# Complete response letter (CRL)

Source: https://onco.cc/terms/complete-response-letter/  
OnCo record `complete-response-letter` (Term). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

The FDA's formal 'not yet' to a drug application, listing what must be fixed before approval: more data, a different trial population, or manufacturing problems. Not the same as 'complete response' to treatment.

## Summary

A CRL ends a review cycle without approval; the sponsor can resubmit (class 1 or 2, with 2- or 6-month review clocks), appeal, or abandon. Reasons in oncology have included trials run only in China without US-relevant populations (sintilimab, camrelizumab-rivoceranib), inadequate confirmatory data for a population, unresolved safety signals, and manufacturing site inspection failures, which caused a wave of CRLs in 2022-25. The FDA began publishing CRLs in 2025. The EMA equivalent is a negative CHMP opinion or a withdrawal of the application before opinion.

## Fields

- Kind: Term
- Last checked: 2026-09-09
- Also known as: CRL; complete response letter; FDA rejection; refusal to file; refuse-to-file; resubmission; class 2 resubmission; negative opinion; CHMP negative opinion; complete response letters

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/Food_and_Drug_Administration
- Wikipedia: https://en.wikipedia.org/wiki/Food_and_Drug_Administration

## Connected records

- terms: [BLA / NDA / MAA (marketing applications) and PDUFA dates](https://onco.cc/terms/bla-nda/), [Confirmatory trial](https://onco.cc/terms/confirmatory-trial/), [ODAC (Oncologic Drugs Advisory Committee)](https://onco.cc/terms/odac/), [Regulators beyond the FDA (EMA/CHMP, MHRA, PMDA, NMPA, TGA)](https://onco.cc/terms/regulatory-agencies/)
- fronts: [Drug Discovery Platforms](https://onco.cc/fronts/drug-discovery/)

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