The FDA’s recent draft guidance for radiopharmaceuticals marks a pivotal moment for the field. For the first time, the agency provided clearer expectations for how these therapies should be developed, tested, and reviewed.
As radiopharmaceuticals continue to gain traction in oncology, the FDA’s action signals a recognition of how important this modality has become. In just a few years, radiopharmaceuticals have moved from niche to mainstream, largely driven by groundbreaking therapies like Pluvicto and Lutathera and the surge of investment from industry leaders.
With that growth comes a need for structure. The FDA’s guidance isn’t about slowing innovation; instead, it’s about creating consistency, clarity, and confidence.
Why the FDA is acting now
The number of INDs and NDAs for radiopharmaceuticals has climbed sharply in recent years. As former FDA Commissioner and now Nucleus RadioPharma’s CEO, Stephen Hahn observed in this BioSpace article, the FDA is “trying to get ahead on a new set of therapies that they see becoming very important for cancer.”
This proactive approach reflects both opportunity and urgency. Radiopharmaceuticals are unique: they combine the precision of targeted therapy with the power of radiation, but they also present unfamiliar safety and manufacturing challenges. The FDA’s goal is to ensure that developers follow consistent scientific and regulatory standards as the field matures to avoid the confusion and inefficiencies that once slowed other emerging modalities like antibody-drug conjugates (ADCs).
In short, the agency wants to help the field grow responsibly. To support that growth, the FDA is defining what responsible development looks like, starting with how teams approach dosing, patient selection, and safety.
Dose optimization: Moving beyond traditional radiation models
Until now, many developers have used dose standards borrowed from external beam radiation, a carryover from traditional oncology practices. However, injected, targeted radiotherapies behave very differently. The FDA’s new guidance emphasizes the need for true dose optimization based on data, not assumptions.
Developers must show a deeper understanding of how each isotope and targeting molecule behaves in the body. That means collecting more detailed pharmacokinetic and dosimetry data early in development, modeling absorbed dose in specific organs, and justifying dosing decisions with evidence rather than precedent.
This shift challenges teams to think beyond convention and creates a path toward more predictable safety and efficacy outcomes.
Patient selection and trial design
One of radiopharma’s greatest strengths—precision—is also one of its most significant variables. The new FDA guidance calls for more explicit criteria to identify patients best suited for these therapies.
Because antigen expression and tumor targeting can differ significantly between patients, trial designs must include detailed inclusion and exclusion criteria that reflect that variability. The FDA also encourages ongoing monitoring for off-target uptake during trials to ensure therapies behave as expected inside the body.
For development teams, this means closer integration between imaging, preclinical data, and clinical design. Selecting the right patients and documenting the rationale will be essential for safety and demonstrating therapeutic value.
Safety monitoring
Radiopharmaceuticals bring radiation directly into the body, making safety monitoring far more complex than for traditional drugs. The FDA’s draft guidance calls for deeper insight into where and how much radiation is being absorbed, not just in the target tumor but across other organs as well.
Developers should anticipate expectations for quantitative data on organ-specific absorbed doses, expanded toxicity endpoints, and stronger correlations between preclinical and human safety findings. Real-time or longitudinal tracking of radiation distribution may also become a standard requirement in specific trial designs.
These updates reflect a simple reality: radiopharmaceuticals are powerful tools, and their safety data must match that power with precision.
Preparing for the new regulatory landscape
The FDA’s draft guidance represents both a challenge and a roadmap. The challenge lies in the heightened expectations for data depth and consistency, especially in dosimetry, patient selection, and safety documentation. The opportunity lies in the clarity the agency is offering.
Developers should revisit their IND strategies to ensure their data packages align with the new guidance. That includes reinforcing preclinical models, validating dosimetry approaches, and strengthening safety justifications early. The more cohesive and data-rich a submission is, the smoother the regulatory path.
Equally important is choosing partners who deeply understand the nuances of radiopharmaceutical development and can anticipate challenges before they arise. Experienced CDMOs can bridge the gap between development and regulatory readiness and help teams design studies, collect data, and scale production in a way that aligns with FDA expectations from the start.
At Nucleus RadioPharma, we’re building the infrastructure, expertise, and partnerships needed to help innovators bring advanced radiotherapies to patients safely, efficiently, and at scale.
Connect with our team to explore how we can help you navigate regulatory shifts and advance your radiopharmaceutical to patients faster.