Regulatory & Marketplace
Brexit White Paper
The UK formally left the EU on 31st January 2020 and the transition period, as set out in the withdrawal agreement, will come to an end on 31st December 2020. During this transition period, the UK has continued to remain under EU pharmaceutical law. From 1st January 2021, the UK will be able to adopt an independent regulatory framework with the Medicines and Healthcare products Regulatory Agency (MHRA) positioned as the stand-alone regulator for medicines and medical devices. Negotiations between the EU and UK are still ongoing to define the future relationship and with only a matter of months left before the end of the transition period, there has been no formal agreement. For the pharmaceutical industry, this presents numerous challenges as companies prepare to continue supply of medicines that comply with new legislation. The preferred outcome for many within the industry will be to implement a mutual recognition agreement for areas such as GMP certification, batch testing, etc. between the UK and EU. It is unclear at this stage if an encompassing mutual recognition agreement is achievable, so all involved parties should be preparing for a ‘no deal’ scenario and review existing guidance to understand risk exposure and mitigating actions. The European Medicines Agency (EMA) updated the regulatory procedural guideline on the withdrawal of the UK and EU rules for medicinal products in March 2020. The practical guidance for procedures related to Brexit for medicinal products (EMA/478309/2017) was also updated to reflect the implications of the withdrawal agreement. From 1st September 2020, the MHRA started to issue guidance on the posttransition period that will come into effect as of 1st January 2021. The UK requirements will differ between Great Britain (GB, consisting of England, 8 INTERNATIONAL PHARMACEUTICAL INDUSTRY
Scotland and Wales) and Northern Ireland due to the Northern Ireland Protocol. The proposal for Northern Ireland will need to be agreed but the current position is that Northern Ireland will remain in compliance with EU legislation and comply with EU requirements with respect to medicinal products and medical devices. Separate guidance has been issued for inter-UK activities from 1st January 2021, where applicable. Control of Clinical Trials / Studies The MHRA guidance confirms that from 1st January 2021, clinical trial sponsors will still need to register trials in a currently established, publicly accessible register. For trials in the UK only, this can be the ISRCTN registry but for trials involving UK and EU sites, this will be recorded in the EU Clinical Trials Register. For UK-based clinical trials, the sponsor or legal representative of a clinical trial will be required in the UK or an approved country. The approved country list will include EU/EEA countries. Where a clinical trial has a rest-of-world sponsor and a UKbased legal representative but covers sites in UK and other sites within the EU/EEA, a legal representative located in the EU/ EEA should be assigned via a substantial amendment submission to the relevant competent authorities. For investigational medicinal products (IMPs) used in UK clinical trials, the supply chain may include UK or approved country (EU/EEA) release sites from 1st January 2021. Where the IMP is supplied from a EU/ EEA manufacturer, the sponsor will have 12 months from 1st January 2021 to ensure a UK MIA(IMP) holder puts in place an assurance system to confirm each batch of IMP has been certified by a QP before release to the trial. This will require a substantial amendment to be submitted to the MHRA to register the details of the UK MIA(IMP) holder performing the ‘supply chain oversight’. Clinical trials involving EU/EEA markets will require the addition of EU/EEA IMP release site to be included via a substantial amendment where this is currently performed by a UK IMP release site only.
Marketing Authorisation Holders For medicinal products registered in the EU/EEA, Article 2 of Regulation (EC) No 726/2004 will still apply that confirms the marketing authorisation holder (MAH) must be established in the EU/EEA. Therefore, an MAH currently established in the UK must be transferred to one in the EU/EEA before the end of the transition period. In the UK, marketing authorisations (MAs) that were registered via the EU centralised procedure will be transferred to a GB national licence but will remain applicable in Northern Ireland. Future EU marketing authorisations will continue to include Northern Ireland. A GB presence for MAs must be registered within 24 months after the end of the transition period. The EMA guidance confirms that at the end of the transition period, UK notified bodies will lose their status as EU notified bodies and will no longer be able to perform conformity assessment activity for medical devices. Product owners will need to apply for a new certificate from a recognised EU notified body or arrange for a file transfer from the current UK notified body to an EU notified body that will take over responsibility. In GB, the current EU medical devices legislation will be given effect in UK law from 1st January 2021. This will not include the EU Medical Devices Regulation nor the EU in vitro Diagnostic Medical Devices Legislation as they will not take effect until after the end of the transition period. Northern Ireland will be aligned with the EU. Medical devices in GB can, until June 2023, retain the CE marking and certification by EU/EEA-based notified bodies. However, all medical devices and in vitro diagnostic medical devices (IVDs) placed on the UK market will need to be registered with the MHRA within the proposed grace period post-transition. Companies that qualify for administrative and/or financial support from the EMA as a small or medium-sized enterprise (SME) must be established in the EU/EEA. Winter 2020 Volume 12 Issue 4
