Submitting IND Safety Reports using us-regional DTD v3.3 versus v2.01: What’s the Difference?

By Christine Straccini, B.Sc., C.C.R.P., Regulatory Associate

Submitting IND safety reports to an IND in eCTD format is slightly different when using us-regional DTD v3.3 versus v2.01. Keep in mind that the following aspects remain UNCHANGED for both versions:

• Each individual IND safety report should be provided in Section 5.3 of the eCTD under its associated study.
• Each safety report should be referenced in the study’s STF using the ‘IND safety report’ file tag.
• The eCTD leaf title should include "Safety Report" along with "initial" or "follow-up", depending on the content of the individual safety report.
• Leaf titles that clearly relate to the individual cases should be used.
• Each IND safety report should be submitted as “new” without replacing any previously submitted information.
• Multiple IND Safety Reports can be submitted in one sequence.

The DIFFERENCES are as follows:

• When using v2.01:
• IND Safety Report submissions are grouped by submission-type.
• Submitted as “amendments” (submission-type) under the IND.
• Related sequence number will be the sequence number of the IND’s original application (submission-type).

• When using v3.3:
• IND Safety Report submissions are grouped by submission-type and submission-subtype.
• Submitted as “IND Safety Reports” (submission-type) and then either as “report” or “amendment” (submission-subtype).
• First IND safety report submission using v3.3 should use a submission-type of “IND Safety Report” and submission-subtype of “report” in order to start the regulatory activity.
• All subsequent IND Safety Report submissions can then be submitted as an “amendment” (submission-subtype) to the first “IND Safety Report” (submission-type) in the application.
• The submission-ID for all IND Safety Report submissions will be the sequence number of the first submission to the “IND Safety Report” regulatory activity with submission-subtype of “report”.

Questions about using v3.3:

Question: Can “report” and “amendment” submission-subtypes be used for initial and follow-up IND Safety Reports, respectively?

Answer: This is possible but then you will need to start a new regulatory activity for each IND Safety Report.  You will not be able to submit multiple IND Safety Reports in one sequence unless they are all either initial or follow-up reports since only one submission-subtype (report or amendment) can be used per sequence.  The same applies for the submission-ID.  You can only include one sequence for the submission-ID so even if you are submitting the same type of report in one sequence they will all need to have the same submission-ID, which may not be the case for follow-up reports. This can get very cumbersome which is why I contacted the CDER ESUB group to get clarification.  It was explained to me that when using v3.3 or when transitioning to v3.3, it is acceptable to use “report” as the submission-subtype for the first IND Safety Report submission, regardless of whether the report(s) is(are) initial or follow-up. All subsequent initial or follow-up safety report submissions will then be submitted as an “amendment” under the same IND Safety Report regular activity.