The Hidden Costs of a Poor IND Strategy—And How to Avoid Them

Intro

In the nuanced landscape of radiopharmaceutical development, the path from bench to bedside hinges critically on a well-executed Investigational New Drug (IND) strategy. While the IND is often viewed as a regulatory checkbox, treating it as such can lead to costly, avoidable consequences that reverberate throughout the lifecycle of a program. For biotech innovators and clinical-stage companies alike, a misstep at this juncture can delay timelines, erode investor confidence, and jeopardize patient access to transformative therapies.

Strategic Framing: Why IND Strategy Is More Than a Submission

The IND is not merely a gatekeeper to first-in-human studies; it is a strategic inflection point. A poor IND strategy in the radiopharmaceutical space can cascade into clinical holds, rework, and operational bottlenecks. Unlike traditional small molecules, radiopharmaceuticals carry unique complexities; from isotope production and handling, to radiation dosimetry and site readiness, that demand early, integrated planning.

Clinical Relevance: The Impact on Trial Initiation and Accrual

Clinical holds due to incomplete or unclear safety data, inadequate Chemistry, Manufacturing, and Controls (CMC) documentation, or underdeveloped dosimetry models can stall promising programs. For radiopharmaceuticals, where patient populations are often narrowly defined and indications highly specific, even minor delays can compromise trial feasibility and competitive positioning. Moreover, failure to align early on imaging-readout endpoints or site qualification criteria can impair protocol execution and patient recruitment.

Exploratory IND (eIND) pathways offer a risk-adapted approach that can reduce preclinical burden and accelerate timelines, particularly valuable in radiopharmaceuticals where microdosing is the norm. FDA guidance allows sponsors to utilize single-species toxicology and limited pharmacology for eINDs, translating into substantial cost and time savings without compromising patient safety.²

Scientific Insight: Mechanistic Complexity Meets Regulatory Rigor

Radiopharmaceuticals blend molecular targeting with radionuclide physics, requiring a dual-level demonstration of both biological plausibility and radiation safety. As noted by Zhang et al.,¹ the latest generation of radiotheragnostics utilizes targeting vectors with high specificity and optimized radionuclide half-lives to enhance therapeutic windows. An IND strategy that fails to contextualize these mechanistic advantages risks undervaluing the asset in FDA interactions.

Recent FDA practices recognize the unique pharmacology of radiopharmaceuticals, particularly diagnostic agents, by expanding microdose toxicology exemptions to include later-phase studies under specific conditions.³ However, this flexibility must be matched with rigorous documentation in manufacturing, as even minor deviations in radionuclide purity or labeling efficiency can trigger significant regulatory scrutiny.

Beyond biology, the interplay of isotope stability, production logistics, and decay kinetics must be comprehensively addressed in the CMC section. The FDA's expectations have evolved: simply stating the radiolabeling procedure is no longer sufficient. Agencies now expect rigorous quality systems that ensure reproducibility and compliance with Good Manufacturing Practices (GMP). For example, PET drugs must adhere to 21 CFR Part 212, while SPECT drugs must follow GMP as outlined in Parts 210 and 211, depending on study phase.²

Operational Context: Pre-IND as a Strategic Lever

Too often, companies bypass the Pre-IND meeting or approach it as a perfunctory step. In reality, the Pre-IND meeting is a strategic milestone—an opportunity to secure regulatory alignment, pressure-test assumptions, and de-risk the development plan. For radiopharmaceuticals, this includes clarifying expectations around radiation safety reviews, imaging agent co-administration, and endpoint validation.

An experienced team that knows how to translate radiopharmaceutical complexity into regulatory clarity can avoid downstream rework and improve FDA rapport. This isn’t just about documentation—it’s about credibility. As described in the NIH's clinical development updates, incorporating radiobiology, dosimetry, and target modulation evidence from phase 0 human trials can enhance regulatory confidence.⁴

Value Alignment: How Theragnostic Insights Helps You Get It Right

At Theragnostic Insights, we recognize that a strong IND strategy is not just regulatory hygiene—it is a competitive advantage. Our translational expertise ensures that every element of your IND package—from preclinical rationale to CMC documentation to clinical protocol design—reflects the unique promise of your radiopharmaceutical asset.

We partner with you to anticipate regulatory expectations, align internal stakeholders, and accelerate decision-making. Whether you’re preparing for a Pre-IND meeting or finalizing your Module 2 summaries, we help you avoid the hidden costs of poor planning and instead, position your therapy for rapid clinical impact.

Because when it comes to radiopharmaceutical development, success isn’t just about crossing regulatory thresholds—it’s about doing so with strategic precision.

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References:

[1] Zhang et al., 2025. Radiopharmaceuticals and their applications in medicine. Nature Signal Transduction and Targeted Therapy. A foundational 2025 review on radiopharmaceutical innovation. https://doi.org/10.1038/s41392-024-02041-6

[2] Schwarz SW, Oyama R., 2015. The role of exploratory INDs for translating radiopharmaceuticals. Journal of Nuclear Medicine. A perspective on IND microdosing flexibilities in radiopharma. https://jnm.snmjournals.org/content/56/4/497

[3] Schwarz SW, Clarke B., 2018. Perspective on how the FDA should review diagnostic radiopharmaceuticals. Journal of Nuclear Medicine. Regulatory evolution for diagnostic radiopharmaceuticals. http://jnm.snmjournals.org/content/59/6/865

[4] Kunos CA et al., 2021. Radiopharmaceutical Chemistry and Drug Development—What’s Changed? Seminars in Radiation Oncology. NIH insights on infrastructure and IND strategy for radiotherapeutics. https://doi.org/10.1016/j.semradonc.2020.07.006

[5] Global Regulatory Partners, 2020. Overview of FDA Requirements for IND. FDA expectations for IND format, content, and process. https://www.globalregulatorypartners.com/wp-content/uploads/Presentation-1-Overview-of-FDA-Requirements-for-IND-16Feb2020-new-1.pdf