In radiopharmaceuticals, preclinical success isn’t just about demonstrating activity but building something that can survive contact with reality. That means processes that can scale, compliance strategies that hold up under scrutiny, and supply plans that won’t collapse under pressure.
Too often, late-stage setbacks can be traced back to choices made in these earliest stages. Here are five pitfalls that frequently trip up programs in preclinical development and strategies to avoid them.
Pitfall 1: Overlooking isotope supply constraints
Science is often the first focus in preclinical, but isotope supply is just as critical. Radiopharmaceuticals rely on a steady, predictable supply of therapeutic isotopes like actinium-225, lutetium-177, copper-67, or lead-212. These isotopes are technically complex to produce, and their short half-lives make the supply chain inherently fragile.
When developers design preclinical programs around a single isotope supplier, they build in a single point of failure. If that source becomes unavailable due to production issues, raw material shortages, or regulatory delays, entire programs can stall.
How to avoid it: Evaluate isotope availability alongside scientific feasibility. Plan for multiple qualified suppliers early, and design processes that can flex between isotope sources if needed. The earlier you design for redundancy, the less likely your program will stall when supply inevitably hits a bump.
Pitfall 2: Assuming GMP standards can wait
A common misconception is that Good Manufacturing Practice (GMP) compliance becomes relevant only once a therapy reaches Phase 2 or 3. In radiopharma, that assumption can be costly. Documentation practices, analytical method development, and process controls must begin in the preclinical stage.
For example, waiting to establish batch records or “suitable for use” criteria until trials begin often results in gaps that regulators will flag, leading to delays in IND approval. Preclinical work that isn’t GMP-aligned also risks requiring extensive rework before it can be transferred to a compliant manufacturing setting.
How to avoid it: Think of GMP as a gradual ramp, not a switch you flip later. Introduce documentation systems, analytical testing, and personnel training early in development. Preclinical studies should be designed with regulatory modules in mind so the data can flow seamlessly into future submissions.
Pitfall 3: Designing processes that cannot scale
Many preclinical teams fall into the trap of developing small-batch, research-focused processes with the intention of “fixing” scalability later. That approach doesn’t work in radiopharma. The short half-lives of isotopes mean manufacturing, QC, and delivery must already function as highly coordinated, time-sensitive processes.
A conjugation method that works for a bench-scale experiment may not translate into reproducible, GMP-compliant production. Likewise, an inefficient labeling process might be manageable in preclinical but will become a major bottleneck when scaled for clinical batches.
How to avoid it: Design preclinical processes with scalability in mind from day one. Ask whether the chemistry, labeling, and QC methods will still hold up in a GMP hot cell environment. Partner with experienced CDMOs who understand R&D flexibility and clinical-scale requirements, as this alignment saves time and cost later.
Pitfall 4: Misaligning regulatory frameworks
Radiopharmaceuticals don’t fit neatly into traditional pharmaceutical regulations. Therapeutic radiopharmaceuticals are governed under 21 CFR 211, not the 21 CFR 212 framework that applies to short-lived PET diagnostics. Facilities, documentation, and compliance standards differ significantly between the two.
Programs that treat therapeutic radiopharma, such as PET or conventional drug development, often face avoidable regulatory setbacks. For example, facilities designed for PET drugs may not have the shielding or aseptic infrastructure needed for therapeutic isotopes. Submissions that assume standard small-molecule templates may miss critical CMC details that regulators expect.
How to avoid it: Align regulatory strategy with therapeutic radiopharma requirements from the start. Conduct early gap analyses to ensure facilities, documentation, and processes meet 21 CFR 211 standards. Engaging regulators in pre-IND conversations is also an effective way to identify and address gaps before they cause delays.
Pitfall 5: Failing to integrate across departments
Radiopharmaceutical development touches multiple disciplines: biology, chemistry, manufacturing, regulatory, supply chain, and logistics. When these groups operate in silos, gaps emerge. For example, an R&D team may design a promising process that regulatory teams later flag as non-compliant, or a supply chain constraint may not be discovered until clinical production is underway.
Preclinical is the stage where these silos must begin to break down. Innovators face costly rework, inefficient tech transfer, and slowed IND timelines without integrated planning.
How to avoid it: Foster collaboration between internal teams, CDMO partners, and regulatory advisors early in preclinical. Treat the stage as a rehearsal for clinical and commercial realities, aligning decisions across every function. Integrated planning helps prevent the “handoff gaps” that often surface too late to fix efficiently.
Proactive planning turns preclinical risk into downstream momentum
Preclinical isn’t just a scientific checkpoint; it’s the foundation for every stage that follows. Overlooking isotope supply, deferring GMP practices, designing non-scalable processes, misaligning regulatory frameworks, or working in silos all increase the risk of costly delays down the road.
At Nucleus RadioPharma, we help our partners anticipate and overcome these challenges. With purpose-built facilities, isotope-agnostic capabilities, and deep expertise across R&D, regulatory, and manufacturing, we’re designed to support radiopharmaceutical innovators from the earliest stages through commercial scale.
If you’re navigating preclinical development, let’s talk about how we can help you build a smoother path forward.