With eCTD submission format becomming binding as of May 5, 2017 for NDA, BLA, and ANDA and May 5, 2018 for Commercial IND and Master Files, the number of submissions to the FDA in eCTD format has significantly increased. According to Jonathan Resnick of the Office of Business Informatics (OBI), CDER received nearly 180,000 eCTD submissions in 2017. As of August 2018, 98% of the regulatory submissions were submitted in eCTD format.
At this year’s Association for Accessible Medicines (AAM) GRx + Biosims 2018 conference that is being held in Baltimore from September 5-7, FDA provided a glimpse of the current state of submission processing and challenges faced by FDA in relation to electronic submissions. The session was held on Sept 6th. It was mentioned that every day the FDA document room processes about 850 submissions. The good news is that FDA is automating processing of inbound submissions by using structured data from the eCTD backbone files and Form 356h to process the increased number of submissions and leverage the submitted structured eCTD and study data. However, FDA noted that data submitted in eCTD backbone files (e.g. us-regional.xml file) and regulatory form (e.g., Form 356h) are not always consistent. In this regard FDA offered to provide additional guidance, if needed, as the Industry prepares forms and enters metadata for electronic submissions.
FDA also provided the top 3 reasons for eCTD rejections and guidance on how to avoid them. The major reason behind rejection of an electronic submission is use of a duplicate sequence number. One example of this is submitting new or revised information using the same sequence number. Another example is when an application has a new owner and does not have a record of all the sequences. To avoid duplicating a sequence number FDA strongly recommends obtaining full sequence history from the prior owner. However, the agency did not clarify that in case a new owner is not able to obtain a complete history from the previous owner, if FDA will be able to help by providing the complete sequence history. Another reason for rejection of a submission is the use of a submission-sub-type which is not allowed for the submission-type and/or type of application. FDA urges the Industry to review the list of valid Submission Type and Sub – Type combinations to avoid making such mistakes and causing additional work for the Agency. The third reason for rejection is inclusion of invalid file types such as exe or zip file.
As FDA is taking this informatics initiative to help the Industry and make their work more efficient, we can take the recommendations provided seriously and take our own initiatives to get it right the first time.