Complete Response Letter (CRL)
What a definition is not
A definition is SPEQ’s plain-language decode of how a term is used in practice, cited to the documents that define it. It is a practitioner reference, not legal or regulatory advice, it does not replace the definition in the source, and where a regulator’s wording differs the regulator’s wording governs.
A Complete Response Letter is FDA’s formal notice that an application — NDA, ANDA, or BLA — cannot be approved in its current form, describing the deficiencies that must be resolved. A CRL is not a rejection; the applicant may resubmit addressing the cited deficiencies, withdraw the application, or request a meeting to discuss the path forward.
CRL deficiencies can be clinical (unresolved efficacy or safety questions), CMC (manufacturing or quality concerns), facility-related (an OAI pre-approval inspection outcome), or a combination — the letter must describe all deficiencies FDA has identified at the time it issues, so an applicant should not expect an entirely new round of issues on a well-prepared resubmission addressing the letter as written.
A CRL is not made public by FDA at the time of issuance, though public companies frequently disclose receiving one given its material effect on a drug’s timeline, and some sponsors later publish CRL content or FDA later publishes a summary once the product is eventually approved or the sponsor discontinues development.
- —FDA’s notice that an application cannot be approved as submitted
- —Not a rejection — resubmission, withdrawal, or a meeting request are all available paths
- —Deficiencies may be clinical, CMC, facility-related, or a combination
- —Not automatically made public by FDA; sponsors often disclose receipt themselves
21 CFR 314.110 (complete response letter to the applicant, NDA/ANDA); PHS Act §351 and 21 CFR Part 601 (BLA, applied under FDA policy)
Frequently asked questions
What is Complete Response Letter (CRL)?
A Complete Response Letter is FDA’s formal notice that an application — NDA, ANDA, or BLA — cannot be approved in its current form, describing the deficiencies that must be resolved. A CRL is not a rejection; the applicant may resubmit addressing the cited deficiencies, withdraw the application, or request a meeting to discuss the path forward.
Which regulations cover Complete Response Letter (CRL)?
21 CFR 314.110 (complete response letter to the applicant, NDA/ANDA); PHS Act §351 and 21 CFR Part 601 (BLA, applied under FDA policy)