Submission & ApprovalLast reviewed April 2026

Refuse to File(RTF)

FDA's decision not to accept a drug or biologic marketing application for substantive review due to administrative or content deficiencies.

Usage Examples

The NDA received an RTF for incomplete bioequivalence data and missing Pediatric Study Plan.
Resubmission after RTF remediation restarted the 60-day filing review and 10-month PDUFA clock.

What is RTF?

A Refuse to File (RTF) is FDA's determination that an NDA, BLA, or ANDA cannot be accepted for substantive review due to inadequate content or administrative deficiencies. Filing review takes 60 calendar days after receipt (NDA/BLA) or 60 days (ANDA). If FDA issues an RTF, the sponsor must address deficiencies and resubmit — restarting the filing review clock.

Common RTF triggers include: incomplete nonclinical or clinical sections required by regulation, missing required Module 1 administrative content, inadequate CMC content to support approval review, incomplete or nonexistent Pediatric Study Plans, missing required electronic submission elements, or eCTD technical validation failures. RTF is the drug-application equivalent of the device RTA notice. It is distinct from a Complete Response Letter (post-substantive-review denial) — RTF means review never started.

Regulatory Context

This term appears most often in submission & approval workflows where submission quality, regulatory evidence, and audit readiness depend on consistent language. It is commonly referenced alongside 21 CFR 314 101, FDCA SECTION 505.

FDAICHEMA

When This Matters

The NDA received an RTF for incomplete bioequivalence data and missing Pediatric Study Plan.
Resubmission after RTF remediation restarted the 60-day filing review and 10-month PDUFA clock.

Common Mistakes

Treating submission readiness as a formatting-only check without lifecycle validation.
Using outdated guidance references across modules and summaries.
Missing cross-functional review between RA, CMC, and quality before submission.

Related Regulations

21 CFR 314 101FDCA SECTION 505

Frequently Asked Questions

RTF is issued during 60-day filing review — the application cannot be accepted. CRL is issued after substantive review (at or near PDUFA date) — review happened but FDA cannot approve. RTF means start over on filing; CRL means respond to specific review findings.

RTF applies to drug/biologic applications (NDA, BLA, ANDA). RTA applies to device submissions (510(k), De Novo). Conceptually similar: acceptance-level determinations based on completeness, not scientific merit. Different review clocks and remediation processes.

Run the FDA Filing Checklist against the application before submission. Ensure eCTD technical validation passes, required Module 1 content is complete, CMC sections are adequate for review, PSP is filed, and all statutory content elements are present.