Activities of Margrete AUKEN related to 2023/0132(COD)
Shadow reports (1)
REPORT on the proposal for a directive of the European Parliament and of the Council on the Union code relating to medicinal products for human use, and repealing Directive 2001/83/EC and Directive 2009/35/EC
Amendments (236)
Amendment 145 #
Proposal for a directive
Recital 2 a (new)
Recital 2 a (new)
(2 a) This Directive should contribute to the implementation of the One Health Approach, stressing the well-established interconnectedness between human, animal, and ecosystem health and the need to include those three dimensions when addressing public health threats. The loss of biodiversity, changes in land use, deforestation, urbanisation, agricultural expansion and intensification, poor air quality, wildlife trafficking and consumption patterns and transmissions of diseases between humans and animals are all factors that have contributed to the increasing disease burden. In addition, pollution from active pharmaceutical ingredients negatively affects the quality of waters and ecosystems, posing risks to public health globally.
Amendment 162 #
Proposal for a directive
Recital 9
Recital 9
(9) Medicinal products for rare diseases and for children, should be subject to the same conditions as any other medicinal product concerning their quality, safety and, efficacy and environmental risk, for example for what concerns the marketing authorisation procedures, quality and the pharmacovigilance requirements. However, specific requirements also apply to them considering their unique characteristics. Such requirements, which are currently defined in separate legislations, should be integrated in general pharmaceutical legal framework in order to ensure clarity and coherency of all the measures applicable to these medicinal products. Furthermore, as some medicinal products authorised for use in children are authorised by the Member States, specific provisions should be integrated in this Directive.
Amendment 172 #
Proposal for a directive
Recital 13
Recital 13
(13) To avoid the duplication of requirements for medicinal products in this Directive and in the Regulation, the general standards in regards to quality, safety and, efficacy and environmental risk of medicinal products laid down in this Directive shall be applicable to medicinal products covered by national marketing authorisation and also to medicinal products covered by centralised marketing authorisation. Therefore, the requirements for an application for medicinal product are valid for both, also the rules on prescription status, product information, regulatory protection and rules on manufacturing, supply, advertising, supervision and other national requirements shall be applicable to medicinal products covered by centralised marketing authorisation.
Amendment 177 #
Proposal for a directive
Recital 16
Recital 16
(16) The new definition for a substance of human origin (SOHO) by the [SoHO Regulation] covers any substance collected from the human body in whatever manner, whether it contains cells or not and regardless of whether it meets the definition of ‘blood’, ‘tissue’ or ‘cell’, for example human breast milk, intestinal microbiota and any other SoHO that may be applied to humans in the future. Such substances of human origin, other than tissues and cells, may become SoHO derived medicinal products, other than ATMPs, when the SoHO is subject to an industrial process involving systematisation, reproducibility and operations performed on a routine basis or batch-wise resulting in a product of standardised consistency. When a process concerns extraction of an active ingredient from the SoHO, other than tissues and cells, or a transformation of a SoHO, other than tissues and cells, by changing its inherent properties, this should also be considered a SoHO derived medicinal product. When a process concerns pooling, concentrating, separating or isolating elements in the preparation of blood componentsSoHO, as well as methods that increase micro- biological quality, this should not be considered as changing their inherent properties.
Amendment 184 #
Proposal for a directive
Recital 18
Recital 18
(18) Advanced therapy medicinal products that are prepared on a non-routine basis according to specific quality standards, and used within the same Member State in a hospital under the exclusive professional responsibility of a medical practitioner and hospital pharmacist, in order to comply with an individual medical prescription for a custom-made product for an individual patient, should be excluded from the scope of this Directive whilst at the same time ensuring that relevant Union rules related to quality and safety are not undermined (‘hospital exemption’). Experience has shown that there are great differences in the application of hospital exemption among Member States. To improve the application of hospital exemption this Directive introduces measures for collection, reporting of data as well as review of these data yearly by the competent authorities and their publication by the Agency in a repository. Furthermore, the Agency should provide a report on the implementation of hospital exemption on the basis of contributions from Member States in order to examine whether an adapted framework should be established for certain less complex ATMPs that have been developed and used under the hospital exemption. In case of unmet medical need, Member States may allow for mutual recognition and cross- border exchange of advanced therapy medicinal products prepared under hospital exemption. When an authorisation for the manufacturing and use of an ATMP under hospital exemption is revoked because of safety concerns, the relevant competent authorities shall inform the competent authorities of other Member States.
Amendment 189 #
Proposal for a directive
Recital 20
Recital 20
(20) In the interest of public health, a medicinal product should only be allowed to be placed on the market in the Union when the marketing authorisation has been granted to the medicinal product, and its quality, safety and, efficacy and environmental risk have been demonstrated. However, exemption should be provided from this requirement in situations characterised by an urgent need to administer a medicinal product to address the specific needs of a patient, or confirmed spread of pathogenic agents, toxins, chemical agents or nuclear radiation that could cause harm. In particular, to fulfil special needs, Member States should be allowed to exclude from the provisions of this Directive medicinal products supplied in response to a bona fide unsolicited order, formulated in accordance with the specifications of an authorised healthcare professional and for use by an individual patient under their direct personal responsibility. Member States should be also allowed to temporarily authorise the distribution of an unauthorised medicinal product in response to a suspected or confirmed spread of pathogenic agents, toxins, chemical agents or nuclear radiation any of which could cause harm.
Amendment 191 #
Proposal for a directive
Recital 22
Recital 22
(22) The particulars and documentations that are to accompany an application for marketing authorisation for a medicinal product demonstrate that the therapeutic efficacy of the product overweight potential risks. The benefit-risk balance of all medicinal products will be assessed when they are placed on the market, five years after market approval, except for generics, and at any other time the competent authority deems appropriate.
Amendment 192 #
Proposal for a directive
Recital 22 a (new)
Recital 22 a (new)
(22 a) As a general rule, marketing authorisation should be granted based on comparative clinical trials on patients who are representative of the population to be treated with the product. To this end, placebo controlled trials should only be accepted where duly justified, necessary and ethical. In addition, patient-reported outcome measures (PROMs) and patient- reported experience measures (PREMs) should be an integral part of clinical data submitted with the marketing authorisation application in order to assess the quality of care and the impact of the treatments on patients. Particular attention should be given to the gender balance of clinical trials so that women can fully and safely benefit from medicines throughout their life-course.
Amendment 199 #
Proposal for a directive
Recital 31
Recital 31
(31) Directive 2010/63/EU of the European Parliament and of the Council43[1] lays down provisions on the protection of animals used for scientific purposes based on the principles of replacement, reduction and refinement. Ultimately, efforts should be made to fully replace procedures on live animals for scientific purposes. Any study involving the use of animals, which provides essential information on the quality, safety and efficacy of a medicinal product, should take into account those principles of replacement, reduction and refinement, where they concern the care and use of live animals for scientific purposes, and should be optimised in order to provide the most satisfactory results whilst using the minimum number of animals. The procedures of such testing should be designed to avoid causing pain, suffering, distress or lasting harm to animals and should follow the available EMA and ICH guidelines. In particular, the marketing authorisation applicant and the marketing authorisation holder should take into account the principles laid down in Directive 2010/63/EU, including, where possible, use new approach methodologies (NAMs) in place of animal testing. These can include but are not limited to: in vitro models, such as microphysiological systems including organ-on-chips, (2D and 3D-) cell culture models, organoids and human stem cells-based models; in silico tools or read-across models. _________________ 43 Directive 2010/63/EU of the European Parliament and of the Council of 22 September 2010 on the protection of animals used for scientific purposes (OJ L 276, 20.10.2010, p. 33)grouping and read-across, aquatic egg models as well as invertebrate species.
Amendment 202 #
Proposal for a directive
Recital 34
Recital 34
(34) There is the possibility under certain duly justified circumstances for marketing authorisations to be granted, subject to specific obligations or conditions, on a conditional basis or under exceptional circumstances. The legislation should allow under similar circumstances for medicinal products with a standard marketing authorisation for new therapeutic indications to be authorised on a conditional basis or, in case of centrally- authorised products, under exceptional circumstances. The products authorised on a conditional basis or under exceptional circumstances should in principle satisfy the requirements for a standard marketing authorisation with the exception of the specific derogations or conditions outlined in the relevant conditional or exceptional marketing authorisation and shall be subject to specific review of the fulfilment of the imposed specific conditions or obligations. The grounds for refusal of a marketing authorisation should apply mutatis mutandis for such cases.
Amendment 206 #
Proposal for a directive
Recital 42
Recital 42
(42) The simplification of procedures should not have an impact on standards or the quality of scientific evaluation of medicinal products to guarantee the quality, safety and, efficacy and environmetal risk and therefore, the scientific evaluation period should remain. However, the reduction of overall period for marketing authorisation procedure from 210 days to 180 days is foreseen.
Amendment 208 #
Proposal for a directive
Recital 44
Recital 44
(44) As regards access to medicinal products, previous amendments to the Union pharmaceutical legislation have addressed this issue by providing for accelerated assessment of marketing authorisation applications or by allowing conditional marketing authorisation for medicinal products for unmet medical need. While these measures accelerated the authorisation of innovative and promising therapies, in some areas, there still exist many public health priorities unaddressed and these medicinal products do not always reach the patient and patients in the Union still have different levels of access to medicinal products. Patient access to medicinal products depends on many factors. Marketing authorisation holders are not obliged to market a medicinal product in all Member States; they may decide not to market their medicinal products in, or withdraw them from, one or more Member States. National pricing and reimbursement policies, the size of the population, the organisation of health systems and national administrative procedures and often high prices of innovative medicines are other factors influencing market launch and patient access.
Amendment 210 #
Proposal for a directive
Recital 44 a (new)
Recital 44 a (new)
(44 a) In order to increase the availability of medicines and contribute to reducing of access inequalities within the Union, the marketing authorisation holders of medicinal products other than generics should submit an application for pricing and reimbursement in Member States upon request. In addition, the Agency should include in its medicine database information on the actual placing on the market and reimbursement status for all centrally authorised medicines.
Amendment 217 #
Proposal for a directive
Recital 47
Recital 47
(47) To ensure dialogue among all actors in the medicines lifecycle, discussions on policy issues related to the application of the rules related to prolongation of regulatory data protection for market launch shall take place in the Pharmaceutical Committee. Tthe Commission may invite bodies responsible for health technology assessment as referred to in Regulation (EU) 2021/2282 or national bodies responsible for pricing and reimbursement, as required, to participate in the deliberations of the Pharmaceutical Committee.
Amendment 223 #
Proposal for a directive
Recital 48
Recital 48
(48) While pricing and reimbursement decisions are a Member State competence, the Pharmaceutical Strategy for Europe announced actions to support cooperation of Member States to improve affordability. The Commission has transformed the group of National Competent Authorities on Pricing and Reimbursement and public healthcare payers (NCAPR) from an ad- hoc forum to a continuous voluntary cooperation with the aim to exchange information and best practices on pricing, payment and procurement policies to improve the affordability and cost- effectiveness of medicines and health system’s sustainability. The Commission is committed to stepping up this cooperation and further supporting information exchange among national authorities, including on price transparency, transparency on investment and costs of research and development and public procurement of medicines, while fully respecting the competences of Member States in this area. The Commission may also invite NCAPR members to participate in deliberations of the Pharmaceutical Committee on topics that may have an impact on pricing or reimbursement policies, such as the market launch incentive.
Amendment 226 #
Proposal for a directive
Recital 49
Recital 49
(49) Joint procurement, whether within a country or across countries, can improve access, affordability, and security of supply of medicines, in particular for smaller countries. Member States interested in joint procurement of medicines can make use of Directive 2014/24/EU47 , which sets out purchasing procedures for public buyers, the Joint Procurement Agreement48 and the proposed revised Financial Regulation49 . Upon request from the Member States the Commission may support interested Member States by facilitating coordination to enable access to medicines for patients in the Union as well as information exchange, in particular for medicines linked to public health emergencies and for rare and chronic diseases. . _________________ 47 Directive 2014/24/EU of the European Parliament and of the Council of 26 February 2014 on public procurement and repealing Directive 2004/18/EC (OJ L 94, 28.3.2014, p. 65). 48 Regulation (EU) 2022/2371 of the European Parliament and of the Council of 23 November 2022 on serious cross-border threats to health and repealing Decision No 1082/2013/EU. 49 COM/2022/223 final.
Amendment 233 #
Proposal for a directive
Recital 50
Recital 50
(50) The establishment of a criteria- based definition of ‘unmet medical need’ is required tonecessary to ensure incentivisees for the development of medicinal products in therapeutic areas that are currently underserved. To ensure that the concept of unmet medical need reflects scientific and technological developments and current knowledge in underserved diseases, the Commission should specify and update using implementing acts, the criteria of satisfactory method of diagnosis, prevention or treatment, ‘remaining high morbidity or mortality’, ‘relevant patient population’ following scientific assessment by the Agency. The Agency will seek input from a broad range of authorities or bodies active along the lifecycle of medicinal products in the framework of the consultation process established under the [revised Regulation (EC) No 726/2004] and also take into account scientific initiatives at EU level or between Member States related to analysing unmet medical needs, burden of disease and priority setting for research and development are appropriately allocated and to prevent unintended extensions of data protection based on unclear interpretation of unmet medical need. The criteria for ‘unmet medical need’ can be subsequently used by Member States to identify specific therapeutic areas of interest.
Amendment 246 #
Proposal for a directive
Recital 52
Recital 52
Amendment 253 #
Proposal for a directive
Recital 54
Recital 54
(54) Micro, small and medium-sized enterprises (‘SMEs’), not-for-profit entities or entities with limited experience in the Union system should benefit from additional time to market a medicinal product in the Member States where the marketing authorisation is valid for the purposes of receiving additional regulatory data protection.
Amendment 255 #
Proposal for a directive
Recital 55
Recital 55
(55) When applying the provisions on market launch incentives, mMarketing authorisation holders and Member States should do their utmost to achieve a mutually agreed supply of medicinal products in accordance with the needs of the Member State concerned, without unduly delaying or hindering the other party from enjoying its rights under this Directive.
Amendment 258 #
(56) Member States have the possibility to waive the condition of launch in their territorrequest a market launch of centrally for the purpose of the prolongation of data protection for market launch. This can be done through a statement of non-objection to prolong the period of regulatory data protection. This is expected to be the case particularly in situations where launch in a particular Member State is materially impossible or because there are special reasons why a Member State wishes that launch take place ldecentrally approved product at any time after the marketing authorisation is valid in the Member State. Subsequently, marketing authorisation holders have nine months to apply for a pricing and reimbursement in that Member State, 18 months where the marketing authorisation holder is an SME, an entity not engaged in economic activity or an entity with a limited experience in the Union system. Alternative timelines may be agreed between the Member State and the marketing authorisation holder. Marketing authorisation holders have the right to launch a product in a Member State before being proactively approached by that Member Stater.
Amendment 260 #
Proposal for a directive
Recital 57
Recital 57
(57) The issuing of documentation from the Member States as regards the prolongation of data protection for the purpose of supply of medicinal productsapplication for pricing and reimbursement in allthe Member States where a marketing authorisation is valid, in particular the waiver to the conditions for such prolongation, does not affect at any time the powers of the Member States as regards the supply, setting of prices for medicinal products or their inclusion in the scope of national health insurance schemes. Member States do not waive the possibility to request release or supply of the product concerned at any time before, during or after the prolongation of the data protection period.
Amendment 263 #
Proposal for a directive
Recital 58
Recital 58
(58) An alternative way of demonstrating supply relates to the inclusion of medicinal products in a positive list of medicinal products covered by the national health insurance system in accordance with Directive 89/105/EEC. The related negotiations between companies and the Member State should be transparent and conducted in good faith.
Amendment 267 #
Proposal for a directive
Recital 59
Recital 59
Amendment 269 #
Proposal for a directive
Recital 60
Recital 60
(60) The Commission and Member States shall continuously monitor any data and learnings from the application of the incentives system in order to improve, including through implementing acts, how these provisions are applied. The Commission shall establish a list of national contact points in this regard.
Amendment 271 #
Proposal for a directive
Recital 61
Recital 61
(61) When a compulsory licence has been granted by a relevant authority in the Union to tackle a public health emergency, regulatory data protection, regulatory data protection, market protection and market exclusivity may, if still in force, prevent the effective use of the compulsory licence as they impede the authorisation of generic medicinal products, and thus access to the medicinal products needed to address the crisis. For this reason, data and market protection and exclusivity should be suspended when a compulsory licence has been issued to tackle a public health emergency. Such a suspension of the regulatory data protection, market protection and market exclusivity should be allowed only in relation to the compulsory licence granted and its beneficiary. The suspension shall comply with the objective, the territorial scope, the duration and the subject matter of the granted compulsory licence. Where necessary to safeguard public health, national competent authorities should be able to also reduce the duration of market and data protection and market exclusivity for medicinal products that are not protected by a patent or a supplementary protection certificate.
Amendment 275 #
Proposal for a directive
Recital 62
Recital 62
(62) The suspension of the regulatory data protection should be granted only for the duration of the compulsory licence. A ‘suspension‘ of data and market protection in cases of public health emergencand market exclusivity shall mean that data and market protection and market exclusivity shall produce no effect in relation to the particular licensee of the compulsory licence while that compulsory licence is in effect. When the compulsory licence ends, the data and market protection shall resume their effect. The suspension should not result in an extension of the original duration.
Amendment 288 #
Proposal for a directive
Recital 63
Recital 63
(63) It is currently possible for applicants for marketing authorisation of generic, biosimilar, hybrid and bio-hybrid medicinal products to conduct studies, trials and the subsequent practical requirements necessary to obtain regulatory approvals for those medicinal products during the term of protection of the patent or Supplementary Protection Certificate (SPC) of the reference medicinal product, without this being considered patent or SPC infringement. The application of this limited exemption is however fragmented across the Union and it is considered necessary, in order to facilitate the market entry of generic, biosimilar, hybrid and bio-hybrid medicinal products that rely on a reference medicinal product, to clarify its scope in order to ensure a harmonised application in all Member States, both in terms of beneficiaries and in terms of activities covered. The exemption must be confined to conduct studies and trials and other activities needed for the regulatory approval process, health technology assessment and, pricing reimbursement request and Bolar exemption for pre-production of products, even though this may require substantial amounts of test production to demonstrate reliable manufacturing. During the term of protection of the patent or SPC of the reference medicinal product, there can be no commercial use of the resulting final medicinal products obtained for the purposes of the regulatory approval process.
Amendment 305 #
Proposal for a directive
Recital 65 a (new)
Recital 65 a (new)
Amendment 307 #
Proposal for a directive
Recital 66
Recital 66
(66) In order to address the challenge of antimicrobial resistance, antimicrobials should be packaged in quantities that are appropriate for the therapy cycle relevant for that product and nper unit dispensing of antimicrobials has been recognised as a core element in medical guidelines and the marketing authorisation holders should ensure, whenever possible, that antimicrobials may be dispensed in a number corresponding to the quantities prescribed by the treating physician. Dispensing the exact number of units needed would help address antimicrobial resistance as well as environmental impact related to stocking and waste. National rules on antimicrobial subject to prescription ensure that they are dispensed in a way that corresponds to the quantities described by the ptrescriptionating physician based on a personalised approach.
Amendment 309 #
Proposal for a directive
Recital 67
Recital 67
(67) The provision of information to healthcare professionals and to patients on the appropriate use, storage and disposal of antimicrobials is a joint responsibility of marketing authorisation holders and of Member States who should ensure appropriate collection and disposal system for all medicinal products.
Amendment 311 #
Proposal for a directive
Recital 68
Recital 68
(68) While this Directive restricts the use of antimicrobials by setting certain categories of antimicrobials under prescription status, due to the growing antimicrobial resistance in the Union, competent authorities of the Member States should considerput in place further measures, where appropriate, for example expanding the prescription status of antimicrobials or the mandatory use of diagnostic tests before prescription. Competent authorities ofshould ensure availability of rapid diagnostic tests in the Member States and should consider such further measures according to the level of antimicrobial resistance in their territory and the needs of patients.
Amendment 313 #
Proposal for a directive
Recital 69
Recital 69
(69) The pollution of waters and soils with pharmaceutical residues is an emerging environmental problem, and there is scientific evidence that the presence of those substances in the environment from their manufacturing, use and disposal poses a risk to the environment and public health. The evaluation of the legislation showed that strengthening of existing measures to reduce the impact of medicinal products' lifecycle on the environment and public health is required. Measures under this RegulationDirective 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 ) and the Industrial Emissions Directive (2010/75/EU55 ). _________________ 50 Directive 2000/60/EC of the European Parliament and of the Council of 23 October 2000 establishing a framework for Community action in the field of water policy (OJ L 327, 22.12.2000, p. 1). 51 Directive 2008/105/EC of the European Parliament and of the Council of 16 December 2008 on environmental quality standards in the field of water policy, amending and subsequently repealing Council Directives 82/176/EEC, 83/513/EEC, 84/156/EEC, 84/491/EEC, 86/280/EEC and amending Directive 2000/60/EC of the European Parliament and of the Council (OJ L 348, 24.12.2008, p. 84). 52 Directive 2006/118/EC of the European Parliament and of the Council of 12 December 2006 on the protection of groundwater against pollution and deterioration (OJ L 372, 27.12.2006, p. 19). 53 Council Directive 91/271/EEC of 21 May 1991 concerning urban waste-water treatment (OJ L 135, 30.5.1991, p. 40). 54 Directive (EU) 2020/2184 of the European Parliament and of the Council of 16 December 2020 on the quality of water intended for human consumption (recast) (OJ L 435, 23.12.2020, p. 1). 55 Directive 2010/75/EU of the European Parliament and of the Council of 24 November 2010 on industrial emissions (integrated pollution prevention and control) (recast) (OJ L 334, 17.12.2010, p. 17).
Amendment 317 #
Proposal for a directive
Recital 69 a (new)
Recital 69 a (new)
(69 a) The wide use of pharmaceuticals in human and veterinary medicines, including antimicrobials, and their concentrations in many environmental reservoirs such as soils, sediments and waterbodies has increased in the past 20 years and their environmental concentration and prospected to grow in the coming years due to increased use and aging populations; the occurence of pharmaceutical substances in the environment negatively impact human health as well as wildlife and ecosystems; 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.
Amendment 319 #
Proposal for a directive
Recital 69 b (new)
Recital 69 b (new)
Amendment 327 #
Proposal for a directive
Recital 70
Recital 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 or the environmental risk is deemed unacceptable, the marketing authorisation should be refused. The ERA should be updated each time when new data or knowledge about relevant risks become available.
Amendment 332 #
Proposal for a directive
Recital 72
Recital 72
(72) TLike every industrial sector, the production of medicines has a negative impact on the environment through CO2 emissions emitted by the medicine’s global supply chains and through pharmaceutical effluents from the production, use and disposal. In addition, 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 duraddressing manufacturing, use and disposal through monitoring, assessing and preventing the enegatirve life cycle of antimicrobimpact, addressing inefficiencies and developing greener pharmaceuticals is crucials, including manufacturing. order to mitigate threats to public health.
Amendment 338 #
Proposal for a directive
Recital 74 a (new)
Recital 74 a (new)
(74 a) In order to reduce duplication, optimise resources, reduce the use of animals in research, address current lack of understanding and resources on the individual and aggregated impact of pharmaceutical substances in the environment, and in line with the Aarhus Convention, all data related to the environmental risk assessment studies should be made publicly available and easily accessible in a database stablished by the Agency.
Amendment 342 #
Proposal for a directive
Recital 79
Recital 79
(79) As a general rule, risk management plans for generic and biosimilar medicinal products should not be developed and submitted, considering that the reference medicinal product has such a plan, except in specific cases, where a risk management plan should be provided. Furthermore, as a general rule a marketing authorisation should be granted for an unlimited period; exceptionally, one renewal may be decided onlyfor products other than generics should be granted for a period of five years in order to allow for the integration of real world evidence and re-assessment of the risk- benefit balance; once renewed, the marketing authorisation should be valid for an unlimited period unless the competent authority exceptionally decides that an additional five-year renewal or revocation of the marketing authorisation is necessary based on justified grounds related to the safety of the medicinal product.
Amendment 344 #
Proposal for a directive
Recital 91
Recital 91
(91) The adaptations may entail adapted, enhanced, waived or deferred requirements compared to standard medicinal products. They could in particular include changes to the dossier requirements for such medicinal products, the way their quality, safety and, efficacy and environmental risk is demonstrated by applicants or tailored manufacturing controls and good manufacturing practices requirements, as well as additional control methods prior and during their administration and use. The adaptions should however not go beyond what is necessary for the attainment of the objective of adaptation to the specific characteristics.
Amendment 350 #
Proposal for a directive
Recital 101
Recital 101
(101) The increasing use of electronic networks for communication of information on adverse reactions to medicinal products marketed in the Union is intended to allow competent authorities to share the information at the same time. In that regard, patients, consumers and healthcare professionals who report adverse reactions should be able to opt in to be notified in case there exists any update on the safety profile of the products.
Amendment 351 #
Proposal for a directive
Recital 104
Recital 104
(104) The use of colours in human and veterinary medicinal products is currently regulated by Directive 2009/35/EC of the European Parliament and of the Council60 , and restricted to those authorised in accordance with Regulation (EC) No 1333/2008 of the European Parliament and of the Council on food additives61 , for which specifications are laid down in Commission Regulation (EU) No 231/201262 . Uses of excipients other than colours in medicinal products are subject to the Union rules on medicinal products and are evaluated as part of the overall benefit risk profile of a medicinal product. _________________ 60 Directive 2009/35/EC of the European Parliament and of the Council of 23 April 2009 on the colouring matters which may be added to medicinal products (OJ L 109, 30.4.2009, p. 10). 61 Regulation (EC) No 1333/2008 of the European Parliament and of the Council of 16 December 2008 on food additives (OJ L 354, 31.12.2008, p. 16). 62 Commission Regulation (EU) No 231/2012 of 9 March 2012 laying down specifications for food additives listed in Annexes II and III to Regulation (EC) No 1333/2008 of the European Parliament and of the Council (OJ L 83, 22.3.2012, p. 1).
Amendment 352 #
Proposal for a directive
Recital 105
Recital 105
(105) Experience has shown the need to maintain to a certain extent the principle of the use in medicinal products of those colours authorised as food additives. However, it is also appropriate to foresee, in exceptional circumstances, the necessity for a specific assessment for the use of the colour in medicines when a food additive is removed from Union list of food additives. Therefore, in this specific case, EMA should carry out its own assessment for the use of the colour in medicines, taking into account the EFSA opinion and its underlying scientific evidence, as well as any additional scientific evidence and giving particular consideration to the use in medicines. EMA should also be responsible for following any scientific evidence for the colours retained for specific medicine use only. Directive 2009/35/EC should therefore be repealed. establish a list of substances which has been banned in food, but for specific reasons are still authorised in medicines. The authorisation of substances on the list should be limited to maximum additional five years. Within that period, marketing authorisation holders who use the excipients should conduct studies to ensure use of available alternatives complying with the Union list of food additives.
Amendment 355 #
Proposal for a directive
Recital 111
Recital 111
(111) Verification of compliance with the legal requirements of manufacturing, distribution and use of medicinal products by relevant entities through a system of supervision, is of fundamental importance to ensure that the objectives of this Directive are effectively achieved. Therefore, the competent authorities of the Member States should have the power to perform on site or remote inspections, as part of the system of supervision at all stages of manufacturing, distribution and use of medicinal products or active substances and rely on the outcome of inspections conducted by trusted third countries competent authorities. To preserve the effectiveness of the inspections, the competent authorities should have the possibility to perform joint inspections and also, where necessary, unannounced inspections.
Amendment 360 #
Proposal for a directive
Recital 125
Recital 125
(125) Sharing accurate information with the general public in order to ensure trust in science and the regulatory system and supporting health literacy of patient and consumers is crucial. 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.
Amendment 361 #
(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 pursuant to Regulation 2016/679 and prohibition of the identification, profiling or tracking of individuals is necessary in this regard.
Amendment 362 #
Proposal for a directive
Recital 128
Recital 128
(128) Member States have varying levels of digital literacy and internet access. In addition, patient and healthcare professional needs may differ. It is therefore necessary that Member States have a discretion on the adoption of measures enabling the electronic provision of product information while ensuring that no patient is left behind, taking into account the needs of different age categories and the different levels of digital literacy in the population, and making sure that product information is easily accessible to all patients. Member States should progressively allow the possibility for electronic product information, as an addition to the paper leaflet, while ensuring 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, 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.
Amendment 364 #
Proposal for a directive
Recital 129
Recital 129
Amendment 371 #
Proposal for a directive
Recital 131
Recital 131
(131) To ensure a high level of transparency of public support to the research and development of medicinal products, the reporting of public contribution for the development of a particular medicinal product should be a requirement for all medicines. Given however the practical difficulty to identify 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, tThe provisions of this Directive ensure, are without prejudice to the rules on the protection of confidential and personal data, and ensure transparency regarding any direct and indirect financial support received from any public authority or, public body, philanthropic and other non-profit organisation including academia to carry out any activities for the research and development of medicinal products. In addition, when submitting a request for pricing and reimbursement, marketing authorisation holders should disclose, upon request, the company’s expenditure related to the research and development costs of the product.
Amendment 376 #
Proposal for a directive
Recital 135
Recital 135
(135) Advertising, even of medicinal products not subject to a prescription, could affect public health and distort competition. Therefore, advertising of medicinal products should meet certain criteria. Persons qualified to prescribe, administer or supply medicinal products can properly evaluate the information available in advertising because of their knowledge, training and experience. The advertising of medicinal products to persons who cannot properly assess the risk associated with their use may lead to medicinal product misuse or overconsumption which is liable to harm public health. Therefore advertisement to the general public of medicinal products that are available only on medical prescription should be prohibited. Furthermore, distribution of samples free of charge to the general public for promotional ends is to be prohibited, also teleshopping for medicinal products shall be prohibited pursuant to Directive 2010/13/EU of the European Parliament and of the Council65 . It should be possible within certain restrictive conditions to provide samples of medicinal products free of charge to persons qualified to prescribe or supply them so that they can familiarise themselves with new products and acquire experience in dealing with them. _________________ 65 Directive 2010/13/EU of the European Parliament and of the Council of 10 March 2010 on the coordination of certain provisions laid down by law, regulation or administrative action in Member States concerning the provision of audiovisual media services (Audiovisual Media Services Directive) (OJ L 095 15.4.2010, p. 1).
Amendment 378 #
Proposal for a directive
Recital 136
Recital 136
(136) Advertising of medicinal products should aim at disseminating objective and unbiased information about the medicinal product. For that purpose, it is expressly forbidden highlight negatively another medicinal product or to suggest that advertised medicinal product might be safer or more effective than another medicinal product. Comparison of medicinal products should only be allowed if such information is listed in the summary of product characteristics 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.
Amendment 379 #
Proposal for a directive
Recital 138 a (new)
Recital 138 a (new)
(138 a)While it is prohibited for companies to use celebrities for advertising of their medicinal products in the EU, patients and consumers are increasingly exposed to such promotional practices due to the global reach of social media. Online advertising, including on social media, may be initiated by companies in other regions or promoted be celebrities and influencers. Therefore, 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 and limit content exposure on consumers and patients which would be otherwise prohibited.
Amendment 380 #
Proposal for a directive
Recital 139 a (new)
Recital 139 a (new)
Amendment 382 #
Proposal for a directive
Recital 150
Recital 150
(150) This Directive seeks to enable the right access to preventive healthcare and to benefit from medical treatment under the conditions established by national laws and practices and to ensure a high level of human health protection in the definition and implementation of all the Union’s policies and activities as laid down in Article 35 of the Charter of Fundamental Rights of the European Union. Similarly, this Directive respects the Aarhus Convention which protects every person’s right to live in a healthy environment.
Amendment 392 #
Proposal for a directive
Article 1 – paragraph 5 – point b
Article 1 – paragraph 5 – point b
(b) medicinal product prepared in a pharmacy in accordance with a pharmacopoeia and intended to be supplied directly to the patients served by the pharmacy in question or to another pharmacy which intends to supply the medicinal product directly to the patient (‘officinal formula’);
Amendment 394 #
Proposal for a directive
Article 1 – paragraph 5 – point c a (new)
Article 1 – paragraph 5 – point c a (new)
(c a) 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.
Amendment 399 #
Proposal for a directive
Article 1 – paragraph 6
Article 1 – paragraph 6
6. Medicinal products referred to in paragraph 5, point (a), (b), (ca) and (cb), may be prepared in duly justified cases in advance by a pharmacy serving a hospital, on the basis of the estimated medical prescriptions l within that hospital for the following seven daysa time limit set based on the appropriate stability of the product.
Amendment 405 #
Proposal for a directive
Article 1 – paragraph 7
Article 1 – paragraph 7
7. Member States shall take the necessary measures to develop the production and use of medicinal products derived from substances of human origin coming from voluntary unpaid donations, in accordance with rules established under [SoHO Regulation].
Amendment 420 #
Proposal for a directive
Article 2 – paragraph 1
Article 2 – paragraph 1
1. By way of derogation from Article 1(1), only this Article shall apply to advanced therapy medicinal products prepared on 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 hospital pharmacist, in order to comply with an individual medical prescription for a custom-made product for an individual patient (‘advanced therapy medicinal products prepared under hospital exemption’).
Amendment 431 #
Proposal for a directive
Article 2 – paragraph 2 c (new)
Article 2 – paragraph 2 c (new)
2 c. By way of derogation from paragraph 1, in case of unmet medical need, Member States may allow for mutual recognition and cross-border exchange of advanced therapy medicinal products prepared under hospital exemption.
Amendment 432 #
Proposal for a directive
Article 2 – paragraph 2 d (new)
Article 2 – paragraph 2 d (new)
2 d. National competent authorities shall provide free of charge scientific advice to the entities developing products under hospital exemption, upon request.
Amendment 435 #
Proposal for a directive
Article 2 – paragraph 3
Article 2 – paragraph 3
3. Member States shall ensure that advanced therapy medicinal products prepared under hospital exemption comply with the requirements equivalent to thegood pharmacy preparation practices that are adapted to hospital processes and based on good manufacturing practices and traceability for advanced therapy medicinal products referred to in Articles 5 and 15 of Regulation (EC) No 1394/200769 respectively, and with pharmacovigilance requirements equivalent to those provided for at Union level pursuant to [revised Regulation (EC) No 726/2004]. _________________ 69 Regulation (EC) No 1394/2007 of the European Parliament and of the Council of 13 November 2007 on advanced therapy medicinal products and amending Directive 2001/83/EC and Regulation (EC) No 726/2004 (OJ L 324, 10.12.2007, p. 1).
Amendment 453 #
Proposal for a directive
Article 2 – paragraph 6
Article 2 – paragraph 6
6. The competent authority of the Member State shall transmit the data related to the use, safety and efficacy of an advanced therapy medicinal product prepared under the hospital exemption approval to the Agency annually. The Agency shall, in collaboration with the competent authorities of Member States and the Commission, set up and maintain a publicly accessible repository of that data. , including information on authorisations, suspensions or withdrawals of products under hospital exemption referred to in paragraph 1.
Amendment 458 #
Proposal for a directive
Article 2 – paragraph 7 – subparagraph 1 – introductory part
Article 2 – paragraph 7 – subparagraph 1 – introductory part
The Commission shall adopt implementing actsdelegated acts related to points (a) and (d) and implementing acts in points (b) and (c) to specify the following:
Amendment 469 #
Proposal for a directive
Article 2 – paragraph 7 – subparagraph 2
Article 2 – paragraph 7 – subparagraph 2
Those delegated acts shall be adopted pursuant to Article 215 and implementing acts shall be adopted in accordance with the examination procedure referred to in Article 214(2).
Amendment 478 #
Proposal for a directive
Article 3 – paragraph 1 – subparagraph 1
Article 3 – paragraph 1 – subparagraph 1
A Member State may, in order to fulfil special needs, exclude from the scope of this Directive medicinal products supplied in response to a bona fide unsolicited order, prepared in accordance with the specifications of an authorised healthcare professional and for use by an individual patient under their direct personal responsibility. However, in such case Member States shall encouragestablish channels for healthcare professionals and patients to report data on the safety of the use of such products to the competent authority of the Member State in accordance with Article 97.
Amendment 480 #
Proposal for a directive
Article 3 – paragraph 1 – subparagraph 2
Article 3 – paragraph 1 – subparagraph 2
For allergen medicinal products supplied in accordance with this paragraph, the competent authorities of the Member State mayshall request the submission of relevant information in accordance with Annex II.
Amendment 488 #
Proposal for a directive
Article 4 – paragraph 1 – point 11
Article 4 – paragraph 1 – point 11
(11) ‘non-clinical’ means a study or a test conducted in vitro, ex vivo, in silico, or in chemico, or a non-human in vivo test related to the investigation of the safety and efficacy of a medicinal product. Such test may include simple and complex human cell-based assays, microphysiological systems including organ-on-chip, computer modelling and simulation, other non-human or human biology-based test methods, aquatic egg models as well as invertebrate species and animal-based tests;
Amendment 492 #
Proposal for a directive
Article 4 – paragraph 1 – point 15
Article 4 – paragraph 1 – point 15
(15) ‘letter of access’ means an original document, signed by the owner of the data or itstheir representative, that states that the data may be used for the benefit of a third party by a competent authority or the Commission for the purposes of this Directive;
Amendment 495 #
Proposal for a directive
Article 4 – paragraph 1 – point 22
Article 4 – paragraph 1 – point 22
(22) ‘antimicrobial’ means any medicinal product with a direct action on micro-organisms used for treatment or prevention of infections or infectious diseases, including antibiotics, antivirals, antiparasitics, antiprotozoals and antifungals;
Amendment 503 #
Proposal for a directive
Article 4 – paragraph 1 – point 29 – introductory part
Article 4 – paragraph 1 – point 29 – introductory part
(29) ‘gene therapy medicinal product’ means a biological medicinal product, except vaccines against infectious diseases, that contains or consists of:
Amendment 509 #
Proposal for a directive
Article 4 – paragraph 1 – point 29 – point b
Article 4 – paragraph 1 – point 29 – point b
(b) a recombinant or synthetic nucleic acid used in or administered to human beings with a view to regulating, replacing or adding a genetic sequence that mediates its effect by transcription or translation of the transferred genetic materials or that contain or consists of cells subjected to these modifications;
Amendment 518 #
Proposal for a directive
Article 4 – paragraph 1 – point 31 – point a
Article 4 – paragraph 1 – point 31 – point a
(a) a method involving an industrial process which includes pooling of donations for subsequent fractionation; or
Amendment 520 #
Proposal for a directive
Article 4 – paragraph 1 – point 31 – point b
Article 4 – paragraph 1 – point 31 – point b
(b) a process that extracts an active ingredient from the substance of human origin or transforms the substance of human origin by changing its inherent properties; when a process concerns pooling, concentrating, separating or isolating elements in the preparation of SoHO, as well as methods that increase micro-biological quality, this should not be considered as changing their inherent properties;
Amendment 524 #
Proposal for a directive
Article 4 – paragraph 1 – point 33
Article 4 – paragraph 1 – point 33
(33) ‘environmental risk assessment’ means the evaluation of the potential and actual risks to the environment, or risks to public health, including antimicrobial resistance, 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;
Amendment 531 #
Proposal for a directive
Article 4 – paragraph 1 – point 41
Article 4 – paragraph 1 – point 41
(41) ‘benefit-risk balance’ means an evaluation of the positive therapeutic effects of the medicinal product in relation to the risks referred to in point (35), subpoint (a);
Amendment 547 #
Proposal for a directive
Article 4 – paragraph 2
Article 4 – paragraph 2
Amendment 552 #
Proposal for a directive
Article 6 – paragraph 3 a (new)
Article 6 – paragraph 3 a (new)
3 a. Applications for market authorisation shall provide evidence from comparative studies with a standard-of- care active comparator, including, but not limited to, randomised controlled trials. In exceptional circumstances, where such studies cannot be provided for scientifically substantiated reasons, the applicant shall submit such duly justified reasoning to the national competent authority as part of the application for marketing authorisation. The Agency shall set the scientific guidelines on criteria for proposing a comparator for a clinical trial, taking into account the results of the consultation of the Commission and the authorities or bodies involved in the mechanism of consultation referred to in Article 162 of [revised Regulation (EC) No 726/2004].
Amendment 553 #
Proposal for a directive
Article 6 – paragraph 3 b (new)
Article 6 – paragraph 3 b (new)
3 b. Applications for marketing authorisation shall include patient experience data (PROMs/PREMs) in the marketing application dossier. Where such data cannot be provided, the applicant should provide a justification to the Agency.
Amendment 561 #
Proposal for a directive
Article 6 – paragraph 7 – subparagraph 2
Article 6 – paragraph 7 – subparagraph 2
The marketing authorisation applicant shall not carry out animal testing in case scientifically satisfactory New Approach Methodologies (NAMs), particularly non- animal testing methods are available.
Amendment 564 #
Proposal for a directive
Article 10 – paragraph 1
Article 10 – paragraph 1
In cases where the medicinal product does not fall within the definition of a generic medicinal product or has changes in strength, pharmaceutical form, route of administration or therapeutic indications, compared to the reference medicinal product, the results of the appropriate non- clinical tests or clinical studies shall be provided to the competent authorities to the extent necessary to establish a scientific bridge to the data relied upon in the marketing authorisation for the reference medicinal product, and to demonstrate the safety and efficacy profile of the hybrid medicinal product. The Agency shall adopt guidelines on the appropriate tests and clinical studies for marketing authorisation of hybrid medicinal products.
Amendment 569 #
Proposal for a directive
Article 12 – paragraph 1
Article 12 – paragraph 1
In cases where a biosimilar medicinal product has changes in strength, pharmaceutical form, route of administration or therapeutic indications, compared to the reference biological medicinal product (‘bio-hybrid’), the results of the appropriate non-clinical tests or clinical studies shall be provided to the competent authorities to the extent necessary to establish a scientific bridge to the data relied upon in the marketing authorisation for the reference biological medicinal product, and to demonstrate the safety orand 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.
Amendment 572 #
Proposal for a directive
Article 13 – paragraph 1
Article 13 – paragraph 1
In cases where no reference medicinal product is or has been authorised for the active substance of the medicinal product concerned, the applicant shall, by way of derogation from Article 6(2), not be required to provide the results of non- clinical tests or clinical studies if the applicant can demonstrate that the active substances of the medicinal product have been in well-established medicinal use within the Union for 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, including from systematic reviews and reports from unpublished studies and data.
Amendment 582 #
Proposal for a directive
Article 17 – paragraph 1 – point a
Article 17 – paragraph 1 – point a
(a) an antimicrobial stewardship and access plan as referred to in Annex I;
Amendment 586 #
Proposal for a directive
Article 17 – paragraph 1 a (new)
Article 17 – paragraph 1 a (new)
1 a. After granting marketing authorisation, the competent authority shall make publicly available the documents referred to in paragraph 1.
Amendment 587 #
Proposal for a directive
Article 17 – paragraph 2
Article 17 – paragraph 2
2. The competent authority mayshall impose obligations on the marketing authorisation holder if it finds the risk mitigation measures contained in the antimicrobial stewardship and access plan unsatisfactory.
Amendment 595 #
Proposal for a directive
Article 17 – paragraph 3
Article 17 – paragraph 3
3. The marketing authorisation holder shall ensure that the pack size of the antimicrobialantimicrobial may be dispensed per unit in a number correspondsing to the usual posology and duration of treatmentquantities prescribed by the treating physician.
Amendment 597 #
Proposal for a directive
Article 17 – paragraph 3 a (new)
Article 17 – paragraph 3 a (new)
3 a. By derogation from paragraph 3, in duly justified cases, national authorities may allow for pack sizes of the antimicrobial to correspond with the usual posology and duration of treatment.
Amendment 601 #
Proposal for a directive
Article 18 – paragraph 4
Article 18 – paragraph 4
4. In its evaluation of the integral combination of a medicinal product with a medical device concerned, the competent authorities shall recognise the results of the assessment of compliance of the medical device part of that integral combination with the general safety and performance requirements in accordance with Annex I of Regulation (EU) 2017/745 including, where relevant, the results of the assessment by a notified body.
Amendment 606 #
Proposal for a directive
Article 21 – paragraph 1
Article 21 – paragraph 1
The applicant of a marketing authorisation for a medicinal product referred to in Articles 9 and 11 shall not be required to submit a risk management plan and a summary thereof, provided that no additional risk minimisation measures exist for the reference medicinal product and provided that the marketing authorisation for the reference medicinal product has not been withdrawn prior to the submission of the application or in other situations as laid down in Article 91.
Amendment 609 #
Proposal for a directive
Article 22 – paragraph 1
Article 22 – paragraph 1
1. When preparing the environmental risk assessment (‘ERA’) to be submitted pursuant to Article 6(2), the applicant shall take into account the scientific guidelines on the environmental risk assessment of medicinal products for human use as referred to in paragraph 65, or provide the 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.
Amendment 611 #
Proposal for a directive
Article 22 – paragraph 1 a (new)
Article 22 – paragraph 1 a (new)
1 a. The ERA shall evaluate possible risks to the environment due to use and disposal of the medicinal product according to the requirements referred to in Annex II. With regard to risks resulting from manufacturing, the ERA shall provide information on discharges and emissions of the active substance and other environmentally relevant substances according to the requirements referred to in Annex II.
Amendment 617 #
Proposal for a directive
Article 22 – paragraph 3
Article 22 – paragraph 3
3. The applicant shall also include in the ERA risk mitigation measures to avoid or where it is not possible, to reduce discharges and emissions of the medicinal product to the environment and information on available techniques that will be used to reduce those discharges and emissions, in particular those occurring in manufacturing effluents before these effluents leave the manufacturing sites and to 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.
Amendment 631 #
4. The ERA for antimicrobialsFor antimicrobials and other substances which may cause antimicrobial resistance, including products with an antimicrobial mode of action, the ERA 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.
Amendment 636 #
Proposal for a directive
Article 22 – paragraph 5
Article 22 – paragraph 5
Amendment 638 #
Proposal for a directive
Article 22 – paragraph 6 – subparagraph 1
Article 22 – paragraph 6 – subparagraph 1
The marketing authorisation holder shall include analytical techniques and explanations in the methodology on the ERA and 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 could lead to a change of the conclusions of the ERA. The update shall include updates on the emissions of the medicinal product in manufacturing effluents and 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.
Amendment 643 #
Proposal for a directive
Article 22 – paragraph 6 – subparagraph 2
Article 22 – paragraph 6 – subparagraph 2
For an ERA conducted prior to [OP please insert the date = 18 months after the date of entering into force of this Directive], the competent authority shall request the marketing authorisation holder to update the ERA if missing information has been identified for medicinal products potentially harmful to the environment. The ERA shall be updated when new information becomes available, every 5 years at the latest.
Amendment 645 #
Proposal for a directive
Article 22 – paragraph 7
Article 22 – paragraph 7
7. For medicinal products referred to in Articles 9 to 12, the applicant may, where appropriate, refer to ERA studies conducted for the reference medicinal product when preparing the ERA and shall provide any other data required in accordance with Annex II and the scientific guidelines as referred to in the first paragraph.
Amendment 647 #
Proposal for a directive
Article 22 – paragraph 7 a (new)
Article 22 – paragraph 7 a (new)
Amendment 653 #
Proposal for a directive
Article 23 – paragraph 1 – subparagraph 1
Article 23 – paragraph 1 – subparagraph 1
By [OP please insert the date = 3012 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 European Centre for Disease Prevention and Control (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.
Amendment 659 #
Proposal for a directive
Article 23 – paragraph 2
Article 23 – paragraph 2
2. The Agency shall set the scientific criteria for the identification of the medicinal products as potentially harmful to the environment and for the prioritisation of their ERA, using a risk based approach. For this task, the Agency mayshall consult all relevant stakeholders and request from marketing authorisation holders the submission of relevant data or information.
Amendment 662 #
Proposal for a directive
Article 23 – paragraph 3
Article 23 – paragraph 3
3. The marketing authorisation holders for medicinal products identified in the programme referred to in paragraph 1 shall submit the ERA to the Agency. The outcome of the assessment of the ERA including the data submitted by the marketing authorisation holder shall be made publicly available by the Agency, including full data sets and summaries of conducted ERA studies, shall be made publicly available by the Agency and shall be proactively shared with drinking water and wastewater operators.
Amendment 675 #
Proposal for a directive
Article 25 – paragraph 6 – subparagraph 2
Article 25 – paragraph 6 – subparagraph 2
If the manufacturer of an active substance refuses to undergo such an inspection, the Agency mayshall suspend or terminate the application for an active substance master file certificate.
Amendment 676 #
Proposal for a directive
Article 25 – paragraph 7
Article 25 – paragraph 7
7. If the active substance master file certificate holder does not fulfil the obligations set out in the paragraphs 5 and 6, the Agency mayshall suspend or withdraw the certificate and, the competent authorities of the Member States mayshall suspend or revoke the marketing authorisation of a medicinal product relying on that certificate or take measures to prohibit the supply of the medicinal product relying on that certificate.
Amendment 680 #
Proposal for a directive
Article 26 – paragraph 4 – subparagraph 2
Article 26 – paragraph 4 – subparagraph 2
If the manufacturer of this substance refuses to undergo such an inspection, the Agency mayshall suspend or terminate the application for the additional quality master file certificate.
Amendment 681 #
2. Colours shall be used in medicinal products only if they are included in one of the following lists:the Union list of authorised food additives in Table 1 in Part B of Annex II to Regulation (EC) No 1333/2008 and comply with the purity criteria and specifications laid down in Commission Regulation (EU) No 231/2012.
Amendment 682 #
Proposal for a directive
Article 27 – paragraph 2 – point a
Article 27 – paragraph 2 – point a
Amendment 683 #
Proposal for a directive
Article 27 – paragraph 2 – point b
Article 27 – paragraph 2 – point b
Amendment 684 #
Proposal for a directive
Article 27 – paragraph 3 – subparagraph 1
Article 27 – paragraph 3 – subparagraph 1
Amendment 685 #
Proposal for a directive
Article 27 – paragraph 3 – subparagraph 1 a (new)
Article 27 – paragraph 3 – subparagraph 1 a (new)
Addition of substances on the list referred to in paragraph three shall be limited to maximum five years. Within that period, marketing authorisation holders who use the excipients shall conduct studies to ensure use of available alternatives complying with the conditions set out in paragraph 2.
Amendment 686 #
Proposal for a directive
Article 27 – paragraph 4 – subparagraph 1
Article 27 – paragraph 4 – subparagraph 1
If a colour used in medicinal product is removed from the Union list of authorised food additives, on the basis of the scientific opinion of the European Food Safety Authority (‘EFSA’), the Agency shall, on the request of the Commission or on its own initiative, without undue delay issue a scientific opinion as regards the use of the colour concerned in medicinal product, taking into account the opinion of the EFSA if relevant. The opinion of the Agency shall be adopted by the Committee for Medicinal Products for Human Use.
Amendment 687 #
Proposal for a directive
Article 27 – paragraph 5
Article 27 – paragraph 5
5. If a colour has been removed from the Union list of authorised food additives for reasons that do not require an EFSA opinion, the Commission shall decide on the use of the colour concerned in medicinal products and, where applicable, include it in the list of colours permitted for use in medicinal products referred to in paragraph 3. The Commission mayshall, in such cases, request the opinion from the Agency.
Amendment 688 #
Proposal for a directive
Article 27 – paragraph 6
Article 27 – paragraph 6
6. A colour that has been removed from the Union list of authorised food additives can still be used as a colour in medicinal products for a maximum of two years until the Commission takes the decision on whether to include the colour on the list of colours permitted for use in medicinal products in accordance with paragraph 3.
Amendment 689 #
Proposal for a directive
Article 27 – paragraph 7 a (new)
Article 27 – paragraph 7 a (new)
7 a. The Agency shall draw up an updated list of excipients used in medicines, based on an in-depth evaluation, in particular with regard to their risks in children and pregnant women.
Amendment 691 #
Proposal for a directive
Article 28 – paragraph 6
Article 28 – paragraph 6
Amendment 696 #
Proposal for a directive
Article 29 – paragraph 1 – point a
Article 29 – paragraph 1 – point a
(a) shall verify whether the particulars and documentations submitted in support of the application comply with Articles 6 and 9 to 14 (‘validation’), and examine whether the conditions for issuing a marketing authorisation set out in Articles 43 toand 454 are complied with;
Amendment 702 #
Proposal for a directive
Article 32 – paragraph 2
Article 32 – paragraph 2
2. The competent authority in the Member State concerned shall examine the application in accordance with Articles 29 and 30 and grant a marketing authorisation in accordance with Articles 43 to 454 and applicable national provisions.
Amendment 703 #
Proposal for a directive
Article 33 – paragraph 2
Article 33 – paragraph 2
2. The competent authorities in the Member State concerned shall examine the applications in accordance with Articles 29, 30 and 34 and grant a marketing authorisation in accordance with Articles 43 to 454.
Amendment 711 #
Proposal for a directive
Article 35 – paragraph 1
Article 35 – paragraph 1
An application for marketing authorisation for mutual recognition procedure for national marketing authorisation, granted under Articles 43 to 454 and in accordance with Article 32, shall be submitted to the competent authorities of other Member States in accordance with the procedure laid down in Article 36.
Amendment 712 #
Proposal for a directive
Article 36 – paragraph 1
Article 36 – paragraph 1
1. An application for mutual recognition of a marketing authorisation, granted under Articles 43 to 454 and in accordance with Article 32, in several Member States in respect of the same medicinal product shall be submitted to the competent authority of the Member State that granted the marketing authorisation (‘reference Member State for the mutual recognition procedure’) and to the competent authorities of the Member States concerned where the applicant seeks to obtain a national marketing authorisation.
Amendment 718 #
Proposal for a directive
Article 36 – paragraph 8
Article 36 – paragraph 8
Amendment 721 #
Proposal for a directive
Article 42 – paragraph 1 – subparagraph 4
Article 42 – paragraph 1 – subparagraph 4
Where, in exceptional circumstances, a draft decision differs from the opinion of the Agency, the Commission shall provide a detailed explanation of the reasons for the differences.
Amendment 722 #
Proposal for a directive
Article 42 – paragraph 1 – subparagraph 5
Article 42 – paragraph 1 – subparagraph 5
The Commission shall send the draft decision to the competent authorities of the Member States and the applicant or the marketing authorisation holder and make the decision, including the justification, publicly available.
Amendment 725 #
Proposal for a directive
Article 43 – paragraph 3
Article 43 – paragraph 3
3. The competent authorities of the Member States shall, without undue delay, make publicly available the national marketing authorisation together with the summary of product characteristics, the package leafletlabelling, the package leaflet, the information related to antimicrobials referred to in Article 17(1), where applicable, as well as any conditions established in accordance with Articles 44, 45 and any obligations imposed subsequently in accordance with Article 17(2) and 87, together with any deadlines for the fulfilment of those conditions and obligations for each medicinal product that they have authorised.
Amendment 735 #
Proposal for a directive
Article 44 – paragraph 1 – subparagraph 1 – point e a (new)
Article 44 – paragraph 1 – subparagraph 1 – point e a (new)
(e a) justification in case marketing authorisation was granted where no comparative data with a standard-of-care active comparator were submitted;
Amendment 740 #
Proposal for a directive
Article 44 – paragraph 1 – subparagraph 1 – point g
Article 44 – paragraph 1 – subparagraph 1 – point g
(g) in case of medicinal products for which there is substantial, on duly justified grounds submitted to the national competent authority, there is uncertainty as to the surrogate endpoint relation to the expected health outcome, where appropriate and relevant for the benefit-risk balance, a post- authorisation obligation to substantiate the clinical benefit;
Amendment 744 #
Proposal for a directive
Article 44 – paragraph 2
Article 44 – paragraph 2
2. The marketing authorisation shall lay down deadlines for the fulfilment of the conditions referred to in paragraph 1, first subparagraph, where necessary.
Amendment 746 #
Proposal for a directive
Article 45
Article 45
Amendment 748 #
Proposal for a directive
Article 46 – paragraph 1 – subparagraph 1
Article 46 – paragraph 1 – subparagraph 1
Without prejudice to paragraph 4 and 4a, a marketing authorisation for a medicinal product shall be valid for an unlimited period5 years.
Amendment 751 #
Proposal for a directive
Article 46 – paragraph 1 – subparagraph 2
Article 46 – paragraph 1 – subparagraph 2
By way of derogation from the first subparagraph, a national marketing authorisation granted in accordance withfor products referred to in Article 45(1)9 shall be valid for five years and be subject to renewal in accordance with paragraph 2an unlimited period.
Amendment 752 #
Proposal for a directive
Article 46 – paragraph 1 – subparagraph 3
Article 46 – paragraph 1 – subparagraph 3
Amendment 754 #
Proposal for a directive
Article 46 – paragraph 2
Article 46 – paragraph 2
2. The marketing authorisation holder mayshall submit an application for a renewal of a national marketing authorisation granted under paragraph 1, second or third subparagraph. Such application shall be submitted at least nine months before the national marketing authorisation ceases to be valid.
Amendment 755 #
Proposal for a directive
Article 46 – paragraph 4
Article 46 – paragraph 4
4. The competent authority of the Member State may renew the national marketing authorisation on the basis of a re-evaluation of the benefit-risk balance. Once renewed, the marketing authorisation shall be valid for an unlimited period, unless the national competent authority decides, on justified grounds, to proceed with one additional five-year renewal.
Amendment 756 #
Proposal for a directive
Article 46 – paragraph 4 a (new)
Article 46 – paragraph 4 a (new)
4 a. When an authorised product previously placed on the market in the authorising Member State is no longer actually present on the market for a period of three consecutive years, the authorisation for that product shall cease to be valid.
Amendment 757 #
Proposal for a directive
Article 46 – paragraph 4 b (new)
Article 46 – paragraph 4 b (new)
4 b. By way of derogation from paragraph 1 and 3, marketing authorisation for a medicinal product shall be withdrawn if the review of the post-authorisation studies referred to in Article 44 paragraph 1 result in a negative risk-benefit assessment.
Amendment 768 #
Proposal for a directive
Article 49 – paragraph 2
Article 49 – paragraph 2
2. If the application complies with all the measures contained in the agreed completed paediatric investigation plan and if the summary of product characteristics reflects the results of studies conducted in compliance with that agreed paediatric investigation plan, the competent authority of the Member State shall include within the marketing authorisation a statement indicating compliance of the application with the agreed completed paediatric investigation plan. The competent authority shall make the assessment report regarding compliance with paediatric investigation plan publicly available.
Amendment 777 #
Proposal for a directive
Article 51 – paragraph 1 – point e a (new)
Article 51 – paragraph 1 – point e a (new)
(e a) is an antiparasitic; or
Amendment 781 #
Proposal for a directive
Article 51 – paragraph 1 – point f
Article 51 – paragraph 1 – point f
(f) contains an active substance, adjuvants or any other ingredient or constituent which are persistent, bioaccumulative and toxic, or very persistent and very bioaccumulative, or persistent, mobile and toxic, or very persistent and very mobile, substances listed in Annex X of the Directive 2000/60/EC or individual priority substances in Annex I of the Directive 2008/105/EC 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.
Amendment 788 #
Proposal for a directive
Article 51 – paragraph 2
Article 51 – paragraph 2
2. Member States shall ensure that prescriptions and dispensation is aligned with the number of units required for the treatment concerned and 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, restrict the use of certain antimicrobials to the use in hospitals, or submitting certain antimicrobial medicinal products to special medical prescription or restricted prescription, including the requirement that second-line treatments cannot be given before a first-line treatment. Additional measures may include mandatory training of healthcare professionals on the environmental impact of medicines use and disposal and stewardship regarding the use of antimicrobials.
Amendment 795 #
Proposal for a directive
Article 55
Article 55
Amendment 799 #
Proposal for a directive
Article 56 – paragraph 3 – subparagraph 1
Article 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, pharmacies or persons authorised to supply medicinal products so that the needs of patients in the Member State in question are covered.
Amendment 1211 #
Proposal for a directive
Article 84 – paragraph 1 – introductory part
Article 84 – paragraph 1 – introductory part
1. A regulatory data protection period of fourtwo years shall be granted for a medicinal product with respect to a new therapeutic indication not previously authorised in the Union, provided that:
Amendment 1221 #
Proposal for a directive
Article 84 – paragraph 1 – point a
Article 84 – paragraph 1 – point a
(a) adequate non-clinical or clinical studies were carried outith an active-comparator were carried out by the marketing authorisation holder in relation to the therapeutic indication demonstrating that it is of significant clinical benefit, and
Amendment 1252 #
Proposal for a directive
Article 85 – paragraph 1 – introductory part
Article 85 – paragraph 1 – introductory part
Patent rights, or supplementary protection certificates under the [Regulation (EC) No 469/2009 - OP please replace reference by new instrument when adopted] shall not be regarded as infringed when a reference medicinal product is used for the purposes of:
Amendment 1306 #
Proposal for a directive
Article 85 – paragraph 1 – point a – point iii a (new)
Article 85 – paragraph 1 – point a – point iii a (new)
(iii a) Bolar examption for pre- production of products
Amendment 1318 #
Proposal for a directive
Article 85 – paragraph 1 – point b
Article 85 – paragraph 1 – point b
(b) the activities conducted exclusively for the purposes set out in point (a), may cover the submission of relevant documents to competent authorities, including the application for a marketing authorisation and the offer, health technology assessment, manufacture, sale, supply, storage, import, export, use and purchase of patented medicinal products or processes, including by third party suppliers and service providers.
Amendment 1353 #
Proposal for a directive
Article 87 – paragraph 1 – subparagraph 1 – introductory part
Article 87 – paragraph 1 – subparagraph 1 – introductory part
At the time of or after the granting of a marketing authorisation, the competent authority of the Member State may impose an obligation on the marketing authorisation holder:
Amendment 1362 #
Proposal for a directive
Article 87 – paragraph 1 – subparagraph 2
Article 87 – paragraph 1 – subparagraph 2
The imposition of such an obligation shall be duly justified, notified in writing, and shall include the objectives and timeframe for submission and conduct of the study. Information on imposed post- authorisation studies shall be noted in the product’s European Public Assessment Report, package leaflet and a medicine repository of the competent authority
Amendment 1365 #
Proposal for a directive
Article 89 – paragraph 1
Article 89 – paragraph 1
1. The marketing authorisation holder shall incorporate any safety or efficacy conditions referred to in Articles 44, 45 and 87 in the risk management system.
Amendment 1366 #
Proposal for a directive
Article 89 – paragraph 2
Article 89 – paragraph 2
2. The Member States shall inform the Agency of the marketing authorisations that they have granted subject to conditions pursuant to Articles 44, 45 and of any obligations imposed in accordance with Article 87.
Amendment 1371 #
Proposal for a directive
Article 101 – paragraph 2
Article 101 – paragraph 2
2. Paragraph 1 shall not preclude the competent authorities of the Member States from charging fees to marketing authorisation holders for performing pharmacovigilance activities on the condition that the independence in the performance of those pharmacovigilance activities is strictly guaranteed and in accordance with provisions laid down in Article 208.
Amendment 1372 #
Proposal for a directive
Article 102 – paragraph 1 – point b a (new)
Article 102 – paragraph 1 – point b a (new)
(b a) where applicable, documentation related to received scientific advice;
Amendment 1373 #
Proposal for a directive
Article 102 – paragraph 1 – point b b (new)
Article 102 – paragraph 1 – point b b (new)
(b b) environmental risk assessment reports;
Amendment 1374 #
Proposal for a directive
Article 102 – paragraph 1 – point b c (new)
Article 102 – paragraph 1 – point b c (new)
(b c) conditions imposed on marketing authorisation holder pursuant to Article 44;
Amendment 1375 #
Proposal for a directive
Article 102 – paragraph 1 – point d a (new)
Article 102 – paragraph 1 – point d a (new)
(d a) periodic safety update reports;
Amendment 1376 #
Proposal for a directive
Article 102 – paragraph 1 – point d b (new)
Article 102 – paragraph 1 – point d b (new)
(d b) information related to antimicrobials referred to in Article 17 and the awareness card, where relevant;
Amendment 1377 #
Proposal for a directive
Article 102 – paragraph 1 – point d c (new)
Article 102 – paragraph 1 – point d c (new)
(d c) information on the shortage status of medicinal products as referred to in Article 121(1)(b) of [revised Regulation (EC) No 726/2004];
Amendment 1378 #
Proposal for a directive
Article 102 – paragraph 1 – point d d (new)
Article 102 – paragraph 1 – point d d (new)
(d d) dates of expiry of IP and regulatory data and market protection periods.
Amendment 1387 #
Proposal for a directive
Article 106 – paragraph 1 – subparagraph 1 a (new)
Article 106 – paragraph 1 – subparagraph 1 a (new)
Member States shall ensure that patients and healthcare professionals who report adverse reactions shall be able to opt in for an automated notifications shall there be any update on the safety profile of the product.
Amendment 1391 #
Proposal for a directive
Article 107 – paragraph 3 a (new)
Article 107 – paragraph 3 a (new)
3 a. The Agency shall make publicly available the reports referred to in paragraph 1 points (a) and (b).
Amendment 1392 #
Proposal for a directive
Article 107 – paragraph 4 – subparagraph 1 – point a
Article 107 – paragraph 4 – subparagraph 1 – point a
(a) where such obligation has been laid down as a condition in the marketing authorisation in accordance with Articles 44 or 45; or
Amendment 1398 #
Proposal for a directive
Article 117 – paragraph 4
Article 117 – paragraph 4
4. Payments to healthcare professionals for participating in non- interventional post-authorisation safety studies shall be transparent and restricted to the compensation for time and expenses incurred.
Amendment 1399 #
Proposal for a directive
Article 120 – paragraph 1
Article 120 – paragraph 1
1. Upon completion of the study, a final study report shall be submitted to the competent authority of the Member State or the Pharmacovigilance Risk Assessment Committee within 12 months of the end of data collection unless a written waiver has been granted by the competent authority of the Member State or the Pharmacovigilance Risk Assessment Committee, as appropriatein duly justified cases.
Amendment 1401 #
Proposal for a directive
Article 123 – paragraph 1 – introductory part
Article 123 – paragraph 1 – introductory part
The Agency shall, in cooperation with competent authorities of the Member States and other interested parties, in particularly those referred to in Article 162 of [reviesed Regulation (EC) No 726/2004], draw up:
Amendment 1402 #
Proposal for a directive
Article 123 – paragraph 1 – point a a (new)
Article 123 – paragraph 1 – point a a (new)
(a a) guidance for national competent authorities and marketing authorisation holders on the effective inclusion of patients, consumers and healthcare professionals in the data collection and communication of the risks of medicinal products within the pharmacovigilance systems referred to in Articles 96 and 99;
Amendment 1428 #
Proposal for a directive
Article 141 – paragraph 2 a (new)
Article 141 – paragraph 2 a (new)
2 a. Invited experts shall provide their declaration of interest ahead of the meeting to the Agency.
Amendment 1429 #
Proposal for a directive
Article 141 – paragraph 5
Article 141 – paragraph 5
5. The herbal medicinal products working group shall draft its rules of procedure, including regarding provisions laid down in Article 208 and Article 147 of [revised Regulation (EC) No 726/2004].
Amendment 1430 #
Proposal for a directive
Article 142 – paragraph 3 – point a
Article 142 – paragraph 3 – point a
(a) preparation, dividing up, changes in packaging or presentation where these processes are carried out, solely for retail and hospital supply, by pharmacists in dispensing pharmacies or by persons legally authorised in the Member States to carry out such processes; or
Amendment 1431 #
Proposal for a directive
Article 143 – paragraph 1 – subparagraph 2 – point a a (new)
Article 143 – paragraph 1 – subparagraph 2 – point a a (new)
(a a) environmental impact assessment of the product’s manufacturing process;
Amendment 1432 #
Proposal for a directive
Article 143 – paragraph 1 – subparagraph 2 – point b a (new)
Article 143 – paragraph 1 – subparagraph 2 – point b a (new)
(b a) proof that the product’s supply chain is diversified, identifying alternatives for each component;
Amendment 1434 #
Proposal for a directive
Article 147 – paragraph 1 – subparagraph 1 – point j a (new)
Article 147 – paragraph 1 – subparagraph 1 – point j a (new)
(j a) comply with risk mitigation measures identified and considered in accordance with Article 22(4).
Amendment 1438 #
Proposal for a directive
Article 159 – paragraph 1 – subparagraph 1
Article 159 – paragraph 1 – subparagraph 1
At the request of a third country, the Commission shall assess whether that country’s regulatory framework applicable to active substances exported to the Union and the respective control and enforcement activities ensure a level of protection of public healthand worker’s health and environment equivalent to that of the Union.
Amendment 1439 #
Proposal for a directive
Article 159 – paragraph 2 – subparagraph 2 – point a
Article 159 – paragraph 2 – subparagraph 2 – point a
(a) the country’s rules for good manufacturing practice, including local environmental manufacturing standards, occupational health and labour rights standards;
Amendment 1441 #
Proposal for a directive
Article 160 – paragraph 1 – introductory part
Article 160 – paragraph 1 – introductory part
The Commission may adopt implementingdelegated acts in accordance with Article 214(2)5 to supplement this Directive by specifying:
Amendment 1443 #
Proposal for a directive
Article 160 – paragraph 1 – point b a (new)
Article 160 – paragraph 1 – point b a (new)
(b a) measures to reduce the negative impact on the environment posed by the development, manufacturing, use and disposal of medicinal product.
Amendment 1453 #
Proposal for a directive
Article 167 – paragraph 2
Article 167 – paragraph 2
2. The wholesale distributors of a medicinal product placed on the market in a Member State shall, within the limits of their responsibilities, ensure appropriate and continued supplies of that medicinal product to pharmacies and persons authorised to supply medicinal products so that the needs of patients in the Member State in question are covered.
Amendment 1463 #
Proposal for a directive
Article 175 – paragraph 1 – subparagraph 2 – point e
Article 175 – paragraph 1 – subparagraph 2 – point e
(e) the provision of inducements to prescribe or supply medicinal products by the gift, offer or promise of any benefit or bonus, whether in money or in kind, except when their intrinsic value is minimal;
Amendment 1466 #
Proposal for a directive
Article 176 – paragraph 3 – point a
Article 176 – paragraph 3 – point a
(a) shall encouragpromote the rational use of the medicinal product, by presenting it objectively and without exaggerating its properties;
Amendment 1472 #
Proposal for a directive
Article 176 – paragraph 4
Article 176 – paragraph 4
4. Any form of advertising that aims to highlight negatively another medicinal product shall be prohibited. Advertising that suggests that a medicinal product is safer or more effective than another medicinal product shall also be prohibited, unless demonstrated and supported by the summary of product characteristics.
Amendment 1475 #
Proposal for a directive
Article 177 – paragraph 1 – point b a (new)
Article 177 – paragraph 1 – point b a (new)
(b a) contain substances listed in Annex X of Directive 2000/60/EC, individual priority substances in Annex I to Directive 2008/105/EC or substances in Annex I of Directive 2006/118/EC;
Amendment 1482 #
Proposal for a directive
Article 177 – paragraph 1 – point b b (new)
Article 177 – paragraph 1 – point b b (new)
(b b) contain hazardous substances during pregnancy;
Amendment 1484 #
Proposal for a directive
Article 177 – paragraph 1 – point b c (new)
Article 177 – paragraph 1 – point b c (new)
(b c) contain substances affected by potential or actual shortage.
Amendment 1486 #
Proposal for a directive
Article 177 – paragraph 2
Article 177 – paragraph 2
2. Medicinal products may be advertised to the general public where, by virtue of their composition and purpose, they are intended and designed for use without the intervention of a medical practithealthcare professioneral for diagnostic purposes or for the prescription or monitoring of treatment, with the advice of the pharmacist, if necessary.
Amendment 1493 #
Proposal for a directive
Article 177 – paragraph 3
Article 177 – paragraph 3
3. Member States shall be entitled to ban, on their territory, advertising to the general public of medicinal products othe cost of which may be reimbursedr than those referred to in paragraph 1.
Amendment 1498 #
Proposal for a directive
Article 177 – paragraph 4
Article 177 – paragraph 4
4. The prohibition contained in paragraph 1 shall not apply to vaccination campaigns carried out by the industry and approved by the competent authorities of the Member States.
Amendment 1501 #
Proposal for a directive
Article 178 – paragraph 1 – point b – point i
Article 178 – paragraph 1 – point b – point i
(i) the name of the medicinal product, as well as the common name if the medicinal product contains only one active substancinternational non-propriety name, as well as the common name;
Amendment 1502 #
Proposal for a directive
Article 178 – paragraph 1 – point b – point ii
Article 178 – paragraph 1 – point b – point ii
(ii) the information necessary for correct use and disposal of the medicinal product;
Amendment 1509 #
Proposal for a directive
Article 180 – paragraph 2 a (new)
Article 180 – paragraph 2 a (new)
2 a. The Commission shall adopt a delegated act, in accordance with Article 215, regarding restrictions and obligations related to advertising of medicinal products on social media, including on the involvement of celebrities and influencers in the promotion of medicinal products online.
Amendment 1511 #
Proposal for a directive
Article 183 – paragraph 1
Article 183 – paragraph 1
1. Where medicinal products are being promoted to persons qualified to prescribe or supply them, no gifts, pecuniary advantages or benefits in kind may be supplied, offered or promised to such persons unless they are inexpensive and relevant to the practice of medicine or pharmacy.
Amendment 1517 #
Proposal for a directive
Article 186 – paragraph 1
Article 186 – paragraph 1
1. Member States shall ensure that there are adequate and effective methods to monitor the advertising of medicinal products. Such methods, which mayshall be based on a system of prior vetting especially when advertising is targeted at the general public, 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.
Amendment 1520 #
Proposal for a directive
Article 186 – paragraph 4 a (new)
Article 186 – paragraph 4 a (new)
4 a. Member State shall set up and maintain a national transparency register of transfers of value regarding the advertising activities referred to in Articles 175, 177, 180, 182, 183, 184 and 185, targeting persons qualified to prescribe medicinal products. The Commission shall on its website publish a listing referring to all national registries.
Amendment 1521 #
Proposal for a directive
Article 186 – paragraph 4 b (new)
Article 186 – paragraph 4 b (new)
4 b. The national registries referred to in paragraph 4a 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) medicinal product concerned; (d) type of advertising activity, referred to in Article 175 paragraph 1 points (b) to (g) and Article 184; (e) monetary value.
Amendment 1522 #
Proposal for a directive
Article 186 – paragraph 4 c (new)
Article 186 – paragraph 4 c (new)
4 c. Marketing authorisation holders shall use the national transparency register referred to in paragraph 4a to submit information referred to in paragraph 4b in relation to each person qualified to prescribe medicinal products in respective Member State where such activity takes place.
Amendment 1523 #
Proposal for a directive
Article 186 – paragraph 5
Article 186 – paragraph 5
5. The paragraphs 1 to 4c shall not exclude the voluntary control of advertising of medicinal products by self- regulatory bodies and recourse to such bodies, if proceedings before such bodies are possible in addition to the judicial or administrative proceedings referred to in paragraph 1.
Amendment 1524 #
Proposal for a directive
Article 187 – paragraph 2 – point d a (new)
Article 187 – paragraph 2 – point d a (new)
(d a) report activities in national registries, as laid down in Article 186 (4c).
Amendment 1540 #
Proposal for a directive
Article 194 – paragraph 1
Article 194 – paragraph 1
1. Member States shall take all necessary measures to ensure that the manufacturing and purifying processes used in the preparation of medicinal products derived from human blood or human plasma are properly validated, attain batch-to-batch consistency and guarantee, insofar as the state of technology permits, the absence of specific viral contamination that may pose a risk to patients.
Amendment 1550 #
2. The competent authorities of the Member States or, in the case of centralised marketing authorisation, the Commission mayshall 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.
Amendment 1553 #
Proposal for a directive
Article 195 – paragraph 3
Article 195 – paragraph 3
3. A marketing authorisation may also be suspended, revoked or varied where the particulars supporting the application as provided for in Articles 6, 9 to 14 or Annexes I to V are incorrect or have not been amended in accordance with Article 90, or where any conditions referred to in Articles 44, 45 and 87 have not been fulfilled or where the controls referred to in Article 191 have not been carried out.
Amendment 1562 #
Proposal for a directive
Article 200 – paragraph 2
Article 200 – paragraph 2
2. Member States shall ensure that adequate financial resources are available to provide the staff and other resources, including appropriate digital infrastructure, necessary for the competent authorities to carry out the activities required by this Directive and [revised Regulation (EC) No 726/2004].
Amendment 1563 #
Proposal for a directive
Article 200 – paragraph 3
Article 200 – paragraph 3
3. The competent authorities of the Member States shall cooperate with each other and with the Agency and the Commission in the performance of their tasks under this Directive and [revised Regulation (EC) No 726/2004] to ensure proper application and due enforcement. The competent authorities of the Member States shall transmit to each other and to the Agency all necessary information.
Amendment 1568 #
Proposal for a directive
Article 201 – paragraph 1 a (new)
Article 201 – paragraph 1 a (new)
1 a. Member States shall ensure a consultation process between national competent authorities for medicinal products and other relevant authorities or bodies for the exchange of information and pooling of expertise related to provisions laid down in this Directive, including, as appropriate, notified bodies under Regulation (EU) 2017/745 and Regulation (EU) 2017/746, bodies responsible for health technology assessment as referred to in Regulation (EU) 2021/2282 and national bodies responsible for pricing and reimbursement.
Amendment 1572 #
Proposal for a directive
Article 206 – paragraph 1 a (new)
Article 206 – paragraph 1 a (new)
Amendment 1573 #
Proposal for a directive
Article 206 – paragraph 1 b (new)
Article 206 – paragraph 1 b (new)
Amendment 1575 #
Proposal for a directive
Article 206 – paragraph 2 – point d a (new)
Article 206 – paragraph 2 – point d a (new)
(d a) non-compliance with the provisions laid down in this Directive on obligations imposed by national competent authorities, including related to product’s efficacy, safety and environmental impact, including antimicrobial resistance;
Amendment 1576 #
Proposal for a directive
Article 206 – paragraph 2 – point d b (new)
Article 206 – paragraph 2 – point d b (new)
(d b) non-compliance with the provisions related to supply obligation;
Amendment 1577 #
Proposal for a directive
Article 206 – paragraph 2 – point d c (new)
Article 206 – paragraph 2 – point d c (new)
(d c) non-compliance with launches of products in Member States, as laid down in article 58a;
Amendment 1579 #
Proposal for a directive
Article 206 – paragraph 3
Article 206 – paragraph 3
Amendment 1586 #
Proposal for a directive
Article 207 – paragraph 1
Article 207 – paragraph 1
Member States shall ensure that appropriate collection and disposal systems are in place for medicinal products that are unused or have expired.
Amendment 1589 #
Proposal for a directive
Article 208 – paragraph 1
Article 208 – paragraph 1
1. In order to guarantee independence and transparency, the Member States shall ensure that members of staff of the competent authority responsible for granting authorisations, rapporteurs and experts concerned with the authorisation and post-authorisation surveillance of medicinal products have no direct or indirect financial or other interests in the pharmaceutical industry that could affect their impartiality. These persons shall make an annual declaration of their financial interests which shall be made publicly available on the authority’s website.
Amendment 1593 #
Proposal for a directive
Article 208 – paragraph 2
Article 208 – paragraph 2
2. In addition, the Member States shall ensure that the competent authority makes publicly available its rules of procedure and those of its committees, including their working groups and expert groups, agendas for its meetings and records of its meetings, accompanied by decisions taken, details of votes and explanations of votes, including minority opinions.
Amendment 1596 #
Proposal for a directive
Article 214 – paragraph 4
Article 214 – paragraph 4
4. The rules of procedure of, meeting agenda and minutes with detailed records including information on decisions taken, details and explanation of votes, including minority opinions shall be made publicly available. Names of members and other national experts participating in the Standing Committee on Medicinal Products shall be made publicly available. on the Commission’s website.
Amendment 1597 #
Proposal for a directive
Article 214 – paragraph 4 a (new)
Article 214 – paragraph 4 a (new)
4 a. Members and experts participating in the Committee shall act in an independent manner and shall have no direct or indirect financial or other interests in the pharmaceutical industry that could affect their impartiality. They shall submit their conflict of interest declaration to the Chair of the Committee ahead of each meeting.
Amendment 1599 #
Proposal for a directive
Article 216 – paragraph 1
Article 216 – paragraph 1
By [OP please insert the date = 107 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.
Amendment 1600 #
Proposal for a directive
Article 217 – paragraph 2
Article 217 – paragraph 2
Amendment 1602 #
Proposal for a directive
Article 218 – paragraph 6
Article 218 – paragraph 6
6. By way of derogation from paragraph 3, the reporting obligations as referred to in Article 57 and 57a, shall not apply with regards to medicinal products authorised in accordance with Directive 2001/83/EC before [OP please insert the date = 18 months after the date of entering into force of this Directive].
Amendment 1606 #
Proposal for a directive
Annex I – point 21 – point a – introductory part
Annex I – point 21 – point a – introductory part
a) an antimicrobial stewardship and access plan which shall in particular outline:
Amendment 1607 #
Proposal for a directive
Annex I – point 21 – point a – point i
Annex I – point 21 – point a – point i
(i) information about risk mitigationrisk mitigation strategy outlining measures to limit antimicrobial resistance development related to the use, prescription and administration of the medicinal product;
Amendment 1608 #
Proposal for a directive
Annex I – point 21 – point a – point ii
Annex I – point 21 – point a – point ii
(ii) how the marketing authorisation holder intends to monitor and report to the competent authority the resistance to the antimicrobial medicinal product.;
Amendment 1609 #
Proposal for a directive
Annex I – point 21 – point a – point ii a (new)
Annex I – point 21 – point a – point ii a (new)
(ii a) strategy to ensure access, including proposed production chain with sufficient capacity, supply systems, approach to product labelling, and the approach to overcome economic barriers to access;
Amendment 1610 #
Proposal for a directive
Annex I – point 21 – point a – point ii b (new)
Annex I – point 21 – point a – point ii b (new)
(ii b) obstacles and constraints to stewardship and access;
Amendment 1611 #
Proposal for a directive
Annex I – point 21 – point a – point ii c (new)
Annex I – point 21 – point a – point ii c (new)
(ii c) exploitation strategy for IP rights, including whether it is planned for the IP rights to be transferred to a third party for non-prioritised territories; exploitation strategy for IP rights, including whether it is planned for the IP rights to be transferred to a third party for non- prioritised territories;
Amendment 1612 #
Proposal for a directive
Annex I – point 21 – point a – point ii d (new)
Annex I – point 21 – point a – point ii d (new)
(ii d) strategy to ensure marketing approvals are received for key territories in a timely manner; and
Amendment 1613 #
Proposal for a directive
Annex I – point 21 – point a – point ii e (new)
Annex I – point 21 – point a – point ii e (new)
(ii e) strategy and methodology for monitoring effectiveness of stewardship and access, including proposed metrics to measure success.
Amendment 1614 #
Proposal for a directive
Annex I – point 21 – point a a (new)
Annex I – point 21 – point a a (new)
a a) The stewardship and access plan should be made publicly available by the EMA when market authorization has been granted.
Amendment 1620 #
Proposal for a directive
Annex IV – paragraph 1 – point a
Annex IV – paragraph 1 – point a
(a) the name of the medicinal product, including in Braille, followed by its strength and pharmaceutical form, and, if appropriate, whether it is intended for babies, children or adults; where the medicinal product contains up to three active substances, the international non- proprietary name(s) (INN) shall be included, or, if one does not exist, the common name;
Amendment 1621 #
Proposal for a directive
Annex IV – paragraph 1 – point g a (new)
Annex IV – paragraph 1 – point g a (new)
(g a) for antimicrobials, a pictogram and a warning that improper use and disposal of the medicinal product contributes to antimicrobial resistance;
Amendment 1622 #
Proposal for a directive
Annex IV – paragraph 1 – point j
Annex IV – paragraph 1 – point j
(j) specific precautions relating to the disposal of unused medicinal products or waste derived from medicinal products, where appropriate, as well as reference to any appropriate collection system in place;
Amendment 1624 #
Proposal for a directive
Annex V – paragraph 1 – point 4 – point a a (new)
Annex V – paragraph 1 – point 4 – point a a (new)
(a a) efficacy-related information and risk-benefit assessment, including information on remaining uncertainty about the medicine’s efficacy and safety profile;
Amendment 1625 #
Proposal for a directive
Annex V – paragraph 1 – point 4 – point b
Annex V – paragraph 1 – point 4 – point b
(b) posology and method of administration for adults and, where necessary for children, and where relevant, a comprehensive and accurate illustrated description of the measuring and/or delivery device,
Amendment 1626 #
Proposal for a directive
Annex V – paragraph 1 – point 6 – point f
Annex V – paragraph 1 – point 6 – point f
(f) special precautions for disposal of a used medicinal product or waste materials derived from such medicinal product, if appropriate. In case of antimicrobial medicinal products in addition to the precautions a warning that inappropriate disposal of the medicinal product contributes to antimicrobial resistance.;
Amendment 1627 #
Proposal for a directive
Annex V – paragraph 1 – point 6 – point f a (new)
Annex V – paragraph 1 – point 6 – point f a (new)
(f a) for products containing substances classified based on Annex I of Regulation (EC) No 1272/2008 as persistent, bioaccumulative and toxic (PBT), very persistent and very bioaccumulative (vPvB), persistent, mobile and toxic (PMT), very persistent and very mobile (vPvM) or are endocrine active agents, a warning that improper use and disposal of the medicinal product, inter alia through toilets, contributes to deteriorating the aquatic environment;
Amendment 1628 #
Proposal for a directive
Annex V – paragraph 1 – point 6 – point f b (new)
Annex V – paragraph 1 – point 6 – point f b (new)
(f b) summary of environmental impact assessment.
Amendment 1631 #
Proposal for a directive
Annex VI – paragraph 1 – point 2 a (new)
Annex VI – paragraph 1 – point 2 a (new)
(2 a) efficacy-related information per therapeutic indication;
Amendment 1632 #
Proposal for a directive
Annex VI – paragraph 1 – point 4 – point b
Annex VI – paragraph 1 – point 4 – point b
(b) the method and, if necessary, route of administration; where relevant, a comprehensive and accurate illustrated description of the measuring and/or delivery device, including all the different steps of medicine preparation and administration;
Amendment 1633 #
Proposal for a directive
Annex VI – paragraph 1 – point 6 a (new)
Annex VI – paragraph 1 – point 6 a (new)
(6 a) a list of pending post-authorisation studies and other obligations;
Amendment 1634 #
Proposal for a directive
Annex VI – paragraph 1 – point 8 a (new)
Annex VI – paragraph 1 – point 8 a (new)
(8 a) for products containing substances classified based on Annex I of Regulation (EC) No 1272/2008 as persistent, bioaccumulative and toxic (PBT), very persistent and very bioaccumulative (vPvB), persistent, mobile and toxic (PMT), very persistent and very mobile (vPvM) or are endocrine active agents, a warning that improper use and disposal of the medicinal product, inter alia through toilets, contributes to deteriorating the aquatic environment.