Changes from plenary report to adopted text

Added(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 Council should not be a prerequisite. Nevertheless, in these cases, Member States should implement appropriate measures in line with the precautionary principle to minimise foreseeable negative environmental impacts resulting from the intended or unintended release of the medicinal products containing or consisting of GMOs into the environment and agree on an appropriate timeline for the delivery of the environmental risk data. [Am. 36]

RemovedRecital 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, while allowing Member States to adopt or maintain legislation ensuring a higher degree of protection against shortages of medicinal products. 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. To combat certain shortages, medicinal products prepared for individual patients in a pharmacy according to a medical prescription ‘magistral formula’, or according to the pharmacopoeia and intended to be supplied directly to patients served by the pharmacy ‘officinal formula’, should be able to be used.

Added(55) For medicinal products, the period for protection of data relating to non-clinical tests and clinical trials should be the same as that provided for in [revised Directive 2001/83/EC].

RemovedRecital 138: (138) The national competent authorities should be empowered to monitor shortages of medicinal products that are authorised through both national and centralised procedures, based on notifications of marketing authorisation holders. The Agency should be empowered to monitor shortages of medicinal products that are authorised through the centralised procedure, also based on notifications of marketing authorisation holders. Information on such shortages should be made available on the European medicines web-portal provided for in this Regulation. When critical shortages are identified, both national competent authorities and the Agency should work in a coordinated manner to communicate the necessary information to patients, consumers and healthcare professionals, including on the estimated duration of the shortage and available alternatives, and manage those critical shortages, whether the medicinal product concerned by the critical shortage is covered by a centralised marketing authorisation or a national marketing authorisation. Marketing authorisation holders and other relevant entities, importers, manufacturers and suppliers, must provide the relevant information to inform the monitoring. Wholesale distributors and other persons or legal entities, including patient organisations or health care professionals and consumers and other persons or legal entities that are authorised or entitled to supply medicinal products to the public, may also report a shortage of a given medic…

Added(56) In order to meet, in particular, the legitimate expectations of patients and to take account of the increasingly rapid progress of science and therapies, accelerated assessment procedures should be set up, reserved for medicinal products of major therapeutic interest, and procedures for obtaining conditional marketing authorisations subject to certain regularly reviewable conditions.

RemovedRecital 138 a (new): (138a) Wholesalers are usually a key supply link between marketing authorisation holders and the users of medicinal products, and in those cases, in order to estimate demand, the quantity requested in wholesale orders should be considered.

Added(57) Compassionate use programmes allow for an early access to medicinal products. Existing provisions should be reinforced to ensure that a common approach is followed, whenever possible, regarding the criteria and conditions for the compassionate use of new medicinal products under Member States' legislation. Moreover, it is important to allow for data on such uses to be collected to inform decisions regarding the benefit-risk balance of the medicinal products concerned.

RemovedRecital 138 b (new): (138b) It is necessary to avoid that measures planned or taken in one Member State to prevent or mitigate a shortage at national level when responding to the legitimate needs of its citizens increase the risk of shortages in another Member State.

Added(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. [Am. 37]

RemovedRecital 139 a (new): (139a) Public procurement procedures can be an effective tool for tackling shortages of medicinal products. At Member State level, invitations to tender based solely on price and where there is only one bidder increase the risk of shortages of medicinal products and of reducing the number of suppliers on the market. At Union level, joint procurement should be recognised as a tool to tackle critical shortages, in particular during a health crisis, as demonstrated by the COVID-19 pandemic.

Added(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. [Am. 38]

RemovedRecital 140: (140) It is recognised that improved access to information contributes to public awareness and increases public trust, gives the public the opportunity to express its observations and enables authorities to take due account of those observations. The general public should therefore have access to information in the Union Register of medicinal products, the Eudravigilance database and the manufacturing and wholesale distribution database, after the deletion of any commercially confidential information by the competent authority, unless there is an overriding public interest in disclosure, in accordance with Regulation (EC) No 1049/2001 of the European Parliament and of the Council57. Regulation (EC) No 1049/2001 gives the fullest possible effect to the right of public access to documents and lays down the general principles and limits on such access. The Agency should therefore give the widest possible access to the documents while carefully balancing the right for information with existing data protection requirements. Certain public and private interests, such as personal data and commercially confidential information, should be protected by way of exception in accordance with Regulation (EC) No 1049/2001.

Added(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. [Am. 39]

RemovedRecital 149: (149) It is therefore appropriate to envisage a centralised assessment of the ERA involving experts from the national competent authorities and the ad hoc Environmental Risk Assessment working party.

Added(59) In principle, only one marketing authorisation may be granted to an applicant for a medicinal product. Duplicate marketing authorisations should only be granted in exceptional circumstances. When those exceptional circumstances are no longer present, notably as regards the protection by a patent or a supplementary protection certificate in one or more Member States, any potentially negative effects on markets from the existence of duplicate marketing authorisations should be minimised through a withdrawal of the initial or the duplicate marketing authorisation.

RemovedRecital 155: (155) This Regulation respects the fundamental rights and observes the principles recognised in particular by the Charter of Fundamental Rights of the European Union and notably human dignity, the integrity of the person, the rights of the child, respect for private and family life, the protection of personal data and the freedom of art and science. Similarly, this Regulation aims to ensure a high level of protection of the environment in accordance with Article 192(1) TFEU.

Added(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) 2016/679 and (EU) 2018/1725 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. [Am. 40]

RemovedArticle 1 – paragraph 1: This Regulation lays down Union procedures for the authorisation, supervision and pharmacovigilance of medicinal products for human use at Union level, establishes rules and procedures at Union and at Member State level relating to the monitoring and management of shortages and critical shortages and the security of supply of medicinal products and lays down the governance provisions of the European Medicines Agency (‘the Agency’) established by Regulation (EC) No 726/2004 which shall carry out the tasks relating to medicinal products for human use that are laid down in this Regulation, Regulation (EU) No 2019/6 and other relevant Union legal acts.

Added(61) The handling of health data requires a high level of protection against cyber attacks. It is necessary for the Agency to be equipped with a high level of security controls and processes against cyber attacks to ensure that the Agency operates normally at all times. To that end, the Agency should establish a plan to prevent, detect, mitigate and respond to cyber attacks so that its operations are secure at all times, while preventing any illegal access to documentation held by the Agency.

RemovedArticle 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 if such an advantage or contribution benefits a relevant part of the target population;

Added(62) Due to the sensitive nature of health data, the Agency should safeguard its processing operations and ensure that they respect the data protection principles of lawfulness, fairness and transparency, purpose limitation, data minimisation, accuracy, storage limitation, integrity and confidentiality. Where the processing of personal data is necessary for the purposes of this Regulation, such processing should be done in accordance with Union law on the protection of personal data. Any processing of personal data under this Regulation should take place in accordance with Regulation (EU) 2016/679 and Regulation (EU) 2018/1725 of the European Parliament and of the Council.

RemovedArticle 2 – paragraph 2 – point 8 – point a: (a) greater efficacy than an authorised medicinal orphan medicinal product in a relevant part of the target population;

Added(63) Access to individual patient data from clinical studies in structured format allowing for statistical analyses is valuable to assist regulators in understanding the submitted evidence and to inform regulatory decision-making on the benefit-risk balance of a medicinal product. The introduction of such possibility in the legislation is important to foster data-driven benefit-risk assessments at all stages of the life cycle of a medicinal product. This Regulation therefore empowers the Agency to request such data as part of the assessment of initial and post-authorisation applications.

RemovedArticle 2 – paragraph 2 – point 8 – point b: (b) greater safety than an authorised medicinal product in a relevant part of the target population;

Added(64) For generic and biosimilar medicinal products, as a general rule, risk management plans should not be developed and submitted, also considering that the reference medicinal product has such a plan; however, in specific cases, a risk management plan for generic and biosimilar medicinal products should be developed and submitted to the competent authorities.

RemovedArticle 2 – paragraph 2 – point 10: (10) ‘regulatory sandbox’ means a regulatory framework during which it is possible to develop, validate and test in a controlled environment innovative or adapted regulatory solutions that facilitate the development and authorisation of innovative products which are likely to fall in the scope of this Regulation but for which there is an absence of existing adapted rules for development and authorisation, pursuant to a specific plan and for a limited time under regulatory supervision.

Added(65) In the preparation of scientific advice and in duly justified cases, the Agency should also be able to 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. [Am. 41]

RemovedArticle 2 – paragraph 2 – point 12: (12) ‘shortage’ means a situation in which the supply of a medicinal product that is authorised and placed on the market in a Member State does not meet the demand for that medicinal product in that Member State whatever the cause.

Added(66) Through the Priority Medicines (PRIME) scheme, the Agency has gained experience of the provision of early scientific and regulatory support to developers of certain medicinal products that, based on preliminary evidence, are likely to address an unmet medical need and are considered promising at an early stage of development. It is appropriate to recognise this early support mechanism, including for priority antimicrobials and repurposed medicinal products when they fulfil the criteria for the scheme, and allow the Agency, in consultation with the Member States and the Commission, to establish selection criteria for promising medicinal products.

RemovedArticle 2 – paragraph 2 – point 14 a (new): (14a) ‘demand’ means the request for a medicinal product by healthcare professionals or patients in response to a 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(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. [Am. 42]

RemovedArticle 2 – paragraph 2 – point 14 b (new): (14b) ‘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(68) Before a medicinal product for human use is authorised for placing on the market of one or more Member States, it generally has to undergo extensive studies to ensure that it is safe, of high quality and effective for use in the target population. However, in the case of certain categories of medicinal products for human use, in order to meet unmet medical needs of patients and in the interest of public health, it may be necessary to grant marketing authorisation on the basis of less complete data than is normally the case. Such marketing authorisation should be granted subject to specific obligations. The categories of medicinal products for human use concerned should be the medicinal products, including orphan medicinal products, that aim at the treatment, prevention or medical diagnosis of seriously debilitating or life-threatening diseases, or that are intended to be used in emergency situations in response to public health threats.

RemovedArticle 5 – paragraph 5: 5. Within 20 days of receipt of an application, the Agency shall check whether all the information and documentation required in accordance with Article 6 have been submitted, that the application does not contain critical deficiencies as defined in the guidelines drawn up pursuant to paragraph 7 of this Article that may prevent the evaluation of the medicinal product and decide whether the application is valid.

Added(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. [Am. 43]

RemovedArticle 6 – paragraph 1 – subparagraph 2: The documentation shall include a declaration to the effect that clinical trials carried out outside the Union meet the ethical requirements of Regulation (EU) No 536/2014. Those particulars and documentation shall take account of the unique, Union nature of the authorisation requested and, otherwise than in exceptional cases relating to the application of the law on trademarks pursuant to Regulation (EU) 2017/1001 of the European Parliament and of the Council66 , shall include the use of a single name for the medicinal product. The use of a single name does not exclude: / (a) the use of additional qualifiers where necessary to identify different presentations of the medicinal product concerned; and / (b) the use of identified versions of the summary of product characteristics as referred to in Article 62 of [revised Directive 2001/83] in situations where elements of the product information are still covered by patent law or supplementary protection certificates for medicinal products.

Added(69) The Union should have the means to carry out a scientific assessment of the medicinal products presented in accordance with the decentralised marketing authorisation procedures. Moreover, with a view to ensuring the effective harmonisation of administrative decisions taken by Member States with regard to medicinal products presented in accordance with decentralised marketing authorisation procedures, it is necessary to endow the Union with the means to resolve disagreements between Member States concerning the quality, safety and efficacy of medicinal products.

RemovedArticle 6 – paragraph 2 – subparagraph 1: For medicinal products that are likely to offer an exceptional therapeutic advancement in the diagnosis, prevention or treatment of a life-threatening, seriously debilitating or serious and chronic condition or that are expected to be of major interest from the point of view of public health or intended for conditions with no authorised alternatives in the Union, the Agency may, 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(70) In the event of a risk to public health, the marketing authorisation holder or the competent authorities should be able to make urgent safety or efficacy restrictions on their own initiative to ensure a swift adaption of the marketing authorisation to maintain the safe and efficacious use of the medicinal product by healthcare professionals and patients. If a review is launched on the same safety or efficacy concern addressed by urgent restrictions initiated by a competent authority, any written observations by the marketing authorisation holder should be considered in that review to avoid duplication of assessment.

RemovedArticle 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. The Agency shall in its annual report highlight key observations and best practices in the replacement, reduction and refinement of animal testing submitted by applicants.

Added(71) The terms of a marketing authorisation for a medicinal product for human use may be varied. While the core elements of a variation are laid down in this Regulation, the Commission should be empowered to complement these elements by laying down further necessary elements, to adapt the system to technical and scientific progress, and to employ digitalisation measures to ensure that unnecessary administrative burden is avoided for marketing authorisation holders and competent authorities.

RemovedArticle 7 – paragraph 1: 1. Without prejudice to Article 22 of [revised Directive 2001/83/EC], the marketing authorisation application of a medicinal product for human use containing or consisting of genetically modified organisms as defined in Article 2(2) of Directive 2001/18/EC shall be accompanied by an environmental risk assessment identifying and evaluating potential adverse effects of the genetically modified organisms on human and animal health, and the environment.

Added(72) To avoid unnecessary administrative and financial burden both for the pharmaceutical industry and the competent authorities, certain streamlining measures should be introduced. Electronic applications for marketing authorisations and for variations to the terms of the marketing authorisation should be made possible.

RemovedArticle 8 – paragraph 1 – point b: (b) identification and characterisation of hazards for the environment, animals and for human health throughout the lifecycle of the medicinal product, including manufacturing; for the purpose of this point, ‘hazards for human health’ include 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(73) To optimise the use of resources for both applicants for marketing authorisations and competent authorities assessing such applications, a single assessment of an active substance master file should be introduced. The outcome of the assessment should be issued through a certificate. To avoid duplication of assessment, the use of an active substance master file certificate should be mandatory for subsequent applications or marketing authorisations for medicinal products for human use containing that active substance from an active substance master file certification holder. The Commission should be empowered to establish the procedure for the single assessment of an active substance master file. To further optimise the use of resources, the Commission should be empowered to extend the certification scheme to additional quality master files, e.g. in case of novel excipients, adjuvants, radiopharmaceutical precursors and active substance intermediates, when the intermediate is a chemical active substance by itself or used in conjugation with a biological substance.

RemovedArticle 8 – paragraph 1 – point e: (e) risk minimisation and mitigation strategies proposed to address identified risks including specific containment measures to limit contact with the medicinal product.

Added(74) To avoid unnecessary administrative and financial burdens for applicants, marketing authorisation holders and competent authorities, certain streamlining measures should be introduced. Electronic application for marketing authorisation and for variations to the terms of the marketing authorisation should be introduced. For generic and biosimilar medicinal products, except in specific cases, risk management plans do not need to be developed and submitted to the competent authorities.

RemovedArticle 9 – paragraph 1 – subparagraph 2: The Committee for Medicinal Products for Human Use shall assess the environmental risk assessment, and where necessary consult the ad-hoc Environmental Risk Assessment working party referred to in Article 150.

Added(75) In a situation of public health emergency, it is of major interest for the Union that safe and efficacious medicinal products can be developed and made available within the Union as soon as possible. Agile, fast and streamlined processes are of the essence. A range of measures already exists at Union level to facilitate, support and speed up the development of and granting marketing authorisations for treatments and vaccines during a public health emergency.

RemovedArticle 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. 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(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. [Am. 44]

RemovedArticle 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 withdrawn by default.

Added(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 Council. [Am. 45]

RemovedArticle 12 – paragraph 4 – point g: (g) where appropriate, details of any recommended obligation to conduct post-authorisation efficacy studies where concerns relating to some aspects of the efficacy of the medicinal product are identified and can be resolved only after the medicinal product has been marketed. Such an obligation to conduct such studies 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] and the consultation process in accordance with Article 162 of this Regulation;

Added(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&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 development and procurement of rapid diagnostic tools to ensure appropriate prescriptions. [Am. 46]

RemovedArticle 12 – paragraph 4 – point h: (h) where appropriate, details of any recommended obligation to conduct any other post-authorisation studies, including post-authorisation treatment optimisation studies, to improve the safe and effective use of the medicinal product;

Added(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. [Am. 47]

RemovedArticle 12 – paragraph 4 – point i: (i) in case of medicinal products for which there is a detailed justification submitted to the Agency as to the grounds of uncertainty as to the surrogate endpoint relation to the expected health outcome, where appropriate and relevant for the benefit-risk balance, with specific attention given to new active substances and therapeutic indications, a post-authorisation obligation to substantiate the clinical benefit:

Added(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. [Am. 48]

RemovedArticle 12 – paragraph 4 – point j a (new): (ja) where appropriate, any justified reasoning for granting marketing authorisation pursuant to Article 18, 19 and 30 of this Regulation;