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.
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. “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 labeling material is linked to the correct version of the promotional pieces as linked document or Vault link annotation. Vault copies the PI labeling material to the 1.14.6 Product Labelling section of the package, and any link annotations to the 1.15.2.1.3 Annotated Labeling 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 labeling 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. 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.
Important: Do not add the supporting document to the cart when generating eCTD Compliance Packages.
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 |
Note: The version binding for submission ready supporting documents should be Always show the Latest 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.
Preparing to Generate Multiple Compliance Packages
Before generating multiple Compliance Packages, you’ll want to verify that your documents are in order and that required fields are populated. This allows Vault to correctly validate documents.
On your documents, verify that:
- The Product field is populated with at least one (1) value.
- At least one value in the Product field is associated to a United States Application
- The Professional / Consumer field is populated and is set to either Professional or Consumer
- The Health Authority Submission field is set to either FDA 2253 or FDA 2253 Accelerated Approval
- The document type is not eCTD Submission Ready Documents, Supporting Documents, or Health Authority Form
When available, Vault automatically populates most Compliance Package metadata during bulk generation using from the following locations in the system:
| Compliance Package Field | Default Data & Location |
|---|---|
| Name | The custom naming format defined in your Vault’s document type configuration |
| Product | The Product field on the promotional material |
| Secondary Brands | The Product field on the promotional material |
| Application | Any United States Application associated to the primary product |
| Secondary Brands Application | Any United States Application associated to secondary products where the Application type matches that of the primary Application |
| Professional / Consumer | The Professional / Consumer field on the promotional material |
| Compliance Package Type | The Health Authority Submission field on the promotional material |
| Country | Defaults to United States |
| Responsible Official | The Responsible Official field on the primary Application object record |
You must manually populate the following fields:
- Correspondence Letter
- Submission Date
- Reg Comments to FDA
- Promotional Material Document Type*
- Launch Material Type
- Dosage
- Indication
- Any custom fields
* The Promotional Material Document Type must be manually populated on Pre Clearance packages. Vault automatically populates the field on Post Marketing packages.
Generating the Compliance Package
To generate a Compliance Package:
- Select the appropriate documents.
- Click the Actions menu and initiate a bulk action.
- On the Refine Selection page, select the promotional pieces you want to use to create the eCTD Compliance Package.
- Click Next.
- Under Generate Compliance Package, select which package to generate.
- Click Next.
- On the Edit Details page, complete the required fields.
- Select Yes or No under Include Linked References to determine whether Vault creates relative PDF links.
- Click Next.
- On the Confirmation page, check that the information displayed is correct.
- 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.
Note: Vault generates Compliance Packages, submission ready copies, and 2253 and Supplementary Forms as the System in the audit trail.
Generating Multiple Compliance Packages
When configured, you can also generate multiple eCTD Compliance Packages at once.
Note: You can only generate multiple Compliance Packages at once for United States applications.
Vault automatically groups documents based on the following fields:
- Product
- Professional / Consumer
- Health Authority Submission
To generate multiple Compliance Packages at once:
- Select the appropriate documents.
- Click the Actions menu and initiate a bulk action.
- On the Refine Selection page, select the promotional pieces you want to use to create the eCTD Compliance Packages. Then, click Next.
- Under Generate Compliance Package, select Create eCTD Compliance Packages. Then, click Next.
- Vault may indicate where there are validation errors. If there are, exit the action to resolve the error and then try again.
- If prompted, select the Primary Product for each group. Vault prompts you to select the primary product if a document in the selection includes more than one (1) product or if more than one (1) product is associated with a US application.
- Select a Primary Product to apply in bulk and click Apply. This bulk change only applies to groups containing the selected product. For example, if you select Cholecap for some groups and WonderDrug and Natevba for others, selecting WonderDrug as the main Primary Product only applies to the WonderDrug groups.
- Click Next.
- On the Preview Compliance Packages page, review and edit package details. If present, click to complete any blank required fields.
- Click Next.
Vault notifies you once all of the selected Compliance Packages are generated. The process may take several minutes to complete.
Correcting Errors & Troubleshooting the Compliance Package
After generating Compliance Packages, you can review the binders and make changes to the components, such as the 2253 or Supplementary Forms or relative PDF links.You can also troubleshoot any validation errors encountered during bulk generation. For more information on package generation errors, see Correcting Errors in eCTD Compliance Packages.
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:
- Upload the ZIP file into a RIM Publishing Vault.
- Create a Submission Content Plan.
- Match documents from the Compliance Package to the content plan structure.
- 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: Do not delete the metadata.xml file. This file will be exported as part of the Export eCTD Compliance Package user action. The XML file will only show Form 2253 information from when the 2253 form and Supplementary form are first generated. It will not show the signature or any changes made after.
The binders include new copies of the specified documents rather than the exact documents selected.
Related Permissions
The following permissions and document type and role permissions now control the ability to work with eCTD Compliance Packages. 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 the eCTD Compliance Package. |
| Security Profile | Object: Promotional Material Document Type: Read | Ability to create the eCTD Compliance Package. |
| Security Profile | Object: Indication: Read | Ability to create Pre-Clearance eCTD Compliance Packages. This permission is optional. |
| Security Profile | Object: Dosage: Read | Ability to create Pre-Clearance eCTD Compliance Packages. This permission is optional. |
| Security Profile | Object: Product Indication Join: Read | Ability to create the eCTD Compliance Package. |
| 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 Role | Material: View Content | 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. |