On 6 August 2018, the MHRA released new guidance on what the Brexit implementation period means for the lifesciences sector, as well as an update on the application of the new EU Clinical Trials Regulation for pharmaceuticals following Brexit.
The Implementation Period
The draft agreement published in March 2018 governing the UK’s withdrawal from the EU (the “Withdrawal Agreement”) states that there will be a transition or implementation period which will run from the date the UK leaves the EU (i.e. 30 March 2019) until 31 December 2020 (the “Implementation Period”). During this time, EU law will continue to apply in the UK (subject to any exceptions or variations contained in the Withdrawal Agreement).
The purpose of the Implementation Period is to allow companies a period during which they can continue to operate as they do now, while making final preparations for their businesses after Brexit. Given that the UK will leave the EU on 29 March 2019, there are inevitably questions as to how this will work in practice. The MHRA's new guidance is intended to update companies on what this would mean for the lifesciences sector and is drafted on the basis that the Implementation Period will happen. However, the Withdrawal Agreement is still in draft form, and therefore the terms of the Implementation Period (presuming that one is agreed) are yet to be finalised. The current aim is to agree this by October 2018.
During the Implementation Period: pharmaceuticals
The guidance confirms that during the Implementation Period:
- batch release testing and Qualified Person certification may continue in the UK and will be recognised by the EU (and vice versa);
- Marketing Authorisation Holders, Qualified Persons and Qualified Persons for Pharmacovigilance may continue to be based in the UK and will have access to EU markets; and
- UK companies will be able to continue applying for Marketing Authorisations via the EU centralised or decentralised procedures.
During the Implementation Period the UK will be able to participate in reviewing new Marketing Authorisation applications, but it will not be able to act as the lead or Reference Member State (“RMS”) and will not have a vote in any decision making. The EU Coordination Groups for the Mutual Recognition and Decentralised Procedures have also confirmed that transfer of an RMS (from the UK to another member state) will not be permitted before a Marketing Authorisation application procedure is completed. Consequently, companies with applications which are still being processed and where the UK is the RMS are advised to “submit responses to outstanding lists of questions as soon as possible" to try and ensure the procedure is completed by 29 March 2019.
During the Implementation Period the UK will not have voting rights at any of the European Medicines Agency (“EMA”) or EU committees, and the MHRA will not be able to act as a lead authority in any Union or joint Member State risk assessments, examinations, approvals or authorisations. The scope of the application of this provision for the medicines sector is still under discussion between the UK and the EU. Although the MHRA may continue to attend EMA and EU committees and any groups where there is a UK interest, it is still to be agreed how this will work in practice. The MHRA confirms that: “the exact nature of this participation is a matter for further discussion”.
During the Implementation Period: medical devices
CE-marking will continue to be recognised for the UK and EU markets, and there will be no need for UK-based companies to appoint an EU authorised representative in the EU. UK notified bodies will also be able to continue to conduct third-party conformity assessments in the UK, the results of which will be recognised for the EU market.
The guidance notes that the new EU Medical Devices Regulation will be fully applied from May 2020, which is during the Implementation Period, but that this is not the case for the new EU Regulation on in vitro diagnostic medical devices (IVDs), which only applies from May 2022. The MHRA notes, however, that some aspects of both EU Regulations already apply in the UK, such that strictly, medical devices and IVDs compliant with the new EU Regulations may already be lawfully placed on the UK market.
The MHRA states that it cannot “pre-judge” what the future arrangements will be, but notes that "the UK has been central to agreeing the new legislation and we are supportive of its aims to strengthen the regulatory system and increase the transparency of information about products on the EU market”. The MHRA is evidently in favour of implementing the new EU legislation post-Brexit so it is to be anticipated that UK manufacturers will be required to operate within a very similar regulatory framework after Brexit and the Implementation Period, even if there is no formal alignment.
EU Clinical Trial Regulation
The MHRA also published a separate update on the new EU Clinical Trial Regulation (“CTR”) for pharmaceuticals. Although the CTR was adopted and entered into force in 2014, its mandatory application has been repeatedly deferred as it is dependent on the full operational functionality of the EU portal and database.
The CTR is currently expected to become fully applicable during 2020, which means it would come into mandatory effect in the UK during the Implementation Period. Should there be further delays to its implementation, taking this beyond the end of the Implementation Period, the MHRA has confirmed that UK law will nonetheless remain aligned with those parts of the CTR that are “within the UK’s control”. Obviously though, the UK would not be able to use the shared central IT portal or participate in the single assessment model (whereby multi-member state clinical trial applications are assessed by a reporting member state) unless a specific UK/EU agreement addressing this is negotiated.
The guidance clearly indicates the government’s preference for close cooperation with the EU across the breadth of the medicines legislation and to ensure that the UK is an attractive location for clinical trials following Brexit. As part of this, the MHRA has confirmed that it will "take every effort" to ensure that parallel submissions by sponsors to the UK will be "as streamlined and efficient as possible", for example by allowing sponsors to use the same application dossier.
The MHRA guidance is consistent with the House of Commons’ July 2018 amendment to the Trade Bill requiring the government to seek to negotiate a trade agreement that will permit the UK to continue to fully participate in the European medicines regulatory network partnership following the UK’s withdrawal from the EU. This would include full participation in the procedures of the EMA, ensuring that patients in the UK would still have access to medicines authorised via the EU centralised procedure following Brexit.
The guidance is helpful in that it focuses on some of the more practical operational issues which will face companies during any Implementation Period. However, the guidance does not address where industry will be left in the event that no Implementation Period is agreed. The latter is likely to be far more disruptive for industry as well as for healthcare providers and, most importantly, patients.
The EMA has acted to re-distribute the UK’s responsibility for various centrally authorised medicines dossiers (i.e. medicines authorised following review by the EMA) amongst the remaining member states. It appears that industry has similarly started to act to transfer activity or responsibility for those products outside of the UK. The EMA published its survey of industry’s Brexit preparedness in July 2018. That report noted that 58% of the 694 centrally authorised medicines (i.e. medicines authorised following review by the EMA) with an important step in their regulatory processes in the UK are on track to ensure their authorisations remain valid in the EU following Brexit. However, the EMA also noted that there were serious concerns that 108 (16%) products would not complete the appropriate steps in time to ensure the authorisations remain valid in the EU.
Finally, it is also clear that the scope of the exclusion of the UK from any role as lead authority or from decision-taking for risk assessments, examinations, approvals and authorisations in respect of medicines is still under discussion. It is possible there may be further restrictions imposed in this regard. In any event, based on the current drafting and guidance, the UK’s post-Brexit role will essentially be that of a ‘rule taker’ as it will be required to respect decisions reached by EU committees regarding the regulation of pharmaceuticals and medical devices available in the UK, without having any meaningful say or right of decision.
In response to the new guidance, the Association of the British Pharmaceutical Industry (“ABPI”) acknowledged that the guidance left some unanswered questions, stating that “The industry will continue to plan for all scenarios, including ‘no deal’. We believe that the best way to protect patients and public health is for the EU and UK to agree continued cooperation on the regulation of medicines". Previously, the House of Commons amendment was well received by industry, with the ABPI and the BioIndustry Association issuing a joint statement welcoming the move, noting the benefits to patients from the maintenance of the flow of medicines between the UK and the EU27.
The full guidance can be accessed via the following links:
What the implementation period means for the life science sector.
Technical information on what the implementation period means for the life science sector.
Clinical Trials Regulation.