What has changed for orphan medicinal products in the UK after Brexit?


It is easy to overlook the consequences of the small but important changes affecting orphan medicinal products in the UK as a result of the country’s departure from the EU, partly because they are just a needle in the haystack of amendments made to the Human Medicines Regulations 2012 due to Brexit.

The most obvious difference between the EU and the new UK system is that there is no pre-authorisation orphan designation in Great Britain (or the UK, although a UK-wide orphan marketing authorisation (MA) can only be considered in the absence of an EU orphan designation, which will be extremely uncommon).

This could be seen by some as an advantageous simplification of the procedure, but in reality, it provides more uncertainly to sponsors and dependence on the EU, as developers will not know who else is developing similar products for the same orphan condition without relying on the more transparent and open EU system. Indeed, in Great Britain, sponsors will enter the race to be the first to obtain an MA for their orphan medicinal products with blinkers and the European Commission Register of Orphan Medicinal (“EC Register”) will be the only source available to them to understand what the competitor landscape looks like at any given point in time.

The UK equivalent of the EC Register is now a mere list of granted orphan MAs, together with a list of expired orphan registrations. The database, published and kept up to date by the MHRA, is rudimentary consisting of a list of orphan registered products in alphabetical order by trade name. The MHRA list does not fulfil the same objective as the EC Register, which was set up to enable an easy and unequivocal tool for the identification of medicines eligible for incentives. To the extent that products are added to the UK list once they are authorised (in the absence of orphan designation prior to the application for the MA), the UK list is a mere compilation of products that have market exclusivity, which does nothing to enhance transparency and openness.

Given the residual and purely testimonial purpose of the UK list, the UK legislature must have considered it unnecessary to retain the different ways in which a designated orphan medicinal product can be removed from the EC Register (Art. 5.12 of the EC Orphan Regulation[1]). As a consequence, from 1 January 2021 MA holders of orphan medicinal products approved in Great Britain (or the UK) cannot voluntarily de-designate their products. This seemingly small change has important consequences that will create relevant differences between the UK and the EU.

Firstly, an MA holder is no longer able to de-designate its product to add non-orphan indications while orphan market exclusivity (OME) exists for its Great Britain or UK product, forcing it to apply for a new MA, under a different brand, if it wants to commercialise its product for non-orphan indications.

Second and most importantly, an MA holder of an orphan medicinal product is no longer able to choose the preferred paediatric reward (the six-months extension of the SPC or two additional years of OME) when its product is both orphan designated and is protected by an SPC or a patent that qualifies for one at the relevant point in time. While in the EU it is commonly accepted[2] that an MA holder of a product which is both orphan designated and protected by an SPC or a patent that qualifies for one can choose the most economically attractive paediatric reward, this is no longer possible in the UK. Having been left without the possibility of removing its product from the list of orphan medicines, and giving up part of the product’s OME as a result, the MA holder of an active orphan medicinal product in Great Britain or the UK cannot opt for the six-months extension of the SPC while the 10 years of OME lasts. The only reward available for these products in the UK will be the extension of the orphan marketing exclusivity to 12 years.

As a result, companies can end up having two very different types of exclusivities nearing the end of the products’ exclusivities in the EU and the UK. Divergences between the two blocks are already happening, even if involuntarily on the part of the UK legislative. Despite the inevitable ties that exist with EU pharmaceutical law as a result of the Northern Ireland Protocol, many more divergences are still to come.

[1] Regulation (EC) No 141/2000 on orphan medicinal products.
[2] Decisions of the Court of the Hague on 30 March 2016 and the Court of Milan of 26 February 2016 declared the validity of the paediatric extension granted by the Dutch and Italian Patent Offices, respectively, for the extended term of the SPC covering the medicinal product Glivec (imatinib mesilate), applied for after the voluntary removal of the product from the EU Register.