Rev 01, published on 23 January 2018
Notice to marketing authorisation holders of centrally authorised
Medicinal products for human and veterinary use
The United Kingdom submitted on 29 March 2017 the notification of its intention to withdraw from the Union pursuant to Article 50 of the Treaty on European Union. This means that unless a ratified withdrawal agreement1 establishes another date, all Union primary and secondary law ceases to apply to the United Kingdom from 30 March 2019, 00:00h (CET).2 The United Kingdom will then become a ‘third country’.3
Preparing for the withdrawal is therefore not just a matter for EU and national authorities, but also for private parties. In view of the considerable uncertainties, in particular concerning the content of a possible withdrawal agreement, marketing authorisation holders of centrally authorised medicinal products for human and veterinary use are reminded of legal repercussions, which need to be considered when the United Kingdom becomes a third country.
Subject to any transitional arrangement that may be contained in a possible withdrawal agreement, as of the withdrawal date, the EU rules in the field of medicinal products for human and veterinary use no longer apply to the United Kingdom. This has, in particular, the following consequences in the different areas of EU law on medicinal products: EU law requires that marketing authorisation holders are established in the EU (or EEA); Some activities must be performed in the EU (or EEA), related for example to pharmacovigilance, batch release etc.
Marketing authorisation holders may be required to adapt processes and to consider changes to the terms of the marketing authorisation in order to ensure its continuous validity and exploitation, once the United Kingdom has left the Union. Marketing authorisation holders will need to act sufficiently in advance to avoid any impact on the continuous supply of medicines for human and veterinary use within the European Union. In particular, the Commission and the European Medicines Agency expect marketing authorisation holders to prepare and proactively screen authorisations they hold for the
1 Negotiations are ongoing with the United Kingdom with a view to reaching a withdrawal agreement.
2 Furthermore, in accordance with Article 50(3) of the Treaty on European Union, the European Council, in agreement with the United Kingdom, may unanimously decide that the Treaties cease to apply at a later date.
3 A third country is a country not member of the EU.
EUROPEAN COMMISSION DIRECTORATE-GENERAL FOR HEALTH AND FOOD SAFETY
need for any changes. The necessary transfer or variation requests will need to be submitted in due time, considering the procedural timelines foreseen in the regulatory framework. The Commission and the European Medicines Agency stand ready to support marketing authorisation holders and will provide a series of Q&As. A dedicated page of the Agency’s website already contains general information pertaining to the outcome of the UK referendum. This page will be updated with further practical information and relevant Q&As and will be subsequently expanded, where necessary. For products authorised in decentralised or mutual recognition procedures, the information will be provided through the websites of the Coordination Groups.
European Commission European Medicines Agency
Questions and Answers
Rev 03, published on 19 June 2018
Questions and Answers related to the United Kingdom’s withdrawal from the European Union with regard to the medicinal products for human and veterinary use within the framework of the Centralised Procedure
This list of Questions and Answers (Q&As) complements the Notice to marketing authorisation holders of centrally authorised medicines products for human and veterinary use, which was updated on 23 January 2018.
The Notice states: “The United Kingdom submitted on 29 March 2017 the notification of its intention to withdraw from the Union pursuant to Article 50 of the Treaty on European Union. This means that unless a ratified withdrawal agreement1 establishes another date, all Union primary and secondary law ceases to apply to the United Kingdom from 30 March 2019, 00:00h (CET).2 The United Kingdom will then become a ‘third country’.3
Preparing for the withdrawal is therefore not just a matter for EU and national authorities, but also for private parties.
In view of the considerable uncertainties, in particular concerning the content of a possible withdrawal agreement, marketing authorisation holders of centrally authorised medicinal products for human and veterinary use are reminded of legal repercussions, which need to be considered when the United Kingdom becomes a third country.
Subject to any transitional arrangement that may be contained in a possible withdrawal agreement, as of the withdrawal date, the EU rules in the field of medicinal products for human and veterinary use no longer apply to the United Kingdom. This has, in particular, the following consequences in the different areas of EU law on medicinal products:
EU law requires that marketing authorisation holders are established in the EU (or EEA); Some activities must be performed in the EU (or EEA), related for example to pharmacovigilance, batch release etc.
Marketing authorisation holders may be required to adapt processes and to consider changes to the terms of the marketing authorisation in order to ensure its continuous validity and exploitation, once the United Kingdom has left the Union.
1 Negotiations are ongoing with the United Kingdom with a view to reaching a withdrawal agreement. 2 Furthermore, in accordance with Article 50(3) of the Treaty on European Union, the European Council, in agreement with the United Kingdom, may unanimously decide that the Treaties cease to apply at a later date. 3 A third country is a country not member of the EU.
Marketing authorisation holders will need to act sufficiently in advance to avoid any impact on the continuous supply of medicines for human and veterinary use within the European Union.
In particular, the Commission and the European Medicines Agency expect marketing authorisation holders to prepare and proactively screen authorisations they hold for the need for any changes. The necessary transfer or variation requests will need to be submitted in due time considering the procedural timelines foreseen in the regulatory framework.”
This list of Q&As has been drafted jointly by the Directorate-General for Health and Food Safety of the European Commission and EMA. This version is an update of the initial list of Q&As published on 31 May 2017 as subsequently amended and it replaces all previous versions of Q&As. The new text introduced in this version of Q&As “Rev 03” published on 19 June 2018 is indicated by the word “NEW”. The Q&As may be further updated and complemented in the future. The advice below applies equally to medicinal products for human or veterinary use, unless otherwise indicated in the heading to the question.
1. What if I am a marketing authorisation holder established in the UK?
According to Article 2 of Regulation (EC) No 726/2004 the marketing authorisation holder must be established in the Union. 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) (see Commission Regulation (EC) 2141/96 and EMA Q&A on transfer). This means that the addressee of the marketing authorisation decision changes to the new addressee. The transfer of the marketing authorisation must be fully completed and implemented by the marketing authorisation holder before 30 March 2019.
1a. What if I am an applicant established in the UK?
Any marketing authorisation applicant must be established in the Union (EEA). Therefore, for marketing authorisation applications (MAAs) that are expected to receive a Commission Decision after 29 March 2019 (postponed to 31 January 2020, with a transitional period to effective withdrawal on 31 December 2020), applicants established in the UK will need to change to a non-UK applicant established in the Union (EEA) before 30 March 2019. It is strongly recommended that applicants established in the UK consider such change, where possible, in advance of the submission of the MAA.
2. What if I am an orphan designation holder established in the UK? (for medicines for human use)
According to Article 2 of Regulation (EC) No 141/2000 the sponsor of an orphan medicinal product designation must be established in the Union (EEA).
For designated orphan medicinal products the holder will therefore need to transfer its designation to a holder established in the Union (EEA) (see Checklist for sponsors applying for the transfer of Orphan Medicinal Product (OMP) designation and the corresponding template) or it will need to change its place of establishment to a Member State of the Union (or EEA) and submit the corresponding documentation through a change of name and/or address of the orphan designation holder procedure provided the legal entity remains the same (see Guideline on the format and content of applications for designation as orphan medicinal products and on the transfer of designations from one sponsor to another, 27.03.2014).
3. What if I am a UK company with a MUMS (Minor Use Minor Species/limited market) status for my product? (for veterinary medicines)
(NEW:) According to Article 79 of Regulation (EC) No 726/2004, the Management Board of the European Medicines Agency should, in the case of veterinary products which have limited markets, or in the case of veterinary medicinal products intended for diseases with a regional distribution, adopt the necessary measures to provide assistance to companies at the time of submission of their applications. This activity supports applicants for marketing authorisations, which in accordance with the general rules have to be established in the Union (EEA) (see Question 1a above).
If the sponsor/applicant is established in the UK, the MUMS incentives provided on the basis of Article 79 of Regulation (EC) No 726/2004 would no longer be applicable with effect from the date of the UK’s withdrawal from the Union, as a sponsor/applicant established within a third country cannot seek and receive MUMS/limited market classification in the Union (EEA). However, MUMS/limited market classification is connected to the product/indication and therefore transferable together with the product.
To formally acknowledge the transfer, the EMA requires a letter from the original sponsor/applicant officially informing the EMA of the transfer of the classification product and the MUMS/limited market classification from the original sponsor/applicant to a sponsor/ applicant established in the Union (EEA). This letter should state the document reference number of the MUMS outcome letter confirming the MUMS classification.
For already authorised MUMS/limited market veterinary medicinal products it is important to note that a transfer of marketing authorisation does not include a transfer of an MUMS/limited designation as this is subject to a different procedure. Therefore, for those authorised MUMS/limited market veterinary medicinal products the marketing authorisation holder needs to transfer the marketing authorisation (see: “What if I am a marketing authorisation holder established in the UK (H + V)?”) and separately the MUMS/ limited market classification (see above). (NEW:) The five year period of validity for MUMS/limited market classification is not affected by the transfer of classification.
4. What if my Qualified Person for Pharmacovigilance (QPPV) resides and carries out his/her tasks in the UK?
According to Article 8 of Directive 2001/83/EC and Article 74 of Directive 2001/82/EC, the qualified person responsible for pharmacovigilance must reside and carry out his/her tasks in a Member State of the Union (EEA). The QPPV will therefore need to change his/her place of residence and carry out his/her tasks in the Union (EEA) or a new QPPV residing and carrying out his/her tasks in the Union (EEA) will need to be appointed. Changes in the QPPV, including contact details (telephone, and fax numbers, postal address and email address) may, for medicinal products for human use, be updated through the Article 57 database only (without the need for a variation) (see Variation Guideline C.I.8). Regarding medicinal products for veterinary use the changes should be updated through a variation (see Variation Guideline (2013/C 223/01), classification C.I.9).
5. What if my Pharmacovigilance System Master File is located in the UK (PSMF)? (for medicines for human use)
According to Commission Implementing Regulation (EU) No 520/2012, the PSMF must be located within the Union (EEA). The supervisory authority for pharmacovigilance is the competent authority of the Member State in which the pharmacovigilance system master file is located. The marketing authorisation holder will therefore need to change the location of the PSMF to a Member State within the Union (EEA). Changes to the location of the PSMF (street, city, postcode, country) may be updated through the Article 57 database only (without the need for a variation) (see Variation Guideline (2013/ C 223/01), classification C.I.8).
6. What if my manufacturing site of the active substance is located in the UK?
As of the date of the withdrawal of the UK from the Union, active substances manufactured in the UK will be considered imported active substances.
Directive 2001/83/EC and Directive 2001/82/EC state that manufacturing authorisation holders are obliged to use, as starting materials, only active substances that have been manufactured in accordance with the detailed guidelines on GMP for starting materials.
In addition, pursuant to Article 46b(2) of Directive 2001/83/EC, active substances for medicinal products for human use shall only be imported in the Union (EEA) if, inter alia, the active substances are accompanied by a written confirmation from the competent authority of the exporting third country which, as regards the plant manufacturing the exported active substance, confirms that the standards of good manufacturing practice and control of the plant are equivalent to those in the Union (EEA).
7. What if my manufacturing site of the finished product is located in the UK?
As of the date of the withdrawal of the UK from the Union, medicinal products manufactured in the UK will be considered imported medicinal products.
The competent authorities of the Union (EEA) shall ensure 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).
For centrally authorised medicinal products the marketing authorisation holder will therefore need to specify an authorised importer established in the Union (EEA) and submit the corresponding variation (see Variation Guideline (2013/ C 223/01), classification B.II.b.2).
In addition, in accordance with Article 51(1)(b) of Directive 2001/83 and Article 55(1)(b) of Directive 2001/82 the marketing authorisation holder will need to specify a site of batch control in the Union (EEA) where each production batch can undergo upon importation a full qualitative analysis, a quantitative analysis of at least all the active substances and all the other tests or checks necessary to ensure the quality of medicinal products in accordance with the requirements of the marketing authorisation.
For centrally authorised medicinal products the marketing authorisation holder will need to change the location of its current UK based site of batch control to a location established in the Union (EEA) and submit the corresponding variation (see Variation Guideline (2013/ C 223/01), classification B.II.b.2).
8. What if my batch release site is located in the UK?
In accordance with Article 51(1) of Directive 2001/83/EC and Article 55(1) of Directive 2001/82/EC, the qualified person 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 (see Variation Guideline (2013/ C 223/01), classification B.II.b.2).
9. I am a UK based SME, would I still have access to financial and administrative assistance in accordance with Commission Regulation (EC) No 2049/2005 (the ‘SME Regulation’)?
In order to be eligible for financial and administrative assistance, companies must be established in the Union (EEA) and meet the definition of an SME.
As of the date of the withdrawal of the UK from the Union, the guidance for non-EEA based companies shall apply also to UK based companies:
to apply for SME status once the company has established a legal entity in the Union (EEA). For proof of establishment, the SME office requires a copy of the certificate of incorporation in the company’s commercial register. In such cases, the SME declaration can be submitted in the name of the newly established subsidiary with details of the parent company to be declared. to indirectly benefit from the SME incentives through an Union (EEA) established SME regulatory consultancy. SME regulatory consultancies may seek to benefit from the provisions of the SME Regulation on behalf of non-EEA based clients, only if both they and the client meet the SME criteria (i.e. fall below headcount and financial thresholds). In this case, both the regulatory consultancy and the non-EEA based company should submit SME declarations. If successful, the regulatory consultancy would receive an SME notification and the non-EEA based company would be listed in an annex to that notification as an SME client company. It is not possible for an SME regulatory consultancy to be considered eligible if they are acting on behalf of non-SME clients, as this would be contrary to the objectives of the SME Regulation.
Further information is available on the EMA website (link) and in the SME User Guide (link).
10. How does UK’s withdrawal from the Union affect my generic or hybrid marketing authorisation or application based on a reference product authorised in the UK?
A generic or hybrid application in accordance with Article 10 of Directive 2001/83/EC or Article 13 of Directive 2001/82/EC refers to information that is contained in the dossier of a reference medicinal product (RefMP) that is or has been authorised in the Union (EEA).4
Generic/hybrid marketing authorisations granted before 30 March 2019 referring to a RefMP authorised by the UK (UK RefMP) remain valid.
Generic/hybrid applications for which marketing authorisations will be granted after 29 March 2019 (postponed to 31 January 2020, with a transitional period to effective withdrawal on 31 December 2020) should refer to a RefMP that is or has been authorised in a EU-27 Member State or a contracting state of the EEA.5 6 (NEW:) Applicants are advised to take this into account already at the time of submission of the application.
11. Can medicinal products used in bioequivalence studies be sourced in the UK?
According to Article 10(1) of Directive 2001/83/EC or Article 13(1) of Directive 2001/82/EC the applicant can submit an abridged application if he can demonstrate that the medicinal product is a generic of a reference medicinal product which is or has been authorised in the EU or EEA for not less than eight years. According to Article 10(2)(b) of Directive 2001/82/EC and Article 13(2)(b) of Directive 2001/83/EC generic medicinal product means a medicinal product which has the same qualitative and quantitative composition in active substance and the same pharmaceutical form as
4 (NEW) See also the electronic application form for marketing authorisation applications, section 1.4.2.2 or 1.4.3.2 5 This will also facilitate management of generic/hybrid product’s life cycle in the post-authorisation phase, considering for example the need to implement changes to the product information of the EEA RefMP also for the generic/hybrid products. 6 The (exceptional) situation where a RefMP is or has been authorised in the UK only is addressed in the EU’s “Position paper on Goods placed on the Market under Union law before the withdrawal date” (footnote 7): https://ec.europa.eu/commission/publications/position-paper-goods-placed-market-under-union-lawwithdrawal-date_en .
the reference medicinal product, and whose bioequivalence with the reference medicinal product has been demonstrated by appropriate bioavailability studies.7
Bioequivalence studies that have been conducted with a medicinal product sourced in the UK can be used in generic/hybrid marketing authorisation applications only if the marketing authorisation for that application will be granted before 30 March 2019.8
12. How does UK’s withdrawal from the Union affect my biosimilar marketing authorisation or biosimilar marketing authorisation application? (for medicines for human use)
The considerations described under questions 10 and 11 regarding the choice of RefMP are also applicable to biosimilars.
The Guideline on similar biological medicinal products should however be consulted for the available scientific guidance when considering using a non-EEA authorised comparator (i.e. a nonEEA authorised version of the reference medicinal product) in the development of a biosimilar. Batches of the RefMP released by the UK after 29 March 2019 (postponed to 31 January 2020, with a transitional period to effective withdrawal on 31 December 2020) will not be considered as a Union (EEA) authorised comparator.
13. How does UK’s withdrawal from the Union affect the Global Marketing Authorisation (GMA) concept?
The concept of ‘global marketing authorisation within the meaning of Article 6(1) of Directive 2001/83/EC and Article 5(1) of Directive 2001/82/EC covers the initial marketing authorisation and all subsequent developments of the original medicinal product, irrespective of their authorisation procedures, namely variation or grant of a separate MA9 to the same MAH. The GMA is accompanied only by a single regulatory data protection period10 which applies both to data relating to the original medicinal product11 and to data presented for any subsequent developments. That regulatory data protection period begins with the grant of the initial marketing authorisation in the Union (EEA).
Marketing authorisations granted before 30 March 2019 by the UK can still be considered as the initial marketing authorisation.
14. How does UK’s withdrawal from the Union affect well-established use applications?
According to Article 10a of Directive 2001/83/EC and Article 13a of Directive 2001/82/EC it is possible to replace results of the pre-clinical and clinical trials by detailed references to published
7 (NEW) See also the electronic application form for marketing authorisation applications, section 1.4.2.3 or 1.4.3.3 8 In exceptional cases where bioequivalence studies are intended for use in new applications which will be submitted before 30 March 2019 and if these bioequivalence studies have been already completed the applicants may consider contacting the competent authority to discuss the particular circumstances of their application in order to avoid unnecessary repetition of studies in humans or animals. 9 C-629/15P, para. 72. 10 C-629/15P, para. 65. 11 (NEW) See also the electronic application form for marketing authorisation applications, section 1.4.2.1 or 1.4.3.1
scientific literature if it can be demonstrated that the active substances of a medicinal product in the claimed therapeutic indication and (for veterinary products) target species have been in wellestablished use within the Union (EEA) for at least ten years, with recognised efficacy and an acceptable level of safety. In this regard, the provisions of Annex I of Directive 2001/83/EC or Annex I of Directive 2001/82/EC shall apply.
Data sourced from the UK, while the UK was a Member State of the Union, can be taken into account to demonstrate that the active substances of a medicinal product in the claimed therapeutic indication and (for veterinary products) target species have been in well-established use within the Union (EEA) for at least ten years, with recognised efficacy and an acceptable level of safety.
15. How does UK’s withdrawal from the Union affect traditional herbal medicinal products (traditional-use registration)? (for medicines for human use)
The traditional-use registration procedure allows the registration of herbal medicinal products without requiring particulars and documents on tests and trials on safety and efficacy, provided that there is sufficient evidence of the medicinal use of the product throughout a period of at least 30 years, including at least 15 years in the Union (EEA).
Data sourced from the UK, while the UK was a Member State of the Union, can be taken into account to demonstrate that the product has been in medicinal use throughout a period of at least 15 years within the Union (EEA).
16. How does UK’s withdrawal from the Union affect the prevalence for orphan drug designation? (for medicines for human use)
For applications for orphan designations or for its maintenance submitted after 29 March 2019 (postponed to 31 January 2020, with a transitional period to effective withdrawal on 31 December 2020), patients in the UK should no longer be taken into account in the calculation of the prevalence of the disease in order to meet the requirements for orphan drug designation as set out in Regulation (EC) No 141/2000 i.e. a condition affecting no more than 5 in 10 thousand persons in the Union (EEA).
17. How does UK’s withdrawal from the Union affect the local representative located in the UK, if also nominated for Member States other than the UK?
The local representative mentioned in the product information should be located in the Union (EEA). Therefore, any local representative located in the UK and nominated for Member States other than the UK will have to be changed to a local representative located in the Union (EEA).
The corresponding amendments to labelling and package leaflet must be fully completed and implemented by the marketing authorisation holder before 30 March 2019, either as part of a regulatory procedure affecting the annexes (e.g. variation, renewal), or through a notification under an Article 61(3) of Directive 2001/83/EC or (for veterinary products) through a Type IAIN variation (see Variation Guideline (2013/ C 223/01), classification C.II.6.a).
17a. How does UK’s withdrawal from the Union affect the local representative for UK mentioned in the product information?
After 29 March 2019 (postponed to 31 January 2020, with a transitional period to effective withdrawal on 31 December 2020), the mentioning of the local representative for UK in the product information will become obsolete.
The deletion of the local representative for UK in the product information will need to be incorporated as part of a future regulatory procedure affecting the annexes (e.g. variation, renewal) and the earliest opportunity after 29 March 2019 (postponed to 31 January 2020, with a transitional period to effective withdrawal on 31 December 2020) should be used.
18. How does UK’s withdrawal from the Union affect the sunset clause?
According to Article 24(4) to (6) of Directive 2001/83/EC, Article 28(4) to (6) of Directive 2001/82/EC and Articles 14(4) to (6) and 39(4) to (6) of Regulation (EC) No 726/2004 any authorisation which within three years of its granting is not followed by the actual placing on the market of the authorised product in the authorising Member State or on the Union market will cease to be valid. When an authorised product previously placed on the market in the authorising Member State or in the Union is no longer actually present on the market for a period of three consecutive years, the authorisation for that product will cease to be valid.
In case a centrally authorised medicinal product has only been marketed in the UK, the placing on the UK market, while UK was a Member State of the Union, will be taken into account to determine the applicability of the sunset clause for the medicinal product concerned. In this respect, if after the UK withdrawal from the Union, the medicinal product is not placed on any other market of the remaining Member States, the three year period for the sunset clause will start running from the last date the medicinal product was placed on the UK market, while UK was a Member State of the Union.
19. What if my product is subject to Official Control Authority Batch Release (OCABR) and is currently tested by a UK Official Medicines Control Laboratory (OMCL)? (NEW)
According to Article 114 of Directive 2001/83/EC and Article 82 of Directive 2001/82/EC, Member States may require the marketing authorisation holder of a human immunological medicinal product or a medicinal product derived from human blood or plasma or immunological veterinary medicinal product to submit samples from each batch of the bulk and/or the medicinal product for examination by an Official Medicines Control Laboratory (OMCL) or a laboratory that a Member State has designated for that purpose before the release on the market. This is referred to as Official Control Authority Batch Release (OCABR).
According to the EU Administrative Procedure for Official Control Authority Batch Release12, prior to marketing in the Union (EEA), batches of medicinal products subject to independent testing should obtain an Official Control Authority Batch Release Certificate common to all Member States. This shall demonstrate that the batch of medicinal product has been examined and tested by an OMCL within the Union (EEA) in accordance with this procedure and with Official Control Authority Batch Release guidelines pertaining to the medicinal product and that it is in compliance with the approved specifications laid down in the relevant monographs of the European Pharmacopoeia (Ph. Eur.) and in the relevant marketing authorisation.
For products placed on the market as of the withdrawal date,13 OCABR cannot be carried out by an OMCL located in the UK. OCABR will need to be carried out by an OMCL located within the Union (EEA) or by a country officially recognised by the EU for mutual recognition of batch release. The marketing authorisation holder will therefore need to identify a OMCL located in the Union (EEA) for official batch release or an officially recognised partner (as stated above) for official batch release. A list of the OMCLs that may be in a position to provide EU OCABR certificates for different products is available to manufacturers from the European Directorate for the Quality of Medicines & Healthcare (EDQM) on request at batchrelease@edqm.eu.
12 Guideline for the administrative procedure to be followed by the competent OMCL authorities for the implementation of Directive 2001/83/EC Article 114 as amended by Directive 2004/27/EC, available at https://www.edqm.eu/en/batch-release-human-biologicals-vaccines-blood-and-plasma-derivatives 13 For goods placed on the EU market before the withdrawal date, the EU is trying to agree solutions with the United Kingdom in the withdrawal agreement. The essential principles of the EU’s position on goods placed on the market under Union law before the withdrawal date are available here: https://ec.europa.eu/commission/publications/position-paper-goods-placed-market-under-union-law
20. What if my product is subject to Official Batch Protocol Review (OBPR) and evaluation is done by a UK Competent Authority? (for veterinary medicines) (NEW)
According to Article 81 of Directive 2001/82/EC Member States may require the marketing authorisation holder for immunological veterinary medicinal products to submit to the competent authorities copies of all the control reports signed by the qualified person in accordance with Article 55 of Directive 2001/82/EC in order to verify that control tests were carried out in accordance with the methods laid down for the purposes of marketing authorisation. This is referred to as an ‘Official Batch Protocol Review’ (OBPR). OBPR may be carried out by a Competent Authority within the Union (EEA) or in a country officially recognised by the EU for mutual recognition of batch release (e.g. Switzerland).
For products placed on the market as of the withdrawal date,14 OBPR cannot be carried out by a UK Competent Authority. The marketing authorisation holder will therefore need to identify another Competent Authority located in the Union (EEA) or an officially recognised partner (as stated above) for official batch protocol review.
21. How does UK’s withdrawal from the Union affect the status of inspection outcomes by the UK competent authority? (NEW)
It is expected that findings of inspections, in particular to determine compliance with good manufacturing practice, good clinical practice and pharmacovigilance obligations, conducted by the UK competent authority before 30 March 2019 are implemented by the inspected entities in accordance with the applicable legislation, in particular Directive 2003/94/EC, Commission Delegated Regulation (EU) No 1252/2014 and Directive 91/412/EEC with regard to good manufacturing practice, Directive 2001/20/EC and Commission Directive 2005/28/EC with regard to good clinical practice and Regulation (EC) No 726/2004, Directive 2001/83/EC and Commission Implementing Regulation (EU) 520/2012 with regard to pharmacovigilance obligations.
22. How does UK’s withdrawal from the Union affect CE certification of medical devices by UK notified bodies? (NEW)
This issue is addressed in the Commission Notice on the withdrawal of the United Kingdom and EU rules in the field of industrial products that also covers medical devices.
23. How does UK’s withdrawal from the Union impact the CHMP scientific opinion for ancillary medicinal substances in medical devices requested by UK notified bodies? (NEW)
According to Article 1(4) of Directive 93/42/EEC where a device incorporates, as an integral part, a substance which, if used separately, may be considered to be a medicinal product within the meaning of Article 1 of Directive 2001/83/EC and which is liable to act upon the body with action
withdrawal-date_en. The concept of placing on the market refers to each individual product, not to a type of product, irrespectively of whether it was manufactured as an individual unit or in series 14 For goods placed on the EU market before the withdrawal date, the EU is trying to agree solutions with the United Kingdom in the withdrawal agreement. The essential principles of the EU’s position on goods placed on the market under Union law before the withdrawal date are available here: https://ec.europa.eu/commission/publications/position-paper-goods-placed-market-under-union-lawwithdrawal-date_en. The concept of placing on the market refers to each individual product, not to a type of product, irrespectively of whether it was manufactured as an individual unit or in series
ancillary to that of the device, that device shall be assessed and authorized in accordance with Directive 93/42/EEC. In accordance with Annex I of Directive 93/42/EEC for a new medical device, the notified body acts as the applicant in an initial consultation procedure with EMA concerning the scientific opinion on the ancillary medicinal substances incorporated in the medical devices.
Union product legislation requires Notified Bodies to be established in a Member State and be designated by a Member State notifying authority.
From the withdrawal date, UK notified bodies will lose their status as EU notified bodies. They will no longer be able to be an applicant in an initial consultation procedure with EMA and EMA will not be able to issue a scientific opinion to them as notified bodies of a third country.
24. How does UK’s withdrawal from the Union impact on the possibility to market a multi-country pack which includes the UK? (NEW)
Multi-country packs are medicinal products that are labelled to allow their placing on the market in several Member States with the same packaging. This possibility is subject to the requirements set out in Directive 2001/83/EC in Title V or Directive 2001/82/EC in Title V and requires that the summary of product characteristics is the same in all the markets concerned. For that reason, multi-country packs with a third country will normally not be possible. Marketing authorisation holders currently using multi-country packs that include the UK may therefore have to adapt their packaging.
Article 57 and Article 62 of Directive 2001/83/EC and Article 63 of Directive 2001/82/EC allow Member States to require inclusion of certain additional labelling information in a restricted area (the so-called “blue box”) provided that all the strict conditions for application of Article 57 or Article 62 of Directive 2001/83/EC and Article 63 of Directive 2001/82/EC are fulfilled. While, in applying these provisions, it may be possible to include additional information on the label or package leaflet, in any event the product labelling and package leaflet must be fully in line with the summary of product characteristics as authorised in the EU.
25. What if Qualified Person’s for Pharmacovigilance (QPPV) back-up arrangements are in the UK? (NEW)
According to Article 2 of Commission Implementing Regulation (EU) No 520/2012 back-up arrangements shall apply in the absence of the 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).
Where a MAH relies on the services of a deputy QPPV as part of its back-up arrangements in the absence of the QPPV, those arrangements should ensure that the deputy QPPV is established and performs his/her tasks in the Union (EEA).
For veterinary medicines, reference is made to the EMA Brexit practical guidance.
European Commission Directorate-General for Health and Food Safety
European Medicines Agency
This article contains European Union public sector information which is reproduced pursuant to Commission Decision of 12 December 2011 on the reuse of Commission documents (2011/833/EU)
Contact McMahon Legal