The European Medicines Agency and the European Commission have recently published a Q&A document pointing out the direct consequences of Brexit with regard to centrally authorised medicinal products for human and veterinary use. In future, UK established pharmaceutical manufacturers will be met with material regulatory requirements governing, for instance, the transfer of marketing authorisation to a holder in an EU or EEA Member State and the requisite documentation of the medicinal products if they are exported to the EU or the EEA to ensure the products comply with the EU's quality requirements.

One of several consequences of Brexit is that, as from 30 March 2019, all primary and secondary law of the EU ceases to apply to the UK, which means that the UK will become a "third country" in line with Switzerland and the USA. Consequently, the UK established pharmaceutical manufacturers will face various legal challenges, which have resulted in numerous requests for guidance being submitted to the European Medicines Agency ("EMA").

On 31 May 2017, the EMA and the European Commission published its first Q&A document, listing the direct impact of UK's withdrawal from the EU on holders of marketing authorisation issued for medicinal products for human and veterinary use within the centralised procedures of EMA. The Q&A document is subject to regular revision as the full consequences of Brexit become known.

Establishment requirement

Pursuant to articles 13 and 39 of the Commission Regulation no. 726/2004, marketing authorisations for human and veterinary medicinal products issued by the European Commission on the basis of an EMA authorisation apply throughout the EU. Generally, marketing authorisations apply for five years, but they may be extended, see article 14 of the Regulation.

A marketing authorisation holder ("MAH") for medicinal products for human and veterinary use must be established in an EU or EEA Member State pursuant to article 2 of the Commission Regulation no. 726/2004. As for centrally authorised medicinal products, the MAH of which is established in the UK, the marketing authorisation must be transferred to a location in an EU or EEA Member State, see article 2 of the Regulation no. 726/2004. This also applies to the designation of orphan medicinal products, see article 2 of the Regulation no. 141/2000.

Qualified person for pharmacovigilance

According to article 8 of Directive 2001/83/EC and article 74 of Directive 2001/82/EC, a pharmaceutical person for pharmacovigilance ("QPPV") must reside and carry out his or her tasks in the Member State in which the MAH is established. As a consequence of Brexit, the QPPVs attached to MAHs residing in the UK will have to change their place of residence and relocate to an EU or EEA Member State in order to be able to carry on with their work. Alternatively, the MAHs must appoint new QPPVs who are already residents of an EU or EEA Member State.

If an MAH replaces its QPPV or the QPPV relocates, the MAH must register the changes through the article 57 database, and if such changes concern medicinal products for veterinary use, the changes must be updated through a variation request.

Pharmacovigilance System Master File

The Pharmacovigilance System Master File (PSMF) must be located within the EU or EEA, see Regulation no. 520/2012. If the MAH is established in the UK after 2019, the MAH must transfer the PSMF to a locality in an EU or EEA Member state. Changes to the location of the PSMF must be registered with the EMA through the article 57 database.

Medicinal products manufactured in the UK after 30 March 2019

Active substances – also known as active pharmaceutical ingredients (APIs) – and finished products manufactured in the UK will be considered imported medicinal products from a third country to the EU or EEA. This entails a number of supplementary documentation requirements as far as the quality of the imported medicinal products are concerned. Any APIs intended for sale in the EU or EEA must be accompanied by a GMP certificate, which indicates whether the product is in accordance with the GMP standards, see article 46n(2) of the Directive 2001/83/EC.

As for finished medicinal products, the manufacturer must designate an authorised importer established in the EU or EEA Member State in which the medicinal product is to be distributed. The authorised importer must carry out a batch control before the products are released for sale, see article 51(1) of Directive 2001/83/EC and article 55(1)(b) of Directive 2001/82/EC. If a batch control is to be take place at a new location, this change of location is subject to authorisation in the form of a variation request.

Financial and administration assistance (SME Commission Regulation )

Under the Commission Regulation no. 2049/2005, micro, small and medium-sized enterprises (SMEs) established in the EU or EEA are given the option to apply for a reduction of fees as well as deferring the payment of fees during the assessment of applications for marketing authorisation for medicinal products for human and veterinary use.

The Regulation also offers administrative assistance from the EMA in the form of translation of the documents that are deemed necessary for issuing a marketing authorisation, see article 10. UK-based enterprises cannot apply for an SME status after 2019; however, such legal status may be obtained through a legal entity (such as a subsidiary) located in the EU or EEA acting as a liaise between the MAH and the EMA.

Comments by Bech-Bruun

Brexit will entail a number of legal challenges to the pharmaceutical industry, not only to pharmaceutical manufacturers resident in the UK, but also to Danish pharmaceutical enterprises with consolidated companies in charge of research, development and manufacture activities located in the UK.

In order for the relevant enterprises to be able to comply with EU legislation and thus secure access to the medicinal products market in the EU and EEA, we recommend that they decide whether the UK-based activities would benefit from being relocated to an EU or EEA Member State and whether future record, licensing and distribution activities should include activities based in the UK.