Changes from plenary report to adopted text

Added(78) To be considered a ‘priority antimicrobial’, a medicinal product should represent a real advancement against antimicrobial resistance and should therefore bring forward non-clinical and clinical data that underpin a significant clinical benefit with respect to antimicrobial resistance. When assessing the conditions for antibiotics, the Agency shall take into account the prioritisation of pathogens as regards the risk of antimicrobial resistance 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 in case there is an equivalent list of priority pathogens adopted at Union level, the Agency should take such Union list into account as a priority.

RemovedArticle 12 – paragraph 4 – point m a (new): (ma) a stewardship and access plan in accordance with Article 17(1), point (a), of [revised Directive 2001/83/EC] and special information requirements in accordance with Article 69 of that Directive for any antimicrobials, as well as any other obligations imposed on the marketing authorisation holder;

Added(78a) To effectively address major ongoing and upcoming public health challenges, in particular antimicrobial resistance, while also building on existing resources, the Health Emergency Preparedness and Response Authority (‘HERA’ or the ‘Authority’) should be established as a separate structure under the legal personality of the European Centre for Disease Prevention and Control (ECDC), which was established by Regulation (EC) No 851/2004 of the European Parliament and of the Council. The Authority should be responsible for creating, coordinating and implementing the long-term European portfolio of biomedical research and development agenda for medical countermeasures against current and emerging public health threats, as well as providing tools to ensure Union-wide access to those products, including tools to support the production, procurement, stockpiling and distribution capacity for medical countermeasures and other priority medical products in the Union. The Authority will play a crucial role in addressing health threats globally. The Authority should primarily focus on the fight against the most urgent health threats, including antimicrobial resistance and shortages of medicinal products. However, in the future as its capacity increases, the Authority should expand the scope of its mission, specifically to tackle other areas of unmet medical need such as rare and neglected diseases. The Authority should have adequate resources to fulfil its mandate. [Am. 49]

RemovedArticle 12 – paragraph 4 – point m b (new): (mb) where applicable, reasoning as to whether the medicinal product satisfies the criteria of Article 83 of [revised Directive 2001/83/EC] regarding medicinal products addressing an unmet medical need.

Added(78b) In addition to the growing threat of antimicrobial resistance, there are other market failures present in the pharmaceutical sector for which further action at Union level is required to meet the public health needs of Union citizens. In particular, there is misalignment between R&D priorities and the public health needs of Union citizens. The market failures in the Union have, in certain instances, resulted in no treatments being available for rare diseases and unequal access to medicinal products, and have led to shortages. This Regulation should therefore address those market failures through providing for a modulated approach to market exclusivities and increased transparency concerning R&D expenditure to better deliver on the objectives of affordability, accessibility and availability of medicinal products in the Union. [Am. 50]

RemovedArticle 13 – paragraph 1 – subparagraph 5: Where the draft decision differs from the opinion of the Agency, the Commission shall provide a detailed explanation of the reasons for the differences and make that information publicly available.

Added(78c) Joint procurement, whether within a country or involving more than one country, can improve access to, affordability, and security of supply of medicinal products. Member States interested in joint procurement of medicinal products should be able to request the Commission to facilitate joint procurement of centrally authorised medicinal products at Union level conducted pursuant to Directive 2014/24/EU of the European Parliament and of the Council. [Am. 51]

RemovedArticle 13 – paragraph 1 – subparagraph 6: The Commission shall send the draft decision and the accompanying reasoning referred to in the fifth subparagraph to the Member States and the applicant.

Added(79) As an alternative, for developers who have not availed of market entry rewards and milestone payment schemes, the creation of a voucher rewarding the development of priority antimicrobials through an additional yearperiod of regulatory data protection has the capacity to provide the needed financial support to developers of priority antimicrobials. However, in order to ensure that the financial reward which is ultimately borne by health systems is mostly absorbed by the developer of the priority antimicrobial and not the buyer of the voucher, the number of available vouchers on the market should be kept to a minimum. It is therefore necessary to establish strict conditions of granting, transfer and use of the voucher and to further give the possibility to the Commission to revoke the voucher under certain circumstances. Additionally, the monetary value paid for the transfer of the voucher should be transferred to the Authority, which should distribute the corresponding amount, in yearly instalments, to the marketing authorisation holder, in order to ensure manufacturing capacity and supply of the priority antimicrobial for which the voucher was created. [Am. 52]

RemovedArticle 13 – paragraph 4: 4. The Agency shall disseminate the documents referred to in Article 12(4), points (a) to (e), and, where relevant, the documents referred to in Article 12(4), points (f) to (mb), together with any deadlines laid down pursuant to paragraph 1, first subparagraph.

Added(80) A transferable data exclusivity voucher should only be available to those antimicrobial products that bring a significant clinical benefit with respect to antimicrobial resistance, and which have the characteristics described in this Regulation. It is also necessary to ensure that an undertaking which receives this incentive is in turn capable to supply the medicinal product to patients across the Union in sufficient quantities and to provide information on all funding received for research related to its development in order to provide a full account of the direct financial and indirect support given to the medicinal product in accordance with Article 57 of [revised Directive 2001/83/EC]. [Am. 53]

RemovedArticle 15 – paragraph 1 – point d: (d) the environmental risk assessment is incomplete or insufficiently substantiated by the applicant or if the risks identified in the environmental risk assessment have not been sufficiently addressed by the risk mitigation measures proposed by the applicant in accordance with Article 22(3) of [revised Directive 2001/83/EC];

Added(81) To ensure a high level of transparency and complete information on the economic effect of the transferable data exclusivity voucher, notably as regards the risk of overcompensation of investment, a developer of a priority antimicrobial is required to provide information on all direct financial support received for research related to the development of the priority antimicrobial. The declaration should include direct financial support received from any source worldwide and any indirect financial support in accordance with Article 57 of [revised Directive 2001/83/EC]. [Am. 54]

RemovedArticle 16 – paragraph 3 – subparagraph 1: The Agency shall immediately publish the assessment report on the medicinal product for human use and the reasons for its opinion in favour of granting marketing authorisation, after deletion of any information of a commercially confidential nature following a notification to relevant patient organisations. The Agency shall ensure that European public assessment report summaries are readable, clear and comprehensible.

Added(82) A transfer of a voucher for a priority antimicrobial may be conducted by sale and may only be transferred once. The value of the transaction which may be monetary or otherwise agreed between the buyer and the seller, shall be made public so as to inform regulators and the public. The identity of the holder of a voucher that has been granted and not yet used should be publicly known at all times so as to ensure a maximum level of transparency and trust. [Am. 55]

RemovedArticle 16 – paragraph 3 – subparagraph 2 – indent 2: – the complete environmental risk assessment submitted to the Agency by the marketing authorisation applicant as well as a summary of environmental risk assessment studies and their results as submitted by the marketing authorisation holder and the assessment of the environmental risk assessment and the information referred to in Article 22(5) of [revised Directive 2001/83/EC] by the Agency.

Added(83) The provisions related to transferable data exclusivity vouchers shall be applicable for a specified period from the entry into force of this Regulation or until a maximum number of vouchers are granted by the Commission in order to limit the total cost of the measure to Member State health systems. The limited application of the measure will also provide the possibility to assess the effect of the measure in addressing the market failure in the development of new antimicrobials addressing antimicrobial resistance and assess the cost on national health systems. Such assessment will provide the necessary knowledge to decide whether to extend the application of the measure. Additionally, by ... [five years from the date of entry into force of this Regulation], the Commission should provide an evaluation report on the effectiveness of both the milestone payment reward schemes and the transferable data exclusivity vouchers in the development of priority antimicrobials. [Am. 56]

RemovedArticle 16 – paragraph 3 – subparagraph 2 – indent 2 a (new): – for antimicrobials, all information referred to in Article 17 of and Annex I to [revised Directive 2001/83/EC] as well as any other obligations imposed on the marketing authorisation holder.

Added(84) The period of application of the provisions on transferable exclusivity vouchers for priority antimicrobials and the total number of vouchers may be extended by the Parliament and the Council upon proposal by the Commission on the basis of the experience acquired.

RemovedArticle 18 – paragraph 1 – introductory part: 1. In exceptional circumstances where, in an application under Article 6 of [revised Directive 2001/83/EC] for a marketing authorisation of a medicinal product or a new therapeutic indication, of an existing marketing authorisation under this Regulation, an applicant is unable to provide comprehensive data on the efficacy and safety of, and, where missing, on the environmental risk posed by, the medicinal product under normal conditions of use, the Commission may, by derogation to Article 6, grant an authorisation under Article 13, subject to specific conditions, where the following requirements are met:

Added(85) Where the Commission considers that there are reasons to believe that a medicinal product could present a potential serious risk to human health, a scientific evaluation of the medicinal product should be undertaken by the Agency, leading to a decision whether to maintain, vary, suspend or revoke the marketing authorisation, and taken on the basis of an overall benefit-risk assessment. The Commission may also act on a centralised marketing authorisation where the conditions attached to it are not complied with.

RemovedArticle 18 – paragraph 2 – subparagraph 2 a (new): Where 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).

Added(86) Medicinal products for rare diseases and for children should be subject to the same provisions as any other medicinal product concerning their quality, safety, and efficacy and environmental risk, for example for what concerns the marketing authorisation procedures, the pharmacovigilance and quality requirements. However, specific requirements also apply to them. Such requirements, which are currently defined in separate legislations, should be integrated in this Regulation in order to ensure clarity and coherency of all the measures applicable to these medicinal products. [Am. 57]

RemovedArticle 19 – paragraph 3: 3. 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.

Added(87) Some orphan conditions occur so infrequently that the cost of developing and bringing to the market a medicinal product to diagnose, prevent or treat the condition cannot be recovered by the expected sales of the medicinal product. However, patients suffering from rare conditions should be entitled to the same quality of treatment as other patients; it is therefore necessary to stimulate the research, development and placing on the market of appropriate medications by the pharmaceutical industry.

RemovedArticle 19 – paragraph 4: 4. 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.

Added(88) Regulation (EC) No 141/2000 of the European Parliament and of the Council has proved to be successful in boosting developments of orphan medicinal products in the Union, even though more progress needs to be done, as 95 % of rare diseases are still without authorised treatment and the treatments available for 5 % of rare diseases are not necessarily transformative or curative; therefore an action at Union level remains preferable to uncoordinated measures by the Member States which may result in distortions of competition and barriers to intra-Union trade. The Union should build on its success, driving and ensuring a similar degree of innovation under this Regulation. [Am. 58]

RemovedArticle 19 – paragraph 7 – subparagraph 1 a (new): 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).

Added(89) The open and transparent Union procedure for the designation of potential medicinal products as orphan medicinal products established by Regulation (EC) No 141/2000 should be maintained. To increase legal clarity and simplification, the specific legal provisions applicable to these medicinal products should be integrated in this Regulation.

RemovedArticle 19 – paragraph 8 – point b: (b) the procedures and requirements for granting a conditional marketing authorisation, for its renewal, for adding a new conditional therapeutic indication to an existing marketing authorisation, and for the withdrawal, suspension or revocation of the conditional marketing authorisation.

Added(90) Objective criteria for the orphan designation based on the prevalence of the life-threatening or chronically debilitating condition for which diagnosis, prevention or treatment is sought and the existence of no satisfactory method of diagnosis, prevention or treatment of the condition in question that has been authorised in the Union should be maintained; a prevalence of not more than five affected persons per 10 000 is generally regarded as the appropriate threshold. The orphan designation criterion on the basis of return on investment has been abolished, since it has never been used. Nevertheless, medicinal products should still be able to lose the orphan status in cases where the population criterion is no longer met. [Am. 59]

RemovedArticle 19 – paragraph 8 a (new): 8a. 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: / (a) specific obligations to be complied with by the marketing authorisation holder; / (b) timelines for compliance with specific obligations; / (c) any delays by the marketing authorisation holder regarding the compliance with specific obligations and the reasons for such delays; / (d) any actions on the conditional marketing authorisation taken in accordance with Article 56.

Added(91) The criterion for orphan designation based on prevalence of a disease may, however, not be appropriate to identify rare diseases in all cases. For example, for conditions which have a short duration and high mortality, measuring the number of people that acquired the disease during a specific time period would better reflect if it is rare within the meaning of this Regulation than measuring the number of people who are ‘affected by it’ in a specific moment of time. With the aim to better identify only those diseases which are rare, the Commission should be empowered to set up specific designation criteria for certain conditions if the one provided for are not appropriate due to scientific reasons and on the basis of a recommendation of the Agency.

RemovedArticle 20 – paragraph 1 – subparagraph 1 – point c a (new): (ca) conducts a post-authorisation treatment optimisation study where the optimal usage of an authorised medicinal product has not been previously established.

Added(92) With the aim to better identify only those diseases which are rare, the Commission should be empowered to supplement the designation criteria by a delegated act if they are not appropriate for certain conditions due to scientific reasons and on the recommendation of the Agency. In addition, the designation criteria require implementing measures to be adopted by the Commission. [Am. 60]

RemovedArticle 20 – paragraph 1 – subparagraph 3: Where the Agency considers that any of the post-authorisations studies referred to in the first subparagraph, points (a) to (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.

Added(92a) What qualifies as a significant benefit in a patient population can change over time. Therefore, while ensuring predictability, the Agency should also take into account any scientific developments and guidance when assessing whether medicinal products meet the significant benefit criteria. [Am. 61]

RemovedArticle 20 – paragraph 4: 4. 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 (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.

Added(93) If a satisfactory method of diagnosis, prevention or treatment of the condition in question has already been authorised in the Union, the orphan medicinal product will have to be of significant benefit to those affected by that condition. In this context, a medicinal product authorised in one Member State is generally deemed as being authorised in the Union. It is not necessary for it to have Union authorisation or to be authorised in all Member States to be considered as a satisfactory method. In addition, commonly used methods of diagnosis, prevention or treatment that are not subject to a marketing authorisation may be considered satisfactory if there is scientific evidence of their efficacy and safety. In certain cases, medicinal products prepared for an individual patient in a pharmacy according to a medical prescription, or according to the prescriptions of a pharmacopoeia and intended to be supplied directly to patients served by the pharmacy, mayshould also be considered as satisfactory treatment if they are well known and safe and this is a general practice for the relevant patient population in the Union. [Am. 62]

RemovedArticle 24 – paragraph 1 – subparagraph 1: 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 a detailed reasoning for such action.

Added(94) The competence to designate a medicinal product as an orphan medicinal product, in the form of a decision, is accorded to the Agency. This is expected to facilitate and expedite the designation procedure, while ensuring high level of scientific expertise.

RemovedArticle 24 – paragraph 1 – subparagraph 2 – point f a (new): (fa) commercial reasons.

Added(95) In order to incite faster authorisation of designated orphan medicinal products, the validity of orphan designation has been set at seven years, with the possibility of extension by the Agency under certain specified conditions; the orphan designation may be withdrawn at the request of the orphan medicine sponsor, who should be able to provide a reasoned justification for the withdrawal request. The Agency should make the reasoned justification for the withdrawal request, when provided by the sponsor, publicly available. [Am. 63]

RemovedArticle 24 – paragraph 3 a (new): 3a. In the cases referred to in paragraph 1, second subparagraph, point (f), the Agency shall immediately inform the Commission. The Commission shall in turn inform the relevant national and Union authorities. Where relevant, national authorities shall forward the information to drinking water and wastewater operators.

Added(96) The Agency is responsible for designation of an orphan medicinal product as well as for the setting up and management of a register of designated orphan medicinal products. That register should be publicly available and the minimum data which should be included in the register have been specified in this Regulation with the empowerment for the Commission to amend or supplement this data by a delegated act.

RemovedArticle 24 – paragraph 4 a (new): 4a. The Agency may decide to extend obligations set out in paragraph 4 in justified cases to a specific non-critical medicinal product on a case-by-case basis.

Added(97) Sponsors of orphan medicinal products designated under this Regulation should be entitled to the full benefit of incentives granted by the Union or by the Member States to support the research and development of medicinal products for the diagnosis, prevention or treatment of such conditions, including rare diseases.

RemovedArticle 24 – paragraph 4 b (new): 4b. The marketing authorisation holder from which the marketing authorisation has been transferred to a third party shall notify the Agency of the transfer as soon as possible. The information regarding the transfer provided shall be made publicly available.

Added(98) Patients suffering from orphan conditions deserve medicinal products of the same quality, safety and efficacy as other patients; orphan medicinal products should therefore be submitted to the normal evaluation process carried out by the Committee of Medicinal Products for Human Use for the applicant to obtain an marketing authorisation for orphan medicinal product, while a separate marketing authorisation may be granted for indications not fulfilling the criteria of an orphan medicinal product.

RemovedArticle 25 – paragraph 1 – subparagraph 3: As soon as the relevant patent or supplementary protection certificate referred to in point (a) expires, the marketing authorisation holder shall without undue delay withdraw the initial or duplicate marketing authorisation.

Added(99) A vast percentage of rare diseases remains without treatment with research and development clustered in the areas where profit is better assured. Therefore, there is a need to target those areas where research is mostly needed and where investments are most risky.

RemovedArticle 26 – paragraph 2: 2. For the purposes of this Article, ‘compassionate use’ shall mean making a medicinal product belonging to the categories referred to in Article 3, paragraphs 1 and 2 available for compassionate reasons to a single or group of patients with a chronically or seriously debilitating disease or whose disease is considered to be life-threatening, treatment resistant, or causing psychological distress or patients in palliative care, and who cannot be treated satisfactorily by an authorised medicinal product. The medicinal product concerned must either be the subject of an application for a marketing authorisation in accordance with Article 6 or the submission of such application is imminent, or it must be undergoing clinical trials in the same indication.

Added(100) Orphan medicinal products addressing a high unmet medical need prevent, diagnose or treat conditions where either no other method of prevention, diagnosis or treatment exists or, if such method already exists, they would bring exceptional therapeutic advancement. In both cases, the criterion of meaningful reduction in disease morbidity or mortality for the relevant patient population should ensure that only most effective medicinal products are covered. The Agency should draw up scientific guidelines on the category of ‘orphan medicinal products addressing a high unmet medical need’.

RemovedArticle 26 – paragraph 3: 3. When applying paragraph 1, the Member State shall notify the Agency, which shall make the notification publicly available.

Added(101) Experience since the adoption of Regulation (EC) No 141/2000 shows that the strongest incentive for industry to invest in the development and making available of orphan medicinal products is where there is a prospect of obtaining market exclusivity for a certain number of years during which part of the investment might be recovered. In addition to the periods of market exclusivity, orphan medicinal products will benefit from the periods of regulatory protection set out in [revised Directive 2001/83/EC], including the prolongations of regulatory data protection. However, where an orphan medicinal product obtains an additional therapeutic indication it will benefit only from the prolongation of market exclusivity.

RemovedArticle 26 – paragraph 4 – subparagraph 2: In the preparation of the opinion, the Committee for Medicinal Products for Human Use may request information and data from marketing authorisation holders and from developers and may engage with them in preliminary discussions. The Committee may also make use of health data generated outside of clinical studies, including real world data, where available, taking into account the reliability of those data.

Added(102) In order to incentivise research and development of orphan medicinal products addressing high unmet needs, to ensure market predictability and to ensure a fair distribution of incentives, a modulation of market exclusivity has been introduced; orphan medicinal products addressing high unmet medical needs benefit from the longest market exclusivity, while market exclusivity for well-established use orphan medicinal products, requiring less investment, is the shortest. In order to ensure increased predictability for developers, the possibility to review the eligibility criteria for market exclusivity after six years after the marketing authorisation has been abolished.

RemovedArticle 26 – paragraph 6: 6. The Agency shall keep an up-to-date list of the opinions adopted in accordance with paragraph 4 and shall publish it in the database referred to in Article 138(1), second subparagraph, point (n), on its website.

Added(103) In order to encourage faster and wider access also to orphan medicinal products, an additional period of one year of market exclusivity is granted to orphan medicinal products for a Union market launch, with the exception of well-established use medicinal products. [Am. 64]

RemovedArticle 26 – paragraph 10: 10. The Agency shall adopt detailed guidelines laying down format and content of notifications referred to in paragraphs 3 and 5, and data exchange under this Article.