US FDA CDER Reveals Why Most eCTD v4 Submissions Fail (And How to Fix Them)

US FDA CDER Publishes Top Reasons for eCTD v4 Rejection

Recent data released by the US FDA’s Center for Drug Evaluation and Research (CDER) highlights ongoing quality challenges in electronic Common Technical Document (eCTD) submissions,  both in the legacy v3.2.2 format and the newer eCTD v4 standard.

eCTD v4: High Error Rate in Early Adoption

Between January 1 and December 31, 2025, CDER reviewed 39 eCTD v4 submissions.
74% contained errors, putting them at high risk for regulatory rejection. The most frequent issues include:

• Sequence mismatches (missing, multiple, or incorrect entries)
  
  
• Duplicate sequence numbers
  
  
• Missing or incorrect information

Comparison with eCTD v3.2.2

In the same period, 361,629 eCTD v3.2.2 submissions were received. While the error rate was far lower (1.7%), the large volume still produced significant numbers of problematic filings:

• Duplicate sequence numbers: 1,841 cases in eCTD v3.2.2 vs. 2 in eCTD v4
  
  
• Missing fillable forms: 201 cases in eCTD v3.2.2 vs. 4 in eCTD v4

What this means for Applicants

The data suggests that many eCTD v4 errors mirror those seen in v3.2.2 submissions, indicating that applicant accuracy and process clarity remain critical factors.  While eCTD v4 adoption is still in its early stages, these findings underline the importance of early validation and thorough internal review before submission.

Recommendations for Applicants:

• Review sequence numbers carefully to avoid gaps or duplicates

• Apply validation tools early in the process

• Verify backbone files and fillable forms for completeness

• Update submission SOPs and train staff on eCTD v4 requirements

   

If you would like to avoid costly FDA rejections and keep your timelines on track, contact our Regulatory Publishing Services.  They combine deep eCTD v4 expertise with meticulous quality control. Our publishing experts are based in the US and in Europe, where they...

• Prepare and validate your sequences to ensure US FDA compliance

• Check backbone files and metadata for accuracy

• Handle formatting, technical validation, and issue resolution before submission

• Provide clear communication and support throughout the process

With our help, your eCTD v4 submissions are error-free, compliant, and ready for FDA review, so you can focus on getting your product approved, not fixing mistakes.