We are all aware, that the United States Food and Drug Administration (USFDA) has extended compliance date for Drug Master Files (DMFs) to be submitted in electronic Common Technical Document (eCTD) format, i.e., 5th May 2018. With less than two months in hand, the first and foremost question every applicant should ponder upon is, what are the DMF Type-wise requirements and how is the data built, validated and published accurately for effective electronic submissions? Before we delve into those queries, let us understand more on the series of DMF updates from the FDA.
ADVANCEMENTS AT THE FDA:
ALL DMFs TO BE SUBMITTED IN eCTD FORMAT
According to the legislation, the FDA now requires all DMFs to be submitted in eCTD format from May 5, 2018 onwards, and all DMFs which are not submitted in this format after the proposed date will be rejected.
If a DMF already exists in paper format with the FDA, it doesn’t need to be resubmitted in the e-CTD format. All new submissions post May 5th, 2018, however, will require to be submitted in the e-CTD format. The DMF holders may continue to hold the same DMF numbers as before, with some minor changes. For instance, if the previous DMF number was 5678, the DMF holder would now have to pad left with two zeros. Thus, 5678 would be converted into 005678, when the DMF is converted into e-CTD format; but would essentially remain the same number.
PACKAGING INFORMATION NOT INCLUDED IN THE DMF
Packaging information, however, isn’t required to be submitted to the FDA in the DMF. Applicants of an NDA, ANDA or BLA, or even the sponsors of an IND are responsible for providing information about packaging components. This information is generally mentioned in the application itself, and is provided to the applicant by the manufacturer of the mentioned packaging component or material.
TYPE III DMF FOR CONFIDENTIALITY
In the case of confidentiality, or if the manufacturer wants to withhold certain proprietary information from the applicant or sponsor, all such information may then be placed in a Type III DMF and incorporated into the application, accompanied by an authorizing letter from the manufacturers which refers to the DMF. If a DMF already exists in paper format with the FDA, it doesn’t need to be resubmitted in the e-CTD format. However, after May 5, 2018, all submissions will only be accepted in the e-CTD format, thereby making the need for paper submissions redundant.
DMFs TO BE UPDATED ANNUALLY
According to the DMF Guidance, DMF holders are recommended to update their DMFs annually. FDA also sends “Overdue Notification Letters” (ONLs) to DMF holders for DMFs that have not been regularly updated in the last three years. If a DMF holder fails to respond to an ONL, his/her DMF may be closed by the FDA.
Even with complete knowledge of all the FDA updates regarding DMFs, sometimes, compiling, validating and publishing the data would be a difficult task unless you start preparing for submissions before time. In addition, if your current DMF is in paper format, converting it into eCTD will be burdensome especially when pacing against the extended deadline. Thus act now to be compliant. Consult.