What changed between the draft committee report and the plenary report

Added:Recital 36: (36) The expertise of the Committee for Advanced Therapies (CAT), the Committee for Orphan Medicinal Products (COMP), the Paediatric Committee (PDCO) and Committee for Herbal Medicinal Products (HMPC) is retained through working groups, working parties, ad hoc working groups, and a pool of experts who are organised based on different domains and who are giving input to the CHMP and PRAC. Their evaluation will continue to encompass all the necessary expertise for each product as part of the rapporteur teams, with the possibility for CHMP and PRAC to call upon additional scientific experts to provide specific input and advice on specific aspects raised during the evaluation. In addition, patients and healthcare professionals will be part of the pool of experts and will also be brought into EMA’s work according to their expertise in a certain disease area. The CHMP and PRAC consists of experts from all Member States while working parties and expert groups consist in majority of experts appointed by the Member States, based on their expertise, and of external experts. The model of rapporteurs remains unchanged. Representation of patients, their caregivers and health care professionals, with expertise in all areas, including rare and paediatric diseases, is increased at the CHMP and PRAC, in addition to the dedicated working groups representing patients and health care professionals. Information regarding the composition and work of the committees and working groups should be publ…

Removed:Recital 83: deleted

Added:Recital 39: (39) To allow for a more informative decision making and for exchange of information and pooling of knowledge on general issues of scientific or technical nature related to the tasks of the Agency regarding medicinal products for human use, in particular to scientific guidelines on unmet medical needs and the design of clinical trials, or other studies and the generation of evidence along the life cycle of medicinal product, the Agency should be able to have recourse to a consultation process of authorities or bodies active along the life cycle of medicinal products. Additionally, to improve regulatory certainty and cross-sectoral cooperation the Commission should, on an annual basis, or more frequently where deemed necessary, organise joint meetings with the advisory bodies established under other Union legislation to assess emerging trends and questions on the regulatory status of products and find agreement on common regulatory status principles. These authorities could be, as appropriate, representatives from Heads of Medicines Agencies, the Clinical Trial Coordination and Advisory Group, the SoHO Coordination Board, the Coordination Group on Health Technology Assessment, Medical Devices Coordination Group, medical devices national competent authorities, national competent authorities for pricing and reimbursement of medicines, national insurance funds or healthcare payers. The Agency should also be able to extend the consultation mechanism to consumers, patients and thei…

Removed:Recital 84: deleted

Added:Recital 43: (43) In the interest of public health, marketing authorisation decisions under the centralised procedure should be taken on the basis of the objective scientific criteria of quality, safety and efficacy of the medicinal product concerned, to the exclusion of economic and other considerations. However, Member States should be able, exceptionally, to prohibit the use in their territory of medicinal products for human use. Member States should provide justification for such prohibition of use to the Commission and the Agency.

Removed:Recital 90: (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 should be mandatory during the review and, where necessary, the marketing exclusivity should be reduced where it is shown on the basis of available evidence that the product is sufficiently profitable, and that therefore the maintenance of market exclusivity regarding the product is no longer justified.

Added:Recital 43 a (new): (43a) The Union is required, pursuant to Article 208 of the Treaty on the Functioning of the European Union (TFEU), to take account of development objectives in policies that are likely to have an impact on low- and middle-income countries. Union pharmaceutical legislation has a role to play in the realisation of global public health objectives by promoting the development of efficacious, safe, accessible, and affordable innovations for antimicrobial resistance, poverty-related, emerging and re-emerging health threats, and neglected diseases, and other conditions of global public health interest. The Commission should continue to encourage research, development and innovation in areas of major global health interest, in line with its international commitments.

Removed:Recital 102: (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.

Added:Recital 45 a (new): (45a) The Agency should pay particular attention to the composition of clinical trials to ensure gender based equity and comprehensive clinical data.

Removed:Recital 123: (123) The summary of the results of all the paediatric clinical trials included in the European clinical trial database created by Regulation (EU) No 536/2014 should be made publicly available within 6 months after the end of the clinical trials unless this is not possible for justified scientific reasons. Non-compliance with Regulation (EU) No 536/2014 should be subject to penalties.

Added:Recital 46: (46) Directive 2010/63/EU of the European Parliament and of the Council on the protection of animals used for scientific purposes49 lays down provisions on the protection of animals used for scientific purposes based on the principles of replacement, reduction and refinement. Any study involving the use of live animals, which provides essential information on the quality, safety and efficacy of a medicinal product, should take into account those principles of replacement, reduction and refinement, where they concern the care and use of live animals for scientific purposes, and should be optimised in order to provide the most satisfactory results whilst using the minimum number of animals. The procedures of such testing should be only used where necessary and be designed to avoid causing pain, suffering, distress or lasting harm to animals and should follow the available Agency and the International Committee for Harmonisation (ICH) guidelines. In particular, the marketing authorisation applicant and the marketing authorisation holder should take into account the principles laid down in Directive 2010/63/EU, giving priority to new approach methodologies (NAMs) in place of animal testing. These can include but are not limited to: in vitro models, such as microphysiological systems including organ-on-chips, (2D and 3D) cell culture models, organoids and human stem cells-based models; in silico tools, in chemico technologies and any combination thereof or read-across, aquatic egg…

Removed:Recital 129: (129) Scientific and technological progresses in data analytics and data infrastructure are essential for the development, authorisation and supervision of medicinal products. The digital transformation has affected regulatory decision-making, making it more data-driven and multiplying the possibilities to access evidence, across the life cycle of a medicinal product. This Regulation recognises the Agency’s experience and capacity to access and analyse data submitted independently from the marketing authorisation applicant or marketing authorisation holder. On this basis, the Agency should, after consulting with the affected marketing authorisation holder, take initiative to update the summary of product characteristics in case new efficacy or safety data has an impact on the benefit-risk balance of a medicinal product.

Added:Recital 47: (47) Procedures should be in place to facilitate joint animal testing, wherever possible, in order to avoid unnecessary testing using live animals covered by Directive 2010/63/EU. Marketing authorisation applicants and marketing authorisation holders should make all efforts to reuse animal study results and make the results obtained from animal studies publicly available. For abridged applications marketing authorisation applicants should refer to the relevant studies conducted for the reference medicinal product.

Removed:Recital 133: deleted

Added:Recital 51 a (new): (51a) As a matter of good practice, marketing authorisations should be granted based on comparative clinical trials on patients who are representative of the population that is to be treated with the product. In addition, patient-reported outcome measures (PROMs) and patient-reported experience measures (PREMs) should be an integral part of clinical data submitted with the marketing authorisation application in order to assess the quality of care and the impact of the treatments on patients.

Removed:Recital 134: deleted

Added:Recital 53 a (new): (53a) Several care pathways should be explored to make therapies available in all Member States, including by advancing provisions for access to cross border care, such as Directive 2011/24/EU1a and Regulation (EC) No 883/20041b of the European Parliament and of the Council. This is particularly important for the advanced therapy medicinal products, as their unique characteristics result in significant infrastructural complexities and system barriers, which can substantially limit their continuous supply. / 1a Directive 2011/24/EU of the European Parliament and of the Council of 9 March 2011 on the application of patients’ rights in cross-border healthcare (OJ L 88, 4.4.2011, p. 45). / 1b Regulation (EC) No 883/2004 of the European Parliament and of the Council of 29 April 2004 on the coordination of social security systems (OJ L 166 30.4.2004, p. 1).

Removed:Recital 135: deleted

Added:Recital 54: (54) [revised Directive 2001/83/EC] permits Member States to temporarily allow the use and supply of unauthorised medicinal products for public health reasons or individual patient needs and that includes medicinal products to be authorised under this Regulation. It is also necessary, that Member States are allowed under this Regulation to make a medicinal product available for compassionate use prior to its marketing authorisation. In those exceptional and urgent situations, where there is a lack of a suitable authorised medicinal product, the need to protect public health or the health of individual patients must prevail over other considerations, in particular the need to obtain a marketing authorisation and consequently, to have available complete information about the risks posed by the medicinal product, including any risks to the environment from medicinal products containing or consisting of genetically modified organisms (GMOs). To avoid delays in making these products available or uncertainties as regards their status in certain Member States, it is appropriate, in those exceptional and urgent situations, that for a medicinal product containing or consisting of GMOs, an environmental risk assessment or consent in accordance with Directive 2001/18/EC or Directive 2009/41/EC of the European Parliament and of the Council52 should not be a prerequisite. Nevertheless, in these cases, Member States should implement appropriate measures in line with the precautionary princ…

Removed:Recital 137: (137) To achieve a better security of supply for medicinal products in the internal market and to contribute thereby to a high level of public health protection, it is appropriate to approximate the rules on monitoring and reporting of actual or potential shortages of medicinal products, including the procedures and the respective roles and obligations of concerned entities in this Regulation. It is important to ensure continued supply of medicinal products, which is often taken for granted across Europe. This is especially true for the most critical medicinal products which are essential to ensure the continuity of care, the provision of quality healthcare and guarantee a high level of public health protection in Europe. Member States should be able to introduce or maintain more robust measures to achieve security of supply for medicines than the safeguards provided for in this Regulation.

Added:Recital 57 a (new): (57a) Given the underserved needs in the area of mental health, the revision should contribute to increased access to treatments, and the development of novel treatments, for patients who need them most.

Removed:Recital 141: (141) To ensure the enforcement of certain obligations relating to the marketing authorisation for medicinal products for human use granted in accordance with this Regulation, the Commission should be able to impose financial penalties. When assessing the responsibility for failures to comply with those obligations and imposing such penalties, it is important that means exist to address the fact that marketing authorisation holders could be part of a wider economic entity. Otherwise, there is a clear and identifiable risk that the responsibility for a failure to comply with those obligations could be evaded, which might have an impact on the ability to impose effective, proportional and dissuasive penalties. The penalties imposed should be effective, proportionate and dissuasive, taking into consideration the economic power of the operator and having regard to the circumstances of the specific case. For the purposes of ensuring legal certainty in the conduct of the infringement procedure, it is necessary to set maximum amounts for penalties. Those maximum amounts should not be linked to the turnover of a particular medicinal product but the economic entity involved.

Added:Recital 57 b (new): (57b) The Commission should support the use of early access pilot programmes to treat patients with complex comorbidities, including physical and mental health conditions who are often excluded from clinical trials. Allowing this would support evidence gathering on the safety and efficacy of these treatments. Such programmes should provide treatment experience for healthcare providers and generate valuable real-world data to inform future authorisations of these treatments.

Removed:Article 2 – paragraph 2 – point 4: (4) ‘orphan medicinal products sponsor’ means any legal or natural person, established in the Union, who submitted an application for or has been granted an orphan designation by a decision referred to in Article 64(4);

Added:Recital 58: (58) There is the possibility under certain duly justified circumstances for marketing authorisations to be granted, subject to specific obligations or conditions, on a conditional basis or under exceptional circumstances. The legislation should allow under similar circumstances for medicinal products with a standard marketing authorisation for new indications to be authorised on a conditional basis or under exceptional circumstances. The medicinal products authorised on a conditional basis or under exceptional circumstances should in principle satisfy the requirements for a standard marketing authorisation with the exception of the specific derogations or conditions outlined in the relevant conditional or exceptional marketing authorisation and shall be subject to specific review of the fulfilment of the imposed specific conditions or obligations. It is also understood that the grounds for refusal of a marketing authorisation shall apply mutatis mutandis for such cases.

Removed:Article 2 – paragraph 2 – point 7: (7) ‘significant benefit’ means a clinically relevant advantage or a major contribution to patient care of an orphan medicinal product;

Added:Recital 60: (60) Regulatory decision-making on the development, authorisation and supervision of medicinal products may be supported by access and analysis of health data, including real world data, where appropriate, i.e. health data generated outside of clinical studies, and data generated via in silico methods, such as computational modelling and simulation, digital molecular representation and mechanistic modelling, digital twin technology and artificial intelligence (AI). The Agency should be able to use such data, including via the Data Analysis and Real World Interrogation Network (DARWIN) and the European Health Data Space interoperable infrastructure. Through these capabilities the Agency may take advantage of all the potential of supercomputing, artificial intelligence and big data science, including results of studies conducted via in silico methods, to fulfil its mandate, without compromising privacy rights. The Agency should put in place sufficient, effective and specific technical and organisational measures to safeguard the fundamental rights and interests of data subjects in line with Regulations (EU) 2016/6791a and (EU) 2018/17251b of the European Parliament and of the Council. Where necessary the Agency may cooperate with the competent authorities of the Member States towards this objective. / 1a Regulation (EU) 2016/679 of the European Parliament and of the Council of 27 April 2016 on the protection of natural persons with regard to the processing of personal data and …

Removed:Article 2 – paragraph 2 – point 12: deleted

Added:Recital 65: (65) In the preparation of scientific advice and in duly justified cases, the Agency should consult authorities established in other relevant Union legal acts or other public bodies established in the Union, as applicable. These may include experts in clinical trials, medical devices, substances of human origin or any other as required for the provision of the scientific advice in question. In addition to providing scientific advice, the Agency should ensure that scientific guidelines are updated and promote an open and public discussion on latest scientific developments.

Removed:Article 2 – paragraph 2 – point 14 a (new): (14a) ‘supply’ means the total volume of stock of a given medicinal product that is placed on the market by a marketing authorisation holder or a manufacturer;

Added:Recital 67: (67) The Agency, in consultation with the Member States and the Commission, should set the scientific selection criteria for medicinal products that receive pre-authorisation support with priority to be given to public health needs and the most promising developments in therapies. In the case of medicinal products for unmet medical needs, based on the scientific selection criteria set by the Agency, any interested developer can submit preliminary evidence to demonstrate that the medicinal product has the potential to provide a major therapeutic advancement with respect to the identified unmet medical need.

Removed:Article 2 – paragraph 2 – point 14 b (new): (14b) ‘demand’ means the request for a medicinal product by a healthcare professional or patient in response to clinical need; the demand is satisfactorily met when the medicinal product is acquired in appropriate time and in sufficient quantity to allow continuity of provision of the best care to patients;

Added:Recital 68 a (new): (68a) There is still a lack of sufficiently detailed and comparable data at Union level to determine the trends and identify possible risk factors that could lead to the development of further measures to limit the risk from antimicrobial resistance and to monitor the effect of measures already introduced. Therefore it is important to collect data on the sales and use of antimicrobials, and data on antimicrobial resistant organisms found in animals, humans and food. To ensure that the information collected can be used effectively, appropriate rules should be laid down concerning the collection and the exchange of data. The Member States should be responsible for collecting data on the use of antimicrobials under the coordination of the Agency.

Removed:Article 5 – paragraph 2: 2. An applicant shall agree with the Agency the submission date of an application for a marketing authorisation. The applicant shall also inform the Agency of its intention of applying for a marketing authorisation under Article 18 or 19.

Added:Recital 76: (76) It is considered appropriate to also have the possibility for the Commission to grant temporary emergency marketing authorisations, to address public health emergencies. Temporary emergency marketing authorisations may be granted provided that, having regard to the circumstances of the public health emergency, the benefit of the immediate availability on the market of the medicinal product concerned outweighs the risk inherent to the fact that additional comprehensive quality, non-clinical, clinical data may still be required. A temporary emergency marketing authorisation should be valid only during the public health emergency. The Commission should be given the possibility to vary, suspend or revoke such marketing authorisations in order to protect public health or when the marketing authorisation holder has not complied with the conditions and obligations set out in the temporary emergency marketing authorisation or when a standard or conditional marketing authorisation has been granted for the relevant indication.

Removed:Article 6 – paragraph 2 – subparagraph 1: For medicinal products, during a public health emergency, that are likely to offer an exceptional therapeutic advancement in the diagnosis, prevention or treatment of a life-threatening condition in the Union, the Agency may, after the Commission has recognised a public health emergency at Union level in accordance with Article 23(1) of Regulation (EU) 2022/2371 and following the advice of the Committee for Medicinal Products for Human Use regarding the maturity of the data related to the development, offer to the applicant a phased review of complete data packages for individual modules of particulars and documentation as referred to in paragraph 1.

Added:Recital 76 a (new): (76a) It is appropriate to have in place transparency measures and standards regarding the Agency’s regulatory activities in relation to medicinal products, in particular those that receive a temporary emergency marketing authorisation. Those measures should include the timely publication of all relevant information on approved medicinal products and medical devices and of clinical data, including clinical trial protocols. The public information regarding clinical trials and marketing authorisation decisions should be in accordance with Regulation (EU) 2022/123 of the European Parliament and of the Council1a. / 1a Regulation (EU) 2022/123 of the European Parliament and of the Council of 25 January 2022 on a reinforced role for the European Medicines Agency in crisis preparedness and management for medicinal products and medical devices (OJ L 20, 31.1.2022, p. 1).

Removed:Article 6 – paragraph 2 – subparagraph 2: The Agency may at any stage suspend or cancel the phased review, where the Committee for Medicinal Products for Human Use considers that the submitted data are not of sufficient maturity or where it is considered that the medicinal product no longer fulfils an exceptional therapeutic advancement or where the Commission terminates the recognition of a public health emergency in accordance with Article 23(2) of Regulation (EU) 2022/2371. The Agency shall inform the applicant accordingly.

Added:Recital 77: (77) The development of antimicrobial resistance is a growing concern and the pipeline of effective antimicrobials is obstructed due to a market failure whereby antimicrobial research and development (R&;amp;D) is hampered by the low commercial value of the antimicrobial medicinal product market. It is therefore necessary to maintain the efficacy of existing antimicrobials for as long as possible and to consider a number of new measures to promote the development of priority antimicrobials that are effective against antimicrobial resistance and to support undertakings, often SMEs, and not-for-profit entities which choose to invest in this area. It is equally necessary to support research and development of novel antimicrobials through the different phases of antimicrobial development, in particular through market entry rewards and milestone reward payments. Additionally, the establishment of subscription models which delink the volume of antimicrobial sales from the reward received, in particular through voluntary joint procurement, can help overcome such market failures. Such measures should facilitate the development of alternative treatments, such as bacteriophages, which are effective against multi-drug resistant bacteria and can be used as an alternative treatment or together with antibiotics. However, addressing anti-microbial resistance will not be possible by relying on R&D alone. To ensure prudent use of existing antibiotics, the Authority should also support the dev…

Removed:Article 6 – paragraph 5 – subparagraph 2: The marketing authorisation applicant shall not carry out animal tests in case scientifically satisfactory non-animal testing methods are available. Where scientifically satisfactory non-animal testing methods are not available, applicants that use animal testing shall ensure that the principle of replacement, reduction and refinement of animal testing for scientific purposes has been applied in compliance with Directive 2010/63/EU with regard to any animal study conducted for the purpose of supporting the application.

Added:Recital 77 a (new): (77a) Reluctance to invest in the development of antimicrobials exists in part because the development of antimicrobials is costly and many developers, often SMEs, cannot afford to proceed to the next stage of development. Additionally, when an antimicrobial is developed, the market is naturally limited by virtue of the need to use antimicrobials prudently. Therefore, it is necessary to consider further Union level action to support the development of antimicrobials and address existing market failures. Accordingly, a milestone payment reward scheme, complemented by a subscription model voluntary joint procurement scheme, should be developed to ensure that a market exists for developers that delink volumes sold from payment received.

Removed:Article 8 – paragraph 1 – point b: (b) identification and characterisation of hazards for the environment, animals and for human health; for the purpose of this point, ‘hazards for human health’ includes the risks to the health of human beings other than the treated patient as the risk to the treated patient shall be assessed as part of the benefit-risk assessment of the medicinal product;

Added:Recital 77 b (new): (77b) Milestone payments are an early-stage financial reward granted upon achieving certain R&D objectives prior to market approval, for example successful completion of phase I. While such mechanisms would serve primarily to provide access to existing antimicrobials, they could also support new antimicrobials in the development phase. A subscription model consists of a series of financial payments to an antibiotic developer for successfully obtaining regulatory approval for an antibiotic that meets specific pre-defined criteria. A subscription model scheme through voluntary joint procurement agreements should alleviate concerns for developers by ensuring there is a market for the antimicrobial when developed.

Removed:Article 9 – paragraph 2: 2. In case of first-in-class medicinal products or when a novel question is raised during the assessment of the submitted environmental risk assessment, the Committee for Medicinal Products for Human Use, or the rapporteur, shall carry out necessary consultations with bodies Member States have set up in accordance with Directive 2001/18/EC. They shall also consult with relevant Union bodies, inter alia the European Environment Agency. Details on the consultation procedure shall be published by the Agency at the latest by [OJ:12 months after the date of entry into force of this Regulation].

Added:Recital 78 a (new): (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 Council1a. 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. / 1a Regulation (…

Removed:Article 10 – paragraph 2: 2. Where within 90 days of the validation of the marketing authorisation application and during the assessment the Committee for Medicinal Products for Human Use considers that the submitted data are not of sufficient quality or maturity to complete the assessment, the assessment can be terminated. The Committee for Medicinal Products for Human Use shall summarise the deficiencies in writing. On this basis, the Agency shall inform the applicant accordingly and set a reasonable time limit to address the deficiencies. The application shall be suspended until the applicant addresses the deficiencies. If the applicant fails to address those deficiencies within the time limit set by the Agency, the application shall be considered as refused.

Added:Recital 78 b (new): (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.

Removed:Article 12 – paragraph 4 – point f: (f) where appropriate, details of any recommended obligation to conduct post-authorisation safety studies or to comply with obligations on the recording or reporting of suspected adverse reactions which are stricter than those referred to in Chapter VIII as well as possible penalties in case of non-compliance;

Added:Recital 78 c (new): (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 Council1a. / 1a Directive 2014/24/EU of the European Parliament and of the Council of 26 February 2014 on public procurement and repealing Directive 2004/18/EC (OJ L 94, 28.3.2014, p. 65).

Added:Recital 79: (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 period 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.

Added:Recital 80: (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].

Added:Recital 81: (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].

Added:Recital 82: (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.

Added:Recital 83: (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.

Added:Recital 86: (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.

Added:Recital 88: (88) Regulation (EC) No 141/2000 of the European Parliament and of the Council55 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.

Added:Recital 90: (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.

Added:Recital 92: deleted

Added:Recital 92 a (new): (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.

Added:Recital 93: (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, should 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.