Common Submission Gaps and Risks That Can Derail Your IND or NDA

You've worked hard to bring your drug to the cusp of an IND or NDA filing. But even strong programs can stumble at the final mile — and often, it’s not the science that causes delays.

For small biotech companies especially, knowing where submissions typically go off-track can save months of heartache, rework and money. Here’s a look at the most common gaps and risks that can derail a big FDA submission — and how you can stay ahead of them.

1. Incomplete or Poorly Written Study Reports

The Submission Gap:

• Missing final Clinical Study Reports (CSRs) or Nonclinical Study Reports

• Draft reports submitted – without a plan to submit final reports

• Reports that don't clearly support the submission’s safety or efficacy arguments

Why It Matters:

The FDA needs complete, polished reports to assess your program. Missing information or unclear conclusions can lead to review delays — or even a Refuse-to-File (RTF) letter.

Pro Tip:

Prioritize finalizing critical study reports early. Don’t rely on last-minute “study synopses” to fill gaps. If all else fails, at least have a plan in place, preferably vetted with FDA, to submit final reports as soon as possible after the initial application.

2. CMC Documentation Gaps

The Submission Gap:

• Missing critical CMC modules (e.g., stability data, analytical methods validation, batch records)

• Unfinished facility readiness or lack of recent GMP inspections

• Last-minute changes to the manufacturing process without bridging data

Why It Matters:

CMC issues are one of the most common reasons for submission delays or major FDA questions.

Pro Tip:

Treat CMC as a parallel, not sequential, effort to nonclinical and clinical. Start early, stay organized, and bring in CMC experts if needed.

3. Noncompliance with eCTD Requirements

The Submission Gap:

• Documents not formatted according to FDA's eCTD specifications (e.g., incorrect bookmarks, hyperlinks, filenames, metadata)

• Problems only discovered during publishing, right before the submission deadline

Why It Matters:

The FDA requires all submissions to be in eCTD format. Noncompliance can lead to technical rejection or require costly last-minute fixes.

Pro Tip:

Start publishing preparations early — not during the final month. That means ensuring documents are content-final before they head to publishing. Submission readiness activities will be easier if documents are properly formatted (and ideally use templates) beforehand. Once publishing begins, perform rolling reviews of sections and/or modules to catch validation errors and linking corrections before crunch time.

4. Unaddressed Prior Feedback from the FDA

The Submission Gap:

• Failing to adequately incorporate or respond to prior FDA advice (e.g., Pre-IND meeting feedback, End-of-Phase 2 feedback)

• Assuming past advice is no longer relevant

Why It Matters:

The FDA expects you to honor prior feedback unless you clearly explain why you've chosen a different path.

Pro Tip:

Maintain a living “FDA Advice Tracker” that documents all feedback and how you addressed each point in the submission.

5. Unclear Responsibility and Ownership

The Submission Gap:

• Last-minute scrambling over who owns which documents or sections

• Critical gaps because people assumed someone else was handling it

Why It Matters:

Disorganized teams miss critical deliverables or fail to integrate pieces properly, leading to submission chaos.

Pro Tip:

Assign one clear owner for every submission component early — even if external vendors are involved. Accountability beats assumptions.

6. Rushed or Incomplete Risk Assessments

The Submission Gap:

• Not identifying high-risk gaps (e.g., missing reports, unstable data, resource constraints)

• Hope-based planning instead of mitigation-based planning

Why It Matters:

FDA reviewers are experts at finding weaknesses. It’s much better for you to find and fix them first.

Pro Tip:

Hold a formal gap/risk workshop 6–9 months before your intended submission date. Build realistic contingency plans — especially for high-risk CMC items and critical data reports.

Final Thoughts

Small biotech teams often punch far above their weight — but tight resources and fast timelines make gap planning even more critical. By proactively targeting these common gaps and risks, you’ll not only build a stronger submission, but also signal to FDA that your team is ready for serious partnership.

Need an experienced eye to help spot submission gaps before the FDA does?

The Sugar Water Operations Team specializes in submission gap analyses, risk mitigation plans, and eCTD-ready publishing for biotech innovators. Let's talk!