For many emerging U.S. biotech companies, the path to first-in-human (FIH) readiness often looks straightforward on paper: complete the required studies, assemble the package, and prepare for an Investigational New Drug (IND) submission. In practice, the most difficult consideration comes much earlier: Do we have the right data and are we presenting it in a way regulators can quickly understand and trust? This question remains one of the most consistent themes in pre-IND regulatory planning across modalities. The answer can be found beginning with a regulatory gap assessment and ending with FDA feedback during the pre-IND phase. The Real Challenge Isn't Just Generating Data Most development teams approaching an IND submission already have scientific expertise in place. Often, they have internal leaders who have contributed to previous submissions or inherited study packages through licensing or in-licensing arrangements. But what creates uncertainty is rarely whether work has been done; rather, whether the available studies are sufficient, aligned, and framed appropriately for regulatory review. Common questions I ask clients at this stage include:
  • Are your current studies sufficient to support FIH entry for your product modality?
  • Have any inherited nonclinical packages created hidden gaps?
  • Could an unexpected finding trigger additional study requirements?
  • Have your preclinical results caused a shift in the original submission strategy?
Answers to these questions help to shape a sponsor's pre-IND questions, their positions, and the eventual FDA responses in pre-IND meetings. However, these assessments can only occur with an understanding of the data collected to date. Equally as important as the data available is how that data is presented to the FDA. A well-designed pre-IND meeting package can become vulnerable if the narrative is fragmented. Why FDA's Evolving Position on Animal Testing Is Raising New Questions A growing area of interest is how teams interpret the FDA's evolving guidance on reducing animal testing. What began with early movement around the initial roadmap to reducing animal testing has been more recently focused on monoclonal antibodies and has expanded into broader discussion around when new approach methodologies (NAM), may support regulatory decision-making. For development teams, this introduces a practical challenge: How do you confidently approach FDA discussions when proposing a reduced nonclinical package? The answer increasingly depends on being able to justify:
  • How the data currently available supports the proposed risk/benefit ratio
  • Why a traditional study may not be necessary
  • What alternative models support decision-making
  • How the overall data package still addresses risk
These discussions, however, need to occur early in development to allow sponsors the opportunity to adapt based on FDA feedback. Sponsors should consider if these discussions are better suited for their product at the INTERACT stage, rather than pre-IND stage. The consideration on development pathway is especially relevant for teams new to drug development because not all modalities behave the same way. So, experience with a different product or modality may not provide a clear path forward. In cell and gene therapy, for example, some traditional pharmacokinetic expectations may not apply in the same way they do for small molecules. That means regulatory strategy must stay closely connected to scientific mechanism and not just precedent or a team's experience. Gap Assessments Are Still One of the Highest-Value Early Investments A formal regulatory gap assessment often provides more value than teams expect. At this stage, the goal is not simply identifying what is missing. It is understanding how regulators are likely to interpret what already exists on your path to IND readiness. A strong assessment helps teams:
  • Identify where studies may be sufficient
  • Anticipate where FDA may ask for clarification
  • Recognize where emerging findings could change submission strategy
  • Prioritize work before expensive downstream delays occur
This becomes especially important when programs involve inherited data, incomplete reports, or evolving modality expectations. Pre-IND Preparation Is Also a Writing Exercise One of the most underestimated parts of IND readiness is that many critical reports are still internal drafts when submission planning begins, creating an important opportunity: before reports are finalized, teams can shape a consistent regulatory narrative across documents. The shift from writing for scientific journals to regulatory writing is not a small step, and if underestimated can significantly blunt the impact of your data. This matters because IND content is highly interconnected. A single nonclinical conclusion may appear repeatedly across multiple documents. If language, interpretation, or emphasis shifts between sections, reviewers notice. And once regulators find something unclear, they often continue pulling it apart. Module 4 Mistakes Are Often Avoidable but Common For newer teams especially, Module 4 authoring can create preventable issues. The challenge is often not missing data; it presents technical information in ways that do not clearly support the overall package. Regulatory writing at this stage means asking:
  • Are reports structured according to expected eCTD logic?
  • Are conclusions easy to follow?
  • Does each study clearly support the broader development argument?
Even teams with strong science benefit from having someone review reports through a regulatory lens before submission pressure intensifies and early mistakes require revision and republishing of previously finalized reports. Unexpected Results Don't Have to Derail the Program Every development program eventually encounters data that was not anticipated. A toxicology signal or another unexpected finding can quickly create uncertainty across internal teams. Where experienced regulatory support becomes valuable is in translating that result into:
  • Likely regulatory impact
  • Whether remediation is required
  • How much urgency is needed
  • What can be defended scientifically
The goal is to support teams to create studies which help mitigate the potential problems through design and if a signal does appear, prevent teams from overreacting-or losing time solving the wrong problem. Why Timing Still Catches Teams Off Guard Nonclinical planning often starts early but finishes late. That is because critical pieces arrive at different times:
  • GLP toxicology reports often come late
  • Stability data may continue evolving
  • Clinical protocol requires repeated updates from external and internal review
  • Publishing and formatting create final-stage pressure
By the time submission is near, teams are often updating the same conclusions across multiple sections simultaneously. This is why nonclinical planning remains one of the longest running workstreams in FIH preparation. What Experienced Regulatory Teams Add Beyond Writing The strongest external support is rarely just document production; its pattern recognition. Organizations that have seen multiple modalities and indications repeatedly identify trends earlier, including where reviewers tend to focus, where modality expectations are shifting, and where teams can tailor effort instead of overbuilding. For life sciences professionals, this is often the most important takeaway: IND readiness is not only about completing studies, but also about translating science into a package that anticipates how regulators think. That translation often determines whether a review stays efficient or becomes a cycle of preventable clarification.   To learn more about pre-IND readiness, contact us to begin the conversation:

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