1. eCTD Lifecycle Gary M Gensinger
Director, Regulatory Review Support Staff
Office of Business Process Support
Center for Drug Evaluation and Research

2. Lifecycle - The eCTD Advantage
Within your individual application
Controls the presentation of documents to the reviewers
Ensures that the reviewers know your intentions
Helps the reviewers trace the evolution of your documents

3. Lifecycle - The eCTD Advantage
Between your applications
Eliminates need to resubmit
Submit once, use as often as necessary
Gives the reviewer all information at a glance

4. eCTD Lifecycle ComponentsID
A unique identifier for a leaf
hlink:xref
Identifies the file’s location
Operation Attribute
Relationship of this leaf to prior leaves
Modified-File
Identifies prior leaf affected by this leaf

5. Lifecycle Components in DepthID
Must be unique in submission
Best practice is unique in application
hlink:xref
Must be stated relative to location of us-regional.xml or index.xml
Necessary for all operations except Delete

6. Lifecycle Components in Depth …Continued
Operation Attribute
New
Referenced file is being used in a new context
Append
Referenced file is being used to add information
Append only files introduced as New or Replace
Replace
Referenced file is being used to replace a previous file
Delete
Leaf is used to signal that a previously submitted leaf is no longer

7. Lifecycle Components in Depth …Continued
Modified-File
Necessary for all operations except New
References the leaf which introduces the file, e.g. ../0000/index.xml#id12345

8. What the heck does ../0000/index.xml#id12345 mean
In the 0000 submission to this application
/index.xml
Look in the eCTD backbone
#id12345
For leaf-id 12345
Don’t worry, the tools generally take care of this

9. Life Cycle has many issues
File Location
Leaf Life Cycle
Application Life Cycle
Document Life Cycle

10. File Location FDA preserves the file structure you provide
Submissions stored by sequence number
Sequence numbers stored in high level folder name according to application type and number
CDER Application Types
“ind”
“nda”
“anda”
“bla”
“dmf”
Application number is 6 digits, no special characters
021756
101342

11. What does this look like to CDER?

12. Why is file location so important?
It supports the leaf lifecycle capabilities afforded by eCTD
It supports the cross-application referencing afforded by eCTD through a know file structure across eCTD submissions
Generally managed by your builder tool

13. File vs Leaf – What’s the difference?
The actual contents of a submission
Includes documents, data, spl, support files
Leaf
XML concept used to introduce files into the application
Leaf vs File Life Cycle
It is the “leaves” that life cycle is applied to, not the documents.

14. Application Life Cycle
Applications are hierarchical collections of submissions
Application life cycle controlled through submission type, sequence, and related sequence
Top-level submission types should not use related sequence

15. Application Life Cycle …Continued
Top-level submission types are:
“original-application"
"annual-report"
"efficacy-supplement"
"labeling-supplement"
"chemistry-manufacturing-controls-supplement"
"other"

16. Application Life Cycle …Continued
Second-level submission types should generally use a single related sequence
Related sequence should always be a top-level submission type
Second-level submission types are:
"amendment"
"resubmission"

17. Application Life Cycle A Bad Example

18. Application Life Cycle A Good Example

19. Document Life Cycle
The ability to reference documents across applications
To use a document in a new context
Consider hyperlinks when sharing files across applications
Hyperlinks create a “virtual” document
May need to share all documents within the “virtual document”

20. Reaching back into the IND …What do you need to know
Name of the file
Location in Original Submission
Operation attribute is NEW
Access in through the hlink:xref element
The key is navigation
It’s just another file

21. Navigating for Document Life Cycle …Generating the hlink:xref
The Directions…building the xlink:href
The Scenario
../ gets you out of the 0000 submission in NDA
Adding ../ gets you out of the NDA
Adding IND012345/0000/m5/5352 gets you to your files location
../../IND012345/0000/m5/5352/study-report.pdf
You want to reference a leaf submitted in 0000 of your IND for NDA282166, sequence 0000
Your file is named study-report.pdf in

22. The Good News
../../IND012345/0000/m5/5352/study-report.pdf
../0000/index.xml#id12345
The intricacies of referencing within and across applications should be handled by your builder tools

23. Before you begin to implement
Check with your tool vendor
Contact us to see if there’s any new information
Discuss submitting a sample

24. Gary Gensinger gary.gensinger@fda.hhs.gov 301.796.0589