What changed between the plenary report and the adopted text

Added: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. [Am. 116]

Added:Article 11 Applications concerning biosimilar medicinal products

Added:For a biological medicinal product that is similar to a reference biological medicinal product (‘biosimilar medicinal product’), the results of appropriate comparability tests and studies shall be provided to the competent authorities. The type and quantity of supplementary data to be provided must comply with the relevant criteria stated in Annex II and the related detailed guidelines. The results of other tests and studies from the reference medicinal product's dossier shall not be provided.

Added:Article 12 Applications concerning bio-hybrid medicinal products

Added:In cases where a biosimilar medicinal product has changes in strength, pharmaceutical form, route of administration or therapeutic indications, compared to the reference biological medicinal product (‘bio-hybrid’), the results of the appropriate non-clinical tests or clinical studies shall be provided to the competent authorities to the extent necessary to establish a scientific bridge to the data relied upon in the marketing authorisation for the reference biological medicinal product, and to demonstrate the safety or efficacy profile of the biosimilar medicinal product. The Agency shall adopt guidelines on the appropriate tests and clinical studies for marketing authorisation of bio-hybrid medicinal products. [Am. 117]

Added:Article 13 Applications based on bibliographic data

Added: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. A justification shall be provided with regard to the relevance of that literature for the medicinal product. [Am. 118]

Added:Article 14 Applications based on consent

Added:Following the granting of a marketing authorisation, the marketing authorisation holder may, by letter of access, allow use to be made of all documentation referred to in Article 6(2) with a view to examining subsequent applications relating to other medicinal products possessing the same qualitative and quantitative composition in terms of active substances and the same pharmaceutical form.

Added:Section 3 Specific requirements for applications for certain categories of medicinal products

Added:Article 15 Fixed dose combination medicinal product, platform technologiesmarketing authorisation and multi-medicinal product packages [Am. 119]

Added:1. Where justified for therapeutic purposes, a marketing authorisation may be granted for a fixed dose combination medicinal product.

Added:2. Where justified for therapeutic purposes, a marketing authorisation may, in exceptional circumstances, be granted for a medicinal product comprised of a fixed component and a variable component that is pre-defined in order to, where appropriate, target different variants of an infectious agent or, where necessary, to tailor the medicinal product to characteristics of an individual patient or a group of patients (‘platform technologymarketing authorisation’). [Am. 120]

Added:An applicant that intends to submit an application for a marketing authorisation for such a medicinal product shall seek, in advance, the agreement concerning the submission of such application by the competent authority concerned.

Added:3. Where justified for public health reasons and when the active substances cannot be combined within a fixed dose combination medicinal product, a marketing authorisation may, in exceptional circumstances, be granted to a multi-medicinal product package.

Added:An applicant that intends to submit a an application for a marketing authorisation for such a medicinal product shall seek, in advance, the agreement concerning the submission of such application by the competent authority concerned.

Added:Article 16 Radiopharmaceuticals

Added:1. A marketing authorisation shall be required for radionuclide generators, kits for radiopharmaceutical preparations (‘kits’), and radionuclide precursors, unless they are used as starting material, active substance or intermediate of radiopharmaceuticals covered by a marketing authorisation under Article 5(1). [Am. 121]

Added:2. A marketing authorisation shall not be required for a radiopharmaceutical prepared at the time of use by a person or by an establishment authorised, according to national legislation, to use such radiopharmaceutical in an approved healthcare establishment exclusively from authorised radionuclide generators, kits or radionuclide precursors in accordance with the manufacturer's instructions.

Added:Article 17 Antimicrobials

Added:1. Where the application for a marketing authorisation concerns an antimicrobial, the application shall, in addition to the information referred to in Article 6, contain the following:

Added:(a) an antimicrobial stewardship and access plan as referred to in Annex I; [Am. 122]

Added:(b) a description of the special information requirements outlined in Article 69 and listed in Annex I.

Added:1a. The competent authority of the Member State shall, following the granting of a marketing authorisation, make publicly available the documents referred to in paragraph 1. [Am. 123]

Added:2. The competent authority mayshall review the information submitted in accordance with paragraph 1, point (b). The competent authority shall impose obligations on the marketing authorisation holder if it finds the risk mitigation measures contained in the antimicrobial stewardship and access plan unsatisfactory. [Am. 124]

Added:3. The marketing authorisation holder shall ensure, wherever possible, that the antimicrobial may be dispensed per unit in a number corresponding to the quantities corresponding to the duration of treatment. If an antimicrobial cannot be dispensed per unit, the marketing authorisation holder shall ensure that the pack size of the antimicrobial corresponds to the usual posology and duration of treatment. [Am. 125]

Added:Article 18 Integral combinations of medicinal products and medical devices

Added:1. For integral combinations of a medicinal product and a medical device the marketing authorisation applicant shall submit data establishing the safe and effective use of the integral combination of the medicinal product and the medical device.

Added:As part of the assessment, in accordance with Article 29, of the integral combination of a medicinal product and a medical device the competent authorities shall assess the benefit-risk balance of the integral combination of a medicinal product and a medical device, taking into account the suitability of the use of the medicinal product together with the medical device, where relevant particularly for paediatric patients, including aspects such as storage, assembly, cleanliness, and the technique required for application or intake. [Am. 126]

Added:2. The relevant general safety and performance requirements set out in Annex I of Regulation (EU) 2017/745 shall apply as far as the safety and performance of the medical device part of the integral combination of a medicinal product with a medical device are concerned.

Added:3. The application for a marketing authorisation for an integral combination of a medicinal product with a medical device shall include the documentation supporting the compliance of the medical device part with the general safety and performance requirements as referred to in paragraph 2 in accordance with Annex II, including, where relevant, the conformity assessment report by a notified body.

Added: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.

Added:5. The marketing authorisation applicant shall, upon request from the competent authority, submit any additional information related to the medical device and that is relevant for the benefit-risk balance assessment of the integral combination of a medicinal product with a medical device referred to in paragraph 1.

Added:Article 19 Medicinal products in exclusive use with medical devices

Added:1. For medicinal products in exclusive use with a medical device the marketing authorisation applicant shall submit data establishing the safe and effective use of the medicinal product taking into account its use with the medical device.

Added:As part of the assessment, in accordance with Article 29, of the medicinal product referred to in the first subparagraph, the competent authorities shall assess the benefit-risk balance of the medicinal product taking into account the use of the medicinal product together with the medical device.

Added:2. For medicinal products in exclusive use with a medical device the medical device shall meet the requirements set out in Regulation (EU) 2017/745.

Added:3. The application for a marketing authorisation for a medicinal product in exclusive use with a medical device shall include the documentation supporting the compliance of the medical device with the general safety and performance requirements as referred to in paragraph 2 in accordance with Annex II, including, where relevant, the conformity assessment report by a notified body.

Added:4. In its evaluation of the medicinal product referred to in paragraph 1 the competent authority shall recognise the results of the assessment of compliance of the medical device concerned 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.

Added:5. The marketing authorisation applicant shall, upon request from the competent authority, submit any additional information related to the medical device and that is relevant for the benefit-risk balance assessment of the medicinal product referred to in paragraph 1, taking into account the use of the medicinal product with the medical device.

Added:6. If the action of the medicinal product is not ancillary to that of the medical device, the medicinal product shall comply with the requirements of this Directive and of the [revised Regulation (EC) No 726/2004], taking into account its use with the medical device, without prejudice to the specific requirements of the Regulation (EU) 2017/745.

Added:In this case, the marketing authorisation applicant shall, upon request from the competent authorities, submit any additional information related to the medical device, taking into account its use with the medicinal product and that is relevant for the post-authorisation monitoring of the medicinal product, without prejudice to the specific requirements of the [revised Regulation (EC) No 726/2004].

Added:Article 20 Combinations of medicinal products with products other than medical devices

Added:1. For combinations of a medicinal product with a product other than a medical device, the marketing authorisation applicant shall submit data establishing the safe and effective use of the combination of the medicinal product and the other product.

Added:As part of the assessment, in accordance with Article 29, of the combination of a medicinal product with a product other than a medical device the competent authority shall assess the benefit-risk balance of the combination of a medicinal product and a product other than a medical device, taking into account the use of the medicinal product together with the other product.

Added:2. The marketing authorisation applicant shall, upon request from the competent authority submit any additional information related to the product other than medical devices and that is relevant for the benefit-risk balance assessment of the combination of medicinal products with the product other than medical devices, taking into account the suitability of the use of the medicinal product with the product referred to in paragraph 1.

Added:Section 4 Specific dossier requirements

Added:Article 21 Risk management plan

Added: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.

Added:Article 22 Environmental risk assessment and other environmental information

Added: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 duly justified reasons for any divergence from the scientific guidelines to the Agency or, as appropriate to the competent authority of the Member State concerned, in a timely manner. Where available, the applicant shall take into account existing ERAs performed under other Union legislation. [Am. 127]

Added:2. The ERA shall indicate whether the medicinal product or any of its ingredients or other constituents is one of the following substances according to the criteria of Annex I to the Regulation (EC) No 1272/2008:

Added:(a) persistent, bioaccumulative and toxic (PBT);

Added:(b) very persistent and very bioaccumulative (vPvB);

Added:(c) persistent, mobile and toxic (PMT), very persistent and very mobile (vPvM);

Added:or are endocrine active agents.

Added:3. The applicant shall also include in the ERA risk mitigation measures to avoid or where it is not possible, limit emissions to air, water and soil of pollutants listed in Directive 2000/60/EC, Directive 2006/118/EC, Directive 2008/105/EC and Directive 2010/75/EU during the manufacturing, use and disposal of the medicinal product. The applicant shall provide detailed explanation that the proposed mitigation measures are appropriate and sufficient to address the identified risks to the environment. Where necessary, the applicant shall also include information on available techniques and on the techniques that will be used to reduce the discharges and emissions of the medicinal product, in particular those occurring in manufacturing effluents before those effluents leave the manufacturing sites. [Am. 128]

Added:4. The ERA for antimicrobials shall include an evaluation of the risk for antimicrobial resistance selection in the environment due to the entire manufacturing supply chain inside and outside the Union, use and disposal, including by healthcare professionals and patients, of the antimicrobial taking into account, where relevant, the existing international standards that have established predicted no effect concentration (PNECs) specific for antibiotics. [Am. 129]

Added:4a. By ... [12 months from the date of entry into force of this Directive], the Commission shall, after having consulted the Agency, the EEA, and the ECDC, issue guidelines on how to conduct the ERA for antimicrobials other than antibiotics. [Am. 130]

Added:5. The Agency shall draw up scientific guidelines in accordance with Article 138 of [revised Regulation (EC) No 726/2004], to specify technical details regarding the ERA requirements for medicinal products for human use. Where appropriate, the Agency shall consult the European Chemical Agency (ECHA), the European Food Safety Authority (EFSA) and the European Environmental Agency (EEA), the EEA, the ECDC and other relevant stakeholders, including drinking water and wastewater operators, on the drafting of these scientific guidelines. [Am. 131]