Cross Application Links in eCTD

A little while ago, a client asked me about referencing documents submitted in one application from another application. Her question was in the context of an IND and an NDA, both submitted in eCTD format – did she have to re-submit documents in her NDA that had already been submitted in her IND?

The ICH guidance is basically silent on this subject, although the structure does not specifically prohibit any valid relative link. EMEA has stated that it is not allowed – in “EU Region Question and Answer and Specification Change Request Document”, see question 13:

“In the EU it is possible to refer to a file located in the same sequence or any previous sequence of the same eCTD. It is not possible to refer to other eCTDs.”

If you think about it a little, it requires each agency to maintain a specific set of folders in order for the links to work, and for the sponsor to understand what that structure is.

For example, if the agency stores eCTDs in a known folder path like this:


then I could provide a relative file path from my “NDA” 222222 back to files in my “IND” 111111. But if the agency does not maintain that exact folder structure, my links will break.

Gary Gensinger of FDA has said in several presentations that FDA will accept references to documents in other applications.

In order to do this, your publishing tool must be able to handle this scenario. A leaf must exist in your new application (you cannot reference leafs from other applications, only content files). You will need to know:

  • Name of the file
  • Location in Original Submission
  • Access in through the hlink:xref element, and the operation attribute is NEW.

    Gary provided the following example:

    With the following commentary:

    You want to reference a leaf submitted in 0000 of your IND 012345 for NDA282166, sequence 0000 – Your file is named study-report.pdf in 5.3.5.2. Using the following relative path will allow you to reference the study report:

    ../../IND012345/0000/m5/5352/study-report.pdf

    ../ gets you out of the 0000 submission in NDA 282166
    Adding ../ gets you out of the NDA 282166
    Adding IND012345/0000/m5/5352 gets you to your files location

    What I haven’t heard is how many people are taking FDA up on this offer.

    By the way, the RPS specification will be designed to allow cross application referencing from the start, and will not reply on a relative folder path.

    Article written by

    I am GlobalSubmit’s director of professional services. My area of expertise is electronic document management and regulatory submissions, specifically eCTD. I have 12 years of biopharmaceutical industry experience in the US, Europe, Israel and Japan, concentrating on content management for Regulatory Affairs & Submissions, Clinical Development, and Manufacturing, and in submission assembly and publishing. I have worked with over 50 pharmaceutical clients. Previously, I was the practice lead for the Subject Matter Experts/Business Analysts group at First Consulting Group (FCG), now part of CSC. I supervised a group of 12 SMEs/BAs. I was instrumental in the development of the FirstDoc® suite. I developed the project delivery methodology for FirstDoc® R&D, including training materials, project plans, workshop methodology and materials, and requirements and design specifications. I managed the design and development of FirstDoc® GMP and FirstDoc® Legal. Please feel free to contact me at kathleen.clark@globalsubmit.com if you are interested in talking about eCTD products or consulting services, or if you have ideas for the blog.

    2 Responses

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    1. Todd
      Todd March 6, 2009 at 11:05 PM | |

      Will this work for ANDAs also?

      directory of “anda123456″?

    Please comment with your real name using good manners.

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