Changes from report parliamentary committee draft to plenary report

RemovedRecital 70: (70) Marketing authorisation applications for medicinal products in the Union should include an Environmental Risk Assessment (ERA) and risk mitigation measures. If the applicant fails to submit a complete or sufficiently substantiated environmental risk assessment or they do not propose risk mitigation measures to sufficiently address the risks identified in the environmental risk assessment, it should be possible to refuse the marketing authorisation. The ERA should be updated when new data or knowledge about relevant risks become available.

AddedRecital 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.

RemovedRecital 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, there is not a scientifically agreed method to set regulatory values for the contribution of manufacturing to antimicrobial resistance other than for antibiotic resistance. The Commission should therefore issue guidelines on how to conduct ERAs for AMR selection for microbials other than bacteria after consulting the EMA, the European Centre for Disease Prevention and Control (ECDC) and the European Environment Agency.

AddedRecital 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.

RemovedRecital 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 and 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, radiopharmaceutical precursors and active substance intermediates, when the intermediate is a chemical active substance by itself or used in conjugation with a biological substance, as well as for raw materials and starting materials used for manufa…

AddedRecital 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.

RemovedSee amendment to new Article 26a.

AddedRecital 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…

RemovedRecital 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 and indelible by users, including especially the target patient groups. 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 serve function and readability, rather than aesthetics, and secondarily consider the environmental sustainability of the leaflet.

AddedRecital 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).

RemovedRecital 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 how indirect public funding instruments, such as tax advantages, have supported a particular product, the reporting obligation 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 any direct financial support received from any public authority or public body of the Union to carry out any activities for the research and development of medicinal products.

AddedRecital 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.

AddedRecital 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.

AddedRecital 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.

AddedRecital 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.

AddedRecital 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.

AddedRecital 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.

AddedRecital 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.

AddedRecital 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…

AddedRecital 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.

AddedRecital 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…

AddedRecital 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.

AddedRecital 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.

AddedRecital 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.

AddedRecital 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.

AddedRecital 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.

AddedRecital 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.

AddedRecital 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.

AddedRecital 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.

AddedRecital 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.

AddedRecital 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.

AddedRecital 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.

AddedRecital 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.

AddedRecital 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 .

RemovedArticle 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 efficacy of the advanced therapy medicinal products prepared under hospital exemption. Before a hospital exemption approval is granted, the competent authority of the Member State shall confirm that no advanced therapy medicinal product is authorised within the Union for the same therapeutic indication, and that the manufacturing of such medicinal product complies with the requirements for preparation on a non-routine basis as set out in paragraph 1.

AddedArticle 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.

RemovedArticle 2 – paragraph 4: 4. Member States shall ensure that data on the use, quality, safety and the efficacy of advanced therapy medicinal products prepared under hospital exemption, as well as any relevant data from patient follow-up, is collected and reported by the hospital exemption approval holder to the competent authority of the Member State at least annually. 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.

AddedArticle 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.

RemovedArticle 2 – paragraph 5: 5. If a hospital exemption approval is revoked due to quality, safety or efficacy concerns the competent authority of the Member States that approved the hospital exemption shall inform the Agency and the competent authorities of the other Member States.

AddedArticle 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].

RemovedArticle 2 – paragraph 6: 6. The competent authority of the Member State shall transmit the data related to the use, quality, 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 a publicly accessible repository of that data, as well as of information on the authorisation, suspension or withdrawal of hospital exemption approvals, which shall be updated regularly.

AddedArticle 1 – paragraph 10 – point a: deleted

AddedArticle 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’).

AddedArticle 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.

AddedArticle 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.

AddedArticle 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.

AddedArticle 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.

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

AddedArticle 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.

RemovedArticle 4 – paragraph 1 – point 18 a (new): (18a) 'radionuclide radiopharmaceuticals' means a radiopharmaceutical where the radionuclide or its salt is the active substance;

AddedArticle 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;

RemovedArticle 4 – paragraph 1 – point 18 b (new): (18b) 'complex radiopharmaceutical' means a radiopharmaceutical where the radionuclide is bound to or within a carrier molecule to achieve the targeted accumulation, including ready-to-use dosage forms and kits for radiopharmaceutical preparation;

AddedArticle 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).

RemovedArticle 4 – paragraph 1 – point 19: (19) ‘radionuclide generator’ means any system incorporating a fixed parent radionuclide from which a daughter radionuclide is produced, where the daughter radionuclide is used either as a medicinal product or as a radionuclide for radiolabelling purposes;

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

RemovedArticle 4 – paragraph 1 – point 30 a (new): (30a) ‘platform technology’ means a technology or collection of technologies used in the 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;

AddedArticle 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

RemovedSee amendments to new Article 26a.

AddedArticle 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;

RemovedArticle 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, will apply regardless of components added to the platform as part of the manufacturing process for a medicinal product;

AddedArticle 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;

RemovedSee amendments to new Article 26a.

AddedArticle 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;

RemovedArticle 4 – paragraph 1 – point 33: (33) ‘environmental risk assessment’ means the evaluation of the potential risks to the environment, including risks to public health arising from risks to the environment, posed by the release of the medicinal product in the environment from the 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;

AddedArticle 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.

RemovedArticle 4 – paragraph 1 – point 53: (53) ‘micro, small and medium-sized enterprises’ means micro, small and medium-sized enterprises as defined in Article 2 of Commission Recommendation 2003/361/EC72 and, from ... [18 months after the date of entry into force of this Directive], it means micro, small and medium-sized enterprises as defined in the delegated act referred to in Article 58a(1);

AddedArticle 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.

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

AddedArticle 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.

RemovedArticle 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.

AddedArticle 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.

RemovedSee amendments to new Article 26a.

AddedArticle 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.

RemovedArticle 15 – title: Fixed dose combination medicinal product and multi-medicinal product packages

AddedArticle 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.

RemovedSee amendments to new Article 26a.

AddedArticle 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.

RemovedArticle 15 – paragraph 1: 1. Where justified for preventative or therapeutic purposes, a marketing authorisation may be granted for a fixed dose combination medicinal product.

AddedArticle 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.

RemovedArticle 15 – paragraph 2 – subparagraph 1: Where justified for preventative or therapeutic purposes, a marketing authorisation may, in exceptional circumstances, 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.

AddedArticle 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.

RemovedSee amendment to Article 4 – paragraph 1 – point 30 a (new).

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

RemovedArticle 16 – paragraph 1: 1. A marketing authorisation shall be required for radiopharmaceuticals.

AddedArticle 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’).

RemovedArticle 22 – paragraph 2 – subparagraph 1: (d) endocrine disruptors.

AddedArticle 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.

RemovedAlignment with the language of Regulation (EC) No 1272/2008.

AddedArticle 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.

RemovedArticle 22 – paragraph 3: 3. Where the ERA identifies a risk to the environment, 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. The applicant shall provide detailed explanation that the proposed mitigation measures are appropriate and sufficient to address the identified risks to the environment.

AddedArticle 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.

RemovedArticle 22 – paragraph 4 – subparagraph 1 a (new): By way of derogation from the first subparagraph, the obligation to conduct a risk assessment for antimicrobial resistance shall only cover the risk for antibiotic resistance. That derogation shall cease to apply by ... [3 years after the date of entry into force of this Directive].

AddedArticle 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.

RemovedArticle 22 – paragraph 4 a (new): 4a. By ... [18 months after the date of entry into force of this Directive], the Commission shall, after having consulted the Agency, the European Environmental Agency (EEA), and the ECDC, issue guidelines on how to conduct the ERA for antimicrobials other than antibiotics.

AddedArticle 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.

RemovedArticle 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 those managing residues from medicinal products and their production in the environment, on the drafting of these scientific guidelines.

AddedArticle 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.

RemovedArticle 22 – paragraph 6 – subparagraph 1: The marketing authorisation holder shall update the ERA with new information without undue delay to the relevant competent authorities, in accordance with Article 90(2), if new information pertaining to the assessment criteria referred to in Article 29 becomes available and leads to a change of the conclusions of the ERA. The update shall include any relevant information from environmental monitoring, including monitoring under Directive 2000/60/EC, from eco-toxicity studies, from new or updated risk assessments under other Union legislation, as referred to in paragraph 1, and environmental exposure data.

AddedArticle 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.

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

AddedArticle 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.

RemovedArticle 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 requested.

AddedArticle 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.

RemovedArticle 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 three years after entering into force of this Directive, while taking into account outcomes from relevant Union initiatives, such as with regard to animal testing.

AddedArticle 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.

RemovedArticle 24 – paragraph 5 – point e a (new): (ea) the risk-based prioritisation of data requirements for active substances, including to avoid unnecessary animal testing.

AddedArticle 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.

RemovedArticle 25 – paragraph 2 – subparagraph 3: The Agency shall establish a repository of active substance master files, their assessments reports and their certificates and ensure that personal data and commercially sensitive information is protected. The Agency shall ensure that the competent authorities of the Member State have access to this repository.

AddedArticle 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.

RemovedArticle 26 – paragraph 1 – subparagraph 1: Marketing authorisation applicants may, instead of submitting the relevant data on an active substance other than a chemical active substance, or on other substances present or used in the manufacture of a medicinal product, including raw materials and starting materials used for the manufacturing of cell therapies and gene therapies, required in accordance with Annex II, rely on an additional quality master file, an additional quality master file certificate granted by the Agency in accordance with this Article (‘additional quality master file certificate’), or a certificate confirming that the quality of that substance is suitably controlled by the relevant monograph of the European Pharmacopeia.

AddedArticle 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.

RemovedArticle 51 – paragraph 1 – point e: (e) is an antimicrobial of systemic administration;

AddedArticle 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.

RemovedArticle 51 – paragraph 1 – point e a (new): (ea) is an antibiotic; or

AddedArticle 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.

RemovedArticle 56 – paragraph 3 – subparagraph 1: The marketing authorisation holder of a medicinal product placed on the market in a Member State shall, within the limits of its responsibility, ensure appropriate and continued supplies of that medicinal product to wholesale distributors in accordance with Articles 166 and 167, pharmacies or persons authorised to supply medicinal products so that the needs of patients in the Member State in question are covered.

AddedArticle 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.

RemovedArticle 57 – paragraph 1: 1. The marketing authorisation holder shall declare to the public any direct financial support received from any public authority or publicly funded body of the Union, 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.

AddedArticle 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.

RemovedArticle 57 – paragraph 2 – point a – point ii: (ii) the public authority or publicly funded body of the Union that provided the financial support referred to in point (i);

AddedArticle 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.

RemovedArticle 57 – paragraph 6 a (new): 6a. The Agency shall provide a publicly accessible website to facilitate access to the electronic links communicated to the Agency in accordance with paragraphs 2 and 3, sorted, where relevant, by medicine and by Member State.

AddedArticle 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.

RemovedArticle 58 a (new): Article 58a / 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, submit in good faith an application for pricing and reimbursement no later than two years from the date when the Member State made its request, or within four years 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 seven 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. / For the purposes of this Directive and [revised Regulation (EC) No 726/2004], the Commission shall by ... [18 months after the date of entry into force of this Directive] adopt delegated acts in accordance with Article 215 to supplement this Directive by laying down the criteria to qualify as a micro, small and medium-sized enterprise, taking into account the specificities of enterprises of this sector within the Union. / The marketing authorisation holder shall notify that it fulfilled the obligations set out in the first subparagraph through the EU Access to Medicines Notification System provided for …

AddedArticle 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.

RemovedArticle 58 b (new): Article 58b / EU Access to Medicines Notification System / 1. The Commission shall, in collaboration with the Member States, set up and maintain an electronic notification system (the “EU Access to Medicines Notification System”) as a single-entry point for the notification of compliance with the obligations set out in Article 58a. The EU Access to Medicines Notification System shall be interoperable with the other 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 following the date of entry into force of this Directive], the Commission shall adopt implementing acts to establish technical and organisational requirements, including on security aspects and data governance, which are necessary for the practical implementation of the EU Access to Medicines Notification System. Those implementing acts shall be adopted in accordance with the examination procedure referred to in Article 214(2). / 4. By ... [5 years after the date of entry into force of this Directive] and every 3 years thereafter, the Commission shall present a report to…

AddedArticle 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.

RemovedArticle 63 – paragraph 3: 3. Member States may decide that the package leaflet shall be made available electronically, or both in paper format and electronically. 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.

AddedArticle 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.

AddedArticle 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.

AddedArticle 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).

AddedArticle 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.

AddedArticle 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.

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

AddedArticle 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

AddedArticle 51 – paragraph 5 – point b: deleted

AddedArticle 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.

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

AddedArticle 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.

AddedArticle 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).

AddedArticle 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.

AddedArticle 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…

AddedArticle 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…

AddedArticle 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.

AddedArticle 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.

AddedArticle 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.

AddedArticle 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.

AddedArticle 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).

AddedArticle 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.

AddedArticle 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.

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

AddedArticle 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.

AddedArticle 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.

RemovedArticle 85 – paragraph 1 – point a – point iii: deleted

AddedArticle 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.

RemovedArticle 85 – paragraph 1 – point b: (b) the activities conducted exclusively for the purposes set out in point (a), may cover the manufacture, sale, supply, storage, import, use and purchase of patented medicinal products or processes, including by third party suppliers and service providers.

AddedArticle 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.

RemovedArticle 86 – paragraph 1 – subparagraph 1: Where an application for marketing authorisation, includes the results of all studies conducted in compliance with an agreed paediatric investigation plan, the holder of the patent or supplementary protection certificate shall be entitled to a six-month extension of the period referred to in Article 13, paragraphs 1 and 2 of [Regulation (EC) No 469/2009 - OP please replace reference by new instrument when adopted]. Where the agreed paediatric investigation plan is conducted in relation to a disease that is different from the one for which the medicinal product is intended in the adult population, the holder of the patent or supplementary protection certificate shall be entitled to a 12-month extension of the period.

AddedArticle 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.

AddedArticle 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];

AddedArticle 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;

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

AddedArticle 125 – title: Registration or authorisation of homeopathic products

AddedArticle 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.

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

AddedArticle 126 – title: Simplified registration procedure for homeopathic products

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

AddedArticle 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;

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

AddedArticle 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.

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

AddedArticle 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.

AddedArticle 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:

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

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

AddedArticle 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;

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

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

AddedArticle 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.

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

AddedArticle 129 – title: Labelling of homeopathic products

AddedArticle 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.

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

AddedArticle 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:

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

AddedArticle 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.

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

AddedArticle 131 – title: Advertising of homeopathic products

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

AddedArticle 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).

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

AddedArticle 132 – title: Exchange of information on homeopathic products

AddedArticle 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.

AddedArticle 133 – title: Other requirements for homeopathic products

AddedArticle 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.

AddedArticle 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.

AddedArticle 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.

AddedArticle 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

AddedArticle 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.

AddedArticle 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.

AddedArticle 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

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

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

AddedArticle 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.

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

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

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

AddedArticle 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;

AddedArticle 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.

AddedArticle 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.

AddedArticle 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.

AddedArticle 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.

AddedArticle 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.

AddedArticle 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.

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

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

AddedArticle 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:

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

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

AddedArticle 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.

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

AddedArticle 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.

AddedArticle 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.

AddedArticle 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.

AddedArticle 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.

AddedArticle 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].

AddedArticle 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.

AddedArticle 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.

AddedArticle 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.

AddedArticle 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;

AddedArticle 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.

RemovedArticle 215 – paragraph 6: 6. A delegated act adopted pursuant to Articles 6(2), 26(3), 24(5), 26a(4), 27(3), 28(2) and (3), 58a(1), 63(4a), 65(2), 67(2), 88(1), 92(4), 126(1), 150(3), 153(4), 161, 207(1c), 210(4) and 213 shall enter into force only if no objection has been expressed either by the European Parliament or by the Council within a period of two months of notification of that act to the European Parliament and the Council or if, before the expiry of that period, the European Parliament and the Council have both informed the Commission that they will not object. That period shall be extended by two months at the initiative of the European Parliament or of the Council.

AddedArticle 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.

AddedArticle 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.

AddedArticle 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.

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

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

AddedAnnex 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

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