FDA Good Review Practice: Refuse to File (RTF)

The FDA has released an updated Good Review Practice (GRP) guidance on Refuse to File (RTF) decisions for NDAs and BLAs — a crucial document for regulatory and CMC professionals involved in product submissions.

Why it matters:

RTF ensures that only complete, high-quality applications enter the review pipeline, preventing wasted time and resources on incomplete dossiers and supporting a faster, more predictable review process.

Key Takeaways:

• Completeness is non-negotiable: FDA will refuse to file if key sections (CMC, nonclinical, or clinical) are missing or inadequate.
• Major deficiencies include: missing datasets, inadequate study design, noncompliant electronic formats, or unreadable files.
• Minor issues (e.g., labeling errors or missing forms) can be corrected within the 60-day filing review period.
• RTF decisions are finalized by Day 60 post-submission. Sponsors can request a Type A meeting within 30 days to discuss the outcome.
• The policy applies to both NDA (21 CFR 314.101) and BLA (21 CFR 601.2) submissions.

What this means for industry:

The RTF framework aligns with the FDA’s Quality Review Initiative — promoting efficiency, transparency, and scientific rigor.

Sponsors are expected to adopt “submission readiness” principles: clear data organization, validated datasets, and proactive quality checks before filing.

Bottom line:

RTF is not a setback — it’s a safeguard. It ensures that applications entering review are complete, defensible, and ready for regulatory scrutiny — accelerating access to safe, effective therapies for patients.

Read also: FDA Pre-approval Inspection

Source: FDA Good Review Practice: Refuse to File (MAPP 6025.4 Rev.1, Oct 2025)