Brexit

hese days, tension rises to the highest level for everyone dealing with the pharmaceutical market in the European region: How hard or soft will the Brexit deal be? Brexit is rapidly approaching. The EU membership of the UK will end on 29 March 2019, less than six months from now. By the time you read this, a decision about the nature of the Brexit may have been taken: Will the UK, at least for medical products, remain in the single market or will they seek another type of future relationship with the EU as a third county?

The government of Theresa May has proposed the so-called Chequers deal in the Brexit White Paper. This is considered a ”soft Brexit,” because it suggests staying in the single market. Furthermore, the UK would remain bound by EU product legislation (in this case, the pharmaceutical and medical products legislation) via a common rulebook. For highly regulated products, the UK would continue participation in the EU agencies like the EMA for medicinal products and medical devices. It is not likely that the UK Government position will be adopted. EU partners do not agree with this “cherry picking:” If you want to stay in the single market, you also must support the other freedoms underpinning the EU; e.g., free movement of persons, services, and capital. The governmental proposals also face domestic challenges, because many want either not to leave the EU at all or to have a “hard Brexit,” including a separate new trade agreement between the UK and the EU.

Impact on the Life Sciences Industry

If a Brexit agreement is reached, a transitional period of two years will go into effect after the date of exit. According to the MHRA’s website, the status of centralised products and products authorised via the Decentralised and Mutual Recognition Procedures will not change during this period. The same goes for the validity of Mutual Recognition Agreements with third countries and the acknowledgment of inspection results from the UK and the EU member states inspection services.

Furthermore, there will not be an immediate necessity to relocate UK-based qualified persons for pharmacovigilance and for batch release to an EU member state. However, if the Brexit is “hard,” the situation would become quite different. The EU would consider the UK as a third country and there is no exception in the legislation for former EU countries. Therefore, many companies are deploying a worst case scenario.

With respect to clinical trials, the European Commission has issued guidance about the consequences of Brexit. The Commission clarifies that in case of a “hard Brexit,” investigational medicinal products from UK-based sponsors will be considered imports into the EU. Furthermore, sponsors from the UK will have to submit an amendment to the clinical trial dossier, appointing a local representative in the EU in a timely fashion.

The impact of Brexit on the businesses of both UK and EU27 depends to a large extent on whether negotiators succeed in closing a deal and on the contents of the agreement, for example with respect to participation.

EMA Schedules Back Activities

The EMA now anticipates a larger than originally expected staff loss as a consequence of the Agency’s move to Amsterdam. It has therefore decided to postpone more of the work that is not absolutely necessary for business continuity. Most of the activities that will be temporarily discontinued are not product-related.

MHRA Loses Its European Work

The EMA does not employ assessors to draft assessment reports in the Centralised Procedure. This work is done by assessment teams constituted of members of the scientific committees of CHMP who are chosen as rapporteur and co-rapporteur. Historically, the UK authority MHRA has often acted as the leading agency. One of the first things that happened since the Brexit decision was the exclusion of MHRA as rapporteur or co-rapporteur in Centralised procedures. This was a real setback for the UK scientists who actually did this important work, as well as for the MHRA. But, as the EMA said, if it is quite unclear if the job can be finished before Brexit, it is better to choose a member state that will still be available then. Unfortunately, this decision has an impact on MHRA’s business model, because acting as rapporteur or co-rapporteur is also one of the Agency’s most important sources of income. Until now, the UK has performed a disproportionately large number of drug reviews. The annual revenues of the MHRA from the EMA are about €50 million ($59 million). This represents around two-fifths of the EMA’s review budget, which in 2018 is approximately €127.6 million ($150 million).

Medical Devices

In the meantime, the term for implementation of the new Medical Device Regulation (2017/745/EU) 2017/745) and In Vitro Diagnostics Regulation (EU) 2017/746/EU) is moving forward. The Medical Device Regulation must be applied as of 27 May 2020; the In Vitro Diagnostics Regulation is applicable from 27 May 2022 onwards. From 27 May 2020, each and every medical device on the market must comply with the new legislation, because the Medical Device Regulation does not grandfather products already on the market. This means not only that documentation and clinical data for existing products may have to be amended, but, more importantly, that new certificates from the notified bodies must be obtained before these dates. Companies may also opt to extend their existing CE certificates one more time beyond 2020 or 2022 (IVDs) if they accept a design and intended purpose “freeze” on their product. This option is only available for devices that currently have a CE certificate, not for currently self-declared devices like software, and the majority of IVDs. Before notified bodies can assess medical devices under the new legislation, they must themselves comply with the new legislation. They must be re-designated before they can function as a notified body under the new legislation, a process that as yet has not been started by the majority of notified bodies. It seems that it will be quite a challenge to get everything sorted out in time. There is a potential risk that some medically necessary technologies will not be available at (M)D-day.

Brexit is an extra issue, because some of the largest notified bodies are established in the UK. In case of a “hard Brexit,” certification by these organisations may not be valid for marketing of the products in the EU.

Falsified Medicines Directive

As of 9 February 2019, the Falsified Medicines Directive is in effect. In practice, this means that almost all medicinal products must carry a unique identifier, in the form of a QR-code, as well as an anti-tampering device (for example, a seal) which shows that no one has tried to open the package. The details have been adopted in an implementing directive. The European Commission has issued a Q&A document about the implementation that may be helpful for marketing authorization holders and applicants.