EMA drafts concept paper for future radiopharmaceuticals guideline
The European Medicines Agency (EMA) last week released a new concept paper for a future guideline on the clinical evaluation of therapeutic radiopharmaceuticals (tRPs) for treating cancer to address the growing number of requests for scientific advice for these products.The proposed guideline will address regulatory and methodological aspects related to clinical trial design in the rapidly growing field of radiopharmaceuticals. It will cover implementing patient-specific dosimetry in clinical trials, which is not covered by current anticancer product guidelines.
EMA noted that radiopharmaceuticals are special types of medicinal products that are regulated by both the pharmaceutical legislation (2001/83/EC) and the radiation protection legislation (Directive 13 2013/59/Euratom). They are defined as a medicinal product which contains one or more radionuclides, radioactive isotopes, when ready for use.
The draft concept paper specifically addresses ready-to-use therapeutic radiopharmaceuticals (tRPs) and not radiopharmaceuticals for diagnostic use.
EMA notes that “the experience gained during the assessment of these procedures indicates that guidance on how to fulfil the requirements for Marketing Authorisation is urgently needed to ensure harmonised interpretations and to deal with recent developments and practices in the field of radiopharmaceuticals.”
The current practice of administering fixed amounts of absorbed radiation doses (AD) to patients in a fixed number of treatment cycles “has been shown to lead to highly variable ADs to both tumour lesions and normal organs,” said EMA. This may lead to “sub- optimal anti-tumour effect and late radiation-induced toxicity, both of which are potentially preventable by adjusting the administered activity to the ADs observed in the individual patient.”
The guideline would standardize relevant terminology such as “dose” in relation to “administered activity” and “absorbed dose” in relation to anti-tumor effect; explore a wide range of administration activity early in the development program in Phase I/II trials to establish the maximum tolerated dose; identify acute dose-limiting toxicities (DLTs); incorporate the evaluation of dosimetry in the clinical development of tRPs; address managing acute toxicity to achieve short- and long-term treatment optimization; and address specific tRPs/situations, such as alpha-emitters and beta-emitters with low photon emissions.
It would also cover developing individually optimized treatments and how these would vary depending on the treatment setting. The paper states that “in late-stage symptomatic disease tumour shrinkage and symptom control might be prioritized above the risk of long-term toxicity given the limited expected survival. At the other end of the spectrum, in a curative setting, relatively high rates of acute and reversible toxicity are generally accepted, while the acceptability of long-term, irreversible toxicity depends on its frequency and impact on quality of life and survival.”
The concept paper will undergo a three-month public consultation period; a final guideline will come into effect six months after the concept paper’s adoption by EMA’s Committee for Medicinal Products for Human Use (CHMP).
Concept paper
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