Brexit and MAH Responsibilities – 5 Critical Points To Consider
The spectre of a ‘no deal’ Brexit looms large in the minds of life science professionals. What impact will this have for the Marketing Authorisation Holders? In this blog, we look at some of the key areas that will affect Marketing Authorisation Holders when Brexit becomes a reality on 30 March 2019.
Editor’s Note: This article was updated in August 2019 to include the most up to date departure date of the UK from the EU.
1. Qualified persons for pharmacovigilance and their deputies currently residing in the UK
The qualified person responsible for pharmacovigilance (QPPV) must reside and carry out his/her tasks in a Member State of the Union (EEA). This is the case for both human (Article 8 of Directive 2001/83/EC) and veterinary (Article 74 of Directive 2001/82/EC) medicinal products. Post Brexit therefore, MAHs must either appoint a new QPPV residing and carrying out his/her tasks in the Union (EEA), or request their QPPV to relocate and carry out his/her tasks in the Union (EEA). All updates to the QPPV details must of course be updated in the Article 57 database for human medicines, and through a variation for veterinary medicines.
Article 2 of Commission Implementing Regulation (EU) No 520/2012 mandates the availability of back-up arrangements in the absence of the QPPV (i.e. Deputy QPPV). As the tasks of QPPV need to be carried in a Member State of the Union (EEA), the back-up arrangements for cases of absence of the QPPV, which replace such tasks, also need to be performed in the Union (EEA).
With most QPPVs thought to currently reside in the UK1, this change will result in major restructuring for MAHs. MAHs are also reminded that PSMF locations must also be within the Union (EEA).
2. Marketing authorisation holders established in the UK
EU law requires that marketing authorisation holders are established in the EU (or EEA) [Article 2 of Regulation (EC) No 726/2004]. Through the EEA Agreement this is extended to include also Norway, Iceland and Liechtenstein. For centrally authorised medicinal products the marketing authorisation holder will therefore normally need to transfer its marketing authorisation to a holder established in the Union (EEA). The transfer of the marketing authorisation must be fully completed and implemented by the marketing authorisation holder before 30 March 2019.
Any marketing authorisation applications that are ongoing, and expect a commission decision after 29 March 2019, will need to change to a non-UK applicant established in the Union (EEA) before October 31st 2019.
3. Batch release from a UK site
Similarly for batch release, Article 51(1) of Directive 2001/83/EC and Article 55(1) of Directive 2001/82/EC requires that the qualified person (QP) of the manufacturing and importation authorisation holder is responsible to certify that each batch of medicinal product intended to be placed on the EEA market was manufactured in accordance with EU GMP requirements and the marketing authorisation. The batch release site has to be located in the Union (EEA). For centrally authorised medicinal products the marketing authorisation holder will therefore need to transfer its current UK based site of batch release to a location established in the Union (EEA) and submit the corresponding variation.
Certification can only be performed by a Qualified Person of the manufacturer and/or importer who is identified in the marketing authorisation and they also need to be located in the Union (EEA).
4. Manufacturing site of active substance or finished product in the UK
Active substances or finished products produced in UK sites will be considered as ‘imported active substances’ or ‘imported medicinal products’ after March 2019.
Active substances originating from a third country, must therefore be accompanied by a written confirmation from the competent authority of the exporting country that the standards of GMP of the plant manufacturing the active substance are at least equivalent to those laid down by the union (EEA).
For finished products, the competent authorities of the Union (EEA) ensures that the import of medicinal products into their territory is subject to an authorisation in accordance with Article 40(3) of Directive 2001/83/EC and Article 44(3) Of Directive 2001/82/EC. The authorisation is granted when a number of conditions, as defined in Articles 41 and 42 of Directive 2001/83/EC and Articles 45 and 46 of Directive 2001/82/EC, are fulfilled (e.g. availability of a qualified person within the Union (EEA), GMP inspection).
Introduction of a new manufacturing site for the active substance or for the finished product and their respective consequential changes can be submitted as a Type II variation separately for the active substance and for the finished product, thereby replacing a large grouping of Quality IB (and IA) variations for the consequential change.
5. Legal basis of MAA’s
With the UK becoming a ‘Third Country’ after Brexit, it also has implications when considering the choice of legal basis for marketing authorisation applications.
Hybrid/generic applications refer to information contained in the dossier of another EU ‘reference product’. Generic/hybrid marketing authorisations granted before the end of October 2019 referring to a Reference product authorised by the UK remain valid. Generic/hybrid applications for which marketing authorisations will be granted after the end of October 2019 should refer to a reference product that is or has been authorised in a EU-27 Member State or a contracting state of the EEA.
Similarly, with well-established use applications and demonstrating use in the community for more than 10 years, UK data to support such claims only cover the period when the UK was a member state of the EU.
The reader is referred to both the Brexit practical guidance document and the Q and A documents on the EMA website for more information.
With negotiations on the final withdrawal agreement currently making little progress, much remains uncertain on the shape of things to come.
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- Pharmaceutical Journal. ‘Into the unknown: UK pharmacovigilance after Brexit’. 17 May 2017. Available at: https://www.pharmaceutical-journal.com/opinion/blogs/into-the-unknown-uk-pharmacovigilance-after-brexit/20202803.blog