Question 14 of 20 Intermediate Troubleshooting
FDA refuses to file an NDA. What do you do?
Short answer
Read the stated reasons, classify each as missing content, poor organization or a substantive gap, and fix them before resubmitting. FDA decides on filing within 60 days of receipt, and the applicant may request an informal conference within 30 days of the refusal and can, in some cases, ask FDA to file over protest.
Why
Under 21 CFR 314.101, FDA decides within 60 days whether an NDA is complete enough for substantive review. Filing is a threshold judgment, not a view on approvability. A refuse-to-file letter states the reasons.
Some are mechanical: a missing module, unreadable datasets, missing Define-XML or an absent statistical analysis plan. Some are substantive: no adequate and well controlled study, or a missing study population the label would need. For refusals under paragraph (d), the applicant can request an informal conference within 30 days, and can then ask FDA to file the application over protest, in which case filing is dated 60 days after the conference request.
Filing over protest is rarely wise, because the same gaps then go into the review. The practical response is root cause analysis: why did internal quality checks miss this? Fix the content, run a full technical validation, and consider a pre-submission discussion before resubmitting.
In the EU, the parallel step is EMA validation of a marketing authorisation application before the clock starts.
A strong answer covers
- Filing decision within 60 days is a threshold check
- Classify reasons as mechanical or substantive
- Informal conference within 30 days and filing over protest
- Root cause in internal quality checks
- Technical validation before resubmission
Common mistakes
- Treating refuse to file as a rejection on the merits.
- Filing over protest without fixing substantive gaps.
- Resubmitting quickly without asking why internal checks failed.
The interviewer might ask next
What quality checks would you add to prevent a refuse-to-file letter next time?