Changes from plenary report to adopted text

AddedArticle 3 Centrally authorised medicinal products

RemovedArticle 104 – paragraph 1 – subparagraph 1 – point i: (i) conclusions of assessments, obligations for post-marketing studies, recommendations, opinions, approvals and decisions taken by the Agency and its Committees under this Regulation and [revised Directive 2001/83/EC].

Added1. A medicinal product listed in Annex I shall only be placed on the Union market if a marketing authorisation for that medicinal product has been granted by the Union in accordance with this Regulation (‘centralised marketing authorisation’).

RemovedArticle 104 – paragraph 1 – subparagraph 1 – point j: (j) conclusions of assessments, recommendations, opinions, approvals, obligations deriving from the conditional marketing authorisations and decisions taken by the coordination group, the competent authorities of the Member States and the Commission in the framework of the procedures set out in Articles 16, 106, 107 and 108 of this Regulation and of Chapter IX, Sections 3 and 7 of [revised Directive 2001/83/EC].

Added2. Any medicinal product not listed in Annex I, may be granted a centralised marketing authorisation in accordance with this Regulation, if the product meets at least one of the following requirements:

RemovedArticle 104 – paragraph 1 – subparagraph 2: The risk management plans referred to in point (c) shall include a description of any additional risk minimisation measures and distribution or implementation plans.

Added(a) the applicant shows that the medicinal product constitutes a significant therapeutic, scientific or technical innovation or that the granting of marketing authorisation in accordance with this Regulation is in the interest of patients' health at Union level, including as regards antimicrobial resistance and medicinal products for public health emergencies;

RemovedArticle 104 – paragraph 2: 2. In the development and review of the web portal, the Agency shall consult relevant stakeholders, including patient and consumer groups, healthcare professionals, not-for-profit entities and industry representatives.

Added(b) it is a medicinal product intended solely for paediatric use.

RemovedArticle 104 – paragraph 3 – subparagraph 1: The Agency shall, in collaboration with the Member States and the Commission, set up and maintain a register of environmental risk assessment studies conducted for the purpose of supporting an environmental risk assessment for medicinal products authorised in the Union.

Added3. Homeopathic medicinal products shall not be granted a marketing authorisation in accordance with this Regulation.

RemovedArticle 104 – paragraph 3 – subparagraph 2: Information in such register shall be publicly available and easily accessible on the Agency’s website, and shall include, as a minimum, the information reported in accordance with Section 1.6 of Annex II to [revised Directive 2001/83/EC], unless restrictions are necessary to protect commercially confidential information. For the purpose of setting up such register, the Agency shall, where not already received, request marketing authorisation holders and competent authorities to submit results of any such study already completed for products authorised in the Union within [OP please add the date = 24 months after the date of application of this Regulation].

Added4. The Commission shall grant and supervise centralised marketing authorisations for medicinal products for human use in accordance with Chapter II.

RemovedArticle 105 – paragraph 3: 3. The Agency shall, in consultation with the Commission, Member States and their relevant authorities, as well as other relevant parties, including experts from academia, draw up a detailed guide regarding the monitoring of medical literature and the entry of relevant information into the Eudravigilance database.

Added5. The Commission is empowered to adopt delegated acts in accordance with Article 175 to amend Annex I to adapt it to technical and scientific progress.

RemovedArticle 109 – paragraph 2: 2. The Agency and the Union Drugs Agency shall exchange information that they receive on the abuse of medicinal products including information related to illicit drugs.

AddedArticle 4 Member State authorisation of generics of centrally authorised medicinal products

RemovedArticle 111 – paragraph 1: The Agency and the Member States shall cooperate to continuously develop pharmacovigilance systems, including those that record adverse events including medication errors, processes and standards for medication safety, capable of achieving high standards of public health protection for all medicinal products, regardless of the routes of marketing authorisation, including the use of collaborative approaches, to maximise use of resources available within the Union.

AddedA generic medicinal product of a reference medicinal product authorised by the Union may be authorised by the competent authorities of the Member States in accordance with [revised Directive 2001/83/EC] under the following conditions:

RemovedArticle 113 – paragraph 1 – introductory part: 1. The Commission may set up on a case-by-case basis a regulatory sandbox pursuant to a specific sandbox plan, based on a recommendation of the Agency and pursuant to the procedure set out in paragraphs 4 to 7, where all the following conditions are met;

Added(a) the application for marketing authorisation is submitted in accordance with Article 9 of [revised Directive 2001/83/EC];

RemovedArticle 113 – paragraph 3: 3. The Agency shall monitor the field of emerging medicinal products and may request information and data from marketing authorisation holders, developers, independent experts and researchers, and representatives of healthcare professionals and of patients and may engage with them in preliminary discussions, where appropriate referring to the consultation mechanism provided for in Article 162.

Added(b) the summary of product characteristics and the package leaflet are in all relevant respects consistent with that of the medicinal product authorised by the Union.

RemovedArticle 113 – paragraph 4 – subparagraph 1: Where the Agency considers it appropriate to set up a regulatory sandbox for medicinal products which are likely to fall under the scope of this Regulation but for which there is an absence of existing adapted rules for development and authorisation, it shall provide a recommendation to the Commission. The Agency shall list eligible products or category of products in that recommendation and shall include the sandbox plan referred to in paragraph 1.

AddedPoint (b), first subparagraph, shall not apply to those parts of summary of product characteristics and package leaflet referring to indications, posologies, pharmaceutical forms, methods or routes of administration or any other way in which the medicinal product may be used which were still covered by a patent or a supplementary protection certificate for medicinal products at the time when the generic medicinal product was marketed and where the applicant for the generic medicinal product has requested not to include this information in their marketing authorisation.

RemovedArticle 113 – paragraph 5: 5. The Agency shall be responsible for developing a sandbox plan based on data submitted by developers of eligible products and following appropriate consultations including, where relevant, with patients, academia, health technology assessment bodies, healthcare professionals or developers. The plan shall set out clinical, scientific and regulatory justification for a sandbox, including the identification of the requirements of this Regulation, [revised Directive 2001/83/EC], Regulation (EC) 1394/2007 that cannot be complied with and a proposal for alternative or mitigation measures, where appropriate. The plan shall also include a proposed timeline for the duration of the sandbox. Where appropriate, the Agency shall also propose measures in order to mitigate any possible distortion of market conditions as a consequence of establishing a regulatory.

AddedChapter II GENERAL PROVISIONS AND RULES ON APPLICATIONS

RemovedArticle 113 – paragraph 6: 6. The Commission shall adopt delegated acts in accordance with Article 175 to supplement this Regulation by taking a decision on the set up of a regulatory sandbox taking into account the recommendation of the Agency and the sandbox plan pursuant to paragraph 4.

AddedSection 1 Application for centralised marketing authorisations

RemovedArticle 113 – paragraph 8 – subparagraph 1 – point b: (b) it is appropriate to protect public health or the environment.

AddedArticle 5 Submission of applications for marketing authorisations

RemovedArticle 113 – paragraph 9: 9. Where after the Decision to establish the regulatory sandbox in accordance with paragraph 6, risks to health are identified but these risks can be fully mitigated by the adoption of supplementary conditions, the Commission may, after consultation of the Agency, amend its decision by means of implementing acts. Those implementing acts shall be adopted in accordance with the examination procedure referred to in Article 173(2). The Commission is empowered to adopt delegated acts in accordance with Article 175 to supplement this Regulation by, on the basis of duly justified reasoning and evidence from the Agency, prolonging the duration of a regulatory sandbox.

Added1. The marketing authorisation holder for medicinal products covered by this Regulation shall be established in the Union. The marketing authorisation holder shall be responsible for the placing on the market of those medicinal products, whether done by that marketing authorisation holder or via one or more persons designated to that effect.

RemovedArticle 114 – paragraph 2: 2. A medicinal product developed as part of a regulatory sandbox may be placed on the market only when authorised in accordance with this Regulation. The initial validity of such authorisation shall not exceed the duration of the regulatory sandbox. The authorisation may, upon a justified recommendation by the Agency, be prolonged at the request of the marketing authorisation holder.

Added2. An applicant shall agree with the Agency the submission date of an application for a marketing authorisation.

RemovedArticle 114 – paragraph 3: 3. In duly justified cases, the marketing authorisation of a medicinal product developed under the regulatory sandbox may include derogations from the requirements set out in this Regulation and [revised Directive 2001/83/EC]. Any derogation from the requirements in context of the sandbox shall ensure that the level of patient safety and protection of public health and ethical principles are upheld. Those derogations may entail adapted, enhanced, waived or deferred requirements. Each derogation shall be limited to what is apt and strictly necessary to attain the objectives pursued, duly justified and specified in the conditions to the marketing authorisation.

Added3. An applicant shall submit an application for a marketing authorisation electronically to the Agency and in the formats made available by the Agency.

RemovedArticle 115 – paragraph 1 – subparagraph 2: Where such mitigation is not possible or proves to be ineffective, the development and testing process shall be suspended without delay until an effective mitigation takes place. If no effective mitigation plan can be provided, the Agency shall end the sandbox without undue delay.

Added4. The applicant shall be responsible for the accuracy of the information and documentation submitted with respect to its application.

RemovedArticle 115 – paragraph 4: 4. The Agency with input from Member States shall submit annual reports to the Commission on the results from the implementation of a regulatory sandbox, including a breakdown on the number of sandboxes granted, trends on medicinal products eligible for a regulatory sandbox, good practices, difficulties encountered, lessons learnt, reflections on possible future adaptations to the regulatory framework and recommendations on their setup and, where relevant, on the application of this Regulation and other Union legal acts supervised within the sandbox. These reports as well as lay summaries shall be made publicly available by the Commission.

Added5. Within 20 days of receipt of an application, the Agency shall check whether all the information and documentation required in accordance with Article 6 have been submitted, that the application does not contain critical deficiencies as defined in the guidelines drawn up pursuant to paragraph 7 of this Article that may prevent the evaluation of the medicinal product and decide whether the application is valid. [Am. 96]

RemovedArticle 116 – paragraph 1 – introductory part: 1. The marketing authorisation holder of a medicinal product in possession of a centralised marketing authorisation or a national marketing authorisation (‘the marketing authorisation holder’) shall notify and explain the reasons to the competent authority of the Member State where the medicinal product has been placed on the market and, in addition, the Agency for a medicinal product covered by a centralised marketing authorisation (these are referred to in this Chapter as ‘the competent authority concerned’) of the following:

Added6. Where the Agency considers that the application is incomplete, or contains critical deficiencies that may prevent the evaluation of the medicinal product, it shall inform the applicant accordingly and set a time limit for submitting the missing information and documentation. That time limit may be extended once by the Agency.

RemovedArticle 116 – paragraph 1 – point c: (c) its decision to temporarily suspend the marketing of a medicinal product in that Member State as soon as possible and no less than six months the start of the temporary suspension of supply of that medicinal product into the market of a given Member State by the marketing authorisation holder;

AddedUpon receipt of the responses from the applicant to the request to submit the missing information and documentation, the Agency will determine whether the application can be considered valid. Where the Agency refuses to validate an application, it shall notify the applicant and state the reasons for such refusal.

RemovedArticle 116 – paragraph 1 – point d: (d) a foreseeable temporary disruption in supply of a medicinal product in a given Member State, of an expected duration of in excess of two weeks or, based on the demand forecast of the marketing authorisation holder and national competent authorities, where available, as soon as possible and no less than six months before the start of such temporary disruption of supply or, if this is not possible and unforeseeable where duly justified, as soon as they become aware of such temporary disruption, to allow the Member State to monitor any potential or actual shortage in accordance with Article 118(1).

AddedIf the applicant fails to provide the missing information and documentation within the time limit, the application shall be considered to have been withdrawn.

RemovedArticle 117 – paragraph 1: 1. By ... [18 months from the date of entry into force of this Regulation], the marketing authorisation holder as defined in Article 116(1) shall have in place and keep up to date a shortage prevention plan, for any medicinal product placed on the market. To put in place the shortage prevention plan, the marketing authorisation holder shall include the minimum set of information set out in Part V of Annex IV and take into account the guidance drawn up by the Agency according to paragraph 2. The shortage prevention plan shall be made available upon request by the Agency or the competent authority of the Member State where the medicinal product has been placed on the market.

Added7. The Agency shall draw up scientific guidelines for the identification of critical deficiencies that may prevent the evaluation of a medicinal product, in consultation with the European Commission and the Member States.

RemovedArticle 117 – paragraph 2: 2. The Agency shall, in collaboration with the working party referred to in Article 121(1) and after consultation with the Healthcare Professionals' Working Party (HPWP) and the Patients' and Consumers' Working Party (PCWP), draw up guidance to marketing authorisation holders as defined in Article 116(1) to put in place the shortage prevention plan.

AddedArticle 6 Centralised marketing authorisation application

RemovedArticle 118 – paragraph 1 – subparagraph 1: Based on the reports referred to in Articles 120(1) and 121(1), point (c), information referred to in Articles 119, 120(2) and 121 and the notification made pursuant to Article 116(1), points (a) to (d), the competent authority concerned as referred to in Article 116(1) shall continuously monitor any potential or actual shortage of those medicinal products through their national IT surveillance systems or data bases and send the information to the Agency without undue delay.

Added1. Each application for a centralised marketing authorisation of a medicinal product for human use shall specifically and completely include the particulars and documentation as referred to in Chapter II of [revised Directive 2001/83/EC]. In the case of applications in accordance with Article 6(2), Article 10 and Article 12 of [revised Directive 2001/83/EC], this shall include the electronic submission of raw data, in accordance with Annex II of that Directive.

RemovedArticle 118 – paragraph 1 a (new): 1a. On the basis of the information provided pursuant to Article 121(2), point (f), the Agency shall monitor and assess any actions planned or taken by a Member State to mitigate a shortage at national level with regard to their impact on the availability and supply of medicinal products at Union level.

AddedThe documentation shall include a declaration to the effect that clinical trials carried out outside the Union meet the ethical requirements of Regulation (EU) No 536/2014. Those particulars and documentation shall take account of the unique, Union nature of the authorisation requested and, otherwise than in exceptional cases relating to the application of the law on trademarks pursuant to Regulation (EU) 2017/1001 of the European Parliament and of the Council, shall include the use of a single name for the medicinal product. The use of a single name does not exclude:

RemovedArticle 118 – paragraph 2: 2. For the purposes of paragraph 1, the competent authority concerned as defined in Article 116(1) may request any additional information from the marketing authorisation holder as defined in Article 116(1). In particular, it may request the marketing authorisation holder to submit a shortage mitigation plan in accordance with Article 119(2), a risk assessment of impact of suspension, cessation or withdrawal in accordance with Article 119(3), or the shortage prevention plan referred to in Article 117. The competent authority concerned shall set a deadline for the submission of the information requested.

Added(a) the use of additional qualifiers where necessary to identify different presentations of the medicinal product concerned; and.

RemovedArticle 120 – paragraph 1: 1. Wholesale distributors and other persons or legal entities that are authorised or entitled to supply medicinal products authorised to be placed on the market of a Member State pursuant to Article 5 of [revised Directive 2001/83/EC] to the public shall report a shortage of a given medicinal product marketed in the Member State concerned to the competent authority in that Member State. In addition, wholesale distributors shall submit regular information on the available stocks of the medicinal products they supply to the competent authority.

Added(b) the use of identified versions of the summary of product characteristics as referred to in Article 62 of [revised Directive 2001/83/EC] in situations where elements of the product information are still covered by patent law or supplementary protection certificates for medicinal products. [Am. 97]

RemovedArticle 120 – paragraph 1 a (new): 1a. When a marketing authorisation holder notifies a temporary disruption in supply of a medicinal product, wholesale distributors as well as other persons or legal entities that are authorised or entitled to supply medicinal products shall provide information upon request in a timely manner to the Agency, the competent authority in a Member State and the relevant marketing authorisation holder on the reasons for the temporary disruption in supply of the product in a Member State.