Changes from report parliamentary committee draft to plenary report

AddedRecital 5: (5) The COVID-19 pandemic further underlined critical issues, which require a reform of the Union pharmaceuticals framework to strengthen its resilience, while improving the availability of medicinal products and to ensure that it corresponds to public health needs and serves the people under all circumstances.

AddedRecital 5 a (new): (5a) The COVID-19 pandemic also highlighted disparities in terms of, the capacity of health systems, national immunisation infrastructure, shortages and preparation. In addition to the measures in this Regulation, Member States should strengthen their national immunisation programmes, ensuring their population is better sufficiently protected against infectious diseases and strengthening pandemic preparedness and response.

AddedRecital 6: (6) It is therefore necessary to replace Regulation (EC) No 726/2004 of the European Parliament and of the Council38 with a new Regulation.

RemovedRecital 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 due justification for such prohibition to the Agency.

AddedRecital 18 a (new): (18a) The Agency should set transparent criteria for the appointment of patients’ and healthcare professionals’ representatives to the Committee for Medicinal Products for Human Use and the Pharmacovigilance Risk Assessment Committee in order to ensure there is a well-balanced representation of medical specialties and diseases amongst appointed members and alternates, and there are robust rules on the prevention of conflicts of interests. Declaration of direct or indirect financial or other interests in the pharmaceutical or other medical industry which could affect the impartiality of appointed stakeholders should be an integral part of the selection process and subsequently should be made publicly available.

RemovedRecital 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. 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 to fulfil its mandate, without compromising privacy rights. In this regard, the Agency should also engage in a systematic early and continuous dialogue on the collection of real-world-data with the Member State Coordination Group on Health Technology Assessment in accordance with Regulation (EU) 2021/2282, payers, healthcare professionals, patient and consumer organisations and developers. Where necessary the Agency may cooperate with the competent authorities of the Member States towards this objective.

AddedRecital 19: (19) Scientific advice for future applicants seeking a marketing authorisation should be provided more generally and in greater depth and should be adapted to the specificities of the medicinal product concerned. Similarly, structures allowing the development of advice for companies, in particular small and medium-sized enterprises (‘SMEs’) and not-for-profit entities, should be put in place. The Agency should also promote open and public exchanges about latest scientific developments and updates of scientific guidelines.

RemovedRecital 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 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. Information on the advice given in relation to the enhanced scientific and regulatory support for priority medicinal products should be included in a dedicated specific section within the European public assessment report.

AddedRecital 20: (20) Promising medicinal products and certain combinations products of medicinal products and medical devices, as well as medicinal products in exclusive use with medical devices that have the potential to significantly address patients’ unmet medical needs should benefit from early and enhanced scientific support, including through supporting patient-relevant in vitro and in silico technologies which are key to the development of those products. Such support will ultimately help patients benefit from new therapies as early as possible.

RemovedRecital 68: (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 a conditional 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.

AddedRecital 20 a (new): (20a) Next to unmet medical needs already recognised in the pediatric, antimicrobial, oncological, rare, and neurodegenerative diseases, attention should also be given to unmet medical needs in the mental health sphere and treatments therein.

RemovedRecital 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 the marketing authorisation holder has been granted a standard or conditional marketing authorisation for the relevant indication.

AddedRecital 21 a (new): (21a) Based on the European Ombudsman’s decision in its strategic inquiry OI/7/2017/KR of 17 July 2019 on how the European Medicines Agency engages with medicine developers in the period leading up to applications for authorisations to market new medicines in the Union, the Agency should enhance the transparency of scientific advice. In addition, staff and experts from national competent authorities providing scientific advice should, to the extent possible, not be involved in a subsequent evaluation of a marketing authorisation application for the same products. However, in duly justified cases, such as where the indication of a medicinal product concerns a rare disease, that expert should be able to carry out a subsequent evaluation of the same product, provided that that is duly documented.

RemovedRecital 76 a (new): (76a) It is imperative to have in place robust transparency measures and standards regarding the Agency’s regulatory activities in relation to medicinal products 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).

AddedRecital 25: (25) In certain cases, shortcomings in Member States’ system of supervision and related enforcement activities could risk to substantially hinder the achievement of the objectives of this Regulation and those of revised Directive 2001/83/EC which could even lead to the emergence of risks to public health or to the environment. To address these challenges, harmonised inspection standards should be ensured through the establishment of a joint audit programme within the Agency. This joint audit programme will also further harmonise the interpretation of good manufacturing and distribution practices on the basis of Union legislative requirements. Moreover, it will support further mutual recognition of inspection outcomes between Member States and with strategic partners. Within the joint audit programme, the competent authorities are subject to regular audits conducted by other Member States to maintain an equivalent and harmonised quality system and to ensure an appropriate implementation of relevant good manufacturing and distribution practices into national laws and equivalence with other EEA inspectorates.

RemovedRecital 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 pharmaceutical companies neglect investment in research and development (R&D) concerning novel antibiotics due to profitability considerations; it is therefore necessary to consider new measures to promote the development of priority antimicrobials that are effective against antimicrobial resistance and to support undertakings, often SMEs, which choose to invest in this area.

AddedRecital 26 a (new): (26a) Pharmaceutical research plays a decisive role in the continuing improvement in public health and in ensuring the Union’s competitiveness. Medicinal products, in particular those that are the result of long, costly research will not continue to be developed in the Union unless they are covered by favourable rules that provide for sufficient protection to encourage such research. However, it is difficult to establish a direct link between these favourable rules and Union competitiveness. Such rules, while making Union markets more attractive, are agnostic to the medicines’ geographical origin and authorised medicines from third countries are equally eligible to receive Union incentives, just as Union-based innovative companies can equally benefit from incentives in third countries.

RemovedRecital 78 a (new): (78a) 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 a stark misalignment between the R&D priorities of the pharmaceutical industry and the public health needs of Union citizens. The market failures in the Union have, in certain instances, also resulted in excessive prices for medicinal products and have led to shortages of medicinal products. This Regulation should therefore address those market failures to better deliver on the objectives of affordability, accessibility and availability of medicinal products in the Union.

AddedRecital 29: (29) Legal entities that are not engaged in an economic activity such as universities, public bodies, research centres or not-for-profit organisations, represent an important source of research in unmet medical needs, of research in different subpopulations, repurposing and optimisation and of innovation and should also benefit from this support scheme. Whereas it should be possible to take account of the particular situation of these entities on an individual basis, such support can best be achieved by means of a dedicated support scheme, including administrative support and through the reduction, deferral and waiver of fees.

RemovedRecital 78 b (new): (78b) Member States, the Union, third countries, international organisations and agencies have identified the key areas of priority pharmaceutical research, including novel antibiotics and antivirals, improved diagnostics and treatments for emerging infectious diseases, affordable and efficacious medicinal products in the areas oncology, neurodegenerative diseases and other areas of unmet medical need for which the development of orphan medicinal products is needed. However, while Member States and the Union offer generous corporate R&D subsidies as well as R&D tax incentives to stimulate pharmaceutical research, there is little evidence to suggest, and no obligation to ensure, that the composition of R&D portfolios of pharmaceutical companies is determined by such direct or indirect subsidies. It is therefore increasingly evident that effective public health policy is undermined by shortcomings in transparency and accountability in public expenditure directed towards health.

AddedRecital 30: (30) The Agency should be empowered to give scientific recommendations on whether a product under development, which could potentially fall under the mandatory scope of the centralised procedure, meets the scientific criteria to be a medicinal product. Such an advisory mechanism would address, as early as possible, questions related to borderline cases with other areas such as in particular substances of human origin, cosmetics or medical devices, which may arise as science develops. To ensure that recommendations given by the Agency take into account the views of equivalent advisory mechanisms in other legal frameworks, the Agency should consult the relevant advisory or regulatory bodies. Where there is a doubt about whether the regulatory status of a particular product under development, which could potentially fall under the mandatory scope of the centralised procedure, meets the scientific criteria to be a medicinal product, the Agency and the relevant advisory bodies responsible for other regulatory frameworks, namely medical devices and substances of human origin should engage in consultations. In such cases, the compendium referred to in Regulation (EU) 2024 /... of the European Parliament and of the Council1a[SoHO Regulation] should be consulted, where relevant. If after consulting the compendium, there remains doubt about the regulatory status the relevant bodies should further consult to determine the regulatory status. The Commission should facilitate the cooperati…

RemovedRecital 78 c (new): (78c) Those market failures highlight the need for a paradigm shift in both the Member States’ and the Union’s approach to generating pharmaceutical R&D in key areas of priority and in public expenditure directed towards health. The establishment of a mission oriented R&D facility at Union level which acts in the public interest could alleviate those market failures. The European Medicines Facility (‘EMF’) should therefore be established as an independent agency under this Regulation. The EMF should be tasked with conducting research and developing novel antimicrobials as well as with regard to other areas of unmet medical need, to support the Union to overcome market failures.

AddedRecital 31: (31) To increase transparency of scientific assessments and all other activities, a user-friendly European medicines web-portal should be created and maintained by the Agency. The portal should provide information for all centrally authorised medicinal products, inter alia on safety, efficacy, environmental risk, patient populations, and where relevant information on antimicrobial resistance, shortages, and pending obligations for marketing authorisation holders. Sufficient budgetary resources should be allocated to the Agency to ensure its transparency obligations and commitments are appropriately implemented.

RemovedRecital 79: deleted

AddedRecital 31 a (new): (31a) The Union Register of medicinal products lists all medicinal products for human and veterinary use as well as orphan medicinal products that have received a marketing authorisation by the Commission through the centralised procedure. The information provided in the Union Register can be used to search for pertinent information on the medicinal product in question, including the active substance, the international non-proprietary name, the anatomical therapeutic chemical (ATC), the indications of the medicinal product, information on the authorisation and any post-authorisation requirements as well as applicable regulatory protection periods.

RemovedRecital 80: deleted

AddedRecital 33 a (new): (33a) To ensure the adequate expertise and evaluation of the environmental risk assessments of pharmaceutical substances, the Agency should establish a new ad hoc Environmental Risk Assessment working party. That working party should be involved where necessary depending on the application for a marketing authorisation. The working party should have the scientific knowledge necessary to characterise and assess the risks, and the mitigation measures for such risks, related to the manufacture, use and disposal of medicinal products. The working party should contribute towards the implementation of the One Health Approach and closing the gap between pharmaceutical and environmental assessment.

RemovedRecital 81: deleted

AddedRecital 35: (35) The Agency’s scientific committees should be supported, in relation to their evaluation duties, by working parties which should be open to experts from the scientific world and appointed for this purpose whilst retaining complete responsibility for the scientific opinions issued by them.

RemovedRecital 82: deleted

AddedRecital 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…

RemovedRecital 83: deleted

AddedRecital 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…

RemovedRecital 84: deleted

AddedRecital 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.

RemovedRecital 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.

AddedRecital 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.

RemovedRecital 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.

AddedRecital 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.

RemovedRecital 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.

AddedRecital 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…

RemovedRecital 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.

AddedRecital 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.

RemovedRecital 133: deleted

AddedRecital 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.

RemovedRecital 134: deleted

AddedRecital 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).

RemovedRecital 135: deleted

AddedRecital 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…

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. 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.

AddedRecital 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.

RemovedRecital 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.

AddedRecital 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.

RemovedArticle 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);

AddedRecital 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.

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;

AddedRecital 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 …

RemovedArticle 2 – paragraph 2 – point 12: deleted

AddedRecital 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.

RemovedArticle 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;

AddedRecital 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.

RemovedArticle 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;

AddedRecital 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.

RemovedArticle 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.

AddedRecital 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.

RemovedArticle 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.

AddedRecital 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).

RemovedArticle 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.

AddedRecital 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…

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. 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.

AddedRecital 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.

RemovedArticle 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;

AddedRecital 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.

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, 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].

AddedRecital 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 (…

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 refused.

AddedRecital 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.

RemovedArticle 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;

AddedRecital 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).

AddedRecital 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.

AddedRecital 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].

AddedRecital 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].

AddedRecital 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.

AddedRecital 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.

AddedRecital 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.

AddedRecital 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.

AddedRecital 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.

AddedRecital 92: deleted

AddedRecital 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.

AddedRecital 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.

AddedRecital 95: (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.

AddedRecital 103: deleted

AddedRecital 104: (104) To maximise the potential benefit of clinical research, continued exploration of new indications should be encouraged. To reward research into and development of new therapeutic indications, an additional period of one year of market exclusivity is provided for a new therapeutic indication (with a maximum of two indications).

AddedRecital 105 a (new): (105a) The Agency should refuse the validation of an application for a marketing authorisation referring to data for a reference medicinal product only on the basis of the grounds set out in this Regulation and [revised Directive 2001/83/EC]. The same should apply to any decision to grant, vary, suspend, restrict or revoke the marketing authorisation. The Agency cannot base its decision on any other grounds. In particular, those decisions cannot be based on the patent or supplementary protection certificate status of the reference medicinal product.

AddedRecital 105 b (new): (105b) One of the overarching goals of this Regulation is to help to meet the medical needs of patients with rare diseases, to improve the affordability of orphan medicinal products and patient access to orphan medicinal products across the Union, and to encourage innovation in areas of need. While other Union programmes and policies also contribute to those goals, people living with a rare disease continue to face common challenges that are numerous and multifactorial, including delayed diagnoses, lack of available transformative treatments, and difficulties to access treatments where they live, reflecting the fragmentation of the market across the Member States. The Union added value in addressing the needs of people living with a rare disease being exceptionally high due to the rarity of patients, experts, data, and resources, it is appropriate for the Commission to complement this Regulation by developing a dedicated framework for rare diseases to bridge relevant legislation, policies and programmes, and support national strategies with a view to better meeting the unmet needs of people living with rare diseases and of their carers. That framework should be needs-driven and goals-based, and developed in consultation with the Member States and patient organisations as well as, where relevant, other interested parties.

AddedRecital 112: (112) With a view to ensuring that research is conducted only when safe and ethical and that the requirement for study data in the paediatric population does not block or delay the authorisation of medicinal products for other populations, the Agency may defer, based on scientific, ethical and technical grounds or considerations related to public health, the initiation or completion of some or all of the measures contained in a paediatric investigation plan for a limited period of time. Such deferral should be extended only in duly justified cases.

AddedRecital 126: (126) It is necessary to take measures for the supervision of medicinal products authorised by the Union, and in particular for the intensive supervision of undesirable effects of these medicinal products, and the collection of real-world data within the framework of Union pharmacovigilance activities, so as to ensure the rapid withdrawal from the market of any medicinal product presenting a negative benefit-risk balance under normal conditions of use.

AddedRecital 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 and real-world data, 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 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. In such cases, the Agency should consult with the marketing authorisation applicant or marketing authorisation holder, before undertaking any such update.

AddedRecital 132 a (new): (132a) To better facilitate patient’ access to innovative medicinal products, it is appropriate to establish common rules for the testing and authorisation of innovative medicinal products and innovative technologies related to such products for which, due to their exceptional nature or characteristics, the Union regulatory framework for medicinal products is not expected to be adapted.

AddedRecital 132 b (new): (132b) On duly justified grounds, regulatory sandboxes should be able to be set up when it is not possible to develop the medicinal product or category of medicinal products in compliance with the requirements applicable to medicinal products due to scientific or regulatory challenges arising from characteristics or methods related to the medicinal product, and those characteristics or methods positively and distinctively contribute to the quality, safety or efficacy of the medicinal product or category of medicinal products, or significantly improve patient access to treatment.

AddedRecital 132 c (new): (132c) The objectives of providing for the possibility of establishing regulatory sandboxes under this Regulation are the following: for the Agency and national competent authorities to increase their understanding of technical and scientific developments, to allow developers in a controlled environment to test and develop innovative medicinal products and related technologies for which the current regulatory framework is not adapted, as agreed with the competent authorities, and to identify possible future adaptations of the legal framework for the authorisation of medicinal products in the Union.

AddedRecital 133: (133) Regulatory sandboxes can provide the opportunity for advancing regulation through proactive regulatory learning, enabling regulators to gain better regulatory knowledge and to find the best means to regulate innovations based on real-world evidence, especially at a very early stage of development of a medicinal product, which can be particularly important in the face of high uncertainty and disruptive challenges, as well as when preparing new policies. SMEs and startups should also have the possibility of utilising regulatory sandboxes whereby they can, as relevant, contribute with their knowhow and experience. Regulatory sandboxes can provide controlled frameworks which, by providing a structured context for experimentation, enable where appropriate in a real-world environment the testing of innovative technologies, products, services or approaches – at the moment especially in the context of digitalisation or the use of artificial intelligence and machine learning in the life cycle of medicinal products from drug discovery, development to the administration of medicinal products – for a limited time and in a limited part of a sector or area under regulatory supervision ensuring that appropriate safeguards are in place. They allow the authorities tasked with implementing and enforcing the legislation to exercise on a case-by-case basis a degree of flexibility in relation to testing innovative medicinal products, for the benefit of bringing such products to patients wit…

AddedRecital 134: (134) In the area of medicinal products, a high level of protection of inter alia citizens, consumers, health, the environment, as well as legal certainty, a level playing field and fair competition always need to be ensured and existing levels of protection need to be respected. Whenever possible, priority should be given to the use of non-animal approaches.

AddedRecital 135: (135) The establishment of a regulatory sandbox should be based on a Commission Decision following a recommendation of the Agency. Such decision should be based on a detailed and comprehensive plan outlining the particularities of the sandbox as well as describing the products to be covered. A regulatory sandbox should be limited in duration and may be terminated at any time based on public health considerations. The learning stemming from a regulatory sandbox should inform future changes to the legal framework to fully integrate the particular innovative aspects into the medicinal product regulation. Where appropriate, adapted frameworks may be developed by the Commission on the basis of the results of a regulatory sandbox.

AddedRecital 135 a (new): (135a) The Union market for medicinal products remains fragmented, despite the Union having a single market and being the second largest market for pharmaceuticals in the world. The organisation of healthcare systems is a national competence of Member States and that allows for decisions to be made closer to the patient, but also brings divergences in both pricing and patient access. Better and closer coordination between national authorities opens the door to a more efficient and effective supply of medicinal products throughout the Union.

AddedRecital 135 b (new): (135b) More often than in the past, Member States experience critical shortages of certain antimicrobials, endangering the health of patients and risking the development of antimicrobial resistance. Those critical shortages are the result of changing infection patterns, which strongly increases demand. On the supply side, the long lead times needed to boost production makes it difficult to respond quickly. This experience underlines the need for a dedicated effort from all actors to address the issue of critical shortages.

AddedRecital 136: (136) Shortages of medicinal products represent a growing threat to public health, with potential serious risks to the health of patients in the Union and impacts on the right of patients to access appropriate medical treatment, including longer delays or interruptions in care or therapy, longer periods of hospitalisation, increased risks of exposure to falsified medicinal products, medication errors, adverse effects resulting from the substitution of unavailable medicinal products with alternative ones, significant psychological distress for patients and increased costs for healthcare systems. Member States should collect data on the impact of shortages of medicinal products on patients and consumers, and share relevant information through the MSSG, in order to inform approaches to management of shortages of medicinal products. The root causes of shortages are multifactorial, with challenges identified along the entire pharmaceutical value chain, from quality and manufacturing problems. In particular, shortages of medicinal products can result from supply chain disruptions and vulnerabilities affecting the supply of key ingredients and components. Therefore, all marketing authorisation holders should have shortage prevention plans in place to prevent shortages. The Agency should provide guidance to marketing authorisation holders on approaches to streamline the implementation of those plans.

AddedRecital 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.

AddedRecital 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…

AddedRecital 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.

AddedRecital 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.

AddedRecital 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.

AddedRecital 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.

AddedRecital 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.

AddedRecital 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.

AddedArticle 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.

AddedArticle 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;

AddedArticle 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;

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

AddedArticle 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.

AddedArticle 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.

AddedArticle 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;

AddedArticle 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;

AddedArticle 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.

AddedArticle 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.

AddedArticle 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.

AddedArticle 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.

AddedArticle 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.

AddedArticle 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;

AddedArticle 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.

AddedArticle 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.

AddedArticle 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].

AddedArticle 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.