Yesterday, the FDA published a draft guidance document titled Refuse to File: NDA and BLA Submissions to CDER (here).  It covers NDAs and BLAs submitted to the Center for Drug Evaluation and Research.  Unlike the long laundry list of issues that could result in a refuse-to-receive (RTR) determination for an 505(j) (ANDA) application, this guidance is more general in nature and not nearly as granular as the RTR guidance for ANDAs.

About three-quarters of the document discusses what is not covered by the guidance, but rather provides a general statement that, if there is information that makes the application incomplete and not ready for substantive review, the application may receive a refuse-to-file (RTF) determination (and RTR is the NDA/BLA equivalent of an RTR for an ANDA.  Minor wording difference in the statute governing 505(j) applications result in the different term).

I don’t want to seem glib, and can assure you that there is substance in the guidance providing concrete examples of issues that could result in an RTF: for example, submitting only one adequate and well controlled study to support approval when, at the pre-NDA, meeting FDA determined it required 2 such studies; materially lacking or poorly organized applications; failure to submit abuse studies for controlled substances, among others cited in the document.

In addition, the document notes that “during the filing review, FDA staff may also identify certain review issues that result in a refusal to file pursuant to § 314.101(d)(3) and other authorities. Review issues typically are not usually considered the basis for an RTF action but are communicated to applicants in official filing correspondence, including RTF letters. However, some review issues may render an application incomplete and may therefore result in a refusal to file.”

The FDA also addresses timing of the issuance of such letters, the FDA decisionmaking process, the required timing of response of the applicant, and how the timeframe may be impacted by a decision by the applicant to file the application over protest.

All in all – good reading, but not much new basically just clarification from the Agency.