Excerpt from U.S. Department of Health and Human Services' Guidance "Refuse to File: NDA and BLA Submissions to CDER Guidance for Industry" | March 08, 2018Read the Full Article Now
d-Wise's Insight on HHS's Guidance
On December 13th, 2017, the FDA Office of New Drugs in the Center for Drug Evaluation and Research (CDER) released a draft guidance, Refuse to File: NDA and BLA Submissions to CDER, for public review and comment. The comment period closed February 12th, 2018.
Sponsor companies fear an FDA refuse-to-file (RTF) notice. As this relates to sponsor biometrics organizations, handwringing often occurs during the first 60 days regarding standardized study datasets with questions such as:
- "Will the Reviewer request changes to our SDTM and ADaM datasets?"
- "Will the FDA ask us to up-version to the latest version of SDTM?"
- "Will we need to map legacy trials to SDTM and ADaM?"
Although the draft guidance does not explicitly reference standardized study datasets, it does state that an RTF may be issued if "required content is not submitted electronically where the FDA has specified the format of such submissions in guidance pursuant to section 745A of the FD&C Act, or required content is not submitted in an electronic format that the FDA can review, process, and archive, where such electronic submissions are required by an applicable regulation. Electronic submission issues that CDER consider to be filing issues include particular organization, file format, coding, or formatting problems that are specified in applicable guidances issued pursuant to section 745A(a) of the FD&C Act." In our opinion, this could be inferred as a circuitous reference the FDA's Technical Rejection Criteria for Study Data. d-Wise sought additional clarification during the public comment period to clarify the intent of the guidance.
The draft guidance emphasizes the importance of agreements between the FDA and sponsor "regarding the content of a complete application...” d-Wise is of the opinion that this includes agreements such as the Study Data Standardization Plan (SDSP). The SDSP, referenced in the FDA's Study Data Technical Conformance Guide, documents the studies and planned standards that will be included in submissions. In our experience assisting customers with their regulatory submissions, we find customers are concerned the FDA Reviewer may change their mind regarding study datasets despite agreements documented in the SDSP.
RTFs are not intended to punish sponsor companies. They help the FDA ensure the application is complete so that the Agency can ensure therapies will benefit patients. d-Wise understands sponsors will always fear an RTF. However, we appreciate that the FDA is attempting to clarify their decision making processes and the criteria for receiving an RTF. If you are reading this blog and have not read the draft guidance, we suggest you do and comment as appropriate. It's in the best interest of your company and the patients that need new therapies.