Changes from plenary report to adopted text

Added(154) This Regulation is based on the double legal basis of Article 114 and Article 168(4), point (c), TFEU. It aims at achieving an internal market as regards medicinal products for human use, taking as a base a high level of protection of health. At the same time, this Regulation sets high standards of quality and safety for medicinal products in order to meet common safety concerns as regards these products. Both objectives are being pursued simultaneously. These two objectives are inseparably linked and one is not secondary to another. Regarding Article 114 TFEU, this Regulation establishes a European Medicines Agency and provides specific provision with regard to the central authorisation of medicinal products, therefore ensuring the functioning of the internal market and the free movement of medicinal products. Regarding Article 168(4), point (c), TFEU, this Regulation sets high standards of quality and safety for medicinal products.

RemovedArticle 69 – paragraph 6: 6. An applicant may submit an application for a separate marketing authorisation for other indications which do not fulfil the requirements set out in Article 63(1).

Added(155) This Regulation respects the fundamental rights and observes the principles recognised in particular by the Charter of Fundamental Rights of the European Union and notably human dignity, the integrity of the person, the rights of the child, respect for private and family life, the protection of personal data and the freedom of art and science. Similarly, this Regulation aims to ensure a high level of protection of the environment in accordance with Article 192(1) TFEU. [Am. 87]

RemovedArticle 70 – paragraph 1 – point a: (a) there is no medicinal product authorised in the Union for such condition; or

Added(156) The objective of this Regulation is to ensure the authorisation of high quality medicinal products, including for paediatric patients and patients suffering from rare diseases throughout the Union. Where this objective cannot be sufficiently achieved by the Member States but can rather, by reason of its scale, 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 Regulation does not go beyond what is necessary in order to achieve that objective.

RemovedArticle 70 – paragraph 1 – point b: (b) where a medicinal product is authorised for such condition, in addition to having a significant benefit, it will bring exceptional therapeutic advancement and the use of the orphan medicinal product results in a meaningful reduction in disease morbidity or mortality for the relevant patient population.

AddedHAVE ADOPTED THIS REGULATION:

RemovedArticle 70 – paragraph 3: 3. Where the Agency adopts scientific guidelines for the application of this Article, it shall consult the Commission, the authorities or bodies and other relevant stakeholders referred to in Article 162.

AddedCHAPTER I SUBJECT MATTER, SCOPE AND DEFINITIONS

RemovedArticle 71 – paragraph 2 – point b: (b) eleven years for orphan medicinal products addressing a high unmet medical need as referred to in Article 70;

AddedArticle 1 Subject matter and scope

RemovedArticle 71 – paragraph 2 – point c: (c) four years for orphan medicinal products which have been authorised in accordance with Article 13 of [revised Directive 2001/83/EC].

AddedThis Regulation lays down Union procedures for the authorisation, supervision and pharmacovigilance of medicinal products for human use at Union level, establishes rules and procedures at Union and at Member State level relating to the monitoring and management of shortages and critical shortages and the security of supply of medicinal products and lays down the governance provisions of the European Medicines Agency (‘the Agency’) established by Regulation (EC) No 726/2004 which shall carry out the tasks relating to medicinal products for human use that are laid down in this Regulation, Regulation (EU) No 2019/6 and other relevant Union legal acts. [Am. 88]

RemovedArticle 71 – paragraph 5: 5. The submission, validation and assessment of the application for the marketing authorisation and granting the marketing authorisation for a generic or biosimilar product to the reference medicinal product, shall not be prevented by the market exclusivity of a similar product to the reference medicinal product.

AddedThis Regulation shall not affect the powers of Member States' authorities as regards setting the prices of medicinal products or their inclusion in the scope of the national health system or social security schemes on the basis of health, economic and social conditions. Member States may choose from the particulars shown in the marketing authorisation those therapeutic indications and pack sizes which will be covered by their social security bodies.

RemovedArticle 71 – paragraph 6: 6. The market exclusivity of the orphan medicinal product shall not prevent the submission, validation, assessment of an application for, or the granting of, a marketing authorisation for a similar medicinal product, including generics and biosimilars, where the remainder of the duration of the initial market exclusivity is less than two years.

AddedArticle 2 Definitions

RemovedArticle 72 – paragraph 1: deleted / (deleted)

AddedFor the purposes of this Regulation, the definitions laid down in Article 4 of [revised Directive 2001/83/EC] shall apply.

RemovedArticle 73 a (new): Article73a / Joint procurement of centrally authorised medicinal products / 1. Upon request from the Member States, the Commission shall facilitate joint procurement of centrally authorised medicinal products at Union level on Member States' behalf. / 2. The Commission is empowered to adopt delegated acts in accordance with Article 175 to supplement this Regulation by further defining the conditions and procedures for joint procurement of centrally authorised medicinal products.

AddedThe following definitions shall also apply:

RemovedArticle 73 b (new): Article73b / Union Framework for Rare Diseases / By ... [24 months from the date of entry into force of this Regulation], the Commission shall, following a consultation with the Member States, patient organisations and other relevant stakeholders, propose a needs-driven and goals-based Union Framework for Rare Diseases with a view to better framing and coordinating Union policies and programmes, and supporting Member States in the elaboration of national strategies to better meet the unmet needs of people living with rare diseases, and their carers.

Added(1) ‘veterinary medicinal product’ means a medicinal product as defined in Article 4, point (1), of Regulation (EU) 2019/6;

RemovedArticle 74 – paragraph 2 – subparagraph 1 – point b: (b) following the acceptance by the Agency of a duly justified request from an applicant in accordance with paragraph 3.

Added(2) ‘designated orphan medicinal product’ means a medicinal product under development which has been granted an orphan designation by a decision referred to in Article 64(4);

RemovedArticle 74 – paragraph 3: 3. When it is not possible, on the basis of scientifically justified reasons, to have a complete paediatric development plan in accordance with the timing given in Article 76(1) an applicant may submit a duly justified request to the Agency to utilise the procedure mentioned in paragraph 2. The Agency has 20 days to accept or refuse the request and shall immediately inform the applicant and state the reasons for refusal.

Added(3) ‘orphan medicinal products’ means a medicinal product which has been granted an orphan marketing authorisation referred to in Article 69;

RemovedArticle 75 – paragraph 1 – point b: (b) that the disease or condition for which the specific medicinal product or class is intended occurs only in adult populations, unless when the product is directed at a molecular target or due to its mechanism of action on the basis of existing scientific data, is responsible for a different disease or condition in the same therapeutic area in children than the one for which the specific medicinal product or class of medicinal products is intended for in the adult population;

Added(4) ‘orphan medicine sponsor’ means any legal or natural person, established in the Union, who submitted an application for or has been granted an orphan designation by a decision referred to in Article 64(4);

RemovedArticle 75 – paragraph 3: deleted

Added(5) ‘similar medicinal product’ means a medicinal product containing a similar active substance or substances as contained in a currently authorised orphan medicinal product, and which is intended for the same therapeutic indication;

RemovedArticle 75 – paragraph 3 a (new): 3a. The Agency shall, after consultation with the Commission and relevant interested parties, draw up guidelines for the application of this Article.

Added(6) ‘similar active substance’ means an identical active substance, or an active substance with the same principal molecular structural features (but not necessarily all of the same molecular structural features) and which acts via the same mechanism. In the case of advanced therapy medicinal products, for which the principal molecular structural features cannot be fully defined, the similarity between two active substances shall be assessed on the basis of the biological and functional characteristics;

RemovedArticle 81 – paragraph 3: 3. The length of the deferral shall be specified in a decision of the Agency and shall be substantiated by scientific and technical grounds or by considerations pertaining to public health and not exceed five years.

Added(7) ‘significant benefit’ means a clinically relevant advantage or a major contribution to patient care of an orphan medicinal product if such an advantage or contribution benefits a substantialrelevant part of the target population; [Am. 89]

RemovedArticle 84 – paragraph 1 a (new): 1a. The procedure provided for in paragraph 1 of this Article shall also apply when the applicant updates the elements of an initial paediatric investigation plan submitted in accordance with Article 74(2).

Added(8) ‘clinically superior’ means that a medicinal product is shown to provide a significant therapeutic or diagnostic advantage above that provided by an orphan medicinal product in one or more of the following ways:

RemovedArticle 84 – paragraph 2 – subparagraph 1: If, following the decision agreeing the paediatric investigation plan referred to in Article 77, paragraphs 1, 2 and 4, or on the basis of the updated paediatric investigation plan received in accordance with Article 77(3), the Agency, on the base of new scientific information available, considers that the agreed plan or any of its elements are no longer appropriate, it shall request, based on detailed scientific grounds, that the applicant propose changes to the paediatric investigation plan.

Added(a) greater efficacy than an authorised medicinal orphan medicinal product in a substantialrelevant part of the target population; [Am. 90]

RemovedArticle 84 – paragraph 2 a (new): 2a. Within the timelines for adoption of a decision provided for in Articles 77, 78, 80, 81, 82 and 84, the Agency shall transmit its scientific conclusions to the applicant.

Added(b) greater safety than an authorised medicinal product in a substantialrelevant part of the target population; [Am. 91]

RemovedArticle 84 – paragraph 2 b (new): 2b. Where marketing authorisation applicants or marketing authorisation holders disagree with the scientific conclusions, they may respond within 20 days of receipt of those conclusions by providing detailed grounds and evidence for re-examination. / The Agency shall assess the request for re-examination and may request more information from the marketing authorisation applicant or marketing authorisation holder in this process. / Within 30 days of receipt of a request for re-examination, the Agency shall confirm its scientific conclusions or commence a re-examination where deemed justified.

Added(c) in exceptional cases, where neither greater safety nor greater efficacy has been shown, demonstration that the medicinal product otherwise makes a major contribution to diagnosis or to patient care.

RemovedArticle 88 – paragraph 1: Where a paediatric investigation plan, agreed in accordance with the provisions of Article 77, paragraphs 1, 2 and 4, is discontinued, the applicant shall notify the Agency of its intention to discontinue the conduct of the paediatric investigation plan and provide the reasons for such discontinuation no less than six months before the discontinuation or as soon as possible.

Added(9) ‘paediatric use marketing authorisation’ means a marketing authorisation granted in respect of a medicinal product for human use which is not protected by a supplementary protection certificate under Regulation (EC) No 469/2009 of the European Parliament and of the Council concerning the supplementary protection certificate for medicinal products [OP please replace reference by new instrument when adopted], or by a patent which qualifies for the granting of the supplementary protection certificate, covering exclusively therapeutic indications which are relevant for use in the paediatric population, or subsets thereof, including the appropriate strength, pharmaceutical form or route of administration for that product.

RemovedArticle 91 – paragraph 3: 3. When products are authorised in accordance with the provisions of this Regulation, the Commission may update the summary of product characteristics and package leaflet, and may vary the marketing authorisation accordingly, including regarding information on dosage accuracy.

Added(10) ‘regulatory sandbox’ means a regulatory framework during which it is possible to develop, validate and test in a controlled environment innovative or adapted regulatory solutions that facilitate the development and authorisation of innovative products which are likely to fall in the scope of this Regulation but for which there is an absence of existing adapted rules for development and authorisation, pursuant to a specific plan and for a limited time under regulatory supervision. [Am. 92]

RemovedArticle 101 – paragraph 1 – subparagraph 3: The Eudravigilance database shall contain information on suspected adverse reactions in human beings arising from use of the medicinal product within the terms of the marketing authorisation as well as from uses outside the terms of the marketing authorisation, including errors in relation to medication, and on those occurring in the course of post-authorisation studies with the medicinal product or associated with occupational exposure.

Added(11) ‘critical medicinal product’ means a medicinal product for which insufficient supply results in serious harm or risk of serious harm to patients and identified using the methodology pursuant to Article 130(1), point (a).

RemovedArticle 101 – paragraph 2 – subparagraph 5: The Agency shall ensure that healthcare professionals and the public have appropriate levels of access to the Eudravigilance database, and that personal data is protected in line with Union data protection and privacy law. The Agency shall work together with all stakeholders, including research institutions, healthcare professionals, and patient and consumer organisations, in order to define the ‘appropriate level of access’ for healthcare professionals and the public to the Eudravigilance database.

Added(12) ‘shortage’ means a situation in which the supply of a medicinal product that is authorised and placed on the market in a Member State does not meet the demand for that medicinal product in that Member State whatever the cause. [Am. 93]

RemovedArticle 101 – paragraph 2 – subparagraph 6: The data held on the Eudravigilance database shall be made publicly available in an aggregated and anonymised format together with an explanation of how to interpret the data.

Added(13) ‘critical shortage in the Member State’ means a shortage of a medicinal product, for which there is no appropriate alternative medicinal product available on the market in that Member State, and that shortage cannot be resolved.

RemovedArticle 101 – paragraph 3 a (new): 3a. The periodic safety update reports shall, in addition, be made publicly available in the web-portal referred to in Article 138(1), second subparagraph, point (n).

Added(14) ‘critical shortage’ means a critical shortage in the Member State for which coordinated Union level action is considered necessary to resolve that shortage in accordance with this Regulation.

RemovedArticle 104 – paragraph 1 – subparagraph 1 – introductory part: The Agency shall, in collaboration with the Member States and the Commission, set up and maintain a European medicines web-portal for the dissemination of information on medicinal products authorised or to be authorised in the Union. The dedicated web-portal shall be set up in accordance with Directive (EU) 2016/2102 of the European Parliament and of the Council1a. By means of that portal, the Agency shall make public the following: / 1a Directive (EU) 2016/2102 of the European Parliament and of the Council of 26 October 2016 on the accessibility of the websites and mobile applications of public sector bodies (OJ L 327, 2.12.2016, p. 1).

Added(14a) ‘demand’ means the request for a medicinal product by healthcare professionals or patients in response to a clinical need; the demand is satisfactorily met when the medicinal product is acquired in appropriate time and in sufficient quantity to allow continuity of provision of the best care to patients; [Am. 94]

RemovedArticle 104 – paragraph 1 – subparagraph 1 – point c: (c) the risk management plans for medicinal products authorised in accordance with this Regulation and the accompanying summaries of the risk management plans;

Added(14b) ‘supply’ means the total volume of stock of a given medicinal product that is placed on the market by a marketing authorisation holder or a manufacturer. [Am. 95]

RemovedArticle 104 – paragraph 1 – subparagraph 1 – point h: (h) the initiation of the procedure provided for in Article 41(2) of this Regulation, and Articles 114, 115 and 116 of [revised Directive 2001/83/EC], the active substances or medicinal products concerned and the issue being addressed, any public hearings pursuant to that procedure and information on how to submit information and to participate in public hearings;