Sending a submission to the Health Authority is the final step of the submissions publishing process. Vault’s integrations with the FDA Electronic Submissions Gateway (ESG) and EU EMA eSubmissions (ESUB) Gateway allow you to publish and submit directly from a Submission record to the relevant Health Authority.
In order to send a submission directly to the Health Authority, your Admin must first set up a Gateway Profile and provide you with a Vault URL to create an AS2 account at the FDA or EMA. This ensures the Health Authority can successfully receive electronic submissions. To learn about creating an AS2 account, view the FDA website or the EMA website.
Note: This feature is only available on RIM Submissions Publishing Vaults.
How Gateway Integration Works
Gateway integration enables you to plan, author, publish, and send submissions to the ESG or ESUB without needing to download documents or submissions from your Vault.
With gateway integration, Vault can validate the required information on a submission before submitting it for transfer and provide status details for the transfer.
Once submitted, Vault adds the following attachments to the Submission record:
- A log summarizing general information about the transmission, including a list of transmitted files and details on errors that may have occurred
- Acknowledgments from the ESG or ESUB, allowing you to track and manage Health Authority responses within Vault
About the FDA Electronic Submissions Gateway
The ESG is provided by the FDA to allow for the transmission of electronic regulatory submissions. It enables the secure submission of regulatory content for review and is the central receipt point for sending information electronically to the FDA. Organizations can submit US submissions and Canadian submissions through the ESG.
Note: If your password on the Vault account used by the FDA to authenticate expires, you’ll need to contact the FDA to update the password. If you don’t update your password, incoming requests from the FDA will fail authentication.
About the EMA eSubmissions Gateway
The ESUB Gateway is provided by the EMA to allow for the transmission of regulatory submissions supporting eCTD Centralised Procedure applications. It enables the secure submission of regulatory content for review and is the central receipt point for sending eCTDs electronically to the EMA.
Creating the XML Delivery File
Before sending your submission for transfer to the EMA, you must create an XML Delivery File outside of Vault and add it as an attachment on the Submission record. See details from the EMA about creating the XML Delivery File.
Within Vault, the filename must include “delivery”, for example, 123_delivery.xml. If your submission has more than one attachment that meets the requirement, Vault uses the latest attachment.
In the event of a resubmission where the delivery file has not changed, Vault uses the latest delivery file attached to the submission in the transmission.
If a new delivery file is needed for a resubmission, add it the new delivery file as an attachment to the submission. At the time of transmission, Vault includes the new, updated delivery file. The previous delivery file remains visible in the Submissions Archive until the next transmission is started that includes the new delivery file.
When there is an existing Delivery XML in Submissions Archive, then the Gateway Confirmation dialog counts it as additional file (for example, Files: 10) over the expected file count (Expected Files: 9).
Sending Submissions to a Gateway
To submit to the EMA or FDA gateway:
- From the Applications tab, navigate to the individual Submission record.
- From the record’s Actions menu, choose Gateway Submission. This may vary based on your Vault’s configuration.
- In the Gateway Submission confirmation dialog, review the submission information. See details below for how Vault validates US and CA submissions to the FDA and EU submissions to the EMA.
- Click Submit.
Resending Submissions to a Gateway
You can reset dossier details to allow for correction and resubmission to the Health Authority when receiving a technical rejection. When configured by an Admin, Vault provides the Prepare Resubmission action on Dossier Details records in the Transmission Successful state.
To prepare a submission for resubmission:
- Navigate to the submission’s related Dossier Details record.
- From the record’s Actions menu, choose Prepare Resubmission. This may vary based on your Vault’s configuration.
- Vault confirms the actions it will execute. If you wish to continue, click Yes.
Vault begins processing the request and displays a Dossier Details successfully updated banner once complete.
Validation for US & CA Submissions
After you initiate the Submit to Gateway action for a US or CA submission, Vault validates the following before sending the submission for transfer:
- Application number
- Submission number
- Center
- Number of files
- Total size of the submission
- Count of validation result errors by Severity
The Gateway Confirmation dialog provides a summary of required submission information for you to confirm before queuing the submission for transfer to the ESG. For US submissions to the FDA, the dialog includes counts of validation results by severity. For CA submissions to Health Canada, the dialog includes counts of validation results by severity, grouped into the following categories: Validation Errors, Validation Warnings, Informational Validations, and Other Validation Errors.
If the submission’s content plan contains any validation errors with the Severity field set to High, you’ll receive a warning and must confirm that you want to continue.
Validation for EU Submissions
After you initiate the Gateway Submission action for an eCTD Centralised Procedure, Vault validates the following before sending the submission for transfer:
- Application number
- Submission number
- Number of files
- Total size of the submission
- XML Delivery File
- Applicant
- Procedure Tracking Number
- XML Submission ID
- Count of validation result errors by severity
The Gateway Confirmation dialog for EU submissions to the EMA includes counts of validation results by severity. The dialog provides a summary of required submission information for you to confirm before queuing the submission for transfer to the ESUB. If the submission’s content plan contains any validation errors with the Severity field set to Error, you’ll receive a warning and must confirm that you want to continue.
FDA Acknowledgment Responses
When sending a submission to the FDA ESG, Vault receives responses as acknowledgments and adds them to the Submission record as attachments. Vault also notifies the user listed within the Submission record’s Published Content Owner field. Each acknowledgment has a prefix of the date and time it was received, as well as the transfer ID. For example, 2017-11-25 18:12:23 ci1433968485346.681040@fdsul08646_te2.txt.
You may receive multiple acknowledgments from the FDA when an issue occurs during processing. Depending on the contents of the acknowledgments, we recommend contacting the FDA or Veeva Support.
The FDA ESG delivers three (3) different acknowledgments to the account from which the submission was sent:
Acknowledgment 1
When the FDA receives a submission, the ESG validates the signature to ensure it was signed by a valid certificate. Once the signature is validated, the FDA sends a Message Delivery Notification (MDN) back to the user. This is considered the first acknowledgment and confirms that the submission was delivered.
The first acknowledgment contains a Message ID and a timestamp showing when the submission was received. The Message ID uniquely identifies each submission and can be used to track and correlate a submission to its Center’s acknowledgment.
Acknowledgment 2
If signature validation is successful, the submission is unpackaged and restored to its original structure. The ESG generates and sends Acknowledgment 2 (Ack2) when unpackaging is complete. Ack2 also contains a timestamp and a Core ID, which the ESG uses to track a submission. Note that if unpackaging is unsuccessful, Ack2 will contain an error. The ESG only processes successfully unpackaged submissions.
Acknowledgment 3
In some cases, Centers may generate and send Acknowledgment 3 (Ack3) with validation results. Ack3 notifies you if the submission was successfully processed. The Ack3 may also include a Technical Rejection Notification that states why the submission was unsuccessful.
EMA Acknowledgment Responses
When sending a submission to the EMA ESUB Gateway, Vault receives responses and adds them to the Submission record as attachments. Each response has a prefix of the date and time it was received, as well as the transfer ID. For example, 2017-11-25 18:12:23 ci1433968485346.681040@fdsul08646_te2.txt.
The EMA ESUB Gateway delivers two (2) different responses to the account from which the submission was sent:
Message Delivery Notification (MDN)
When the EMA receives a submission, the ESUB validates the signature to ensure it was signed by a valid certificate. Once the signature is validated, the EMA sends a Message Delivery Notification (MDN) back to the user listed within the Submission record’s Published Content Owner field. This confirms that the submission was delivered, but doesn’t confirm that the EMA received a valid submission.
The MDN filename is prefixed with “ema_atch”, followed by the date and time. For example, ema_atch_2019-09-13T13-33-53.523Z.
Acknowledgment
After the submission has been delivered, the EMA reviews it for technical compliance. The acknowledgment notification confirms whether the submission passed or failed based on the current eCTD submission validation criteria.
If the submission is compliant, the acknowledgment confirms that it has been imported into the EMA’s review system. If the submission fails, you can find the error description in the XML and make the appropriate changes before you send the submission again. You may also receive a failure acknowledgment if you used the incorrect filename.
Vault Notifications & Logs
When you send a submission, you receive an email and a Vault notification. Both success and failure notifications include a link to the submission within Vault.
Vault also generates a gateway transmission log, which you can use to confirm the header and list of files sent to the Health Authority, as well as troubleshoot gateway submission errors. Vault adds the log to the Submission record as an attachment.