What changed between the plenary report and the adopted text

Added:(109) There may be cases where manufacturing or testing steps of medicinal products need to take place in sites close to patients, for example advanced therapy medicinal products with short shelf-life. In such cases, these manufacturing or testing steps may need to be decentralised to multiple sites to reach patients across the Union. When the manufacturing or testing steps are decentralised, they should be carried out under the responsibility of the qualified person of an authorised central site. Additionally, in order to ensure the smooth functioning of decentralised sites under this framework with the activities relevant for other Union legal frameworks, competent authorities of Member States supervising the decentralised site should coordinate their activities and supervisory tasks with the relevant authorities responsible for the supervision of the manufacturing or testing activities under other Union acts. The decentralised sites should not require a separate manufacturing authorisation from the one granted to the relevant central site but should be registered by the competent authority of the Member State in which the decentralised site is established. In the case of medicinal products containing, consisting or derived from autologous SoHO, the decentralised sites have to be registered as a SoHO entity as defined in and pursuant to [SoHO Regulation] for the activities of donor review and eligibility assessment, donor testing and collection, or just for collection in the case of products manufactured for autologous use. [Am. 64]

Removed:Article 24 – paragraph 4: 4. The Agency in cooperation with the competent authorities of the Member States shall conduct a proof-of-concept pilot of ERA monographs to be completed within 30 months after entering into force of this Directive, while taking into account outcomes from relevant Union initiatives with regard to animal testing.

Added:(110) The quality of medicinal products manufactured or available in the Union should be guaranteed by requiring that the active substances used in their composition comply with the principles of good manufacturing practice in relation to those medicinal products. It has proved necessary to reinforce the Union provisions on inspections and to compile a Union database of the results of those inspections.

Removed:Article 26 – paragraph 3 – point b: (b) additional quality master files for which a certificate may be used in order to provide specific information on the quality of a substance, preparation or other material present or used in the manufacture of a medicinal product, including cell therapies and gene therapies;

Added:(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.

Removed:Article 26 a (new): Article26a / Additional platform technology master files / 1. Marketing authorisation applicants may, instead of submitting the relevant data related to a platform technology, rely on an additional platform technology master file or an additional platform technology master file certificate granted by the Agency in accordance with this Article (‘additional platform technology master file certificate’). / 2. Article 25(1) to (5), (7) and (8) shall also apply mutatis mutandis to additional platform technology master file certificates. / 3. To adequately describe the platform technology master file, appropriate information as laid down in scientific guidelines published by the Agency shall be provided. / 4. The Commission is empowered to adopt delegated acts in accordance with Article 215 to supplement this Directive by specifying: / (a) the rules governing the content and format of the application for an additional platform technology master file certificate; / (b) additional platform technology master files for which a certificate may be used in order to provide specific information on the platform technology on the basis of which a substance present or used in the manufacturing of a medicinal product is manufactured; / (c) the rules for the examination of applications for making publicly available of additional platform technology master file certificates; / (d) the rules for introducing changes to the additional platform technology master file and the certificate; / (e) the r…

Added:(112) The frequency of controls should be established by the competent authorities having regard to the risk and to the level of compliance expected in different situations. That approach should allow those competent authorities to allocate resources where the risk is the highest. In some cases, the system of supervision should be applied irrespective of the level of risk or suspected non-compliance, for example prior to granting manufacturing authorisations.

Removed: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. The opinion of the Agency shall be adopted by the Committee for Medicinal Products for Human Use.

Added:(113) Within the procedure for "Certification of Suitability to the monographs of the European Pharmacopoeia" the European Directorate for the Quality of Medicines and Healthcare verifies by means of inspections whether the data submitted by the applicant established by the Council of Europe confirms the suitability of monographs to control the chemical purity, microbiological quality and TSE risk (if relevant). It also verifies whether the manufacturing complies with good manufacturing practice for active substances. Depending of the outcome of the inspection, a certificate of compliance or non-compliance of good manufacturing practice, is issued by the European Directorate for the Quality of Medicines and Healthcare or by the Member State participating in the inspection.

Removed: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 shall, in such cases, request the opinion from the Agency.

Added:(114) Each undertaking that manufactures or imports medicinal products should set up a mechanism to ensure that all information supplied about a medicinal product conforms to the approved conditions of use.

Removed:Article 28 – paragraph 6 a (new): 6a. The Commission shall submit a report on the application of adapted frameworks to the European Parliament and to the Council. The first report shall be submitted five years from [OP please insert the date =18 months from the date of entry into force of this Directive] and then every five years thereafter.

Added:(115) The conditions governing the supply of medicinal products to the public should be harmonised.

Removed:Article 29 – paragraph 3: 3. Where the competent authority of the Member State considers that the marketing authorisation application is incomplete, or contains critical deficiencies that may prevent the evaluation of the medicinal product it shall inform the applicant accordingly and shall set a time limit for submitting the missing information and documentation. If the applicant fails to provide the missing information and documentation within the time limit set, the application shall be considered to have been withdrawn by default.

Added:(116) In this connection persons moving around within the Union have the right to carry a reasonable quantity of medicinal products lawfully obtained for their personal use. It should also be possible for a person established in one Member State to receive from another Member State a reasonable quantity of medicinal products intended for their personal use.

Removed:Article 29 – paragraph 4 – subparagraph 2: The competent authority of the Member State shall summarise the deficiencies in writing. On this basis, the competent authority of the Member State shall inform the applicant accordingly and set a reasonable time limit to address the deficiencies. The application shall be suspended until the applicant addresses the deficiencies. If the applicant fails to address those deficiencies within the time limit set by the competent authority of the Member State, the application shall be considered as withdrawn by default.

Added:(117) By virtue of [revised Regulation (EC) No 726/2004], certain medicinal products are the subject of a Union marketing authorisation. In this context, the prescription status of medicinal products covered by a Union marketing authorisation needs to be established. It is therefore important to set the criteria on the basis of which Union decisions will be taken.

Removed:Article 29 – paragraph 4 a (new): 4a. When making public the information on the ERA and the antimicrobial stewardship and access plan referred to in Article 17, the competent authority shall delete any information of a commercially confidential nature.

Added:(118) It is therefore appropriate to harmonise the basic principles applicable to the prescription status of medicinal products in the Union or in the Member State concerned, while taking as a starting point the principles already established on this subject by the Council of Europe as well as the work of harmonisation completed within the framework of the United Nations, concerning psychotropic or narcotic substances - the United Nations Single Convention of 1961 on narcotic drugs and Convention on Psychotropic Substances of 1971.

Removed:Article 34 – paragraph 3: 3. The competent authority of the reference Member State for the decentralised procedure shall inform the Coordination group for decentralised and mutual recognition procedures of an application, which shall thereafter notify the competent authorities of all Member States. The competent authority of a Member State may request for justified public health reasons to enter the procedure and shall inform the applicant and the competent authority of the reference Member State for the decentralised procedure of its request within 30 days from the date of submission of the application. The applicant shall provide the competent authorities of those Member States entering the procedure with the application without undue delay.

Added:(119) Many operations involving the wholesale distribution of medicinal products may cover several Member States simultaneously.

Removed:Article 34 – paragraph 4 – subparagraph 2: The competent authority of the reference Member State for the decentralised procedure shall summarise the deficiencies in writing. On this basis, the competent authority of the reference Member State for the decentralised procedure shall inform the applicant and the competent authorities of the Member States concerned accordingly and set a time limit to address the deficiencies. The application shall be suspended until the applicant addresses the deficiencies. If the applicant fails to address those deficiencies within the time limit set by the competent authority of the reference Member State for the decentralised procedure, the application shall be considered as withdrawn by default.

Added:(120) It is necessary to exercise control over the entire chain of distribution of medicinal products, from their manufacture or import into the Union through to supply to the public, so as to guarantee that such products are stored, transported and handled in suitable conditions. The requirements that should be adopted for this purpose will considerably facilitate the withdrawal of defective products from the market and allow more effective efforts against counterfeit products.

Removed:Article 36 – paragraph 4: 4. The competent authority of the reference Member State for the decentralised procedure shall inform the Coordination group for decentralised and mutual recognition procedures of an application, which shall thereafter notify the competent authorities of all Member States. The competent authority of a Member State may request for justified public health reasons to enter the procedure and shall inform the applicant and the competent authority of the reference Member State for the mutual recognition procedure of its request within 30 days from the date of submission of the application. The applicant shall provide the competent authorities of those Member States entering the procedure with the application without undue delay.

Added:(121) Any person involved in the wholesale distribution of medicinal products should be in possession of a special authorisation. Pharmacists and persons authorised to supply medicinal products to the public, and who confine themselves to this activity, should be exempt from obtaining this authorisation. It is however necessary, in order to control the complete chain of distribution of medicinal products, that pharmacists and persons authorised to supply medicinal products to the public keep records showing transactions in products received.

Removed:Article 37 – paragraph 2 – subparagraph 1: The coordination group shall be composed of one representative per Member State and one representative from patients’ organisations appointed for a renewable period of three years. Alternates may be appointed for a renewable period of three years. Members of the coordination group may arrange to be accompanied by experts.

Added:(122) Marketing authorisation is to be subject to certain essential conditions and it is the responsibility of the Member State concerned to ensure that such conditions are met; whereas each Member State is to recognize authorisations granted by other Member States.

Removed: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.

Added:(123) Certain Member States impose on wholesalers who supply medicinal products to pharmacists and on persons authorised to supply medicinal products to the public certain public service obligations. Those Member States should be able to continue to impose those obligations on wholesalers established within their territory. They should also be able to impose them on wholesalers in other Member States on condition that they do not impose any obligation more stringent than those that they impose on their own wholesalers and provided that such obligations may be regarded as warranted on grounds of public health protection and are proportionate in relation to the objective of such protection.

Removed: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 leaflet, the antimicrobial stewardship and access plan and special information requirements referred to in Article 17(1), points (a) and (b), as well as any conditions established in accordance with Articles 17, 44, 45 and any obligations imposed subsequently in accordance with Article 87, together with any deadlines for the fulfilment of those conditions and obligations for each medicinal product that they have authorised.

Added:(123a) Pharmacists and other health care professionals have an important role in primary care, particularly to compound, dispense and sell medicinal products that patients need, to provide advice on their proper use and possible adverse effects and to support patients suffering of acute and chronic illnesses. In a hospital environment, hospital pharmacists set up pharmaceutical consultations and designate personalised pharmaceutical plans, in cooperation with other health professionals, patients and carers. Hospital pharmacists and community pharmacists could play a significant role in the use of electronic package leaflets, as well as for understanding the information contained in paper leaflets. [Am. 65]

Removed:Article 43 – paragraph 4: 4. The competent authority of the Member State may consider and decide upon additional evidence available, independently from the data submitted by the marketing authorisation holder. On that basis, the summary of product characteristics shall be updated if the additional evidence has an impact on the benefit-risk balance of a medicinal product. The competent authority shall inform the marketing authorisation holder of its decision, including the grounds for that decision, without unnecessary delay.

Added:(124) Rules should be laid down as to how the labelling and package leaflets are to be presented. The package leaflet should be easily legible, clearly comprehensible by users, including especially the target patient groups, and indelible. Patient leaflets are in the category of consultative reading which means that relevant information should be found without reading the whole leaflet. For readability and legibility, the package leaflet can benefit from a typographic hierarchy and a legible typeface. Design choices should primarily serve function and readability, rather than aesthetics. [Am. 66]

Removed:Article 44 – paragraph 1 – subparagraph 1 – point g: (g) in case of medicinal products for which, on duly justified grounds set out in the assessment report, there is substantial uncertainty as to the surrogate endpoint relation to the expected health outcome, where appropriate and relevant for the benefit-risk balance, with particular attention to new active substances and therapeutic indications, a post-authorisation obligation to substantiate the clinical benefit;

Added:(125) Sharing accurate information with the general public in order to promote trust in science and the regulatory system and supporting health literacy of patients and consumers is crucial. Where relevant, competent authorities should also share up to date information with healthcare professionals, including pharmacists, and the scientific community. The provisions governing the information supplied to users should provide a high degree of consumer protection, in order that medicinal products may be used correctly on the basis of full and comprehensible information. [Am. 67]

Removed:Article 47 – paragraph 1 – point d: (d) the environmental risk assessment is incomplete or insufficiently substantiated, and the reason for the incomplete nature of the environmental risk assessment is not duly justified and substantiated by the applicant, or if the risks identified in the environmental risk assessment have not been sufficiently addressed by the applicant or by the risk mitigation measures included by the applicant, in accordance with Article 22(3);

Added:(126) The marketing of medicinal products whose labelling and package leaflets comply with this Directive should not be prohibited or impeded on grounds connected with the labelling or package leaflet.

Removed:Article 47 – paragraph 1 – point d a (new): (da) For medicinal products where the reference medicinal product received its first marketing authorisation before 30 October 2005, the national marketing authorisation may be refused if the view is taken that the environmental risk assessment is incomplete or insufficiently substantiated and those medicinal products can be identified as potentially harmful to the environment.

Added:(127) The use of electronic and technological possibilities other than paper package leaflets, which is complementary to the paper leaflets which are crucial for patients with limited digital health literacy, can facilitate access to medicinal products, medicinal products distribution and should always guarantee equal or better quality of information to all patients compared to the paper form of product information. Ensuring the protection of personal data in accordance with Regulation (EU) 2016/679 and prevention of the identification, profiling or tracking of individuals is necessary in that regard. [Am. 68]

Removed: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 conclusions of the assessment regarding compliance with the agreed completed paediatric investigation plan publicly available.

Added:(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 StatesA package leaflet should progressively allow the possibility forbe made available electronically and be included in paper format, except where the Member State, following a consultation, decides to make only the electronic product information, while ensuring available. Electronic product information should be available in full compliance with the rules on protection of personal data, and adhere to harmonised standards developed at EU level. The information in digital format should be easily accessible to all patients. Based on the findings from hospital pilots, the obligation to provide a paper leaflet should not be applied for medicinal products which are not intended for self-administration by the patient. [Am. 69]

Removed:Article 51 – paragraph 1 – point e: (e) is an antibiotic or any other antimicrobial for which there is an identified risk of antimicrobial resistance; or

Added:(129) Where Member States decide thatshould make the package leaflet should be made available electronically and in paper format, except where the Member State decides to make only the electronic product information available. Where the package leaflet is only availablein principle only electronically, theyMember States should also ensure that a paper version of the package leaflet is to be made available on demand and without additional cost to patients. They should also ensure that the information in digital format is easily accessible to all patients, for instance by including in the outer packaging of the product a digitally readable barcode, which would direct the patient to the electronic version of the package leaflet. [Am. 70]

Removed:Article 51 – paragraph 1 – point f: (f) contains an active substance, adjuvants or any other ingredients or constituent parts which are persistent, bioaccumulative and toxic, or very persistent and very bioaccumulative, or persistent, mobile and toxic, or very persistent and very mobile for which medical prescription is required as risk minimisation measure with regard to the environment, unless the use of the medicinal product and the patient safety require otherwise.

Added:(130) The use of multi-language packages can be a tool for access to medicinal products, in particular for small markets and in public health emergencies. Where multi-language packages are used, Member States may allow the use on the labelling and package leaflet of an official language of the Union that is commonly understood in the Member States where the multi-language package is marketed. While electronic medicinal product information can facilitate the redistribution of packages between Member States, language requirements on labels can remain a challenge. The granting of an exemption to the requirement for an official language, as well as the obligation to use the international non-proprietary name for medicinal products not intended for self-administration by the patient, in addition to providing electronic product information, could improve the availability of medicinal products and enable easier redistribution between Member States. [Am. 71]

Removed:Article 51 – paragraph 1 a (new): 1a. The Commission shall adopt implementing acts to add further antimicrobial products that shall be subject to prescription status where the Agency has identified a risk of antimicrobial resistance. Those implementing acts shall be adopted in accordance with the examination procedure referred to in Article 214(2).

Added:(131) To ensure a high level of transparency of public support to the research and development of medicinal products, the reporting of public contribution for the development of a particular medicinal product should be a requirement for all medicines. Given however the practical difficulty to identify in third countries how indirect public funding instruments, such as tax advantages, have supported a particular product, the reporting obligation on financial support from entities outside of the Union should only concern the direct public financial support, such as direct grants or contracts. Therefore, the provisions of this Directive ensure, without prejudice to the rules on the protection of confidential and personal data, transparency regarding any direct financial support received from any public authority or public body or philanthropic or not-for-profit organisation or fund to carry out any activities for the research and development of medicinal products. [Am. 72]

Removed:Article 51 – paragraph 2: 2. Member States may set additional conditions on the prescription of antimicrobials, restrict the validity of medical prescription and limit the quantities prescribed to the amount required for the treatment or therapy concerned by authorising the use of pre-cut blister units or submitting certain antimicrobial medicinal products to special medical prescription or restricted prescription.

Added:(132) To ensure the accuracy of the information made publicly available by the marketing authorisation holder, the declared information has to be subject to audit by an independent auditor.

Removed:Article 51 – paragraph 2 a (new): 2a. A prescription for antibiotic products shall be subject to the following conditions: / (a) be limited to the amount required for the treatment or therapy concerned; / (b) only be prescribed for a limited duration to cover the period of risk when used as prophylaxis; / (c) in the event that a diagnostic test has not been performed, a justification shall be required.

Added:(133) In order to ensure a harmonised and consistent reporting of public contribution for the development of a particular medicinal products, the Commission should be able to adopt implementing acts to clarify the principles and format that the marketing authorisation holder should adhere to when reporting this information.

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

Added:(134) This Directive is without prejudice to the application of measures adopted pursuant to Directive 2006/114/EC of the European Parliament and of the Council or pursuant to Directive 2005/29/EC of the European Parliament and of the Council. Therefore the provisions regarding the advertising of medicinal products of this Directive should therefore be considered, where relevant, as a lex specialis with respect to Directive 2005/29/EC.

Removed:Article 51 – paragraph 4 – point c a (new): (ca) the risk of antimicrobial resistance, including any mitigating measures in that regard, from use of the medicinal product

Added:(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 Council. 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.

Removed:Article 51 – paragraph 5 – point b: deleted

Added:(135a) Clear, impartial and independent information from healthcare professionals to the public about a medicinal product and its correct use can play an important role in informing citizens and combatting misinformation, in particular during health emergencies such as the COVID-19 pandemic. Member States should ensure that the ability of healthcare professionals to share clear, impartial and independent information, whether in a direct conversation with a patient or in broader communication, should not be hindered. [Am. 73]

Removed:Article 57 – paragraph 1: 1. The marketing authorisation holder shall declare to the public any direct financial support received from any public authority, publicly funded body or philanthropic or not-for-profit organisation or fund, irrespective of its geographic location, and any indirect financial support received from any public authority or publicly funded body of the Union or its Member States in relation to any activities for the research and development of the medicinal product covered by a national or a centralised marketing authorisation, irrespective of the legal entity that received that support.

Added:(136) Advertising of medicinal products should aim at disseminating objective and unbiased information about the medicinal product. For that purpose, it is expressly forbidden highlight negatively another medicinal product or to suggest that advertised medicinal product might be safer or more effective than another medicinal product. Comparison of medicinal products should only be allowed if such information is listed in the summary of product characteristics for the relevant indications and patient population of the medicinal product being advertised. This prohibition covers any medicinal product, also biosimilars, and therefore it would be misleading to refer in the advertising, that a biosimilar medicinal product would not be interchangeable with the original biological medicinal product or another biosimilar from the same original biological medicinal product. Additional strict rules about negative and comparative advertising of competitor medicinal products will prohibit claims that can mislead persons qualified to prescribe, administer or supply them. [Am. 74]

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