A year has now passed since the decision of the British people to leave the European Union ('Brexit'), but formal negotiations have only just begun. In the intervening time, little detailed information has been available from both sides about the aims of the negotiations and, more specifically, what they mean for industry sectors such as the life sciences. It is into this vacuum that the European Commission and the European Medicines Agency ("EMA") published, on 2 May 2017, a Notice to Marketing Authorisation Holders of Centrally Authorised Medicinal Products for Human and Veterinary Use. This document was followed on 31 May 2017 by two guidance documents for marketing authorisation ("MA") holders and manufacturers importing into the EU and the European Economic Area ("EEA"): Q&A for centrally authorised medicines, published by the European Commission and the EMA; and, a parallel document for holders of national MAs obtained through the mutual recognition and decentralised procedures, published by the Coordination Group for Mutual Recognition and Decentralised Procedures – Human ("CMDh").
In addition, there has been a General Election and a new government in the UK without a majority. The impact of this development in the Brexit negotiations remains to be seen. In particular, the Lancaster House speech referred to below may no longer reflect the current thinking of the new government. It remains, however, the most complete statement that we have and it is authored by the same Prime Minister as remains in office. We have therefore assumed for the purposes of this discussion that this statement remains true.
This article outlines the legal, practical and political context for the EMA and CMDh documents and what it tells us more broadly about the likely outcomes for MA holders, post-Brexit.
Directives and Regulations post-Brexit
The starting point when looking at the impact of Brexit on the regulation of MAs in the UK is the effect of the Repeal Act, announced by Prime Minister Theresa May on 2 October 2016 and re-affirmed in the Queen's speech on 21 June 2017. This Act will come into force upon Brexit to implement in UK law all those EU laws necessary to ensure a smooth transition in the immediate term after Brexit takes effect. This primarily means the enactment into UK law of most, if not all, EU Regulations; those legislative instruments that currently have 'direct effect' on UK law, but are not part of UK law itself. Most EU Directives, on the other hand, are already implemented by the UK and other Member States in national legislation, in a manner open to their own discretion. For example, Directive 2001/83 (the "Directive"), which addresses, amongst other matters, MAs, is implemented in the UK by a statutory instrument.
As regards obtaining an MA, there are three specific routes available in the EU (and in the EEA states of Norway, Iceland and Liechtenstein). These are provided by both Regulation and Directive:
- The centralised procedure ("CP"), which is governed by Regulation 726/2004 (the "Regulation"). This procedure allows applicants to obtain an MA that is binding on EU and EEA Member States. Applications for central MAs are made directly to the EMA and are evaluated by the appropriate EMA committee which, for most human medicines, is the CHMP or the Committee for Medicines for Human Use. The centralised procedure is compulsory for certain medicines, such as biotech products.
- The mutual recognition procedure ("MRP"), which is set out in the Directive. The MRP is used for medicines that have already received an authorisation in one EEA Member State at the time of application. The application for mutual recognition may be addressed to one or more EEA Member States. The original Member State where the MA has been granted – the "Reference Member State" ("RMS"), as it is called – will prepare an assessment report, and the other Member States – the "Concerned Member States" ("CMS") – will receive and consider the RMS's assessment report. Subject to objections on the basis of serious harm to public health, the MA must be recognised by the CMS.
- The decentralised procedure ("DCP") which is also set out in the Directive, as amended. Like mutual recognition, it relies on the recognition by national authorities of a first assessment performed in one Member State – the RMS. However, unlike the MRP, the DCP is used for the authorisation of medicines which have not received an authorisation at the time of application, so there is more scope for the CMSs to be involved and feed into the analysis of the application. Like the MRP, however, a favourable decision by the RMS to grant an MA must be recognised by the CMSs, subject to serious public health concerns.
Can these procedures simply continue post-Brexit by the existing implementation in UK law of the Directive and by enactment of the Regulation into UK law by the Repeal Act? The answer is that whilst the Medicines and Healthcare Products Regulatory Agency ("MHRA") can continue to grant MAs in the UK according to exactly the same regulatory requirements as in the EU/EEA, it cannot participate in the CP, MRP and DCP procedures at the pan-European level because these require cooperation and mutual recognition between the EU and EEA Member States. Post-Brexit, the UK will no longer be an EU/EEA Member State and so will not be able to cooperate in the same way with the Member States (although there has been more talk of the EEA model since the General Election, at least as an interim measure, as discussed below).
Cooperation or no cooperation, post-Brexit
A cooperation and mutual recognition agreement would therefore be required between the UK and the EU in order for the UK to participate, through the MHRA, in the regulation of MAs using the pan-European procedures of the CP, MRP and DCP (see Table).
Click here to view table.
The European Commission's and EMA's summary of the impact of Brexit on the manufacture and marketing of drugs with existing MA holders in the UK is outlined in the Q&A document published on 31 May 2017. A parallel list of requirements relevant to nationally authorised medicinal products through the MRP and DCP has been published by CMDh.
These documents set out the requirements of the Directive and the Regulation for MA holders and manufacturers importing from the UK into the EU/EEA, on the basis that, after Brexit, the UK will be a 'Third Country'. The requirements listed include: to transfer MAs of authorised products to holders established in the EU/EEA; for authorisation or certification of UK based manufacturers of active ingredients and finished products in order to import into the EU/EEA; for batch control to take place within the EU/EEA; and for batch release sites to be moved to the EU/EEA.
If no cooperation agreement can be reached, one possibility is that the UK legislates to unilaterally recognise authorisations granted in the EU. This would avoid the need for applicants to duplicate their authorisations in the UK. It is, however, a politically unattractive position for the UK to take. The more probable outcome is that the UK requires EU/EEA-based pharmaceutical companies to comply with precisely the same requirements, in respect of the UK, as those set out for the EU/EEA by the EMA and CMDh Q&A documents.
Practical and political considerations
The implementation of EU legislation on medicines authorisation into UK law, post-Brexit, means that the rules governing authorisations in the UK and the EU/EEA will be identical for the foreseeable future. The consequence of a failure to reach a cooperation and mutual recognition deal is therefore not just that applicants will need authorisations in both the EU and the UK. As detailed in the Q&A documents, there will also be the unnecessary duplication of certifications and approvals, batch control and release, as well as other measures, for medicines moving between the UK and the EU/EEA, and vice versa under existing MAs. This is a situation that is likely to be practically, commercially and politically unacceptable to both sides. Most seriously of all, it poses the risk of disrupting the supply of certain medicines to consumers.
There is also the role of the MHRA to consider. For example, in the year 2015 / 2016 the UK alone, through the MHRA, was the reference Member State in 43 percent of approvals in the EU/EEA under the MRP and DCP. When the RMS is the UK, the MHRA also holds the dossier and will have carried out the assessment for authorisations that have been granted through mutual recognition and decentralised procedures. It will, in addition, have ongoing responsibilities relating, in particular, to amendments to the dossier. If it can no longer participate, the dossier and these functions will need to be transferred. The MHRA also frequently carries out assessments on behalf of the EMA during the centralised procedure. Without the MHRA to provide these roles, additional pressure will be placed on regulators of other Member States and on the EMA.
Taking all of these points into account, it should be obvious that there is a benefit to both applicants and regulators for the MHRA to remain part of the CP, MRP and DCP, post-Brexit. The question remains whether or not it is possible to achieve this politically. The failure of the Conservative government to obtain a majority of MPs in Parliament in the June 2017 General Election has raised speculation that the UK may need to seek a watered-down Brexit in which it remains in the EEA, at least for a transitional period. EEA membership should mean continuation of the UK's participation in the CP, MRP and DCP. However, it is far from clear that this will happen. Even with an exit from the EU and the EEA, there is still cause for optimism. This is to be found in Theresa May's Lancaster House speech on 17 January 2017. There she made these statements, which were later reiterated in a Government White Paper on 3 February 2017:
"That Agreement may take in elements of current Single Market arrangements in certain areas…as it makes no sense to start again from scratch when Britain and the remaining Member States have adhered to the same rules for so many years."
In other words, the Government is not intending to scrap regulatory cooperation for the sake of it, particularly in certain areas. Those areas are hinted at when Mrs May refers to "medical technologies", amongst other matters, for which "Britain will remain at the forefront of collective endeavours".
It is important, when trying to draw conclusions about the future relationship between the UK and the EU on medicinal products authorisation, as with other aspects of Brexit, to remember that withdrawal from the EU is still subject to a long period of negotiation, both on the UK's exit and its future relationship with the EU. Even after the date of Brexit, there may be a transitional period before the full extent of any new relationship with the EU is realised.
There is nonetheless reason to suppose that a negotiated solution will be reached in which the efficiencies of the current system of medicines authorisation can be maintained in the life sciences sector. This is because it benefits the EU, the UK, industry and consumers alike.