What changed

DRAFT EUROPEAN PARLIAMENT LEGISLATIVE RESOLUTION

on the Council position at first reading with a view to the adoptionproposal offor a directive of the European Parliament and of the Council on the Union code relating to medicinal products for human use, and repealing DirectivesDirective 2001/83/EC and Directive 2009/35/EC

(07106/2/2026–(COM(2023)0192 C100244/2026– C90143/2023 – 2023/0132(COD))

(Ordinary legislative procedure: secondfirst reading)

The European Parliament,

– having regard to the CouncilCommission positionproposal atto firstParliament readingand (07106/2/2026–the C100244/2026),Council (COM(2023)0192),

– having regard to Article 294(2) and Article 114(1) and Article 168(4), point (c), of the Treaty on the Functioning of the European Union, pursuant to which the Commission submitted the proposal to Parliament (C90143/2023),

– having regard to Article 294(3) of the Treaty on the Functioning of the European Union,

– having regard to the opinion of the European Economic and Social Committee of 25 October 2023,

– after consulting the Committee of the Regions,

– having regard to its position at first reading on the Commission proposal to Parliament and the Council (COM(2023)0192),

– having regard to Rule 59 of its Rules of Procedure,

– having regard to Articlethe 294(7)opinion of the TreatyCommittee on the Functioning ofIndustry, theResearch Europeanand Union,Energy,

– having regard to the provisional agreement approved by the committee responsible under Rule 75(4) of its Rules of Procedure,

– having regard to the letter from the Committee on Legal Affairs,

– having regard to Rule 68 of its Rules of Procedure,

– having regard to the report of the Committee on the Environment, Public Health and Food Safety (A9-0140/2024),

– having regard to the recommendation for second reading of the Committee on Public Health (A100000/2026),

1. Adopts its position at first reading hereinafter set out;

1. Approves the Council position at first reading;

2. Calls on the Commission to refer the matter to Parliament again if it replaces, substantially amends or intends to substantially amend its proposal;

2. Notes that the act is adopted in accordance with the Council position;

3. Instructs its President to sign the act with the President of the Council, in accordance with Article 297(1) of the Treaty on the Functioning of the European Union

4. Instructs its Secretary-General to sign the act, once it has been verified that all the procedures have been duly completed, and, in agreement with the Secretary-General of the Council, to arrange for its publication in the Official Journal of the European Union;

3. Instructs its President to forward its position to the Council, the Commission and the national parliaments.

SHORT JUSTIFICATION

Recital 2: (2) The most recent comprehensive revision took place between 2001 and 2004 while targeted revisions on post-authorisation monitoring (pharmacovigilance) and on falsified medicines 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 or highly burdensome treatments, or with treatments targeting only sub-populations of a disease. Moreover, some patients may not benefit from innovation because medicines may be unaffordable or not placed on the market in the Member State concerned. There is also a greater awareness of the environmental impact of medicines. More recently, the COVID-19 pandemic has stress tested the framework.

The Council position at first reading reflects the agreement reached between the European Parliament and the Council in interinstitutional negotiations at early second reading stage.

Recital 2 a (new): (2a) This Directive should contribute 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 diseases burdens of, humans and animals. In addition, pollution from active pharmaceutical ingredients negatively affects the quality of waters and ecosystems, posing risks to public health globally.

Recital 3: (3) This revision is part of the implementation of the Pharmaceutical strategy for Europe and aims to promote innovation, in particular for unmet medical needs, while reducing regulatory burden and the environmental impact of medicines; create an attractive environment for research, development and manufacturing of medicines in the Union; ensure access, including affordability, to innovative and established medicines 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 keeps medicines affordable for health systems and patients while rewarding innovation.

Recital 3 a (new): (3a) In parallel with this revision, the Union should strengthen the European pharmaceutical ecosystem to accelerate research and development of a new medicinal product and support innovation through the establishment of public-private partnerships, the multiplication of university hospital institutes, centres of excellence and bioclusters.

Recital 3 b (new): (3b) A range of Union programmes can be used to fund pharmaceutical research projects, such as Horizon Europe, InvestEU, EU4Health, cohesion policy and the Digital Europe Programme. The Union should also prioritise in its research agenda participation in cross-country collaboration enabling transnational research to meet public health needs.

Recital 4: (4) This revision focuses on provisions relevant to achieve its specific objectives; therefore it covers all but provisions concerning falsified medicines, homeopathic products and traditional herbal medicines. Nevertheless, for the sake of clarity, it is necessary to replace Directive 2001/83/EC of the European Parliament and of the Council38 with a new Directive. The provisions on falsified medicines, homeopathic products and traditional herbal medicines are therefore maintained in this Directive without changing their substance compared to previous harmonisations. However, in view of the changes in the governance of the Agency, the Herbal Committee is replaced by a working group.

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

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

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

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

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

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

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

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

Recital 15: (15) In order to take account both of the emergence of new therapies and of the growing number of so-called ‘borderline’ products between the medicinal product sector and other sectors, certain definitions and derogations should be modified, so as to avoid any doubt as to the applicable legislation. In cases where there is still a lack of clarity of the regulatory status of a product, the competent authorities or the Agency and the relevant advisory bodies responsible for other regulatory frameworks, namely medical devices and substances of human origin should engage in consultations. In such cases, the compendium referred to in Regulation (EU) 2024/... of the European Parliament and of the Council1a [SoHO Regulation] should be consulted, where relevant. If after consulting the compendium, there remains doubt about the regulatory status the relevant bodies should further consult to determine that regulatory status. The Commission and the Member States should facilitate the cooperation between the Agency, national competent authorities and advisory bodies established by other Union legislation. The opinions and the recommendations of the Agency and the relevant advisory bodies on the regulatory status of the product should be made publicly available after the consultations have taken place. With the same objective of clarifying situations when a product fully falls within the definition of a medicinal product and also meet the definition of other regulated products, the for me…

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

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

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

Recital 22 a (new): (22a) Particular attention should be given to the composition of clinical trials to ensure gender-based equity and comprehensive clinical data.

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

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

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

Recital 31: (31) Directive 2010/63/EU of the European Parliament and of the Council43 lays down provisions on the protection of animals used for scientific purposes based on the principles of replacement, reduction and refinement. Any study involving the use of animals, which provides essential information on the quality, safety and efficacy of a medicinal product, should take into account those principles of replacement, reduction and refinement, where they concern the care and use of live animals for scientific purposes, and should be only used as necessary and be optimised in order to provide the most satisfactory results whilst using the minimum number of animals. The marketing authorisation applicant should not carry out animal tests where scientifically satisfactory non-animal testing methods are available. Where scientifically satisfactory non-animal testing methods are not available, applicants that use animal testing should ensure that the principle of replacement, reduction and refinement of animal testing for scientific purposes has been applied with regard to any animal study conducted for the purpose of supporting the application. The procedures of such testing should be designed to avoid causing pain, suffering, distress or lasting harm to animals and should follow the available EMA and ICH guidelines. In particular, the marketing authorisation applicant and the marketing authorisation holder should take into account the principles laid down in Directive 2010/63/EU, includi…

Recital 32: (32) Procedures should be in place to facilitate joint animal testing, wherever possible, in order to avoid unnecessary testing using live animals covered by Directive 2010/63/EU. Marketing authorisation applicants and marketing authorisation holders should make all efforts to reuse animal study results and make the results obtained from animal studies publicly available. For abridged applications marketing authorisation applicants should refer to the relevant studies conducted for the reference medicinal product.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Recital 56: deleted

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

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

Recital 58 a (new): (58a) Cross-border healthcare is an important pathway for patients to access medicinal products that might otherwise not be available to them. To support access to medicinal products, in particular in the case of small patient populations, such as for paediatric or rare diseases, which are often disadvantaged when it comes to access to medicinal products, or where the administration of a medicinal product requires special competences or infrastructure, the full implementation of Directive 2011/24/EU of the European Parliament and of the Council1a should be supported. It is important to consider in that regard all alternative paths to making available medicinal products to patients. Competent authorities of the Member States should therefore utilise the NCAPR to exchange and share best practice regarding the implementation of cross-border access agreements and negotiations. / 1a Directive 2011/24/EU of the European Parliament and of the Council of 9 March 2011 on the application of patients’ rights in cross-border healthcare (OJ L 88, 4.4.2011, p. 45).

Recital 59: deleted

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

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

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

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

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

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

Recital 67: (67) The provision of information to healthcare professionals and to patients on the appropriate use, storage and disposal of antimicrobials is a joint responsibility of marketing authorisation holders and of Member States. Member States should ensure appropriate collection and disposal system for all medicinal products.

Recital 67 a (new): (67a) Pharmacists and other health care professionals should play a role in antimicrobial stewardship, including advising on the prudent use of antibiotics and other antimicrobials, as well as their correct disposal.

Recital 68: (68) While this Directive restricts the use of antimicrobials by setting antibiotics and antimicrobials wich have an identified risk of resistance under prescription status, due to the growing antimicrobial resistance in the Union, competent authorities of the Member States should consider further a number of measures, including expanding the prescription status of antimicrobials, restricting the use of certain antimicrobials to the use in hospitals, mandatory training of healthcare professionals on the environmental impact of medicines use and stewardship regarding the use of antimicrobials, or the mandatory use of diagnostic tests before prescription. Member States should also ensure that measures are in place to safeguard the prescription for antibiotic products from influence by any form of economic incentive provided directly or indirectly to persons who prescribe medicinal products, given the risks associated with antimicrobial resistanceand for avoiding risks to the environment, in line with the European Union Strategic Approach to Pharmaceuticals in the Environment. Additionally, the combined use of several antimicrobial active substances may represent a particular risk with respect to the development of antimicrobial resistance. Such combined use should therefore only be prescribed in exceptional cases where the benefit-risk balance of the combination is favorable. Competent authorities of the Member States should promote the availability of rapid diagnostic tests in…

Recital 69: (69) 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 from their manufacturing, 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 the Water Framework Directive (2000/60/EC50), the Environmental Quality Standard Directive (2008/105/EC51) the Groundwater Directive (2006/118/EC52), the Urban Wastewater Treatment Directive (91/271/EEC53), the Drinking Water Directive (2020/218454), the Industrial Emissions Directive (2010/75/EU55) and the Waste Framework Directive (2008/98/EC55a). / 55a Directive 2008/98/EC of the European Parliament and of the Council of 19 November 2008 on waste and repealing certain Directives (OJ L 312, 22.11.2008, p. 3).

Recital 69 a (new): (69a) Emissions of active substances during manufacturing can be a threat to the environment and public health. Therefore, environmental risks should be assessed and addressed through the entire lifecycle of medicinal products, starting from manufacturing, through use and to disposal.

Recital 69 b (new): (69b) Unitary packaging of medicinal products, in particular in hospital pharmacies, where this packaged and distributed in bulk could result in a decrease of packaging materials used and thereby contribute to environmental footprint of medicinal products, including its waste. It can also contribute to mitigating medicine shortages and antimicrobial resistance. The use of single dose unit containing all relevant information, in hospital environment, could furthermore represent an improvement in the risk of medication errors and therefore increase patient protection. Member States should promote the use of unit dose pre-cut blisters in hospital environment and, progressively, in dispensing pharmacies, when necessary.

Recital 69 c (new): (69c) The use of pharmaceuticals in human and veterinary medicinal products, including antimicrobials, has increased their concentrations in many environmental reservoirs such as soils, sediments and waterbodies in the past 20 years, and the environmental concentration is likely to increase further as the population grows and ages. The discharge of pharmaceuticals into the environment can not only harm ecosystems and wildlife, but can also undermine the effectiveness of those same pharmaceuticals. The chemical and metabolic stability of certain pharmaceuticals means that up to 90 % of their active substances are released into the environment in their original form after use.

Recital 70 a (new): (70a) In exceptional cases where the ERA is incomplete due to missing data and this can be duly justified and substantiated by the marketing authorisation holder, it should still be possible, for reasons in the interest of public health, for the medicinal product to be placed on the market with certain post-authorisation conditions and obligations. Where a medicinal product has been authorised and the ERA is incomplete due to missing data, the marketing authorisation holder should submit the completed ERA in the timeline agreed with the authorities and deliver upon any other post-authorisation obligations.

Recital 71: (71) Marketing authorisation applicants should take into account environmental risk assessment procedures of other EU legal frameworks that may apply to chemicals dependent on their use. Further to this Regulation, there are four main other frameworks: (i) Industrial chemicals (REACH, (Regulation (EC) No 1907/2006); (ii) Biocides (Regulation (EC) No 528/2012); (iii) Pesticides (Regulation (EC) No 1107/2009); and (iv) Veterinary medicines (Regulation (EU) 2019/6)). As a part of the Green Deal, the Commission has proposed a ‘one-substance one-assessment’ (OS-OA) approach for chemicals56 , in order to increase the efficiency of the registration system, reduce costs and unnecessary animal testing. The ERA covers the risks associated with production. Compliance with relevant Union and Member State legislation in terms of environmental protection at the stage of manufacturing should generally be considered as a relevant risk mitigation measure in terms of production. This should also apply for production in third countries with a level of environmental protection equivalent to that of the Union. More environmentally friendly pharmaceuticals would contribute positively to human health.

Recital 72: (72) The emissions and discharges of antimicrobials to the environment from manufacturing sites may lead to antimicrobial resistance (“AMR”), which is a global concern regardless where the emissions and discharges take place. Therefore, the ERA scope should be extended to cover the risk of AMR selection during the entire life cycle of antimicrobials, including manufacturing. At the date of adoption of this Directive, for the purpose of the ERA, there is not a scientifically agreed method to measure antimicrobial resistance other than for antibiotic resistance. The Commission should therefore issue, after consulting the European Medicines Agency (EMA), the European Centre for Disease Prevention and Control (ECDC) and the European Environment Agency (EEA), guidelines on how to conduct ERAs for AMR selection for microbials other than bacteria.

Recital 74 a (new): (74a) According to the Aarhus Convention on Access to Information, Public Participation in Decision-Making and Access to Justice in Environmental Matters1a, the public has a right to obtain information on environmental matters, including on the ERA of a pharmaceutical product. / 1a OJ L 124, 17.5.2005, p. 4.

Recital 93: (93) To optimise the use of resources for both applicants for marketing authorisation and competent authorities and avoid duplication of assessment of chemical active substances of medicinal products which includes cell and gene therapies, marketing authorisation applicants should be able to rely on an active substance master file certificate or a monograph of the European Pharmacopeia, instead of submitting the relevant data as required in accordance with Annex II. An active substance master file certificate may be granted by the Agency when the relevant data on the active substance concerned is not already covered by a monograph of the European Pharmacopeia or by another active substance master file certificate. 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 use of a certification scheme also for additional master files, including 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, raw materials, viral vectors and other starting materials, growth media, radiopharmaceutical precursors and active substance intermediates, when the intermediate is a chemical active substance by itself or used in conjugation with a biolo…

Recital 101: (101) 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 that regard, Member States should seek to inform directly those stakeholders who report adverse reactions in case there exists any update on the safety profile of the medicinal products.

Recital 109: (109) There may be cases where manufacturing or testing steps of medicinal products need to take place in sites close to patients, for example advanced therapy medicinal products with short shelf-life. In such cases, these manufacturing or testing steps may need to be decentralised to multiple sites to reach patients across the Union. When the manufacturing or testing steps are decentralised, they should be carried out under the responsibility of the qualified person of an authorised central site. Additionally, in order to ensure the smooth functioning of decentralised sites under this framework with the activities relevant for other Union legal frameworks, competent authorities of Member States supervising the decentralised site should coordinate their acitivities and supervisory tasks with the relevant authorities responsible for the supervision of the manufacturing or testing activities under other Union acts. The decentralised sites should not require a separate manufacturing authorisation 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 established. In the case of medicinal products containing, consisting or derived from autologous SoHO, the decentralised sites have to be registered as a SoHO entity as defined in and pursuant to [SoHO Regulation] for the activities of donor review and eligibility assessment, donor testing and collection, or just for collection in t…

Recital 123 a (new): (123a) Pharmacists and other health care professionals have an important role in primary care, particularly to compound, dispense and sell medicinal products that patients need, to provide advice on their proper use and possible adverse effects and to support patients suffering of acute and chronic illnesses. In a hospital environment, hospital pharmacists set up pharmaceutical consultations and designate personalised pharmaceutical plans, in cooperation with other health professionals, patients and carers. Hospital pharmacists and community pharmacists could play a significant role in the use of electronic package leaflets, as well as for understanding the information contained in paper leaflets.

Recital 124: (124) Rules should be laid down as to how the labelling and package leaflets are to be presented. The package leaflet should be easily legible, clearly comprehensible by users, including especially the target patient groups, and indelible. Patient leaflets are in the category of consultative reading which means that relevant information should be found without reading the whole leaflet. For readability and legibility, the package leaflet can benefit from a typographic hierarchy and a legible typeface. Design choices should primarily serve function and readability, rather than aesthetics.

Recital 125: (125) Sharing accurate information with the general public in order to promote trust in science and the regulatory system and supporting health literacy of patients and consumers is crucial. Where relevant, competent authorities should also share up to date information with healthcare professionals, including pharmacists, and the scientific community. The provisions governing the information supplied to users should provide a high degree of consumer protection, in order that medicinal products may be used correctly on the basis of full and comprehensible information.

Recital 127: (127) The use of electronic and technological possibilities other than paper package leaflets, which is complementary to the paper leaflets which are crucial for patients with limited digital health literacy, can facilitate access to medicinal products, medicinal products distribution and should always guarantee equal or better quality of information to all patients compared to the paper form of product information. Ensuring the protection of personal data in accordance with Regulation (EU) 2016/679 and prevention of the identification, profiling or tracking of individuals is necessary in that regard.

Recital 128: (128) Member States have varying levels of digital literacy and internet access. In addition, patient and healthcare professional needs may differ. It is therefore necessary that Member States have a discretion on the adoption of measures enabling the electronic provision of product information 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. A package leaflet should be made available electronically and be included in paper format, except where the Member State, following a consultation, decides to make only the electronic product information available. Electronic product information should be available in full compliance with the rules on protection of personal data, and adhere to harmonised standards developed at EU level. The information in digital format should be easily accessible to all patients. Based on the findings from hospital pilots, the obligation to provide a paper leaflet should not be applied for medicinal products which are not intended for self-administration by the patient.

Recital 129: (129) Member States should make the package leaflet available electronically and in paper format, except where the Member State decides to make only the electronic product information available. Where the package leaflet is only available electronically, Member States should also ensure that a paper version of the package leaflet is to be made available on demand and without additonal cost to patients. They should also ensure that the information in digital format is easily accessible to all patients, for instance by including in the outer packaging of the product a digitally readable barcode, which would direct the patient to the electronic version of the package leaflet.

Recital 130: (130) The use of multi-language packages can be a tool for access to medicinal products, in particular for small markets and in public health emergencies. Where multi-language packages are used, Member States may 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-language package is marketed. While electronic medicinal product information can facilitate the redistribution of packages between Member States, language requirements on labels can remain a challenge. The granting of an exemption to the requirement for an official language, as well as the obligation to use the international non-proprietary name for medicinal products not intended for self-administration by the patient, in addition to providing electronic product information, could improve the availability of medicinal products and enable easier redistribution between Member States.

Recital 131: (131) To ensure a high level of transparency of public support to the research and development of medicinal products, the reporting of public contribution for the development of a particular medicinal product should be a requirement for all medicines. Given however the practical difficulty to identify in third countries how indirect public funding instruments, such as tax advantages, have supported a particular product, the reporting obligation on financial support from entities outside of the Union should only concern the direct public financial support, such as direct grants or contracts. Therefore, the provisions of this Directive ensure, without prejudice to the rules on the protection of confidential and personal data, transparency regarding financial support received from any public authority or public body or philanthropic or non-for profit organisation or fund to carry out any activities for the research and development of medicinal products.

Recital 135 a (new): (135a) Clear, impartial and independent information from healthcare professional to the public about a medicinal product and its correct use can play an important role in informing citizens and combatting misinformation, in particular during health emergencies such as the COVID-19 pandemic. Member States should ensure that the ability of healthcare professionals to share clear, impartial and independent information, whether in a direct conversation with a patient or in broader communication, should not be hindered.

Recital 136: (136) Advertising of medicinal products should aim at disseminating objective and unbiased information about the medicinal product. For that purpose, it is expressly forbidden highlight negatively another medicinal product or to suggest that advertised medicinal product might be safer or more effective than another medicinal product. Comparison of medicinal products should only be allowed if such information is listed in the summary of product characteristics for the relevant indications and patient population of the medicinal product being advertised. This prohibition covers any medicinal product, also biosimilars, and therefore it would be misleading to refer in the advertising, that a biosimilar medicinal product would not be interchangeable with the original biological medicinal product or another biosimilar from the same original biological medicinal product. Additional strict rules about negative and comparative advertising of competitor medicinal products will prohibit claims that can mislead persons qualified to prescribe, administer or supply them.

Recital 138 a (new): (138a) Because of the global reach of social media, patients and consumers are increasingly exposed to the promotional practices of using celebrities to advertise medicinal products. The Commission should assess the exposure and impact of pharmaceutical advertising and promotions online, and adopt specific rules to regulate such advertising and promotional practices.

Recital 139 a (new): (139a) Even minimal inducement can result in biased decisions with regard to prescription behaviour by physicians. Therefore, to avoid conflict of interest, Member States should maintain a transparency register of transfer of value regarding advertising activities which target persons qualified to prescribe medicinal products. The Commission should establish a web portal to list all national registers of transfers of value to persons qualified to prescribe medicinal products.

Recital 145: (145) In order to ensure uniform conditions for the implementation of this Directive, implementing powers should be conferred on the Commission. Those powers should be exercised in accordance with Regulation (EU) No 182/2011 of the European Parliament and of the Council66 .

Recital 149: (149) In order to supplement or amend certain non-essential elements of this Directive, the power to adopt acts in accordance with Article 290 TFEU should be delegated to the Commission in respect of 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 master files to provide information on a constituent of a medicinal product, the procedure for examination of application of a quality master file certificate or a platform technology master file certificate, the publication of such certificates, the procedure for changes to the master file and its certificate, and access to the master file and its assessment report; determining the situations in which post-authorisation efficacy studies may be required; specifying the categories of medicinal products to which a marketing authorisation subject to specific obligations could be granted and specifying the procedures and requirements for granting such a marketing authorisation and for its renewal; 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…

Article 1 – paragraph 2: 2. This Directive shall apply to medicinal products for human use intended to be placed on the market in Member States.

Article 1 – paragraph 4 – subparagraph 1 a (new): In cases where, taking into account all its characteristics, questions arise as to the regulatory status of a substance or a product, the competent authority or, in the case of a centralised marketing authorisation the Agency shall consult other relevant advisory and regulatory bodies with a view to reaching a decision on the regulatory status f the substance or a product concerned. In any decision on such question, the competent authority or the Agency shall make publicly available the views of other authorities or bodies consulted.

Article 1 – paragraph 5 – point b: (b) medicinal product prepared in a pharmacy in accordance with a pharmacopoeia and intended to be supplied directly to the patients served by the pharmacy in question or to another pharmacy which intends to supply the medicinal product directly to the patient (‘officinal formula’);

Article 1 – paragraph 5 – point c a (new): (ca) medicinal product prepared in advance, in duly justified cases, by the pharmaceutical department of a hospital (‘hospital formula’), supplied on medical prescription to one or several patients by the hospital’s pharmaceutical department.

Article 1 – paragraph 6: 6. Medicinal products referred to in paragraph 5, points (a) and (b), may be prepared in duly justified cases in advance by a pharmacy serving a hospital, on the basis of the estimated medical prescriptions within that hospital for the following seven days, or when duly justified based on the stability of the medicinal product within a different time limit.

Article 1 – paragraph 7: 7. Member States shall take the necessary measures to develop the production and use of medicinal products derived from substances of human origin coming from voluntary unpaid donations in accordance with Regulation (EU) 2024/... [SoHO Regulation].

Article 1 – paragraph 10 – point a: deleted

Article 2 – paragraph 1: 1. By way of derogation from Article 1(1), only this Article shall apply to advanced therapy medicinal products prepared a non-routine basis in accordance with the requirements set in paragraph 3 and used within the same Member State in a hospital under the exclusive professional responsibility of a medical practitioner and, where relevant, a hospital pharmacist. To satisfy the criteria of 'non-routine basis', the exemption shall be made only in order to comply with an individual medical prescription for a custom-made product to meet the special need of an individual patient (‘advanced therapy medicinal products prepared under hospital exemption’).

Article 2 – paragraph 2 – subparagraph 2: The application for a hospital exemption approval shall be submitted to the competent authority of the Member State where the hospital is located. The application shall include evidence on quality, safety and expected efficacy of the advanced therapy medicinal products prepared under hospital exemption.

Article 2 – paragraph 3: 3. Member States shall ensure that advanced therapy medicinal products prepared under hospital exemption comply with the good pharmacy preparation practices that are adapted to hospital processes while still equivalent to the good manufacturing practices and traceability for advanced therapy medicinal products referred to in Articles 5 and 15 of Regulation (EC) No 1394/2007 of the European Parliament and of the Council69 respectively, and with pharmacovigilance requirements equivalent to those provided for at Union level pursuant to [revised Regulation (EC) No 726/2004]. This shall include site inspections as well as traceability and pharmacovigilance plans and the evaluation of the preclinical and clinical data generated by the applicant.

Article 2 – paragraph 4: 4. Member States shall ensure that data on the use, safety and the efficacy of advanced therapy medicinal products prepared under hospital exemption, as well as any relevant data from patient follow-up for a sufficient period of time after the administration of the advanced therapy medicinal product, is collected and reported by the hospital exemption approval holder to the competent authority of the Member State at least annually. The data shall be collected and reported in a structured and standardised way that enables robust, reliable and comparable results and conclusions. The competent authority of the Member State shall review such data and shall verify the compliance of advanced therapy medicinal products prepared under hospital exemption with the requirements referred to in paragraph 3. Competent authorities shall ensure that scientific and regulatory advice is provided to non-profit and academic institutions in order to ensure appropriate reporting mechanisms.

Article 2 – paragraph 6: 6. The competent authority of the Member State shall transmit the data related to the use, safety and efficacy of an advanced therapy medicinal product prepared under the hospital exemption approval to the Agency annually. The Agency shall, in collaboration with the competent authorities of Member States and the Commission, set up and maintain via regular updates a repository of that data as well as of information on the authorisation, suspension or withdrawal of hospital exemption approvals, which shall be updated regularly. The repository shall be publicly available except for personal data and commercially confidentail information.

Article 2 – paragraph 7 – subparagraph 1 – point a: deleted

Article 2 – paragraph 7 – subparagraph 1 – point c a (new): (ca) the modalities of guidance for academic and other not-for-profit entities through the requirements of the hospital exemption clause.

Article 2 – paragraph 7 – subparagraph 1 – point d: deleted

Article 2 – paragraph 7 – subparagraph 2 a (new): By ... [24 months from the date of entry into force of this Directive], the Commission shall adopt delegated acts in accordance with Article 215 to supplement this Directive by establishing: / (a) details of the application for the approval of hospital exemption referred to in paragraph 1, second subparagraph, including the evidence on quality, safety and efficacy of the advance therapy medicinal products prepared under hospital exemption for the approval and the subsequent changes; / (b) the modalities for harmonised implementation of the preparation and use of advanced therapy medicinal products under hospital exemption on a non-routine basis.

Article 2 – paragraph 8: 8. The Agency shall provide to the Commission a report on the experience acquired with the hospital exemption approvals on the basis of contributions from Member States and the data referred to in paragraph 4. The report shall be made publicly available. The first report shall be provided three years after [OP please insert the date =18 months after the date of entering into force of this Directive] and then every five years thereafter.

Article 2 – paragraph 8 a (new): 8a. By way of derogation from paragraph 1, Member States may authorise the cross-border exchange of advanced therapy medicinal products prepared under hospital exemption in justified cases of medical need and in the absence of other solutions for the individual patient. A second medical practitioner and a hospital pharmacist in the receiving Member State shall be designated for the exclusive professional responsibility of the use and collection of follow-up data for the advanced therapy medicinal product. Information about the cross-border exchange shall be submitted to the competent authorities of both Member States, and shall be shared in the public repository referred to in paragraph 6 by the competent authority of the Member State of origin of the advanced therapy medicinal product.

Article 3 – paragraph 1 – subparagraph 1: A Member State may, in order to fulfil special needs, exclude from the scope of this Directive medicinal products supplied in response to a bona fide unsolicited order, prepared in accordance with the specifications of an authorised healthcare professional and for use by an individual patient under their direct personal responsibility, or prepared in accordance with the specifications of a competent authority. However, in such case Member States shall encourage and establish channels for healthcare professionals and patients to report data on the safety of the use of such products to the competent authority of the Member State in accordance with Article 97.

Article 4 – paragraph 1 – point 11: (11) ‘non-clinical’ means a study or a test conducted in vitro, ex vivo, in silico, or in chemico, or a non-human in vivo test related to the investigation of the safety and efficacy of a medicinal product. Such test may include simple and complex human cell-based assays, microphysiological systems including organ-on-chip, computer modelling and other in silico methods, other non-human or human biology-based test methods, including aquatic egg models as well as invertebrate species, and animal-based tests;

Article 4 – paragraph 1 – point 22: (22) ‘antimicrobial’ means any medicinal product with a direct action on micro-organisms used for treatment or prevention of infections or infectious diseases, including antibiotics, antivirals, antifungals and antiprotozoals;

Article 4 – paragraph 1 – point 26: (26) ‘combination of a medicinal product with a product other than a medical device’ means a combination of a medicinal product with a product other than a medical device (as defined by Regulation (EU) 2017/745 and Regulation (EU) 2017/746 of the European Parliament and of the Council1a) and where the two are intended for use in the given combination in accordance with the summary of product characteristics; / 1a Regulation (EU) 2017/746 of the European Parliament and of the Council of 5 April 2017 on in vitro diagnostic medical devices and repealing Directive 98/79/EC and Commission Decision 2010/227/EU (OJ L 117 5.5.2017, p. 176).

Article 4 – paragraph 1 – point 29 – introductory part: (29) “gene therapy medicinal product” means a type 1 or type 2 medicinal product; / (deleted) / (deleted)

Article 4 – paragraph 1 – point 29 a (new): (29a) “type 1 gene therapy medicinal product” means a medicinal product that contains or consists of a substance or a combination of substances that edit the host genome in a sequence-specific manner or that contain or consists of cells subjected to such modification;

Article 4 – paragraph 1 – point 29 b (new): (29b) “type 2 gene therapy medicinal product” means a medicinal product, except a vaccine against infectious disease that contains or consists of a recombinant or synthetic nucleic acid used in or administered to human beings with a view to regulating, replacing or adding a genetic sequence that mediates its effect by transcription or translation of the transferred genetic materials or that contain or consists of cells subjected to these modifications;

Article 4 – paragraph 1 – point 30 a (new): (30a) ‘platform technology’ means a technology or collection of technologies that is comprehensive, well-characterised, reproducible and used to support the development, manufacturing process, quality control, or testing of medicinal products or their components that rely on prior knowledge and are established under the same underlying scientific principles

Article 4 – paragraph 1 – point 30 b (new): (30b) ‘platform technology master file’ means a document, prepared by the owner of the platform technology, that contains data of a platform technology for which the underlying scientific principles, under which the platform technology is established, have reasonable scientific certainty to remain unchanged across medicinal products and to apply regardless of components added to the platform for a medicinal product;

Article 4 – paragraph 1 – point 31 – point a: (a) a method involving an industrial process which includes pooling of donations, for purposes beyond processing of substances of human origin for concentrates or pathogen inactivation; or

Article 4 – paragraph 1 – point 33: (33) ‘environmental risk assessment’ means the evaluation of the risks to the environment, or risks to public health, posed by the release of the medicinal product in the environment from the manufacturing, use and disposal of the medicinal product and the identification of risk prevention, limitation and mitigation measures. For medicinal product with an antimicrobial mode of action, the ERA also encompasses an evaluation of the risk for antimicrobial resistance selection in the environment due to the manufacturing, use and disposal of that medicinal product;

Article 4 – paragraph 1 – point 34: (34) ‘antimicrobial resistance’ means the ability of a micro-organism to survive or to grow in the presence of a concentration of an antimicrobial agent that is usually or was previously sufficient to inhibit or kill that micro-organism;

Article 4 – paragraph 1 – point 62: (62) ‘homeopathic product’ means a medicinal product prepared from homeopathic stocks in accordance with a homeopathic manufacturing procedure described by the European Pharmacopoeia or, in the absence thereof, by the pharmacopoeias currently used officially in the Member States;

Article 4 – paragraph 1 – point 70: (70) ‘public service obligation’ means to ensure permanently an adequate range of medicinal products to meet the requirements of a specific geographical area and to deliver the supplies requested within a very short time over the whole of the area in question.

Article 4 – paragraph 2: 2. The Commission is empowered to adopt delegated acts in accordance with Article 215 to amend the definitions in paragraph 1, points (2) to (6), (8), (14), (16) to (28) and (30) in the light of technical and scientific progress and taking into account definitions agreed at Union and international level without extending the scope of the definitions.

Article 6 – paragraph 2 a (new): 2a. A marketing authorisation may be granted for a medicinal product on the basis of an active substance master file, an additional quality master file or a platform technology master file where such a file exists and is referred to in the application.

Article 6 – paragraph 4: 4. The risk management system referred to in Annex I shall be proportionate to the identified risks and the potential risks to human health or the environment of the medicinal product, and the need for post-authorisation safety data.

Article 6 – paragraph 5 – subparagraph 2 a (new): In the absence of a paediatric investigation plan in accordance with the first subparagraph point (a), or where in this regard a comparative study has not been carried out, a justification shall be submitted and where relevant also evidence shall be obtained from post-marketing long-term studies.

Article 6 – paragraph 7 – subparagraph 2: The marketing authorisation applicant shall not carry out animal testing in case scientifically satisfactory non-animal testing methods are available. Where scientifically satisfactory non-animal testing methods are not available, applicants that use animal testing shall ensure that the principle of replacement, reduction and refinement of animal testing for scientific purposes has been applied in compliance with Directive 2010/63/EU with regard to any animal study conducted for the purpose of supporting the application.

Article 10 – paragraph 1: In cases where the medicinal product does not fall within the definition of a generic medicinal product or has changes in strength, pharmaceutical form, route of administration or therapeutic indications, compared to the reference medicinal product, the results of the appropriate non-clinical tests or clinical studies shall be provided to the competent authorities to the extent necessary to establish a scientific bridge to the data relied upon in the marketing authorisation for the reference medicinal product, and to demonstrate the safety and efficacy profile of the hybrid medicinal product. The Agency shall adopt guidelines on the appropriate tests and clinical studies for marketing authorisation of hybrid medicinal products.

Article 12 – paragraph 1: In cases where a biosimilar medicinal product has changes in strength, pharmaceutical form, route of administration or therapeutic indications, compared to the reference biological medicinal product (‘bio-hybrid’), the results of the appropriate non-clinical tests or clinical studies shall be provided to the competent authorities to the extent necessary to establish a scientific bridge to the data relied upon in the marketing authorisation for the reference biological medicinal product, and to demonstrate the safety or efficacy profile of the biosimilar medicinal product. The Agency shall adopt guidelines on the appropriate tests and clinical studies for marketing authorisation of bio-hybrid medicinal products.

Article 13 – paragraph 1: In cases where no reference medicinal product is or has been authorised for the active substance of the medicinal product concerned, the applicant shall, by way of derogation from Article 6(2), not be required to provide the results of non-clinical tests or clinical studies if the applicant can demonstrate that the active substances of the medicinal product have been in well-established medicinal use within the Union the same therapeutic use and route of administration and for at least ten years, with recognised efficacy and an acceptable level of safety in terms of the conditions set out in Annex II. In that event, the test and trial results shall be replaced by appropriate bibliographic data in the form of scientific literature. A justification shall be provided with regard to the relevance of that literature for the medicinal product.

Article 15 – title: Fixed dose combination medicinal product, platform marketing authorisation and multi-medicinal product packages

Article 15 – paragraph 2 – subparagraph 1: Where justified for therapeutic purposes, a marketing authorisation may be granted for a medicinal product comprised of a fixed component and a variable component that is pre-defined in order to, where appropriate, target different variants of an infectious agent or, where necessary, to tailor the medicinal product to characteristics of an individual patient or a group of patients (‘platform marketing authorisation’).

Article 16 – paragraph 1: 1. A marketing authorisation shall be required for radionuclide generators, kits for radiopharmaceutical preparations (‘kits’), and radionuclide precursors, unless they are used as starting material, active substance or intermediate of radiopharmaceuticals covered by a marketing authorisation under Article 5(1).

Article 17 – paragraph 1 – point a: (a) an antimicrobial stewardship and access plan as referred to in Annex I;

Article 17 – paragraph 1 a (new): 1a. The competent authority of the Member State shall, following the granting of a marketing authorisation, make publicly available the documents referred to in paragraph 1.

Article 17 – paragraph 2: 2. The competent authority shall review the information submitted in accordance with paragraph 1 point (b). The competent authority shall impose obligations on the marketing authorisation holder if it finds the risk mitigation measures contained in the antimicrobial stewardship and access plan unsatisfactory.

Article 17 – paragraph 3: 3. The marketing authorisation holder shall ensure, wherever possible, that the antimicrobial may be dispensed per unit in a number corresponding to the quantities corresponding to the duration of treatment. If an antimicrobial cannot be dispensed per unit, the marketing authorisation holder shall ensure that the pack size of the antimicrobial corresponds to the usual posology and duration of treatment.

Article 18 – paragraph 1 – subparagraph 2: As part of the assessment, in accordance with Article 29, of the integral combination of a medicinal product and a medical device the competent authorities shall assess the benefit-risk balance of the integral combination of a medicinal product and a medical device, taking into account the suitability of the use of the medicinal product together with the medical device, where relevant particularly for paediatric patients, including aspects such as storage, assembly, cleanliness, and the technique required for application or intake.

Article 22 – paragraph 1: 1. When preparing the environmental risk assessment (‘ERA’) to be submitted pursuant to Article 6(2), the applicant shall take into account the scientific guidelines on the environmental risk assessment of medicinal products for human use as referred to in paragraph 5, or provide the duly justified reasons for any divergence from the scientific guidelines to the Agency or, as appropriate to the competent authority of the Member State concerned, in a timely manner. Where available, the applicant shall take into account existing ERAs performed under other Union legislation.

Article 22 – paragraph 3: 3. The applicant shall also include in the ERA risk mitigation measures to avoid or where it is not possible, limit emissions to air, water and soil of pollutants listed in Directive 2000/60/EC, Directive 2006/118/EC, Directive 2008/105/EC and Directive 2010/75/EU during the manufacturing, use and disposal of the medicinal product. The applicant shall provide detailed explanation that the proposed mitigation measures are appropriate and sufficient to address the identified risks to the environment. Where necessary, the applicant shall also include information on available techniques and on the techniques that will be used to reduce the discharges and emissions of the medicinal product, in particular those occurring in manufacturing effluents before those effluents leave the manufacturing sites.

Article 22 – paragraph 4: 4. The ERA for antimicrobials shall include an evaluation of the risk for antimicrobial resistance selection in the environment due to the entire manufacturing supply chain inside and outside the Union, use and disposal, including by healthcare professionals and patients, of the antimicrobial taking into account, where relevant, the existing international standards that have established predicted no effect concentration (PNECs) specific for antibiotics.

Article 22 – paragraph 4 a (new): 4a. By ... [12 months from the date of entry into force of this Directive], the Commission shall, after having consulted the Agency, the EEA, and the ECDC, issue guidelines on how to conduct the ERA for antimicrobials other than antibiotics.

Article 22 – paragraph 5: 5. The Agency shall draw up scientific guidelines in accordance with Article 138 of [revised Regulation No (EC) 726/2004], to specify technical details regarding the ERA requirements for medicinal products for human use. Where appropriate, the Agency shall consult the European Chemical Agency (ECHA), the European Food Safety Authority (EFSA), the EEA, the ECDC and other relevant stakeholders, including drinking water and wastewater operators, on the drafting of these scientific guidelines.

Article 22 – paragraph 6 – subparagraph 2: For an ERA conducted prior to [OP please insert the date = 18 months after the date of entering into force of this Directive], the competent authority shall request the marketing authorisation holder to update the ERA to include risk mitigation measures as referred to in paragraph 3. The competent authority shall also request the marketing authorisation holder to update the ERA if missing information has been identified for medicinal products potentially harmful to the environment.

Article 22 – paragraph 7: 7. For medicinal products referred to in Articles 9 to 12, the applicant may refer to ERA studies conducted for the reference medicinal product when preparing the ERA and shall provide any other data and the scientific guidelines as referred to in the paragraph 1 of this Article.

Article 22 – paragraph 7 a (new): 7a. The outcome of the assessment of the ERA, including the data submitted by the marketing authorisation holder, shall be made publicly available by the Agency or, as appropriate, by the competent authority of the Member State.

Article 22 – paragraph 7 b (new): 7b. When making public the information on the ERA, including the antimicrobial stewardship and access plan referred to in Article 17, the competent authority shall delete any information of a commercially confidential nature.

Article 23 – paragraph 1 – subparagraph 1: By [OP please insert the date = 24 months after the date of the entry into force of this Directive] the Agency shall, after consultation with the competent authorities of the Member States, the ECDC, the European Chemical Agency (ECHA), the European Food Safety Authority (EFSA) and the European Environmental Agency (EEA), establish a programme for the ERA to be submitted in accordance with Article 22 of the medicinal products authorised before 30 October 2005 that have not been subject to any ERA and that the Agency has identified as potentially harmful to the environment in accordance with paragraph 2.

Article 23 – paragraph 2: 2. The Agency shall set the scientific criteria for the identification of the medicinal products as potentially harmful to the environment and for the prioritisation of their ERA, using a risk based approach. For this task, the Agency shall consult relevant stakeholders, including actors managing residues from medicinal products and their production in the environment and may request from marketing authorisation holders the submission of relevant data or information.

Article 23 – paragraph 3: 3. The marketing authorisation holders for medicinal products identified in the programme referred to in paragraph 1 shall submit the ERA to the Agency. The outcome of the assessment of the ERA including the data and a summary of ERA studies and their results as submitted by the marketing authorisation holder shall be made publicly available by the Agency.

Article 24 – paragraph 1: 1. The Agency shall, in collaboration with the competent authorities of the Member States, set-up an active substance based review system of ERA data (‘ERA monographs’) for authorised medicinal products and publicise relevant information about that system. An ERA monograph shall include a comprehensive set of physiochemical data, fate data and effect data based on an assessment of a competent authority.

Article 24 – paragraph 2: 2. The setting-up of the system of ERA monographs shall be based on a risk-based prioritisation of active substances and data requirements.

Article 24 – paragraph 4: 4. The Agency in cooperation with the competent authorities of the Member States shall conduct a proof-of-concept pilot of ERA monographs to be completed within 30 months after entering into force of this Directive, while taking into account outcomes from relevant Union initiatives with regard to animal testing.

Article 26 – paragraph 3 – point b: (b) additional quality master files for which a certificate may be used in order to provide specific information on the quality of a substance, preparation or other material present or used in the manufacture of a medicinal product, including cell therapies and gene therapies;

Article 26 a (new): Article26a / Additional platform technology master files / 1. Marketing authorisation applicants may, instead of submitting the relevant data related to a platform technology, rely on an additional platform technology master file or an additional platform technology master file certificate granted by the Agency in accordance with this Article (‘additional platform technology master file certificate’). / 2. Article 25(1) to (5), (7) and (8) shall also apply mutatis mutandis to additional platform technology master file certificates. / 3. To adequately describe the platform technology master file, appropriate information as laid down in scientific guidelines published by the Agency shall be provided. / 4. The Commission is empowered to adopt delegated acts in accordance with Article 215 to supplement this Directive by specifying: / (a) the rules governing the content and format of the application for an additional platform technology master file certificate; / (b) additional platform technology master files for which a certificate may be used in order to provide specific information on the platform technology on the basis of which a substance present or used in the manufacturing of a medicinal product is manufactured; / (c) the rules for the examination of applications for making publicly available of additional platform technology master file certificates; / (d) the rules for introducing changes to the additional platform technology master file and the certificate; / (e) the r…

Article 27 – paragraph 4 – subparagraph 1: If a colour used in medicinal product is removed from the Union list of authorised food additives, on the basis of the scientific opinion of the European Food Safety Authority (‘EFSA’), the Agency shall, on the request of the Commission or on its own initiative, without undue delay issue a scientific opinion as regards the use of the colour concerned in medicinal product, taking into account the opinion of the EFSA. The opinion of the Agency shall be adopted by the Committee for Medicinal Products for Human Use.

Article 27 – paragraph 5: 5. If a colour has been removed from the Union list of authorised food additives for reasons that do not require an EFSA opinion, the Commission shall decide on the use of the colour concerned in medicinal products and, where applicable, include it in the list of colours permitted for use in medicinal products referred to in paragraph 3. The Commission shall, in such cases, request the opinion from the Agency.

Article 28 – paragraph 6 a (new): 6a. The Commission shall submit a report on the application of adapted frameworks to the European Parliament and to the Council. The first report shall be submitted five years from [OP please insert the date =18 months from the date of entry into force of this Directive] and then every five years thereafter.

Article 29 – paragraph 3: 3. Where the competent authority of the Member State considers that the marketing authorisation application is incomplete, or contains critical deficiencies that may prevent the evaluation of the medicinal product it shall inform the applicant accordingly and shall set a time limit for submitting the missing information and documentation. If the applicant fails to provide the missing information and documentation within the time limit set, the application shall be considered to have been withdrawn by default.

Article 29 – paragraph 4 – subparagraph 2: The competent authority of the Member State shall summarise the deficiencies in writing. On this basis, the competent authority of the Member State shall inform the applicant accordingly and set a reasonable time limit to address the deficiencies. The application shall be suspended until the applicant addresses the deficiencies. If the applicant fails to address those deficiencies within the time limit set by the competent authority of the Member State, the application shall be considered as withdrawn by default.

Article 29 – paragraph 4 a (new): 4a. When making public the information on the ERA and the antimicrobial stewardship and access plan referred to in Article 17, the competent authority shall delete any information of a commercially confidential nature.

Article 34 – paragraph 3: 3. The competent authority of the reference Member State for the decentralised procedure shall inform the Coordination group for decentralised and mutual recognition procedures of an application, which shall thereafter notify the competent authorities of all Member States. The competent authority of a Member State may request for justified public health reasons to enter the procedure and shall inform the applicant and the competent authority of the reference Member State for the decentralised procedure of its request within 30 days from the date of submission of the application. The applicant shall provide the competent authorities of those Member States entering the procedure with the application without undue delay.

Article 34 – paragraph 4 – subparagraph 2: The competent authority of the reference Member State for the decentralised procedure shall summarise the deficiencies in writing. On this basis, the competent authority of the reference Member State for the decentralised procedure shall inform the applicant and the competent authorities of the Member States concerned accordingly and set a time limit to address the deficiencies. The application shall be suspended until the applicant addresses the deficiencies. If the applicant fails to address those deficiencies within the time limit set by the competent authority of the reference Member State for the decentralised procedure, the application shall be considered as withdrawn by default.

Article 36 – paragraph 4: 4. The competent authority of the reference Member State for the decentralised procedure shall inform the Coordination group for decentralised and mutual recognition procedures of an application, which shall thereafter notify the competent authorities of all Member States. The competent authority of a Member State may request for justified public health reasons to enter the procedure and shall inform the applicant and the competent authority of the reference Member State for the mutual recognition procedure of its request within 30 days from the date of submission of the application. The applicant shall provide the competent authorities of those Member States entering the procedure with the application without undue delay.

Article 37 – paragraph 2 – subparagraph 1: The coordination group shall be composed of one representative per Member State and one representative from patients’ organisations appointed for a renewable period of three years. Alternates may be appointed for a renewable period of three years. Members of the coordination group may arrange to be accompanied by experts.

Article 42 – paragraph 1 – subparagraph 5: The Commission shall send the draft decision to the competent authorities of the Member States and the applicant or the marketing authorisation holder and make the decision, including the justification, publicly available.

Article 43 – paragraph 3: 3. The competent authorities of the Member States shall, without undue delay, make publicly available the national marketing authorisation together with the summary of product characteristics, the package leaflet, the antimicrobial stewardship and access plan and special information requirements referred to in Article 17(1), points (a) and (b), as well as any conditions established in accordance with Articles 17, 44, 45 and any obligations imposed subsequently in accordance with Article 87, together with any deadlines for the fulfilment of those conditions and obligations for each medicinal product that they have authorised.

Article 43 – paragraph 4: 4. The competent authority of the Member State may consider and decide upon additional evidence available, independently from the data submitted by the marketing authorisation holder. On that basis, the summary of product characteristics shall be updated if the additional evidence has an impact on the benefit-risk balance of a medicinal product. The competent authority shall inform the marketing authorisation holder of its decision, including the grounds for that decision, without unnecessary delay.

Article 44 – paragraph 1 – subparagraph 1 – point g: (g) in case of medicinal products for which, on duly justified grounds set out in the assessment report, there is substantial uncertainty as to the surrogate endpoint relation to the expected health outcome, where appropriate and relevant for the benefit-risk balance, with particular attention to new active substances and therapeutic indications, a post-authorisation obligation to substantiate the clinical benefit;

Article 47 – paragraph 1 – point d: (d) the environmental risk assessment is incomplete or insufficiently substantiated, and the reason for the incomplete nature of the environmental risk assessment is not duly justified and substantiated by the applicant, or if the risks identified in the environmental risk assessment have not been sufficiently addressed by the applicant or by the risk mitigation measures included by the applicant, in accordance with Article 22(3);

Article 47 – paragraph 1 – point d a (new): (da) For medicinal products where the reference medicinal product received its first marketing authorisation before 30 October 2005, the national marketing authorisation may be refused if the view is taken that the environmental risk assessment is incomplete or insufficiently substantiated and those medicinal products can be identified as potentially harmful to the environment.

Article 49 – paragraph 2: 2. If the application complies with all the measures contained in the agreed completed paediatric investigation plan and if the summary of product characteristics reflects the results of studies conducted in compliance with that agreed paediatric investigation plan, the competent authority of the Member State shall include within the marketing authorisation a statement indicating compliance of the application with the agreed completed paediatric investigation plan. The competent authority shall make the conclusions of the assessment regarding compliance with the agreed completed paediatric investigation plan publicly available.

Article 51 – paragraph 1 – point e: (e) is an antibiotic or any other antimicrobial for which there is an identified risk of antimicrobial resistance; or

Article 51 – paragraph 1 – point f: (f) contains an active substance, adjuvants or any other ingredients or constituent parts which are persistent, bioaccumulative and toxic, or very persistent and very bioaccumulative, or persistent, mobile and toxic, or very persistent and very mobile for which medical prescription is required as risk minimisation measure with regard to the environment, unless the use of the medicinal product and the patient safety require otherwise.

Article 51 – paragraph 1 a (new): 1a. The Commission shall adopt implementing acts to add further antimicrobial products that shall be subject to prescription status where the Agency has identified a risk of antimicrobial resistance. Those implementing acts shall be adopted in accordance with the examination procedure referred to in Article 214(2).

Article 51 – paragraph 2: 2. Member States may set additional conditions on the prescription of antimicrobials, restrict the validity of medical prescription and limit the quantities prescribed to the amount required for the treatment or therapy concerned by authorising the use of pre-cut blister units or submitting certain antimicrobial medicinal products to special medical prescription or restricted prescription.

Article 51 – paragraph 2 a (new): 2a. A prescription for antibiotic products shall be subject to the following conditions: / (a) be limited to the amount required for the treatment or therapy concerned; / (b) only be prescribed for a limited duration to cover the period of risk when used as prophylaxis; / (c) in the event that a diagnostic test has not been performed, a justification shall be required.

Article 51 – paragraph 2 b (new): 2b. Member States shall, wherever possible, provide per unit prescription and dispensing for the treatment or therapy concerned.

Article 51 – paragraph 4 – point c a (new): (ca) the risk of antimicrobial resistance, including any mitigating measures in that regard, from use of the medicinal product

Article 51 – paragraph 5 – point b: deleted

Article 57 – paragraph 1: 1. The marketing authorisation holder shall declare to the public any direct financial support received from any public authority, publicly funded body or philanthropic or not-for-profit organisation or fund, irrespective of its geographic location, and any indirect financial support received from any public authority or publicly funded body of the Union or its Member States in relation to any activities for the research and development of the medicinal product covered by a national or a centralised marketing authorisation, irrespective of the legal entity that received that support.

Article 57 – paragraph 2 – point a – point ii: (ii) the entity that provided the financial support referred to in point (i);

Article 57 – paragraph 2 – point a – point iii a (new): (iiia) where relevant, any independent legal entity from which it obtained a licence in relation to, or acquired the medicinal product in its previous phases of development, and at which stage of the research and development process. The marketing authorisation holder shall, to the extent possible, include in the report information on funding received as referred to paragraph 1 specific to the relevant medicinal product.

Article 57 – paragraph 6: 6. The Commission shall adopt implementing acts to lay down the principles and format for the information to be reported pursuant to paragraph 2, by [12 months from the date of entry into force of this Directive]. Those implementing acts shall be adopted in accordance with the examination procedure referred to in Article 214(2).

Article 57 – paragraph 6 a (new): 6a. The Agency shall provide on its website the links to the information communicated to the Agency in accordance with paragraphs 2 and 3, sorted, where relevant, by medicinal product and by Member State.

Article 58 a (new): Article58a / Obligation to submit an application for pricing and reimbursement in all Member States / 1. The marketing authorisation holder shall, upon request by a Member State in which the marketing authorisation is valid, in good faith and within the limits of its responsibilities, submit an application for pricing and reimbursement for the medicinal product and, where relevant, negotiate. In the case of a positive decision to permit the marketing of the medicinal product in accordance with Directive 89/105/EEC, the obligation in Article 56(3) of this Directive to ensure appropriate and continued supply to cover the needs of patients in that Member State shall apply. The application for pricing and reimbursement for the medicinal product shall be submitted no later than 12 months from the date when the Member State made its request, or within 24 months from that date for any of the following entities: / (i) SMEs; / (ii) entities not engaged in an economic activity (‘not-for-profit entity’); and / (iii) undertakings that, by the time of granting the marketing authorisation, have received not more than five centralised marketing authorisations for the undertaking concerned or, in the case of an undertaking belonging to a group, for the group of which it is part, since the establishment of the undertaking or the group, whichever is earliest. / The deadlines set out in the first subparagraph of this paragraph shall be prolonged by six months following the notification of the m…

Article 58 b (new): Article58b / EU Access to Medicines Notification System / 1. The Commission shall set up and maintain an electronic notification system for the notification of compliance with the obligations set out in Article 58a (the ‘EU Access to Medicines Notification System’). The EU Access to Medicines Notification System shall be interoperable with other relevant Union-wide data repositories for medicinal products. / 2. The marketing authorisation holder shall use the EU Access to Medicines Notification System to notify their compliance with the obligations set out in Article 58a. In the Member States where the marketing authorisation is valid, the national competent authority shall use the EU Access to Medicines Notification System to indicate that the marketing authorisation holder has fulfilled its obligations set out in Article 58a. / 3. By ... [3 years from the date of entry into force of this Directive], the Commission shall adopt implementing acts to establish technical and organisational requirements. Those implementing acts shall be adopted in accordance with the examination procedure referred to in Article 214(2). / 4. By ... [5 years from the date of entry into force of this Directive], the Commission shall assess the feasibility of extending the EU Access to Medicines Notification System to other areas of the process for pricing of medicinal products as set out in Directive 89/105/EEC and, if appropriate, adopt implementing acts to establish this extended system. Those imp…

Article 63 – paragraph 3: 3. Member States may decide that for individual medicinal products, categories of medicinal products or for all medicinal products, the package leaflet shall be made available both in paper format and electronically or electronically only. In the latter case, the decision shall be made only following a consultation of patients, carers and other relevant stakeholders. In the absence of such specific rules in a Member State, a package leaflet shall be made available electronically and be included in paper format in the packaging of a medicinal product. If the package leaflet is only made available electronically, the patient’s right to a printed copy of the package leaflet should be guaranteed upon request and free of charge and it should be ensured that the information in digital format is easily accessible to all patients as well as written and designed in a clear and understandable way.

Article 63 – paragraph 3 a (new): 3a. If a Member State has decided that the package leaflet is only to be made available electronically, patients shall be made aware of their right to a printed copy of the package leaflet.

Article 63 – paragraph 3 b (new): 3b. If a Member State decides that the package leaflet shall be made available electronically, a paper package leaflet in addition to the electronic format may be made available on a voluntary basis by the marketing authorisation holder in addition to the electronic package leaflet.

Article 63 – paragraph 4 a (new): 4a. By way of derogation from paragraph 3, where the medicinal product is intended for dispensation and administration by a qualified healthcare professionals rather than for self-administration by the patient, the package leaflet may be made available only electronically.

Article 63 – paragraph 5: deleted

Article 63 – paragraph 6: 6. By ... [12 months from the date of entry into force of this Directive], the Commission shall adopt implementing acts in accordance with the examination procedure referred to in Article 214(2) to establish common standards for the electronic version of the package leaflet, the summary of product characteristics and the labelling, taking into account available technologies.

Article 63 – paragraph 6 a (new): 6a. The Agency shall make available a system to accommodate the electronic product information after consultation with Member States and the relevant stakeholders. The system shall be available at the latest by [24 months from the date of entry into force of this Directive].

Article 63 – paragraph 7: 7. When accessing the package leaflet electronically, the individual right to privacy shall be ensured. Any technology giving access to the information shall ensure the protection of personal data in accordance with Regulation (EU) 2016/679 and Directive 2002/58/EC and shall not allow the identification, profiling or tracking of individuals, nor shall it be used for commercial purposes including for advertising or marketing activities.

Article 64 – paragraph 3: 3. Following a consultation with target patient groups and other relevant stakeholders, the Commission shall adopt guidelines to ensure that the package leaflet is legible, clear and easy to use.

Article 66 – paragraph 1: 1. The particulars laid down in Annex IV shall appear on immediate packagings other than those referred to in the paragraphs 2 and 3 and shall allow, at the request of the national competent authorities, single dispensation, particularly in the event of a shortage or major public health issue.

Article 66 – paragraph 2 a (new): 2a. Each single dose of the blister pack shall include the following labelling particulars: / (a) the name of the medicinal product followed by its strength and pharmaceutical form; / (b) a data matrix code in which the following information is encoded: (i) the Global Trading Index Number (GTIN) / (ii) the expiry date; / (iii) the batch number.

Article 67 – paragraph 1 – subparagraph 2: Medicinal products not subject to prescription shall not bear the safety features referred to in Annex IV, unless, by way of exception, they have been listed in accordance with the procedure referred to in paragraph 2, second subparagraph, point (b), or where the marketing authorisation holder chooses to do so voluntarily.

Article 67 – paragraph 7 a (new): 7a. For the purpose of patient safety, Member States may decide that medicinal products imported or distributed in parallel shall be repackaged in new outer packaging.

Article 69 – paragraph 1: 1. The marketing authorisation holder shall ensure availability of educational material to healthcare professionals, regarding the appropriate use of diagnostic tools, testing or other diagnostic approaches related to antimicrobial-resistant pathogens, that may inform on the use of the antimicrobial. Any informational material shall be compatible with the summary of product characteristics.

Article 69 – paragraph 2 – subparagraph 2: Member States shall ensure that the awareness card is made available in paper format or both in paper format and electronically in the packaging of an antimicrobial.

Article 69 – paragraph 3 – subparagraph 1 a (new): Members States shall introduce appropriate disposal systems for antimicrobials in the community setting, and inform the general public on the correct disposal methods for antimicrobial.

Article 69 – paragraph 3 a (new): 3a. The Commission may adopt implementing acts laying down further standards for the awareness card after consulting the Agency. Those implementing acts shall be adopted in accordance with the examination procedure referred to in Article 214(2).

Article 73 – paragraph 1: The outer packaging, the immediate packaging and the package leaflet may include symbols or pictograms designed to clarify certain information set out in Articles 64(1), 65 and 69 and other information compatible with the summary of product characteristics that is useful for the patient, to the exclusion of any element of a promotional nature.

Article 74 – paragraph 4: 4. The competent authorities of the Member State may also grant a full or partial exemption to the obligation that the labelling and the package leaflet must be in an official language or official languages of the Member State where the medicinal product is placed on the market, as specified, for the purposes of this Directive, by that Member State. Where a competent authority grants a full or partial exemption to the language requirements that apply to the label or package leaflet, the patients’ right to a printed copy in the official language or official languages of the Member State shall be guaranteed upon request and free of charge. / For the purpose of multi-language packages, Member States may 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-language package is marketed.

Article 77 – paragraph 1 – point a a (new): (aa) the wording on prudent use and safe disposal of antimicrobials;

Article 80 – paragraph 2 a (new): 2a. The period referred in paragraph 2 of this Article shall be extended by an additional period of one year, where the marketing authorisation holder obtains, during the data protection period referred to in Article 81, an authorisation for an additional therapeutic indication, provided that significant clinical benefit in comparison with existing therapies has been demonstrated by the marketing authorisation holder with supporting data. That extension may only be granted once.

Article 80 – paragraph 4: 4. By way of derogation from paragraphs 1 and 2, when a compulsory licence has been granted by a relevant Member State authority in the Union under conditions laid down in Union law and in compliance with international agreements to a party, the data and market protection shall be suspended with regard to that party insofar as the compulsory licence requires, and during the duration period of the compulsory licence in the Member State(s) where the compulsory license has been granted.

Article 80 – paragraph 4 a (new): 4a. The marketing authorisation holder for the medicinal product for which a compulsory licence has been granted shall be informed of the decision without delay.

Article 81 – paragraph 1: 1. The regulatory data protection period shall be seven years and six months from the date when the marketing authorisation for that medicinal product was granted in accordance with Article 6(2). For marketing authorisations that belong to the same global marketing authorisation the period of data protection shall start from the date when the initial marketing authorisation was granted in the Union.

Article 81 – paragraph 2 – subparagraph 1 – point a: deleted / (deleted) / (deleted) / (deleted)

Article 81 – paragraph 2 – subparagraph 1 – point b: (b) 12 months, where the marketing authorisation applicant demonstrates at the time of the initial marketing authorisation application that the medicinal product addresses an unmet medical need as referred to in Article 83;

Article 81 – paragraph 2 – subparagraph 1 – point c a (new): (ca) six months, where the marketing authorisation holder demonstrates that a significant share of research and development, including preclinical and clinical, related to the medicinal product has been done within the Union and at least in part in collaboration with public entities, including university hospital institutes, centres of excellence or bioclusters located in the Union.

Article 81 – paragraph 2 – subparagraph 1 – point d: deleted

Article 81 – paragraph 2 – subparagraph 3: deleted

Article 81 – paragraph 2 – subparagraph 3 a (new): By ... [12 months from the date of entry into force of this Directive], the Commission shall adopt delegated acts in accordance with Article 215 to supplement this Directive by setting out the procedural aspects and criteria related to the first subparagraph, point (ca), of this paragraph.

Article 81 – paragraph 3 a (new): 3a. The regulatory protection referred to in paragraphs 1 and 2 shall not exceed eight years and six months.

Article 82: deleted

Article 83 – paragraph 3: 3. Where the Agency adopts scientific guidelines for the application of this Article it shall consult the Commission and the authorities or bodies and the stakeholders referred to in Article 162(1) and (2), respectively, of [revised Regulation (EC) No 726/2004].

Article 85 – paragraph 1 – introductory part: Patent rights, or supplementary protection certificates under the [Regulation (EC) No 469/2009 - OP please replace reference by new instrument when adopted] shall not be regarded as infringed when necessary studies, trials and other activities are conducted for the purpose of:

Article 85 – paragraph 1 – point a – introductory part: deleted

Article 85 – paragraph 1 – point a – point i: (i) obtaining a marketing authorisation and subsequent variations;

Article 85 – paragraph 1 – point a – point ii: (ii) conducting a health technology assessment as defined in Regulation (EU) 2021/2282;

Article 85 – paragraph 1 – point a – point iii: (iii) obtaining pricing and reimbursement approval; and

Article 85 – paragraph 1 – point a – point iii a (new): (iiia) the subsequent practical requirements associated with such activities.

Article 85 – paragraph 1 – point b: The activities conducted exclusively for the purposes set out in the first paragraph, shall cover as relevant the submission of the application for a marketing authorisation and the offer, manufacture, sale, supply, storage, import, use and purchase of patented medicinal products or processes, including by third party suppliers and service providers.

Article 85 a (new): Article 85a / Non-interference of intellectual property rights / 1. Member States shall consider the procedures and decisions referred to in Article 85 as regulatory or administrative procedures which, as such, are independent from the enforcement of intellectual property rights. / 2. The protection of intellectual property rights shall not be a valid ground to refuse, suspend, delay, withdraw or revoke decisions referred to in Article 85. / 3. Paragraphs 1 and 2 shall apply without prejudice to the Union and national legislation relating to the protection of intellectual property.

Article 86 a (new): Article 86a / Reporting on access to medicinal products / The Commission, in collaboration with the Member States, shall develop indicators to measure access to medicinal products within the Union. Those indicators shall be evidence-based, measurable, and regularly reviewed to reflect the evolving healthcare landscape within the Union. / The Commission shall publish a report assessing access to medicinal products and barriers to improving such access in each Member State and at aggregated Union level. The report shall be publically available. / Based on the report, the Commission shall create a dedicated website with easily accessible information on the access indicators and access to medicinal products in the Union, intended for the general public and relevant stakeholders. / The report shall be drawn up for the first time by [the date of the end of the second year from the date of entry into force of this Directive] and every five years thereafter.

Article 87 – paragraph 1 – subparagraph 1 – point c – paragraph 1: (c) to conduct a post-authorisation environmental risk assessment study, collection of monitoring data or information on use, if there are concerns about the risks to the environment or public health, including antimicrobial resistance, due to an authorised medicinal product, or related active substance; where the post-authorisation environmental risk assessment study concerns an antimicrobial, it shall include relevant and comparable data on the volume of sales and the use per types of antimicrobial medicinal products; the Agency shall cooperate with Member States and with other Union agencies to analyse those data and shall publish an annual report; the Agency shall take into account those data when adopting any relevant guidelines and recommendations.

Article 87 – paragraph 1 – subparagraph 2: The imposition of such an obligation shall be duly justified, notified in writing, and shall include the objectives and timeframe for submission and conduct of the study. Information on imposed post-authorisation studies shall be noted in the product’s European Public Assessment Report and a database of the competent authority.

Article 92 – paragraph 3: 3. The procedures for examination of applications for variations shall be proportionate to the risk and impact involved. Those procedures shall range from procedures that allow implementation only after approval based on a complete scientific assessment to procedures that allow immediate implementation and subsequent notification by the marketing authorisation holder to the competent authority. Such procedures may also include updates by the marketing authorisation holder of their information held in a database. Where deemed justified by the Agency, accelerated assessment procedures shall also be envisaged for variations which are of major interest from the point of view of public health.

Article 94 – paragraph 1: 1. On the basis of relevant paediatric clinical studies received in accordance with Article 45(1) of Regulation (EC) No 1901/2006 of the European Parliament and of the Council76 , the competent authorities of the Member States may, following a consultation of the marketing authorisation holder, vary the marketing authorisation of the medicinal product concerned accordingly and update the summary of product characteristics and package leaflet of the medicinal product concerned. The competent authorities shall exchange information regarding the studies submitted and, as appropriate, their implications for any marketing authorisations concerned.

Article 96 – paragraph 1 – subparagraph 1: Member States shall operate a pharmacovigilance system for the fulfilment of their pharmacovigilance tasks and their participation in the Union pharmacovigilance activities including the pharmacovigilance of the post-authorisation safety and efficacy long-term studies in children, including where relevant data from the off-label use of the product.

Article 97 – paragraph 1 – point e a (new): (ea) facilitate the protection of patients in relation to adverse events through the development and implementation of plans for safe administration and handling of medicinal products, which may include the use of digital medication safety systems in hospitals and ambulatory care settings.

Article 102 – paragraph 1 – point b a (new): (ba) the outcome of the assessment of the ERA, including the data submitted by the marketing authorisation holder, in accordance with Article 22(7a) and Article 29(4a);

Article 102 – paragraph 1 – point d a (new): (da) where relevant, information related to antimicrobials, in accordance with Article 17(2) and Article 29(4a);

Article 102 – paragraph 1 – point d b (new): (db) where relevant, the awareness card with information on antimicrobial resistance and the appropriate use and disposal of antimicrobials;

Article 102 – paragraph 1 – point d c (new): (dc) periodic safety update reports;

Article 102 – paragraph 1 – point d d (new): (dd) information on the shortage status of medicinal products as referred to in Article 121(1), point (b), of [revised Regulation (EC) No 726/2004];

Article 105 – paragraph 2: 2. Marketing authorisation holders shall not refuse to consider reports of suspected adverse reactions received electronically or by any other appropriate means from patients, carers or other relevant persons, such as family members, or healthcare professionals.

Article 106 – paragraph 1 – subparagraph 1: Each Member State shall record all suspected adverse reactions that occur in its territory and that are brought to its attention from healthcare professionals and patients. This shall include all authorised medicinal products and medicinal products used in accordance with Article 3, paragraphs 1 or 2. Member States shall involve patients and healthcare professionals, as appropriate, in the follow-up of any reports they receive in order to comply with Article 97(1), points (c) and (e), and shall seek to inform directly those stakeholders that reported a suspected adverse drug reaction on decisions taken in relation to the safety of the medicinal product.

Article 106 – paragraph 5: 5. Member States shall ensure that reports of suspected adverse reactions arising from an error, including those associated with the use, administration, and dispensation of a medicinal product, by professionals, that are brought to their attention are made available to the Eudravigilance database and to any authorities, bodies, organisations or institutions, responsible for patient safety within that Member State concerned. They shall also ensure that the authorities responsible for medicinal products within that Member State are informed of any suspected adverse reactions brought to the attention of any other authority within that Member State. These reports shall be appropriately identified in the forms referred to in Article 102 of [revised Regulation (EC) No 726/2004]

Article 106 – paragraph 5 a (new): 5a. Reports of adverse reactions arising from incorrect administration or dispensation of a medicinal product shall be available in the Eudravigilance database and shall be included in periodic safety update reports. Where relevant, Member States shall take corrective action to achieve high standards of medication safety in healthcare settings after consultation of healthcare professionals and other relevant stakeholders.

Article 107 – paragraph 3 a (new): 3a. The Agency or the national competent authorities, as appropriate, shall make publicly available the reports referred to in paragraph 1, points (a) and (b).

Article 123 – paragraph 1 – introductory part: The Agency shall, in cooperation with competent authorities of the Member States and other interested parties, including those referred to in Article 162 of [revised Regulation (EC) No 726/2004], draw up:

Article 123 – paragraph 1 – point a a (new): (aa) guidance for national competent authorities on the effective inclusion of patients and healthcare professionals in the data collection and communication of the risks of medicinal products within the pharmacovigilance activities;

Chapter X – title: Homeopathic products and traditional herbal medicinal products

Article 125 – title: Registration or authorisation of homeopathic products

Article 125 – paragraph 1: 1. Member States shall ensure that homeopathic products manufactured and placed on the market in the Union are registered in accordance with Articles 126 and 127 or authorised in accordance with Article 133(1), except where such homeopathic products are covered by a registration or authorisation granted in accordance with national legislation on or before 31 December 1993. In case of registrations, Chapter III, Sections 3 and 4, and Article 38, paragraphs 1, 2 and 3 shall apply.

Article 125 – paragraph 2: 2. Member States shall establish a simplified registration procedure referred to in Article 126 for the homeopathic products.

Article 126 – title: Simplified registration procedure for homeopathic products

Article 126 – paragraph 1 – subparagraph 1 – introductory part: Homeopathic products that satisfy all of the following conditions may be subject to a simplified registration procedure:

Article 126 – paragraph 1 – subparagraph 1 – point b: (b) no specific therapeutic indication appears on the labelling of the homeopathic product or in any information relating thereto;

Article 126 – paragraph 1 – subparagraph 1 – point c: (c) there is a sufficient degree of dilution to guarantee the safety of the homeopathic product

Article 126 – paragraph 1 – subparagraph 2: For the purposes of point (c), the homeopathic product may not contain either more than one part per 10000 of the mother tincture or more than 1/100th of the smallest dose used in allopathy with regard to active substances whose presence in an allopathic homeopathic product results in the obligation to submit a doctor’s prescription.

Article 126 – paragraph 1 – subparagraph 4: At the time of registration, Member States shall determine the prescription status for the dispensing of the homeopathic product.

Article 126 – paragraph 2: 2. The criteria and rules of procedure provided for in Article 1(10), point (c), Article 30, Chapter III, Section 6, Articles 191, 195 and 204 shall apply by analogy to the simplified registration procedure for homeopathic products, with the exception of the proof of therapeutic efficacy.

Article 127 – paragraph 1 – introductory part: An application a simplified registration may cover a series of homeopathic products derived from the same homeopathic stock or stocks. The following shall be included with the application in order to demonstrate, in particular, the pharmaceutical quality and the batch-to-batch homogeneity of the homeopathic products concerned:

Article 127 – paragraph 1 – point d: (d) the manufacturing authorisation for the homeopathic product concerned;

Article 127 – paragraph 1 – point e: (e) the copies of any registrations or authorisations obtained for the same homeopathic product in other Member States;

Article 127 – paragraph 1 – point f: (f) one or more mock-ups of the outer packaging and the immediate packaging of the homeopathic products to be registered;

Article 127 – paragraph 1 – point g: (g) the data concerning the stability of the homeopathic product.

Article 128 – title: Application of decentralised and mutual recognition procedures to homeopathic products

Article 128 – paragraph 1: 1. Article 38, paragraphs 4 and 6, Articles 39 to 42 and 95 shall not apply to the homeopathic products referred to in Article 126.

Article 128 – paragraph 2: 2. Chapter III, Sections 3 to 5, shall not apply to the homeopathic products referred to in Article 133(2).

Article 129 – title: Labelling of homeopathic products

Article 129 – paragraph 1: Homeopathic products, with the exception those referred to in Article 126(1), shall be labelled in accordance with the provisions of Chapter VI and shall be identified by a reference on their labels, in clear and legible form, to their homeopathic nature.

Article 130 – title: Specific requirements for labelling of certain homeopathic products

Article 130 – paragraph 1 – subparagraph 1 – introductory part: The labelling and, where appropriate, the package insert for homeopathic products referred to in Article 126(1) in addition to the clear mention of the words ‘homeopathic product’, shall bear the following, and no other, information:

Article 130 – paragraph 1 – subparagraph 1 – point k: (k) ‘homeopathic product without approved therapeutic indications’;

Article 130 – paragraph 1 – subparagraph 2: As regards the first subparagraph, point (a), if the homeopathic product is composed of two or more stocks, the scientific names of the stocks on the labelling may be supplemented by an invented name.

Article 130 – paragraph 2 – point a: (a) the price of the homeopathic product;

Article 131 – title: Advertising of homeopathic products

Article 131 – paragraph 1: 1. Chapter XIII shall apply to homeopathic products.

Article 131 – paragraph 2 – subparagraph 1: By derogation from paragraph 1, Article 176(1) shall not apply to homeopathic products referred to in Article 126(1).

Article 131 – paragraph 2 – subparagraph 2: However, only the information specified in Article 130(1) may be used in the advertising of such homeopathic products.

Article 132 – title: Exchange of information on homeopathic products

Article 132 – paragraph 1: Member States shall communicate to each other all the information necessary to guarantee the quality and safety of homeopathic products manufactured and marketed within the Union, and in particular the information referred to in Articles 202 and 203.

Article 133 – title: Other requirements for homeopathic products

Article 133 – paragraph 1: 1. Homeopathic products other than those referred to in Article 126(1) shall be granted a marketing authorisation in accordance with Articles 6 and 9 to 14 and labelled in accordance with Chapter VI.

Article 133 – paragraph 2 – subparagraph 1: A Member State may introduce or retain in its territory specific rules for the non-clinical tests and clinical studies of homeopathic products other than those referred to in Article 126(1), in accordance with the principles and characteristics of homeopathy as practised in that Member State.

Article 133 – paragraph 3: 3. Chapter IX shall apply to homeopathic products, with the exception of those referred to in Article 126(1). Chapter XI, Chapter XII, Section 1, and Chapter XIV shall apply to homeopathic products.

Article 140 – paragraph 2 – subparagraph 1 – point b: (b) the user should consult a doctor or a qualified healthcare practitioner if the symptoms persist during the use of the traditional herbal medicinal product or if adverse effects occur; and

Article 140 – paragraph 2 – subparagraph 1 – point b a (new): (ba) the user consult a doctor or a qualified healthcare practitioner for information about possible contraindications or pharmacological interactions with other medications.

Article 140 – paragraph 3: 3. In addition to the requirements set out in Chapter XIII, any advertisement for a traditional herbal medicinal product registered under this Section shall contain the following statement: Traditional herbal medicinal product for use in specified therapeutic indication(s) exclusively based upon long-standing use. For more information, consult a healthcare professional.

Article 142 – paragraph 3 – point a: (a) preparation, dividing up, changes in packaging or presentation where these processes are carried out, solely for retail and hospital supply, by pharmacists in dispensing pharmacies or by persons legally authorised in the Member States to carry out such processes; or

Article 147 – paragraph 1 – subparagraph 1 – point j a (new): (ja) use an appropriate wastewater treatment system;

Article 147 – paragraph 1 – subparagraph 1 – point j b (new): (jb) comply with relevant risk mitigation measures identified in accordance with Article 22.

Article 148 – paragraph 9: 9. Where relevant, competent authorities of the Member State supervising the central and decentralised sites shall liaise with the competent authority of the Member State responsible for the supervision of the marketing authorisation.

Article 160 – paragraph 1 – introductory part: The Commission is empowered to adopt delegated acts in accordance with Article 215 to supplement this Directive by specifying:

Article 160 – paragraph 1 – point b a (new): (ba) measures to reduce the negative impact on the environment posed by the manufacturing of medicinal products.

Article 163 – paragraph 1: 1. The competent authority of the Member State concerned shall take all appropriate measures to ensure that the wholesale distribution of medicinal products is subject to an authorisation to engage in activity as a wholesaler in medicinal products (“wholesale distribution authorisation”). The wholesale distribution authorisation shall indicate the premises, the categories of medicinal products and the wholesale distribution operations for which it is valid.

Article 166 – paragraph 1 – point m: (m) cooperate with all relevant stakeholders, including marketing authorisation holders and competent authorities of the Member States on the security of supply.

Article 168 – paragraph 1 – introductory part: 1. For all supplies of medicinal products to a person authorised or entitled to supply medicinal products to the public in the Member State concerned, the authorised wholesaler shall provide a document, which may be submitted in electronic format, that makes it possible to ascertain the following:

Article 172 – paragraph 1 – point a: (a) the natural or legal person offering the medicinal products is authorised or entitled to supply medicinal products to the public, also at a distance, in accordance with national legislation of the Member State in which that person is established and complies, where applicable, with the conditions referred to in paragraph 2 of this Article;

Article 175 – paragraph 1 – subparagraph 2 – point e: (e) the provision of inducements to prescribe or supply medicinal products by the gift, offer or promise of any benefit or bonus, whether in money or in kind;

Article 176 – paragraph 3 – point b a (new): (ba) shall not induce to an excessive or abusive use of the medicinal product.

Article 176 – paragraph 4: 4. Any form of advertising that aims to highlight negatively another medicinal product shall be prohibited. Advertising that suggests that a medicinal product is safer or more effective than another medicinal product shall also be prohibited, unless demonstrated and supported by the summary of product characteristics for the relevant indications and patient population.

Article 177 – paragraph 1 – point b a (new): (ba) are antibiotics or antimicrobials for which there is an identified risk of antimicrobial resistance as referred to in Article 51(1a).

Article 177 – paragraph 2: 2. Medicinal products may be advertised to the general public where, by virtue of their composition and purpose, they are intended and designed for use without the intervention of a healthcare professional for diagnostic purposes or for the prescription or monitoring of treatment, with the advice of the pharmacist, if necessary.

Article 177 – paragraph 4: 4. The prohibition contained in paragraph 1 shall not apply to vaccination campaigns approved by the competent authorities of the Member States.

Article 178 – paragraph 1 – point b – point ii: (ii) the information necessary for correct use and disposal of the medicinal product;

Article 178 – paragraph 1 – point b – point iii: (iii) an express, legible invitation to read carefully the instructions on the package leaflet or on the outer packaging, as the case may be, and to consult a medical practitioner or a pharmacist for additional information.

Article 178 – paragraph 2 a (new): 2a. The Commission shall adopt delegated acts in accordance with Article 215 to supplement this Directive by specifying requirements in relation to direct and indirect advertising of medicinal products through social media and other media platforms and product placements by celebrities and influencers.

Article 179 – paragraph 1 – point h: (h) suggests that the safety or efficacy of the medicinal product is due to the fact that it is natural or not chemical;

Article 183 – paragraph 1: 1. Where medicinal products are being promoted to persons qualified to prescribe or supply them, no gifts, pecuniary advantages or benefits in kind may be supplied, offered or promised to such persons.

Article 185 – paragraph 1 – point g: (g) no samples of medicinal products containing substances classified as antibiotic, psychotropic or narcotic within the meaning of international conventions may be supplied.

Article 186 – paragraph 1: 1. Member States shall ensure that there are adequate and effective methods to monitor the advertising of medicinal products. At least for advertisements targeted at the general public, such methods shall be based on a system of prior vetting, and shall in any event include legal provisions under which persons or organisations regarded under national law as having a legitimate interest in prohibiting any advertisement inconsistent with this Chapter, may take legal action against such advertisement, or bring such advertisement before the competent authority of the Member State either to decide on complaints or to initiate appropriate legal proceedings.

Article 186 – paragraph 4 a (new): 4a. Member States shall set up and maintain a national transparency register of transfers of value regarding the advertising activities referred to in Articles 175, 177, 180 and 182 to 185, targeting persons qualified to prescribe medicinal products. The Commission shall publish on its website a list referring to all national registries.

Article 186 – paragraph 4 b (new): 4b. The national registries referred to in paragraph 4a of this Article shall include at least the following information: / (a) the name of the marketing authorisation holder; / (b) the name of a person qualified to prescribe medicinal products; / (c) the medicinal product concerned; / (d) the type of advertising activity, referred to in Article 175(1), second subparagraph, points (b) to (g) and Article 184; / (e) the monetary value.

Article 186 – paragraph 4 c (new): 4c. Marketing authorisation holders shall use the national transparency register referred to in paragraph 4a to submit the information referred to in paragraph 4b in relation to each person qualified to prescribe medicinal products in the Member State where such activity takes place.

Article 186 – paragraph 5: 5. Paragraphs 1 to 4c shall not exclude the voluntary control of advertising of medicinal products by self-regulatory bodies.

Article 187 – paragraph 2 – point d a (new): (da) report activities in national registries, as laid down in Article 186 (4c).

Article 188 – paragraph 5 – introductory part: 5. Where the competent authority of the Member State considers it necessary, in particular where there are grounds for suspecting non-compliance with the rules of this Directive, including with the principles of good manufacturing practice and good distribution practices, referred to in Articles 160 and 161, or based on a risk assessment, it may have its official representatives carry out the measures referred to in paragraph 1, second subparagraph at the premises or on the activities of:

Article 188 – paragraph 5 – point d: (d) distributors of medicinal products or manufacturers or distributors of active substances located in third countries;

Article 188 – paragraph 5 a (new): 5a. The Agency shall draw up guidelines on the use of the Union database.

Article 193 – paragraph 2: 2. Where, in the interests of public health, the laws of a Member State so provide, the competent authorities of the Member State may require the marketing authorisation holder for medicinal products derived from human blood or human plasma to submit samples from each batch of the bulk or the medicinal product for testing by an Official Medicines Control Laboratory or a laboratory that a Member State has designated for that purpose before being released into free circulation, unless the competent authorities of another Member State have previously examined the batch in question and declared it to be in conformity with the approved specifications. In such a case the declaration of conformity issued by another Member State shall be recognised. Member States shall ensure that any such examination is completed within 60 days of the receipt of the samples.

Article 194 – title: Processes for the preparation of medicinal products derived from substances of human origin

Article 194 – paragraph 1: 1. Member States shall take all necessary measures to ensure that the manufacturing and purifying processes used in the preparation of medicinal products derived from substances of human origin are properly validated, attain batch-to-batch consistency and guarantee, insofar as the state of technology permits, the absence of relevant risks for human health, including contaminations.

Article 194 – paragraph 2: 2. To this end manufacturers shall notify the competent authorities of the Member States of the methods used to ensure the quality and safety of the substances of human origin, as set out in Regulation (EU) 2024/...[SoHO Regulation]. The competent authority of the Member State may submit samples of the bulk or the medicinal product for testing by a State laboratory or a laboratory designated for that purpose, either during the examination of the application pursuant to Article 29, or after a marketing authorisation has been granted.

Article 195 – paragraph 2: 2. The competent authorities of the Member States or, in the case of centralised marketing authorisation, the Commission may suspend, revoke or vary a marketing authorisation if a serious risk to the environment or public health has been identified and not sufficiently addressed by the marketing authorisation holder and if the risks cannot be mitigated through the grant of the conditions specified in Articles 44(1), first subparagraph, point (h) or 87(1), first subparagraph, point (c) following a decision of suspension or modification. Any such decision shall take into account the clinical benefits of the medicinal product and the needs of patients, including alternative treatments available.

Article 196 – paragraph 1 – point f: (f) a serious risk to the environment or to public health via the environment has been identified and not sufficiently addressed by the marketing authorisation holder through the grant of the conditions specified in Articles 44(1), first subparagraph, point (h), or 87(1), first subparagraph, point (c); any such decision shall also take into account the clinical benefits of the medicinal product and the needs of patients, including alternative treatments available.

Article 200 – paragraph 2: 2. Member States shall ensure that adequate financial resources are available to provide the staff and other resources, including appropriate digital infrastructure, necessary for the competent authorities to carry out the activities required by this Directive and [revised Regulation (EC) No 726/2004].

Article 200 – paragraph 4 – subparagraph 1: The competent authority of the Member State may process personal health data from sources other than clinical studies, including real world data, to support their public health tasks and, in particular, the evaluation and monitoring to medicinal products, for the purpose of improving the robustness of the scientific assessment or verifying claims of the applicant or marketing authorisation holder.

Article 201 – paragraph 1: 1. Member States, in applying this Directive, shall ensure that when questions arise with regard to the regulatory status of a medicinal product, in relation to their link to substances of human origin as referred to in Regulation (EU) No [SoHO Regulation], the competent authorities of the Member States shall consult the Agency and the relevant authorities established under that Regulation.

Article 201 – paragraph 2 a (new): 2a. In order to improve regulatory certainty and cross-sectoral cooperation, the Commission shall, where necessary, organise joint meetings between the Agency and the relevant advisory and regulatory bodies established under other Union legislation to assess, for the purposes of this Directive, emerging trends and questions on the regulatory status of products and to find agreement on common regulatory status principles. The summaries and conclusions of those joint meetings shall be made publicly available, including the opinions and conclusions of each of the respective bodies.

Article 206 – paragraph 1 a (new): 1a. When determining the type and level of penalties to be imposed in the case of infringements, the competent authorities of the Member States shall give due regard to all relevant circumstances of the specific infringement and to the following: / (a) the nature, gravity and extent of the infringement; / (b) the repetitive or singular character of the infringement; / (c) where appropriate, the intentional or negligent character of the infringement; / (d) any action taken by the infringing party to mitigate or remedy the damage caused; / (e) the level of cooperation with the competent authorities, in order to remedy the infringement and mitigate the possible adverse effects of the infringement;

Article 206 – paragraph 2 – point e a (new): (ea) non-compliance with the obligations set out in Article 58a shall be subject to the imposition of effective, proportionate and dissuasive financial penalties.

Article 207 – title: Collection and management of unused or expired medicinal products

Article 207 – paragraph 1: Member States shall ensure that appropriate collection and management systems are in place for medicinal products that are unused or have expired and that the collected medicinal products are managed properly without any technically avoidable leakage to the environment.

Article 207 – paragraph 1 a (new): 1a. By ... [18 months from the date of entry into force of this Directive], Member States shall draw up national plans including measures designed to: / (a) monitor the rates of correct and incorrect disposal of unused and expired medicinal products; / (b) inform the general public about the environmental risks associated with incorrect disposal of medicinal products, in particular those that contain substances referred to in Article 22(2); / (c) inform healthcare professionals about the environmental risks associated with incorrect disposal of unused or expired medicinal products, in particular those that contain substances referred to in Article 22(2); / (d) increase the rate of correct disposal of unused or expired medicinal products; and / (e) designate public or private actors, or both, responsible for the collection systems referred to in paragraph 1.

Article 207 – paragraph 1 b (new): 1b. Member States shall submit the national plans to the Commission.

Article 208 – paragraph 1: 1. In order to guarantee independence and transparency, the Member States shall ensure that members of staff of the competent authority responsible for granting authorisations, rapporteurs and experts concerned with the authorisation and surveillance of medicinal products have no direct or indirect financial or other interests in the pharmaceutical industry that could affect their impartiality and their independence. These persons shall make an annual declaration of their financial interests and update them annually and whenever necessary. The declaration shall be made available upon request.

Article 208 – paragraph 2: 2. In addition, the Member States shall ensure that the competent authority makes publicly available its rules of procedure and those of its committees, including their working groups and expert groups, agendas for its meetings and records of its meetings, accompanied by decisions taken, details of votes and explanations of votes, including minority opinions.

Article 214 – paragraph 4: 4. The rules of procedure, lists of participating entities of its meetings, agendas for its meetings and records of its meetings, accompanied by decisions taken, and, where applicable, details of votes and explanations of votes, including minority opinions, of the Standing Committee on Medicinal Products shall be made publicly available.

Article 216 – paragraph 1: By [OP please insert the date = 10 years following 18 months after the date of entering into force of this Directive], the Commission shall present a report to the European Parliament and the Council on the application of this Directive, including an assessment of the fulfilment of its objectives and the resources required to implement it, including regarding the revised framework for regulatory data protection periods.

Article 216 – paragraph 1 a (new): 1a. By ...[2 years from the date of entry into force of this Directive], the Commission shall submit a report to the European Parliament and Council evaluating the appropriateness of the framework of homeopathic products, in particular aspects of public health and patient protection. The report shall, where appropriate, be accompanied by a legislative proposal.

Article 216 a (new): Article 216a / Fostering research on, and innovation and production of, medicinal products in the Union / 1. The Commission shall establish a strategy on fostering research on, and innovation and production of, medicinal products in the Union, based on the results published in the report provided for paragraph 2. Member States shall be encouraged to participate in that strategy. / 2. By... [two years from the date of entry into force of this Directive] the Commission shall present an impact assessment evaluating potential measures to be implemented at Union level and at a Member State level to foster research on, and innovation and production of, critical medicinal products in the Union. That report shall evaluate the effect of measures such as: / (a) funding and push and pull incentives directed to foster research and innovation in the Union, including public and private funding for preclinical and clinical research and innovation; / (b) public-private partnerships in research and innovation; / (c) regulatory support for public research and innovation entities; / (d) incentives for production of critical medicinal products within the Union. / Any proposed measures shall be in line with the development of the strategic autonomy of the Union regarding medicinal products.

Annex I – point 21 – point a – introductory part: a) an antimicrobial stewardship and access plan which shall in particular outline:

Annex I – point 21 – point a – point ii a (new): (iia) information about measures for a strategy to promote access, including proposed production chain capacity;

Annex I – point 21 – point a – point ii b (new): (iib) information about measures to ensure marketing approvals are received for key territories in a timely manner; and

Annex I – point 21 – point a – point ii c (new): (iic) information about measures to monitor effectiveness of stewardship and access.

Annex IV – paragraph 1 – point a: (a) the name of the medicinal product, including in Braille, followed by its strength and pharmaceutical form, and, if appropriate, whether it is intended for babies, children or adults; where the medicinal product contains up to three active substances, the international non-proprietary name (INN) shall be included, unless it is already part of the name of the medicinal product, or, if one does not exist, the common name;

Annex IV – paragraph 1 – point g a (new): (ga) for antimicrobials, a warning that improper use and unsafe disposal of the medicinal product contributes to antimicrobial resistance;

Annex IV – paragraph 1 – point j: (j) specific precautions relating to the disposal of unused medicinal products or waste derived from medicinal products as well as reference to any appropriate collection system in place;

Annex V – paragraph 1 – point 6 – point f: (f) special precautions for disposal of a medicinal product or waste materials derived from such medicinal product as well as any designated collection system in place. In case of antimicrobial medicinal products in addition to the precautions a warning that inappropriate disposal of the medicinal product contributes to antimicrobial resistance;

Annex VI – paragraph 1 – point 2 a (new): (2a) a key information section reflecting the results of consultations with patients’ organisations to ensure that the leaflet is legible, clear and easy to use;

Annex VI – paragraph 1 – point 4 – point b: (b) the method and, if necessary, route of administration, and where relevant a description of the measuring or delivery device, as well as the relevant individual steps of medicine preparation and administration;

Annex VI – paragraph 2 a (new): The package leaflet may also contain information on the importance of therapeutic adherence and available support for adherence in the Member State.

EXPLANATORY STATEMENT

The Union general pharmaceutical legislation was established in 1965 with the dual objective of safeguarding public health and harmonising the internal market for medicines. The latest proposal of the European Commission for revision of this legislation includes a new Directive and a new Regulation to replace pharmaceutical legislation currently in force, with the overall objectives of promoting innovation, ensuring access to innovative and established medicines for patients, and creating a balanced and competitive system that keeps medicines affordable for health systems while rewarding innovation. Of the ‘Pharmaceutical Package’, this Directive contains all the requirements for authorisation, monitoring, labelling and regulatory protection, placing on the market and other regulatory procedures for all medicines authorised at EU and national level.

The Rapporteur supports the objectives of the European Commission’s proposal and finds that a revision of current Union general pharmaceutical legislation comes at the right time: Europe is increasingly falling behind other regions in pharmaceutical research and development investments, novel technologies challenge the existing legislative framework, and the COVID-19 pandemic demonstrated the need for timely and equitable access to medicines.

Incentivising Innovation

The Rapporteur believes that increasing the number of innovative medicinal products available to Europeans is of crucial benefit to patients and society. In this regard, the Directive must present a framework for rewarding innovation which is attractive to the global pharmaceutical industry, including the wider research-based life-science environment.

Making Europe competitive is an objective which requires a multifactorial solution. However, among the key factors, which is within the scope of this Directive, is the system of incentives and namely the regulatory data protection. Regulatory data protection affects companies’ decisions to invest in innovation and to bring scientific innovation to launch on the Union market. In this regard, the Rapporteur finds that the level of regulatory data protection offered on the Union market should be competitive with what is being offered in other markets. Furthermore, there should be certainty and long-term predictability regarding the level of regulatory data protection to be expected, which means that a significant amount of the total regulatory data protection should remain within the ‘baseline’.

The Rapporteur agrees with the European Commission’s proposal that further incentives on top of an attractive baseline of regulatory data protection may help steer innovation and finds that a definition of unmet medical need should be considered from both the individual patient and societal perspectives. That is, innovation for unmet medical need should be sufficiently incentivised, while the definitions applied for deciding which medicinal products address an unmet medical need should consider the patient perspective centrally. In this regard, the Rapporteur finds that the concept of ‘quality of life’ of patients should be considered.

Outside of regulatory data protection, the Rapporteur also proposes to increase the reward for completion of a paediatric investigation plan where this is completed for a different disease than the one for which a medicinal product is intended in the adult population.

Access to Medicines

The European Commission has proposed an incentive which will grant a prolongation of data protection if a medicinal product is supplied in accordance with the needs of the Member States concerned within two years from the marketing authorisation (or within three years in the case of SMEs, not-for-profit entities or companies with limited experience in the EU system). The Rapporteur opposes this measure, by which the European Commission intends to promote access to medicinal products. Firstly, because the release and continuous supply of medicinal products is not only within the control of the marketing authorisation holder but also relies on the Member State competent authorities. Thus, it would be disproportionate to place all responsibility, and direct consequences, for a failure to launch only on the marketing authorisation holder. Secondly, linking the failure to comply with the conditionality of supply in every Member State to losing out on regulatory data protection will be to the detriment of innovation, as described above. Finally, the Rapporteur is concerned about how this measure would work in relation to orphan medicinal products and ATMPs.

Rather, the Rapporteur proposes to place an obligation on marketing authorisation holders to submit in every Member State, which requested them to do so, an application for pricing and reimbursement. In case of non-compliance with the obligation, a proportional financial penalty shall be applied by affected Member States. This can promote access to medicinal products across Europe, while ensure predictability in the expectations, as well as in the possible penalties, of marketing authorisation holders. Marketing authorisation holders of orphan medicinal products and ATMPs shall be subject to an adapted obligation, and in special cases the European Commission may exempt specific medicinal products. To further the processes surrounding the obligation, the European Commission shall set up an “EU Access to Medicines Notification System”.

Environmental Health

The Rapporteur welcomes the initiative of the European Commission to strengthen measures related to the environmental impact of medicines, and, by extension, the impact on human health of negative environmental impacts. However, these should be proportionate and not unjustly have a negative effect on patients.

Notably, the Rapporteur finds that in case of serious risks to the environment a marketing authorisation may be suspended or varied, but should only be revoked in cases where those risks clearly outweigh the loss of positive therapeutic effect of the medicine. The Rapporteur also asks the Commission to ensure that the proper guidelines for conducting environmental risk assessments for antimicrobials other than antibiotics are in place before obligations in this regard shall apply. When specifying technical details for the environmental risk assessments, all relevant stakeholders shall be consulted. As regards medicines for which a prescription is needed, the Rapporteur wishes to ensure continued patient access to antimicrobials not for systemic use.

The Rapporteur suggests to place extended obligations on the Member States with regard to the appropriate collection and management of unused or expired medicines. In this regard, Member States are asked to draw up national plans, including measures designed to inform the public and healthcare professionals about environmental risks in regard to incorrect disposal of medicines and increase its rate of correct disposal of medicines.

Patient-centred Information

The Rapporteur places emphasis on the importance of properly ensuring accurate information to patients about the medicines they consume. The first objective of package leaflets shall be to meet the needs of patients. Whether the leaflet is in electronic or in paper format, its content must be legible, clear and easy to use. The Rapporteur proposes that the package leaflet shall contain a ‘key information section’ to support this objective.

The addition by the European Commission of electronic information can, in this regard, benefit some patients. However, where no other position has been taken, the information should be available in the form of both paper leaflets and electronic product information. The decision to make information available only electronically shall lay with each Member State, and in this case, patients shall be made aware of their right to a printed copy. However, where the medicinal product is not intended to be delivered directly to, and administered by, the patient the Commission may take the decision to make only the electronic product information mandatory.

Awareness cards shall be available in paper format, or in both paper format and electronically, to support that this information is duly received by patients. The Rapporteur supports the proposal of the European Commission that Member States may make exemptions to the language requirements of labelling, however, patients should, in this case, still be able to request a copy in the official language of their Member State.