Introduction
In 2015, the concept of grouped submissions was introduced with the implementation of the US Module 1 specification v3.3. Although the practice has been around for several years, it can still be a challenge for even the most seasoned eCTD professionals to understand. In very basic terms, a grouped submission allows sponsors to build a single eCTD sequence that, due to specific parameters on the backbone, allows information to be submitted to multiple applications. There are, however, restrictions on the type of submissions where this method is allowed. This blog will focus on one scenario where grouped submissions are permitted and can be extremely efficient: when submitting Advertising and Promotional Materials that refer to multiple products.
Ad Promo Submissions for Multiple Products
As sponsors grow their portfolios, they may eventually have multiple approved products for the same therapeutic area, and subsequently want to create advertising materials that reference more than one of their products. In this case, the materials in question must be submitted to all relevant applications. The options are to either build and submit a separate sequence for each product, or to submit one single grouped submission.
Please note in order to group submissions, the products must be the same application type. You can group NDAs with NDAs, and BLAs with BLAs, but you cannot group an NDA and a BLA.
Module 1 Submission Level Metadata
The most critical element to a successful grouped submission is ensuring that you have your Module 1 Regional metadata filled out correctly.
In a grouped submission, you choose one application to be your lead, or “parent” submission. This will be the submission where you physically build out your files. The other applications, or “child” submissions, will not need to have any files built. However, a unique sequence number must be assigned for each application in the group. Within the parent submission, you will build out the content necessary for your submission just as you would for a standard eCTD application. Then, ensure that within your submission level metadata, you have the application and sequence numbers for the child submissions associated.
Each eCTD compilation software has its own unique functionality in how to fill out your submission level metadata - be sure to consult with your software provider for exact mechanism by which you can complete grouped metadata. Please note that grouped submissions are not the same as “Cross-Reference” submissions.
The screenshot below provides an example of a properly constructed Application Information session for a grouped submission – note that the parent submission will have the value “true” for the field “Application Containing files”, where the child submission(s) should read “false”, as they will not have any files.
The parent submission is the only structure sent to the agency. When the FDA imports a submission with this metadata populated correctly, their system receives the parent sequence, reads the backbone, and recognizes that additional sequences should be created in the child applications. It then creates the necessary structures for all applications so that the files display to reviewers.
Building a Grouped 2253 Submission
Building a grouped 2253 submission is very similar to building a standard single sequence. (See WAYS’ previous blog for a full refresher on the process). The submission level metadata is filled out for all sequences as discussed previously, and then the documents are built out in the parent submission.
The documents required are as follows:
Module 1.1
A completed 2253 form – information should be filled out for the parent application.
A single page “2253 Attachment for Multi-Product Submissions” should also be included as a separate leaf beneath the form, and should include the following for each child application:
Application Type/Number
Product Name
Date/file name of most recent PI
Module 1.14.6
Current product labeling for all products referenced in the materials (can be physical PDFs or cross-reference leaves)
Module 1.15.2
Final materials
Non 2253 Grouped Ad Promo Submissions
Grouped non 2253 Ad Promo submissions are built very similarly to their non-grouped counterparts, with the primary difference being the submission level metadata. For a refresher on how to build out the different types of non-2253 Ad Promo Submissions, feel free to access the On-Demand recording of WAYS’ webinar: Ad Promo Submissions: Preparing for the eCTD Mandate
Listed below are notable content requirements, which will vary based on the type of submission (Correspondence, submission of draft materials, etc.)
Module 1.1 (if applicable)
2253 form with parent application information completed (remember, only CBER wants a 2253 form with draft materials)
A single page “2253 Attachment for Multi-Product Submissions” should also be included as a separate leaf beneath the form, and should include the following for each child application:
Application Type/Number
Product Name
Date/file name of most recent PI
Module 1.15.1
Cover letter should be placed in the proper subsection.
Subject line should clearly indicate the parent submission information and indicate a multi-product submission.
The child submission type/numbers should then be listed, as well as sequence numbers and the product names.
An additional attachment is not needed, as the information is captured in the cover letter
Module 1.15.2 (if applicable)
Draft materials
If annotated labeling is needed, be sure to provide an annotated label for all products
Common Errors
The table below highlights common errors seen by the agency when receiving grouped Ad Promo submissions:
Resources