Planning and Management of Radiopharmaceutical Development Processes Using Technology Readiness Level Scale

INTRODUCTION. The demand for new diagnostic and treatment solutions using radiopharmaceuticals (RPs), along with the growing nuclear medicine market, drives active development and rapid introduction of innovative RPs into circulation. These products possess a complex multi-component structure and specific radioactivity, a feature to be taken into account when planning and controlling research during drug development and subsequent technology transfer.

AIM. This study aimed to optimise RP development process using Technology Readiness Level (TRL) scale.

DISCUSSION. The authors analysed application of an industry-specific TRL scale for RPs. This scale considers key points for RPs: isotope content and biological molecules in the compound; necessity of quality control for specific parameters such as radiochemical purity, stability, and biological activity, as well as market circulation specifics. Correctly choosing intended use and marketing option of a developed RP is critically important, as this defines not only registration strategy but also quality requirements for the resulting product. Experience of JSC “Rosatom Science” has highlighted potential key risks, such as equipment contamination, radioactive decay rate during logistics, and other parameters. The key points in applying the scale to generic RPs were also high-lighted: the first four stages of the scale accelerated; necessity to select an original target molecule, as well as design differences of preclinical and clinical trials to obtain convincing evidence of generic bioequivalence to the reference product.

CONCLUSIONS. The adapted TRL scale for RPs is a validated tool that enables a comprehensive control over key development stages, timely risk identification and mitigation. The scale contributes to accelerating market introduction of innovative and generic RPs through transparent and stepwise planning, standard process monitoring, and use of the full development cycle, including marketing strategy.

1. Kunos CA, Mankoff DA, Schultz MK, et al. Radiopharmaceutical chemistry and drug development — what’s changed? Semin Radiat Oncol. 2021;31(1):3–11. https://doi.org/10.1016/j.semradonc.2020.07.006

2. Zhang S, Wang X, Gao X, et al. Radiopharmaceuticals and their applications in medicine. Signal Transduct Target Ther. 2025;10:1. https://doi.org/10.1038/s41392-024-02041-6

3. Lunev AS, Petrosova KA, Ternovskaya KE, et al. Analysis of current rules and regulations for preclinical studies of radiopharmaceuticals. Bulletin of the Scientific Centre for Expert Evaluation of Medicinal Products. Regulatory Research and Medicine Evaluation. 2024;14(1):81–90 (In Russ.). https://doi.org/10.30895/1991-2919-2024-14-1-81-90

4. Klementyeva OE, Smirnova AV, Kulbachevskaya NYu, et al. Non-clinical studies of radiopharmaceuticals: analysis of national and international regulatory practice (review). Regulatory Research and Medicine Evaluation. 2024;14(3):251–64 (In Russ.). https://doi.org/10.30895/1991-2919-2024-14-3-251-264

5. Goryachev DV, Lysikova IV, Chernaia AA, Kushnir DD. Planning a clinical development programme for radiopharmaceuticals: an analysis of international guidelines and expertise. Regulatory Research and Medicine Evaluation. 2025;15(1):105-120 (In Russ.). https://doi.org/10.30895/1991-2919-2025-15-1-105-120

6. Labushkina AA, Klementyeva OE, Kodina GE, Samoilov AS. Development of methodological documents regulating the clinical trials of new radiopharmaceutical drugs. Medical Radiology and Radiation Safety. 2023;68(3):71–7 (In Russ.). https://doi.org/10.33266/1024-6177-2023-68-3-71-77

7. Kosenko VV, Trapkova AA, Kalmykov SN. Regulation of radiopharmaceutical products. Bulletin of the Scientific Centre for Expert Evaluation of Medicinal Products. Regulatory Research and Medicine Evaluation. 2022;12(4):379–88 (In Russ.). https://doi.org/10.30895/1991-2919-2022-12-4-379-388

8. Kapadia R, Shevalkar G, Das U, et al. Introduction to quality by design. In: Jain NK, Neha Bajva, eds. Introduction to quality by design (QbD). Singapore: Springer; 2024. https://doi.org/10.1007/978-981-99-8034-5_1

9. Pyatigorsky AM, Brkich GE, Beregovykh VV, Pyatigorskaya NV. Comprehensive assessment of technological readiness of an innovative project during the development of a pharmaceutical product. Annals of the Russian Academy of Medical Sciences. 2023;78(3):234–41 (In Russ.). https://doi.org/10.15690/vr-amn8349

10. Gundogdu E, Demir ES, Özgenç E, et al. Applying quality by design principles in the development and preparation of a new radiopharmaceutical: technetium-99m-imatinib mesylate. ACS Omega. 2020;5(10):5297–305. https://doi.org/10.1021/acsomega.9b04327

11. Aksenova EI, Gorbatov SYu, Pivovarova OA. Determining the level of technological readiness of developments in medicine based on the TRL methodology. Probl Sotsialnoi Gig Zdravookhranenniiai Istor Med. 2021;29(special issue):1395–9 (In Russ.). https://doi.org/10.32687/0869-866X-2021-29-s2-1395-1399

12. Koshevenko AS, Degrave TV, Burenkov PV, et al. Roles of individual institutions in achieving pharmaceutical sovereignty as exemplified by the Medical Technology Transfer Centre of the Scientific Centre for Expert Evaluation of Medicinal Products. Regulatory Research and Medicine Evaluation. 2024;14(5):505–12 (In Russ.). https://doi.org/10.30895/1991-2919-2024-14-5-505-512

13. Poroikov VV, Dmitriev AV, Druzhilovskiy DS, et al. In silico estimation of the safety of pharmacologically active substances using machine learning methods: A review. Safety and Risk of Pharmacotherapy. 2023;11(4):372–89 (In Russ.). https://doi.org/10.30895/2312-7821-2023-11-4-372-389

14. Sarvepalli S, Vadarevu S. Role of artificial intelligence in cancer drug discovery and development. Cancer Lett. 2025;627:217821. https://doi.org/10.1016/j.canlet.2025.217821

15. Anikeeva MYu, Gorbunova YuA, Pikina NA. Elements of strategic planning of patent protection for pharmaceutical inventions. Regulatory Research and Medicine Evaluation. 2024;14(5):513–20 (In Russ.). https://doi.org/10.30895/1991-2919-2024-14-5-513-520

16. Kodina GE, Malysheva AO, Larenkov AA, Bruskin AB. Possible impurities in radiopharmaceuticals and corresponding test methods. Bulletin of the Scientific Centre for Expert Evaluation of Medicinal Products. Regulatory Research and Medicine Evaluation. 2022;12(3):244–62 (In Russ.). https://doi.org/10.30895/1991-2919-2022-12-3-244-262

17. Larenkov AA, Mitrofanov YuA, Rakhimov MG. Features and practical aspects of radiochemical purity determination of receptor-specific Lu-177 radiopharmaceuticals as exemplified by [177Lu]Lu–PSMA-617. Bulletin of the Scientific Centre for Expert Evaluation of Medicinal Products. Regulatory Research and Medicine Evaluation. 2022;12(4):455–67 (In Russ.). https://doi.org/10.30895/1991-2919-2022-12-4-455-467

18. Shatik SV, Maystrenko DN, Stanzhevskiy AA. Peculiarities of the regulatory status of radiopharmaceuticals manufactured in medical organisations. Bulletin of the Scientific Centre for Expert Evaluation of Medicinal Products. Regulatory Research and Medicine Evaluation. 2022;12(4):389–94 (In Russ.). https://doi.org/10.30895/1991-2919-2022-12-4-389-394