As one of the last actions in 2016 (effective December 17, 2016) the FDA enforced some new criteria that will allow them to reject an eCTD submission if there is non-compliance with key study data requirements.

FDA notes in their guidance “The standards apply to the following types of submissions to CDER and CBER:


  • NDAs, ANDAs, BLAs, and all subsequent submissions to these types of applications, including amendments, supplements, and reports, even if the original submission was filed before the requirements went into effect.
  • Commercial INDs (for products that are intended to be distributed commercially).”


There are different severities for these problems.

High severity:

      • Demographic dataset (DM) and the define.xml must be submitted in Module 4 for non-clinical data; DM dataset,
      • the subject- level analysis dataset (ADSL) and define.xml must be submitted in Module 5 for clinical data
      • Trial Summary (TS) dataset must be present for each study in eCTD section 4.2 and 5.3

Medium severity:

  • Correct STF file-tags must be used for all standardized datasets in section 4.2 and 5.3
    • Analysis-dataset-adam
    • Data-tabulations-dataset-sdtm
    • Data-tabulations-dataset-send
  • For each study in eCTD section 4.2 and section 5.3, no more than one dataset of the same name should be
    submitted as new

Some key information about this:

  • Clinical and non-clinical trials that will be reviewed by CDER/CBER must use the standards in the FDA Data Standards Catalog
  • FDA will validate submissions upon receipt and will assess conformance to required study data standards
  • A technical rejection notice will be sent if the submission fails validation
  • Customers must adhere to the Study Data Technical Conformance Guide when preparing submission for FDA review
  • FDA will provide 30 days’ notice on the FDA eCTD Website prior to the validation criteria being effective