The chance of "no deal" remains

The UK Government has acknowledged that the Brexit process is in "crisis". In just the space of a week: the draft Withdrawal Agreement was rejected by the House of Commons in the UK Parliament for a second time, by another historically large margin; the Speaker of the Commons (who is constitutionally politically neutral) has used a 400-year-old precedent to prevent the Agreement being presented to Parliament for a third time without "substantial" changes; and, the EU Council has agreed to extend the Brexit date until 22 May, provided that the Agreement does return to Parliament and is ratified. If that does not happen then the Prime Minister has to tell the EU what her plan (or the plan Parliament has forced on her) is by 12 April.

During the same week as these developments, the Commons also made a resolution against "no-deal". Does this rule out a no-deal Brexit scenario? The answer, in short, is no. The House of Common's resolution that the UK should not leave the EU with no-deal, although placing great political pressure on the government, is not legally binding. Indeed, the law under the European Union (Withdrawal) Act 2018, which Parliament passed only last year, states that the UK will leave the EU on 29 March 2019. This date must be changed by a statutory instrument to accommodate the latest EU deadlines, but unless the mood of Parliament changes and the Withdrawal Agreement is approved, there is now a risk that the UK leaves the EU with no-deal on 12 April.

Guidance on no deal

On the working assumption that the UK will leave the EU without the Withdrawal Agreement in place, what does this mean for pharmaceutical and medical device companies? It is reported that no-deal preparations have been well advanced in Whitehall – the centre of the civil-service – for months, but the Government has chosen not to advertise the fact for fear of turning it into a reality...

These plans for the big trade issues such as temporary rates of customs duty, reliefs and obtaining an EORI number have only recently emerged. For its part the European Commission has published a "no-deal" Contingency Action Plan for specific sectors, which includes guidance on customs and the export of goods.

Although these issues are outside the scope of this article, guidance on the specific issues affecting the regulation of the pharmaceuticals and medical devices sector is also available from the Commission and the UK. We have previously reported on this guidance in Synapse, and update this here together with the key resources on a no-deal Brexit available from France, Germany and the Netherlands:

European Commission guidance on a "no-deal" Brexit

In preparation for Brexit, the European Commission has published jointly with the EMA a Q&A document outlining the steps that need to be taken to allow the marketing of medicines in the EU and EEA market after Brexit (it assumes this is 29 March 2019, at present). The document does not mention the failure of the UK and EU to agree the Withdrawal Agreement or any measures on their future relationship, but the document is drafted on this assumption. The Q&A document states that the following measures would need to be taken by marketing authorisation holders and manufacturers importing from the UK into the EU. The requirements listed include, amongst other matters, those set out in Table 1.

Table 1: European Commission guidance on a "no-deal" Brexit

Right/issue

Key points

Marketing authorisations

These must be transferred to holders established in the EU (or EEA) in order to be recognized in those countries. The transfer of these authorisations must be completed before 30 March 2019 (assuming an exit date of 29 March).

If granted in the UK before 30 March 2019 these will still be considered the initial marketing authorisation for the purpose of the global marketing authorisation concept.

Generic, abridged marketing authorisations granted on the basis of a UK authorised reference medicinal product before 30 March 2019 will remain valid. Subsequent authorisations will only be granted on the basis of a reference medicinal product authorized by an EU member state or a contracting member of the EEA. The same measures apply in respect of biosimilars.

Active ingredients

UK based manufactures of active ingredient must only use starting materials that have been manufactured in accordance with GMP guidelines. Active substances may only be imported into the EU/EEA if they are accompanied by written confirmation from the competent authority that the standards of goods manufacturing practice and control of the plant are equivalent to those in the EU/EEA.

Certificates that active ingredients comply with GMP must be transferred to a holder in the EU.

Finished product

UK based manufacturers of finished product wishing to import into the EU/EEA will be subject to authorisation on the basis of a number of conditions, including the availability of a qualified person in the EEA and GMP inspection.

Batch control and release

The location of batch control and release sites must be situated within the EU/EEA and authorized importers established in the EU/EEA identified.

QPs

Relevant Qualified Persons must be located in the EU/EEA.

Orphan drugs

Orphan drug designations must be transferred to a holder in the EEA/EU.

Medical devices

Holders of CE marked products must transfer the relevant certificate and file for that product to an EU Notified Body. See Notice to Stakeholders. (Compare to the UK, which will continue to recognise CE marking conducted by EU notified bodies post-Brexit).

UK guidance on a "no-deal" Brexit

The UK Government has published a series of notes: Guidance for industry and organisations involved in health and care about contingency plans for a no-deal Brexit, which are intended to provide guidance to businesses and individuals on planning for a no deal Brexit. This series of Notes covers a number of issues relevant to the authorisation and marketing of life sciences products, in particular pharmaceuticals and medical devices. For more detail on the matters in Table 2 and import and export procedures, reference should also be had to the MHRA guidance and publications on a no deal scenario.

Table 2: UK guidance on a 'no-deal' Brexit

Right/issue

Key points

Marketing authorisations

From 29 March 2019 (again assuming this exit date), centrally authorised marketing authorisations will be 'grandfathered' onto the MHRA register as UK marketing authorisations, meaning that all existing authorisations granted by this route will continue. Further guidance from the MHRA.

After Brexit, separate marketing authorisations must be filed for the UK to those for the EU/EEA. This means that the UK will no longer participate in the centralised procedure for authorisation (operated through the EMA), and will not participate in the decentralised or mutual recognition procedures (either as a reference state or by recognising EU reference states). Further guidance from the MHRA.

Applications that are still progressing in the centralised procedure at the time of Brexit, must be transferred to the MHRA. If the Committee for Medicinal Products for Human Use (CHMP) has issued an opinion on such an application by exit day, the MHRA will take this into account. Applications that are still in the decentralised or mutual recognition procedures at the time of Brexit will be subject to provisions allowing the MHRA to complete the assessment and approve successful applications as UK marketing authorisations. Further guidance from the MHRA.

Generic, abridged applications will not be possible for drugs where the MHRA does not have access to the data underlying the original authorisation. This appears to refer to data held by the EMA (relevant to marketing authorisations obtained through the centralised procedure) or the relevant authority of a non-UK reference member state. The implication of this is that generics companies must file a complete set of regulatory data including all clinical trials in order to obtain authorisation for these in the UK, otherwise generic or biosimilar products will not be available in the UK.

Batch control and release

The UK will continue to accept batch testing of human medicines carried out in countries named on a list set out by the MHRA (including EU/EEA). This measure recognises that, immediately after Brexit, medicines regulation in the EU/EEA will be the same as that in the UK and so the testing of each batch of product for compliance with a marketing authorisation does not need to be duplicated in the UK when already performed in the EU/EEA. This measure is intended to assist in movement of medicines from the EU/EEA to the UK and will be welcomed. It has not, so far, been reciprocated by the EU.

QPs

Holders of 'grandfathered' marketing authorisations and Qualified Persons must be established in the UK for the purpose of market access in the UK market. There is a grace period for this purpose until the end of 2020. Until then, the MHRA will require a contact in the UK. Except for the grace period, this requirement reflects measures that the EU will put in place for the EU/EEA market. guidance from the MHRA.

Orphan drugs

The UK will continue to offer incentives in the form of market exclusivity and full or partial refunds for marketing authorisation fees to encourage the development of medicines in rare diseases. Further Guidance from the MHRA and Procedures for UK-PIPs in the event the UK leaves the EU without a deal.

Medical devices

The UK will continue to recognise CE marking conducted by EU notified bodies post-Brexit, for a "time-limited" period. In other words, for the time-limited period in question, the UK will not require separate marking by UK notified bodies. This arrangement has not, so far, been reciprocated by the EU (see above); where a manufacturer is not established in the UK, it must designate a UK Responsible Person to register and act on its behalf. Further guidance from the MHRA.

A further guidance note, titled Patents if there's no Brexit deal, confirms, as expected, that there will be no change to patenting in the UK (which is not regulated by the EU) and that the supplementary protection certificate system will continue under UK law, with all the current conditions and requirements remaining. As regards the Unified Patent Court and Unitary Patent the Note states that the UK will explore whether it would be possible to remain within these systems in a "no deal" scenario.

Additionally, for an initial period, the UK will recognise exhaustion in the EU/EEA, allowing parallel trading of products into the UK from the EU/EEA to continue. It remains to be seen whether the EU will reciprocate this measure. Note however, from a further Technical Note Exhaustion of intellectual property rights if there's no Brexit deal that the EU/EEA may not reciprocate and there may be restrictions on the parallel import of goods from the UK to the EEA.

Separately, the UK Government has announced that UK clinical trial applications will continue to be authorised by the MHRA and ethics committees as they are now, in a "no-deal" scenario. The UK's ability to participate in multinational trials would also not change. The Government also says it is seeking to preserve the current position that a sponsor or their "legal representative" should be based in the EU or EEA. However, while the legal representative will only need to be based in the EU or EEA it is anticipated that it will be necessary to have an individual based in the UK who has overall responsibility for the trial and can be contacted to discuss urgent issues arising in connection with a trial. Further guidance on clinical trials is available from the MHRA.

"No deal" guidance issued in Austria, France, Germany and the Netherlands

Various agencies concerned with pharmaceuticals and medical devices in Austria, France, Germany and the Netherlands have also published guidance, as shown in Table 3:

Table 3: Guidance on no deal Brexit from Austria, France, Germany and the Netherlands

Country

Guidance

Austria

The Austrian Federal Office for Safety in Health Care has published information on the effects on market authorisation holders and authorities due to Brexit and provides further information (as well as application sheets) for businesses in the healthcare sector.

France

The French Drug Agency has published various guidelines relating to Brexit, covering amongst other matters: batch testing of pharmaceuticals, marketing authorisation holders, importation of raw materials for pharmaceutical use, sponsorship of clinical trials, and medical devices.

Germany

The Federal Ministry of Justice and Consumer Protection has published a statement with regard to patents and SPCs after Brexit indicating the same impacts of Brexit as identified in the UK.

The Federal Association of German Industry has provided Brexit guidelines for small and medium-sized enterprise policy, referring amongst other matters to chemical substances and pharmaceutical products. The Association of German Chambers of Industry and Commerce, has similarly issued guidance.

The Federal Institute for Drugs and Medical Devices (BfarM) provides information regarding clinical trials and, echoing the guidelines of the Commission and EMA, the Institute also draws particular attention to the persons or activities that must be located within the EU or the EEA in order for the medicinal products to be marketed in the EU in the case of a "no deal" (BfArM has also published a number of recommendations and FAQs regarding Brexit in English: FAQ Brexit and Consequences of Brexit BfArM's preparations).

The German Ministry of Health also has specific information and FAQs regarding Brexit on its Website.

The Netherlands

The Ministry of Health, Welfare and Sport has published Brexit guidelines for businesses in the healthcare sector, containing guidelines directed at manufacturers, market authorization holders and wholesalers which trade medicinal products etc. on the European market.

Prospects

Many companies in the UK and the EU will have already implemented contingency plans, others will not have done so. With growing concern across the UK at what is happening in government and Parliament, Theresa May will probably find a way around the Speaker's ruling to bring the draft Withdrawal Agreement back a third time before Parliament this week.

However, it is still not a probability that Parliament will ratify it. The possibility of a no-deal therefore remains on the new 12 April date if no other alternatives are found. There may, therefore, be just a few days for the above guidance on no deal to be considered by companies operating in the pharmaceuticals and medical devices sectors.