How to Perform a Submission Gap Analysis and Submission Risk Assessment For Your IND or NDA

If you're preparing a major FDA submission like an IND, NDA or BLA, you already know it's a monumental milestone. But before you hit "send," you should first step back and ask: Are we ready?

For small biotech companies, where resources and time are often limited, performing a submission gap analysis and submission risk assessment early in the process can be the difference between a smooth FDA review and a major (and costly) delay.

Here’s a simple, practical guide to help you get started:

1. Understand the End Goal

Before you start assessing anything, clarify the regulatory requirements for your submission. For an IND, you’ll need to show that your drug is reasonably safe to begin human studies. For an NDA, you must demonstrate that your drug is safe, effective, and that your manufacturing is reliable.

Action Tip: 

Use FDA guidance documents, your regulatory strategy, and example review documents (e.g., publicly available FDA reviews) to map out what’s expected. Take advantage of preNDA or preIND meetings to clarify expectations and strategy with the FDA.

2. Create a Submission Readiness Checklist

Break your submission down into its major parts — for example:

• Nonclinical (toxicology, pharmacology)

• Clinical (study reports, data)

• CMC (Chemistry, Manufacturing, and Controls)

• Regulatory (forms, administrative documents)

For each section, list:

• Required components

• Status (draft, in-review, final, sent to publishing)

• Owner (who’s responsible)

• Target dates

Action Tip: 

Some document management systems and regulatory information management systems like Veeva or Kivo offer this kind of functionality, but there’s nothing wrong with software like Microsoft Project Planner or even simply a detailed spreadsheet. The most important part is to track the data in a way that’s clear, shows you exactly where you are in the process, and where you still need to go.

3. Perform a Submission Gap Analysis

A gap analysis asks:"What is missing, incomplete, or non-compliant?"

Go through your checklist line by line:

• Are all required documents and datasets available?

• Are the documents in final or near-final state?

• Have templates been used, and/or formatting completed where possible to ensure consistency and more efficient submission readiness?

• Have all technical requirements (e.g., eCTD submission standards) been followed?

• Are there any incomplete studies, pending analyses, or reports still in progress?

Action Tip: 

Bring in a fresh set of eyes — an experienced regulatory consultant can often spot missing pieces that internal teams overlook.

4. Conduct a Submission Risk Assessment

A risk assessment asks:"If something is missing or delayed, how big is the impact — and how likely is it to happen?"

For each gap or concern identified:

• Assign a risk score based on likelihood (how probable) and impact (how serious)

• Classify risks as High, Medium, or Low

• Develop mitigation plans for each high-risk item (e.g., contingency plans, escalation paths)

Example:

• Risk: Clinical Study Report for pivotal Phase 2 study delayed

• Likelihood: Medium

• Impact: High (critical to IND approval)

• Mitigation: Weekly status checks with CRO, backup medical writer engaged, publisher informed and on standby with publishing strategy in place

Action Tip: 

Focus your energy on high-impact/high-likelihood risks. Not everything needs a fire drill — prioritize where it matters most.

5. Set Up Regular Checkpoints

Risk and readiness aren't "one and done" — they change as you move closer to your submission date.

Plan regular review meetings to:

• Update the checklist

• Reassess gaps and risks

• Adjust mitigation strategies

Action Tip:

Weekly submission meetings during the final 3–6 months before filing, depending on the type and complexity of the submission, are standard practice in large companies. Small biotechs should borrow this habit. Depending on the point in the timeline, you may not need all key players at every meeting, but keeping everyone informed with detailed meeting minutes and action items will make sure everyone is on the same page.

Why This Matters

Performing a gap analysis and risk assessment may feel like extra work at a time when everyone is already stretched thin. But it's one of the best ways to:

• Avoid last-minute surprises

• Reduce the risk of a Clinical Hold or a Refuse-to-File (RTF) letter from the FDA

• Keep your submission timeline realistic and achievable

Small biotechs don’t have the luxury of massive regulatory teams — but with careful planning, you can still achieve big-company results.

Need help preparing for your IND, BLA or NDA?

Our team specializes in helping biotech companies perform readiness assessments, manage large submissions, and stay on track for success. Contact us today to learn more!