You can use an eCTD Compliance binder and connected promotional pieces to generate an FDA Form 2253 from within Vault. Vault automatically populates the form using field values from the binder and from connected documents. With the correct configuration, Vault can generate the supplementary sheet required for multi-product 2253 submissions.

Please note that you must use XFA form mapping in order to utilize the FDA’s 2253 form. When you create an eCTD Compliance Package, Vault automatically generates a new Compliance Package with Submission Ready Copies of documents and converts Vault link annotations to relative PDF links.

Preparing to Generate a Package

Before generating a Compliance Package and submitting it to the FDA, you’ll want to verify that your references and promotional materials are in order. Note that “promotional material” refers to the material you perform the Create Post Marketing Compliance Package or the Create Pre Clearance Compliance Package action on.

On your promotional material:

  • Ensure that any necessary Vault link annotations are on the document versions to be included.
  • Verify that the following fields are populated on all documents:
    • Material Type
    • Professional/Consumer
    • Dissemination/Publication Date
    • Submission Required is set to Yes and that the Submission Type is set to FDA 2253, if applicable
  • Determine which reference documents must be included, and delete any that are unnecessary. For example, if you deleted a Vault link annotation from a document, and the reference document is now unused, you can delete the reference document from the Linked Document section to prevent it from being copied into the Compliance Package.
  • Ensure that the correct version of any relevant supporting documents are included, and delete any that are unnecessary.
  • Upload any additional Clean Version documents in a ZIP file using the eCTD Submission Package rendition type.
  • In the Linked Documents section, verify that the PI labelling material is linked to the correct version of the promotional pieces as linked document or Vault link annotation. Vault copies the PI labelling material to the 1.14.6 Product Labelling section of the package, and any link annotations to the 1.15.2.1.2 Annotated Version section.
  • Verify that the only documents linked to the promotional material via a Linked Document relationship and/or the eCTD Support Documents relationship are the ones you want copied into the Compliance Package.
  • Ensure that all anchors linking to the promotional piece are in the same version of the reference/PI labelling material. If they aren’t, Vault will not convert some of the anchors to destinations in the binder.
  • On the Dosage and Indication objects, verify that an Admin has created records for the products included in the Compliance Package. Note that this only applies if you are generating a Pre-Clearance Compliance Package.

Adding Supporting Documents

To add supporting documents to the Compliance Package, upload the documents to Vault classified as the Supporting Document type and one of the following subtypes:

  • eCTD Compliance Annotated Material
  • eCTD Compliance Annotated Label
  • eCTD Compliance Annotated Reference
  • eCTD Compliance Clean Material

Then, create an eCTD Support Documents type document relationship between the supporting document and the relevant material included in the bulk action. Vault pulls Supporting Documents into the binder even if Linked References equals No on the Compliance Package.

Vault generates the submission ready versions of supporting documents when you add them to an eCTD Package as follows:

Original Document Subtype Submission Ready Version Document Type eCTD Package Folder
eCTD Compliance Annotated Material Annotated Material Annotated Version
eCTD Compliance Annotated Label Annotated Label Annotated Labeling Version
eCTD Compliance Annotated Reference Annotated Reference Annotated References
eCTD Compliance Clean Material Clean Material Clean Version

Adding Clean Version Documents

You can also add many Clean Version documents to the Compliance Package using a rendition type. Compress the documents into a ZIP file and add them to the promotional material with the eCTD Submission Package rendition type. You can then generate or regenerate the Compliance Package.

Adding Video/Audio Files

To add video or audio files to the Compliance Package, add Vault link annotations to the storyboard document as desired and bring forward any Vault link annotations from previous versions.

You can indicate that a video or an audio file should be included in the Compliance Package using the Final Video/Audio rendition type. If you have more than one video or audio file, we recommend using supporting documents or uploading them as a ZIP file to the eCTD Submission Package rendition type.

To use the Final Video/Audio rendition method, add the video or audio file to the storyboard as the Final Video/Audio rendition type. You can then generate the Compliance Package, selecting the storyboard along with the other documents.

When generating the Compliance Package, Vault automatically creates two (2) clean versions in the same section: one (1) copy of the storyboard, and one (1) copy of the Final Video/Audio rendition. If you annotated the storyboard, then Vault additionally creates one (1) copy of the storyboard with Vault link annotations converted to relative PDF links.

If the promotional material is an audio or video file, you’ll need to upload the file as a new document version after generating the Compliance Package, replacing the storyboard document. This ensures that the promotional material reaching a Steady state is the audio or video file, not the storyboard.

To use the supporting documents method, upload your video and audio files as standard eCTD subtypes under the Supporting Documents document type. Then add the uploaded file to the promotional document using the eCTD Support Documents relationship on the promotional material. You can also upload your storyboard as the supporting document to the Final Audio/Video file.

Generating the Compliance Package

To generate a Compliance Package:

  1. Select the appropriate documents.
  2. Click the Actions menu and initiate a bulk action.
  3. On the Refine Selection page, select the promotional pieces you want to use to create the eCTD Compliance Package.
  4. Click Next.
  5. Under Generate Compliance Package, select which package to generate.
  6. Click Next.
  7. On the Edit Details page, complete the required fields.
  8. Select Yes or No under Include Linked References to determine whether Vault creates relative PDF links.
  9. Click Next.
  10. On the Confirmation page, check that the information displayed is correct.
  11. Click Finish.

Vault notifies you after Compliance Package generation is complete. The process may take several minutes to complete.

PromoMats does not submit the Compliance Package to the FDA. You’ll need to move the generated Compliance Package through its workflow for review and approval. Then, you can export the generated Compliance Package to a separate publishing tool to submit it to the FDA. You can then mark the binder as Submitted in PromoMats.

Organizations with a PromoMats and a RIM Vault can configure a standard Vault to Vault connection, enabling seamless flow from compliance package generation in PromoMats to package submission in RIM.

Correcting Errors in the Compliance Package

After generating the Compliance Package, the binder enters the Draft state, and users can review and make changes to the 2253 or Supplementary Form, relative PDF links, reference documents, PI labelling material, supporting documents, or promotional material version. Do not make changes to the binder metadata, as Vault automatically generates metadata when creating the Compliance Package. Changes to the binder metadata will not be reflected in the binder.

To make changes to the documents:

  1. Navigate to the eCTD Source document. To find this document, open the document to be updated and click the eCTD Source relationship link.
  2. Update the eCTD Source document or linked supporting documents.
  3. Return to the binder.
  4. Click the Actions menu and select Regenerate Compliance Package.

Vault notifies you after Compliance Package generation is complete. The process may take several minutes to complete.

Regenerating the Compliance Package moves the binder to the Draft state, up-versions it, and updates all documents in the binder that are linked to the eCTD Source documents. Vault up-versions the 1.15.2.1.2 Annotated Version by 0.2, while others up-version by 0.1. If you manually add any documents to the binder that aren’t linked to the eCTD Source through a Vault link annotation or document link, they will not be up-versioned. If you add a new Vault link annotation, linked document, or supporting document to the Promotional material before regenerating the Compliance Package, Vault copies the document and adds the Submission Ready copy to the binder. You must edit the eCTD Source documents directly to ensure edits are reflected upon regeneration. If you remove any linked or supporting documents from the promotional material, you’ll need to delete the copied versions from the binder.

The Regenerate Compliance Package user action does not work if you manually add documents to the eCTD binder after regenerating the package.

Adding Material

If previously configured in your Vault, you can click the Actions menu and perform a user action to add documents to the binder and regenerate the Compliance Package. You can only add documents with the same Product as the Product selected when generating the eCTD Compliance Package.

On regeneration, Vault creates submission-ready copies of the new material and updates forms and the Correspondence Letter where necessary. If the added documents have supporting documents linked via the eCTD Support Documents relationship, Vault creates and adds submission-ready copies of the supporting documents.

To add documents and regenerate the Compliance Package, you must have the Edit Document and Version permission on the lifecycle state.

Vault notifies you after Compliance Package regeneration is complete. The process may take several minutes to complete.

You can open Vault-generated relative PDF links in PromoMats or in a desktop version of Adobe™. In PromoMats, click the relative PDF link in a document to open the linked material in a mini-browser window.. To check the relative PDF links in Adobe™:

  1. Click Export Compliance Package.
  2. Unzip the exported file.
  3. Open applicable documents in Adobe™. You will not be able to do this on an internet browser.
  4. Click the relative PDF links.

To replace Vault link annotations and linked documents after generating the Compliance Package:

  1. Navigate to the clean material Promotional piece eCTD Source document in the binder. To find this document, open the document to be updated and click the eCTD Source relationship link in the Document Relationships section.
  2. Update Vault link annotations and linked documents as desired.
  3. Return to the binder.
  4. Click the Actions menu and select Regenerate Compliance Package.

When Compliance Package generation is complete, delete the binder documents from which you removed Vault link annotations. These documents were not up-versioned in the 1.15.2.1.3 Annotated Labeling Version, 1.15.2.1.4 Annotated References, and 1.14.6 Product Labeling sections. If you manually added the documents to the Compliance Package during this process, or if the documents were added as part of the regeneration process, Vault did not up-version them. Do not delete these documents if you want to keep them.

Note that, for Pre Clearance Compliance Packages, you may need to add additional manual annotations to the documents in Adobe™ before submitting the package to the FDA.

Reviewing the Compliance Package

When you are satisfied with the binder, you can move it to the In Review state, allowing the eCTD Regulator to review the Compliance Package. If the eCTD Regulator rejects the binder, you’ll need to move it to the Revise and Resubmit state, make the necessary changes, and regenerate the binder. Then, move the binder to the In Review state and allow the eCTD Regulator to review the package again. Once the eCTD Regulator approves the Compliance Package, move the binder to the Submission Ready state.

Reviewing the Correspondence Letter

Before exporting a Pre Clearance Compliance Package, you’ll also need to review the Correspondence Letter. For submission to the FDA, the Correspondence Letter must be a PDF file. The Correspondence Letter that is generated as part of the Pre Clearance Compliance Package is a Microsoft Word™ document. You can edit the document by updating the metadata directly. Once you’ve reviewed the Correspondence Letter, you’ll need to download the viewable rendition. Upload the PDF file as a new version of the Correspondence Letter document. Then, return to the eCTD binder and click Edit Binder. In the Correspondence Letter section, click the Actions menu and select Set Version Binding. Select Always show the latest version, then click Done editing to save your changes. This allows Vault to export the Correspondence Letter as a PDF file as part of the Compliance Package.

Exporting the Compliance Package

After the eCTD Regulator approves the binder, the Compliance Package Publisher can perform the Export Compliance Package user action, download the ZIP file, and extract the documents. The Compliance Package Publisher can then import the documents into a RIM Publishing Vault.

To import the Compliance Package to RIM Publishing Vault:

  1. Upload the ZIP file into a RIM Publishing Vault.
  2. Create a Submission Content Plan.
  3. Match documents from the Compliance Package to the content plan structure.
  4. Using RIM Publishing, prepare the content for submission to the FDA.

If you need to edit the package content while working in the RIM Publishing Vault, you’ll need to return to PromoMats, move the binder to the Revise and Resubmit state, and update the contents.

When the package is finalized for submission in RIM Publishing, you can submit the package to the FDA. After submitting the Compliance Package, return to your PromoMats Vault and move the binder to the Submitted state. You’ll also need to move the promotional material to the Steady state.

Compliance Package Components

Vault includes the following documents in each package:

Package Type Documents Included
Post Marketing Compliance Package 2253 form
Supplementary form if there is more than one product
Product Labelling material
Clean Material
Metadata.xml

If references are included:
Annotated Material
Annotated Label
Annotated Reference
Pre-Clearance Compliance Package (Center APLB) 2253 form
Supplementary form if there is more than one product
Product Labelling material
Clean Material
Metadata.xml
Correspondence Letter

If references are included:
Annotated Material
Annotated Label
Annotated Reference
Pre-Clearance Compliance Package (Center OPDP) Product Labelling material
Clean Material
Metadata.xml
Correspondence Letter

If references are included:
Annotated Material
Annotated Label
Annotated Reference

Note that the binders include new copies of the specified documents rather than the exact documents selected.

FAQ

Why were some documents not converted to PDF?

When generating the binder, Vault up-versions all Submission Ready Copy documents included to Draft v0.2 as a PDF unless the original source doesn’t have a PDF rendition. This may happen with large documents. You’ll need to upload a PDF of the document and manually create the relative PDF links and destinations.

What information is included in the metadata.xml file?

When you use the Export Compliance Package user action, Vault generates a ZIP file. After extracting files from the ZIP, you’ll see the contents of the binder and an XML file. The XML file contains details about documents in the binder, including 2253 and Supplementary Form field data where applicable. Download a sample metadata.xml file.

No. If the link annotation and anchor are in the same document, it won’t be converted to a relative PDF link.

If a link annotation links to multiple documents, the destination will only link to one (1) of the documents when converted to a relative PDF link. If there are multiple link annotations on the same text or area, the destination will only link to one (1) of the documents when converted.

Will the eCTD Source relationship type take me to the document used to create the Compliance Package?

The eCTD Source relationship links to the latest version of the document Vault used to create the document copy included in the Compliance Package.

Why does the Export Compliance Package notification show a higher document count than I selected at the beginning?

The binder generates Submission Ready Copies of the documents selected at the start of the bulk action, including documents linked through link annotations or linked documents, such as reference materials and PI labelling materials.

What happens if I add another XML file to the Attachments section of the binder metadata?

When you export the Compliance Package, the XML file generated includes any XML files included in the Attachments section. If you notice data is missing after exporting, you can add it as a separate XML file in the Attachments section of the binder. Then, export the Compliance Package again and the XML file generated will contain all files from the Attachments section.

Is the latest version of the 2253 form always shown in the binder, regardless of the binder version?

Yes. Performing the Generate Form 2253 action up-versions the 2253 and Supplementary forms. The latest version of the forms are available on all versions of the binder.

If I manually add documents to the eCTD Compliance Binder after it has been generated, will those documents be included in the export?

Yes. All documents in the binder are included in the export and corresponding XML file. However, it is your responsibility to ensure that the manually-added documents are correctly named to meet FDA requirements that Vault link annotations are converted to relative PDF links.

To do this, you’ll need to archive or delete the binder and its contents and restart the bulk action with the new promotional materials.

Can I change the Material Type after generating the eCTD Compliance Package?

No. To change the Material Type, you’ll need to archive or delete the binder and its contents and create a new Compliance Package.

Can I change the Center from OPDP to APLB (or vice versa) after generating the Pre-Clearance Compliance Package?

No. To change the Center field, you’ll need to archive or delete the binder and its contents and create a new Pre-Clearance Compliance Package.

Can I update the Correspondence Letter after generating the Pre-Clearance Compliance Package?

Yes. You can edit document fields directly on the Correspondence Letter after the Compliance Package generates. When you’re finished editing, refresh the page to update the document. Note that changes to the eCTD Source materials will only appear on the Correspondence Letter after regenerating the Compliance Package and then re-rendering the Correspondence Letter.

Can I update the Include Linked References field on the binder metadata after generating the Post Marketing or Pre Clearance Compliance Package?

No. To update the Include Linked References field, you’ll need to archive or delete the binder and its contents and create a new eCTD Compliance Package.

Why isn’t the reference material where I expect it to be?

If the same reference material has destinations for multiple materials, it only appears in one (1) section, but includes destinations of the relative PDF links from the other material. This is also true of PI labelling material.

Why isn’t PI labelling material included in my eCTD Compliance Package?

Verify with an Admin that the eCTD Compliance Package is configured correctly. When uploading PI labelling material, your Admin must be sure to assign the same document type as identified in on the Application Settings page. The document must be linked to the promotional material with a link annotation or document link. To ensure that Vault populates section (6) of the 2253 form, your Admin must attach the PI labelling document to the Current PI/Label Number field on the product record.

Why am I receiving a server issue when exporting the Compliance Package?

Exporting the Compliance Package in Firefox® or Safari® browsers may result in a server error. We recommend using the Google Chrome™ browser to export the package.

What file types can I add as the Final Video/Audio rendition type?

You can add any file type as the Final Video/Audio rendition type. Note that you should only add the Final Video/Audio rendition type to the document with the final version of the video or audio file that you are submitting to the FDA.

Which permissions do I need for eCTD Compliance Packages?

See the list of related permissions below.

How are documents named in the binder?

You can view the naming rules for documents here.

How many documents can I include in an eCTD Compliance Package?

You can include a maximum of 50 Promotional Materials in a Compliance Package. The total number of materials and supporting documents in an eCTD Compliance Package cannot exceed 200.

Why aren’t my supporting documents being added to my Compliance Package?

There are two (2) criteria for adding supporting documents to a Compliance Package:

  • The supporting document must be one of the standard eCTD document subtypes in the Supporting Documents document type.
  • The supporting document must be linked to the promotional material using the eCTD Support Documents document relationship.

If one or both of the criteria are not met, Vault will not add the supporting documents to the Compliance Package.

The following permissions and document type and role permissions now control the ability to work with eCTD Compliance Packages. Note that you must apply the document role permissions to states in the lifecycle your promotional material is using. By default, this is the Material lifecycle.

Type Permission Label Controls
Security Profile Object: Center: Read Ability to create, review, and/or approve the eCTD Compliance Package.
Security Profile Object: Promotional Material Document Type: Read Ability to create, review, and/or approve the eCTD Compliance Package.
Security Profile Object: Indication: Read Ability to create, review, and/or approve the eCTD Compliance Package.
Security Profile Object: Dosage: Read Ability to create, review, and/or approve the eCTD Compliance Package.
Security Profile Object: Product Indication Join: Read Ability to create, review, and/or approve the eCTD Compliance Package.
Security Profile Object: Promotional Material Information: Read Ability to review and/or approve the eCTD Compliance Package.
Security Profile Object: Promotional Material Information: Create Ability to create the eCTD Compliance Package using the bulk action with relative PDF links automatically created and correspondence letter populated.
Security Profile Object: Indication: Edit Ability to edit the Indication object and create object records.
Security Profile Object: Dosage: Edit Ability to edit the Dosage object and create object records.
Security Profile Object: Product Indication Join: Edit Ability to edit the Product Indication Join object and create object records.
Document Type eCTD Submission Ready Documents: Create Binder Ability to create eCTD Submission Ready Document binders.
Document Type eCTD Submission Ready Documents: Create Document Ability to create eCTD Submission Ready Document type documents.
Document Type Health Authority Form: Create Document Ability to create Health Authority Form type documents.
Document Role Material: Annotate Ability to generate the eCTD Binder and all applicable documents when linked references (relative PDF links) are included. Add this permission to the state the document is in when the bulk action is performed to create the eCTD binder.
Document Role Reference: Annotate Ability to generate the eCTD Binder and all applicable documents when linked references (relative PDF links) are included. Add this permission to the state the document is in when the bulk action is performed to create the eCTD binder.
Document Role eCTD Submission Ready Documents: Download Source Ability to export the compliance package.
Document Role Edit Document Ability to add documents to the binder and regenerate the Compliance Package.
Document Role Version Ability to add documents to the binder and regenerate the Compliance Package.