(1)

The Union general pharmaceutical legislation laid down in, inter alia, Directive 2001/83/EC of the European Parliament and of the Council (3), was established in 1965 with the dual objective of safeguarding public health and harmonising the internal market for medicinal products. It has developed considerably since then, but these overarching objectives have guided all revisions. The legislation governs the granting of marketing authorisations for all medicinal products for human use by defining conditions and procedures to enter and remain on the market. A fundamental principle is that a marketing authorisation is granted only to medicinal products with a favourable benefit-risk balance after assessment of their quality, safety and efficacy.

(2)

The most recent comprehensive revision of the Union general pharmaceutical legislation took place between 2001 and 2004 while targeted revisions on post-authorisation monitoring (pharmacovigilance) and on falsified medicinal products were adopted subsequently. In the almost 20 years since the last comprehensive revision, the pharmaceutical sector has changed and has become more globalised, both in terms of development and manufacture. Moreover, science and technology have evolved at a rapid pace. However, there continues to be unmet medical needs, i.e. diseases without or only with suboptimal treatments for the concerned patient populations. Moreover, some patients might not benefit from innovation because medicinal products might be unaffordable or might not be placed on the market in the Member State concerned. There is also a greater awareness of the environmental impact of medicinal products. More recently, the COVID-19 pandemic has stress tested the legal framework.

(3)

This Directive contributes to the implementation of the One Health Approach, stressing the well-established interconnectedness between human, animal and ecosystem health, and the need to include those three dimensions when addressing public health threats. Environmental stress and degradation, including biodiversity loss, contribute to the transmission of diseases between, and the disease burden on, humans and animals. In addition, pollution from active pharmaceutical ingredients negatively affects the quality of waters and ecosystems and causes antimicrobial resistance to increase rapidly, posing risks to public health globally.

(4)

This Directive is part of the implementation of the ‘Pharmaceutical strategy for Europe’ adopted by the Commission in its communication of 25 November 2020. It aims to promote innovation, in particular for unmet medical needs, while reducing regulatory burden and the environmental impact of medicinal products; create an attractive environment for research, development and manufacturing of medicinal products in the Union; ensure access, including affordability, to innovative and established medicinal products for patients, with special attention to enhancing security of supply and addressing risks of shortages, taking into account the challenges of the smaller markets of the Union; and create a balanced and competitive system that ensures medicinal products remain affordable for health systems and patients while rewarding innovation.

(5)

Complementarily to this Directive, the Union takes other actions, such as the ‘Life Sciences Strategy’ set out in the Commission communication of 2 July 2025, to strengthen the European pharmaceutical ecosystem to accelerate research and development of new medicinal products and support innovation.

(6)

A range of Union programmes are used to fund pharmaceutical research projects, such as Horizon Europe, InvestEU, EU4Health, cohesion policy and the Digital Europe Programme. The Union is also to prioritise in its research agenda participation in cross-country collaboration enabling transnational research to meet public health needs.

(7)

The essential aim of any rules governing the authorisation, manufacture, supervision, distribution and use of medicinal products is to safeguard public health. Such rules should also ensure the free movement of medicinal products and the elimination of obstacles to trade in medicinal products to all patients in the Union.

(8)

This Directive is consistent with the Union’s objectives with regard to promotion of research, innovation, digitalisation, trade, international development and industrial competitiveness.

(9)

The legal 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.

(10)

As parties to the United Nations Convention on the Rights of Persons with Disabilities of 12 December 2006, the Union and its Member States are bound by its provisions to the extent of their competences. This includes the right to access information as set out in Article 21 of that Convention and the right to the enjoyment of the highest attainable standard of health without discrimination on the basis of disability as set out in Article 25 of that Convention.

(11)

This Directive maintains the level of harmonisation that has already been achieved in Union pharmaceutical legislation. 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 from the application of the Union pharmaceutical legislation and the evaluation of its functioning, the legal framework needs 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 legislation should be adapted to meet scientific developments such as genomics, accommodate cutting-edge medicinal products, e.g. personalised medicinal products, novel treatments and technological transformation such as data analytics, digital tools and the use of artificial intelligence. These adaptations also contribute to the competitiveness of the Union pharmaceutical industry.

(12)

The revision of Directive 2001/83/EC focuses on provisions that are relevant to achieve its specific objectives. It therefore covers all provisions except those concerning falsified medicinal products, homeopathic medicinal products and traditional herbal medicinal products. Nevertheless, for the sake of clarity, it is necessary to repeal Directive 2001/83/EC and replace it with a new Directive. The current provisions of Directive 2001/83/EC on falsified medicinal products, homeopathic medicinal products and traditional herbal medicinal products are therefore maintained in this Directive without substantive changes compared to previous harmonisations. However, in view of the changes in the governance of the European Medicines Agency (the ‘Agency’), the Committee for Herbal Medicinal products is replaced by a working group. In addition, labelling requirements for homeopathic medicinal products have been updated to include additional information on the interaction between homeopathic medicinal products and other medicinal products.

(13)

Without affecting the rules laid down in this Directive, Member States remain solely responsible for their own national security. They are responsible in defending their essential State functions, including ensuring their territorial integrity and safeguarding national security. In particular, under Article 346 TFEU, no Member State is obliged to supply information the disclosure of which it considers contrary to the essential interests of its security. For this reason, Member States should be able to waive some of the information requirements related to the marketing of medicinal products where those medicinal products are supplied for military or defence purposes and insofar as the application of such requirements implies a risk to national security or defence.

(14)

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 as regards marketing authorisation procedures, quality and pharmacovigilance requirements. However, specific requirements also apply to them considering their unique characteristics. Such requirements, which are currently laid down in separate legal acts, should be integrated in the Union general pharmaceutical legal framework in order to ensure clarity and coherency of all the measures applicable to such 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. It is important to address problems encountered which concern medicinal products for children, such as the failure to complete paediatric clinical studies or to obtain data required for marketing authorisation in a timely manner, which results in significant delay in the approval of medicinal products for children compared to approvals for medicinal products for adults.

(15)

The system of a directive and regulation for the Union general pharmaceutical legislation should be maintained to avoid fragmentation of national legislation on medicinal products for human use, given that national legislation is based on a system of marketing authorisations granted by the competent authorities of the Member States (national marketing authorisations) and marketing authorisations granted by the Union (centralised marketing authorisations). National marketing authorisations are granted and managed on the basis of national law implementing the Union pharmaceutical legislation. The evaluation of the Union general pharmaceutical legislation has not shown that the choice of legal instrument has caused specific problems or created disharmonisation. In addition, REFIT Platform opinion, in the 2019 Annual Burden Survey, showed that there was no support among the Member States to turn Directive 2001/83/EC into a Regulation.

(16)

This Directive should work in synergy with Regulation (EU) 2026/… of the European Parliament and of the Council (4) (+) to enable innovation and promote the competitiveness of the Union pharmaceutical industry, in particular of micro, small and medium-sized enterprises. In this respect, a balanced system of incentives is proposed that rewards innovation especially in areas of unmet medical need and innovation that stems from development in the Union. Moreover, companies are incentivised to apply early for marketing authorisations within the Union to bring innovation to the Union and its patients faster. To make the regulatory system more efficient and innovation-friendly, this Directive also aims to reduce administrative burden and simplify procedures for undertakings.

(17)

The definitions and the scope of Union pharmaceutical legislation 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, 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.

(18)

To avoid the duplication of requirements for medicinal products in this Directive and in Regulation (EU) 2026/… (+), the general standards in regard to quality, safety, efficacy and environmental risk of medicinal products laid down in this Directive should be applicable to medicinal products covered by a national marketing authorisation and also to medicinal products covered by a centralised marketing authorisation. Therefore, the requirements for a marketing authorisation application for a medicinal product should be valid for both, and the rules on prescription status, product information, regulatory data protection and regulatory market protection as well as the rules on manufacturing, supply, advertising, supervision and controls and other requirements should also be applicable to medicinal products covered by a centralised marketing authorisation.

(19)

The determination of whether a product falls within the definition of a medicinal product is to 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.

(20)

In order to take account of both the emergence of new therapies and 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. Similarly, it should be clarified that in situations where a product falls within the definition of a medicinal product under this Directive, but also falls within the definition of a product regulated under another legislative act, the rules for medicinal products under this Directive should apply. Furthermore, to ensure the clarity of applicable rules, it is also appropriate to improve the consistency of the terminology used in Union pharmaceutical legislation and clearly indicate the products excluded from the scope of this Directive.

(21)

The new definition of a substance of human origin (SoHO) introduced by Regulation (EU) 2024/1938 of the European Parliament and the Council (5) 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, can become SoHO-derived medicinal products other than advanced therapy medicinal products (ATMPs), where the SoHO is subject to an industrial process involving pooling of donations, systematisation, reproducibility and operations performed on a routine basis or batch-wise resulting in a product of standardised consistency. The pooling of a limited number of donations for the preparation of SoHO is not in itself an industrial process. Where a process concerns extraction of an active ingredient from the SoHO, other than tissues and cells, or the transformation of a SoHO, other than tissues and cells, by changing its inherent properties, this should also be considered a SoHO-derived medicinal product. Where a process concerns concentrating, separating, inactivating pathogens or isolating elements, or a combination of those processes, in the preparation of SoHO, such a process in and of itself should normally not be considered as changing their inherent properties.

(22)

According to current scientific knowledge, haptens, when combined with an endogenous carrier substance, are allergens and should be construed as such for the purpose of pharmaceutical legislation.

(23)

For the avoidance of doubt, it is appropriate to underline that the safety and quality of human organs intended for transplantation are regulated exclusively by Directive 2010/53/EU of the European Parliament and of the Council (6), and the safety and quality of SoHO intended for medically assisted reproduction are regulated exclusively by Regulation (EU) 2024/1938.

(24)

Advanced therapy medicinal products prepared within a Member State on a non-routine basis in accordance with specific quality standards and used within the same Member State in a hospital under the exclusive professional responsibility of a medical practitioner, in order to comply with an individual medical prescription for a custom-made product to meet the needs of an individual patient, should be subject to an exemption from the general requirements set out in this Directive and Regulation (EU) 2026/… (+), while ensuring that relevant Union rules relating to quality and safety are not undermined (‘advanced therapy medicinal products prepared under hospital exemption’). Experience has shown that there are significant variations in the implementation of the hospital exemption among Member States. To improve the implementation of the hospital exemption, this Directive introduces measures for the collection and reporting of data as well as for the review of such data yearly by the competent authorities and their publication by the Agency in a repository. Furthermore, the Agency should prepare a report on the implementation of the hospital exemption based on contributions from Member States to assess whether an adapted framework should be developed for certain less complex ATMPs that have been developed and used under hospital exemption. If an approval for the manufacturing and use of an ATMP under hospital exemption is revoked due to safety concerns, the relevant competent authority of the Member State should notify the Agency, which should then disseminate that information to the other Member States’ competent authorities.

(25)

This Directive should be without prejudice to Council Directive 2013/59/Euratom (7), including with respect to justification and optimisation of the 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 are to comply with the requirements of that Directive as regards individual planning of exposures of target volumes, and the appropriate verification of their delivery, taking into account that doses to non-target volumes and tissues are to be as low as reasonably achievable and consistent with the intended radiotherapeutic purpose of the exposure.

(26)

In the interest of public health, a medicinal product should only be allowed to be placed on the market in the Union if a marketing authorisation has been granted for that medicinal product, and if the quality, safety and efficacy of the medicinal product have been demonstrated. However, exemptions from those requirements should be provided for in situations characterised by an urgent need to administer a medicinal product to address the special needs of individual patients, or in the event of a suspected or confirmed spread of pathogenic agents, toxins, chemical agents or nuclear radiation that could cause harm. In particular, in order to meet special needs, Member States should be allowed to exempt from the requirements set out in this Directive medicinal products supplied in response to a bona fide unsolicited order or anticipated bona fide unsolicited order, formulated or used in accordance with the specifications of an authorised healthcare professional and intended to meet the special needs of individual patients under the direct personal responsibility of that authorised healthcare professional. Member States should also be allowed to temporarily authorise the use and 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.

(27)

Pharmacies, including hospital pharmacies, play a crucial role in providing medicinal products to patients. They prepare specific medicinal products, known as magistral formulas, that are tailored to meet the special needs of individual patients based on the written instructions of a doctor. In certain situations, it is necessary, in order to cater for the needs of individual patients, to prepare those magistral formulas in advance on the basis of anticipated medical prescriptions within a specified period. This could include situations of urgency in which it is necessary for the magistral formula to be immediately available or situations where advance preparations are necessary to ensure dose accuracy or the quality of the medicinal product. Purely financial reasons should not justify the use of this possibility.

(28)

Additionally, pharmacies are responsible for preparing standard medicinal products, referred to as officinal formulas. Those medicinal products are prepared in accordance with established guidelines found in pharmacopoeias. Officinal formulas are designed for general use and adhere to standardised recipes that are set by authoritative pharmaceutical bodies. Unlike magistral formulas, they are not customised for individual patients. Generally, those preparations should be exempt from the authorisation requirements set out in this Directive, but remain subject to national regulations.

(29)

In exceptional cases, to ensure the availability of specific medicinal products or suitable alternatives for patients in a Member State, it should be possible for that Member State to exempt temporarily those medicinal products from the requirements set out in this Directive, to meet the specific needs of individual patients in that Member State. In addition, to mitigate shortages effectively in a Member State, it is important to address the patients’ needs at population level and allow the preparation of such medicinal products, subject to strict conditions. Any other reasons, such as financial interests, should not be a justification for allowing those exemptions. Such exemptions should never aim to distort competition and should be interpreted narrowly, and only be used to mitigate or resolve a shortage in a Member State or in a situation where there is no relevant authorised medicinal product available on the market. Member States should, in any event, undertake their best efforts to find suitable alternatives under the rules set out in this Directive and in Regulation (EU) 2026/… (+).

(30)

It is recognised that improved access to information contributes to public awareness about the assessment and authorisation of medicinal products. When assessing the marketing authorisation application for a medicinal product, the competent authority of the Member State should draw up an assessment report on the quality, safety, efficacy, and the environmental risk assessment (ERA), as applicable, of the medicinal product and the reasons for its opinion. The competent authority of the Member State should make publicly available a summary of the assessment report and a summary of the ERA, after the deletion of any information of a commercially confidential nature and written in a manner that is understandable to the public. To the extent information under the ERA would entail environmental information within the meaning of Directive 2003/4/EC of the European Parliament and of the Council (8), the provisions of that Directive should apply.

(31)

Marketing authorisation decisions should be taken on the basis of the objective scientific criteria of the 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 certain medicinal products.

(32)

The particulars and documents that are to accompany a marketing authorisation application for a medicinal product should demonstrate that the therapeutic efficacy of the product overweighs potential risks. The benefit-risk balance of all medicinal products is assessed when they are placed on the market, and at any other time the competent authority of the Member State or the Agency, as applicable, deems appropriate.

(33)

In the context of the development and marketing authorisation of medicinal products, it is crucial that particular attention is given to the composition of clinical trials, to ensure comprehensive clinical data and, where appropriate, gender-based equity.

(34)

As market forces alone have proven insufficient to stimulate adequate research into, and the development and marketing authorisation of, medicinal products for the paediatric population, a system of obligations, rewards and incentives should be established.

(35)

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 patients, especially children, to unnecessary clinical trials or due to the nature of the medicinal products, that requirement should not apply to generic medicinal products or biosimilar medicinal products and medicinal products authorised through the well-established medicinal use procedure, nor should it apply to homeopathic medicinal products and traditional herbal medicinal products authorised through the simplified registration procedures set out in this Directive.

(36)

In order to ensure that the data supporting the marketing authorisation concerning the paediatric use of a medicinal product to be authorised under this Directive and Regulation (EU) 2026/… (+) have been correctly developed, the competent authority of the Member State should check compliance with the agreed paediatric investigation plan and any waivers and deferrals during the scientific assessment of a valid marketing authorisation applications.

(37)

For medicinal products covered by a supplementary protection certificate under Regulation (EC) No 469/2009 of the European Parliament and of the Council (9), a six month extension of that certificate should be granted by way of reward where all the measures included in the agreed paediatric investigation plan are complied with and relevant information on the results of the studies conducted is included in the product information.

(38)

Certain particulars and documents that are normally to be included in a marketing authorisation application should not be required if a medicinal product is a generic medicinal product or a biosimilar medicinal product that is authorised or has been authorised in the Union. Both generic medicinal products and biosimilar medicinal products are important to ensure access to medicinal products for a wider patient population, at more affordable prices, and create a competitive internal market. In a joint statement, the competent 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 their reference medicinal product (or vice versa) or replaced by another biosimilar medicinal product of the same reference medicinal product.

(39)

Experience has shown that it is advisable to specify precisely the cases in which the results of toxicological and pharmacological tests or clinical studies do not have to be provided in order to obtain a marketing authorisation for a medicinal product that is essentially similar to an authorised medicinal product, while ensuring that innovative undertakings are not placed at a disadvantage. For such specified categories of medicinal products an abridged procedure should allow applicants to rely on data submitted by previous applicants and therefore to submit only some specific documentation.

(40)

For generic medicinal products, only the equivalence of the generic medicinal product with the reference medicinal product should be demonstrated. For biosimilar medicinal products, only the results of comparability tests and studies should be provided to the competent authorities of the Member States or the Agency, as applicable. For hybrid medicinal products i.e. in cases where the medicinal product does not fall within the definition of a generic medicinal product or differs in strength, pharmaceutical form, route of administration or therapeutic indications, compared to the reference medicinal product, the results of the relevant non-clinical tests or clinical studies should 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-hybrid medicinal products i.e. in cases where the biological medicinal product does not fall within the definition of a biosimilar medicinal product or differs in strength, pharmaceutical form, route of administration or therapeutic indications, compared to the reference biological medicinal product. Where applicable, a scientific bridge should establish that the active substance of the hybrid medicinal product or bio-hybrid medicinal product does not differ significantly in properties with regard to safety or efficacy. Where it differs significantly in respect of those properties, the marketing authorisation applicant should submit a full application.

(41)

It should be possible for regulatory decision-making on the development, marketing authorisation and supervision of medicinal products to be supported by access to and analysis of health data, including real world data i.e. health data generated outside clinical studies, where appropriate. The competent authorities of the Member States or the Agency, as applicable, 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.

(42)

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 the principles of replacement, reduction and refinement and apply them in accordance with Directive 2010/63/EU of the European Parliament and of the Council (10), where they concern the care and use of live animals for scientific purposes, and should only be used as necessary and be optimised in order to provide the most satisfactory results whilst using the minimum number of animals. The procedures of such testing should be designed to avoid causing pain, suffering, distress or lasting harm to animals and should follow the available guidelines of the Agency and of the International Council for Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use. The marketing authorisation applicant should not carry out animal tests where scientifically satisfactory non-animal testing methods are available. 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 read-across models. Where scientifically satisfactory non-animal testing methods are not available, applicants that use animal testing should ensure that the rules of Directive 2010/63/EU are applied, including the principles of reduction and refinement of animal testing for scientific purposes with regard to any animal study conducted for the purpose of supporting the application.

(43)

Procedures should be in place to facilitate joint animal testing, wherever possible, in order to avoid unnecessary testing using live animals in accordance with 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.

(44)

With respect to clinical trials, in particular those conducted outside the Union, on medicinal products destined to be authorised within the Union, it should be verified, at the time of the evaluation of the marketing authorisation application, that the trials were conducted in accordance with principles of good clinical practice and ethical requirements equivalent to those in Regulation (EU) No 536/2014 of the European Parliament and of the Council (11).

(45)

There is the possibility, under certain circumstances, for marketing authorisations to be granted subject to specific obligations or conditions, on a conditional basis or under exceptional circumstances. This Directive should allow for medicinal products with a standard marketing authorisation for new therapeutic indications to be authorised on a conditional basis or under exceptional circumstances, under similar 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 should be subject to specific review of the fulfilment of the specific conditions or obligations imposed. The grounds for refusal of a marketing authorisation should apply mutatis mutandis to such cases.

(46)

In justified cases, even when comprehensive safety and efficacy data have been supplied, post-authorisation studies could be imposed by the competent authorities of the Member States to enhance the safe and effective use of the medicinal product or to allow for evidence-based treatment optimisation.

(47)

Furthermore, it should be possible to impose on marketing authorisation holders an obligation to conduct post-authorisation ERA studies, to collect monitoring data or information on use, or to implement appropriate risk mitigation measures, where identified or potential concerns about risks to the environment or public health, including antimicrobial resistance, need to be further investigated or mitigated after the medicinal product has been marketed.

(48)

Where the competent authorities consider that there are reasons to believe that a medicinal product could present a potential serious risk to public health, a scientific evaluation of the medicinal product should be undertaken, subject to the relevant procedures, leading to a decision to maintain, vary, suspend or revoke the marketing authorisation. The competent authorities should also be able to act where the conditions attached to the authorisation are not complied with, including the obligation to conduct post-authorisation ERA studies.

(49)

With the exception of those medicinal products that are subject to the centralised marketing authorisation procedure established by Regulation (EU) 2026/… (+), a marketing authorisation for a medicinal product should be granted by a competent authority in one Member State. In order to avoid unnecessary administrative and financial burdens for marketing authorisation applicants and the competent authorities of the Member States, a full in-depth assessment of a marketing authorisation application for a medicinal product should be carried out only once. It is appropriate therefore to lay down special procedures for the mutual recognition of national marketing authorisations. Moreover, it should be possible to submit the same marketing authorisation application through the decentralised procedure in parallel in several Member States for the purpose of a common assessment under the lead of one of the Member States concerned.

(50)

Moreover, rules should be established under those authorisation procedures to resolve any disagreements between Member States in a coordination group for decentralised and mutual recognition procedures (the ‘coordination group’) relating to medicinal products without undue delay. In the event of a disagreement between Member States about the quality, the safety or the efficacy of a medicinal product, a scientific assessment of the matter should be undertaken according to a Union standard, leading to a single decision on the points of disagreement, which should be binding on the Member States concerned. That decision should be adopted following a rapid procedure ensuring close cooperation between the Commission and the Member States.

(51)

In cases of major disagreement that cannot be solved, the case should be settled by means of a Commission Decision. However, it should be possible to refer the matter to the Committee for Medicinal Products for Human Use for a scientific opinion before the Commission adopts its decision by means of an implementing act.

(52)

In order to better protect public health and avoid any unnecessary duplication of effort during the examination of marketing authorisation applications for medicinal products, Member States should systematically draw up an assessment report in respect of each medicinal product that is authorised by them, and exchange reports upon request. Furthermore, a Member State should be able to suspend the examination of a marketing authorisation application for a medicinal product that is under active consideration in another Member State with a view to recognising the decision reached by the latter Member State.

(53)

In order to ensure as broad as possible access to medicinal products, a Member State that is interested in having access to a particular medicinal product for which a marketing authorisation is applied for under the decentralised or mutual recognition procedure should be able to opt into the procedure and become a Member State concerned by that procedure.

(54)

In order to increase availability of medicinal products, in particular on smaller markets, in cases where an applicant does not apply for a marketing authorisation for a medicinal product in the context of the mutual recognition procedure in a given Member State, it should be possible for that Member State to authorise the placing on the market of the medicinal product where justified for public health reasons.

(55)

In the case of generic medicinal products for which the reference medicinal product has been granted a marketing authorisation under the centralised procedure, applicants seeking a marketing authorisation should be able to choose either of the two procedures, namely the national procedure or the centralised procedure, on certain conditions. Similarly, the decentralised or mutual recognition procedure should remain available as an option for certain medicinal products, even if they represent a therapeutic innovation or are of benefit to society or to patients. Since generic medicinal products account for a major part of the market in medicinal products, their access to the Union market should be facilitated in the light of the experience acquired and the procedures to involve other Member States concerned in the marketing authorisation procedure should be therefore further simplified.

(56)

The simplification of procedures should not have an impact on standards or the quality of scientific evaluation of medicinal products to guarantee the quality, safety and efficacy of medicinal products and therefore, the scientific evaluation period should, in principle, remain the same. However, this Directive provides for the reduction of the overall period for marketing authorisation procedure from 210 days to 180 days.

(57)

Member States should ensure that adequate financial resources are available to the competent authorities of the Member States in order for them to carry out their tasks under this Directive and Regulation (EU) 2026/… (+). In addition, Member States should ensure that 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.

(58)

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 authorisations for medicinal products which address unmet medical needs. While those measures accelerated the authorisation of innovative and promising therapies in some areas, certain public health priorities remain unaddressed. Additionally, those 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 can 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.

(59)

Addressing unequal patient access and affordability of medicinal products have become key priorities of the Pharmaceutical Strategy for Europe, as also highlighted by Council conclusions of 17 June 2016 on strengthening the balance in the pharmaceutical systems in the European Union and its Member State (12) and of 15 June 2021 on access to medicines and medical devices for a stronger and resilient EU (13) and the European Parliament resolution of 2 March 2017 on EU options for improving access to medicines (14). Member States called for revised mechanisms and incentives for the development of medicinal products, tailored to the level of unmet medical needs, 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.

(60)

Access to medicinal products also comprises affordability. In this regard, the Union pharmaceutical legislation respects the competence of the Member States in terms of pricing and reimbursement. In a complementary manner, it aims to have a positive impact on affordability and sustainability of health systems with measures that support competition from generic medicinal products and biosimilar medicinal products. The competition from generic medicinal products and biosimilar medicinal products should also, in turn, improve patients’ access to medicinal products.

(61)

To ensure dialogue among all actors in the medicinal products lifecycle, discussions on policy issues related to the application of the rules related to access to and availability of medicinal products should take place in the Pharmaceutical Committee. It should be possible for the Commission to invite bodies responsible for health technology assessment as referred to in Regulation (EU) 2021/2282 of the European Parliament and of the Council (15) or national bodies responsible for pricing and reimbursement, as required, to participate in the deliberations of the Pharmaceutical Committee.

(62)

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. 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 medicinal products 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 medicinal products, while fully respecting the competences of Member States in this area. It should also be possible for the Commission to invite NCAPR members to participate in deliberations of the Pharmaceutical Committee on topics that may have an impact on pricing or reimbursement policies, such as the market launch incentives provided for in this Directive.

(63)

Joint procurement, whether within a country or across countries, can improve access to as well as affordability and security of supply of medicinal products, in particular for smaller countries. Member States interested in joint procurement of medicinal products can make use of Directive 2014/24/EU of the European Parliament and of the Council (16), which sets out purchasing procedures for public buyers, and Regulations (EU) 2022/2371 (17) and (EU, Euratom) 2024/2509 (18) of the European Parliament and of the Council. Upon request from the Member States, the Commission can support interested Member States by facilitating coordination to enable access to medicinal products for patients in the Union as well as information exchange, in particular for medicinal products for rare and chronic diseases.

(64)

The establishment of a criteria-based definition of ‘unmet medical need’ is necessary 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, the Agency should, in the form of scientific guidelines, specify the conditions concerning clinically relevant improvement in efficacy, or in safety with at least comparable efficacy, in comparison with existing medicinal products or other methods of prevention, diagnosis or treatment authorised in the Union. The guidelines should cover clinical efficacy endpoints such as survival, symptoms and health-related quality of life, and clinical safety endpoints such as side effects, and provide further technical details regarding their assessment. The Agency should 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 Regulation (EU) 2026/… (+) and also take into account scientific initiatives at Union 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.

(65)

The inclusion of new therapeutic indications in an authorised medicinal product contributes to improving patients’ access to additional therapies and therefore should be incentivised.

(66)

Repurposing of medicinal products to new therapeutic indications should be supported as it can provide significant health benefits to patients in a timely and affordable manner.

(67)

For marketing authorisation applications for medicinal products containing a new active substance, the submission of clinical trials that include an evidence-based existing treatment as a comparator, in line with scientific advice provided by the Agency, should be incentivised. This is in order to foster the generation of comparative clinical evidence that is relevant and that can therefore be used to support subsequent health technology assessments and decisions on pricing and reimbursement by Member States.

(68)

The competent authorities of the Member States and the Agency should support the design of comparative clinical trials, wherever possible, when providing pre-authorisation scientific advice.

(69)

The holder of a marketing authorisation for a medicinal product placed on the market in a Member State should, within the limits of its responsibility, ensure the appropriate and continuous supply of a medicinal product throughout its lifetime, including by maintaining appropriate stock levels, to wholesale distributors, pharmacies or other persons authorised to supply medicinal products so that the needs of patients in the Member State in question are met. Member States may specify in their national legislation the obligation for the marketing authorisation holder to ensure adequate supply of medicinal products to wholesale distributors in order to guarantee that the needs of patients in the Member States concerned are met.

(70)

Access to medicinal products in all Member States and guaranteeing a timely, stable, reliable and high-quality supply of medicinal products are essential objectives to achieve an overall high level of protection of human health in the Member States, thus contributing to the protection of human health and human life in the Union. The responsibility of ensuring a timely, adequate and continuous supply of medicinal products so that the needs of patients in a Member State are covered rests, mainly, on the marketing authorisation holder. In principle, when a marketing authorisation is granted, the medicinal product is placed on the market by the marketing authorisation holder on its own initiative. Practice shows, however, that in certain Member States the placing on the market of authorised medicinal products does not occur or is delayed or occurs in quantities that do not correspond to the needs of those Member States. Therefore, Member States should, based on grounds of public health protection with due regard to the principle of proportionality and in compliance with Union law, in particular concerning the free movement of goods and competition, be able to require from the marketing authorisation holder specific actions with a view to complying with its market launch and supply obligations under this Directive and Regulation (EU) 2026/… (+). To this aim, Member States should be able to request the marketing authorisation holder to do one or more of the following actions: to submit a valid pricing and reimbursement application, to participate in any relevant national or Union procurement procedures or to establish and implement a roll-out plan that is acceptable for the Member State concerned. The implementation of the roll-out plan should ensure sufficient and continuous supply to meet the needs of the patients in the Member State concerned.

(71)

A roll-out plan aims to ensure a predictable and continuous supply of medicinal products in a given Member State. It responds to the need of coordinated planning between the marketing authorisation holder and the competent authorities of the Member States. It would allow national authorities to anticipate availability and plan public-health measures and companies to plan manufacturing and distribution. Following a request by a Member State, the marketing authorisation holder should prepare a draft roll-out plan specifying the quantities and timing of supply of the medicinal product for a defined period of time taking into account the supply needs declared by the Member State and other objective considerations such as manufacturing or distribution capacity. Based on the draft roll-out plan submitted by the marketing authorisation holder, the Member State concerned and the marketing authorisation holder should discuss the plan, which will require the final agreement of the Member State concerned. Later, both the Member State and the marketing authorisation holder may require an update of the roll-out plan, to reflect any important developments such as evolving demand, or changes in manufacturing or distribution capacity. For the development, agreement, adaptation and effective implementation of the roll-out plan, the marketing authorisation holder and the Member State should be obliged to cooperate fully and provide timely and accurate information.

(72)

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 the other party’s exercise of its rights under this Directive or unduly impeding the exercise of those rights.

(73)

Cross-border healthcare, including under Directive 2011/24/EU, is an additional pathway for patients to access a treatment that might otherwise not be available to them, notably in cases where the medicinal product cannot be administered to the patient in their home Member State.

(74)

The possibility of using compulsory licences in situations of national emergency or other circumstances of extreme urgency is explicitly provided for under the Agreement on Trade-Related Aspects of Intellectual Property Rights (the ‘TRIPS Agreement’) (19). Where a compulsory licence has been granted by a relevant authority in the Union pursuant to Regulation (EU) 2025/2645 of the European Parliament and of the Council (20) or under national compulsory licensing frameworks, regulatory data protection or regulatory market protection can, if still in force, prevent the effective use of the compulsory licence as it impedes the authorisation of generic medicinal products, and thus access to the medicinal products needed to address a crisis. For this reason, regulatory data protection and regulatory market protection should be suspended when a compulsory licence has been issued. Such a suspension of the regulatory data protection and regulatory market protection should be allowed only in relation to the compulsory licence granted and its beneficiary. The suspension should comply with the objective, the territorial scope, the duration and the subject matter of the granted compulsory licence.

(75)

The suspension of the regulatory data protection and of the regulatory market 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 the regulatory data protection and the regulatory market protection means that the regulatory data protection and the regulatory market protection 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 regulatory data protection and the regulatory market protection should resume. However, the period of compulsory licensing should not be recouped, and therefore the suspension should not result in an extension of the original duration of the regulatory protection.

(76)

It is currently possible for applicants for marketing authorisation for generic, biosimilar, hybrid and bio-hybrid medicinal products to conduct studies, trials and activities to fulfil the subsequent practical requirements necessary to obtain regulatory approvals for those medicinal products during the term of protection of the patent or supplementary protection certificate of the reference medicinal product, without this being considered as a patent or supplementary protection certificate infringement. The application of this limited exception is, however, fragmented across the Union and it is considered necessary, in order to facilitate the market entry of generic, biosimilar, hybrid and bio-hybrid medicinal products, to clarify the scope of this exception in order to ensure a harmonised application thereof in all Member States, both in terms of beneficiaries and in terms of the activities covered. The exception must be limited to conducting the necessary studies, trials and other activities needed to obtain a marketing authorisation, conduct health technology assessments and obtain pricing and reimbursement approvals as well as submit an application for procurement tenders, to the extent that the submission of an application for procurement tenders does not entail the sale or offering for sale of the medicinal product concerned during the term of protection, even though those activities can require substantial amounts of test production to demonstrate reliable manufacturing. During the term of protection of the patent or supplementary protection certificate of the reference medicinal product, there can be no commercial use of the final medicinal products obtained for the purposes of the regulatory approval process.

(77)

The exception should allow inter alia, to conduct studies to support pricing and reimbursement approvals as well as the manufacture or purchase of patent protected active substances for the purpose of seeking marketing authorisations during the term of protection of the patent or supplementary protection certificate of the reference medicinal product, contributing to the market entry of generic and biosimilar medicinal products the first day following the expiry of the term of protection of the patent or supplementary protection certificate, and timely access to these products.

(78)

The competent authorities should refuse to validate a marketing authorisation application 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 a marketing authorisation. The competent authorities cannot base their decision on any other grounds. In particular, such decisions should not be based on the patent or supplementary protection certificate status of the reference medicinal product. It also stems from those rules that the protection of intellectual property rights is not a valid ground to refuse, revoke or suspend decisions related to relevant pricing and reimbursement approvals, health technology assessment procedures, or where applicable, applications for procurement tenders. Member States remain free to introduce rules to ensure the readiness to supply a medicinal product on their market for the period following the expiry of the term of protection of the patent or supplementary protection certificate.

(79)

The One Health Approach is needed in order to address antimicrobial resistance, one of the most significant, current health threats. 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 and use and disposal of antimicrobials, to raise awareness among patients, consumers and healthcare professionals and to promote the prudent and responsible use of antimicrobials.

(80)

In order to address the challenge of antimicrobial resistance, where a pack of antimicrobials is intended for direct dispensing to patient, antimicrobials should be packaged in quantities that are appropriate for the therapy cycle relevant for that medicinal product and national rules on antimicrobials subject to medical prescription should ensure that those are dispensed in a way that corresponds to the quantities described by the medical prescription.

(81)

The provision of information to healthcare professionals and to patients on the appropriate use, storage and disposal of antimicrobials is the joint responsibility of marketing authorisation holders and of Member States. Member States should ensure that an appropriate collection and management system is in place for all unused or expired medicinal products.

(82)

Pharmacists and other healthcare professionals should play a role in antimicrobial stewardship, including advising on the prudent use of antibiotics and other antimicrobials, as well as on their correct disposal.

(83)

While this Directive restricts the use of antimicrobials by setting categories of antimicrobials that are subject to medical prescription, due to the growing antimicrobial resistance in the Union, the competent authorities of the Member States should consider further measures such as expanding the prescription status of antimicrobials, initiatives for prudent use of antimicrobials in hospitals taking into account that the combined use of several antimicrobial active substances may represent a particular risk, sufficient training of healthcare professionals on stewardship regarding the use of antimicrobials and the mandatory use of diagnostic tests before prescription. The competent authorities of the Member States should consider such further measures according to the level of antimicrobial resistance in their territory and the needs of patients. With regards to antimicrobials for topical use, Member States should have the possibility to waive the mandatory ‘subject to medical prescription’ status, including taking into account the maximum single dose, the maximum daily dose, the strength, the pharmaceutical form and certain types of packaging.

(84)

The pollution of waters and soils with pharmaceutical residues is an emerging environmental problem, and there is scientific evidence that the presence of those substances in the environment resulting from their manufacture, use and disposal poses a risk to the environment and public health. The evaluation of the legislation showed that strengthening of existing measures to reduce the impact of medicinal products’ lifecycle on the environment and public health is required. Measures under this Directive complement the main environmental legislation, in particular Council Directive 91/271/EEC (21) as well as Directives 2000/60/EC (22), 2006/118/EC (23), 2008/98/EC (24), 2008/105/EC (25), 2010/75/EU (26) and 2020/2184 (27) of the European Parliament and of the Council.

(85)

Marketing authorisation applications for medicinal products in the Union should include an ERA and risk mitigation measures. However, when preparing their ERAs, the applicants for marketing authorisations of generic medicinal products and biosimilar medicinal products should be able to refer to ERA studies conducted for the reference medicinal product or to ERA studies conducted for any other medicinal product containing the same active substances. The same applies to hybrid medicinal products and biohybrid medicinal products as well as to fixed-dose combination medicinal products. If applicants fail to submit a complete or sufficiently substantiated ERA or if they do not propose risk mitigation measures to sufficiently address the risks identified in the ERA, the marketing authorisation should be refused. The ERA should be updated when new data or knowledge about relevant risks become available.

(86)

Marketing authorisation applicants should take into account risk assessment procedures under other Union legal frameworks that may apply to chemicals depending on their use. In addition to this Directive, there are four main other legal frameworks: (i) Regulation (EC) No 1907/2006 of the European Parliament and of the Council (28) (industrial chemicals (REACH)); (ii) Regulation (EU) No 528/2012 of the European Parliament and of the Council (29) (biocides); (iii) Regulation (EC) No 1107/2009 of the European Parliament and of the Council (30) (pesticides); and (iv) Regulation (EU) 2019/6 of the European Parliament and of the Council (31) (veterinary medicinal products). In its communication on the European Green Deal of 11 December 2019, the Commission proposed a ‘one-substance one-assessment’ (OS-OA) approach for chemicals, in order to increase the efficiency of the registration system, reduce costs and unnecessary animal testing.

(87)

The emissions and discharges of antimicrobials to the environment from manufacturing sites can lead to antimicrobial resistance, which is a global concern regardless where the emissions and discharges take place. Therefore, the scope of the ERA should be extended to cover the risk of antimicrobial resistance selection throughout the entire life cycle of antimicrobials, including manufacturing. In order to specify technical details to conduct the ERA, the Agency should issue guidelines on how to measure antimicrobial resistance other than antibiotic resistance.

(88)

This Directive should also include provisions for a risk-based approach regarding the ERA obligations of marketing authorisation holders before October 2005 and the setting-up of an ERA monograph system for active substances. This ERA monograph system should be available to applicants for use when conducting an ERA for a new marketing authorisation application.

(89)

For medicinal products authorised prior to October 2005, which have not been the subject of an ERA, specific provisions should be introduced to set up a risk-based prioritisation programme for the ERA submission or update by the marketing authorisation holders. For generic, biosimilar, hybrid and bio-hybrid medicinal products and fixed-dose combination medicinal products, for which the reference medicinal product was authorised before 30 October 2005 and is included in that programme, the ERA could be submitted after the outcome of the ERA for the relevant reference medicinal product has been made publicly available by the Agency, unless the marketing authorisation holders concerned have participated in a joint ERA study conducted for the relevant active substance. The same should apply for new marketing authorisation applications for such generic, biosimilar, hybrid and bio-hybrid medicinal products and fixed-dose combination medicinal products for which the reference medicinal product was authorised before 30 October 2005 and is included in that programme.

(90)

Northern Ireland has historically relied on the supply of medicinal products from or through parts of the United Kingdom other than Northern Ireland. Following the withdrawal of the United Kingdom of Great Britain and Northern Ireland from the European Union and the European Atomic Energy Community, to prevent shortages of medicinal products and ultimately to ensure a high level of public health protection, specific provisions have been put in place. This Directive replaces Directive 2001/83/EC listed in point 20 of Annex 2 to the Protocol on Ireland / Northern Ireland (the ‘Windsor Framework’) and would therefore apply to and in the United Kingdom in respect of Northern Ireland in accordance with Article 5(4) of the Windsor Framework, read in conjunction with Article 13(3) thereof. To ensure the continued effectiveness of the specific provisions that have already been put in place, it is therefore appropriate to stipulate that certain provisions of this Directive should not apply to and in the United Kingdom in respect of Northern Ireland. The power to adopt acts in accordance with Article 290 of the Treaty on the Functioning of the European Union should be delegated to the Commission in order to amend or supplement certain rules whose application is to be suspended where the Commission finds that the level of protection of public health ensured by the United Kingdom is no longer essentially equivalent to that guaranteed within the Union or where sufficient information is not available to the Commission to enable it to establish whether an essentially equivalent level of protection of public health is ensured by the United Kingdom and that situation is not remedied within the specified time limit. It is of particular importance that the Commission carry out appropriate consultations during its preparatory work, including at expert level, and that those consultations be conducted in accordance with the principles laid down in the Interinstitutional Agreement of 13 April 2016 on Better Law-Making (32). In particular, to ensure equal participation in the preparation of delegated acts, the European Parliament and the Council receive all documents at the same time as Member States’ experts, and their experts systematically have access to meetings of Commission expert groups dealing with the preparation of delegated acts.

(91)

To ensure that all children in the Union have access to medicinal products specifically authorised for paediatric use, when an agreed paediatric investigation plan has led to the authorisation of a paediatric indication for a medicinal product already marketed for other therapeutic indications, the marketing authorisation holder should be obliged to place the medicinal product on the same markets within two years of the date on which the medicinal product is authorised for that paediatric indication.

(92)

It is necessary in the interest of public health to ensure the continuing availability of safe and effective medicinal products authorised for paediatric indications. Therefore, if a marketing authorisation holder intends to withdraw such a medicinal product from the market, arrangements should be in place so that the paediatric population can continue to have access to the medicinal product in question. In order to help achieve this, the competent authorities of the Member States or the Agency, as applicable, should be informed in good time of any such intention and should make that intention publicly available.

(93)

To avoid unnecessary administrative and financial burdens both for the marketing authorisation holders and the competent authorities of the Member States or the Agency, as applicable, certain streamlining measures should be introduced, in line with the digital by default principle. Electronic applications for marketing authorisations and for variations of the terms of marketing authorisations should be introduced.

(94)

As a general rule, risk management plans should not be developed or submitted for generic medicinal products and biosimilar medicinal products, considering that the reference medicinal product has such a plan, except in specific cases where a risk management plan should be provided. In addition, risk management plans for hybrid medicinal products and bio-hybrid medicinal products should be limited to the differences between those medicinal products and the reference medicinal product, as indicated in the marketing authorisation application, provided that no additional risk minimisation measures exist for the reference medicinal product and that the marketing authorisation for the reference medicinal product has not been withdrawn prior to the submission of the application.

(95)

As a general rule, marketing authorisations should be granted for an unlimited period. Where, by way of derogation, a national marketing authorisation has been granted for a limited period, it should be possible for the marketing authorisation holder to submit an application for a renewal of that authorisation. Decisions on renewals should be based only on a re-evaluation of the benefit-risk balance of the medicinal product.

(96)

In the event of a risk to public health, the marketing authorisation holder or the competent authorities of the Member States or the Commission should be able to impose urgent safety or efficacy restrictions on their own initiative. In such cases, when the Union interest referral procedure is launched, any duplication of assessments should be avoided.

(97)

To address patients’ needs, an increasing number of innovative medicinal products derive from or are combined with other medicinal products that may be manufactured or tested and regulated under more than one Union legal framework. Similarly, the same sites are increasingly overseen by authorities established under different Union legal frameworks. To ensure safe and efficient production and supervision of such products and appropriate delivery to patients, it is important to ensure consistency between those frameworks. Consistency and proper alignment can only be ensured through appropriate cooperation in the development of the practices and principles applied under the different Union legal frameworks. Appropriate cooperation should therefore be embedded within several provisions of this Directive, such as those regarding classification advice, supervision, or the development of guidelines.

(98)

For products that combine a medicinal product and a medical device including an in vitro diagnostic medical device, the applicability of two regulatory frameworks, namely Regulation (EU) 2017/745 (33) or (EU) 2017/746 of the European Parliament and of the Council (34), as applicable, should be specified and the appropriate interaction between this Directive and the two other applicable regulatory frameworks should be ensured. The same should apply to combinations of medical products with products other than medical devices.

(99)

To ensure that the competent authorities have all the information needed for their assessment in the case of integral combinations of a medicinal product with a medical device, or of combinations of a medicinal product with a product other than a medical device, the marketing authorisation applicant should submit data demonstrating the safe and effective use of the integral combination of the medicinal product with the medical device or of the combination of a medicinal product with the other product. The competent authority should assess the benefit-risk balance of the integral combination of the medicinal product with the medical device or of the combination of the medicinal product with the product other than a medical device, taking into account the suitability of the use of the medicinal product together with the medical device or with the other product.

(100)

To ensure that the competent authorities of the Member States or the Agency, as applicable, have all the information needed for their assessment of medicinal products in exclusive use with a medical device or with an in vitro diagnostic medical device, that is to say, medicinal products that are presented in a package with a medical device or with an in vitro diagnostic medical device, or that are to be used with a medical device or with an in vitro diagnostic medical device referenced in the summary of product characteristics, the marketing authorisation applicant shall submit data demonstrating the safe and effective use of the medicinal product taking into account its use with the medical device or in vitro diagnostic medical device. The competent authorities of the Member States or the Agency, as applicable, should assess the benefit-risk balance of the medicinal product, taking into account the use of the medicinal product with the medical device or the in vitro diagnostic medical device.

(101)

This Directive also clarifies that a medical device that is part of an integral combination of a medicinal product with a medical device should comply with the general safety and performance requirements set out in Annex I to Regulation (EU) 2017/745. A medicinal product in exclusive use with a medical device or with an in vitro diagnostic medical device needs to meet all of the requirements of Regulation (EU) 2017/745 or (EU) 2017/746, as applicable. If the action of a medicinal product in exclusive use with a medical device or with an in vitro diagnostic medical device is not ancillary to that of the medical device or the in vitro diagnostic medical device, the medicinal product should comply with the requirements of this Directive and of Regulation (EU) 2026/… (+) taking into account its use with the medical device or in vitro diagnostic medical device, without prejudice to the specific requirements of Regulation (EU) 2017/745 or (EU) 2017/746, as applicable.

(102)

For integral combinations of a medicinal product with a medical device, medicinal products in exclusive use with a medical devices or with an in vitro diagnostic medical device and combinations of a medicinal product with a product other than a medical device, the competent authorities of the Member States or the Agency, as applicable, should also be able to request the marketing authorisation applicant to transmit any additional information needed and the marketing authorisation applicant should be bound to submit any such information requested. For medicinal products in exclusive use with a medical device or with an in vitro diagnostic medical device that is not ancillary to that of the medical device or the in vitro diagnostic medical device, the marketing authorisation applicant should also, upon request from the competent authorities of the Member States or the Agency, as applicable, submit any additional information relating to the medical device or in vitro diagnostic medical device, taking into account its use with the medicinal product, and that is relevant for the post-authorisation monitoring of the medicinal product, without prejudice to the specific requirements of Regulation (EU) 2026/… (+).

(103)

For integral combinations of a medicinal product with a medical device and for combinations of a medicinal product with a product other than a medical device, the marketing authorisation holder should also bear the overall responsibility for the whole products in terms of compliance of the medicinal product with the requirements of this Directive and Regulation (EU) 2026/…+ and should ensure coordination of the information flow between the sectors throughout the assessment procedure and the lifecycle of the medicinal product.

(104)

In order to ensure the quality, safety and efficacy of medicinal products at all stages of manufacturing and distribution, the marketing authorisation holder should be responsible, when necessary, for tracing back an active substance, excipient or any other substance that is used in the manufacture of a medicinal product and intended to be part of the medicinal product or expected to be present in the medicinal product, for example impurities, degradation products or contaminants.

(105)

In the interest of public health, marketing authorisation holders should be able to ensure the traceability of any substance that is used, intended or expected to be present in a medicinal product at all stages of manufacturing and distribution, and should be able to identify any natural or legal person from whom they have been supplied these substances. Therefore, procedures and systems should be put in place to provide that information where necessary to ensure the quality, safety or efficacy of medicinal products.

(106)

It is recognised that the development of pharmaceuticals is an area where neither science, nor technology stand still. The last decades have seen new categories of medicinal products emerging, such as biological medicinal products, biosimilar medicinal products, advanced therapy medicinal products and, in the future, phage therapies. Those categories of products, in some instances, require adapted rules to fully take account of their specific characteristics. For that reason, a forward-looking legal framework should include provisions to enable such adapted frameworks subject to strict criteria and under a Commission empowerment guided by the scientific input of the Agency.

(107)

The adaptations required for certain medicinal products or categories of medicinal products can entail specific requirements and targeted technical adaptations of the requirements compared to standard medicinal products. They could in particular include changes to the dossier requirements for such medicinal products, the way their quality, safety and efficacy is demonstrated by applicants or tailored manufacturing controls and good manufacturing practice requirements, as well as additional control methods prior and during their administration and use. Those adaptations should however not go beyond what is necessary for the attainment of the objective of adaptation to the specific characteristics or methods related to the medicinal product or category of medicinal products concerned.

(108)

In order to increase preparedness and response capacity against health threats, in particular the emergence of antimicrobial resistance, adapted frameworks could prove useful in facilitating rapid changes to antimicrobials composition in order to preserve their efficacy. The use of established platforms would allow efficient and timely adaptation of those medicinal products to the clinical context.

(109)

To optimise the use of resources for both marketing authorisation applicants and competent authorities and to avoid duplication of assessments of chemical active substances of medicinal products, marketing authorisation applicants should be able to rely on an active substance master file certificate or a certificate of suitability to the monograph of the European Pharmacopoeia, instead of submitting the relevant data as required in accordance with Annex II. It should be possible for an active substance master file certificate to be granted by the Agency in cases where the relevant data on the active substance concerned are not already covered by a monograph of the European Pharmacopoeia or by another active substance master file certificate. Where a certificate of suitability to a monograph of the European Pharmacopoeia or an active substance master file certificate is used as part of the marketing authorisation application, it should be possible to provide additional quality data that are not covered by those processes, as part of the marketing authorisation dossier to demonstrate the suitability of the active substance in the context of its intended use in the medicinal product. The Commission should be empowered to establish the procedure for the single assessment of an active substance master file. To further optimise the use of resources, the Commission should be empowered to allow the use of a certification scheme also for additional quality master files i.e. for active substances other than chemical active substances, or for other substances present or used in the manufacture of a medicinal product, required in accordance with Annex II, e.g. in case of novel excipients, adjuvants, radiopharmaceutical precursors and active substance intermediates, when the intermediate is a chemical active substance by itself or used in combination with a biological substance.

(110)

The concept of platform technology master files allows the reliance on data – encompassing aspects of quality, non-clinical, and clinical information – that have been pre-evaluated in the marketing authorisation application of a medicinal product. Platform technologies include, but are not limited to, viral and bacterial vector systems, recombinant protein-based methods, nucleic acid sequences, viral and bacterial vectors and synthetic biology approaches such as oligonucleotides and mRNA. The platform technology master file that documents the platform technology should be certified by the Agency to allow future uses. In the context of applying for marketing authorisations, products developed and manufactured using platform technology master files are to focus on the customisation of the platform to address the particular attributes of the medicinal product in question. This methodology avoids the duplication of assessments and minimizes the repetition of studies, thereby streamlining the development and regulatory evaluation processes for medicinal products. A fundamental requirement for the effective application of platform technology is the presence of a common dataset that remains applicable across medicinal products using the same technology. To qualify the use of a platform technology master file, applicants are obliged to demonstrate the applicability of the common dataset, substantiate the development and manufacturing platform, and furnish scientific justification that underscores the relevance of the platform data to the medicinal product in question. While the owner of a platform technology master file and the marketing authorisation holder are not necessarily the same, for example, some platform technologies can emanate from academic research and development, the marketing authorisation holder relying on a platform technology master file should retain full responsibility for its marketing authorisation, including the parts covered by the master file.

(111)

For reasons of public health and legal consistency, and with a view to reducing the administrative burden and strengthening predictability for economic operators, variations of all types of marketing authorisations should be subject to harmonised rules.

(112)

It should be possible for the terms of a marketing authorisation for a medicinal product to be varied after it has been granted. While the core elements of a variation are laid down in this Directive, the Commission should be empowered to complement those elements by laying down further necessary elements, to adapt the system to scientific and technological progress, including digitalisation, and to ensure that unnecessary administrative burden is avoided for both the marketing authorisation holders and the competent authorities of the Member States.

(113)

The competent authorities of the Member States should have the power to evaluate additional evidence that can affect the benefit-risk balance of medicinal products, beyond what is provided by marketing authorisation holders. Where justified, the competent authorities of the Member States should be able to recommend that the marketing authorisation holder varies the terms of its marketing authorisation.

(114)

Scientific and technological progress in data analytics and data infrastructure provide valuable support to the development, marketing authorisation and supervision of medicinal products. The digital transformation has affected regulatory decision-making, making it more data-driven and multiplying the possibilities for regulatory authorities to access evidence across the lifecycle of a medicinal product. This Directive recognises the competent authorities of the Member States’ capacity to access and analyse data submitted independently from the marketing authorisation applicant or marketing authorisation holder. On that basis, the competent authorities of the Member States should take the initiative to recommend that the summary of product characteristics be updated in case new efficacy or safety data have an impact on the benefit-risk balance of a medicinal product.

(115)

Access to individual patient data from clinical studies in structured format allowing for statistical analyses can assist regulators in understanding the submitted evidence and inform regulatory decision-making on the benefit-risk balance of a medicinal product. The introduction of such a possibility in the legislation is important to further enable data-driven benefit-risk assessments at all stages of the lifecycle of a medicinal product. This Directive therefore empowers competent authorities of Member States to request, as necessary, such data as part of the assessment of initial and post-marketing authorisation applications. Due to the sensitive nature of health data, the competent authorities should safeguard its processing operations and ensure that they respect the data protection principles of lawfulness, fairness and transparency, purpose limitation, data minimisation, accuracy, storage limitation, integrity and confidentiality. Where the processing of personal data is necessary for the purposes of this Directive, such processing should be done in accordance with Union law on the protection of personal data. Any processing of personal data under this Directive should take place in accordance with Regulations (EU) 2016/679 (35) and (EU) 2018/1725 (36) of the European Parliament and of the Council.

(116)

Pharmacovigilance rules are necessary for the protection of public health in order to prevent, detect and assess adverse reactions to medicinal products placed on the Union market, as the full safety profile of medicinal products can only be known after they have been placed on the market.

(117)

In order to ensure the continued safety of medicinal products in use, it is necessary to ensure that pharmacovigilance systems in the Union are continually adapted to take account of scientific and technical progress.

(118)

It is necessary to take account of changes arising as a result of international harmonisation of definitions, terminology and technological developments in the field of pharmacovigilance.

(119)

The increasing use of electronic networks for communication of information on adverse reactions to medicinal products marketed in the Union is intended to allow competent authorities to share the information at the same time. In order to simplify the reporting of suspected adverse reactions, the marketing authorisation holders and the Member States should report those reactions only to the Union pharmacovigilance database and data-processing network referred to in Regulation (EU) 2026/… (+) (the ‘Eudravigilance database’). The Eudravigilance database will be equipped to immediately forward reports on suspected adverse reactions received from marketing authorisation holders to the Member States on whose territory the reaction occurred. It should be possible for the Agency, in consultation with the Commission, Member States and marketing authorisation holders, to draw up and publish a detailed guide regarding the monitoring of relevant adverse reaction databases maintained outside the Union and the entry of relevant information from those databases into the Eudravigilance database.

(120)

Member States and marketing authorisation holders should operate a pharmacovigilance system to collect information that is useful for the monitoring of medicinal products, including information on suspected adverse reactions arising from use of a medicinal product within the terms of the marketing authorisation as well as from use outside the terms of the marketing authorisation, including off-label use, overdose, misuse, abuse and medication errors by patients and healthcare professionals. Mistakes in the prescribing, dispensing, storing, preparation and administration of a medicine are common types of medication errors. Suspected adverse reactions should be recorded and reported by Member States and marketing authorisations holders to the Eudravigilance database for the monitoring of safety of medicinal products. The reports should be part of the continuous evaluation of the benefit-risk balance of the medicinal products. Summaries of data relevant to the benefit-risk balance should be included in periodic safety update reports. Marketing authorisation holders should also record and report information on adverse reactions occurring in the context of post-authorisation studies, including post-authorisation studies in specific populations such as children, for evaluation of the benefit-risk balance.

(121)

It is the interest of the Union to ensure that the pharmacovigilance systems for centrally authorised medicinal products and those authorised by other procedures are consistent.

(122)

Marketing authorisation holders should be proactively responsible for on-going pharmacovigilance of the medicinal products they place on the market including for an appropriate period after the marketing authorisation has been withdrawn or revoked.

(123)

The use of colours in human and veterinary medicinal products is currently regulated by Directive 2009/35/EC of the European Parliament and of the Council (37) and is restricted to those authorised in accordance with Regulation (EC) No 1333/2008 of the European Parliament and of the Council (38), for which specifications are laid down in Commission Regulation (EU) No 231/2012 (39). The use of excipients other than colours in medicinal products is subject to the Union rules on medicinal products and is evaluated as part of the overall benefit-risk profile of a medicinal product.

(124)

Experience has shown the need to maintain to a certain extent the principle of the use in medicinal products of those colours authorised as food additives. However, it is also appropriate to provide for a specific assessment of the use of a colour in medicinal products when a food additive is removed from the Union list of authorised food additives. Therefore, in this specific case, the Agency should carry out its own assessment of the use of the colour concerned in medicinal products, taking into account the European Food Safety Authority opinion and its underlying scientific evidence, as well as any additional scientific evidence and giving particular consideration to the use of the colour concerned in medicinal products. The Agency should also be responsible for following any scientific evidence for the colours retained for specific medicine use only. Directive 2009/35/EC should therefore be repealed.

(125)

With regard to supervision and inspections, manufacturing and import of excipients, functional excipients, starting materials or intermediate products should be under surveillance due to their possible ancillary action on the active substance and to their possible impact on the quality, safety and efficacy of the medicinal products.

(126)

The main purpose of any regulation on the manufacture and distribution of medicinal products is to safeguard public health.

(127)

Manufacturing and wholesale distribution authorisations are to be subject to certain essential conditions and it is the responsibility of the Member State concerned to ensure that such conditions are met; each Member State is to recognise authorisations granted by other Member States.

(128)

It should be ensured that, in the Member States, the supervision and control of the manufacture and the distribution of medicinal products are carried out by official representatives of the competent authority who fulfil minimum conditions of qualification.

(129)

There may be cases where manufacturing activities, including testing, of medicinal products need to take place in sites close to patients, taking into account the specific properties of the medicinal product as well as considerations related to its quality, safety and efficacy, for example advanced therapy medicinal products with a short shelf-life or where proximity to the patient being treated or customisation for an individual patient is to the patient’s benefit. In such cases, it can be necessary for manufacturing to be decentralised to multiple sites to reach patients across the Union. The use of decentralised manufacturing should be approved during the marketing authorisation procedure where deemed appropriate by the competent authority of the Member State or the Agency. Where the manufacturing steps are decentralised, they should be carried out under the responsibility of the qualified person of an authorised central site. The decentralised sites should not be required to obtain a manufacturing authorisation separate from the one granted to the relevant central site but should be registered by the competent authority of the Member State in which the decentralised site is located and supervised by that authority. In the case of medicinal products containing, consisting of or derived from SoHO, the decentralised sites are to be registered as SoHO entities as defined in and in accordance with Regulation (EU) 2024/1938 for the activities of donor review and eligibility assessment, donor testing and collection, where applicable. In respect of decentralised sites falling within the scope of this Directive and engaging in activities covered by other Union legal acts, in order to ensure their effective functioning, the competent authorities of the Member States supervising the central site and the decentralised sites should cooperate and exchange information with the authorities supervising those activities under other Union legal acts. This cooperation should, where appropriate, pertain to the coordination of authorisation, registration and supervision activities, including joint inspections, related to the central site and the decentralised sites, aiming to ensure efficiency of those activities.

(130)

The quality of medicinal products manufactured or available in the Union should be guaranteed by requiring that the active substances used in their composition comply with the principles of good manufacturing practice in relation to those medicinal products.

(131)

Verification of compliance with the legal requirements of manufacturing, distribution and use of medicinal products by relevant entities through a system of supervision, is of fundamental importance to ensure that the objectives of this Directive are effectively achieved. Therefore, the competent authorities of the Member States should be empowered to perform on site or remote inspections, as part of the system of supervision at all stages of manufacturing, distribution and use of medicinal products or active substances. It has proved necessary to reinforce the Union provisions on inspections and to compile a Union database of the results of those inspections. The competent authorities of the Member States should have the possibility to rely on the outcome of inspections conducted by trusted non-Union regulatory authorities. To preserve the effectiveness of the inspections, the competent authorities should also have the possibility to perform joint inspections and also, where necessary, unannounced inspections.

(132)

The frequency of controls should be established by the competent authorities having regard to the risk and to the level of compliance expected in different situations. That approach should allow those competent authorities to allocate resources where the risk is highest. In some cases, the system of supervision should be applied irrespective of the level of risk or suspected non-compliance, for example in the context of granting manufacturing authorisations.

(133)

Within the procedure for ‘Certification of Suitability to the monographs of the European Pharmacopoeia’, the European Directorate for the Quality of Medicines and Healthcare of the Council of Europe is to verify, by means of inspections, whether the data submitted by the applicant confirms the suitability of monographs to control the chemical purity, microbiological quality and, if relevant, Transmissible Spongiform Encephalopathy risk. It is also to verify whether the manufacturing complies with good manufacturing practice for active substances. Depending on the outcome of the inspection, a certificate of compliance or non-compliance with good manufacturing practice is issued by the European Directorate for the Quality of Medicines and Healthcare of the Council of Europe or by the Member State participating in the inspection.

(134)

Each undertaking that manufactures or imports medicinal products should set up a mechanism to ensure that all information supplied about a medicinal product is in conformity with the approved conditions of use.

(135)

The conditions governing the supply of medicinal products to the public should be harmonised.

(136)

In relation to the supply of medicinal products to the public, persons moving around within the Union have the right to carry a reasonable quantity of medicinal products lawfully obtained for their personal use. It should also be possible for a person established in one Member State to obtain a reasonable quantity of medicinal products from another Member State, where those products are intended for that person’s personal use.

(137)

Pursuant to Regulation (EU) 2026/… (+), certain medicinal products are subject to a centralised marketing authorisation. In this context, the prescription status of medicinal products covered by a centralised marketing authorisation needs to be established. It is therefore important to set the criteria on the basis of which Union decisions will be taken.

(138)

It is also appropriate to harmonise the basic principles applicable to the prescription status of medicinal products in the Union or in the Member State concerned, while taking as a starting point the principles already established on this subject by the Council of Europe as well as the work of harmonisation completed within the framework of the United Nations Single Convention on narcotic drugs of 1961 and the United Nations Convention on Psychotropic Substances of 1971.

(139)

Many operations involving the wholesale distribution of medicinal products can cover several Member States simultaneously.

(140)

It is necessary to exercise control over the entire chain of distribution of medicinal products, from their manufacture or import into the Union through to their supply to the public, so as to guarantee that such products are stored, transported and handled in suitable conditions. The requirements that should be adopted for this purpose will considerably facilitate the withdrawal of defective products from the market and allow more effective efforts against counterfeit products.

(141)

Any person involved in the wholesale distribution of medicinal products should be in possession of a special authorisation. Pharmacists and other persons authorised to supply medicinal products to the public, who confine themselves to that activity, should be exempt from obtaining a special authorisation. It is however necessary, in order to control the complete chain of distribution of medicinal products, that pharmacists and other persons authorised to supply medicinal products to the public keep records showing transactions in products received.

(142)

Certain Member States impose certain public service obligations on wholesale distributors who supply medicinal products to pharmacists and on other persons authorised to supply medicinal products to the public. Those Member States should be able to continue to impose those obligations on wholesale distributors established within their territory. They should also be able to impose them on holders of a wholesale distribution authorisation that has been granted by another Member State on condition that they do not impose any obligation more stringent than those that they impose on their own wholesale distributors and provided that such obligations can be regarded as justified on grounds of public health protection and are proportionate in relation to the objective of such protection.

(143)

Rules should be laid down as to how the labelling and package leaflets are to be presented. The package leaflet should be accessible, easily legible, clearly comprehensible by users, including especially the target patient groups, and indelible. Design choices should primarily serve function and readability, rather than aesthetics.

(144)

The provisions governing the information supplied to users should provide a high degree of consumer protection, so that medicinal products are used correctly on the basis of full and comprehensible information.

(145)

The placing on the market of medicinal products the labelling and package leaflet of which comply with this Directive should not be prohibited or impeded on grounds connected with the labelling or package leaflet.

(146)

The use of electronic and technological possibilities for package leaflets other than in paper format can facilitate access to medicinal products and medicinal products distribution. It should always guarantee equal quality of information to all patients compared to product information in paper format. It can additionally enable other forms of transmission of such information to persons with sensory impairments, for example through audiovisual or other means.

(147)

Member States have varying levels of digital literacy and internet access. In addition, patient and healthcare professional needs can differ. It is therefore necessary that Member States have discretion with respect to the adoption of measures allowing package leaflets to be made available exclusively electronically for specific categories of medicinal products or for all medicinal products while ensuring that no patient is left behind, taking into account the needs of different age categories and the different levels of digital literacy in the population, and making sure that product information is easily accessible to all patients. Member States should, where appropriate, consider allowing package leaflets to be made available only electronically, while ensuring full compliance with the rules on protection of personal data, notably with Regulation (EU) 2016/679, and should prevent the identification, profiling or tracking of individuals and should adhere to harmonised standards developed at EU level.

(148)

Where Member States decide that the package leaflet should be made available only electronically, the marketing authorisation holders concerned should ensure that a paper version of the package leaflet is made available to patients upon request and free of charge. Marketing authorisation holders should also ensure adherence to all specifications, common standards and formats specified by the relevant implementing acts and guidance and that the information in digital format is easily accessible to all patients, for instance by including on the outer packaging of the product a digitally readable element, for example a QR code, a data matrix code, a barcode, or any other appropriate technology which would direct the patient to the electronic version of the package leaflet in a simple, user friendly and effective manner.

(149)

The use of multi-country packages that are also multilingual can be a tool for access to medicinal products, in particular for small markets and in public health emergencies. Where such packages are used, it should be possible for Member States to also allow the use on the labelling and package leaflet of an official language of the Union that is commonly understood in the Member States where the multi-country package that is also multilingual is marketed.

(150)

Security of supply in Malta continues to be hindered by the low availability of medicinal products with package leaflets in the official languages of that Member State. For this reason, it is appropriate to allow for the competent authorities of Malta to maintain in force marketing authorisations that were granted, extended or maintained in accordance with Article 126c of Directive 2001/83/EC and that are valid at the time of entry into force of this Directive until after the rules on electronic product information become applicable in all Member States, taking also into account the deferred application of those rules for medicinal products already placed on the market.

(151)

To ensure a high level of transparency of public support to the research and development of medicinal products, the reporting of any public contribution to the development of a particular medicinal product should be a requirement for all medicinal products. Given however the practical difficulty to identify how indirect public funding instruments, such as tax advantages, have supported a particular medicinal product, the reporting obligation should only concern the direct public financial support, such as direct grants or contracts, received from any public authority, publicly funded body, philanthropic organisation, or not-for-profit organisation or fund. Therefore, the provisions of this Directive ensure, without prejudice to the rules on the protection of confidential and personal data, transparency regarding any direct financial support received from any public authority or publicly funded body, philanthropic organisation, or not-for-profit organisation or fund to carry out any activities for the research and development of medicinal products.

(152)

To ensure the accuracy of the information on public financial support made publicly available by the marketing authorisation holder, that information should be subject to an audit by an independent external auditor.

(153)

In order to ensure a harmonised and consistent reporting of any public contribution to the development of a particular medicinal product, the Commission should adopt implementing acts to lay down the principles and format to which the marketing authorisation holder should adhere when reporting that information.

(154)

This Directive is without prejudice to the application of measures adopted pursuant to Directive 2006/114/EC of the European Parliament and of the Council (40) or pursuant to Directive 2005/29/EC of the European Parliament and of the Council (41). Therefore, the provisions of this Directive regarding the advertising of medicinal products should be considered, where relevant, as a lex specialis with respect to Directive 2005/29/EC.

(155)

Advertising of medicinal products, even of medicinal products not subject to medical prescription, could affect public health and distort competition. Therefore, the advertising of medicinal products should meet certain criteria. Persons qualified to prescribe, administer or supply medicinal products can properly evaluate the information available in advertising because of their knowledge, training and experience. The advertising of medicinal products to persons who cannot properly assess the risk associated with their use can lead to medicinal product misuse or overconsumption which is liable to harm public health. Therefore, the advertising to the general public of medicinal products that are available on medical prescription only should be prohibited. Furthermore, distribution of samples free of charge to the general public for promotional ends is to be prohibited, also teleshopping for medicinal products is prohibited under Directive 2010/13/EU of the European Parliament and of the Council (42). It should be possible, under certain restrictive conditions, to provide samples of medicinal products free of charge to persons qualified to prescribe or supply them so that they can familiarise themselves with new products and acquire experience in dealing with them.

(156)

The advertising of medicinal products should aim to disseminate objective and unbiased information about the medicinal product. For that purpose, it is expressly forbidden to highlight negatively another medicinal product or to suggest that an advertised medicinal product might be safer or more effective than another medicinal product. Comparison of medicinal products should only be allowed if it is based on information that is supported objectively by the summaries of product characteristics of the medicinal products concerned. This prohibition covers any medicinal product, including biosimilar medicinal products, and therefore it would be misleading to suggest, in the advertisement, that a biosimilar medicinal product would not be interchangeable with the original biological medicinal product or another biosimilar medicinal product similar to the same original biological medicinal product. Additional strict rules about negative and comparative advertising of competitor medicinal products should aim to prohibit claims that can mislead persons qualified to prescribe, administer or supply them.

(157)

The dissemination of information which encourages the purchase of medicinal products should be considered to fall under the concept of advertising of medicinal products, even where that information does not refer to a specific medicinal product but refers to unspecified medicinal products.

(158)

The advertising of medicinal products should be subject to strict conditions and effective, adequate monitoring. Reference in this regard should be made to the monitoring mechanisms set up by Directive 2006/114/EC.

(159)

Medical sales representatives have an important role in the promotion of medicinal products. Therefore, certain obligations should be imposed upon them, in particular the obligation to supply the person visited with a summary of product characteristics.

(160)

Even minimal inducement can result in biased decisions with regard to prescription behaviour by physicians. Therefore, to avoid conflicts of interest, in the absence of national rules governing the disclosure of transfers of value, Member States should establish and maintain a publicly available list of links to the disclosure platforms operated by trade associations or by marketing authorisation holders for the reporting of transfers of value related to the advertising activities.

(161)

Innovative, combination medicinal products and other developed medicinal products are complex as regards their composition and administration. Therefore, people who are qualified to administer medicinal products, as well as people who are qualified to prescribe such products, need to be familiar with all the characteristics of those medicinal products, in particular their safe administration and use, including comprehensive instructions for patients. For that purpose, providing information about medicinal products subject to medical prescription to persons qualified to administer them is also clearly allowed.

(162)

Persons qualified to prescribe, administer or supply medicinal products should have access to a neutral, objective source of information about products available on the market. It is nevertheless for the Member States to take all measures necessary to this end, in the light of their own particular situation.

(163)

In order to avoid waste, reduce the burden on the environment, mitigate shortages and realise cost savings, it is feasible to allow re-dispensing of medicinal products, under strict conditions. Through the practice of re-dispensing, a pharmacy can take back and re-dispense a medicinal product that has already been supplied to a patient. Member States should ensure that re-dispensing can only be done by the same pharmacy that initially supplied the medicinal product. A pharmacy should only be allowed to re-dispense medicinal products to an individual patient identified by name, on the basis of informed consent. The returned medicinal products should be allowed to be re-dispensed only after the pharmacy has verified that the medicinal product concerned is not a falsified medicinal product, that the expiry date has not passed and that the medicinal product has been stored under appropriate conditions. To check these parameters, instruments such as a tamper-proof bag and temperature logger can be used. The pharmacy should record the medicinal product and the recipient for the purpose of inspections. Re-dispensing might not be feasible for all medicinal products. Member States should be able to identify and list in national legislation which specific medicinal products are allowed to be re-dispensed in that Member State, such as oral oncological medicinal products, which could provide for a pilot category. Member States should lay down rules on liability for potential harm resulting from the use of the medicinal products that have been re-dispensed when such harm is a consequence of a failure to ensure appropriate storage or transport conditions between the initial dispensing of the medicinal product and its return to the pharmacy, or a failure to ensure that the medicinal product re-dispensed has not been falsified. This provision should not affect the possibility for Member States to set additional restrictive conditions under which medicinal products can be re-dispensed. Member States should ensure that the collection and re-dispensing of medicinal products are not used for obtaining economic gains and allowing penetration of the re-dispensed medicinal products to the supply chain.

(164)

In order to ensure that information on the use of the medicinal products in children are appropriately taken into account at the moment of marketing authorisation, it is necessary to introduce a requirement for new medicinal products or when developing paediatric indications of already authorised medicinal 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 submitting a marketing authorisation application or an application for a new therapeutic indication, new pharmaceutical form or new route of administration. In order to ensure that the data supporting the marketing authorisation concerning the use of a medicinal product in children are adequate, the competent authorities responsible for the authorisation of a medicinal product should check that the studies conducted comply with the agreed paediatric investigation plan or whether any waivers or deferrals have been granted, when validating the marketing authorisation applications.

(165)

To provide healthcare professionals and patients with information on the safe and effective use of medicinal products in the paediatric population, the results of the studies conducted in accordance with a paediatric investigation plan, irrespective of whether or not those results support the use of the medicinal product in children, should be included in the summary of product characteristics and, if appropriate, in the package leaflet of the medicinal product. Information on waivers should also be included in the product information. When all the measures provided for in the paediatric investigation plan have been complied with, that fact should be recorded in the marketing authorisation, and that should then be the basis upon which companies can obtain rewards.

(166)

Relevant data and information collected through clinical studies conducted before the introduction in the Union of a paediatric medicines Regulation and received by the competent authorities should be assessed without undue delay and taken into consideration for eventual variations of existing marketing authorisations.

(167)

In order to ensure uniform conditions for the implementation of this Directive, implementing powers should be conferred on the Commission in order to: lay down details of the application for a hospital exemption approval, specify the content and format for the collection and reporting of data on ATMPs prepared under hospital exemption, lay down the practical arrangements for the exchange of knowledge between holders of a hospital exemption approval and the modalities for the preparation and use of ATMPs under hospital exemption, on a non-routine basis; set out the content and format of the request to use decentralised manufacturing and specify the application of decentralised manufacturing; establish a list of colours permitted for use in medicinal products other than those included in the Union list of authorised food additives and to adopt decisions as to whether a colour is to be added to that list; adopt decisions on applications, after receiving the opinion of the Committee for Medicinal Products for Human Use or the position of the majority of the Member States represented within the coordination group, as applicable, and after obtaining the opinion of the Standing Committee on Medicinal Products for Human Use, in particular, in the event of divergent positions of Member States in a decentralised or mutual recognition procedure or in relation to harmonisation of summary of product characteristics, in the event of divergent decisions by Member States concerning a national marketing authorisation, its variation, suspension or revocation or the summary of product characteristics, or in the event of divergent positions of Member States in the context of the Union interest referral or the urgent Union procedure or the procedure for regulatory action on periodic safety update reports or following the submission of a final study report on non-interventional post-authorisation safety studies; lay down the principles and format for the information on the public financial support received to be reported; establish common standards and formats for the electronic version of the package leaflet, the summary of product characteristics and the labelling, establish criteria for the provision of such product information through secure digital platforms and services and for the provision, establishment, management and accessibility of such digital platforms and services, establish the procedures to validate the electronic version of the package leaflet and to make it available to patients, specify information on the packaging on how to access this electronic version and specify the details on how to include the commonly recognised global antimicrobial resistance symbol in the package leaflet and information on antimicrobial resistance and the importance of appropriate use and disposal of antimicrobials; harmonise the performance of the pharmacovigilance activities provided for in this Directive by setting out the content and rules on the maintenance of the pharmacovigilance system master file, minimum requirements for the quality system for the performance of pharmacovigilance activities, rules on the use of internationally agreed terminology, formats and standards for the performance of such activities, minimum requirements for the monitoring of data in the Eudravigilance database, the format and content of the electronic transmission of suspected adverse reactions and the format and content of electronic periodic safety update reports and risk management plans, the format of protocols, abstracts and final study reports for the non-interventional post-authorisation safety studies; establish a list of herbal substances, herbal preparations and combinations thereof for use in traditional herbal medicinal products; include a third country in a list after assessing its regulatory framework applicable to active substances exported to the Union and apply the relevant requirements; and specify the design and the technical, electronic and cryptographic requirements for verification of the authenticity of the common logo that is to be displayed on the website relating to the offer for sale at a distance to the public of medicinal products. Those powers should be exercised in accordance with Regulation (EU) No 182/2011 of the European Parliament and of the Council (43).

(168)

Due to the need to reduce the overall time taken to authorise medicinal products, the time between the opinion of the Committee for Medicinal Products for Human Use and any final decision from the Commission concerning national marketing authorisations, in particular for referrals, should be reduced, in principle, to 46 days.

(169)

On the basis of the opinion of the Committee for Medicinal Products for Human Use, the Commission should adopt a draft decision on the referral or the application concerned. In duly justified cases, it should be possible for the Commission to refer the opinion of the Committee for Medicinal Products for Human Use or the position of the majority of the Member States represented within the coordination group back to the Agency or to the coordination group, as applicable, for further consideration. The Commission’s draft decision may diverge from the opinion of the Committee for Medicinal Products for Human Use. The Commission should adopt its final decision by means of implementing acts after obtaining the opinion of the Standing Committee on Medicinal Products for Human Use. 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 is to use the available mechanisms under Regulation (EU) No 182/2011 and notably the possibility to obtain the Committee’s opinion by written procedure and within expeditious deadlines, which, in principle, do not exceed 10 calendar days.

(170)

The power to adopt acts in accordance with Article 290 of the Treaty on the Functioning of the European Union should be delegated to the Commission to adopt any necessary changes to Annex II in order to: take into account scientific and technical progress; amend Annexes I to VI in order to adapt them to scientific and technical progress as well as amend the ERA requirements as regards the obligation to indicate whether the medicinal product or any of its ingredients or constituents is an endocrine active agent or has been assigned to hazard classes referred to in this Directive, the obligation to include in the ERA risk mitigation measures to avoid or limit emissions in the environment of ingredients and constituents of medicinal products listed as pollutants in specific EU legislation and to explain how such measures can address the identified risks to the environment, the obligation to include in the ERA for antimicrobials an evaluation of the risk for antimicrobial resistance selection in the environment due to the manufacturing supply chain, use and disposal of the antimicrobial and the obligation to update the ERA with any relevant information, including relevant information from environmental monitoring, eco-toxicity studies, risk assessments under other Union legal acts and environmental exposure data or, for specified ERAs, with information that has been identified as missing concerning medicinal products that are potentially harmful to the environment; amend the list of labelling particulars in Annex IV in order to take account of scientific progress or patients’ needs; amend the list of medicinal products and categories of medicinal products in Annex VII in order to take account of scientific and technical progress; amend certain definitions in order to take account of technical and scientific progress and taking into account definitions agreed at Union and international level without amending the scope of the definitions; and amend the requirements as regards the degree of dilution of a homeopathic medicinal product to guarantee its safety as laid down in this Directive in order to take account of scientific progress. It is of particular importance that the Commission carry out appropriate consultations during its preparatory work, including at expert level, and that those consultations be conducted in accordance with the principles laid down in the Interinstitutional Agreement of 13 April 2016 on Better Law-Making. In particular, to ensure equal participation in the preparation of delegated acts, the European Parliament and the Council receive all documents at the same time as Member States’ experts, and their experts systematically have access to meetings of Commission expert groups dealing with the preparation of delegated acts.

(171)

The power to adopt acts in accordance with Article 290 of the Treaty on the Functioning of the European Union should be delegated to the Commission in order to supplement certain non-essential elements of this Directive in respect of: specifying the content and format of ERA monographs, the procedures for adopting and updating the ERA monographs, the procedures for submission of information, studies and data, the risk-based criteria for the selection and prioritisation of active substances in relation to ERA monographs and the use of ERA monographs in the context of new marketing authorisation applications for medicinal products to support the ERA for those medicinal products; specifying the procedure for examination of application of active substance master file certificate, the publication of such certificates, the procedure for changes to the active substance master file and its certificate, access to the active substance master file and its assessment report; specifying additional quality master files to provide information on a constituent of a medicinal product, the procedure for examination of application of a quality master file certificate, the publication of such certificates, the procedure for changes to the quality master file and its certificate, and access to the additional quality master file and its assessment report; identifying the substances to which the provisions on additional quality master file apply; determining the situations in which post-authorisation efficacy studies may be required; laying down the adapted framework for medicinal products and categories of medicinal products listed in Annex VII as well as the documentation to be submitted in that regard; setting out a reduced list of mandatory labelling particulars outlined in Annex IV that shall appear on the outer packaging of multi-country packages that are also multilingual; laying down detailed rules for the safety features in Annex IV setting out the characteristics and technical specifications of the unique identifier of the safety features that enables the authenticity of medicinal products to be verified and individual packs to be identified and setting out the lists of medicinal products or categories subject to medical prescription that are not to bear the safety features and those not subject to medical prescription that are to bear the safety features; specifying exemptions to variation and the categories in which variations should be classified and establishing procedures for the examination of applications for variations to the terms of marketing authorisations as well as specifying conditions and procedures for cooperation with third countries and international organisations for examination of applications for such variations; specifying the criteria and the verifications in relation to the assessment of the potential falsified character of medicinal products; specifying the annual notification to be made by the qualified person to the competent authority of the Member State where a decentralised site is located, on the inventory of the changes that have taken place as regards the information provided in the registration form relating to that decentralised site; specifying the principles of good manufacturing and good distribution practices for medicinal products and active substances, in line with other principles of good practice established under any other Union legal framework, as well as the rules applicable to excipients as regards the formalised risk assessment for ascertaining the appropriate good manufacturing practice taking into account requirements under other appropriate quality systems as well as the source and intended use of the excipients and previous instances of quality defects; and laying down the principles applicable to the system of supervision, the joint inspections, the exchange of information and cooperation in the coordination of inspections in the system of supervision and the trusted non-Union regulatory authorities. It is of particular importance that the Commission carry out appropriate consultations during its preparatory work, including at expert level, and that those consultations be conducted in accordance with the principles laid down in the Interinstitutional Agreement of 13 April 2016 on Better Law-Making. In particular, to ensure equal participation in the preparation of delegated acts, the European Parliament and the Council receive all documents at the same time as Member States’ experts, and their experts systematically have access to meetings of Commission expert groups dealing with the preparation of delegated acts.

(172)

This Directive seeks to enable the right of access to preventive healthcare and the right to benefit from medical treatment under the conditions established by national laws and practices and to ensure a high level of human health protection in the definition and implementation of all Union policies and activities as laid down in Article 35 of the Charter of Fundamental Rights of the European Union.

(173)

Since the objectives of this Directive, namely to establish rules on medicinal products ensuring the protection of public health and the environment as well as the functioning of the internal market, cannot be sufficiently achieved by the Member States as national rules would lead to disharmonisation, unequal patient access to medicinal products and barriers to the internal market, but can rather, by reason of their effects, be better achieved at Union level, the Union may adopt measures, in accordance with the principle of subsidiarity as set out in Article 5 of the Treaty on European Union. In accordance with the principle of proportionality as set out in that Article, this Directive does not go beyond what is necessary in order to achieve those objectives.

(174)

The European Data Protection Supervisor was consulted in accordance with Article 42(1) of Regulation (EU) 2018/1725 and delivered an opinion on 19 June 2023.

(175)

In accordance with the Joint Political Declaration of 28 September 2011 of Member States and the Commission on explanatory documents (44), Member States have undertaken to accompany, in justified cases, the notification of their transposition measures with one or more documents explaining the relationship between the components of a directive and the corresponding parts of national transposition instruments. With regard to this Directive, the legislator considers the transmission of such documents to be justified,