The quality control and definition of specification of novel radionuclides and radiopharmaceuticals should follow the scope of existing specific monographs, general monographs and chapters as applicable, trying to achieve European Pharmacopeia (Ph.Eur. compliance). Being available a specific monograph on the Ph.Eur. for a substance/preparation, the monograph is mandatory (both for regulators and for applicants) provided the applicant justifies that the monograph is suitable to control that preparation. All the tests prescribed in a monograph for an active substance or for a finished product should be conducted on a routine basis. Tests may be performed after the release of the product if specified typically specified in the respective monograph. If in-house methods are used, they must be validated.
In particular, the involvement of metrology is of utmost importance in defining calibration standards for the novel PRISMAP radionuclides, which is crucial to support pre-clinical studies for the translational radiopharmaceutical development process.
This portal provides documents useful to define general standards that are required to meet regulatory issues in the clinical translation process, namely related with quality and safety data for specific radionuclides and their radiopharmaceuticals, as well as standards in relation to metrology. These data form a solid basis to support both radionuclide producers and the translational research within and outside PRISMAP, while providing a guide for pharmaceutical authorities in their evaluation process.
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.
This reports addresses the requirements of a portable system to perform primary standardisations of the activity of a short-lived radionuclide at a production facility, covering the aspects of the sample preparation and radiochemistry, as well as the need primary standardization.
Pharmacopoeial guidelines/ European Pharmacopoeia (Ph. Eur.) 10th Edition: Monographs, chapters, general texts www.edqm.eu/en/european-pharmacopoeia
Radiopharmaceuticals - Scientific guideline/this document describes the specific additional information that needs to be submitted in relation to radiopharmaceuticals, in the context of applications for marketing authorisations or variations to authorised medicinal product www.ema.europa.eu/en/radiopharmaceuticals-scientific-guideline
Quality guidelines for radiopharmaceuticals within the International Pharmacopoeia, developed by the IAEA in cooperation with WHO www.who.int/teams/health-product-policy-and-standards/standards-and-specifications/norms-and-standards-for-pharmaceuticals/pharmacopoeia/radiopharmaceuticals
ICH Q2(R2) Validation of analytical procedures - Scientific guideline www.ema.europa.eu/en/ich-q2r2-validation-analytical-procedures-scientific-guideline
EANM guideline on the validation of analytical methods for radiopharmaceuticals ejnmmipharmchem.springeropen.com/counter/pdf/10.1186/s41181-019-0086-z.pdf