Definition
Refuse to File (RTF) is FDA’s determination during the initial 60-day filing review that an NDA, BLA, or major supplement is so deficient that substantive review cannot proceed. An RTF means the application clock never starts.
How RTF Works
After receiving an application, FDA has 60 days to determine if it’s complete enough for filing. If critical elements are missing or the application is fundamentally deficient, FDA issues an RTF letter.
Common RTF Reasons
- Missing or incomplete pivotal study reports
- Insufficient bioavailability/bioequivalence data
- Major CMC deficiencies
- Unorganized or poorly indexed submissions
- Missing safety data requirements
- Incomplete electronic submission formatting
RTF vs CRL Comparison
| Aspect | Refuse to File | Complete Response Letter |
|---|---|---|
| Timing | Within 60 days | At PDUFA date |
| Review Stage | Before substantive review | After complete review |
| Application Status | Never formally filed | Reviewed but not approvable |
| PDUFA Fee | May require new fee | Already paid |
Why BD Teams Track RTF
For business development professionals, RTF decisions signal regulatory preparation issues:
- Deal Implication: RTF delays timeline significantly and may indicate sponsor inexperience with FDA process
- Due Diligence Focus: Ask about pre-submission meetings and FDA feedback to assess RTF risk
- Opportunity Signal: Companies recovering from RTF may need regulatory consulting partners