BREXIT - Regulatory considerations

Latest updates

24/12/2020 - Publication of the EU-UK Trade and Cooperation Agreement: protecting European interests, ensuring fair competition, and continued cooperation in areas of mutual interests


22/12/2020The European Commission published a Notice on the Application of the pharmaceutical acquis in Malta and other countries dependent on medicines supply from or through Great Britain - updated 25/1/2021

  • Form to be used for informing the Medicines Authority of intentions of moving certain activities to the EU - to be submitted monthly - first deadline 25 January, from next month deadline every 20th of the month.  Form to be sent to mailbox brexitexemptions.medicinesauthority@gov.mt.  A comminication on this was sent to all stakeholders.  If you have not received it and you would like more information, please contact us.
  • If no exemption request is received by the deadline, the consequence will be that the product is not in line with the EU acquis and the marketing authorisation will be suspended until the required information or the necessary variations to rectify the situation are received by the Medicines Authority.  Please also note that MA transfers should be submitted latest by end of February to avoid suspension of the Marketing Authorisation.

 

17/12/2020 Updated guidance on latest developments, including the Ireland/Norther Ireland protocol can be found here.

 

Regulatory Considerations

  1. Introduction

    On 29 March 2017, the European Council received the notification by the United Kingdom (UK) of its intention to withdraw from the European Union. This allows for the opening of negotiations as foreseen by the Treaty.  The United Kingdom’s decision to leave the Union creates significant uncertainties that have the potential to cause disruption, in particular in the United Kingdom but also, to a lesser extent, in other Member States (MS). National authorities, businesses and other stakeholders must take all the necessary steps to plan for the exiting of the UK from the European Union.

    The implications of Brexit with regard to the UK’s role in the licensing of medicinal products will be determined by the terms of the ongoing exit negotiations. The Marketing Authorisation Holder (MAH) must be located within the EU/EEA. In addition, for marketing authorisations issued through the mutual recognition procedure (MRP) or decentralised procedure (DCP), the RMS must be based in the EU/EEA.

    Guidance documents on the effect of post-Brexit on licensing procedures have been issued by the European Medicines Agency (EMA) and the Coordination Group for Mutual Recognition and Decentralised procedures – human (CMDh). Further information can be found in the hereunder section 7.0 Reference for more information.

    1. Actions to date, Malta Medicines Authority

      Our Strategic Plan for 2016‐2020, includes access to health products as a key strategic goal. In executing our mitigation strategy in light of Brexit, Protection of Public Health, patient supply and availability of quality products, remains at the forefront. 

    2. Advocacy

      Together with other Member States, whose regulatory framework is supported heavily by the MHRA’s medicines registration, the MMA has been active and ever present in discussions and lobbying at a European level in order to minimise and mitigate the disruption resulting from a hard Brexit. Given the latest developments, the MMA considers it advisable to urge the local stakeholders to implement a tangible plan for a hard Brexit. Information which may be useful to stakeholders in developing their strategy is being provided in this guidance document, with potential one to one advisory sessions with MMA.

    3. Stakeholder engagement and advisory services

      The MMA had invited all local stakeholders to get in touch in order to plan effectively for worst case scenarios. Whilst participation to this meeting was encouraging, we reiterate that the MMA is available for one to one meetings with local stakeholders, to fully discuss safeguarding the patient’s access to essential medicines, before the end of 2020.  We are available to hold virtual meetings in view of the current situation. Please send an email to mailbox mrp-dcp.adm@gov.mt.

  2. Impact of Brexit on the EU Regulatory Network

    The Malta Medicines Authority’s (MMA) main priority is the protection of public health and ensuring continuity of supply of medicinal products for the patients.   To be able to achieve this, the Medicines Authority will provide any support necessary to its stakeholders. It is therefore important that all companies who require guidance and support to maintain their medicinal products on the market contact the MMA as soon as possible to effectively plan and prepare for the UK’s exit from the EU/European Economic Area (EEA).

    It is the aim of the MMA to support all stakeholders already present on the Maltese market or stakeholders who need to relocate to an EU/EEA country as a result of Brexit. Where feasible, we hope to provide pragmatic solutions to the anticipated challenges arising from the UK’s exit from the EU/EEA.

    The MMA would like to assure stakeholders that it is our intention to continue working closely with the UK to ensure continued product supply to the Maltese market. Malta is fully prepared to assume a greater role in EU regulatory activities and to increase our already significant contribution to the EU regulatory networks. In light of the pending withdrawal of the UK from the EU, information which may be useful to stakeholders is provided in this guidance document.

    During the transition period, EU pharmaceutical law will continue to apply to the UK, menaing that until the end of the transition period pharmaceutical companies can continue to carry out activities in the UK and supply their medicines as before.  However, companies have to ensure that necessary changes are in place before the end of the transition period to minimise the potential for supply disruptions after this period.  The transitional period will end on 31/12/2020.

  3. Advice on handling changes post Brexit and potential licensing scenarios for marketing authorisation holders

    The MMA is committed to ensuring that the impact of Brexit on medicinal product availability is assessed and proactively addressed by all relevant stakeholders and that, where necessary, timely actions are taken to ensure continuity of supply.

    The MMA is offering support to companies when managing any supply problems that might arise when marketing authorisations have to be transferred from the UK to other EU markets as a result of Brexit.

    Stakeholders need to identify products at risk by considering the compliance requirements post Brexit, and make use of options being provided by the MMA to mitigate the risk to patient access.  The MMA is recommending that MAHs plan for the situation where the UK becomes a third country which involves:

    • Marketing Authorisation Holders located in the UK must move to another EU/EEA MS
    • Batch release and testing must be carried out in a EU MS
    • EU QPPV must be moved to a EU MS
    • PSMF location must move to a EU MS
    • Effective stock management

    Any variations required for a marketing authorisation (MA), for example, a change to site of batch release or change in location of QPPV, should be completed prior to the date of the UK’s departure from the EU. It is recommended that MAHs identify and action authorisations they hold for any required changes. Variation applications need to be submitted in sufficient time to ensure they are completed on time.

    Where transfer and variation applications are not submitted before 31 December 2020, the MAs will be suspended until the MAs are in line with the EU requirements.  This is to avoid unnecessary withdrawal of applications and to give more time to companies to move their operations outside the UK.

    1. Joint packs with other Member States

      The MMA will work with companies to ensure that existing joint labels with the UK are maintained and that multi-lingual labels with other EU markets are developed.

      Regulatory issues which may arise for critical medicinal products should be highlighted as soon as possible so that pragmatic solutions will be sought for critical medicinal products to remain on the Maltese market.

    2. Other Regulatory Strategy Options:

      Duplicate procedure

      Duplicate registration may offer an alternative route to established procedures, in order to allow MAH to accommodate for upcoming changes. There is no definition of a “duplicate” in the pharmaceutical legislation. However, for practical purpose, a duplicate application is defined by reference to the first application or marketing authorisation as follows:

      • same dossier (copy of modules 1, 2, 3, 4 and 5);
      • same legal basis according to Directive 2001/83/EC, as amended; - different tradename;
      • same or different applicant/marketing authorisation holder. 

      By submitting simultaneously or subsequently duplicate applications, the applicants should indicate in the cover letter and in the Module 1of the dossier:

      • that the application is a duplicate;
      • that the dossier is identical to the medicinal product taken as reference (first application or marketing authorisation);
      • if other duplicate applications are pending or submitted simultaneously. The applicants should indicate the procedure number(s), the RMS and all CMSs and in the case of several applicants, if they are linked or not.

      If you have any queries on the above and you need guidance and support please send an email to mrp-dcp.adm@gov.mt or refer to CMDh guidance.

      Day 0 MRP (Simplified Procedure)

      The MMA agrees to accept the assessment of the RMS or the National Competent Authority (in the instance where the product had been authorised nationally), without any comments or questions. The approved product information will also be accepted without any comments. The MMA will not request any update of the assessment report or the dossier, nor will there be any changes related to such procedure, except that in this simple way Malta joins an MRP. These procedures can be finalised once the application has been accepted by the RMS and MMA, hence a “MRP day zero procedure”. Procedures have already been finalised successfully with various RMS countries. 

      More information on the Day 0  MRP (Simplified Procedure)

      Applicants should inform the Medicines Authority of their intention to submit such an application to the RMS.

      The applicant sends a request to the RMS requesting the use of this simplified procedure.

      The RMS requests confirmation from the CMS regarding the criticality of the product applied for.

      The CMS confirms the need for the product and guarantees that:

      1. There will be no need for the RMS to update the assessment report since these will be accepted from the RMS without any comments
      2. No CMS comments will be sent by MT as CMS to the RMS thus enabling the application to be approved immediately
      3. The addition of MT will not change the renewal cycle or PSUR submission timelines
      4. The product information specifically the SmPC, package leaflet and labelling will be accepted as authorised in the RMS

      An application form is then sent to MT as CMS. This submission should include:

      1. A cover letter clearly stating that the submitted dossier is identical to the one currently approved in the RMS and that it is being submitted as a ‘Day 0’ procedure
      2. The dossier preferably in eCTD format, together with any subsequent approved variations and a confirmation of their approval
      3. Latest approved PI by the RMS
      4. MT as CMS validates the application form within a 14 day validation period

      • RMS then sets a Day 0
      • A Day 0 procedure is concluded on the same day it started (i.e. following validation) by the RMS.
      • The End Of Procedure documents are sent by the RMS to the CMS
      • Following this, the applicant submits the MT specific product information.
      • The Medicines Authority then issues the MA during the 30 days national phase of the procedure

      The Medicines Authority requires one renewal, and an administrative renewal is acceptable.

      If you have any queries on the above and you need guidance and support please send an email to mrp-dcp.adm@gov.mt.

    3. National marketing authorisations, Article 126(a) authorisations and parallel import authorisations

      National Marketing Authorisations

      For national authorisations which are authorised in UK and Malta only, the marketing authorisation in Malta will remain valid subject to MAH transfer to Malta or another EU member state. The responsibilities for post-authorisation regulatory procedures must be carried out by the new MAH (refer to Section 7 for pharmacovigilance), located in a Member State of the EU-27/EEA.  All other activities - batch testing site, batch release site, EU-QPPV and PSMF must be located in the EU-27.  Variations must be submitted where relevant to regularise the marketing authorisation.

      Authorisations in accordance with article 126(a) granted on the basis of marketing authorisations in the UK will remain valid until their expiry date and will not become automatically invalidated on 31 December 2020 if they are in line with European legislation i.e. the holder of the licence and all regulatory activities are located in the EU.  Alternative sources should be sought as these licences cannot be renewed after Brexit. New authorisations on the basis of article 126(a) referring to marketing authorisations granted by the UK cannot be granted after the withdrawal date (31/12/2020) as the UK will become a third country. Moreover, products sourced from the UK after the withdrawal date will be considered as products imported from a third country and will need to comply with all the requirements of the EU law for imported products. Please make reference to the relevant Q&A in the relevant CMDh practical guidance: https://www.hma.eu/fileadmin/dateien/Human_Medicines/CMD_h_/BREXIT/CMDh_373_2018_Rev.4_04_2020_clean_x_PG_on_Brexit.pdf.  The holder of the authorisation must be located in the EU-27/EEA.

      Companies should identify alternative source countries in the EU. Repackaging of the medicinal product should be performed if the pack is not available in English/Maltese language. Please refer to the Guidelines on Repackaging of medicinal products for human use.

      Authorisation holders of Article 126(a) which are the Marketing Authorisation Holders of the medicinal product are wherever possible, requested to use the ‘MRP day zero or day 30 procedure’ also referred to as the ‘simplified procedure’. Please refer to Section 4.2 for more information on this procedure.  Marketing Authorisation Holders are also encouraged to include Malta as Concerned Member State in MR and DC procedures wherever possible.

      The Medicines Authority is also discussing the possibilities of reduced fees by the RMS countries to enable companies to seek registration using European procedures, especially in small countries.  Some countries already have reduced fees for these procedures – if you require more information about this please send an email to mrp-dcp.adm@gov.mt

      Parallel Importation

      Parallel importation from and to Great Britain is no longer possible after the end of the transition period (31/12/2020) and all licences making reference to products originating from Great Britain will no longer be valid and cannot be used to import products into Malta.  Parallel product authorisations (PIs) can currently be granted for medicines imported from an EU Member State or a country within the EEA.  A PI holder must be located within the EU/EEA. Therefore alternative sources for products currently being imported from the UK as source country must be identified. 

      For registration of alternative products from other Member States refer to Guideline on fees for authorisation and post-authorisation procedures. Until Brexit date, reduced fees are being charged for registration of alternative products to cover the ones already registered on the basis of a UK marketing authorisation.  Please include this form with your application if you are eligible for a reduced fee.

      A Q&A on parallel importation of products originating from the United Kindgdom was published by the European Commission - Brexit Guidance for Stakeholders (October 2019).

    4. Procedures for MAHs to transfer MAH to EU/EEA based MAH

      A marketing authorisation may be transferred from the existing authorisation holder to another holder using a transfer procedure. The transfer procedure must be used where the legal entity of an authorisation/licence holder is changed as marketing authorisations are transferred to a new company number.  More information on transfers can be found here.

    5. Authorised generic medicinal products which refer to an UK reference product

      Marketing authorisations for generic/hybrids granted in accordance with Directives 2001/82/EC and 2001/83/EU prior to Brexit date, will continue to be valid authorisations notwithstanding that a reference product may no longer be an EU authorised product.

    6. Joint/Multi-lingual labelling

      The MMA recognises that the maintenance of joint/multi-lingual labelling with other markets can be key to companies retaining medicinal products on the Maltese market. The MMA has facilitated, where possible, joint/multi-lingual labelling with the UK and other markets. Through collaborations with other European competent authorities, the MMA is seeking support to facilitate additional opportunities for multi-lingual labelling.

  4. Pharmacovigilance Operations

    MAHs will need to ensure that their EU QPPV and their pharmacovigilance system master file (PSMF) are located within the EU/EEA. This is necessary to remain in compliance with the requirements outlined in article 104 of Directive 2001/83/EC, as amended, and in Article 7 of Commission Implementing Regulation No. 520/2012. Requirements for coordination of pharmacovigilance inspections undertaken by Member States, including the sharing of information on inspections planned and conducted inspections are provided for in EU legislation (Article 111 of Directive 2001/83/EC, Article 19 of Regulation No 726/2004) and associated Union procedures.

  5. Changes to Import and Export Requirements

    The following advice regarding the importation, export, storage and distribution of medicinal products are based on the assumption that the UK will become a third country from 31/12/2020, leaving the European single market and customs union. It does not take into account however any possible future mutual recognition agreement (MRA) on good manufacturing practice (GMP) Inspection between the EU and the UK. Therefore, this advice may be subject to change in the future as the Brexit negotiations progress.

    Any Maltese company that receives finished medicinal product from the UK, will be required to hold a manufacturer’s/importer’s authorisation. In addition the batches must be tested and certified in the EU/EEA after importation.

    1. Finished product and active substances coming from the UK

      Any companies that receive finished medicine sourced from the UK, including exempt/unlicensed medicinal products, will be required to hold a manufacturing importation authorisation (MIA). If a medicinal product is being procured, held, supplied or exported by a UK entity, then that entity will require a wholesale authorisation which the UK will employ post-Brexit. For products transiting through the UK only, it is not envisaged that there will be any additional requirements other than potential additional customs clearance/checks e.g. from a French distribution entity transiting via the UK to Malta. With respect to active substances for use in human medicinal products sourced from companies in the UK, an active substance distributor will also be required to register as an importer of active substances. In order to import active substances manufactured in the UK, under the Falsified Medicines Directive, the UK will need to be listed by the EU Commission as having a supervisory system for active pharmaceutical ingredients equivalent to that of the EU. There is no provision for an MRA on GMP inspection between the EU and UK at this time.

    2. Product Testing for Qualified person (QP) certification and/or release

      For EU markets, all products that originate from the UK, or those imported via the UK, must be imported by a manufacturer/importer located within the EU/EEA and certified after being batch released by a Qualified Person (QP) at that site. No changes are anticipated to Annex 16 of the EU Guide to GMP as result of Brexit as certification must take place within the EU/EEA in accordance with current legislation and guidance. 

    3. Process for changing the site of batch release to Malta

      A company should apply to the MMA for a manufacturer's/importer's authorisation (MIA) for batch certification/release in Malta. A GMP inspection will be conducted on receipt of an application. The batch certification activities must take place at the authorised address.   

    4. GMP certification

      Update 25 February 2019 - Q&A related to the United Kingdom's withdrawal from the European Union with regard to national authorised medicinal products for human use - http://www.hma.eu/fileadmin/dateien/Human_Medicines/CMD_h_/BREXIT/CMDh_361_2017_Rev3_01_2019_TC_QA_on_BREXIT.pdf.  Updated guidance on the acceptance of GMP certificates granted by the UK can be found here.

  6. References for more information

    Medicines Authority - Brexit Guidance for Stakeholders.

    European authorities working to avoid shortages of medicines due to Brexit - questions and answers.

    Getting ready for the end of the transition period: https://ec.europa.eu/info/european-union-and-united-kingdom-forging-new-partnership/future-partnership/getting-ready-end-transition-period_en

    The European Union and the United Kingdom - forging a new partnership: https://ec.europa.eu/info/european-union-and-united-kingdom-forging-new-partnership_en

    Heads of Medicines Agencies (HMA). Co-ordination Group for Mutual Recognition and Decentralised Procedures (CMDh) - https://www.hma.eu/535.html

    https://ec.europa.eu/info/files/medicinal-products-human-use-veterinary_en

    Position paper on Goods placed on the Market under Union law before the withdrawal date

    The EMA have also updated their post authorisation procedural advice for users of centralised procedure (August 2018).

    Updated guidance on latest developments, including the Ireland/Northern Ireland protocol can be found here.

    Last updated:  27 January 2021