Usage Examples
- The NDA drew an RTF at day 60 for missing CMC content, so we never got a filing date.
- If we get an RTF, we have 30 days to ask for the informal conference before that option closes.
- Run the filing checklist now - a resubmission after an RTF costs us another 60-day filing review.
What is Refuse to File (RTF)?
Refuse to File is FDA's determination, made within 60 days of receiving an NDA, that the application is not sufficiently complete to permit a substantive review, so no filing date and no review clock begin.
Refuse to File exists because FDA's substantive review is a finite, expensive resource and an application missing required content cannot be reviewed to a meaningful conclusion. Rather than spend a full review cycle discovering that a required section was never submitted, FDA runs a completeness check in the 60 days after it receives the application and declines to open the review at all when the application fails that check.
Refuse to File covers the completeness and form of the application, not the merits of the drug. FDA may refuse to file an NDA, or decline to consider an ANDA received, if any single listed ground applies: no completed application form, a submission not in the form required by 21 CFR 314.50 or 314.94, or missing required content. Refuse to File does not mean FDA judged the evidence and disagreed; that decision comes later.
Refuse to File reaches the sponsor as a letter roughly 60 days after FDA receives the application, stating the grounds relied on. Two routes follow. The applicant can request an informal conference in writing within 30 days of the notification and afterwards ask FDA to file the application over protest and review it as filed, or correct the deficiencies and resubmit into a fresh 60-day filing review.
Not to be confused with
- Complete Response Letter (CRL)
- a CRL reflects FDA's complete review of the data submitted in the application (21 CFR 314.110). Refuse to File means that review was never opened, because the application was never filed.
- Refuse to Receive (RTR)
- the ANDA-side outcome of the same regulation. FDA does not "refuse to file" an ANDA; it declines to consider the ANDA received, so the application is not substantially complete rather than not filed.
- Refuse to Accept (RTA)
- the device-side acceptance screen applied to submissions such as 510(k)s at CDRH. Refuse to File is the drug marketing-application counterpart and runs on the 60-day clock in 21 CFR 314.101(a)(1).
- Filing over protest
- not a separate FDA decision but the applicant's move after the informal conference, asking FDA to file and review the application as submitted (21 CFR 314.101(a)(3)). Filing over protest ends the refusal; it does not cure the deficiencies FDA identified.
Refuse to File is avoided by satisfying the grounds in 21 CFR 314.101 before submission, and managed by using the rights in the same section afterwards.
What you must do
- 1Submit the application in the form required for its pathway; a submission not in the required form is an express ground for refusal21 CFR 314.101(d)(2)
- 2Include a completed application form and every content element the section lists, because any one ground standing alone is enough for FDA to refuse to file21 CFR 314.101(d)
- 3Plan for a filing decision no later than 60 days after FDA receives the application, not on the day it is submitted21 CFR 314.101(a)(1)
- 4Build the review timeline from the date of filing, which is the date 60 days after FDA received the application21 CFR 314.101(a)(2)
- 5If FDA refuses to file, submit the request for an informal conference in writing within 30 days of the date of FDA's notification21 CFR 314.101(a)(3)
- 6After the informal conference, decide explicitly whether to ask FDA to file the application over protest and review it as filed21 CFR 314.101(a)(3)
Common mistakes
Treating the submission date as the start of the review clock
the date of filing is the date 60 days after FDA received the application, and a Refuse to File means no filing date is ever set. Teams that anchor launch, manufacturing, and financing plans to the submission date lose two months before review begins, and lose the entire cycle if the application is refused.
Remediating only the deficiencies named in the letter
21 CFR 314.101(d) allows any single ground to support a refusal, and FDA has no obligation to keep looking once one is found. A resubmission built solely against the letter walks into a second refusal on a defect that was present the first time and never mentioned.
Letting the 30-day conference window lapse
the request for an informal conference must be in writing within 30 days of FDA's notification. Sponsors who spend that month assembling a remediation plan forfeit the only path to filing over protest, and are left with a resubmission and another full 60-day filing review.
When This Matters
- The NDA drew an RTF at day 60 for missing CMC content, so we never got a filing date.
- If we get an RTF, we have 30 days to ask for the informal conference before that option closes.
- Run the filing checklist now - a resubmission after an RTF costs us another 60-day filing review.
Frequently Asked Questions
A Refuse to File means FDA never began the substantive review, while a Complete Response Letter reflects FDA's complete review of the data submitted. An RTF arrives around day 60 of the filing review and sets no filing date. A CRL arrives at the end of the review cycle under 21 CFR 314.110.
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