{"entity":{"id":"complete-response-letter","kind":"term","name":"Complete response letter (CRL)","aka":["CRL","complete response letter","FDA rejection","refusal to file","refuse-to-file","resubmission","class 2 resubmission","negative opinion","CHMP negative opinion","complete response letters"],"tldr":"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.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Food_and_Drug_Administration","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Food_and_Drug_Administration"}],"tags":[],"related":["bla-nda","confirmatory-trial","regulatory-agencies","odac"],"cancers":[],"sections":["drug-discovery"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Regulation & policy"},"route":"/terms/complete-response-letter/","neighbours":{"term":[{"id":"bla-nda","kind":"term","name":"BLA / NDA / MAA (marketing applications) and PDUFA dates","route":"/terms/bla-nda/"},{"id":"confirmatory-trial","kind":"term","name":"Confirmatory trial","route":"/terms/confirmatory-trial/"},{"id":"odac","kind":"term","name":"ODAC (Oncologic Drugs Advisory Committee)","route":"/terms/odac/"},{"id":"regulatory-agencies","kind":"term","name":"Regulators beyond the FDA (EMA/CHMP, MHRA, PMDA, NMPA, TGA)","route":"/terms/regulatory-agencies/"}],"section":[{"id":"drug-discovery","kind":"section","name":"Drug Discovery Platforms","route":"/fronts/drug-discovery/"}]}}