Regulation (EU) 2019/5 of the European Parliament and of the Council of 11 December 2018 amending Regulation (EC) No 726/2004 laying down Community procedures for the authorisation and supervision of medicinal products for human and veterinary use and establishing a European Medicines Agency, Regulation (EC) No 1901/2006 on medicinal products for paediatric use and Directive 2001/83/EC on the Community code relating to medicinal products for human use (Text with EEA relevance)

‘2 Any medicinal product not appearing in Annex I may be granted a marketing authorisation by the Union in accordance with this Regulation, if: (a) the medicinal product contains an active substance which, on 20 May 2004, was not authorised in the Union; or (b) the applicant shows that the medicinal product constitutes a significant therapeutic, scientific or technical innovation or that the granting of authorisation in accordance with this Regulation is in the interest of patients' health at Union level.’;

‘2 The Commission shall, by means of implementing acts, take a final decision within 15 days after obtaining the opinion of the Standing Committee on Medicinal Products for Human Use. Those implementing acts shall be adopted in accordance with the examination procedure referred to in Article 87(2).’;

‘5 The Commission shall, by means of implementing acts, adopt detailed rules for the implementation of paragraph 4 which specify the applicable time limits and procedures. Those implementing acts shall be adopted in accordance with the examination procedure referred to in Article 87(2).’;

‘1 The Commission is empowered to adopt delegated acts in accordance with Article 87b, in order to supplement this Regulation by determining the situations in which post-authorisation efficacy studies may be required under point (cc) of Article 9(4) and point (b) of Article 10a(1).’;

‘1 Without prejudice to paragraphs 4 and 5 of this Article and to Article 14-a, a marketing authorisation shall be valid for five years.’;

1 In duly justified cases, to meet unmet medical needs of patients, a marketing authorisation may, for medicinal products intended for the treatment, prevention or medical diagnosis of seriously debilitating or life-threatening diseases, be granted prior to the submission of comprehensive clinical data provided that the benefit of the immediate availability on the market of the medicinal product concerned outweighs the risk inherent in the fact that additional data are still required. In emergency situations, a marketing authorisation for such medicinal products may be granted also where comprehensive pre-clinical or pharmaceutical data have not been supplied.

2 For the purposes of this Article, “unmet medical needs” means a condition for which there exists no satisfactory method of diagnosis, prevention or treatment authorised in the Union or, even if such a method exists, in relation to which the medicinal product concerned will be of major therapeutic advantage to those affected.

3 Marketing authorisations may be granted pursuant to this Article only if the risk-benefit balance of the medicinal product is favourable and the applicant is likely to be able to provide comprehensive data.

4 Marketing authorisations granted pursuant to this Article shall be subject to specific obligations. Those specific obligations and, where appropriate, the time limit for compliance shall be specified in the conditions to the marketing authorisation. Those specific obligations shall be reviewed annually by the Agency.

5 As part of the specific obligations referred to in paragraph 4, the holder of a marketing authorisation granted pursuant to this Article shall be required to complete ongoing studies, or to conduct new studies, with a view to confirming that the risk-benefit balance is favourable.

6 The summary of product characteristics and the package leaflet shall clearly mention that the marketing authorisation for the medicinal product has been granted subject to specific obligations as referred to in paragraph 4.

7 By way of derogation from Article 14(1), a marketing authorisation granted pursuant to this Article shall be valid for one year, on a renewable basis.

8 When the specific obligations referred to in paragraph 4 of this Article have been fulfilled, the Commission may, following an application by the marketing authorisation holder, and after receiving a favourable opinion from the Agency, grant a marketing authorisation valid for five years and renewable pursuant to Article 14(2) and (3).

9 The Commission is empowered to adopt delegated acts in accordance with Article 87b in order to supplement this Regulation by specifying: (a) the categories of medicinal products to which paragraph 1 of this Article applies; and (b) the procedures and requirements for granting a marketing authorisation pursuant to this Article and for its renewal.’;

1 Variations shall be classified in different categories depending on the level of risk to public health and the potential impact on the quality, safety and efficacy of the medicinal product concerned. Those categories shall range from changes to the terms of the marketing authorisation that have the highest potential impact on the quality, safety or efficacy of the medicinal product, to changes that have no or minimal impact thereon.

2 The procedures for examination of applications for variations shall be proportionate to the risk and impact involved. Those procedures shall range from procedures that allow implementation only after approval based on a complete scientific assessment to procedures that allow immediate implementation and subsequent notification by the marketing authorisation holder to the Agency.

3 The Commission is empowered to adopt delegated acts in accordance with Article 87b in order to supplement this Regulation by: (a) specifying the categories in which variations shall be classified; and (b) establishing procedures for the examination of applications for variations to the terms of marketing authorisations.

A marketing authorisation may be transferred to a new marketing authorisation holder. Such a transfer shall not be considered to be a variation. The transfer shall be subject to prior approval by the Commission, following the submission of an application for the transfer to the Agency. The Commission is empowered to adopt delegated acts in accordance with Article 87b in order to supplement this Regulation by establishing procedures for the examination of applications to the Agency for the transfer of marketing authorisations.’;

Where the Agency concludes that a holder of a marketing authorisation granted pursuant to Article 14-a failed to comply with the obligations laid down in the marketing authorisation, the Agency shall inform the Commission accordingly. The Commission shall adopt a decision to vary, suspend or revoke that marketing authorisation in accordance with the procedure set out in Article 10.’;

A European Medicines Agency is hereby established. The Agency shall be responsible for coordinating the existing scientific resources put at its disposal by Member States for the evaluation, supervision and pharmacovigilance of medicinal products for human use and of veterinary medicinal products.’;

1 The Executive Director shall implement the budget of the Agency in accordance with Regulation (EU) 2018/1046 of the European Parliament and of the Council (“the Financial Regulation”).

2 By 1 March of financial year n+1, the Agency’s accounting officer shall send the provisional accounts for year n to the Commission’s accounting officer and to the Court of Auditors.

3 By 31 March of financial year n+1, the Executive Director shall send the report on the budgetary and financial management for year n to the European Parliament, to the Council, to the Commission and to the Court of Auditors.

4 By 31 March of financial year n+1, the Commission’s accounting officer shall send the Agency’s provisional accounts for year n, consolidated with the Commission’s provisional accounts, to the Court of Auditors. On receipt of the Court of Auditors’ observations on the Agency’s provisional accounts pursuant to Article 246 of the Financial Regulation, the Agency’s accounting officer shall draw up the Agency’s final accounts and the Executive Director shall submit them to the Management Board for an opinion.

5 The Management Board shall deliver an opinion on the Agency’s final accounts for year n.

6 The Agency’s accounting officer shall, by 1 July of financial year n+1, send the final accounts, together with the Management Board’s opinion, to the European Parliament, to the Council, to the Court of Auditors and to the Commission’s accounting officer.

7 The final accounts for year n shall be published in the Official Journal of the European Union by 15 November of financial year n+1.

8 The Executive Director shall send to the Court of Auditors a reply to its observations by 30 September of financial year n+1. The Executive Director shall also send that reply to the Management Board.

9 The Executive Director shall submit to the European Parliament, at the latter’s request, any information required for the smooth application of the discharge procedure for the financial year concerned, as laid down in Article 261(3) of the Financial Regulation.

10 The European Parliament, upon a recommendation from the Council, shall, before 15 May of financial year n+2, give a discharge to the Executive Director in respect of the implementation of the budget for year n.

11 The financial rules applicable to the Agency shall be adopted by the Management Board after the Commission has been consulted. They shall not depart from Commission Delegated Regulation (EU) No 1271/2013 unless specifically required for the Agency’s operation and with the Commission’s prior consent.

The Commission may, in agreement with the Management Board and the relevant committee, invite representatives of international organisations with an interest in the harmonisation of technical requirements applicable to medicinal products for human use and to veterinary medicinal products to participate as observers in the work of the Agency. The conditions for participation shall be determined in advance by the Commission.’;

1 The Commission may impose financial penalties in the form of fines or periodic penalty payments on the holders of marketing authorisations granted under this Regulation if they fail to comply with any of the obligations laid down in Annex II in connection with the marketing authorisations.

2 The Commission may, insofar as specifically provided for in the delegated acts referred to in point (b) of paragraph 10, impose the financial penalties referred to in paragraph 1 also on a legal entity or legal entities other than the marketing authorisation holder provided that such entities form part of the same economic entity as the marketing authorisation holder and that such other legal entities: (a) exerted a decisive influence over the marketing authorisation holder; or (b) were involved in, or could have addressed, such failure to comply with the obligation by the marketing authorisation holder.

3 Where the Agency or a competent authority of a Member State is of the opinion that a marketing authorisation holder has failed to comply with any of the obligations, as referred to in paragraph 1, it may request the Commission to investigate whether to impose financial penalties pursuant to that paragraph.

4 In determining whether to impose a financial penalty and in determining its appropriate amount, the Commission shall be guided by the principles of effectiveness, proportionality and dissuasiveness and take into consideration, where relevant, the seriousness and the effects of the failure to comply with the obligations.

5 For the purposes of paragraph 1, the Commission shall also take into account: (a) any infringement procedure initiated by a Member State against the same marketing authorisation holder on the basis of the same legal grounds and the same facts; and (b) any sanctions, including penalties, already imposed on the same marketing authorisation holder on the basis of the same legal grounds and the same facts.

6 Where the Commission finds that the marketing authorisation holder has failed, intentionally or negligently, to comply with its obligations, as referred to in paragraph 1, it may adopt a decision imposing a fine not exceeding 5 % of the marketing authorisation holder’s Union turnover in the business year preceding the date of that decision. Where the marketing authorisation holder continues to fail to comply with its obligations referred to in paragraph 1, the Commission may adopt a decision imposing periodic penalty payments per day not exceeding 2,5 % of the marketing authorisation holder’s average daily Union turnover in the business year preceding the date of that decision. Periodic penalty payments may be imposed for a period running from the date of notification of the relevant Commission's decision until the failure to comply with the obligation by the marketing authorisation holder, as referred to in paragraph 1, has been brought to an end.

7 When conducting the investigation on a failure to comply with any of the obligations referred to in paragraph 1, the Commission may cooperate with national competent authorities and rely on resources provided by the Agency.

8 Where the Commission adopts a decision imposing a financial penalty, it shall publish a concise summary of the case, including the names of the marketing authorisation holders involved and the amounts of and reasons for the financial penalties imposed, having regard to the legitimate interest of the marketing authorisation holders for the protection of their business secrets.

9 The Court of Justice of the European Union shall have unlimited jurisdiction to review decisions whereby the Commission has imposed financial penalties. The Court of Justice of the European Union may cancel, reduce or increase the fine or periodic penalty payment imposed by the Commission.

10 The Commission is empowered to adopt delegated acts in accordance with Article 87b in order to supplement this Regulation by laying down: (a) procedures to be applied by the Commission when imposing fines or periodic penalty payments, including rules on the initiation of the procedure, measures of inquiry, rights of the defence, access to file, legal representation and confidentiality; (b) further detailed rules on the imposition by the Commission of financial penalties on legal entities other than the marketing authorisation holder; (c) rules on duration of procedure and limitation periods; (d) elements to be taken into account by the Commission when setting the level of and imposing fines and periodic penalty payments, as well as the conditions and methods for their collection.’;

At least every 10 years, the Commission shall publish a general report on the experience acquired as a result of the operation of the procedures laid down in this Regulation and in Chapter 4 of Title III of Directive 2001/83/EC.’;

By 2019, the Commission shall review the regulatory framework for fees payable to the Agency in relation to medicinal products for human use and veterinary medicinal products. The Commission shall put forward, as appropriate, legislative proposals with a view to update that framework. When reviewing the regulatory framework for fees payable to the Agency, the Commission shall pay attention to potential risks related to the fluctuations in the fee revenue of the Agency.’;

1 The Commission shall be assisted by the Standing Committee on Medicinal Products for Human Use established by Article 121 of Directive 2001/83/EC. That committee shall be a committee within the meaning of Regulation (EU) No 182/2011 of the European Parliament and of the Council .

2 Where reference is made to this paragraph, Article 5 of Regulation (EU) No 182/2011 shall apply.

1 The power to adopt delegated acts is conferred on the Commission subject to the conditions laid down in this Article.

2 The power to adopt delegated acts referred to in Articles 10b(1), 14-a(9), 16a(3), the second paragraph of Article 16b, and Article 84a(10) shall be conferred on the Commission for a period of five years from 28 January 2019. The Commission shall draw up a report in respect of the delegation of power not later than nine months before the end of the five-year period. The delegation of power shall be tacitly extended for periods of an identical duration, unless the European Parliament or the Council opposes such extension not later than three months before the end of each period.

3 The delegation of power referred to in Articles 10b(1), 14-a(9), 16a(3), the second paragraph of Article 16b, and Article 84a(10) may be revoked at any time by the European Parliament or by the Council. A decision to revoke shall put an end to the delegation of the power specified in that decision. It shall take effect the day following the publication of the decision in the Official Journal of the European Union or at a later date specified therein. It shall not affect the validity of any delegated acts already in force.

4 Before adopting a delegated act, the Commission shall consult experts designated by each Member State in accordance with the principles laid down in the Interinstitutional Agreement of 13 April 2016 on Better Law-Making .

5 As soon as it adopts a delegated act, the Commission shall notify it simultaneously to the European Parliament and to the Council.

6 A delegated act adopted pursuant to Articles 10b(1), 14-a(9), 16a(3), the second paragraph of Article 16b, and Article 84a(10) shall enter into force only if no objection has been expressed either by the European Parliament or by the Council within a period of three months of notification of that act to the European Parliament and to the Council or if, before the expiry of that period, the European Parliament and the Council have both informed the Commission that they will not object. That period shall be extended by three months at the initiative of the European Parliament or of the Council.

‘1 Variations shall be classified in different categories depending on the level of risk to public health and the potential impact on the quality, safety and efficacy of the medicinal product concerned. Those categories shall range from changes to terms of the marketing authorisation that have the highest potential impact on the quality, safety or efficacy of the medicinal product, to changes that have no or minimal impact thereon.

2 The procedures for examination of applications for variations shall be proportionate to the risk and impact involved. Those procedures shall range from procedures that allow implementation only after approval based on a complete scientific assessment to procedures that allow immediate implementation and subsequent notification by the marketing authorisation holder to the competent authority.

2a The Commission is empowered to adopt delegated acts in accordance with Article 121a in order to supplement this Directive by: (a) specifying the categories in which variations shall be classified; and (b) establishing procedures for the examination of applications for variations to the terms of marketing authorisations.

3 When adopting the delegated acts referred to in this Article, the Commission shall endeavour to make possible the submission of a single application for one or more identical changes made to the terms of different marketing authorisations.

4 A Member State may continue to apply national provisions on variations applicable at the time of entry into force of Commission Regulation (EC) No 1234/2008 to marketing authorisations granted before 1 January 1998 to medicinal products authorised only in that Member State. Where a medicinal product subject to national provisions in accordance with this Article is subsequently granted a marketing authorisation in another Member State, Regulation (EC) No 1234/2008 shall apply to that medicinal product from that date.

1 The power to adopt delegated acts is conferred on the Commission subject to the conditions laid down in this Article.

2 The power to adopt delegated acts referred to in Articles 22b, 23b(2a), 47, 52b and 54a shall be conferred on the Commission for a period of five years from 28 January 2019. The Commission shall draw up a report in respect of the delegation of power not later than nine months before the end of the five-year period. The delegation of power shall be tacitly extended for periods of an identical duration, unless the European Parliament or the Council opposes such extension not later than three months before the end of each period.

3 The delegation of power referred to in Articles 22b, 23b(2a), 47, 52b and 54a may be revoked at any time by the European Parliament or by the Council. A decision to revoke shall put an end to the delegation of the power specified in that decision. It shall take effect the day following the publication of the decision in the Official Journal of the European Union or at a later date specified therein. It shall not affect the validity of any delegated acts already in force.

4 Before adopting a delegated act, the Commission shall consult experts designated by each Member State in accordance with the principles laid down in the Interinstitutional Agreement of 13 April 2016 on Better Law-Making .

5 As soon as it adopts a delegated act, the Commission shall notify it simultaneously to the European Parliament and to the Council.

6 A delegated act adopted pursuant to Articles 22b, 23b(2a), 47, 52b and 54a shall enter into force only if no objection has been expressed either by the European Parliament or by the Council within a period of two months of notification of that act to the European Parliament and to the Council or if, before the expiry of that period, the European Parliament and the Council have both informed the Commission that they will not object. That period shall be extended by two months at the initiative of the European Parliament or of the Council.

‘3 The Commission may, in relation to medicinal products authorised in accordance with Regulation (EC) No 726/2004, impose, in accordance with the procedure laid down in Article 84a of that Regulation, financial penalties in the form of fines or periodic penalty payments for the failure to comply with the obligations set out in this Regulation that are listed in Annex II to Regulation (EC) No 726/2004.’.

1 Regulations (EC) No 2141/96, (EC) No 2049/2005, (EC) No 507/2006 and (EC) No 658/2007 shall remain in force and continue to apply unless and until repealed.

2 Regulation (EC) No 1234/2008 shall continue to apply unless and until repealed as regards medicinal products for human use that are covered by Regulation (EC) No 726/2004 and Directive 2001/83/EC and that are not excluded from the scope of Regulation (EC) No 1234/2008 pursuant to Article 23b(4) and (5) of Directive 2001/83/EC.

This Regulation shall enter into force on the twentieth day following that of its publication in the Official Journal of the European Union. Points (2) to (5), (10), (12) to (16), (18), (26), (28), (29), (31), (37), (38), (40), (42) to (44) and (46) of Article 1, and Articles 2, 3 and 4 shall apply from 28 January 2019. Points (1), (6) to (9), (11), (17), (19) to (25), (27), (30), (32) to (36), (39), (41) and (45) of Article 1 shall apply from 28 January 2022.