Rumors of rules governing Drug Master File (DMF) submissions are swirling. I’ve heard a pair of questions lately.
“Do I need to resubmit my DMF files in eCTD format?”
“Should I resubmit my files electronically?”
The answer depends on the agency.
The U.S. FDA and Health Canada have each updated their submission requirements for DMFs. Understanding each agency’s requirements will be critical to compliance in the coming months as eCTD mandates go into effect.
Submitting DMFs to FDA
The US FDA’s eCTD submission mandate, set to take effect for certain submission types on May 5, 2017, was expected for quite some time by those of us in industry. Preparations should be well under way.
As I’ve discussed in the past, the transition from paper to eCTD for marketing applications (ANDAs, BLAs, and NDAs) and INDs is a relatively straightforward process and there is no requirement to resubmit, in eCTD format, information that was previously submitted in paper.
However, there’s been some confusion about what is required to convert a DMF from paper to eCTD. A recent update to the FDA’s submission requirements for DMFs website, specifically the section on electronic DMFs, states “all Sections within Modules 1, 2 and 3 should be submitted.” This statement has been the source of speculation within the industry that the entire DMF must be resubmitted.
I contacted the electronic submissions experts and the DMF experts at FDA for clarification. Each group confirmed that FDA does not require you to resubmit previously submitted information when converting an existing DMF. As is true for other application types, FDA’s only requirement is that subsequent submissions are provided electronically once a sponsor transitions to eCTD.
Submitting DMFs to Health Canada
Health Canada (HC) posted a Notice on October 5, 2015 that explains its policy for electronic DMFs, including how to convert a paper DMF into an electronic DMF.
As of January 1, 2016, paper DMF submissions are no longer accepted. Also effective now, HC is asking that any updates made to a DMF be submitted electronically and “the first update must include a complete DMF conversion in [electronic] format for the existing DMF in paper format.”
The next milestone date is March 31, 2016. Here, the posted HC guidance states “all existing DMFs in paper format must be replaced by a complete DMF conversion in [electronic] format.”
I again reached out for clarification, this time to the electronic submissions experts in HC’s Office of Submissions and Intellectual Property. They confirmed that a full copy of the DMF must be provided in your conversion submission “as a replacement for the existing DMF.”
HC does give you the option to use their “non-eCTD electronic-only” format or the eCTD format. However, I recommend that you avoid the “non-eCTD electronic-only” format and submit in eCTD to HC. Most companies are likely submitting a DMF for the same product to other agencies that accept eCTD. Submitting to HC in eCTD format eliminates the hassle of creating a separate version of the application in an alternate format.
Navigating the Transition
The conversion from paper to eCTD presents significant challenges for many DMF holders. Staying compliant will require additional effort from companies with paper DMFs already organized in CTD format, including:
- Ensuring that the appropriate level of granularity is used in eCTD submission documents;
- Ensuring that document content is optimized for eCTD submission; and
- Ensuring that documents conform to FDA’s PDF specifications and/or HC’s Technical Requirements.
Companies with older applications that aren’t already organized in CTD format face the additional hurdle of reorganizing/re-authoring content to fit the eCTD format.
These challenges may sound easy to overcome to those unfamiliar with eCTD submissions. However, that assumption could prove costly and put compliance at risk. With the HC mandate in effect, and less than 18 months until the FDA mandate goes into effect, DMF holders should start the transition to eCTD now.