FDA Radiopharmaceutical Dosing: Beyond EBRT Limits & Safety Follow-Up

In an interview with Targeted Oncology, Harpreet Singh, MD, chief medical officer at Precision for Medicine and former director of the Division of Oncology 2, US FDA, discusses the FDA's new draft guidance on radiopharmaceutical dosing.

Watch the first part of the interview with Dr Singh.

The classic guidance that the FDA was previously issuing was primarily focused on external beam radiation therapy (EBRT) and the associated dosing limitations. This draft guidance represents a significant shift in perspective.

It effectively states that instead of adhering strictly to the limits established for EBRT, developers can now exceed those previous dose limits with appropriate scientific and clinical justification. This is a critical part of the dose escalation implications within the guidance. Trialists can now administer doses that were previously considered too high, or that were only being exceeded on an ad hoc, case-by-case basis, because researchers now have a clearer biological rationale that the pharmacokinetics and radiobiology of radiopharmaceuticals are fundamentally different from those of external beam radiation.

The guidance also calls for clinical trials to operationalize more robust dose selection strategies, such as incorporating dose-randomized cohorts. This will directly influence the operational framework of future radiopharmaceutical trials.

Another key feature is the emphasis on fixed cycle dosing, providing very prescriptive advice regarding optimal cycle length and dosing schedules, which directly impacts how patients will receive and be managed on this therapy.

Finally, the section on safety monitoring is very clear and demanding. This will certainly require a significant operational lift from sponsors. While this guidance is still in draft form, the feedback from sponsors and stakeholders may very well inform the FDA's final stance. However, as it stands today, the FDA is strongly encouraging 5 years of follow-up for patients treated with these therapies to gather long-term safety data.

Singh notes that she is hearing from some in industry that this 5-year follow-up period may be quite cumbersome. It necessitates enhanced patient tracking, potentially more monitoring visits, and additional costs. Singh believes the FDA, whose primary mission is patient safety, is taking a necessary long-term view of these novel agents. In her general experience, such requirements can be modified over time, or perhaps relaxed on a case-by-case basis, as more long-term data is generated confirming the safety profile—or lack of significant long-term effects—of these radiopharmaceutical agents.

Watch more of the interview with Dr Singh.