Definition
Complete Response Letter (CRL) is FDA’s formal communication indicating that the review of an NDA, BLA, or supplement is complete but the application cannot be approved in its current form. The CRL identifies specific deficiencies that must be resolved.
How CRLs Work
When FDA identifies issues preventing approval, it issues a CRL by the PDUFA date instead of an Approval Letter. The CRL details all deficiencies and describes what the sponsor must do to address them.
Common CRL Reasons
- Insufficient efficacy evidence from clinical trials
- Unresolved safety signals or concerns
- Manufacturing or CMC deficiencies
- Facility inspection failures
- Labeling or prescribing information issues
- Inadequate risk management plans
Sponsor Options After CRL
| Option | Description | Timeline |
|---|---|---|
| Respond with Data | Submit additional information | FDA reviews in 6 months (Class 1) or 10 months (Class 2) |
| Request Meeting | Discuss deficiencies with FDA | 30-60 days to schedule |
| Withdraw Application | Discontinue pursuit | Immediate |
| Dispute Resolution | Formal appeal process | Variable |
Why BD Teams Track CRLs
For business development professionals, CRLs represent critical risk factors:
- Deal Implication: CRLs can significantly delay approval and affect deal valuations; milestone payments may be impacted
- Due Diligence Focus: Understand CRL reasons and sponsor’s remediation strategy before investment
- Opportunity Signal: Companies with CRL-stage assets may seek partners with expertise to address deficiencies