Changes from report parliamentary committee draft to plenary report

AddedArticle 40 – paragraph 2 a (new): 2a. The Commission shall adopt delegated acts in in accordance with Article 175 to supplement this Regulation by setting up the eligibility of pathogens for the protection periods referred to in paragraph 2 of this Article in accordance with the WHO priority pathogens list or an equivalent established at Union level, with 12 months of data protection for an authorised product ranked ‘critical’, 9 months of data protection for those ranked ‘high’ and 6 months of data protection for those ranked ‘medium’.

Change 22

ChangedArticle 43:40 – paragraph 3: deleted / (deleted) / (deleted) / (deleted) / (deleted)

Change 23

RemovedArticle 45 – paragraph 4 a (new): 4a. Where specific conditions referred to in paragraph 1 to 4 are not fulfilled within the timeframe given by the Agency or the marketing authorisation holder does not provide duly justified reasons for not fulfilling the conditions, the Commission may vary the marketing authorisation of the affected medicinal product accordingly and update the summary of the product characteristics and package leaflets by means of implementing acts. Those implementing acts shall be adopted in accordance with the examination procedure referred to in Article 173(2).

AddedArticle 40 – paragraph 4 – subparagraph 1 – point a: (a) demonstrate capacity and ensure the supply of the priority antimicrobial in sufficient quantities for the expected needs of the Union market, as defined in a contract with the Authority;

RemovedArticle 47 – paragraph 1: 1. An application for variation of a centralised 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. The electronic format shall include a baseline sequence in regards to the Common Technical Document (CTD).

AddedArticle 40 – paragraph 4 – subparagraph 1 – point b: (b) provide information on all direct financial support and indirect financial support in accordance with Article 57 of [revised Directive 2001/83/EC] received for research related to the development of the priority antimicrobial;

AddedArticle 40 – paragraph 4 – subparagraph 1 – point b a (new): (ba) submit the stewardship and access plan as referred to Article 17(1), point (a), of and Annex I to [revised Directive 2001/83/EC],

AddedArticle 40 – paragraph 4 – subparagraph 1 – point b b (new): (bb) submit of a global access plan to supply third countries in critical need, including through development partners or voluntary licensing.

AddedArticle 40 – paragraph 4 a (new): 4a. The priority antimicrobial shall be added to the list of antimicrobials which are to be reserved for treatment of certain infections in humans and added to the Union list as established by Commission Implementing Regulation (EU) 2022/12551a. / 1a Commission Implementing Regulation (EU) 2022/1255 of 19 July 2022 designating antimicrobials or groups of antimicrobials reserved for treatment of certain infections in humans, in accordance with Regulation (EU) 2019/6 of the European Parliament and of the Council (OJ L 191, 20.7.2022, p. 58).

AddedArticle 41 – paragraph 1 – subparagraph 1: A voucher may be used to extend the data protection for a period of 6, 9 or 12 months of the priority antimicrobial or another medicinal product authorised in accordance with this Regulation of the same or different marketing authorisation holder.

AddedArticle 41 – paragraph 1 – subparagraph 2: A voucher shall only be used once and in relation to a single centrally authorised medicinal product and only if that product is within its first four years of regulatory data protection. The voucher shall not be used for a product which already benefited from the maximum regulatory data protection period as set out in Article 81 of [revised Directive 2001/83/EC].

AddedArticle 41 – paragraph 3: 3. A voucher may be transferred to another marketing authorisation holder once and shall not be transferred further.

AddedArticle 41 – paragraph 3 a (new): 3a. The monetary value paid for the transfer of the voucher shall be directed to the Authority, which shall in yearly instalments transfer the amount to the marketing authorisation holder, in order to ensure the manufacturing capacity and supply of the priority antimicrobial. The Commission shall adopt delegated acts in accordance with Article 175 to supplement this Regulation by setting up the framework for the conditions and functioning of annual instalments.

AddedArticle 42 – paragraph 1 – point b: (b) where it is not used within four years after the conditions set out in Article 41 have been fulfilled by the seller.

AddedArticle 42 – paragraph 2: 2. The Commission may revoke the voucher as referred to in Article 41(3) if a request for supply, procurement or purchase of the priority antimicrobial in the Union has not been fulfilled. To protect the buyer from damage resulting from a possible revocation of a voucher after the transfer, seller and buyer shall make contractual liability arrangements.

AddedArticle 43 – paragraph 1: This Chapter shall apply immediately from ... [the date of entry into force of this Regulation] and for 15 years or until the date when the Commission has granted a total of 10 vouchers in accordance with this Chapter, whichever date is the earliest.

AddedArticle 43 – paragraph 1 a (new): By ... [five years from the date of entry into force of this Regulation], the Commission shall submit an evaluation report to the European Parliament and to the Council containing a scientific assessment measuring the progress with regard to antimicrobial research and development and the effectiveness of the incentives and rewards in this Chapter.

AddedArticle 45 – paragraph 4 – subparagraph 1: The Agency 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 for any such request. The marketing authorisation holder shall also respond fully and within the time limit set any such request of a competent authority regarding the implementation of any measures previously imposed, including risk minimisation measures.

AddedArticle 47 – paragraph 1: 1. An application for variation of a centralised 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. The electronic format shall include a baseline sequence in relations to the Common Technical Document (CTD).

Article 48 – paragraph 1 – subparagraph 1: An entity not engaged in an economic activity (‘not-for-profit entity’) may submit to the Agency or to a competent authority of the Member State substantive non-clinical or clinical evidence for a new therapeutic indication.

Change 24

ChangedArticle 48 – paragraph 1 – subparagraph 2: The Agency may, at the request of a Member State, the Commission, or on its own initiative and on the basis of all available evidence, including any additional evidence that may be submitted by the marketing authorisation holders for the medicinal products concerned, make a scientific evaluation of the benefit-risk of the use of a medicinal product with a new therapeutic indication.

Change 25

RemovedArticle 48 – paragraph 2: 2. In cases where the opinion is favourable, marketing authorisation holders of the medicinal products concerned shall be notified and given the possibility to comment. After consultation with the marketing authorisation holder, the Agency may submit a variation to update the product information with the new therapeutic indication. The marketing authorisation holder shall inform relevant stakeholders, such as healthcare professionals, of the added indication.

AddedArticle 48 – paragraph 1 – subparagraph 3: The opinion of the Agency shall be made publicly available and the competent authorities of the Member States and the marketing authorisation holder shall be informed.

Article 48 – paragraph 3: deleted

Change 26

RemovedArticle 52 – paragraph 6 – point c a (new): (ca) the inspectors are free of any conflicts of interest.

AddedArticle 52 – paragraph 2 – subparagraph 1 – point a: (a) to lend its assistance by participating in a joint inspection with the supervisory authority of the site to assess compliance with good manufacturing practice (GMP) as well as any practices relating to environmental and worker safety. In that case the supervisory authority leads the inspection and the follow up thereof. After completion of the inspection, the supervisory authority grants the relevant GMP certificate and enters the certificate in the Union database; or

RemovedArticle 54 – paragraph 4 – subparagraph 1: Under the joint audit programme, the auditors shall issue an audit report after each audit. The audit report shall include, where relevant, appropriate recommendations on measures that the Member State concerned shall consider to ensure that its relevant quality system and its enforcement activities are consistent with Union quality standards.

AddedArticle 53 – paragraph 2: 2. In cooperation with the Agency, the Commission shall adopt detailed guidelines laying down the principles applicable to those international inspection programmes. The guidelines shall include rules on impartially, independence and conflict of interest of inspectors.

RemovedArticle 54 – paragraph 6: 6. The compilation of Union procedures on inspections and exchange of information referred to in Article 3(1) of Directive 2017/1572 shall be updated, whenever needed, by the Agency to cover rules applicable to the functioning, structure, and tasks of the joint audit programme.

AddedArticle 56 – paragraph 2 a (new): Where the marketing authorisation holder fails to comply with the obligations in the post-authorisation studies laid down in accordance with Article 20, the Commission may adopt a decision to vary, suspend, or revoke that marketing authorisation in accordance with the procedure laid down in Article 13.

RemovedArticle 55 – paragraph 5: 5. In cases referred to in paragraph 4, the Member State shall ensure by all means possible that healthcare professionals are rapidly informed of its action and the reasons for the action. Networks set up by professional associations may be used to this effect. The Member States shall inform the Commission and the Agency of actions taken for this purpose.

AddedArticle 58 – paragraph 3: 3. In the preparation of the scientific advice referred to in paragraph 1 of this Article the Agency may consult authorities established in other Union legal acts as relevant for the provision of the scientific advice in question, other public bodies established in the Union, in particular those listed in Article 162 or other bodies, as applicable, or in duly justified cases public bodies established in third countries.

Change 27

ChangedArticle 58 – paragraph 4: 4. The Agency shall include in the European public assessment report the key areas of the scientific advice as well as a detailed log of the pre-submission activities of the medicinal product, including the names of the experts involved, once the corresponding marketing authorisation decision has been taken in relation to the medicinal product, after deletion of any information of a commercially confidential nature. That report shall be made publicly available.

Change 28

ChangedArticle 58 – paragraph 4 a (new): 4a. The Agency shall, to the greatest extent possible, ensure that there is a separation between those responsible for providing scientific advice to a given medicinal product developer and those subsequently responsible for the evaluation of the marketing authorisation application for the same medicinal product. / When appointing rapporteurs for the purpose of evaluating marketing authorisation applications, the Agency’s Committee on Medicinal Products for Human Use shall duly take into account any involvement of individuals as coordinators in providing scientific advice for the same medicinal product in the pre-submission stage of activities. / If, in exceptional cases, the Agency appoints as rapporteur an expert who had a prominent role in providing scientific advice on the same medicinal product during the pre-submission stage of activities, the Agency shall document and publish detailed information for the decision with the European public assessment report. The Agency shall nonetheless ensure that at least one of two rapporteurs had no prominent role in the pre-submissiontwo activitiesrapporteurs for that medicinal product. / Where a separation betweenmarketing thoseauthorisation responsibleapplication forhas providingnot scientifictaken advicepart toin aany givenpre-submission medicinalactivities productconcerning developerthe andmedicinal thoseproduct. subsequentlyThe responsiblereasons for theany evaluationexceptions ofshall thebe marketingdocumented authorisationand applicationpublished forwith the same medicinal product is notEuropean possible,public itassessment shallreport beand recorded in the summary minutes of the meetings in accordance with Article 147(2)147(2).

Article 60 – paragraph 1 – introductory part: 1. The Agency may offer enhanced scientific and regulatory support, including as applicable consultation with other bodies as referred to in Articles 58 and 59 and accelerated assessment mechanisms, for certain medicinal products that, based on preliminary evidence submitted by the developer fulfil at least one of the following conditions:

Change 29

ChangedArticle 60 – paragraph 1 – point c: (c) are expected to be of major interest from the point of view of public health, in particular as regards therapeutic innovation, including advanced therapy medicinal products, taking into account the early stage of development, or antimicrobials with any of the characteristics mentioned in Article 40(3).40(3) or provided for in the ‘WHO priority pathogens list for R&D of new antibiotics’, specifically those listed as priority 1 (critical) or priority 2 (high), or taking into account as a priority any equivalent list of priority pathogens adopted at Union level.

Change 30

ChangedArticle 60 – paragraph 4 a (new): 4a. Where a priority medicinal product benefits from enhanced scientific and regulatory support from the Agency, the European public assessment report shall include a specific section on the Agency’s pre-submission activities, and information on the key areas of the scientific advice and regulatory support provided and on the follow-up by the requester, including corresponding information and data which show that the conditions for the application of the PRIME scheme have been fulfilled.

Change 31

RemovedArticle 63 – paragraph 1 – point a: (a) the condition affects not more than five in 10 000 persons in the Union when the application for an orphan designation is submitted or the medicinal product is intended for the diagnosis, prevention or treatment of a life-threatening, seriously debilitating or serious and chronic condition in the Union and, without incentives, it is unlikely that the marketing of the medicinal product in the Union would generate a sufficient return to justify the necessary investment;

AddedArticle 61 – paragraph 1 – subparagraph 1: For products under development which may fall within the categories of medicinal products to be authorised by the Union listed in Annex I, a developer or a competent authority of the Member States may submit a duly substantiated request to the Agency for a scientific recommendation with a view to determining on scientific grounds whether the concerned product is potentially a ‘medicinal product’, including an ‘advanced therapy medicinal product’ as defined in Article 2 of Regulation (EC) No 1394/2007 of the European Parliament and of the Council71. The Agency may rely on the relevant expertise of working parties and pools of experts when making its recommendation.

RemovedArticle 65 – paragraph 2 – point c a (new): (ca) detailed reasons for the transferring of the orphan designation

AddedArticle 61 – paragraph 2 – subparagraph 1: When forming the recommendation referred to in paragraph 1, the Agency shall consult, where appropriate and where there is a doubt as to the regulatory status of a product under development, relevant advisory or regulatory bodies established in other Union legal acts in related fields. In the case of products which are based on substances of human origin, the Agency shall first consult the compendium referred to in Regulation (EU) 2024/... [SoHO Regulation] and where necessary, conduct joint meetings with the Substances of Human Origin (SoHO) Coordination Board as established in that Regulation.

RemovedArticle 66 – paragraph 5: 5. At any time, an orphan designation may be withdrawn at the request of the orphan medicine sponsor. The orphan medicine sponsor shall provide a reasoned justification for the withdrawal request which shall be made publicly available.

AddedArticle 61 – paragraph 2 – subparagraph 3: The Agency shall publish the recommendations delivered in accordance with paragraph 1, after deletion of all information of a commercially confidential nature.

AddedArticle 61 – paragraph 2 – subparagraph 3 a (new): For transparency purposes, the respective opinions and conclusions of the Agency and the relevant advisory bodies on the regulatory status of the product shall be made publicly available after the consultations and, where applicable, the joint meetings have taken place.

AddedArticle 62 – paragraph 1 – subparagraph 1: In the case of duly substantiated disagreement with the Agency’s scientific recommendation, in accordance with Article 61(2), a Member State may request the Commission to decide whether the product is a product referred to in Article 61(1).

AddedArticle 62 – paragraph 2: 2. The Commission may ask the Agency and the relevant advisory or regulatory bodies involved in the delivery of the scientific recommendation for clarifications or refer the recommendation back to the Agency for further consideration where a Member State's substantiated request raises new questions of a scientific or technical nature or on its own initiative.

AddedArticle 62 – paragraph 3: 3. The decision of the Commission referred to in paragraph 1 shall be adopted by means of implementing acts, in accordance with the examination procedure referred to in Article 173(2), taking into account the scientific recommendation of the Agency and other advisory bodies.

AddedArticle 63 – paragraph 2: deleted

AddedArticle 64 – paragraph 2 – subparagraph 1 – point d: (d) justification that the criteria laid down in Article 63(1) are fulfilled and a description of the stage of development, including the expected therapeutic indication.

AddedArticle 64 – paragraph 4 – subparagraph 1: The Agency shall adopt a decision granting or refusing the orphan designation based on the criteria referred to in Article 63(1) within 90 days of the receipt of a valid application. The application is considered valid if it includes all the particulars and documentation referred to in paragraph 2.

AddedArticle 65 – paragraph 2 – point c a (new): (ca) reasons for the transfer of the orphan designation.

AddedArticle 66 – paragraph 5: 5. At any time, an orphan designation may be withdrawn at the request of the orphan medicine sponsor. The orphan medicine sponsor may provide a reasoned justification for the withdrawal request, which shall be made publicly available.

Article 67 – paragraph 3 – point f a (new): (fa) where applicable, any request made in accordance with Article 66(2) and any decisions taken in that respect.

Change 32

RemovedArticle 68 – paragraph 2: 2. Medicinal products designated as orphan medicinal products under the provisions of this Regulation shall be eligible for incentives made available by the Union and by the Member States to support research into, and the development and availability of, orphan medicinal products and in particular aid for research for small- and medium-sized undertakings and not-for-profit organisations provided for in framework programmes for research and technological development.

AddedArticle 68 – paragraph 1 – introductory part: 1. The orphan medicine sponsor shall, prior to the submission of an application for marketing authorisation, request advice from the Agency on the following:

RemovedArticle 70 – paragraph 1 – introductory part: 1. An orphan medicinal product shall be considered as addressing a high unmet medical need where it fulfils the following two requirements:

AddedArticle 68 – paragraph 1 – point a: (a) the conduct of the various tests and trials necessary to demonstrate the quality, safety, efficacy and environmental impact of the medicinal product, as referred to Article 138(1), second subparagraph, point (p);

RemovedArticle 70 – paragraph 1 – point b: (b) the use of the orphan medicinal product results in a substantial reduction in disease morbidity or mortality for the relevant patient population.

AddedArticle 68 – paragraph 2: 2. Medicinal products designated as orphan medicinal products under the provisions of this Regulation shall be eligible for incentives made available by the Union and by the Member States to support research into, and the development and availability of, orphan medicinal products and in particular aid for research for small- and medium-sized undertakings and entities not engaged in economic activity provided for in framework programmes for research and technological development.

AddedArticle 69 – paragraph 2 – subparagraph 1: In addition, the applicant shall demonstrate that the medicinal product has been granted an orphan designation and that the criteria set out in Article 63(1) are fulfilled for the therapeutic indication sought.