s radionuclides.
PRISMAP workshop: “Radionuclide Production to Nuclear Medicine Clinical Applications: Regulatory Standards and Harmonisation of Quality and Safety”, held in February 2022, provided the basis for this document, which gives guidance for the early phase clinical research with novel radionuclides. It describes the current standards and a harmonised view of the European regulatory framework. The document complements the existing regulatory framework and is not considered legally binding.
Six chapters cover different aspects in radiopharmaceutical development. Each chapter includes dedicated guidelines and guidance documents from regulatory authorities and professional organisations, as well as references to scientific publications on the respective topic.
Experimental Nuclear Reaction Data (EXFOR) www-nds.iaea.org/exfor
Dedicated cross section for medical isotopes and monitors
Production yield estimators
TENDL is a nuclear data library which provides the output of the TALYS nuclear model code system for direct use in both basic physics and applications. The 11th version is TENDL-2021, which is based on both default and adjusted TALYS calculations and data from other sources (previous releases can also be found using that link) tendl.web.psi.ch/tendl_2021/tendl2021.html
JANIS (Java-based nuclear information software) is a display program designed to facilitate the visualisation and manipulation of nuclear data. Its objective is to allow the user of nuclear data to access numerical values and graphical representations without prior knowledge of the storage format www.oecd-nea.org/jcms/pl_39933/what-is-janis
TALYS and the TALYS-related packages are open source software and datasets (GPL License) for the simulation of nuclear reactions) www-nds.iaea.org/talys
PHITS (Particle and Heavy Ion Transport code System) is a general purpose Monte Carlo particle transport simulation code developed under collaboration between JAEA, RIST, KEK and several other institutes. It can deal with the transport of all particles over wide energy ranges, using several nuclear reaction models and nuclear data libraries phits.jaea.go.jp