What changed between the plenary report and the adopted text

Added:(6) The regulatory framework for medicinal products for human use should also take into account the needs of the undertakings in the pharmaceutical sector and trade in medicinal products within the Union, without jeopardising the quality, safety and efficacy of medicinal products. [Am. 7]

Removed:Recital 27: (27) Certain particulars and documentation that are normally to be submitted with an application for a marketing authorisation should not be required if a medicinal product is a generic medicinal product or a similar biological medicinal product (biosimilar) that is authorised or has been authorised in the Union. Both generic and biosimilar medicinal products are important to ensure access of medicinal products to a wider patient population at more affordable prices and create a competitive internal market. In a joint statement authorities of the Member States confirmed that the experience with approved biosimilar medicinal products over the past 15 years has shown that in terms of efficacy, safety and immunogenicity they are comparable to their reference medicinal product and are therefore interchangeable and can be used instead of its reference product (or vice versa) or replaced by another biosimilar of the same reference product.

Added:(7) The EU and all its Member States as parties to the United Nations Convention on the Rights of Persons with Disabilities are bound by its provisions to the extent of their competences. This includes the right to access information as set out in Article 21 and the right to the enjoyment of the highest attainable standard of health without discrimination on the basis of disability as set in Article 25.

Removed:Recital 30: (30) Regulatory decision-making on the development, authorisation and supervision of medicines may be supported by access and analysis of health data, including real world data i.e. health data generated outside of clinical studies where appropriate. The competent authorities should be able to use such data, including via the European Health Data Space interoperable infrastructure. Data generated via in silico methods, such as computational modelling and simulation, molecular modelling, mechanistic modelling, digital twin and artificial intelligence, where appropriate, could also be used to support regulatory decision making.

Added:(8) This revision maintains the level of harmonisation that has been achieved. Where necessary and appropriate, it further reduces the remaining disparities, by laying down rules on the supervision and control of medicinal products and the rights and duties incumbent upon the competent authorities of the Member States with a view to ensuring compliance with legal requirements. In the light of experience gained on the application of the Union pharmaceutical legislation and the evaluation of its functioning, the regulatory framework need to be adapted to scientific and technological progress, the current market conditions and economic reality within the Union. Scientific and technological developments induce innovation and development of medicinal products, including for therapeutic areas where there is still unmet medical need. To harness these developments, the Union pharmaceutical framework should be adapted to meet scientific developments such as genomics, accommodate cutting edge medicinal products, e.g. personalised medicinal products, novel health treatments and technological transformation such as data analytics, digital tools and the use of artificial intelligence. These adaptations also contribute to competitiveness of the Union pharmaceutical industry. [Am. 8]

Removed:Recital 31: (31) Directive 2010/63/EU of the European Parliament and of the Council43 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 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 only used as necessary and be optimised in order to provide the most satisfactory results whilst using the minimum number of animals. The marketing authorisation applicant should not carry out animal tests where scientifically satisfactory non-animal testing methods are available. Where scientifically satisfactory non-animal testing methods are not available, applicants that use animal testing should ensure that the principle of replacement, reduction and refinement of animal testing for scientific purposes has been applied with regard to any animal study conducted for the purpose of supporting the application. The procedures of such testing should be designed to avoid causing pain, suffering, distress or lasting harm to animals and should follow the available EMA and 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, includi…

Added:(8a) This Directive should aim to enhance the Union’s open strategic autonomy with regard to its public health objectives. Increasing the number of EU-based clinical trials and the local production of active pharmaceutical ingredients would support a more resilient and sustainable European health ecosystem. [Am. 9]

Removed:Recital 32: (32) 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.

Added:(9) Medicinal products for rare diseases and for children, should be subject to the same conditions as any other medicinal product concerning their quality, safety and efficacy, for example for what concerns the marketing authorisation procedures, quality and the pharmacovigilance requirements. However, specific requirements also apply to them considering their unique characteristics. Such requirements, which are currently defined in separate legislations, should be integrated in general pharmaceutical legal framework in order to ensure clarity and coherency of all the measures applicable to these medicinal products. Furthermore, as some medicinal products authorised for use in children are authorised by the Member States, specific provisions should be integrated in this Directive. Effort should be made to address problems encountered which concern medicinal products for children, such as the failure to timely accomplish paediatric clinical studies and to obtain data required for marketing authorisation, which results in significant delay in the approval of medicinal products for children compared to adults. [Am. 10]

Removed:Recital 34 a (new): (34a) Where the environmental risk assessment is incomplete or insufficiently substantiated for a medicinal product authorised before 30 October 2005, it should be possible for the national marketing authorisation to be revoked. However, due consideration to avoid restricting patient access to such medicinal products should be given before any decision is taken on revocation.

Added:(10) The system of a directive and regulation for the general pharmaceutical legislation should be maintained to avoid fragmentation of national legislation on medicinal products for human use, given that the legislation is based on a system of national Member States and Union marketing authorisations. Member States national marketing authorisations are granted and managed on the basis of national law implementing the Union pharmaceutical law. The evaluation of the general pharmaceutical legislation has not shown that the choice of legal instrument has caused specific problems or created disharmonisation. In addition, a REFIT Platform opinion in 2019 showed that there was not support among the Member States to turn Directive 2001/83/EC into a Regulation.

Removed:Recital 44: (44) As regards access to medicinal products, previous amendments to the Union pharmaceutical legislation have addressed this issue by providing for accelerated assessment of marketing authorisation applications or by allowing conditional marketing authorisation for medicinal products for unmet medical need. While these measures accelerated the authorisation of innovative and promising therapies in some areas, some public health priorities are still unaddressed and these medicinal products do not always reach the patient and patients in the Union still have different levels of access to medicinal products. Patient access to medicinal products depends on many factors. Marketing authorisation holders are not obliged to market a medicinal product in all Member States; they may decide not to market their medicinal products in, or withdraw them from, one or more Member States often due to commercial reasons. National pricing and reimbursement policies, the size of the population, the organisation of health systems and national administrative procedures are other factors influencing market launch and patient access. In addition, a complex regulatory environment and associated administrative burden can prevent SMEs, research institutes and academic institutions from developing promising innovative treatments and from applying for conditional market authorization.

Added:(11) The Directive should work in synergy with the Regulation to enable innovation and promote competitiveness of the Union pharmaceutical industry, in particular of SMEs. In this respect a balanced system of incentives is proposed that rewards innovation especially in areas of unmet medical need and, innovation that reaches patients and improves access across the Union and innovation that stems from development in the Union. To make the regulatory system more efficient and innovation-friendly the Directive also aims at reducing administrative burden and simplifying procedures for undertakings. [Am. 11]

Removed:Recital 44 a (new): (44a) In order to increase the availability of medicines and contribute to reducing access inequalities within the Union, the marketing authorisation holders of medicinal products should submit an application for pricing and reimbursement in Member States upon request.

Added:(11a) This Directive should be consistent with the Union’s objectives with regard to promotion of research, innovation, digitalisation, trade, international development and industrial competitiveness. [Am. 12]

Removed:Recital 45: (45) Addressing unequal patient access and affordability of medicinal products has become a key priority of the Pharmaceutical Strategy for Europe, as also highlighted by Council conclusions45 and a resolution of the European Parliament46. Member States called for revised mechanisms and incentives for development of medicinal products tailored to the level of unmet medical need, while ensuring health system sustainability, patient access and availability of affordable medicinal products in all Member States. Monitoring and evaluating access to medicinal products at Union level is important to understand the results achieved through incentives.

Added:(12) The definitions and scope of Directive 2001/83/EC should be clarified in order to achieve high standards for the quality, safety and efficacy of medicinal products and to address potential regulatory gaps, without changing the overall scope or affecting national competences in that regard, due to scientific and technological developments, e.g. low-volume products, bedside-manufacturing or personalised medicinal products that do not involve an industrial manufacturing process. [Am. 13]

Removed:Recital 46 a (new): (46a) Member States apply diverse procedures and measures in the pricing and reimbursement of medicinal products. Those procedures and measures significantly affect access to medicinal products, especially with regard to the speed at which access is achieved. Likewise, Member States apply specific procedures and measures pertaining to the promotion of competition from generic and biosimilar medicinal products. Having regard to Member State competences, and recognising the disparities which can be observed in access to medicinal products across the Union, the exchange of best practice among national competent authorities in that area should be given greater priority. In that regard, the Commission should play a distinct role in facilitating the exchange of best practices.

Added:(13) To avoid the duplication of requirements for medicinal products in this Directive and in the Regulation, the general standards in regards to quality, safety and, efficacy and environmental risk of medicinal products laid down in this Directive shall be applicable to medicinal products covered by national marketing authorisation and also to medicinal products covered by centralised marketing authorisation. Therefore, the requirements for an application for medicinal product are valid for both, also the rules on prescription status, product information, regulatory protection and rules on manufacturing, supply, advertising, supervision and other national requirements shall be applicable to medicinal products covered by centralised marketing authorisation. [Am. 14]

Removed:Recital 47: (47) To ensure dialogue among all actors in the medicines lifecycle, discussions on policy issues related to the application of the rules related to prolongation of regulatory data protection shall take place in the Pharmaceutical Committee. The Commission may invite bodies responsible for health technology assessment as referred to in Regulation (EU) 2021/2282 or national bodies responsible for pricing and reimbursement, as required, to participate in the deliberations of the Pharmaceutical Committee.

Added:(14) The determination of whether a product falls within the definition of a medicinal product must be made on a case-by-case basis taking into account the factors set out in this Directive, such as the product’s presentation or pharmacological, immunological or metabolic properties.

Removed:Recital 48: (48) While pricing and reimbursement decisions are a Member State competence, the Pharmaceutical Strategy for Europe announced actions to support cooperation of Member States to improve affordability. While the price paid within a given Member State reflects the preference of a national health system, more coordination on pricing and procurement could contribute to more equal and timely access to medicinal products, including for Member States with lower purchasing power. The Commission can support initiatives such as the Beneluxa Initiative on Pharmaceutical Policy and the Valletta Declaration. The Commission has transformed the group of National Competent Authorities on Pricing and Reimbursement and public healthcare payers (NCAPR) from an ad-hoc forum to a continuous voluntary cooperation with the aim to exchange information and best practices on pricing, payment and procurement policies to improve the affordability and cost-effectiveness of medicines and health system’s sustainability. The Commission is committed to stepping up this cooperation and further supporting information exchange among national authorities, including on public procurement of medicines, while fully respecting the competences of Member States in this area. The Commission should issue guidance on how to best implement ‘most economically advantageous tender’ (‘MEAT’ criteria) in public procurement, which aims to ensure the best value for money rather than looking at the lowest price criteria alone. Th…

Added:(15) In order to take account both of the emergence of new therapies and of the growing number of so-called ‘borderline’ products between the medicinal product sector and other sectors, certain definitions and derogations should be modified, so as to avoid any doubt as to the applicable legislation. In cases where there is still a lack of clarity of the regulatory status of a product, the competent authorities or 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 that regulatory status. The Commission and the Member States should facilitate the cooperation between the Agency, national competent authorities 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. With the same objective of clarifying situations when a product fully falls within the definition of a medicinal product and also meet the definition of other regulated products, the rules for medicinal products under this Directive apply. Furthermore, to ensure the clarity of applicable rules, it is also appropriate to improve the consistency of the terminology of the pharmaceutical legislation and clearly indicate the products excluded from the scope of this Directive. [Am. 15]

Removed:Recital 49: (49) Joint procurement, whether within a country or across countries, can improve access, affordability, and security of supply of medicines, in particular for smaller countries. Member States interested in joint procurement of medicines can make use of Directive 2014/24/EU47 , which sets out purchasing procedures for public buyers, the Joint Procurement Agreement48 and the proposed revised Financial Regulation49 . Upon request from the Member States the Commission may support interested Member States by facilitating coordination to enable access to medicines for patients in the Union as well as information exchange, in particular for medicines for rare and chronic diseases. In the event of joint procurement of medicinal products as a medical countermeasure in cases of serious cross-border threats to health, Regulation (EU) 2022/2371 of the European Parliament and of the Council49a applies. / 49a Regulation (EU) 2022/2371 of the European Parliament and of the Council of 23 November 2022 on serious cross-border threats to health and repealing Decision No 1082/2013/EU.

Added:(16) The new definition for a substance of human origin (SOHO) by the [SoHO Regulation] covers any substance collected from the human body in whatever manner, whether it contains cells or not and regardless of whether it meets the definition of ‘blood’, ‘tissue’ or ‘cell’, for example human breast milk, intestinal microbiota and any other SoHO that may be applied to humans in the future. Such substances of human origin, other than tissues and cells, may become SoHO derived medicinal products, other than ATMPs, when the SoHO is subject to an industrial process involving systematisation, reproducibility and operations performed on a routine basis or batch-wise resulting in a product of standardised consistency. When a process concerns extraction of an active ingredient from the SoHO, other than tissues and cells, or a transformation of a SoHO, other than tissues and cells, by changing its inherent properties, this should also be considered a SoHO derived medicinal product. When a process concerns concentrating, separating or isolating elements in the preparation of blood components, this should not be considered as changing their inherent properties.

Removed:Recital 50: (50) The establishment of a criteria-based definition of ‘unmet medical need’ is required to incentivise the development of medicinal products in therapeutic areas that are currently underserved. To ensure that the concept of unmet medical need reflects scientific and technological developments and current knowledge in underserved diseases, and prevents extensions of data protection that would not be in line with this objective due to unclear interpretation of ‘unmet medical need’, the Commission should specify the criteria of satisfactory method of diagnosis, prevention or treatment, ‘remaining high morbidity or mortality’, ‘relevant patient population’ following scientific assessment by the Agency. The Agency will seek input from a broad range of authorities or bodies active along the lifecycle of medicinal products in the framework of the consultation process established under the [revised Regulation (EC) No 726/2004] and also take into account scientific initiatives at EU level or between Member States related to analysing unmet medical needs, burden of disease and priority setting for research and development. The Agency should also seek input from other relevant stakeholders, including relevant patient populations. The criteria for ‘unmet medical need’ can be subsequently used by Member States to identify specific therapeutic areas of interest, but does not need to have any automatic effect on Member States’ decisions on pricing and reimbursement of medicinal products w…

Added:(17) For avoidance of doubt, the safety and quality of human organs intended for transplantation are regulated only by Directive 2010/53/EU of the European Parliament and of the Council, and the safety and quality of substances of human origin intended for medically assisted reproduction are regulated only by [SoHO Regulation or if not in force, Directive 2004/23/EC].

Removed:Recital 50 a (new): (50a) The concept of morbidity in the definition of ‘unmet medical need’ should encompass a multiplicity of factors. Morbidity should be understood to include aspects of quality of life of patients, a high burden of disease and treatment and the inability to perform daily life activities. The assessment of ‘unmet medical need’ should therefore take into account relevant patient experience data.

Added:(18) Advanced therapy medicinal products that are prepared on a non-routine basis according to specific quality standards, and used within the same Member State in a hospital under the exclusive professional responsibility of a medical practitioner and hospital pharmacist, in order to comply with an individual medical prescription for a custom-made product for an individual patient, should be excluded from the scope of this Directive whilst at the same time ensuring that relevant Union rules related to quality and safety are not undermined (‘hospital exemption’). Experience has shown that there are great differences in the application of hospital exemption among Member States. To improve and harmonise the application of hospital exemption this Directive introduces measures for collection, reporting of data as well as review of these data yearly by the competent authorities and their publication by the Agency in a repository. Furthermore, the Agency should provide a report on the implementation of hospital exemption on the basis of contributions from Member States in order to examine whether an adapted framework should be established for certain less complex ATMPs that have been developed and used under the hospital exemption. When an authorisation for the manufacturing and use of an ATMP under hospital exemption is revoked because of safety concerns, the relevant competent authorities shall inform the competent authorities of other Member States. Competent authorities should support academic institutions and other non-profit entities through the requirements of the hospital exemption clause. [Am. 16]

Removed:Recital 51 a (new): (51a) Repurposing of off-patent medicinal products to develop new therapeutic options should be supported as it can expand access in an affordable manner, providing significant benefits to patients;

Added:(18a) The Agency should establish a programme with the objective to guide academic and other not-for-profit entities through the centralised marketing authorisation procedure. That programme should be able to draw on results of the Agency’s pilot programme for enhanced support to academic and non-profit developers of advanced therapy medicinal products, which started in September 2022. [Am. 17]

Removed:Recital 52: (52) For the marketing authorisation application for medicinal products containing a new active substance, the submission of clinical trials that include as a comparator an evidence-based existing treatment should be incentivised, in order to foster the generation of comparative clinical evidence that is relevant and can accordingly support subsequent health technology assessments and decisions on pricing and reimbursement by Member States. National competent authorities and the Agency should promote, where possible, the use of comparative studies that compare the new active substance to the existing treatment when giving regulatory advice prior to granting a marketing authorisation for medicinal products.

Added:(19) This Directive should be without prejudice to the provisions of Council Directive 2013/59/Euratom, including with respect to justification and optimisation of protection of patients and other individuals subject to medical exposure to ionising radiation. In the case of radiopharmaceuticals used for therapy, marketing authorisations, posology and administration rules have to notably respect that Directive’s requirements that exposures of target volumes are to be individually planned, and their delivery appropriately verified taking into account that doses to non-target volumes and tissues are to be as low as reasonably achievable and consistent with the intended therapeutic purpose of the exposure.

Removed:Recital 53: (53) A marketing authorisation holder should, within its responsibilities, ensure the appropriate and continuous supply of a medicinal product throughout its lifetime.

Added:(20) In the interest of public health, a medicinal product should only be allowed to be placed on the market in the Union when the marketing authorisation has been granted to the medicinal product, and its quality, safety and, efficacy and environmental risk have been demonstrated. However, exemption should be provided from this requirement in situations characterised by an urgent need to administer a medicinal product to address the specific needs of a patient, or confirmed spread of pathogenic agents, toxins, chemical agents or nuclear radiation that could cause harm. In particular, to fulfil special needs, Member States should be allowed to exclude from the provisions of this Directive medicinal products supplied in response to a bona fide unsolicited order, formulated in accordance with the specifications of an authorised healthcare professional and for use by an individual patient under their direct personal responsibility. Member States should be also allowed to temporarily authorise the distribution of an unauthorised medicinal product in response to a suspected or confirmed spread of pathogenic agents, toxins, chemical agents or nuclear radiation any of which could cause harm. [Am. 18]

Removed:Recital 54: (54) Micro, small and medium-sized enterprises (‘SMEs’), not-for-profit entities or entities with limited experience in the Union system should benefit from additional time to submit an application for pricing and reimbursement for a medicinal product in the Member States where the marketing authorisation is valid, and where a Member State has requested it.

Added:(21) Marketing authorisation decisions 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 or any other considerations. However, Member States should be able exceptionally to prohibit the use in their territory of medicinal products.

Removed:Recital 55: (55) Marketing authorisation holders and Member States should do their utmost to achieve a mutually agreed supply of medicinal products in accordance with the needs of the Member State concerned, without unduly delaying or hindering the other party from enjoying its rights under this Directive.

Added:(22) The particulars and documentations that are to accompany an application for marketing authorisation for a medicinal product demonstrate that the therapeutic efficacy of the product overweight potential risks. 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.

Removed:Recital 56: deleted

Added:(22a) Particular attention should be given to the composition of clinical trials to ensure gender-based equity and comprehensive clinical data. [Am. 19]

Removed:Recital 57: (57) The application for pricing and reimbursement in the Member States does not affect at any time the powers of the Member States as regards the supply, setting of prices for medicinal products or their inclusion in the scope of national health insurance schemes.

Added:(23) As market forces alone have proven insufficient to stimulate adequate research into, and the development and authorisation of, medicinal products for the paediatric population, a system of both obligations and rewards and incentives has been put in place.

Removed:Recital 58: (58) An alternative way of demonstrating supply relates to the inclusion of medicinal products in a positive list of medicinal products covered by the national health insurance system in accordance with Council Directive 89/105/EEC. The related negotiations between companies and the Member State should be conducted in good faith, and all parties should adhere to the deadlines set out in Directive 89/105/EEC1a. / 1a Council Directive 89/105/EEC of 21 December 1988 relating to the transparency of measures regulating the prices of medicinal products for human use and their inclusion in the scope of national health insurance systems (OJ L 40, 11.2.1989, p. 8).

Added:(24) It is therefore necessary to introduce a requirement for new medicinal products or when developing paediatric indications of already authorised products covered by a patent or a supplementary protection certificate to present either the results of studies in the paediatric population in accordance with an agreed paediatric investigation plan or proof of having obtained a waiver or deferral, at the time of filing a marketing authorisation application or an application for a new therapeutic indication, new pharmaceutical form or new route of administration. However, in order to avoid exposing children to unnecessary clinical trials or due to the nature of the medicinal products, that requirement should not apply to generics or similar biological medicinal products and medicinal products authorised through the well-established medicinal use procedure, nor to homeopathic medicinal products and traditional herbal medicinal products authorised through the simplified registration procedures of this Directive. [Am. 20]

Removed:Recital 58 a (new): (58a) Cross-border healthcare is an important pathway for patients to access medicinal products that might otherwise not be available to them. To support access to medicinal products, in particular in the case of small patient populations, such as for paediatric or rare diseases, which are often disadvantaged when it comes to access to medicinal products, or where the administration of a medicinal product requires special competences or infrastructure, the full implementation of Directive 2011/24/EU of the European Parliament and of the Council1a should be supported. It is important to consider in that regard all alternative paths to making available medicinal products to patients. Competent authorities of the Member States should therefore utilise the NCAPR to exchange and share best practice regarding the implementation of cross-border access agreements and negotiations. / 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).

Added:(25) In order to ensure that the data supporting the marketing authorisation concerning the use of a product in children to be authorised under this regulation have been correctly developed, the competent authorities should check compliance with the agreed paediatric investigation plan and any waivers and deferrals at the validation step for marketing authorisation applications.

Removed:Recital 59: deleted

Added:(26) In order to reward the compliance with all the measures included in the agreed paediatric investigation plan, for products covered by a supplementary protection certificate, if relevant information on the results of the studies conducted is included in the product information, a reward should be granted in the form of a six month extension of the supplementary protection certificate created by [Regulation (EC) No 469/2009 of the European Parliament and of the Council- OP please replace reference by new instrument when adopted].

Removed:Recital 61: (61) When a compulsory licence has been granted under conditions laid down in Union law and in compliance with international agreements by a relevant authority in the Union, regulatory data protection may, if still in force, prevent the effective use of the compulsory licence as they impede the authorisation of generic medicinal products, and thus access to the medicinal products needed to address the crisis. For this reason, data and market protection should be suspended. Such a suspension of the regulatory data protection should be allowed only in relation to the compulsory licence granted and its beneficiary. The suspension shall comply with the objective, the territorial scope, the duration and the subject matter of the granted compulsory licence.

Added:(27) Certain particulars and documentation that are normally to be submitted with an application for a marketing authorisation should not be required if a medicinal product is a generic medicinal product or a similar biological medicinal product (biosimilar) that is authorised or has been authorised in the Union. Both generic and biosimilar medicinal products are important to ensure access of medicinal products to a wider patient population at more affordable prices and create a competitive internal market. In a joint statement authorities of the Member States confirmed that the experience with approved biosimilar medicinal products over the past 15 years has shown that in terms of efficacy, safety and immunogenicity they are comparable to their reference medicinal product and are therefore interchangeable and can be used instead of its reference product (or vice versa) or replaced by another biosimilar of the same reference product. [Am. 21]

Removed:Recital 62: (62) The suspension of the regulatory data protection should be granted only for the duration of the compulsory licence in the Member States where the compulsory licence has been granted. A ‘suspension‘ of data and market protection in accordance with a compulsory licence granted by a relevant authority in the Union under conditions laid down in Union law and in compliance with international agreements shall mean that data and market protection shall produce no effect in relation to the particular licensee of the compulsory licence while that compulsory licence is in effect. When the compulsory licence ends, the data and market protection shall resume their effect. The suspension should not result in an extension of the original duration.

Added:(28) Experience has shown that it is advisable to stipulate precisely the cases in which the results of toxicological and pharmacological tests or clinical studies do not have to be provided with a view to obtaining authorisation for a medicinal product that is essentially similar to an authorised product, while ensuring that innovative undertakings are not placed at a disadvantage. For these specified categories of medicinal products an abridged procedure allows applicants to rely on data submitted by previous applicants and therefore to submit only some specific documentation.

Removed:Recital 64: (64) It will allow all necessary steps to support timely access to generic medicinal products, inter alia, to conduct studies to support pricing and reimbursement as well as the manufacture or purchase of patent protected active substances for the purpose of seeking marketing authorisations during that period, contributing to the timely market entry of medicinal products, in particular the market entry of generics and biosimilars on day one of loss of the patent or SPC protection.

Added:(29) For generic medicinal products only the equivalence of the generic medicinal product with the reference medicinal product has to be demonstrated. For biological medicinal products, only the results of comparability tests and studies are provided to the competent authorities. For hybrid medicinal products i.e. in cases where the medicinal product does not fall within the definition of a generic medicinal product or has changes in strength, pharmaceutical form, route of administration or therapeutic indications, compared to the reference medicinal product, the results of the appropriate non-clinical tests or clinical studies shall be provided to the extent necessary to establish a scientific bridge to the data relied upon in the marketing authorisation for the reference medicinal product. The same applies to bio-hybrids i.e. in cases where a biosimilar medicinal product has changes in strength, pharmaceutical form, route of administration or therapeutic indications, compared to the reference biological medicinal product. In the latter two situations, the scientific bridge establishes that the active substance of the hybrid does not differ significantly in properties with regard to safety or efficacy. Where it differs significantly in respect of those properties, the applicant needs to submit a full application.

Removed:Recital 65: (65) The timely availability of generic and biosimilar medicinal products were highlighted as priorities in the conclusions of the Council on strengthening the balance in the pharmaceutical systems in the European Union and its Member States1a. in the conclusions of the Council on Access to medicines and medical devices for a Stronger and Resilient EU1b and in the resolution of the European Parliament of 2 March 2017 on EU options for improving access to medicines1c .The competent authorities should refuse the validation for an application for a marketing authorisation referring to data of a reference medicinal product only on the basis of the grounds set out in this Directive. The same applies to any decision to grant, vary, suspend, restrict or revoke the marketing authorisation. The competent authorities cannot base their decision on any other grounds. In particular, those decisions cannot be based on the patent or SPC status of the reference medicinal product. It is therefore appropriate to explicitly prohibit that practice. / 1a OJ C 269, 23.7.2016, p. 31. / 1b OJ C 269 I, 7.7.2021, p. 3. / 1c OJ C, 263, 25.7.2018, p. 4.

Added:(30) Regulatory decision-making on the development, authorisation and supervision of medicines may be supported by access and analysis of health data, including real world data i.e. health data generated outside of clinical studies, where appropriate. The competent authorities should be able to use such data, including via the European Health Data Space interoperable infrastructure. Data generated via in silico methods, such as computational modelling and simulation, molecular modelling, mechanistic modelling, digital twin and artificial intelligence, where appropriate, could also be used to support regulatory decision making. [Am. 22]

Removed:Recital 65 a (new): (65a) The One Health Approach is needed in order to address antimicrobial resistance, one of the most significant, current health threats. It is estimated that more than 35 000 people in the Union/European Economic Area and more than 1,2 million people globally die each year as a direct consequence of an infection due to bacteria resistant to antibiotics1a. High levels of cooperation are required across sectors and globally. This Directive puts in place coordinated action in order to ensure prevention and minimisation of environmental risks throughout the supply chain, use and disposal, awareness raising among patients, consumers and healthcare professionals and prudent and responsible use of antimicrobials. / 1a Murray, C.J.L., Ikuta, K.S., Sharara, F., et al. ‘Global burden of bacterial antimicrobial resistance in 2019: a systematic analysis’, Lancet, Vol. 399, No 10325, pp. 629-655.

Added:(31) Directive 2010/63/EU of the European Parliament and of the Council 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 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 only used as necessary and be optimised in order to provide the most satisfactory results whilst using the minimum number of animals. The marketing authorisation applicant should not carry out animal tests where scientifically satisfactory non-animal testing methods are available. Where scientifically satisfactory non-animal testing methods are not available, applicants that use animal testing should ensure that the principle of replacement, reduction and refinement of animal testing for scientific purposes has been applied with regard to any animal study conducted for the purpose of supporting the application. The procedures of such testing should be designed to avoid causing pain, suffering, distress or lasting harm to animals and should follow the available EMA and 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 new approach methodologies 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 or grouping and read-across, aquatic egg models as well as invertebrate species. [Am. 23]

Removed:Recital 66: (66) In order to address the challenge of antimicrobial resistance, antimicrobials should be packaged in quantities that are appropriate for the therapy cycle relevant for that product, including where possible the per unit dispensing, and national rules on antimicrobial subject to prescription ensure that they are dispensed in a way that corresponds to the quantities described by the prescription. Dispensing the exact number of units needed could help address antimicrobial resistance as well as environmental impact.