FDA Points at the Disconnect in What it Tells Companies and What They Disclose
(Thursday, February 18, 2021)
Only 16% of the times when a company gets a Refuse to File (RTF) notification, it tells the public about it, and even then, only 5% of the times, the company accurately discloses the reasons for the refusal, FDA reports. Companies obviously want to control the negative information about their applications and FDA want to shine light on that. By law, FDA is not allowed to disclose the contents of the RTF letters or Complete Response Letter (CRL) issued when an NDA or BLA is not approved (i.e., rejected). It is up to the sponsors of those applications what they publicly announce. And not surprisingly, they tend to either not announce at all or manipulate the information contained in the RTF or CRL letters to control the negative news. In the latest report by FDA, RTF are rare; only about 4% of the applications submitted to the FDA get them. Overwhelmingly (~85% of the times), the RTFs are for scientific deficiencies such as unacceptable clinical trial data (statistical analysis plan deficiencies or incomplete data sets) or manufacturing issues (lack of characterization data or issues with the manufacturing process). Interestingly, sponsors should not have been surprised by the RTF as in most cases, according to the FDA, the sponsor was informed about these scientific issues prior to submission of the NDA or BLA (likely in the pre-NDA/BLA meeting or other communications) but the sponsor chose to either ignore those suggestions or planned to appeal them post-submission. Most likely, the sponsors addressed the deficiencies and resubmitted and the application was accepted; only in 5 cases out of 2475 applications did a sponsor receive 2 RTF letters. It took the applicants a median of 6 months (182 days) to resubmit; in some cases, it took about an year to respond to the RTF, indicating that these were substantive deficiencies in the original application that required additional work. Applications that received RTFs took a median of about 2+ years from the original submission date for the approval decision by the FDA. The latest report from FDA builds on a previous such study that shed similar light on the CRLs issued to sponsors. Just as seen with public disclosure of CRLs, the applicants were very stingy in disclosing the contents of the RTFs. Only about 15.5% of the times did an applicant publicly acknowledge the RTFs, and in those cases also, only 5.4% of applicants accurately disclosed the reasons for the RTF letters (less than 1% of the total RTFs). This is not a surprising finding, and FDA certainly wants the public to know the limitations of the current laws regarding public disclosure of RTFs and CRLs. That said, the report should help future submitters of applications to review their applications for common deficiencies so they can avoid RTFs.

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AUTHOR               

 Dr. Mukesh Kumar
​ Founder & CEO, FDAMap

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