Non-clinical Studies of Radiopharmaceuticals: Analysis of National and International Regulatory Practice (Review)

INTRODUCTION. Currently in the Russian Federation and the Eurasian Economic Union (EAEU), the conduct of non-clinical studies of radiopharmaceuticals is regulated by general guidelines on non-clinical studies, which are applicable to multiple groups of medicinal products but do not accommodate the characteristics of radiopharmaceuticals.

AIM. The study aimed to substantiate the need for methodological guidelines regulating non-clinical studies of radiopharmaceuticals, taking into account global regulatory practice.

DISCUSSION. The authors analysed the Russian and EAEU guidelines regulating non-clinical studies in general as well as international publications on non-clinical studies of radiopharmaceuticals, including guidelines by the US Food and Drug Administration (FDA), the European Medicines Agency (EMA), and the International Atomic Energy Agency (IAEA). The analysis revealed the need for terminology harmonisation. This article describes the aspects specific to radiopharmaceuticals that limit the applicability of general guidelines to non-clinical studies of radiopharmaceuticals. Subchronic toxicity studies based on inactive formulations do not account for the contribution of radionuclide emission to the biological effects of therapeutic radiopharmaceuticals. The authors suggest that systemic toxicity studies of finished dosage forms should use single-dose chronic toxicity protocols.

CONCLUSIONS. It is necessary to develop and implement up-to-date methodological guidelines for conducting non-clinical studies of radiopharmaceuticals to reduce potential risks in the application of these medicinal products. This requires factoring in different requirements for diagnostic and therapeutic radiopharmaceuticals, with due consideration of radiation safety requirements. When drafting guidelines for non-clinical studies of radiopharmaceuticals, regulators should keep in mind the applicable guidelines by the FDA, EMA, and IAEA. A list of mandatory studies should be compiled, and uninformative studies should be excluded from the requirements for radiopharmaceuticals.

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