The impact of Brexit has been a major topic for debates amongst the industry experts for the past two years. It has left companies on both the sides, the United Kingdom (UK) and Europe, hanging on a loose thread. As the date of Brexit is drawing closer, industries are aggressively looking for contingency plans for sustaining their business, if the UK leaves with a ‘no-deal’. Coming to the scenario of Life Sciences regulations, if the UK leaves the European Union (EU) with a no-deal, the former will no longer be a member of the EU medicines and medical device Regulatory networks. Simply put, companies of EU will not be able to make submissions in the UK.

To ensure that companies from EU can still submit Regulatory and notification information to the UK, Medicines and Healthcare Products Regulatory Agency (MHRA) has come up with an alternative. The agency is preparing to deliver a new IT system in case their access to EU’s system is ceased after Brexit. Recently, the MHRA conducted a webinar for companies to take them through the tentative submission portal, and its registration and submission processes.

The new system for submissions to the UK and to the MHRA is called as the “eSubmission Portal” as of now and will be an equivalent to Common European Submission Portal (CESP) or any other EU portal.

Registration Process for eSubmission Portal:

Even though the MHRA wants registration process to be on the same lines with the CESP or any other EU portal, the specifics are yet to be agreed upon. But, the agency cannot migrate the existing administrative details of CESP to their database as the data controller of the current CESP company is the Health Products Regulatory Authority (HPRA) and the current negotiation status does not allow the MHRA to request the HPRA for details. The agency will be providing the companies with more information in the coming two months, i.e., February and March.

To register themselves on the portal, a company needs to follow the following steps:

1. The company needs to fill a form as an initial request for access
2. The portal will revert with a link containing a form
3. The form requires information related to the company
4. Once the details are submitted, MHRA reviews it
5. Post review, admin access is granted to the company

The admin has the right to add and manage as many users as he/she may want. Once the access is granted to the admin, he/she can sign in the portal and submit documents. The portal supports a number of formats of submissions which can help companies to submit documents directly to the UK, to the MHRA. Some of them include:

To make submissions for clinical trials via eSubmission portal, a company must generate its EudraCT (European Union Drug Regulating Authorities Clinical Trials) number from the European Clinical Trial database from its official website and login into IRAS and create the application. Alternatively, the admin can also login to EudraCT to create and complete the application and download it.

Submission Process:

1. Clinical Trial Submissions
   1. Login to the eSubmission portal and select the submission type as “clinical trial submission”.
   2. Fill in the details asked in the form regarding the submission. There are two routes for submission: webform and SFTP.
   3. In the case of a webform, once the details are filled, upload the .zip file of documents and submit the file.
   4. In case of SFTP, once the details are filled, download the delivery file in XML format and upload both, the .zip file of documents and the delivery file, on the SFTP client and submit.
   5. Post the submissions, the agency will send a confirmation to the company via email.

To submit a PSMF document to the MHRA, the company can choose either a webform or an SFTP route.

Submission Process:

2. Qualified Person for Pharmacovigilance (QPPV) and Pharmacovigilance System Master File (PSMF)
   1. First, login to the eSubmission portal and select the submission type as “Type 1a variation” and fill in the delivery details.
   2. In case of a web form, once the details are filled, upload the .zip file along with the variation form of Market Authorization and submit.
   3. In case of SFTP, once the details are filled, download the delivery file in XML format and upload both, the .zip file of documents along with the variation form of Market Authorization and the delivery file, on the SFTP client and submit.
   4. Post the submissions, the agency will send a confirmation to the company via email.

As of now, all the PSURs in Europe are submitted to the European Medical Agency and not MHRA. But once the UK leaves EU, it will again allow the submission of PSURs to the MHRA via eSubmission portal.

Submission Process:

3. Periodic Safety Update Reports (PSUR)
   1. Login to the eSubmission portal and select the submission type as “PSUR”.
   2. Complete the webform by filling in the details.
   3. Upload the PSUR in eCTD format onto the portal and submit.
   4. Post the submission, the agency will send a confirmation to the company via email.

Reference: Gov.uk

Features of eSubmission Portal

• Dashboard – The portal provides admins with real-time downloadable reports and submission metrics for better monitoring of submissions and troubleshooting.
• Track and Search – Admins can navigate through all the documents submitted to the MHRA over the period of time with their status (success/failure). The feature is useful for web submissions only.
• Two-way Communications – This feature is available only for PSURs and pediatrics submissions. It sends the admin an email notification every time the agency sends a message on the portal.
• General Information – General information such as announcements and updates are also available on the portal.
• Guidance – Any information regarding the agency or the portal can be found on the portal with the help of FAQs and Training documents/videos. Admins can also contact concern authorities through the portal.
• Support – Admins can raise tickets in case any issue is observed.

Though still under development, the portal is just the initial step taken by the MHRA to smoothen the transition if the UK leaves EU without a deal. The agency will conduct more webinars in the near future to address more stakeholders on new systems and processes for medicinal products and the UK medical device manufacturers and suppliers.

Streamlining submission process is highly necessary for a company to make a compliant submission. With new updates on the way and less time for transition, consulting a Regulatory expert in publishing and submissions to achieve compliance is highly advised. Stay up-to-date.