At Ennov’s recent Regulatory User Group meeting, my colleague Steve Clark provided an update on regulatory news covering the last six months.  Our users appreciated the information – everyone tries to keep up, but it’s so easy to miss an update.

Steve covered IDMP, news from the European Health Authorities and China, and recent FDA updates.  This blog post summarizes FDA updates since my last blog post summarizing changes as of March 2021. 

FDA has re-issued their eCTD Validation Criteria three times since March:

• May 28: update to the severity level to “High”, guidance source, and effective date for eCTD Validation Criteria 1306 and 1323. [These errors are triggered when a file is submitted that does not have a corresponding leaf element in the backbone/regional xml/index.xml.]  Update to the description for eCTD Validation 1553. [This error occurs when an incorrect FDA form is included in an/Promotional Labeling submission.]
• June 24: update to the effective date of the eCTD Validation Criteria 1551 and 1553. Update to the description for eCTD Validation 1553.   These errors are related to 2253 submissions and occur when they are submitted without product labeling or with the incorrect FDA form.
• August 16: update of corrective action for eCTD Validation Criteria 1306, 1323, 1636, 1789, 2033 and 5030.  On this date, the requirement began for M1 v. 2.5 and Supportive Files and M1 v. 2.5 Attribute List.

Related to these updates, the FDA posted several Federal Register notices concerning rejection of eCTD sequences.

• On August 25, 2021, FDA published a Federal Register Notice announcing that beginning March 1, 2022, FDA will reject submissions which fail Electronic Common Technical Document (eCTD) validations 1306 or 1323.
• On August 30, another https://www.govinfo.gov/content/pkg/FR-2021-08-30/pdf/2021-18587.pdf to announce to announce that eCTD validations 1551 and 1553 have been added to the Specifications for eCTD Validation Criteria (available at https://www.fda.gov/media/87056/download) as high validation errors. Beginning October 18, 2021, FDA will reject submissions that fail either of these validations.

Most recently, on October 1, FDA re-issued the Technical Conformance Guide with several changes:

• Updated section: Section 2.3 (Transitioning to eCTD Format and Resubmission of non-eCTD Documents) – Removed subsection “Transitioning from Paper to eCTD using us-regional v2.01”
• Updated Section 3.1.1 (FDA Regional eCTD Backbone Files).  This now notes that if you are unable to acquire a DUNS number prior to submission, you may enter 999999999.  It also provides a reminder that M1 DTD V2.01 will no longer be supported as of March 1, 2022.
• Updated Section 3.1.6 (Advertisements and Promotional Labeling Material)
• Added section: Section 3.5.8 (aECG Waveform).  This clarified that aECG file(s) should be submitted under the relevant study by the application owner. The aECG file(s) should be referenced within the study’s STF (study tagging file) and use a file-tag of “ecg”.   Generally, these are only submitted for QT studies supporting ICH E14 QT assessment. See FAQs.

Related to this last update, FDA also re-issued the File Format Specification on October 1 to add a the Zip file format type: .zip (for grouping large sets of aECG xml files).  The File Format Specification had also been updated May 28 to add the file format Chemical file format type: .sdf.

Technical Rejection Criteria for study data was updated August 16 with the addition of a reference to the Study Data Technical Conformance Guide for technical recommendations.   Effective September 15, 2021, the FDA will begin enforcing the Technical Rejection Criteria for study data.  You can learn more about this in the slides from FDA’s May 21 Webinar, FDA Study Data Technical Rejection Criteria (TRC): What you need to know!

The eCTD Data Standards list was also updated several times to clarify when all of these standard versions take effect.

Transmitting Electronic Submissions Using eCTD Specifications was updated  June 14 to clarify instructions on use of the ESG.  It also added a retirement date for CD-ROM and DVD options, if anyone is still using those!

On August 31, a CDER Webinar provided education on Promotional Submissions in eCTD Format – Grouped Submissions.  Materials include the recorded webinar and slides.

And finally, in some non-eCTD news: FDA has a new electronic format for 510(k) device submissions, and after the draft is approved, will be mandatory.  But it’s not based on eCTD 4.0 as many had hoped.