FDA releases draft guidance on how incompleteness of an NDA or BLA can lead to “refusal to file”

The US Food and Drug Administration (FDA) can decide not to review a new drug application (NDA) or biologics license application (BLA) if they are deemed incomplete. The FDA has released draft guidance on what incompleteness means and when it may lead to a “refusal to file” decision.

The purpose of the guidance is to clarify circumstances under which the FDA’s Centre for Drug Evaluation and Research (CDER) may refuse to file a NDA, supplemental NDA, a BLA or supplemental BLA for a therapeutic biological product regulated by CDER. The draft does not contain information on abbreviated new drug applications (ANDAs) for generic drugs. The guidance accentuates the importance of submitting a complete application to minimise the risk of a refuse-to-file (RTF) action by the FDA.

To help companies’ correct issues, rather than wait for the FDA to issue a complete response letter, RTF actions allow the FDA to inform a sponsor as quickly as possible of deficiencies in an NDA or BLA.

The FDA states “incomplete applications, including applications for which minor components have not been received within 30 calendar days after receipt of the original application, as may have been agreed upon at a pre-submission meeting, may also be refused for filing”.

Filing issues are generally grouped into two categories: deficiencies that can be corrected before filing and are not discussed in the draft and complex significant deficiencies that cannot be corrected before filing and may result in a refusal to file.

The draft guidance also states that: “Applications for new molecular entity NDAs or original BLAs received between October 1st 2012, through to September 30th 2017 that are filed over protest will not be reviewed under the Program. Alternatively, the applicant may amend the NDA and resubmit it, and the review division will make a separate determination whether the resubmitted NDA may be filed.”

To read the draft guidance on when the FDA can refuse to file NDA and BLA submissions, please click here.