As a New Year present to us all, on 3 January 2019, the MHRA published updated guidance on the regulation of medicines, medical devices and clinical trials in the event that the UK leaves the EU on 29 March 2019 without a deal, known as a “hard Brexit”.
Following publication of the technical notice in August 2018, which we considered in an earlier blog, a consultation was launched in order to seek views on the mechanics behind some of the proposals. The consultation ended on 1 November 2018; the responses were reviewed and the technical notice updated. However, the notice states in a number of places that further guidance will be published in due course.
The overall approach in a no-deal scenario is for the MHRA to be a stand-alone medicines and medical devices regulator, which will require it to carry out certain functions that are currently undertaken at EU-level. The key points are considered below:
- Conversion of CAPs to UKMAs: On 26 November 2018, the MHRA sent a letter to marketing authorisation holders (MAHs) of centrally authorised products (CAPs) on how CAPs will be automatically converted to UK marketing authorisations (UKMAs) after Brexit, unless the MAH opts out of this process. The updated technical notice states that MAHs will have one year from the date of Brexit to provide the MHRA with baseline data on CAPs. Any variation to the new UKMAs will be dependent on this baseline data having been submitted. Whilst the full dossier of baseline data is being prepared, the MHRA will accept ‘basic’ baseline data in order to enable variations and other post-authorisation submissions to be processed. Note that abridged applications (e.g. for generic products) will have to be based on a reference product that has been authorised in the UK, but this can include CAPs that have been converted to UKMAs.
- New applications concerning new active substances or biosimilars: In addition to the current 210-day assessment route for national MAs, the MHRA will offer a targeted assessment of new applications for products containing new active substances or biosimilars that have been submitted to the EMA after Brexit, and that have received a positive opinion from the CHMP. The MHRA’s assessment of the same data will be completed within 67 days of submission of the application. Alternatively, applicants can opt for a full accelerated assessment, which the MHRA will complete within 150 days. Applicants will also have the opportunity to engage in a ‘rolling review’, meaning that staged applications can be made throughout the product’s development to better manage development risks. Separately, the MHRA intends to identify strategies to reduce the existing national assessment timetable from 210 days to 180 days.
- Orphan medicines: Orphan status of medicines will be determined at the point of MA grant; the criteria will be based on the current EU criteria (with “UK-specifics”), and the 10-year period of market exclusivity will be maintained following grant of a UKMA. The MHRA will refund MA application fees to applicants whose products receive orphan status. The MHRA does not intend to replicate the need to obtain orphan designation before the application is made, however this system will be monitored.
- Paediatric medicines: The MHRA will offer the same rewards for compliance with a paediatric investigation plan as would be available in the EU; namely a 6 month extension of a UK supplementary protection certificate, or 2 years additional market exclusivity for orphan products.
- Legal presence in the UK: MAHs for UKMAs will be required to have a UK presence by the end of 2020. A UK qualified person for pharmacovigilance (QPPV) must be established in the UK from the day of exit, however, a temporary exemption will allow an EU QPPV to assume responsibility for UKMAs until a UK QPPV can be established. As regards manufacturing licences, a QP for products manufactured in the UK or directly imported into the UK from an unapproved country (approved countries including EU and EEA countries), must reside and operate in the UK. For MAHs without a UK presence on the day of exit, a UK-based contact person must be put in place within 4 weeks.
- Wholesalers: The UK will continue to recognise QP certification from EU/EEA countries after Brexit. All existing holders of UK wholesale dealer authorisations will be permitted to purchase medicines that have been QP certified in the EEA. Wholesalers who wish to continue this type of supply must notify the MHRA within 6 months of EU exit, and will be required to put in place an assurance system to certify that any medicines they import have been QP certified. A new role will be created in order to oversee this activity, namely a “responsible person for import” (RP-I).
- Packaging and labelling: MAHs have until the end of 2021 to implement administrative changes required as a result of Brexit on the packaging of products already on the market.
- Conformity of products: For a limited time, the MHRA will continue to allow devices to be placed on the UK market that are in conformity with the applicable EU legislation. The future process for bringing a medical device to market in the UK will be subject to consultation. Devices that are currently on the market having been assessed by UK notified bodies will no longer be in conformity with the EU legislation after Brexit, and will not be able to be placed on the EU market.
- The new Medical Devices Regulations: By virtue of the EU (Withdrawal) Act 2018, the key requirements of Regulation 2017/745 on medical devices and Regulation 2017/746 on in vitro diagnostic medicinal devices will be mirrored in the UK Medical Devices Regulations 2002, and will be brought into force in line with the transitional timetable for the EU Regulations.
- Registration: After Brexit, all medical devices will need to be registered with the MHRA prior to being placed on the UK market. The MHRA will also operate a grace period to allow time for compliance, which will range from between 4 and 12 months, depending on the class of device.
- Existing approvals: The MHRA will continue to recognise existing approvals for clinical trials relating to both the clinical trial authorisation, and the positive opinion from the ethics committees.
- Location of trial sponsor: The MHRA will require the sponsor (or their legal representative) to be in the UK or in an approved country (which includes EU and EEA countries).
- The new Clinical Trials Regulation: Since Regulation 536/2014 will not be in force in the EU on the day of exit, it will not be automatically incorporated into domestic law as a result of the EU (Withdrawal) Act 2018. However, the UK Government has committed to align, where possible, the UK framework with the new Regulation.
As we noted previously, the details set out by the MHRA are the UK’s position in the event no deal is reached with the EU. However, it is still unclear whether any of these points will be reciprocated by the EU. Note also that following the various technical notices that have been released, the UK Government has now launched a portal as a single source of information to help businesses prepare for Brexit.