Regulation (EU) No 1235/2010 of the European Parliament and of the Council of 15 December 2010 amending, as regards pharmacovigilance of medicinal products for human use, 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, and Regulation (EC) No 1394/2007 on advanced therapy medicinal products Text with EEA relevance

‘1 Within 15 days after receipt of the opinion referred to in Article 5(2), the Commission shall prepare a draft of the decision to be taken in respect of the application. Where a draft decision envisages the granting of a marketing authorisation, it shall include or make reference to the documents mentioned in points (a) to (d) of Article 9(4). Where a draft decision envisages the granting of a marketing authorisation subject to the conditions referred to in points (c), (ca), (cb), or (cc) of Article 9(4), it shall lay down deadlines for the fulfilment of the conditions, where necessary. Where the draft decision differs from the opinion of the Agency, the Commission shall attach a detailed explanation of the reasons for the differences. The draft decision shall be forwarded to Member States and the applicant.’;

‘6 The Agency shall disseminate the documents referred to in points (a) to (d) of Article 9(4), together with any deadlines laid down pursuant to the third subparagraph of paragraph 1 of this Article.’;

1 After the granting of a marketing authorisation, the Agency may impose an obligation on the marketing authorisation holder: (a) to conduct a post-authorisation safety study if there are concerns about the risks of an authorised medicinal product. If the same concerns apply to more than one medicinal product, the Agency shall, following consultation with the Pharmacovigilance Risk Assessment Committee, encourage the marketing authorisation holders concerned to conduct a joint post-authorisation safety study; (b) to conduct a post-authorisation efficacy study when the understanding of the disease or the clinical methodology indicate that previous efficacy evaluations might have to be revised significantly. The obligation to conduct the post-authorisation efficacy study shall be based on the delegated acts adopted pursuant to Article 10b while taking into account the scientific guidance referred to in Article 108a of Directive 2001/83/EC. The imposition of such an obligation shall be duly justified, notified in writing, and shall include the objectives and timeframe for submission and conduct of the study.

2 The Agency shall provide the marketing authorisation holder with an opportunity to present written observations in response to the imposition of the obligation within a time limit which it shall specify, if the marketing authorisation holder so requests within 30 days of receipt of the written notification of the obligation.

3 On the basis of the written observations submitted by the marketing authorisation holder, and of the opinion of the Agency, the Commission shall withdraw or confirm the obligation. Where the Commission confirms the obligation, the marketing authorisation shall be varied to include the obligation as a condition of the marketing authorisation and the risk management system shall be updated accordingly.

1 In order to determine 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) of this Regulation, the Commission may adopt, by means of delegated acts in accordance with Article 87b, and subject to the conditions of Articles 87c and 87d, measures supplementing the provisions in point (cc) of Article 9(4) and point (b) of Article 10a(1).

2 When adopting such delegated acts, the Commission shall act in accordance with the provisions of this Regulation.’;

The marketing authorisation holder shall incorporate any conditions referred to in points (c), (ca), (cb) and (cc) of Article 9(4) or in Article 10a, or in Article 14(7) and (8) in his risk management system.’;

1 After a marketing authorisation has been granted in accordance with this Regulation, the marketing authorisation holder shall, in respect of the methods of manufacture and control provided for in points (d) and (h) of Article 8(3) of Directive 2001/83/EC, take account of scientific and technical progress and introduce any changes that may be required to enable the medicinal product to be manufactured and checked by means of generally accepted scientific methods. He shall apply for approval of corresponding variations in accordance with this Regulation.

2 The marketing authorisation holder shall forthwith provide the Agency, the Commission and the Member States with any new information which might entail the amendment of the particulars or documents referred to in Article 8(3), Article 10, 10a, 10b and 11, or Article 32(5) of Directive 2001/83/EC, in Annex I thereto, or in Article 9(4) of this Regulation. In particular, the marketing authorisation holder shall forthwith inform the Agency and the Commission of any prohibition or restriction imposed by the competent authorities of any country in which the medicinal product is marketed and of any other new information which 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 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.

3 The marketing authorisation holder shall ensure that the product information is kept up to date with the current scientific knowledge including the conclusions of the assessment and recommendations made public by means of the European medicines web-portal established in accordance with Article 26.

4 In order to be able to continuously assess the risk-benefit balance, the Agency may at any time ask the marketing authorisation holder to forward data demonstrating that the risk-benefit balance remains favourable. The marketing authorisation holder shall answer fully and promptly any such request. The Agency 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 the copy at the latest 7 days after receipt of the request.’;

1 The obligations of marketing authorisation holders laid down in Article 104 of Directive 2001/83/EC shall apply to marketing authorisation holders for medicinal products for human use authorised in accordance with this Regulation. Without prejudice to paragraphs 2, 3 and 4 of this Article, holders of marketing authorisations granted before 2 July 2012 shall, by way of derogation from Article 104(3)(c) of Directive 2001/83/EC not be required to operate a risk management system for each medicinal product.

2 The Agency may impose an obligation on a marketing authorisation holder to operate a risk management system, as referred to in point (c) of Article 104(3) of Directive 2001/83/EC, if there are concerns about the risks affecting the risk-benefit balance of an authorised medicinal product. In that context, the Agency shall also oblige the marketing authorisation holder to submit a detailed description of the risk-management system which he intends to introduce for the medicinal product concerned. The imposition of such obligations shall be duly justified, notified in writing, and shall include the timeframe for submission of the detailed description of the risk-management system.

3 The Agency shall provide the marketing authorisation holder with an opportunity to present written observations in response to the imposition of the obligation within a time limit which it shall specify, if the marketing authorisation holder so requests within 30 days of receipt of the written notification of the obligation.

4 On the basis of the written observations submitted by the marketing authorisation holder, and of the opinion of the Agency, the Commission shall withdraw or confirm the obligation. Where the Commission confirms the obligation, the marketing authorisation shall be varied accordingly, to include the measures to be taken as part of the risk management system as conditions of the marketing authorisation referred to in point (ca) of Article 9(4).

The obligations of marketing authorisation holders laid down in Article 106a(1) of Directive 2001/83/EC, and the obligations of the Member States, the Agency and the Commission laid down in paragraphs 2, 3 and 4 of that Article shall apply to the safety announcements referred to in point (e) of Article 57(1) of this Regulation concerning medicinal products for human use authorised in accordance with this Regulation.

1 The Agency shall, in collaboration with the Member States, set up, maintain and make public a list of medicinal products that are subject to additional monitoring. That list shall include the names and active substances of: (a) medicinal products authorised in the Union that contain a new active substance which, on 1 January 2011, was not contained in any medicinal product authorised in the Union; (b) any biological medicinal product not covered by point (a) that was authorised after 1 January 2011.

2 At the request of the Commission, following consultation with the Pharmacovigilance Risk Assessment Committee, medicinal products that are authorised pursuant to this Regulation subject to conditions referred to in points (c), (ca), (cb) and (cc) of Article 9(4), or in Articles 10a, Article 14(7) and (8) and in Article 21(2), may also be included in the list. At the request of a national competent authority, following consultation with the Pharmacovigilance Risk Assessment Committee, medicinal products that are authorised pursuant to Directive 2001/83/EC, subject to the conditions referred to in Articles 21a, 22, 22a and 104a of that Directive, may also be included in the list.

3 The list shall include an electronic link to the product information and to the summary of the risk management plan.

4 The Agency shall remove a medicinal product from the list 5 years after the Union reference date referred to in Article 107c(5) of Directive 2001/83/EC. However, the Commission or the national competent authority, as appropriate, may, following a recommendation of the Pharmacovigilance Risk Assessment Committee, extend that period until such time as they conclude that the conditions referred to in Article 14a and Article 21(2) of this Regulation or referred to in Articles 22b and 104a of Directive 2001/83/EC have been fulfilled.

5 For medicinal products included in that list, the summary of product characteristics and the package leaflet shall include the statement “This medicinal product is subject to additional monitoring”. That statement shall be preceded by a black symbol which shall be selected by the Commission following a recommendation of the Pharmacovigilance Risk Assessment Committee by 2 January 2012, and shall be followed by an appropriate standardised explanatory sentence.

1 The Agency shall, in collaboration with the Member States and the Commission, set up and maintain a database and data processing network (hereinafter the “Eudravigilance database”) to collate pharmacovigilance information regarding medicinal products authorised in the Union and to allow competent authorities to access that information simultaneously and to share it. 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, and on those occurring in the course of post-authorisation studies with the medicinal product or associated with occupational exposure.

2 The Agency shall, in collaboration with the Member States and the Commission, draw up the functional specifications for the Eudravigilance database, together with a timeframe for their implementation. The Agency shall prepare an annual report on the Eudravigilance database and send it to the European Parliament, the Council and the Commission. The first annual report shall be prepared by 2 January 2013. The Management Board of the Agency shall on the basis of an independent audit report that takes into account the recommendation of the Pharmacovigilance Risk Assessment Committee confirm and announce when the Eudravigilance database has achieved full functionality and the system meets the functional specifications drawn up pursuant to the first subparagraph. Any substantial change to the Eudravigilance database and the functional specifications shall take into account the recommendations of the Pharmacovigilance Risk Assessment Committee. The Eudravigilance database shall be fully accessible to the competent authorities of the Member States and to the Agency and the Commission. It shall also be accessible to marketing authorisation holders to the extent necessary for them to comply with their pharmacovigilance obligations. The Agency shall ensure that healthcare professionals and the public have appropriate levels of access to the Eudravigilance database, while guaranteeing personal data protection. 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. The data held on the Eudravigilance database shall be made publicly accessible in an aggregated format together with an explanation of how to interpret the data.

3 The Agency shall, in collaboration either with the marketing authorisation holder or with the Member State that submitted an individual suspected adverse reaction report to the Eudravigilance database, be responsible for operating procedures that ensure the quality and integrity of the information collected in the Eudravigilance database.

4 Individual suspected adverse reaction reports and follow-ups submitted to the Eudravigilance database by marketing authorisation holders shall be transmitted electronically upon receipt to the competent authority of the Member State where the reaction occurred.

The Agency shall, in collaboration with the Member States, develop standard web-based structured forms for the reporting of suspected adverse reactions by healthcare professionals and patients in accordance with the provisions referred to in Article 107a of Directive 2001/83/EC.

The Agency shall, in collaboration with the national competent authorities and the Commission, set up and maintain a repository for periodic safety update reports (hereinafter the “repository”) and the corresponding assessment reports so that they are fully and permanently accessible to the Commission, the national competent authorities, the Pharmacovigilance Risk Assessment Committee, the Committee for Medicinal Products for Human Use and the coordination group referred to in Article 27 of Directive 2001/83/EC (hereinafter the “coordination group”). The Agency shall, in collaboration with the national competent authorities and the Commission, and after consultation with the Pharmacovigilance Risk Assessment Committee, draw up the functional specifications for the repository. The Management Board of the Agency shall, on the basis of an independent audit report that takes into account the recommendations of the Pharmacovigilance Risk Assessment Committee, confirm and announce when the repository has achieved full functionality and meets the functional specifications drawn up pursuant to the second paragraph. Any substantial change to the repository and the functional specifications shall always take into account the recommendations of the Pharmacovigilance Risk Assessment Committee.

1 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 in the Union. By means of that portal, the Agency shall make public at least the following: (a) the names of members of the Committees referred to in points (a) and (aa) of Article 56(1) of this Regulation and the members of the coordination group, together with their professional qualifications and with the declarations referred to in Article 63(2) of this Regulation; (b) agendas and minutes from each meeting of the Committees referred to in points (a) and (aa) of Article 56(1) of this Regulation and of the coordination group as regards pharmacovigilance activities; (c) a summary of the risk management plans for medicinal products authorised in accordance with this Regulation; (d) the list of medicinal products referred to in Article 23 of this Regulation; (e) a list of the locations in the Union where pharmacovigilance system master files are kept and contact information for pharmacovigilance enquiries, for all medicinal products authorised in the Union; (f) information about how to report to national competent authorities suspected adverse reactions to medicinal products and the standard structured forms referred to in Article 25 for their web-based reporting by patients and healthcare professionals, including links to national websites; (g) Union reference dates and frequency of submission of periodic safety update reports established in accordance with Article 107c of Directive 2001/83/EC; (h) protocols and public abstracts of results of the post-authorisation safety studies referred to in Articles 107n and 107p of Directive 2001/83/EC; (i) the initiation of the procedure provided for in Articles 107i to 107k of 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; (j) conclusions of assessments, recommendations, opinions, approvals and decisions taken by the Committees referred to in points (a) and (aa) of Article 56(1) of this Regulation and by the coordination group, the national competent authorities and the Commission in the framework of the procedures of Articles 28, 28a and 28b of this Regulation and of sections 2 and 3 of Chapter 3 and Chapter 4 of Title IX of Directive 2001/83/EC.

2 Before the launch of this portal, and during subsequent reviews, the Agency shall consult relevant stakeholders, including patient and consumer groups, healthcare professionals and industry representatives.

1 The Agency shall monitor selected medical literature for reports of suspected adverse reactions to medicinal products containing certain active substances. It shall publish the list of active substances being monitored and the medical literature subject to this monitoring.

2 The Agency shall enter into the Eudravigilance database relevant information from the selected medical literature.

3 The Agency shall, in consultation with the Commission, Member States and interested parties, draw up a detailed guide regarding the monitoring of medical literature and the entry of relevant information into the Eudravigilance database.

1 The obligations of marketing authorisation holders and of Member States laid down in Articles 107 and 107a of Directive 2001/83/EC shall apply to the recording and reporting of suspected adverse reactions for medicinal products for human use authorised in accordance with this Regulation.

2 The obligations of marketing authorisation holders laid down in Article 107b of Directive 2001/83/EC and the procedures under Article 107b and Article 107c of that Directive shall apply to the submission of periodic safety update reports, the establishment of Union reference dates and changes to the frequency of submission of periodic safety update reports for medicinal products for human use authorised in accordance with this Regulation. The provisions applicable to the submission of periodic safety update reports laid down in the second subparagraph of Article 107c(2) of that Directive shall apply to holders of marketing authorisations which were granted before 2 July 2012 and for which the frequency and dates of submission of the periodic safety update reports are not laid down as a condition to the marketing authorisation until such time as another frequency or other dates of submission of the reports are laid down in the marketing authorisation or are determined in accordance with Article 107c of that Directive.

3 The assessment of the periodic safety update reports shall be conducted by a rapporteur appointed by the Pharmacovigilance Risk Assessment Committee. The rapporteur shall closely collaborate with the rapporteur appointed by the Committee for Medicinal Products for Human Use or the Reference Member State for the medicinal products concerned. The rapporteur shall prepare an assessment report within 60 days of receipt of the periodic safety update report and send it to the Agency and to the members of the Pharmacovigilance Risk Assessment Committee. The Agency shall send the report to the marketing authorisation holder. Within 30 days of receipt of the assessment report, the marketing authorisation holder and the members of the Pharmacovigilance Risk Assessment Committee may submit comments to the Agency and to the rapporteur. Following the receipt of the comments referred to in the third subparagraph, the rapporteur shall within 15 days update the assessment report taking into account any comments submitted, and forward it to the Pharmacovigilance Risk Assessment Committee. The Pharmacovigilance Risk Assessment Committee shall adopt the assessment report with or without further changes at its next meeting and issue a recommendation. The recommendation shall mention the divergent positions with the grounds on which they are based. The Agency shall include the adopted assessment report and the recommendation in the repository set up under Article 25a, and forward both to the marketing authorisation holder.

4 In the case of an assessment report that recommends any action concerning the marketing authorisation, the Committee for Medicinal Products for Human Use shall, within 30 days of receipt of the report by the Pharmacovigilance Risk Assessment Committee, consider the report and adopt an opinion on the maintenance, variation, suspension or revocation of the marketing authorisation concerned, including a timetable for the implementation of the opinion. Where this opinion of the Committee for Medicinal Products for Human Use differs from the recommendation of the Pharmacovigilance Risk Assessment Committee, the Committee for Medicinal Products for Human Use shall attach to its opinion a detailed explanation of the scientific grounds for the differences together with the recommendation. Where the opinion states that regulatory action concerning the marketing authorisation is necessary, the Commission shall adopt a decision to vary, suspend or revoke the marketing authorisation. Article 10 of this Regulation shall apply to the adoption of that decision. Where the Commission adopts such a decision, it may also adopt a decision addressed to the Member States pursuant to Article 127a of Directive 2001/83/EC.

5 In the case of a single assessment of periodic safety update reports concerning more than one marketing authorisation in accordance with Article 107e(1) of Directive 2001/83/EC which includes at least one marketing authorisation granted in accordance with this Regulation, the procedure laid down in Articles 107e and 107g of that Directive shall apply.

6 The final recommendations, opinions and decisions referred to in paragraphs 3 to 5 of this Article shall be made public by means of the European medicines web-portal referred to in Article 26.

1 Regarding medicinal products for human use authorised in accordance with this Regulation, the Agency shall, in collaboration with the Member States, take the following measures: (a) monitor the outcome of risk minimisation measures contained in risk management plans and of conditions referred to in points (c), (ca), (cb) and (cc) of Article 9(4) or in points (a) and (b) of Article 10a(1), and in Article 14(7) and (8); (b) assess updates to the risk management system; (c) monitor the data in the Eudravigilance database to determine whether there are new risks or whether risks have changed and whether those risks impact on the risk-benefit balance.

2 The Pharmacovigilance Risk Assessment Committee shall perform the initial analysis and prioritisation of signals of new risks or risks that have changed or changes to the risk-benefit balance. Where it considers that follow-up action may be necessary, the assessment of those signals and agreement on any subsequent action concerning the marketing authorisation shall be conducted in a timescale commensurate with the extent and seriousness of the issue.

3 The Agency and national competent authorities and the marketing authorisation holder shall inform each other in the event of new risks or risks that have changed or changes to the risk-benefit balance being detected.

1 For non-interventional post-authorisation safety studies concerning medicinal products for human use authorised in accordance with this Regulation which fulfil one of the requirements referred to in Articles 10 and 10a of this Regulation, the procedure provided for in paragraphs 3 to 7 of Article 107m, Articles 107n to 107p and Article 107q(1) of Directive 2001/83/EC shall apply.

2 Where, in accordance with the procedure referred to in paragraph 1 of this Article, the Pharmacovigilance Risk Assessment Committee issues recommendations for the variation, suspension or revocation of the marketing authorisation, the Committee on Medicinal Products for Human Use shall adopt an opinion taking into account the recommendation, and the Commission shall adopt a decision in accordance with Article 10. Where the opinion of the Committee on Medicinal Products for Human Use differs from the recommendation of the Pharmacovigilance Risk Assessment Committee, the Committee on Medicinal Products for Human Use shall attach to its opinion a detailed explanation of the scientific grounds for the differences, together with the recommendation.

1 The Agency shall collaborate with the World Health Organisation in matters of pharmacovigilance and shall take the necessary steps to submit to it, promptly, appropriate and adequate information regarding the measures taken in the Union which may have a bearing on public health protection in third countries. The Agency shall make available promptly all suspected adverse reaction reports occurring in the Union to the World Health Organisation.

2 The Agency and the European Monitoring Centre for Drugs and Drug Addiction shall exchange information that they receive on the abuse of medicinal products including information related to illicit drugs.

At the request of the Commission, the Agency shall participate in collaboration with the Member States in international harmonisation and standardisation of technical measures in relation to pharmacovigilance.

The Agency and the Member States shall cooperate to continuously develop pharmacovigilance systems capable of achieving high standards of public health protection for all medicinal products, regardless of the routes of marketing authorisation, including the use of collaborative approaches, to maximise use of resources available within the Union.

The Agency shall perform regular independent audits of its pharmacovigilance tasks and report the results to its Management Board on a 2-yearly basis.

The Commission shall make public a report on the performance of pharmacovigilance tasks by the Agency on 2 January 2014 at the latest and subsequently every 3 years thereafter.’;

1 The Pharmacovigilance Risk Assessment Committee shall be composed of the following: (a) one member and one alternate member appointed by each Member State, in accordance with paragraph 3 of this Article; (b) six members appointed by the Commission, with a view to ensuring that the relevant expertise is available within the Committee, including clinical pharmacology and pharmacoepidemiology, on the basis of a public call for expressions of interest; (c) one member and one alternate member appointed by the Commission, on the basis of a public call for expressions of interest, after consulting the European Parliament, in order to represent healthcare professionals; (d) one member and one alternate member appointed by the Commission, on the basis of a public call for expressions of interest, after consulting the European Parliament, in order to represent patient organisations. The alternate members shall represent and vote for the members in their absence. The alternate members referred to in point (a) may be appointed to act as rapporteurs in accordance with Article 62.

2 A Member State may delegate its tasks in the Pharmacovigilance Risk Assessment Committee to another Member State. Each Member State may represent no more than one other Member State.

3 The members and alternate members of the Pharmacovigilance Risk Assessment Committee shall be appointed on the basis of their relevant expertise in pharmacovigilance matters and risk assessment of medicinal products for human use, in order to guarantee the highest levels of specialist qualifications and a broad spectrum of relevant expertise. For this purpose, Member States shall liaise with the Management Board and the Commission in order to ensure that the final composition of the Committee covers the scientific areas relevant to its tasks.

4 The members and alternate members of the Pharmacovigilance Risk Assessment Committee shall be appointed for a term of 3 years, which may be prolonged once and thereafter renewed following the procedures referred to in paragraph 1. The Committee shall elect its Chairman from among its members for a term of 3 years, which may be prolonged once.

5 Paragraphs 3, 4, 6, 7 and 8 of Article 61 shall apply to the Pharmacovigilance Risk Assessment Committee.

6 The mandate of the Pharmacovigilance Risk Assessment Committee shall cover all aspects of the risk management of the use of medicinal products for human use including the detection, assessment, minimisation and communication relating to the risk of adverse reactions, having due regard to the therapeutic effect of the medicinal product for human use, the design and evaluation of post-authorisation safety studies and pharmacovigilance audit.’;

In order to harmonise the performance of the pharmacovigilance activities provided for in this Regulation, the Commission shall adopt implementing measures as provided for in Article 108 of Directive 2001/83/EC covering the following areas: (a) the content and maintenance of the pharmacovigilance system master file kept by the marketing authorisation holder; (b) the minimum requirements for the quality system for the performance of pharmacovigilance activities by the Agency; (c) the use of internationally agreed terminology, formats and standards for the performance of pharmacovigilance activities; (d) the minimum requirements for the monitoring of data included in the Eudravigilance database to determine whether there are new risks or whether risks have changed; (e) the format and content of electronic transmission of suspected adverse reactions by Member States and marketing authorisation holders; (f) the format and content of electronic periodic safety update reports and risk management plans; (g) the format of protocols, abstracts and final study reports of the post-authorisation safety studies. Those measures shall take account of the work on international harmonisation carried out in the area of pharmacovigilance and shall, where necessary, be revised to take account of technical and scientific progress. Those measures shall be adopted in accordance with the regulatory procedure referred to in Article 87(2).

1 The power to adopt the delegated acts referred to in Article 10b shall be conferred on the Commission for a period of 5 years from 1 January 2011. The Commission shall draw up a report in respect of the delegated powers not later than 6 months before the end of the 5 year period. The delegation of powers shall be automatically extended for periods of an identical duration, unless the European Parliament or the Council revokes it in accordance with Article 87c.

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

3 The power to adopt delegated acts is conferred on the Commission subject to the conditions laid down in Articles 87c and 87d.

1 The delegation of powers referred to in Article 10b may be revoked at any time by the European Parliament or by the Council.

2 The institution which has commenced an internal procedure for deciding whether to revoke the delegation of powers shall endeavour to inform the other institution and the Commission within a reasonable time before the final decision is taken, indicating the delegated powers which could be subject to revocation and possible reasons for a revocation.

3 The decision of revocation shall put an end to the delegation of the powers specified in that decision. It shall take effect immediately or at a later date specified therein. It shall not affect the validity of the delegated acts already in force. It shall be published in the Official Journal of the European Union.

1 The European Parliament or the Council may object to a delegated act within a period of 2 months from the date of notification. At the initiative of the European Parliament or the Council that period shall be extended by 2 months.

2 If, on expiry of the period referred to in paragraph 1, neither the European Parliament nor the Council has objected to the delegated act, it shall be published in the Official Journal of the European Union and shall enter into force on the date stated therein. The delegated act may be published in the Official Journal of the European Union and enter into force before the expiry of that period if the European Parliament and the Council have both informed the Commission of their intention not to raise objections.

3 If either the European Parliament or the Council objects to the delegated act within the period referred to in paragraph 1, it shall not enter into force. The institution which objects shall state the reasons for objecting to the delegated act.’.

‘3 The Executive Director of the Agency shall ensure appropriate coordination between the Committee for Advanced Therapies and the other Committees of the Agency, in particular the Committee for Medicinal Products for Human Use, the Pharmacovigilance Risk Assessment Committee and the Committee for Orphan Medicinal Products, their working parties and any other scientific advisory groups.’.

1 The obligation on the part of the marketing authorisation holder to maintain and make available on request a pharmacovigilance system master file in respect of one or more medicinal products for human use provided for in Article 104(3)(b) of Directive 2001/83/EC as amended by Directive 2010/84/EU, which applies to medicinal products for human use authorised pursuant to Regulation (EC) No 726/2004 by virtue of Article 21 of Regulation (EC) No 726/2004 as amended by this Regulation, shall apply to marketing authorisations granted before 2 July 2012 as from either: (a) the date on which those marketing authorisations are renewed; or (b) the expiry of a period of 3 years starting from 2 July 2012, whichever is the earlier.

2 The procedure provided for in Articles 107m to 107q of Directive 2001/83/EC as amended by Directive 2010/84/EU, which apply by virtue of Article 28b of Regulation (EC) No 726/2004 as amended by this Regulation, shall apply only to studies which have commenced after 2 July 2012.

3 The obligation of the Agency under the second subparagraph of Article 28c(1) of Regulation (EC) No 726/2004 as amended by this Regulation shall apply once the full functionality of Eudravigilance has been announced by the Management Board.

This Regulation shall enter into force on the day following its publication in the Official Journal of the European Union. It shall apply from 2 July 2012.