Changes from plenary report to adopted text

RemovedEXPLANATORY STATEMENT

Added(b) except for the data referred to in point (a), the application file is complete and satisfies all the requirements of this Regulation;

RemovedThe Rapporteur welcomes the long-awaited proposals on both the pharmaceutical Regulation and the Directive as a centrepiece of the European Health Union, which provide a much-needed revision for the crucial legislative framework providing the pharmaceutical rules in the Union. Given that the provisions set out in both the Regulation and Directive are intrinsically interconnected, the Rapporteur considers it essential that these legal texts are considered closely together.

Added(c) specific conditions are included in the decision of the Commission, in particular to ensure the safety of the medicinal product as well to ensure that the marketing authorisation holder notifies to the competent authorities any incident relating to its use and takes appropriate action where necessary.

RemovedThis revision will help the Union to provide a high level of public health by ensuring quality, safety, and efficacy of medicinal products for European patients. Furthermore, it will be a step towards securing timely and equitable access for patients across all Member States. The Rapporteur is committed to delivering on the overarching objectives of ensuring greater accessibility, affordability, and availability of medicinal products for patients across the whole Union.

Added2. The maintenance of the authorised new therapeutic indication and the validity of the marketing authorisation granted in accordance with paragraph 1 shall be linked to the reassessment by the Agency of the conditions referred to in paragraph 1 after two years from the date when the new therapeutic indication was authorised or the marketing authorisation was granted, and thereafter at a risk-based frequency to be determined by the Agency and specified by the Commission in the marketing authorisation.

RemovedFurthermore, the Rapporteur welcomes the stepping away from the model of “one-size-fits-all" towards a stepwise approach of incentive models, where actual innovation is promoted and rewarded. The Rapporteur further builds on this principle in his approach to amendments on the modulation of incentives.

AddedThis reassessment shall be conducted on the basis of an application by the marketing authorisation holder to maintain the authorised new therapeutic indication or renew the marketing authorisation under exceptional circumstances.

RemovedIncreasingly in the past years the European Union has experienced occasions of shortages of critical and essential medicinal products, to the detriment of patients across the EU. The measures proposed by the European Commission are therefore very much welcomed, as we will be setting a framework to counter shortages, react efficiently and in a coordinated matter. Measures introduced include shortage management and security of supply of medicinal products and in particular critical medicinal products. Further developing the tasks and responsibilities of the EMA towards shortage prevention is another positive addition in the text.

AddedWhere specific conditions referred to in paragraph 1, point (c), of this Article 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 suspend, revoke or vary the marketing authorisation by means of implementing acts. Those implementing acts shall be adopted in accordance with the examination procedure referred to in Article 173(2). [Am. 120]

RemovedIn a similar vein, the Rapporteur is positive regarding the enhanced provisions on the Environmental Risk Assessment proposed by the Commission and the proposed restructuring of the European Medicines Agency that will facilitate streamlined procedures and accelerated marketing authorisations.

AddedArticle 19 Conditional marketing authorisation

RemovedThe Rapporteur is also dubious of Chapter IX of the proposal which introduces a regulatory sandbox for medicinal products. Firstly, the rapporteur considers the provisions in the Commission’s proposal vague in nature and has not been satisfied with explanations or examples of which types of products could be eligible for such a regulatory sandbox. The rapporteur also bases his decision of the deletion of this chapter after consultation with several stakeholders, and notably industry actors who expressed reluctance with the introduction of another parallel regulatory framework. The Rapporteur and several stakeholders consider that the frameworks within the pharmaceutical rules are broad and encompassing. There is concern that such a sandbox could provide a way of circumventing rules and obligations laid down in the other frameworks provided for in the Regulation. Additionally, the rapporteur would oppose derogations from the requirements set out in both the Regulation and the Directive, particularly with regards to the Environmental Risk Assessment.

Added1. In duly justified cases, to meet an unmet medical need of patients, as referred to in Article 83(1), point (a), of [revised Directive 2001/83/EC], a conditional marketing authorisation or a new conditional therapeutic indication to an existing marketing authorisation authorised under this Regulation may be granted by the Commission to a medicinal product that is likely to address the unmet medical need in accordance with Article 83(1), point (b), of [revised Directive 2001/83/EC], prior to the submission of comprehensive clinical data provided that the benefit of the immediate availability on the market of that medicinal product outweighs the risk inherent in the fact that additional data are still required.

RemovedFurthermore, the Rapporteur also perceives shortcomings within the Commission proposal, notably on incentives for the development of priority antimicrobials.

AddedIn emergency situations, a conditional marketing authorisation or a new conditional therapeutic indication referred to in the first subparagraph may be granted also where comprehensive non-clinical or pharmaceutical data have not been supplied.

RemovedAntimicrobial resistance is a rapidly increasing public health threat, already responsible for 35,000 deaths annually in the EU alone and 1.3 million deaths globally. In this regard, the Rapporteur recognises the severity of this issue and the need for the creation of new priority microbials as envisaged in the Regulation. It is also the conviction of the rapporteur that the EU must take action to prevent excessive use of antimicrobials and pharmaceutical waste in the environment, which contribute to the proliferation of antimicrobial resistance. However, the Rapporteur expresses severe scepticism towards the proposed solution of the Transferable Exclusivity Voucher (TEV) which are an indirect and non-transparent form pricing which will cost national health budgets in an unpredictable manner and delay the entry of generic medicines to the market, to the detriment of patients. It is incomprehensible to the Rapporteur that the Commission would propose such a measure without even the accompanying requirement and conditionality to guarantee supply of the priority antimicrobial from which the voucher was awarded. Additionally, the Rapporteur feels that safeguards are missing for the continuous supply of the antimicrobial after the voucher has been sold to another company.

Added2. Conditional marketing authorisations or a new conditional therapeutic indication referred to in paragraph 1 may be granted only if the benefit-risk balance of the medicinal product is favourable and the applicant is likely to be able to provide comprehensive data.

RemovedIn the absence of the TEV, the Rapporteur proposes the establishment of the ‘European Medicines Facility’ (EMF) as a Union Agency. The EMF should set out specific purpose led R&D projects focusing on health priorities in the public interest at a Union level. These projects should follow a strategic roadmap addressing priority antimicrobials, as well as medicinal products addressing high unmet medical needs and unmet medical needs which have not been sufficiently addressed by the private sector and where the private R&D pipeline is unlikely to deliver on medicinal products and therapies. The Rapporteur introduces the overarching idea of the EMF in this draft report and will further supplement the proposal in later amendments.

Added3. Conditional marketing authorisations or a new conditional therapeutic indication, granted pursuant to this Article shall be subject to specific obligations. Those specific obligations, in particular for ongoing or new studies as referred to in paragraph 4, and, where appropriate, the time limit for compliance shall be specified in the conditions to the marketing authorisation. Those specific obligations shall be reviewed annually by the Agency for the first three years after granting the authorisation and every two years thereafter. [Am. 121]

RemovedAdditionally, the Rapporteur considers it necessary and complementary to mandate the Commission to establish a Union push and pull incentives scheme as an additional measure to incentivise the development of novel antibiotics which could include the likes of market-entry rewards, ‘play or pay’ fees, or subscription payment mechanisms.

Added4. As part of the specific obligations referred to in paragraph 3, the marketing authorisation holder of a conditional marketing authorisation granted pursuant to this Article shall be required to complete ongoing studies, or to conduct new studies in accordance with Article 20, with a view to confirming that the benefit-risk balance is favourable. [Am. 122]

RemovedThis report also includes several smaller tweaks and more adaptations of a technical nature. However, the Rapporteur would like to briefly highlight increased emphasis on the involvement of patients and consumer organisations and the strengthening of provisions on transparency and conflicts of interests throughout the text.

Added5. The summary of product characteristics and the package leaflet shall clearly mention that the conditional marketing authorisation for the medicinal product has been granted subject to specific obligations as referred to in paragraph 3.

RemovedGiven the time constraints in the preparation of this draft report, the Rapporteur reserves the right to further amend and supplement this draft report with additional measures, clarifications and to further develop ideas introduced in the text. The Rapporteur is looking forward to engaging constructively with all shadow rapporteurs on this Regulation and equally the rapporteur and shadows on the Directive where coordination is necessary.

Added6. By way of derogation from Article 17(1), an initial conditional marketing authorisation granted pursuant to this Article shall be valid for one year, on a renewable basis for the first three years after granting the authorisation and every two years thereafter.

RemovedThe list in the Annex of entities or persons from whom the rapporteur has received input from contains all contributions received, even if not all of it has been used in order to draft the report. Additionally, all meetings in regard to the Regulation can be found on the dedicated profile of the Rapporteur on the website of the European Parliament.

Added7. When the specific obligations referred to in paragraph 3 have been fulfilled for a conditional marketing authorisation granted pursuant to this Article, the Commission may, following an application by the marketing authorisation holder, and after having received a favourable opinion from the Agency, grant a marketing authorisation pursuant to Article 13.

Added7a. Where the specific obligations referred to in paragraph 3 are not complied with within the timeframe stipulated by the Agency or the marketing authorisation holder does not provide duly justified reasons for not complying with the obligations, the Commission may suspend, revoke or vary the marketing authorisation by means of implementing acts. Those implementing acts shall be adopted in accordance with the examination procedure referred to in Article 173(2). [Am. 123]

Added8. The Commission is empowered to adopt delegated acts in accordance with Article 175 to supplement this Regulation by establishing the following:

Added(a) the categories of medicinal products to which paragraph 1 applies;

Added(b) the procedures and requirements for granting a conditional marketing authorisation, for its renewal, and for adding a new conditional therapeutic indication to an existing marketing authorisation, and for the withdrawal, suspension or revocation of the conditional marketing authorisation. [Am. 124]

Added8a. The Agency shall publish in the database referred to in Article 138(1), second subparagraph, point (n), the list of conditional marketing authorisations, together with the following information:

Added(a) specific obligations to be complied with by the marketing authorisation holder;

Added(b) timelines for compliance with specific obligations;

Added(c) any delays by the marketing authorisation holder regarding the compliance with specific obligations and the reasons for such delays;

Added(d) any actions on the conditional marketing authorisation taken in accordance with Article 56. [Am. 125]

AddedArticle 20 Imposed post-authorisation studies

Added1. After the granting of a marketing authorisation, the Agency may consider that it is necessary that the marketing authorisation holder:

Added(a) conducts 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;

Added(b) conducts 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 21 while taking into account the scientific guidance referred to in Article 123 of [revised Directive 2001/83/EC];

Added(c) conducts a post-authorisation environmental risk assessment study to further investigate the risks to the environment or public health due to the release of the medicinal product in the environment, if new concerns emerge on the authorised medicinal product, or other medicinal products containing the same active substance.

Added(ca) conducts a post-authorisation treatment optimisation study where the optimal usage of an authorised medicinal product has not been previously established. [Am. 126]

AddedIf this obligation would apply to several medicinal products, the Agency shall encourage the marketing authorisation holders concerned to conduct a joint post authorisation environmental risk assessment study.

AddedWhere the Agency considers that any of the post-authorisations studies referred to in the first subparagraph, points (a) to (c)(ca), is necessary, it shall inform the marketing authorisation holder thereof in writing, stating the grounds for its assessment and shall include the objectives and timeframe for submission and conduct of the study. [Am. 127]

Added2. The Agency shall provide the marketing authorisation holder with an opportunity to present written observations in response to its letter within a time limit which it shall specify, if the marketing authorisation holder so requests within 30 days of receipt of the letter.

Added3. On the basis of the written observations the Agency shall review its opinion.

Added4. Where the opinion of the Agency confirms the need for any of the post-authorisation studies referred to in paragraph 1, first subparagraph, points (a) to (c)(ca), to be carried out, the Commission shall vary the marketing authorisation, by means of implementing acts, adopted pursuant to Article 13 to include the obligation as a condition of the marketing authorisation unless the Commission returns the opinion to the Agency for further consideration. For obligations under paragraph 1, points (a) and (b), the marketing authorisation holder shall update the risk management system accordingly. [Am. 128]

AddedArticle 21 Post authorisation efficacy studies

AddedThe Commission is empowered to adopt delegated acts in accordance with Article 175, to supplement this Regulation by determining the situations in which post-authorisation efficacy studies may be required under Article 12(4), point (g), and Article 20(1), point (b).

AddedArticle 22 Risk management system

AddedThe marketing authorisation holder shall incorporate any condition of authorisation reflecting the elements referred to in Article 12(4), points (d) to (g), or in Article 20, or in Article 18(1) and Article 19 in their risk management system.

AddedArticle 23 Liability of the marketing authorisation holder

AddedThe granting of a marketing authorisation shall not affect the civil or criminal liability of the manufacturer or of the marketing authorisation holder pursuant to the applicable national law in Member States.

AddedArticle 24 Suspension of marketing, withdrawal from the market of a medicinal product, withdrawal of a marketing authorisation by the marketing authorisation holder

Added1. In addition to the notification made pursuant to Article 116, the marketing authorisation holder shall notify the Agency without undue delay of any action they take to suspend the marketing of a medicinal product, to withdraw a medicinal product from the market, to request the withdrawal of a marketing authorisation or not to apply for the renewal of a marketing authorisation, together with the reasonsa detailed reasoning for such action. [Am. 129]

AddedThe marketing authorisation holder shall declare if such action is based on the following grounds:

Added(a) the medicinal product is harmful;

Added(b) it lacks therapeutic efficacy;

Added(c) the benefit-risk balance is not favourable;