Changes from plenary report to adopted text

Added3. On the basis of the written observations submitted by the marketing authorisation holder, the competent authority of the Member State shall withdraw or confirm the obligation. Where the competent authority of the Member State confirms the obligation, the marketing authorisation shall be varied to include the obligation as a condition of the marketing authorisation and, where appropriate, the risk management system shall be updated accordingly.

AddedArticle 88 Delegated acts on post-authorisation efficacy studies

Added1. In order to determine the situations in which post-authorisation efficacy studies may be required under Articles 44 and 87, the Commission may adopt, by means of delegated acts in accordance with Article 215, measures supplementing the provisions in Articles 44 and 87.

Added2. When adopting such delegated acts, the Commission shall act in accordance with the provisions of this Directive.

AddedArticle 89 Recording of conditions related to marketing authorisations

Added1. The marketing authorisation holder shall incorporate any safety or efficacy conditions referred to in Articles 44, 45 and 87 in the risk management system.

Added2. The Member States shall inform the Agency of the marketing authorisations that they have granted subject to conditions pursuant to Articles 44, 45 and of any obligations imposed in accordance with Article 87.

AddedArticle 90 Update of marketing authorisation related to scientific and technological progress

Added1. After a marketing authorisation has been granted in accordance with Chapter III, the marketing authorisation holder shall, in respect of the methods of manufacture and control stated in the application for that marketing authorisation, take account of scientific and technical progress and introduce any changes that may be required to enable the medicinal product to be manufactured and controlled by means of generally accepted scientific methods.

AddedThose changes shall be subject to the approval of the competent authority of the Member State concerned.

Added2. The marketing authorisation holder shall without undue delay provide the competent authority of the Member State with any new information that might entail the amendment of the particulars or documentations referred to in Articles 6, 9 to 13, 62, 41(5), Annex I or Annex II.

AddedIn particular, the marketing authorisation holder shall without undue delay inform the competent authority of the Member State of any prohibition or restriction imposed on the marketing authorisation holder or any entity in contractual relationship with the marketing authorisation holder by the competent authorities of any country in which the medicinal product is marketed and of any other new information that might influence the evaluation of the benefits and risks of the medicinal product concerned. The information shall include both positive and negative results of clinical trials or other studies in all therapeutic indications and populations, whether or not included in the marketing authorisation, as well as data on the use of the medicinal product where such use is outside the terms of the marketing authorisation.

Added3. The marketing authorisation holder shall ensure that the terms of the marketing authorisation including the summary of product characteristics, the labelling and package leaflet are kept up to date with current scientific knowledge, including the conclusions of the assessment and recommendations made publicly available by means of the European medicines web-portal set up in accordance with Article 104 of [revised Regulation (EC) No 726/2004].

Added4. The competent authority of the Member State may at any time request the marketing authorisation holder to submit data demonstrating that the benefit-risk balance remains favourable. The marketing authorisation holder shall answer fully and within the time limit set, any such request. The marketing authorisation holder shall also respond fully and within the time limit set to any request of a competent authority regarding the implementation of any measures previously imposed, including risk minimisation measures.

Added5. The competent authority of the Member State may at any time ask the marketing authorisation holder to submit a copy of the pharmacovigilance system master file. The marketing authorisation holder shall submit that copy at the latest seven days after receipt of the request.

Added6. The marketing authorisation holder shall also respond fully and within the time limit set to any request of a competent authority regarding the implementation of any measures previously imposed with regard to risks to the environment or public health, including antimicrobial resistance.

AddedArticle 91 Update of risk management plans

Added1. The marketing authorisation holder of a medicinal product referred to in Articles 9 and 11 shall submit to the competent authorities of the Member States concerned a risk management plan and a summary thereof, where the marketing authorisation for the reference medicinal product is withdrawn but the marketing authorisation for the medicinal product referred to in Articles 9 and 11 is maintained.

AddedThe risk management plan and the summary thereof shall be submitted to the competent authorities of the Member States concerned within 60 days of the withdrawal of the marketing authorisation for the reference medicinal product by means of a variation.

Added2. The competent authority of the Member State may impose an obligation on a marketing authorisation holder for a medicinal product referred to Articles 9 and 11 to submit a risk management plan and summary thereof where:

Added(a) additional risk minimisation measures have been imposed concerning the reference medicinal product; or

Added(b) it is justified on pharmacovigilance grounds.

Added3. In the case referred to in paragraph 2, point (a), the risk management plan shall be aligned with the risk management plan for the reference medicinal product.

Added4. The imposition of the obligation referred to in paragraph 3 shall be duly justified in writing, notified to the marketing authorisation holder and shall include the deadline for submission of the risk management plan and the summary by means of a variation.

AddedArticle 92 Variation of marketing authorisation

Added1. An application for variation of a marketing authorisation by the marketing authorisation holder shall be made electronically in the formats made available by the Agency, unless the variation is an update by the marketing authorisation holder of their information held in a database.

Added2. 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 and to administrative changes.

Added3. 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. Such procedures may also include updates by the marketing authorisation holder of their information held in a database. Where deemed justified by the Agency, accelerated assessment procedures shall also be envisaged for variations which are of major interest from the point of view of public health. [Am. 220]

Added4. The Commission is empowered to adopt delegated acts in accordance with Article 215 to supplement this Directive by establishing the following:

Added(a) the categories referred to in paragraph 2 in which variations shall be classified;

Added(b) rules for the examination of applications for variations to the terms of marketing authorisations, including procedures for updates through a database;

Added(c) the conditions for submission of a single application for more than one change to the terms of the same marketing authorisation and for the same change to the terms of several marketing authorisations;

Added(d) specifying exemptions to the variation procedures where the update of information in the marketing authorisation referred to in Annex I may be directly implemented;

Added(e) the conditions and procedures for cooperation with competent authorities of third countries or international organisations on examination of applications for variations to the terms of marketing authorisation.

AddedArticle 93 Variation of marketing authorisation under the decentralised or mutual recognition procedure

Added1. Any application by the marketing authorisation holder to vary a marketing authorisation that has been granted in accordance with the provisions of Chapter III, Sections 3 and 4, shall be submitted to all the Member States that have previously authorised the medicinal product concerned. The same shall apply where the initial marketing authorisations were granted through separate procedures.

Added2. In case of arbitration submitted to the Commission, the procedure laid down in Articles 41 and 42 shall apply by analogy to variations made to marketing authorisations.

AddedArticle 94 Variation of marketing authorisations on the basis of paediatric studies

Added1. On the basis of relevant paediatric clinical studies received in accordance with Article 45(1) of Regulation (EC) No 1901/2006 of the European Parliament and of the Council, the competent authorities of the Member States may, following a consultation of the marketing authorisation holder, vary the marketing authorisation of the medicinal product concerned accordingly and update the summary of product characteristics and package leaflet of the medicinal product concerned. The competent authorities shall exchange information regarding the studies submitted and, as appropriate, their implications for any marketing authorisations concerned. [Am. 221]

Added2. The activities pursuant to paragraph 1 shall be concluded within five years from [OP please insert the date = 18 months after the date of entering into force of this Directive].

Added3. When a medicinal product has been authorised under the provisions of Chapter III, on the basis of the information received in accordance with Article 91 of [revised Regulation (EC) No 726/2004], the competent authorities of the Member States may vary the marketing authorisation of the medicinal product concerned accordingly and update the summary of product characteristics and package leaflet.

Added4. The Member States shall exchange information regarding the studies submitted and, as appropriate, their implications for any marketing authorisations concerned.

Added5. The Agency shall coordinate the exchange of information.

AddedArticle 95 Union interest referral procedure

Added1. The Member States or the Commission shall, in specific cases where the interests of the Union are involved, refer the matter to the Committee for Medicinal Products for Human Use for the application of the procedure laid down in Articles 41 and 42 before any decision is reached on an application for a marketing authorisation or on the suspension or revocation of a marketing authorisation, or on any other variation of the marketing authorisation that appears necessary. The Member States and the Commission shall take due account of any requests by the applicant or the marketing authorisation holder.

AddedWhere the referral results from the evaluation of data relating to pharmacovigilance of an authorised medicinal product, the matter shall be referred to the Pharmacovigilance Risk Assessment Committee and Article 115(2) may be applied. The Pharmacovigilance Risk Assessment Committee shall issue a recommendation according to the procedure laid down in Article 41. The final recommendation shall be forwarded to the Committee for Medicinal Products for Human Use or to the coordination group, as appropriate, and the procedure laid down in Article 115 shall apply.

AddedHowever, where one of the criteria listed in Article 114(1) is met, the procedure laid down in Articles 114, 115 and 116 shall apply.

AddedThe Member State concerned or the Commission shall clearly identify the question that is referred to the Committee for consideration and shall inform the applicant or the marketing authorisation holder.

AddedThe Member States and the applicant or the marketing authorisation holder shall supply the Committee with all available information relating to the matter in question.

Added2. Where the referral to the Committee concerns a range of medicinal products or a therapeutic class, the Agency may limit the procedure to certain specific parts of the authorisation.

AddedIn that event, Article 93 shall apply to those medicinal products only if they were covered by the authorisation procedures referred to in Chapter III, Sections 3 and 4.

AddedWhere the scope of the procedure initiated under this Article concerns a range of medicinal products or a therapeutic class, medicinal products covered by a centralised marketing authorisation that belong to that range or class shall also be included in the procedure.

Added3. Without prejudice to paragraph 1, a Member State may, where urgent action is necessary to protect public health at any stage of the procedure, suspend the marketing authorisation and prohibit the use of the medicinal product concerned on its territory until a definitive decision is adopted. It shall inform the Commission, the Agency and the other Member States, no later than the following working day, of the reasons for its action.

Added4. Where the scope of the procedure initiated under this Article, as determined in accordance with paragraph 2, includes medicinal products covered by a centralised marketing authorisation, the Commission may, where urgent action is necessary to protect public health, at any stage of the procedure suspend the marketing authorisations and prohibit the use of the medicinal products concerned until a definitive decision is adopted. The Commission shall inform the Agency and the Member States no later than the following working day of the reasons for its action.

AddedChapter IX Pharmacovigilance

AddedSection 1 General provisions

AddedArticle 96 Member State pharmacovigilance system

Added1. Member States shall operate a pharmacovigilance system for the fulfilment of their pharmacovigilance tasks and their participation in the Union pharmacovigilance activities including the pharmacovigilance of the post-authorisation safety and efficacy long-term studies in children, including where relevant data from the off-label use of the product. [Am. 222]

AddedThe pharmacovigilance system shall be used to collect information on the risks of medicinal products as regards health of the patients or the public. That information shall in particular refer to adverse reactions in human beings, arising from use of the medicinal product within the terms of the marketing authorisation as well as from use outside the terms of the marketing authorisation, and to adverse reactions associated with occupational exposure.

Added2. Member States shall, by means of the pharmacovigilance system referred to in paragraph 1, evaluate all information scientifically, consider options for risk minimisation and prevention and take regulatory action concerning the marketing authorisation as necessary. They shall perform a regular audit of their pharmacovigilance system and take corrective actions if necessary.