Changes from plenary report to adopted text

Added2. For medicinal products that are likely to offer an exceptional therapeutic advancement in the diagnosis, prevention or treatment of a life-threatening, seriously debilitating or serious and chronic condition or that are expected to be of major interest from the point of view of public health or intended for conditions with no authorised alternatives in the Union, the Agency may, following the advice of the Committee for Medicinal Products for Human Use regarding the maturity of the data related to the development, offer to the applicant a phased review of complete data packages for individual modules of particulars and documentation as referred to in paragraph 1. [Am. 98]

RemovedArticle 121 – paragraph 1 – point -a (new): (-a) collect and assess the information on potential and actual shortages provided by marketing authorisation holders, importers, manufacturers and suppliers of medicinal products or active substances, wholesale distributors, healthcare professionals, patients and consumers, and other persons or legal entities that are authorised or entitled to supply medicinal products to the public;

AddedThe Agency may at any stage suspend or cancel the phased review, where the Committee for Medicinal Products for Human Use considers that the submitted data are not of sufficient maturity or where it is considered that the medicinal product no longer fulfils an exceptional therapeutic advancement. The Agency shall inform the applicant accordingly.

RemovedArticle 121 – paragraph 1 – point b: (b) publish information and provide regular updates on actual shortages of medicinal products, that competent authority has assessed the shortage on a publicly available and user-friendly website and ensure such information, including regarding available alternatives, has been actively communicated to representatives of healthcare professionals and patients; competent authorities shall as soon as possible inform the Agency of any measure planned or taken at national level to mitigate the shortage or expected shortage.

Added3. A fee shall apply for a marketing authorisation application and shall be payable to the Agency for the examination of the application.

RemovedArticle 121 – paragraph 1 – point b a (new): (ba) create a system allowing patients to report shortages of medicinal products and request pharmacies supplying hospitals and hospital pharmacies to electronically communicate data on available stock of the medicinal product concerned, in order to avert or mitigate an imminent or existing supply shortage relevant to the supply of a medicinal product.

Added4. Where appropriate, the application may include an active substance master file certificate or an application for an active substance master file or any other quality master file certificate or application as referred to in Article 25 of [revised Directive 2001/83/EC].

RemovedArticle 121 – paragraph 1 – point c a (new): (ca) address recommendations to health professionals on the alternative medicinal products to use to pursue treatments in the event of shortages;

Added5. The marketing authorisation applicant shall demonstrate that the principle of replacement, reduction and refinement of animal testing for scientific purposes has been applied in compliance with Directive 2010/63/EU with regard to any animal study conducted in support of the application.

RemovedArticle 121 – paragraph 1 – point c b (new): (cb) consider the use of appropriate regulatory measures to mitigate the shortage.

AddedThe marketing authorisation applicant shall not carry out animal tests in case scientifically satisfactory non-animal testing methods are available. The Agency shall in its annual report highlight key observations and best practices in the replacement, reduction and refinement of animal testing submitted by applicants. [Am. 99]

RemovedArticle 121 – paragraph 2 – point f: (f) inform the Agency of any actions foreseen or taken by that Member State to mitigate the shortage at national level without undue delay.

Added6. The Agency shall ensure that the opinion of the Committee for Medicinal Products for Human Use is given within 180 days after receipt of a valid application. In the case of a medicinal product for human use containing or consisting of genetically modified organisms, the opinion of that Committee shall take into account the evaluation of the environmental risk assessment in accordance with Article 8.

RemovedArticle 121 – paragraph 2 a (new): 2a. After the expansion of the ESMP referred to in Article 122(6) and for the purpose of Article 118(1) and Article 121(2), point (a), competent authorities of the Member States shall set up national IT systems which are interoperable with the ESMP and allow for the automated exchange of information with the ESMP while avoiding duplication of reporting.

AddedOn the basis of a duly reasoned request, the Committee for Medicinal Products for Human Use may call for the duration of the analysis of the scientific data in the file concerning the application for marketing authorisation to be extended.

RemovedArticle 121 – paragraph 5 – point a: (a) report to the Agency on any information received from the marketing authorisation holder as defined in Article 116(1) of the medicinal product concerned or from other actors pursuant to Article 120(1a) and (2);

Added7. When an application is submitted for a marketing authorisation in respect of medicinal products for human use which are of major interest from the point of view of public health and in particular from the viewpoint of therapeutic innovation, the applicant may request an accelerated assessment procedure. The same shall apply for products referred to in Article 60. The request shall be duly substantiated.

RemovedArticle 121 – paragraph 5 – point d: (d) inform the Agency of any actions foreseen or taken by that Member State in accordance with points (b) and (c) and report on any other actions taken to mitigate or resolve the critical shortage in the Member State, as well as the results of these actions, without undue delay.

AddedIf the Committee for Medicinal Products for Human Use accepts the request, the time-limit laid down in Article 6(6), first subparagraph, shall be reduced to 150 days.

RemovedArticle 121 – paragraph 6: 6. The Member States may request that the MSSG provide further recommendations, referred to in Article 123(4). Where Member States take an alternative course of action which is not in line with the recommendations of the MSSG at national level, they shall communicate the reasons for doing so to the MSSG in a timely manner.

AddedArticle 7 Environmental risk assessment for medicinal products containing or consisting of genetically modified organisms

RemovedArticle 121 a (new): Article121a / National websites on medicines shortages / The website referred to in Article 121( 1), point (b), shall include at least the following information: / (a) trade name of the medicinal product and international non-proprietary name, for interoperability purposes; / (b) the therapeutic indication for the medicinal product of which there is a shortage; / (c) reasons for the shortages and mitigation measures taken to address the shortages; / (d) the start and expected end dates of the shortage; / (e) other relevant information for healthcare professionals and patients, including information about therapeutic alternatives available.

Added1. Without prejudice to Article 22 of [revised Directive 2001/83/EC], the marketing authorisation application of a medicinal product for human use containing or consisting of genetically modified organisms as defined in Article 2(2) of Directive 2001/18/EC shall be accompanied by an environmental risk assessment identifying and evaluating potential adverse effects of the genetically modified organisms on human and animal health, and the environment. [Am. 100]

RemovedArticle 122 – paragraph 1: 1. For the purposes of Article 118(1) and (1a), the Agency may request additional information from the competent authority of the Member State, through the working party referred to in Article 121(1), point (c). The Agency may set a deadline for the submission of the information requested.

Added2. The environmental risk assessment for the medicinal products referred to in paragraph 1 shall be conducted in accordance with the elements described in Article 8 and the specific requirements set out in Annex II to [revised Directive 2001/83/EC] based on the principles set out in Annex II to Directive 2001/18/EC taking into account the specificities of medicinal products.

RemovedArticle 122 – paragraph 1 a (new): 1a. For the purpose of Article 118(1a) and based on the information provided pursuant to Article 121(1), point (cb), and Article 121(2), the Agency shall assess the actions planned or taken by a Member State to mitigate a shortage at national level with regard to any potential or actual negative impacts of those actions on the availability and security of supply in another Member State and at Union level. The Agency shall inform the Member State concerned and the MSSG, as well as the Member States potentially or actually impacted, of its assessment in a timely manner through the single point of contact working party referred to in Article 3(6) of Regulation (EU) 2022/123. The Agency shall also inform the Commission of its assessment.

Added3. Articles 13 to 24 of Directive 2001/18/EC shall not apply to medicinal products for human use containing or consisting of genetically modified organisms.

RemovedArticle 122 – paragraph 2 a (new): 2a. For the purpose of identifying the medicinal products for which the shortage cannot be resolved without Union coordination pursuant to paragraph 2, the Agency may consult market authorisation holders and other relevant stakeholders.

Added4. Articles 6 to 11 of [revised Directive 2001/18/EC] as well as Articles 4 to 13 of Directive 2009/41/EC shall not apply to operations related to the supply and clinical use, including the packaging and labelling, distribution, storage, transport, preparation for administration, administration, destruction or disposal of medicinal products containing or consisting of genetically modified organisms, with the exception of their manufacture, in any of the following cases:

RemovedArticle 122 – paragraph 4 – introductory part: 4. For the purposes of fulfilling the tasks referred to in Articles 118(1), 123 and 124, the Agency shall ensure the following, in consultation with the working party referred to in Article 121(1), point (c), and in consultation with the Patients’ and Consumers’ Working Party (PCWP) and the Healthcare Professionals’ Working Party (HCPWP) and other relevant stakeholders:

Added(a) where such medicinal products have been excluded from the provisions of [revised Directive 2001/83/EC] by a Member State pursuant to Article 3(1) of that Directive;

RemovedArticle 122 – paragraph 6: 6. For the purposes of implementing this Regulation, the Agency shall expand the scope of the ESMP. The Agency shall ensure that data is interoperable between the ESMP and Member States’ IT systems and, where relevant, with other relevant IT systems and databases, without duplication of reporting.

Added(b) where the use and distribution of such medicinal products have been temporarily authorised by a Member State pursuant to Article 3(2) of [revised Directive 2001/83/EC]; or

RemovedArticle 123 – paragraph 2: 2. The MSSG shall review the status of the critical shortage whenever necessary and shall update the list when it considers that a medicinal product needs to be added or that the critical shortage has been resolved based on the report pursuant to Article 122(5). The MSSG may recommend monitoring forecasts of supply and demand for medicinal products for human use in the Union and monitoring of available stocks in the whole supply chain.

Added(c) where such medicinal products are made available by a Member State pursuant to Article 26(1).

RemovedArticle 123 – paragraph 4: 4. The MSSG shall, without undue delay, provide recommendations on measures to resolve or to mitigate the critical shortage in accordance with the methods referred to in Article 122(4), point (d), to relevant marketing authorisation holders, the Member States, the Commission, the representatives of healthcare professionals or other entities.

Added5. In the cases referred to in paragraph 4, Member States shall implement appropriate measures to minimise foreseeable negative environmental impacts resulting from the intended or unintended release of the medicinal products containing or consisting of genetically modified organisms into the environment.

RemovedArticle 123 – paragraph 4 – subparagraph 1 a (new): Member States, within the MSSG, may decide to activate the ‘Voluntary Solidarity Mechanism for medicines’ to: / (a) notify a critical shortage of a medicinal product at national level to other Member States and the Commission; / (b) identify, with the support of the Agency, the availabilities of the medicinal product in other Member States; / (c) organise, with the support of the Agency, meetings with the issuing Member States, the donating party and other relevant parties to discuss operational requirements; / (d) request the activation of the Union Civil Protection Mechanism to coordinate and logistically support the voluntary transfer of medicinal products.

AddedThe competent authorities of the Member States shall ensure that information related to the use of medicinal products referred to in paragraph 4, is available and provided to the competent authorities established by Directive 2009/41/EC, when necessary and in particular in the event of an accident referred to in Article 14 and Article 15 of Directive 2009/41/EC.

RemovedArticle 124 – paragraph 2 – subparagraph 2: For the purposes of this paragraph, the Agency shall set a deadline for the submission of the information requested.

AddedArticle 8 Content of the environmental risk assessment for medicinal products containing or consisting of genetically modified organisms

RemovedArticle 124 – paragraph 3: 3. The Agency shall establish within its web-portal referred to in Article 104 a publicly available and user-friendly webpage that provides information on all actual critical shortages of medicinal products, including the reasons for the shortages. After assessing the shortages, the Agency shall provide recommendations to healthcare professionals and patients. The webpage shall include the information referred to in Article 121a in addition to the list of Member States affected by each shortage. This webpage shall also provide references to the lists of actual shortages published by the competent authorities of the Member State pursuant to Article 121(1), point (b), the ESMP and include, to the extent possible, information from other relevant sources and databases identified by the Agency and include reference to alternative treatment options or products and appropriate communication.

AddedThe environmental risk assessment referred to in Article 7(2) shall contain the following elements:

RemovedArticle 125 – paragraph 1 – point a: (a) provide any additional information that the Agency may request, including regular information on the available stocks of medicinal products;

Added(a) description of the genetically modified organism and the modifications introduced as well as characterisation of the finished product;

RemovedArticle 125 – paragraph 1 – point f: (f) inform the Agency of the end date of the critical shortage without undue delay;

Added(b) identification and characterisation of hazards for the environment, animals and for human health throughout the lifecycle of the medicinal product, including manufacturing; for the purpose of this point, ‘hazards for human health’ include the risks to the health of human beings other than the treated patient as the risk to the treated patient shall be assessed as part of the benefit-risk assessment of the medicinal product; [Am. 101]

RemovedArticle 126 – paragraph 2 a (new): 2a. The Commission shall take the appropriate steps to address any concerns raised by the assessment of the Agency referred to in Article 122(1a).

Added(c) exposure characterisation, assessing the likelihood or probability that the identified hazards materialise;

RemovedArticle 127 – paragraph 1: 1. The competent authority of the Member State shall, after consultation with healthcare professionals and patient organisations, identify critical medicinal products in that Member State, using the methodology set out in Article 130(1), point (a).

Added(d) risk characterisation taking into account the magnitude of each possible hazard and the likelihood or probability of that adverse effect occurring;

RemovedArticle 128 – paragraph 2: 2. The marketing authorisation holder as defined in Article 116(1) shall be responsible for providing correct, not misleading, and complete information as requested by the competent authority concerned as defined in Article 116(1) and shall have the duty to cooperate and to disclose on their own motion any relevant information without undue delay to that competent authority and to update the information as soon as that information becomes available.

Added(e) risk minimisation and mitigation strategies proposed to address identified risks including specific containment measures to limit contact with the medicinal product. [Am. 102]

RemovedArticle 129 – paragraph 1: For the purposes of Article 127(4) and Article 130(2), point (c), and Article 130(4), point (c), where relevant, upon request from the competent authority concerned as defined in Article 116(1), entities including other marketing authorisation holders as defined in Article 116(1), importers and manufacturers of medicinal products or active substances and relevant suppliers of these, wholesale distributors, stakeholder representative associations or other persons or legal entities that are authorised or entitled to supply medicinal products to the public shall provide any information by the deadline set by the Agency and provide updates whenever necessary.

AddedArticle 9 Procedure for the environmental risk assessment for medicinal products containing or consisting of genetically modified organisms

RemovedArticle 130 – paragraph 1 – subparagraph 1 – point a: (a) develop a common methodology to identify critical medicinal products, including the evaluation of vulnerabilities and the availability of appropriate alternatives with respect to the supply chain of those medicines, in consultation with the Patients’ and Consumers’ Working Party (PCWP) and the Healthcare Professionals’ Working Party (HCPWP), as well as other relevant stakeholders;

Added1. The applicant shall submit an environmental risk assessment referred to in Article 7(1) to the Agency.

RemovedArticle 130 – paragraph 2 – subparagraph 1 – point b: (b) the marketing authorisation holder of the medicinal product, including the shortage prevention and mitigation plan, referred to in Article 117 and Article 119(2);

AddedThe Committee for Medicinal Products for Human Use shall assess the environmental risk assessment, and where necessary consult the ad-hoc Environmental Risk Assessment working party referred to in Article 150. [Am. 103]

RemovedArticle 130 – paragraph 5: 5. Following the adoption of the Union list of critical medicinal products in accordance with Article 131, the Agency shall assess any relevant information received from the marketing authorisation holder pursuant to Article 133 and the competent authority of the Member State in accordance with Article 127, paragraphs 7 and 8 and report on that information to the MSSG.