In July, we considered the implications of the UK Government’s Brexit White paper, setting out its proposals for the UK’s ongoing relationship with the EU post-Brexit and how this would apply to the supply and manufacture of medicinal products and medical devices. Acknowledging the need for a contingency plan if no agreement can be reached, the Medicines and Healthcare Regulatory Agency (MHRA) has now published guidance entitled “How medicines, medical devices and clinical trials would be regulated if there’s no Brexit deal“. Below, we set out the key points arising from that guidance.
The regulation of medicines and medical devices in the UK is currently subject to both EU and UK legislation and oversight. For example, in relation to medicinal products, Directive 2001/83 and Regulation 726/2004, which govern marketing and supply in the EU, are implemented into UK law by the Human Medicines Regulations 2012 (HMR). For medical devices, Directives 93/42 (on medical devices), 98/79 (on in vitro medical devices) and 90/385 (on active implantable medical devices) set out the regulations in the EU, and are implemented in the UK through the Medical Devices Regulations 2002 (MDR). In addition, the new Regulations 2017/745 (on medical devices) and 2017/746 (on in vitro medical devices) will apply from 2020 and 2022, respectively.
In the event of a no-deal Brexit, full regulatory authority will pass to the UK, and the European legislation will cease to apply to the UK on 29 March 2019 (exit day), although UK legislation that implements EU law will remain in force. Under the EU (Withdrawal) Act 2018 (EUWA), all existing EU rules will be converted into UK law at the moment of exit to the extent they are not already part of UK law.
While the HMR means that the bulk of EU law is already part of UK domestic law, in the longer term, there will be changes to the HMR to reflect certain practical implications of the UK’s withdrawal from the EU. For example, the MHRA’s guidance indicates that:
- Existing centralised marketing authorisations, assessed by the EMA’s CHMP and granted by the European Commission, will be converted automatically to UK marketing authorisations on 29 March 2019, unless marketing authorisation holders (MAHs) opt out.
- Existing products authorised under the decentralised and mutual recognition procedures will be unaffected as MAHs already hold a UK marketing authorisation.
- New applications for UK marketing authorisation will be submitted to the MHRA for national assessment.
- The outcome of applications for marketing authorisation via the EU procedures in progress on exit day will not be valid in the UK, although the MHRA will “take account” of EU decisions where possible.
- The UK will adopt the current EU data and market protection periods. The start date of data or market protection applicable in the UK will be the earlier of the product’s date of authorisation in the EU or in the UK.
- Existing marketing authorisations for generic products based on reference products with EU marketing authorisations will remain valid. However, as the MHRA will not have access to the data provided in support of EU authorised products, all new generic applications will need to be based on reference products authorised in the UK.
- The MHRA will continue to require a named individual in the UK who can be contacted in the event of a safety issue, and who has the authority to require independent re-testing of medicines or to withdraw a product from the market.
- The MHRA will require MAHs of UK authorisations to be established in the UK by the end of 2020. An application for Change of Ownership will need to be submitted to the MHRA to change from an EU MAH to a UK MAH.
- The MHRA will require a Qualified Person for Pharmacovigilance (QPPV) to be established in the UK from exit day, although those MAHs without a current UK presence will have until the end of 2020 to do so. In any case, companies will be required to make arrangements for providing the MHRA with access to safety data related to UK authorisations at any time. For example, the EU QPPV may take on responsibility for UK authorisations until the UK QPPV is established.
- A Qualified Person (QP) for products manufactured in the UK, or directly imported into the UK from a country not on a designated country list, must reside and operate in the UK. A QP for products manufactured in a country on a designated country list and imported into the UK, or manufactured in a third country and imported into the UK from a country on a designated country list, can reside in a country on the designated country list.
- The UK will continue to use the EU Good Manufacturing Practice and Good Distribution Practice guidelines.
- The UK will align with the EU/EEA exhaustion regime to ensure that parallel imports of goods, including pharmaceuticals, can continue from the EU/EEA.
The amendment of the HMR also offers an opportunity to revise certain aspects of the law to determine a new UK approach, for example, with regard to the regulation of orphan and paediatric medicines. The MHRA’s guidance indicates that the UK will continue to offer incentives to encourage paediatric medicines onto the UK market, and will make provisions for a UK Paediatric Investigation Plan (PIP). The guidance is less clear with regard to orphan medicines, although it suggests that the MHRA will consider offering incentives for these types of products. The MHRA has announced plans for a consultation on some of the key proposed legislative changes, which is to be held in the early autumn.
Again, the bulk of EU legislation is already implemented into UK law through the MDR. In the event of a no-deal Brexit, the MHRA’s guidance indicates that:
- The UK will recognise EU CE-marked medical devices for a limited time. However, the MHRA’s guidance makes clear that this is a temporary position and that, in the longer term, the process for bringing a medical device onto the UK market will be subject to consultation.
- As UK-based Notified Bodies will no longer be able to assess the conformity of medical devices for the purposes of the EU legislation, the MHRA will no longer be able to oversee Notified Bodies.
- The UK will comply with “all key elements” of Regulations 2017/745 and 2017/746. (The guidance does not detail which elements of the Regulation the MHRA considers to be “key”.)
- The MHRA will continue to monitor the safety of medical devices on the UK market, but will have authority to take decisions regarding the marketing of such devices in the UK without reference to the EU regulatory network or the European Courts.
The EU Clinical Trials Directive 2001/20 has been implemented in the UK through the UK Medicines for Human Use (Clinical Trials) Regulations 2004, and is managed by the MHRA at a national level. The law applicable to UK clinical trials will, therefore, be unaffected by a no-deal Brexit. However, the MHRA intends to:
- Refine the ethical approvals process to allow for a single application and a single national decision in the UK.
- Preserve the requirement for the clinical trial sponsor (or its legal representative) to be based in the EU/EEA, but introduce a further requirement for sponsors to appoint an individual based in the UK with responsibility for the trial, particularly for the purposes of discussing urgent issues, such as safety matters or trial suspensions.
- Develop a UK transparency system, aligned with the current EU provisions. The details of such a system would be subject to consultation.
The MHRA has said that Regulation 536/2014 on clinical trials will not be incorporated into UK law under the EUWA, although the UK will align with it “where possible”.
The details set out by the government are the UK’s position in the event there is no deal reached with the EU. However, it is unclear whether any of these points will be reciprocated by the EU (for example, whether the EU will accept parallel trade of medicinal products from the UK, or include UK authorisations in any calculation of the data and market protection rights). The UK, at least, is operating on the basis that there may be some difficulties post-Brexit for products travelling across the border, and has asked companies to stockpile medicines and devices to avoid any disruption to UK patients.