Brexit. We can help you.
If you are affected by Brexit, we can help you stay compliant.
The United Kingdom (UK) formally left the EU on the 31st of January 2020 and entered into a transition period immediately thereafter, which came to an end on the 31st of December 2020.
The UK is now classed as a third country by the European Medicines Agency (EMA).
If you are based in the UK or hold a marketing authorization (MA) in the UK, you are affected by the UK’s decision to leave the European Union (EU).
We are ready to offer a range of services to help you stay compliant post-Brexit.
How this could affect you – Pharmacovigilance.
UK QPPV and National Contact Person for Pharmacovigilance.
From 1st of January 2021 onwards, for all UK MAs, the Marketing Authorization Holder (MAH) must have permanently and continuously at its disposal a qualified person responsible for pharmacovigilance (QPPV) who resides and operates in the EU or the UK and is responsible for the establishment and maintenance of the pharmacovigilance system.
If the QPPV is not based in the UK, a national contact person for pharmacovigilance (NCP) needs to be nominated by the 31st of December 2021 and notified to the Medicines & Healthcare products Regulatory Agency (MHRA) via the MHRA Submissions Portal within two weeks of appointment.
For all UK MAs, the MAH must maintain and make available upon request of the MHRA a Pharmacovigilance System Master File (PSMF) that describes the pharmacovigilance system for the UK authorized products.
The UK PSMF must be accessible electronically from the same location in the UK from which the ADR reports are accessible. A UK PSMF number shall be requested via the MHRA Submissions Portal by the 30th of June 2022, unless there is a change in the details of the QPPV or if the MAH is applying for a new MA prior to this date.
Notification of the PV system details to the MHRA.
Existing holders of UK MAs shall submit Type IAIN variations related to the summary of the pharmacovigilance system (SPS) to the MHRA by the 30th of June 2022 (unless the QPPV details change prior to this date).
MAHs are required to submit individual case safety reports (ICSRs) to the UK directly through reporting to the MHRA. MAHs with products on the UK market shall have access to the applicable MHRA Submissions portal and report ICSRs through either the MHRA Gateway or the MHRA ICSR submissions portal.
The MHRA eSUSAR system can be used to report suspected unexpected serious adverse reactions (SUSARs) from clinical trials.
Signal detection, safety referrals and major safety reviews.
MAHs are obliged to notify the MHRA of signals arising from any data source from 1st of January 2021, including standalone signal notifications.
MAHs are obliged to notify the MHRA of emerging safety issues within three working days after establishing that a signal or a safety issue from any source meets the definition of an emerging safety issue.
From 1st of January 2021, where there are concerns regarding a medicine or class of medicines that are authorized in the UK, the MHRA may conduct a major safety review to review the available data and consider what regulatory action may be needed.
Risk Management Plan (RMP), Periodic Safety Update Report (PSUR), Post-Authorization Safety Studies (PASS) protocol and/or results.
The EU format for the aforementioned documents and reports is acceptable for submission to the MHRA. Additional annexes may be requested by the MHRA. New routes of submission (MHRA portal) are applicable, including fees.
How this could affect you – Regulatory Affairs.
UK and EU MAH’s.
Marketing Authorization Holder’s (MAHs) currently established in the UK who hold Marketing Authorizations (MAs) in the EEA will need to transfer them to a MAH already established in the EU/EEA, through the Marketing Authorization Transfer process (MAT).
Products authorized in the UK can have MAHs established in the EU/EEA or UK (Great Britain or Northern Ireland).
Converted Centralized MAs.
From January 1st 2021, all centralized MAs were automatically converted to Great Britain MAs and were issued with a Great Britain Product Licence number (PLGB).
The implementation of the Northern Ireland Protocol means that existing centralized MAs remain valid in Northern Ireland, and they retain the EU licence number.
MAH’s had the option to opt out of the conversion process prior to 1st January 2021 by notifying the MHRA in writing.
For all converted centralized MAs, MAHs must submit certain information by 31st December 2021. This includes an initiating sequence including an updating application form, Summary of Product Characteristics (SmPC) and packaging details. Full guidance is available on the MHRA website.
MRP/DCP Products Authorized Prior to 1st January 2021.
For products already authorized prior to 1st January 2021, they were already issued with national UK MAs as part of these procedures. The MAH has the option to:
- Maintain a UK-wide (i.e., which will include Northern Ireland). In this case the Great Britain MA will be aligned with but not part of the DCP/MRP and Northern Ireland will remain as part of the DCP/MRP as a CMS.
- Request separate MAs are issued for Northern Ireland (as a CMS as part of the DCP/MRP and for Great Britain.
- Remove Northern Ireland from the MRP/CDP and just maintain a national MA for Great Britain only.
There are several options for MAH’s to obtain a MAA in the UK and which route you take will depend on the timing of any MAA application and the route of application that would have been taken pre-brexit.
European Commission (EC) Decision Reliance Procedure.
For products eligible for assessment by the EMA centralized procedure, there is an option to rely on a decision taken by the EC and obtain a MA in Great Britain (England, Scotland and Wales).
The MAH will be required to submit the dossier to the MHRA upon receipt of the EMA’s positive CHMP opinion. The MHRA will then determine the GB MA within the same 67-day timeline as it takes for the EC to issue their decision.
This route of authorization is only currently available until 31st December 2023.
Decentralized and mutual recognition reliance procedure.
The MHRA is able to grant a UK or GB MA when MAs have been approved in EU Member States via the DCP or MRP procedures. As with the EC Decision Reliance Procedure described above, the MHRA aim to approve the MAA within 67 days of receipt of a valid application.
For products that are not eligible for reliance procedures, a national application remains the most obvious route to MA in the UK or GB. The MHRA have announced the option of an accelerated 150-day assessment for high quality MAAs and the option to submit for rolling review.
UK Post Brexit Initiatives.
The MHRA is now part of the Access Consortium that align and share reviews of MAAs with the national regulatory authorities of Australia, Canada, Singapore and Switzerland.
The MHRA is also involved with Project Orbis, a programme coordinated by the US FDA, to review and approve oncology products in Australia, Canada, UK, Singapore, Switzerland, Brazil and the US.
The MHRA will review Orphan Drug Designation (ODD) applications at the time a MAH submits a MAA. The application should be included in the MAA submission.
If an EU ODD already exists, the MAH can only apply for a GB ODD at the time of the UK/GB MAA. If no EU ODD exists, the MAH can apply for a UK-wide ODD.
Paediatric Investigation Plans & Waivers.
Products that require PIPs or PIP waivers in the EEA will also need one for a UK or GB MA to be validated. The UK has adopted the EU requirements including the EMA class waiver list.
EU PIPs or waivers agreed prior to 1st January 2021 have been adopted as UK PIPs and re-submission or reassessment is not required.
After 1st January 2021, PIP and waiver requests will need to be submitted to the MHRA for review. If there is already an assessment ongoing for an EU PIP prior to 1st January 2021, the MHRA will aim to align with the position of the EMA’s PDCO. If there is not an EU PIP/waiver application under assessment as of 1st January 2021 then a full UK PIP/PIP waiver assessment will be required and the MHRA wish to be kept informed of any ongoing or parallel EU assessment PIP assessment.
Importation and Batch Release Requirements.
Products going into the EU/EEA from the UK.
From the 1st January 2022, any product imported from the GB into the EU will be treated as coming from a third country and the usual requirements of import, QC testing and EU batch release will be required. Batch release by an importer or manufacturer based in Northern Ireland will be recognized in the EU/EEA, and in this instance the additional importation and testing requirements summarized above will not be needed.
Products going into the UK from the EU.
The UK will continue to recognize products batch tested and QP released for GB licences. From the 1st January 2022, import into the UK for GB products will need to be overseen by a UK based Responsible Person for Import (RPi).
If a product is intended for Northern Ireland, the usual EU/EEA requirements for import, QC testing and batch release apply.
How we can help.
We offer a significant strategic advantage by providing an end-to-end service with Regulatory Affairs and Pharmacovigilance and have the legal and commercial infrastructures in place to ensure post-Brexit compliance for both regions affected by Brexit (UK, European Economic Area (EEA)).
- We can establish a Pharmacovigilance system both for an EU MAH located in the EU, and a UK MAH with a PSMF located in the UK at a point where the reports of suspected adverse reactions are accessible electronically or physically.
- We can act as a MAH in the EEA and in the UK.
- We can handle your RMS switching and prepare, publish, and submit all the variations and transfers of MAs for your products.
- We can handle all necessary PSMF updates and adaptions to cover UK/EEA specific requirements.
- We can establish a legal entity in the EEA and the UK on your behalf.