Changes from plenary report to adopted text

Added(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) 2024/1938 of the European Parliament and of the Council 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 cooperation between the Agency and advisory bodies established by other Union legislation. The opinions and the recommendations of the Agency and the relevant advisory bodies on the regulatory status of the product should be made publicly available after the consultations have taken place. [Am. 22]

RemovedRecital 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.

Added(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. [Am. 23]

RemovedRecital 78 c (new): (78c) Joint procurement, whether within a country or involving more than one country, can improve access to, affordability, and security of supply of medicinal products. Member States interested in joint procurement of medicinal products should be able to request the Commission to facilitate joint procurement of centrally authorised medicinal products at Union level conducted pursuant to Directive 2014/24/EU of the European Parliament and of the Council1a. / 1a Directive 2014/24/EU of the European Parliament and of the Council of 26 February 2014 on public procurement and repealing Directive 2004/18/EC (OJ L 94, 28.3.2014, p. 65).

Added(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. [Am. 24]

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

Added(32) Experience with the functioning of the regulatory system has shown that the existing European Medicines Agency multi-scientific committee structure often creates complexity in the scientific assessment process among committees, duplication of work and non-optimised use of expertise and resources. In addition, the Agency and the competent authorities of the Member States are confronted with challenges related to limited capacity and appropriate expertise to deal with increasing number of procedures related to existing medicinal products and assessment of new ones, in particular cutting edge innovative and complex medicinal products.

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

Added(33) To optimise the functioning and efficiency of the regulatory system, the structure of the Agency’s scientific committees is simplified and reduced to two main Committees for medicinal products for human use, the Committee for Medicinal Products for Human Use (CHMP) and Pharmacovigilance Risk Assessment Committee (PRAC).

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

Added(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. [Am. 25]

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

Added(34) The simplification of procedures should not have an impact on standards or the quality of scientific evaluation of the medicinal products to guarantee the quality, safety and efficacy of medicinal products. It should also allow for the reduction of the scientific evaluation period from 210 days to 180 days.

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

Added(35) The Agency’s scientific committees should be able to delegate some ofsupported, in relation to their evaluation duties, by to 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. [Am. 26]

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

Added(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 publicly available. [Am. 27]

RemovedRecital 88: (88) Regulation (EC) No 141/2000 of the European Parliament and of the Council55 has proved to be successful in boosting developments of orphan medicinal products in the Union, even though more progress needs to be done, as 95 % of rare diseases are still without authorised treatment and the treatments available for 5 % of rare diseases are not necessarily transformative or curative; therefore an action at Union level remains preferable to uncoordinated measures by the Member States which may result in distortions of competition and barriers to intra-Union trade. The Union should build on its success, driving and ensuring a similar degree of innovation under this Regulation.

Added(37) Scientific committees like the CAT have been instrumental to ensure expertise and capacity building in an emerging technological field. However, after more than 15 years, advanced therapy medicinal products are now more common. The full integration of their assessment in the work of the CHMP will facilitate the assessment of medicinal products within the same therapeutic class, independent of the technology on which they are based. It will also ensure that all biological medicinal products are assessed by the same committee.

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 has been abolished, since it has never been used. Nevertheless, medicinal products should still be able to lose the orphan status in cases where the population criterion is no longer met.

Added(38) To allow for more informative advice on clinical trial applications and therefore a more integrated development advice in view of future data requirements for marketing authorisation applications, the Agency can engage in consultation with representatives from Member States with clinical trial expertise. Nevertheless, decisions on clinical trial applications should remain within the competence of the Member States, in accordance with Regulation (EU) No 536/2014 of the European Parliament and of the Council.

RemovedRecital 92: deleted

Added(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 their caregivers, healthcare professionals, academia, industry, associations representing payers, or other stakeholders, as relevant. [Am. 28]

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

Added(40) Member States should ensure adequate funding of competent authorities to carry out their tasks under this Regulation and under [revised Directive 2001/83/EC]. In addition, in line with the Joint Statement of the European Parliament, the Council of the EU and the European Commission on decentralised agencies, Member States should ensure adequate resources are assigned by the competent authorities of the Member States for the purpose of their contributions to the work of the Agency, taking into account the cost-based remuneration they receive from the Agency.

RemovedRecital 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.

Added(41) In the context of cooperation with international organisations to support global public health, it is important to leverage the scientific assessment performed by the Union and to promote reliance by third country regulatory authorities based on the use of certificates of medicinal products for authorised medicinal products in the Union. An applicant may request independently or as part of an application under the centralised procedure a scientific opinion from the Agency for the use of the medicinal product for markets outside the Union. The Agency should cooperate with the World Health Organization and relevant third country regulatory authorities and bodies to issue such scientific opinions.

RemovedRecital 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.

Added(42) The Agency may cooperate with competent authorities of third countries in the context of performing its tasks. Such regulatory cooperation should be coherent with the broader economic relationship of the Union with the third country concerned, taking account of the relevant international agreements between the Union and that third country.

RemovedRecital 103: deleted

Added(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. [Am. 29]

RemovedRecital 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).

Added(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. [Am. 30]

RemovedRecital 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.

Added(44) The quality, safety and efficacy criteria of [revised Directive 2001/83/EC] should apply to medicinal products authorised by the Union under the centralised procedure. The benefit-risk balance of all medicinal products will be assessed when they are placed on the market, and at any other time the competent authority deems appropriate.

RemovedRecital 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.

Added(45) Marketing authorisation applications, like any other application submitted to the Agency, should follow the digital by default principle and hence be sent to the Agency in electronic form. Applications should be assessed based on the file submitted by the applicant in accordance with the different legal basis provided by [revised Directive 2001/83/EC]. At the same time, the Agency and the relevant committees may take into account any information that is in its possession. Applicants shall be requested to generally submit raw data, in particular with regard to the clinical trials performed by the applicant in order to ensure a full assessment of the quality, safety and efficacy of the medicinal product.

RemovedRecital 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.

Added(45a) The Agency should pay particular attention to the composition of clinical trials to ensure gender based equity and comprehensive clinical data. [Am. 31]

RemovedRecital 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.

Added(46) Directive 2010/63/EU of the European Parliament and of the Council on the protection of animals used for scientific purposes 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, including, where possible, use ofgiving 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 models as well as invertebrate species. Ultimately, efforts should be made to fully replace procedures on live animals for scientific purposes. The Agency should in its annual report highlight key observations and best practices in the replacement, reduction and refinement of animal testing submitted by applicants. [Am. 32]

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 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.

Added(47) Procedures should be in place to facilitate joint animal testing, wherever possible, in order to avoid unnecessary duplication of 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. [Am. 33]

RemovedRecital 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.

Added(48) The summary of product characteristics and the package leaflet should reflect the assessment of the Agency and be part of its scientific opinion. The opinion may recommend certain conditions that should be part of the marketing authorisation, for example on the safe and efficacious use of the medicinal product or on post-authorisation obligations that have to be complied with by the marketing authorisation holder. Those conditions may include the requirement to conduct post-authorisation safety or efficacy studies or other studies that are considered necessary to optimise the treatment, for example where the proposed dose scheme by the applicant, whilst acceptable and justifying a positive benefit-risk balance, could be further optimised post-authorisation. Where the applicant disagrees with parts of the opinion, the applicant may request its re-examination.

RemovedRecital 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.

Added(49) Due to the need to reduce overall approval times for medicinal products, the time between the opinion of the Committee for Medicinal Products for Human Use (CHMP) and the final decision on the application for a marketing authorisation should in principle be no longer than 46 days.

RemovedRecital 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.

Added(50) On the basis of the opinion of the Agency the Commission should adopt a decision on the application by means of implementing acts. In justified cases, the Commission may return the opinion for further examination or deviate in its decision from the opinion of the Agency. Taking into account the need to make medicinal products swiftly available to patients, it should be acknowledged that the chairperson of the Standing Committee on Medicinal Products for human use will use the available mechanisms under Regulation (EU) 182/2011 of the European Parliament and of the Council and notably the possibility to obtain the committee’s opinion by written procedure and within expeditious deadlines which, in principle, will not exceed 10 calendar days.

RemovedRecital 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…

Added(51) As a general rule a marketing authorisation should be granted for an unlimited time; however, one renewal may be decided only on justified grounds related to the safety of the medicinal product.

RemovedRecital 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.

Added(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. [Am. 34]

RemovedRecital 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.

Added(52) There is a need to provide for the ethical requirements of Regulation (EU) No 536/2014 to apply to medicinal products authorised by the Union. In particular, with respect to clinical trials conducted outside the Union on medicinal products destined to be authorised within the Union, at the time of the evaluation of the application for authorisation, it should be verified that these trials were conducted in accordance with the principles equivalent to these of Regulation (EU) No 536/2014 as regards the rights and safety of the subject and the reliability and robustness of the data generated in the clinical trial.

RemovedRecital 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.

Added(53) Environmental risks may arise from medicinal products containing or consisting of genetically modified organisms. It is thus necessary to subject such medicinal products to an environmental risk-assessment procedure similar to the procedure under Directive 2001/18/EC of the European Parliament and of the Council, to be conducted in parallel with the evaluation, under a single Union procedure, of the quality, safety and efficacy of the medicinal product concerned. The environmental risk-assessment should be conducted in accordance with the requirements set out in this Regulation and in [revised Directive 2001/83/EC] which are based on the principles set out in Directive 2001/18/EC but taking into account the specificities of medicinal products.

RemovedRecital 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.

Added(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/EU and Regulation (EC) No 883/2004 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. [Am. 35]

RemovedRecital 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.