The road from discovery to commercialization is complex for any therapeutic—but in radiopharmaceuticals, that journey brings an entirely different level of scientific and regulatory intricacy.
Developers working in radiopharmaceuticals often find that traditional drug development rules don’t fully apply. Minor missteps early in the process, especially in chemistry, manufacturing, and controls (CMC), can result in costly delays later. A straightforward, proactive approach to CMC planning is essential for keeping programs on track and ready for regulatory review.
While our recent webinar, “From Tinker to Treasure – The CMC Journey of Radiopharma,” sparked great discussion among those who joined us live, we’re recapping the most valuable takeaways here for anyone looking to deepen their understanding or catch up on what they missed.
Why CMC in radiopharma doesn’t fit the traditional mold
Unlike conventional pharmaceuticals, radiopharmaceuticals don’t always follow standard CMC templates.
For example, the drug substance in a radiopharmaceutical often can’t be isolated or tested in its final form due to the radioactive component. Instead, the regulatory focus shifts to precursors—the proprietary molecules that will eventually be radiolabeled—and the final drug product itself. That changes the structure and emphasis of documentation submitted in regulatory modules like IND Module 3.
Developers should anticipate that CMC submissions will require a thorough explanation of precursor development, detailed manufacturing steps, and rigorous drug product testing, since that’s where the bulk of quality data resides. Treating this as a plug-and-play process will likely lead to friction later on.
GMP isn’t a switch, it’s a ramp
There’s a persistent myth that GMP (Good Manufacturing Practice) compliance can be tackled in phases—start when Phase 2 ends, tighten things up by Phase 3, and lock it all down before commercialization. But in radiopharma, GMP-readiness must be a continuous, cumulative effort.
Rather than waiting for regulatory triggers, development teams benefit from thinking of GMP as a gradual ramp. That means introducing documentation practices, analytical method development, and personnel training as early as the preclinical stage. Establishing batch records and “suitable for use” criteria early can prevent bottlenecks and inspection issues later.
A more strategic approach to testing in early development
Speed is a constant pressure in radiopharma development, especially given the short half-life of many isotopes. That urgency can tempt teams to minimize in-process and release testing to conserve time. However, shaving off tests early in the name of efficiency often leads to data gaps, failed validations, and regulatory pushback.
Instead of limiting testing, it is better to build a strong data package that will support future justifications for reduced testing. Particularly in early phases, comprehensive data on identity, purity, potency, and impurities set the foundation for confident regulatory submissions and future scale-up.
Multiple isotope sources? Be prepared
Another unique challenge in radiopharma is dealing with multiple radioisotope sources, such as generator-produced vs. cyclotron-produced isotopes. These sources can create different impurity profiles and may require variations in formulation or testing protocols. Filing an IND that includes multiple isotope sources is possible, but only if the development process clearly demonstrates consistent product quality regardless of origin.
Maintaining flexibility in sourcing is smart, but only when backed by robust data and a clear rationale. That means including impurity controls and formulation testing tailored to each source, even when differences appear subtle.
For global innovators entering the U.S. market
Radiopharmaceutical companies developing products overseas—especially in Europe or Asia—often face unexpected friction when entering the U.S. regulatory system. Processes aligned to EU monographs or general pharmacopoeias may fall short of the FDA’s product-specific expectations.
A practical solution is to conduct a CMC gap analysis early and plan for a pre-IND meeting with the FDA. These steps help identify missing or incompatible data before investing in redundant or misaligned work. Regulatory clarity upfront can save significant cost and time by focusing resources on only what’s necessary for IND readiness.
Integrated teams build stronger regulatory submissions
The most successful radiopharma programs don’t treat regulatory, manufacturing, and development as isolated silos. They bring CDMOs, regulatory advisors, and internal teams together early to ensure alignment across every CMC touchpoint. Waiting until Phase 3 to integrate these efforts often exposes gaps that are too costly (or too late) to fix.
Strategic collaboration also helps avoid one of the most common pitfalls: underestimating the complexity of regulatory expectations. It’s not uncommon for programs to reach the New Drug Application (NDA) stage only to find their data insufficient. That’s not just a costly lesson for sponsors, it’s a delay for patients waiting on much-needed innovation.
A partnership that bridges the gaps
To address these exact challenges, Nucleus RadioPharma and Facet Life Sciences have partnered to support radiopharmaceutical innovators throughout the entire product lifecycle—from early development to regulatory approval.
Their combined expertise ensures sponsors can confidently navigate the CMC journey, avoid costly missteps, and bring breakthrough therapies to patients faster.
Want to learn how Nucleus can support your program? Contact us.
Missed the live discussion? Watch the full webinar here.