Changes from report parliamentary committee draft to plenary report

AddedArticle 69 – paragraph 3 – subparagraph 1: The Committee for Medicinal Products for Human Use shall assess whether the medicinal product fulfils the requirements set out in Article 63(1). In the situation referred in paragraph 2, subparagraph 2, that Committee shall also assess whether the medicinal product addresses a high unmet medical need as specified in Article 70(1).

AddedArticle 69 – paragraph 4: 4. The orphan marketing authorisation shall cover only those therapeutic indications, which fulfil the requirements set out in Article 63(1) at the time when the orphan marketing authorisation is granted.

AddedArticle 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).

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

AddedArticle 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.

Article 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.

Change 33

ChangedArticle 71 – paragraph 2 – point a:b: (a)(b) eighteleven years for orphan medicinal products otheraddressing thana thosehigh referredunmet tomedical inneed pointsas (b),referred (ba)to andin (c);Article 70;

Change 34

ChangedArticle 71 – paragraph 2 – point b a (new):c: (ba)(c) fivefour years for a new orphan therapeutic indication of medicinal products which have alreadybeen receivedauthorised marketingin authorisationaccordance inwith theArticle Union13 ;of [revised Directive 2001/83/EC].

Change 35

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

AddedArticle 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.

RemovedArticle 71 – paragraph 2 a (new): 2a. For the medicinal products referred to in paragraph 2, points (ba) and (c), the market exclusivity in respect of the orphan indication shall not prevent the entry of generic and biosimilar medicinal products on the market, provided that they are for other uses that are not subject to the market protection applicable in accordance with paragraph 2. / The periods set out in paragraph 2, points (a) and (b), of this Article may however be reduced to five years if, by the end of the fourth year in respect of the medicinal product concerned, it is established by the Agency that the criteria laid down in Article 63(1), point (a), are no longer met, inter alia, where it is shown on the basis of available evidence that the product is sufficiently profitable not to justify maintenance of market exclusivity. To that end, a Member State shall inform the Agency that the criterion on the basis of which market exclusivity was granted may not be met and the Agency shall then initiate the procedure laid down in Article 67(2). The sponsor shall provide the Agency with the information necessary for that purpose.

AddedArticle 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.

Article 72 – paragraph 1: deleted / (deleted)

Change 36

RemovedArticle 72 – paragraph 2 – subparagraph 1: The period of market exclusivity shall be prolonged by an additional 12 months for orphan medicinal products referred to in Article 71(2), points (a) and (b), if at least three years before the end of the exclusivity period, the orphan marketing authorisation holder obtains a marketing authorisation for one or more new therapeutic indications for a different orphan condition.

AddedArticle 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.

RemovedArticle 72 – paragraph 4: 4. Article 71(3) equally applies to the prolongations of market exclusivity referred to in paragraph 1.

AddedArticle 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.

Article 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.

Article 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.

Change 37

ChangedArticle 75 – paragraph 1 – point a:b: (a)(b) that the disease or condition for which the specific medicinal product or class ofis medicinalintended productsoccurs only in adult populations, unless when the product is verydirected likelyat a molecular target or due to beits ineffectivemechanism of action on the basis of existing scientific data, is responsible for a different disease or unsafecondition in partthe same therapeutic area in children than the one for which the specific medicinal product or allclass of medicinal products is intended for in the paediatricadult population;

Change 38

RemovedArticle 94 – paragraph 2 – subparagraph 3: If for justified scientific reasons it is not possible to submit the summary of the result of the trial within 6 months it shall be submitted to the EU database at the latest within twelve months after the trial has ended. The justification for the delay needs also to be submitted in the EU database. Non-compliance withRegulation (EU) No 536/2014 shall be subject to penalties.

AddedArticle 75 – paragraph 3: deleted

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. By means of that portal, the Agency shall make public the following. The dedicated webportal shall be set up in accordance with Directive (EU) 2016/2102 of the European Parliament and of the Council1a: / 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).

AddedArticle 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.

AddedArticle 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.

AddedArticle 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).

AddedArticle 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.

AddedArticle 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.

AddedArticle 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.

AddedArticle 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.

AddedArticle 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.

AddedArticle 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.

AddedArticle 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.

AddedArticle 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.

AddedArticle 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).

AddedArticle 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).

Article 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;

Change 39

RemovedArticle 104 – paragraph 1 – subparagraph 2: The risk mitigation plans and summaries referred to in point (c) shall include a description of any additional risk minimisation measures.

AddedArticle 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;

RemovedArticle 104 – paragraph 3 – subparagraph 2: Information in such register shall be publicly available and be easily accessible on the Agency’s website, unless restrictions are necessary to protect commercially confidential information. For the purpose of setting up such register, the Agency may request marketing authorisation holders and competent authorities to submit results of any such study already completed for products authorised in the Union within [OP please add the date = 24 months after the date of application of this Regulation].

AddedArticle 104 – paragraph 1 – subparagraph 1 – point i: (i) conclusions of assessments, obligations for post-marketing studies, recommendations, opinions, approvals and decisions taken by the Agency and its Committees under this Regulation and [revised Directive 2001/83/EC].

AddedArticle 104 – paragraph 1 – subparagraph 1 – point j: (j) conclusions of assessments, recommendations, opinions, approvals, obligations deriving from the conditional marketing authorisations and decisions taken by the coordination group, the competent authorities of the Member States and the Commission in the framework of the procedures set out in Articles 16, 106, 107 and 108 of this Regulation and of Chapter IX, Sections 3 and 7 of [revised Directive 2001/83/EC].

AddedArticle 104 – paragraph 1 – subparagraph 2: The risk management plans referred to in point (c) shall include a description of any additional risk minimisation measures and distribution or implementation plans.

AddedArticle 104 – paragraph 2: 2. In the development and review of the web portal, the Agency shall consult relevant stakeholders, including patient and consumer groups, healthcare professionals, not-for-profit entities and industry representatives.

AddedArticle 104 – paragraph 3 – subparagraph 1: The Agency shall, in collaboration with the Member States and the Commission, set up and maintain a register of environmental risk assessment studies conducted for the purpose of supporting an environmental risk assessment for medicinal products authorised in the Union.

AddedArticle 104 – paragraph 3 – subparagraph 2: Information in such register shall be publicly available and easily accessible on the Agency’s website, and shall include, as a minimum, the information reported in accordance with Section 1.6 of Annex II to [revised Directive 2001/83/EC], unless restrictions are necessary to protect commercially confidential information. For the purpose of setting up such register, the Agency shall, where not already received, request marketing authorisation holders and competent authorities to submit results of any such study already completed for products authorised in the Union within [OP please add the date = 24 months after the date of application of this Regulation].

Article 105 – paragraph 3: 3. The Agency shall, in consultation with the Commission, Member States and their relevant authorities, as well as other relevant parties, including experts from academia, draw up a detailed guide regarding the monitoring of medical literature and the entry of relevant information into the Eudravigilance database.

Change 40

RemovedArticle 113: deleted

AddedArticle 109 – paragraph 2: 2. The Agency and the Union Drugs Agency shall exchange information that they receive on the abuse of medicinal products including information related to illicit drugs.

RemovedArticle 114: deleted / (deleted) / (deleted) / (deleted) / (deleted) / (deleted) / (deleted) / (deleted)

AddedArticle 111 – paragraph 1: The Agency and the Member States shall cooperate to continuously develop pharmacovigilance systems, including those that record adverse events including medication errors, processes and standards for medication safety, 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.

RemovedArticle 115: deleted / (deleted) / (deleted) / (deleted) / (deleted) / (deleted) / (deleted) / (deleted)

AddedArticle 113 – paragraph 1 – introductory part: 1. The Commission may set up on a case-by-case basis a regulatory sandbox pursuant to a specific sandbox plan, based on a recommendation of the Agency and pursuant to the procedure set out in paragraphs 4 to 7, where all the following conditions are met;

RemovedArticle 116 – paragraph 1 – point d: (d) a temporary disruption in supply of a medicinal product in a given Member State based on the demand forecast of the marketing authorisation holder no less than six months before the start of such temporary disruption of supply or, if this is not possible and where duly justified, as soon as they become aware of such temporary disruption, to allow the Member State to monitor any potential or actual shortage in accordance with Article 118(1).

AddedArticle 113 – paragraph 3: 3. The Agency shall monitor the field of emerging medicinal products and may request information and data from marketing authorisation holders, developers, independent experts and researchers, and representatives of healthcare professionals and of patients and may engage with them in preliminary discussions, where appropriate referring to the consultation mechanism provided for in Article 162.

RemovedArticle 117 – paragraph 1: 1. By ... [12 months after the date of entry into force of this Regulation], the marketing authorisation holder as defined in Article 116(1) shall prepare a shortage prevention plan and send it to the competent authority as defined in Article 116(1), for any medicinal product placed on the market. The shortage prevention plan shall be kept up to date and ready to be sent to the public authority upon its request. To put in place the shortage prevention plan, the marketing authorisation holder shall include the minimum set of information set out in Part V of Annex IV and take into account the guidance drawn up by the Agency according to paragraph 2.

AddedArticle 113 – paragraph 4 – subparagraph 1: Where the Agency considers it appropriate to set up a regulatory sandbox for medicinal products which are likely to fall under the scope of this Regulation but for which there is an absence of existing adapted rules for development and authorisation, it shall provide a recommendation to the Commission. The Agency shall list eligible products or category of products in that recommendation and shall include the sandbox plan referred to in paragraph 1.

RemovedArticle 117 – paragraph 2: 2. The Agency shall, in collaboration with the working party referred to in Article 121(1) and after consultation with healthcare professionals and patient and consumer organisations, draw up guidance to marketing authorisation holders as defined in Article 116(1) to put in place the shortage prevention plan.

AddedArticle 113 – paragraph 5: 5. The Agency shall be responsible for developing a sandbox plan based on data submitted by developers of eligible products and following appropriate consultations including, where relevant, with patients, academia, health technology assessment bodies, healthcare professionals or developers. The plan shall set out clinical, scientific and regulatory justification for a sandbox, including the identification of the requirements of this Regulation, [revised Directive 2001/83/EC], Regulation (EC) 1394/2007 that cannot be complied with and a proposal for alternative or mitigation measures, where appropriate. The plan shall also include a proposed timeline for the duration of the sandbox. Where appropriate, the Agency shall also propose measures in order to mitigate any possible distortion of market conditions as a consequence of establishing a regulatory.

RemovedArticle 117 – paragraph 3 a (new): 3a. The shortage prevention plans shall be made available to healthcare professionals and patient and consumer organisations on a dedicated website by the competent authority.