Directive 2022/642 - Amendment of Directives 2001/20/EC and 2001/83/EC as regards derogations from certain obligations concerning certain medicinal products for human use made available in the United Kingdom in respect of Northern Ireland and in Cyprus, Ireland and Malta - Main contents

EN

Official Journal of the European Union

L 118/4

The Agreement on the withdrawal of the United Kingdom of Great Britain and Northern Ireland from the European Union and the European Atomic Energy Community (3) (the ‘Withdrawal Agreement’) was concluded on behalf of the Union by Council Decision (EU) 2020/135 (4) and entered into force on 1 February 2020. The transition period referred to in Article 126 of the Withdrawal Agreement, during which Union law continued to apply to and in the United Kingdom in accordance with Article 127 of the Withdrawal Agreement, ended on 31 December 2020. On 25 January 2021, the Commission issued a Notice (5) on the application of the Union’s pharmaceutical acquis in markets historically dependent on medicinal products supply from or through Great Britain, namely Cyprus, Ireland, Malta and Northern Ireland, from the end of that transition period until 31 December 2021.

In accordance with the Protocol on Ireland/Northern Ireland (the ‘Protocol’), which forms an integral part of the Withdrawal Agreement, the provisions of Union law listed in Annex 2 to the Protocol apply, under the conditions set out in that Annex, to and in the United Kingdom in respect of Northern Ireland. That list includes Article 13 of Directive 2001/20/EC of the European Parliament and of the Council (6) regarding the manufacture and import of investigational medicinal products, Directive 2001/83/EC of the European Parliament and of the Council (7) and Regulation (EC) No 726/2004 of the European Parliament and of the Council (8). Therefore, medicinal products placed on the market in Northern Ireland are to comply with those provisions of Union law.

Directives 2001/20/EC and 2001/83/EC lay down the rules for medicinal products for human use and investigational medicinal products intended to be placed on the market in the Member States.

Cyprus, Ireland, Malta and Northern Ireland have historically relied on the supply of medicinal products from or through parts of the United Kingdom other than Northern Ireland, and the supply chains for those markets have not yet been fully adapted to comply with Union law. To prevent shortages of medicinal products and ultimately to ensure a high level of public health protection, Directives 2001/20/EC and 2001/83/EC need to be amended to provide for derogations for medicinal products supplied to Cyprus, Ireland, Malta and Northern Ireland from or through parts of the United Kingdom other than Northern Ireland. In order to ensure uniform application of Union law in the Member States, the derogations applicable in Cyprus, Ireland and Malta should be of a temporary nature only.

In accordance with Article 13(1) of Directive 2001/20/EC, read in conjunction with the Protocol, the import of investigational medicinal products from third countries into the Union or Northern Ireland is subject to the holding of a manufacturing and import authorisation. To ensure continued access to new, innovative or improved treatments for clinical trial participants in Northern Ireland, as well as in Cyprus, Ireland and Malta after 31 December 2021, such a manufacturing and import authorisation should not be required for investigational medicinal products imported into those markets from parts of the United Kingdom other than Northern Ireland provided that certain conditions are fulfilled. To ensure uniform application of Union law in the Member States, the derogations applicable in Cyprus, Ireland and Malta should be of a temporary nature only.

Regulation (EC) No 726/2004 lays down Union procedures for the authorisation of medicinal products. Upon authorisation in the Union, medicinal products are available to patients in Northern Ireland. It is possible, however, that the competent authorities of the United Kingdom in respect of parts of the United Kingdom other than Northern Ireland issue a marketing authorisation for a medicinal product before a marketing authorisation has been granted for the same medicinal product in the Union. In such exceptional cases, and in order to ensure that patients in Northern Ireland have access to those medicinal products at the same time as patients in other parts of the United Kingdom, the competent authorities of the United Kingdom in respect of Northern Ireland should be able to supply those medicinal products to patients in Northern Ireland temporarily and until a marketing authorisation is granted or refused in the Union. In order to ensure the full effectiveness of the centralised procedure for granting marketing authorisations set out in Regulation (EC) No 726/2004, those temporary authorisations should be limited in time and should cease to be valid when the Commission takes a decision to grant or refuse the authorisation to market that medicinal product.

In accordance with Article 8(2) of Directive 2001/83/EC, read in conjunction with the Protocol, a marketing authorisation is only able to be granted to an applicant established in the Union or in Northern Ireland. A number of operators were not able to comply with that requirement by 31 December 2021. To ensure access to certain medicinal products in Northern Ireland, it is crucial that the holders of marketing authorisations granted by the competent authorities of the United Kingdom in respect of Northern Ireland are allowed to be established in parts of the United Kingdom other than Northern Ireland. Similarly, to ensure access to certain medicinal products in Cyprus, Ireland, Malta and Northern Ireland, it is necessary to allow the competent authorities of Cyprus, Ireland, Malta and Northern Ireland to grant marketing authorisations in the context of the mutual recognition or the decentralised procedure to marketing authorisation holders established in parts of the United Kingdom other than Northern Ireland.

It follows from Articles 17 and 18 of Directive 2001/83/EC, read in conjunction with the Protocol, that applicants for a marketing authorisation wishing to obtain both a marketing authorisation for the United Kingdom in respect of Northern Ireland as well as a marketing authorisation for one or more Member States need to include the United Kingdom in respect of Northern Ireland in the scope of their marketing authorisation application in accordance with the mutual recognition or the decentralised procedure. Where medicinal products are also authorised in parts of the United Kingdom other than Northern Ireland, the requirement to comply with that obligation could hamper the continuous access to medicinal products for patients in Northern Ireland. To avoid that issue, it is necessary to allow applicants in such situations the possibility to apply for a marketing authorisation for the United Kingdom in respect of Northern Ireland either in accordance with the mutual recognition or the decentralised procedure, or in accordance with the national marketing authorisation procedure applicable in relation to the United Kingdom in respect of Northern Ireland. In the case of such a national marketing authorisation procedure, the marketing authorisation should be granted in compliance with Union law, including the requirements on quality, safety and efficacy of medicinal products.

In accordance with Article 51(1), point (b), of Directive 2001/83/EC, medicinal products imported into the Union are to undergo quality control testing in the Union. Article 20, point (b), of that Directive allows the importers which place medicinal products supplied from or through parts of the United Kingdom other than Northern Ireland on the market in Cyprus, Ireland, Malta or Northern Ireland, or wholesale distributors placing such medicinal products on those markets, to have, in justifiable cases, certain controls carried out in parts of the United Kingdom other than Northern Ireland. Taking into account the historical dependence of Cyprus, Ireland, Malta and Northern Ireland on the supply of medicinal products from or through parts of the United Kingdom other than Northern Ireland and the related risks of shortages of medicinal products in those jurisdictions, a justifiable case within the meaning of Article 20, point (b), of Directive 2001/83/EC should be considered to occur when each batch of the medicinal product concerned is released by a qualified person on a site in the Union or by a qualified person on a site in parts of the United Kingdom other than Northern Ireland applying quality standards equivalent to those laid down in Union law, thereby ensuring an equivalent level of protection of human health. Since Article 20, point (b), of Directive 2001/83/EC only provides for batch testing to be carried out in a third country on a case-by-case basis, it is necessary to lay down conditions harmonising the implementation of that provision with regard to medicinal products supplied to Cyprus, Ireland, Malta and Northern Ireland from or through parts of the United Kingdom other than Northern Ireland.

It follows from Article 40(3) of Directive 2001/83/EC, read in conjunction with the Protocol, that importers of medicinal products from third countries into a Member State are to hold a manufacturing authorisation granted by the Member State where the importer is established or, in the case of importers established in Northern Ireland, by the United Kingdom in respect of Northern Ireland. To avoid a situation in which operators withdraw from or significantly reduce medicinal products supply to Cyprus, Ireland, Malta and Northern Ireland, it is necessary to derogate exceptionally from that requirement under certain conditions and to allow imports of medicinal products from or through parts of the United Kingdom other than Northern Ireland into Cyprus, Ireland, Malta and Northern Ireland by wholesale distributors that do not hold the relevant manufacturing authorisation, while ensuring an equivalent level of protection of human health.

In a situation where medicinal products are exported from a Member State to parts of the United Kingdom other than Northern Ireland, and subsequently imported into Cyprus, Ireland, Malta or Northern Ireland, it should be possible to waive specific controls, namely quality control testing, intended to guarantee the quality of those medicinal products imported from third countries, provided that appropriate arrangements have been made by the Union to ensure that the necessary controls are carried out in the exporting country.

It follows from Article 48 of Directive 2001/83/EC, read in conjunction with Article 49 of that Directive and with the Protocol, that the manufacturing authorisation holder is to have at its disposal a qualified person who resides and operates in the Union or Northern Ireland. To ensure a continuous access to certain medicinal products to patients in Northern Ireland, it is appropriate to allow the qualified person to reside and operate in parts of the United Kingdom other than Northern Ireland.

It follows from Article 104(3) of Directive 2001/83/EC, read in conjunction with the Protocol, that the qualified person responsible for pharmacovigilance is to reside and operate in the Union or Northern Ireland. A number of operators were not able to comply with that requirement by 31 December 2021. To ensure that access to certain medicinal products for patients in Northern Ireland is not hampered, it is appropriate to allow the qualified person responsible for pharmacovigilance to reside and operate in parts of the United Kingdom other than Northern Ireland.

To avoid shortages of medicinal products in Cyprus and Malta, the competent authorities of Cyprus and Malta should be allowed, for public health reasons and for a certain period, to grant, maintain in force and extend marketing authorisations on the basis of Article 126a of Directive 2001/83/EC which rely on marketing authorisations granted by the competent authorities of parts of the United Kingdom other than Northern Ireland, even if the marketing authorisation holder is no longer established in the Union, provided that certain conditions are fulfilled. Since Union law no longer applies in parts of the United Kingdom other than Northern Ireland, it is necessary to provide that the competent authorities of Cyprus and Malta ensure that such authorisations comply with Union law. In order to ensure that the functioning of the Union market is not undermined, it is necessary to establish the conditions for enhanced supervision and enforcement of the rules relevant for the application of the derogations introduced by this Directive. The Commission should monitor developments in parts of the United Kingdom other than Northern Ireland that could affect the level of protection regarding the regulatory functions covered by this Directive. If the Commission finds that the level of protection of public health ensured by the United Kingdom by means of rules governing the production, distribution and use of medicinal products, as well as by means of the effective enforcement of those rules, is no longer essentially equivalent to that guaranteed within the Union, or if the Commission lacks information to assess whether an essentially equivalent level of protection is guaranteed, the Commission should enter into consultation with the United Kingdom to find a mutually agreed remedy to that situation. If no such remedy is found within the prescribed period, the Commission should, as a last resort, be empowered to adopt delegated acts suspending the application of one or more provisions introduced by this Directive.

In order to ensure transparency, the competent authorities of Cyprus, Ireland, Malta and the United Kingdom in respect of Northern Ireland should publish a list of medicinal products to which they intend to apply or have applied the derogations set out in this Directive. In order to make that list easily searchable, it should contain the same information as that included in the package leaflet or summary of product characteristics of the medicinal products concerned.

Since the objectives of this Directive cannot be sufficiently achieved by the Member States but can rather, by reason of the scale or effects of the action, be better achieved at Union level, the Union may adopt measures, in accordance with the principle of subsidiarity as set out in Article 5 of the Treaty on European Union. In accordance with the principle of proportionality, as set out in that Article, this Directive does not go beyond what is necessary in order to achieve those objectives.

Directives 2001/20/EC and 2001/83/EC should therefore be amended accordingly.

In order to ensure legal continuity for operators active in the pharmaceutical sector and to guarantee the continuous access of patients in Cyprus, Ireland, Malta and Northern Ireland to medicinal products, this Directive should enter into force as a matter of urgency on the day of its publication in the Official Journal of the European Union and the measures adopted by the Member States to comply with it should apply retroactively from 1 January 2022,

the investigational medicinal products imported into Cyprus, Ireland, Malta or Northern Ireland have undergone certification of batch release either in the Union, as provided for in paragraph 3, point (a), or in parts of the United Kingdom other than Northern Ireland in compliance with the requirements set out in paragraph 3, point (b);

the investigational medicinal products are only made available to subjects in the Member State into which those investigational medicinal products are imported, or, if imported into Northern Ireland, are only made available to subjects in Northern Ireland.’.

the following Article is inserted:

‘Article 5a

By way of derogation from Article 6, the competent authorities of the United Kingdom in respect of Northern Ireland may temporarily authorise the supply to patients in Northern Ireland of a medicinal product belonging to the categories referred to in Article 3(1) and (2) of Regulation (EC) No 726/2004 provided that all of the following conditions are fulfilled:

The maximum validity of the temporary authorisation shall be six months. Notwithstanding the specified validity, the temporary authorisation shall cease to be valid if the medicinal product concerned has been granted a marketing authorisation in accordance with Article 10 of Regulation (EC) No 726/2004, or if such marketing authorisation has been refused in accordance with that Article.’;

in Article 8, the following paragraphs are inserted:

‘2a.   By way of derogation from paragraph 2, marketing authorisations may be granted by the competent authorities of the United Kingdom in respect of Northern Ireland to applicants established in parts of the United Kingdom other than Northern Ireland.

2b.   By way of derogation from paragraph 2, marketing authorisations may be granted by the competent authorities of the United Kingdom in respect of Northern Ireland and, until 31 December 2024, by the competent authorities of Cyprus, Ireland and Malta, in accordance with the mutual recognition or the decentralised procedure laid down in Chapter 4 of this Title, to marketing authorisation holders established in parts of the United Kingdom other than Northern Ireland.

The competent authorities of the United Kingdom in respect of Northern Ireland and, until 31 December 2024, the competent authorities of Cyprus, Ireland and Malta may extend marketing authorisations already granted prior to 20 April 2022 to marketing authorisation holders established in parts of the United Kingdom other than Northern Ireland.

The marketing authorisations granted or extended by the competent authorities of Cyprus, Ireland or Malta in accordance with the first and second subparagraph shall cease to be valid at the latest on 31 December 2026.’;

the following Article is inserted:

‘Article 18a

• 1. 

  By way of derogation from Article 17(1), second subparagraph, Article 17(2) and Article 18, if an application for marketing authorisation is submitted in one or more Member States and in the United Kingdom in respect of Northern Ireland, or if an application for marketing authorisation is submitted in the United Kingdom in respect of Northern Ireland for a medicinal product which is already being examined or has already been authorised in a Member State, the application regarding the United Kingdom in respect of Northern Ireland shall not have to be submitted in accordance with Articles 28 to 39 provided that all of the following conditions are fulfilled:

• 2. 

  The marketing authorisation holder of a medicinal product for which a marketing authorisation has already been granted for the United Kingdom in respect of Northern Ireland in accordance with Articles 28 to 39 before 20 April 2022 shall be allowed to withdraw the marketing authorisation for the United Kingdom in respect of Northern Ireland from the mutual recognition or the decentralised procedure and to submit an application for a marketing authorisation for that medicinal product to the competent authorities of the United Kingdom with respect to Northern Ireland in accordance with paragraph 1.’;

in Article 20, the following paragraph is added:

‘With regard to quality control testing carried out in parts of the United Kingdom other than Northern Ireland regarding medicinal products included in the list referred to in Article 127d other than those authorised by the Commission, the competent authorities of the United Kingdom in respect of Northern Ireland and, until 31 December 2024, the competent authorities of Cyprus, Ireland and Malta may consider that there is a justifiable case within the meaning of point (b) of the first paragraph, without carrying out a case-by-case assessment provided that:

Article 40 is amended as follows:

in Article 48, the following paragraph is added:

‘3.   Where the manufacturing authorisation is granted by the competent authority of the United Kingdom in respect of Northern Ireland, the qualified person referred to in paragraph 1 may reside and operate in parts of the United Kingdom other than Northern Ireland. This paragraph shall not apply where the manufacturing authorisation holder already has at its disposal a qualified person who resides and operates in the Union on 20 April 2022.’;

in Article 104(3), the following subparagraph is added:

‘By way of derogation from the second subparagraph, where the marketing authorisation is granted by the competent authority of United Kingdom in respect of Northern Ireland, the qualified person referred to in point (a) of the first subparagraph may reside and operate in parts of the United Kingdom other than Northern Ireland. This subparagraph shall not apply where the marketing authorisation holder already has at its disposal a qualified person who resides and operates in the Union on 20 April 2022.’;

the following Article is inserted:

‘Article 111c

• 1. 

  The Commission shall continuously monitor developments in the United Kingdom that could affect the level of protection regarding the regulatory functions referred to in Article 8(2a) and (2b), Article 20, second paragraph, Article 40(1a) and (3a), Article 48(3), Article 104(3) and Article 126c that are carried out in parts of the United Kingdom other than Northern Ireland taking into account, in particular, the following elements:

• 2. 

  Where the Commission finds that the level of protection of public health ensured by the United Kingdom through rules governing the production, distribution and use of medicinal products as well as the effective enforcement of those rules is no longer essentially equivalent to that guaranteed within the Union, or where sufficient information is not available to the Commission to enable it to establish whether an essentially equivalent level of protection of public health is ensured by the United Kingdom, the Commission shall inform the United Kingdom through a written notification of that finding and of the detailed reasons therefor.

For a period of six months following the written notification made pursuant to the first subparagraph, the Commission shall enter into consultations with the United Kingdom with a view to remedying the situation giving rise to that written notification. In justified cases, the Commission may extend that period by three months.

• 3. 

  If the situation giving rise to the written notification made pursuant to paragraph 2, first subparagraph, is not remedied within the time-limit referred to in paragraph 2, second subparagraph, the Commission shall be empowered to adopt a delegated act specifying the provisions among those referred to in paragraph 1 whose application shall be suspended.

• 4. 

  Where a delegated act pursuant to paragraph 3 has been adopted, the provisions referred to in the introductory sentence of paragraph 1 as specified in the delegated act shall cease to apply on the first day of the month following the entry into force of the delegated act.

• 5. 

  Where the situation giving rise to the adoption of the delegated act pursuant to paragraph 3 has been remedied, the Commission shall adopt a delegated act specifying those suspended provisions that shall apply again. In that case, the provisions specified in the delegated act adopted pursuant to this paragraph shall apply again on the first day of the month following the entry into force of the delegated act referred to in this paragraph.’;

Article 121a is amended as follows:

the following Article is inserted:

‘Article 126c

• 1. 

  By way of derogation from Article 126a, until 31 December 2024, in the absence of a marketing authorisation or of a pending application for a marketing authorisation the competent authorities of Cyprus and Malta may authorise for justified public health reasons the placing on their national market of a medicinal product authorised in parts of the United Kingdom other than Northern Ireland.

The competent authorities of Cyprus and Malta may also maintain in force or, until 31 December 2024, extend marketing authorisations that were granted pursuant to Article 126a before 20 April 2022 which authorise the placing on their national market of a medicinal product authorised in parts of the United Kingdom other than Northern Ireland.

Authorisations that are granted, extended or maintained in force pursuant to the first or second subparagraph shall not be valid after 31 December 2026.

• 2. 

  By way of derogation from Article 8(2), the competent authorities of Malta and Cyprus may grant marketing authorisations as referred to in paragraph 1 of this Article to marketing authorisation holders established in parts of the United Kingdom other than Northern Ireland.

• 3. 

  Where the competent authorities of Cyprus or Malta grant or extend a marketing authorisation as referred to in paragraph 1, they shall ensure compliance with the requirements of this Directive.

• 4. 

  Before granting a marketing authorisation pursuant to paragraph 1, the competent authorities of Cyprus or Malta:

the following Articles are inserted:

‘Article 127c

The derogations set out in Article 8(2a) and(2b), Article 18a, Article 20, second paragraph, Article 40(1a) and (3a), Article 48(3), Article 104(3a) and Article 126c shall not affect the obligations of the marketing authorisation holder to ensure the quality, safety and efficacy of the medicinal product placed on the markets of Cyprus, Ireland, Malta or Northern Ireland laid down in this Directive.

Article 127d

• 1. 

  By 20 May 2022, the competent authorities of Cyprus, Ireland, Malta and the United Kingdom in respect of Northern Ireland shall establish, notify to the Commission and publish on their website a list of medicinal products to which they have applied or intend to apply the derogations as set out in this Directive.

• 2. 

  The competent authorities of Cyprus, Ireland, Malta and the United Kingdom in respect of Northern Ireland shall ensure that the list referred to in paragraph 1 is updated and managed in an independent manner, at least on a six-monthly basis.’.