What changed between the draft committee report and the plenary report

DRAFT EUROPEAN PARLIAMENT LEGISLATIVE RESOLUTION

7 unchanged paragraphs

on the proposal for a directive of the European Parliament and of the Council on the Union code relating to medicinal products for human use, and repealing Directive 2001/83/EC and Directive 2009/35/EC

(COM(2023)0192 – C90143/2023 – 2023/0132(COD))

(Ordinary legislative procedure: first reading)

The European Parliament,

– having regard to the Commission proposal to Parliament and the 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,

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

Change 1

Changed:– having regard to the opinionafter ofconsulting the Committee of the Regions of ...,Regions,

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

– having regard to the opinion of the Committee on Industry, Research and Energy,

Changed:– having regard to the reportletter offrom the Committee on the Environment, Public Health and Food SafetyLegal (A90000/2023),Affairs,

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

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

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

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

Change 2

Removed: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, and create an attractive environment for research, development and production of medicines in the Union while reducing regulatory burden and the environmental impact of medicines; ensure access 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 while rewarding innovation.

Added: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.

Removed:Recital 11 a (new): (11a) This Directive should be consistent with the Union’s objectives with regard to promotion of research, innovation and industrial competitiveness, including with regard to a globally competitive system of intellectual property (IP) incentives. The provisions of this Directive should be coordinated with the Union’s industrial and digital strategies as well as its trade policy to ensure that the Union is capable of competing with challenger regions, as highlighted by the resolution of the European Parliament of 24 November 2021 on a pharmaceutical strategy for Europe 1a. Likewise, the conclusions of the Council of 23 March 2023 on competitiveness, single market and the economy have stressed the importance of strengthening incentives for investments in innovation. In that regard, it should be considered how the European life science sector, including the pharmaceutical industry, contributes as a whole to meeting those objectives and thus how this Directive should work to support it. / 1a OJ C 224, 8.6.2022, p. 47.

Added: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.

Removed: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, 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 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. 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.

Added: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.

Removed: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 European Medicines Agency (EMA) pilot programme for enhanced support to academic and non-profit developers of advanced therapy medicinal products, started in September 2022.

Added: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.

Removed:Recital 19: (19) This Directive should be without prejudice to the provisions of Council Directive 2013/59/Euratom41.

Added: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.

Removed:Recital 26: (26) In order to reward the compliance with all the measures included in the agreed paediatric investigation plan, for products covered by a supplementary protection certificate, if relevant information on the results of the studies conducted is included in the product information, a reward should be granted in the form of an extension of the supplementary protection certificate created by [Regulation (EC) No 469/2009 of the European Parliament and of the Council42 - OP please replace reference by new instrument when adopted].

Added: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.

Removed:See amendment to Article 86 – paragraph 1 – subparagraph 1.

Added: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.

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

Added: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.

Added: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.

Added: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.

Added: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.

Added: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.

Added: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.

Added: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.

Added: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…

Added: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…

Added: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.

Added: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.

Added: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.

Added: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.

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

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

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

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

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

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

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

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

Added: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.

Change 3

Removed:Recital 49: (49) 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. In the event of joint procurement of medicinal products as a medical countermeasure in cases of serious cross-border threats to health, the provisions of Regulation (EU) 2022/2371 of the European Parliament and of the Council49a apply. / 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 (OJ L 314, 6.12.2022, p. 26).

Added: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…

Removed:Recital 50: (50) The establishment of a criteria-based definition of ‘unmet medical need’ is required to incentivise the development of medicinal products in therapeutic areas that are currently underserved. To ensure that the concept of unmet medical need reflects scientific and technological developments and current knowledge in underserved diseases, the Commission should specify and update using implementing acts, the criteria of satisfactory method of diagnosis, prevention or treatment, ‘remaining high morbidity or mortality’, 'quality of life', ‘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. The criteria for ‘unmet medical need’ can be subsequently used by Member States to identify specific therapeutic areas of interest.

Added: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.

Removed:See amendment to Article 83.