Pharmaceutical package: extracts from adopted ENVI reports 

REGULATION

Conditional marketing authorisation

• “8 a. The Agency shall publish in the database referred to in Article 138(1)(n) the list of conditional marketing authorisations, together with the following information:

(a) specific obligations to be fulfilled by the marketing authorisation holder;

(b) timelines for compliance with specific obligations;

(c) any delays by the marketing authorisation holder regarding the fulfilment of obligations and the reasons for it;

(d) any actions on the conditional marketing authorisation taken in accordance with Article 56.” (Art. 19.8a new)

Scientific advice

• “4a.The Agency shall, to the greatest extent possible, ensure that there is a separation between those responsible for providing scientific advice to a given medicinal product developer and those subsequently responsible for the evaluation of the marketing authorisation application for the same medicinal product.

The Agency shall ensure that at least one of the two rapporteurs for a marketing authorisation application has not taken part in any pre-submission activities concerning the medicinal product. The reasons for any exceptions shall be documented and published with the European Public Assessment Report and recorded in the summary minutes of the meetings in accordance with Article 147(2).” (Art. 58.4a new)

Shortage prevention plan

• “By ... [18 months after 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.” (...) (Art. 117.1)

Monitoring and management of shortages

• Role of the competent authority of the Member State

“(-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;” (Art. 121.1 -a new)

(b) publish information and regularly update 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 proactively communicated to representatives of healthcare professionals and patients; competent authorities shall as soon as possible inform the Agency of any measure foreseen or taken at national level to mitigate the shortage or expected shortage. (Art. 121.1 b)

“(b a) create a system allowing patients to report shortages of medicinal products and request from pharmacies supplying hospitals and hospital pharmacies, to electronically communicate data on available stock of the respective medicinal product, in order to avert or mitigate an imminent or existing supply shortage relevant to the supply of a medicinal product.” (Art. 121.1 b a new)

“(c a) address recommendations to health professionals on the alternative medicinal products to use to pursue treatments in the event of shortages;” (Art. 121.1 c a new)

“(c b) consider the use of appropriate regulatory measures to mitigate the shortage.” (Art. 121.1 c b new)

National websites on medicines shortages

• “The website referred to in article 121 paragraph 1(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 in shortage;

(c) reasons of the shortages and mitigation measures taken to address the shortage;

(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.” (Art. 121 a new)

European Medicines Agency - transparency

• “2b. Patients, clinical experts and other relevant experts shall declare any financial and other interests relevant to the joint work in which they are due to participate. Such declarations and any actions taken as a result shall be recorded in the summary minutes of the meeting and in the outcome documents of the joint work in question.” (Art.147.2b new)
• “2 c. The Agency shall make available the rules of procedure, agendas, minutes and members of the Management Board, committees, working parties and advisory committees on its website.” (Art.147.2c new)

Orphan medicinal products - market exclusivity

• Where an orphan marketing authorisation is granted and without prejudice to intellectual property law, the Union and the Member States shall not grant a marketing authorisation or extend an existing marketing authorisation, for the same therapeutic indication, in respect of a similar medicinal product for the duration of market exclusivity set out in paragraph 2.

(a) nine years for orphan medicinal products other than those referred to in points (b) and (c);

(b) eleven years for orphan medicinal products addressing a high unmet medical need as referred to in Article 70;

(c) four years for orphan medicinal products which have been authorised in accordance with Article 13 of [revised Directive 2001/83/EC].

Regulatory sandboxes

• “(132 a) To better facilitate patient’ access to innovative medicines, it is appropriate to establish common rules for the testing and authorisation of innovative medicinal products and innovative technologies related to such products that, due to their exceptional nature or characteristics, are expected to not completely fit the EU medicines regulatory framework.” (Recital 132 a new)
• (132 b) On duly justified grounds, regulatory sandboxes may be set up when it is not possible to develop the medicinal product or category of products in compliance with the requirements applicable to medicinal products due to scientific or regulatory challenges arising from characteristics or methods related to the product, and those characteristics or methods positively and distinctively contribute to the quality, safety or efficacy of the medicinal product or category of products, or provide a major advantage contribution to patient access to treatment. (Recital 132 b new)
• (132 c) The objectives of the possibility to establish regulatory sandboxes under this Regulation are the following: for the Agency and national competent authorities to increase their understanding of technical and scientific developments, to allow developers in a controlled environment to test and develop innovative medicinal products and related technologies that are not fitting the current regulatory framework, as agreed with the competent authorities, and to identify possible future adaptations of the legal framework for the authorisation of medicinal products in the Union. (Recital 132 c new)
• Definition: ” (10) ‘regulatory sandbox’ means a regulatory framework during which it is possible to develop, validate and test in a controlled environment innovative or adapted regulatory solutions that facilitate the development and authorisation of innovative products which are likely to fall in the scope of this Regulation but for which there is an absence of existing adapted rules for development and authorisation, pursuant to a specific plan and for a limited time under regulatory supervision.” (Art. 2.2.10)

Priority antimicrobials

• Milestone payment reward scheme

“2. The Commission, in consultation with the Agency shall award milestone payments and support to potential priority antimicrobial products addressing the priority pathogens referred to in paragraph 1. The milestone payments shall be financed through resource matching by the Commission, including within the framework of Article 12 paragraph 2(b)(i) of Regulation (EU) 2021/695 and Regulation (EU) 2021/522.” (...) (Art 39 a new)

• Joint procurement of antimicrobials

“1. The Commission and any of the Member States may engage, as contracting parties, in a joint procurement procedure conducted pursuant to Article 165(2) of Regulation (EU, Euratom) 2018/1046 with a view to the advance purchase of antimicrobials.

1. A joint procurement procedure as referred to in paragraph 1 shall be preceded by a Joint Procurement Agreement between the parties determining the practical arrangements governing the subscription model system and other procedures including the length of the subscription contract and the possibility of the parallel procurement.
2. The joint procurement agreement shall take the form of a multi-year subscription and include the following conditions:

(a) delinkage or partial delinkage of funding from the volume of sales of the antimicrobial;

(b) commitment to continuous and sufficient supply in pre-agreed quantities;

(c) commitment to the stewardship and access plans as referred to in Article 17 of [revised Directive] ;

(d) commitment to the environmental risk assessment as referred to in Article 22 of [revised Directive];

(e) submission of a global access plan to supply third countries in critical need, including through development partners or voluntarily licensing.

1. Participation in the joint procurement procedure is open to all Member States and third countries, including the European Free Trade Association States and Union candidate countries, as well as the Principality of Andorra, the Principality of Monaco, the Republic of San Marino and the Vatican City State, by way of derogation from Article 165(2) of Regulation (EU, Euratom) 2018/1046.
2. The Commission shall inform the European Parliament about procedures concerning the joint procurement of antimicrobials and, upon request, grant access to the contracts that are concluded as a result of those procedures, subject to the adequate protection of business secrecy, commercial relations and the interests of the Union. The Commission shall communicate information to the European Parliament regarding sensitive documents in accordance with Article 9(7) of Regulation (EC) No 1049/2001.” (Art 39 b new)

• Transferable data exclusivity voucher

“1. Following a request by the applicant for a marketing authorisation, made before the marketing authorisation is granted, the Commission may, by means of implementing acts, grant a transferable data exclusivity voucher to a ‘priority antimicrobial’ referred to in Article 39a, paragraph 1, under the conditions referred to in paragraph 4 based on a scientific assessment by the Agency.” (Art. 40.1)

“2. The voucher referred to in paragraph 1 shall give the right to its holder to a maximum of additional 12 months of data protection for one authorised medicinal product.” (Art. 40.2)

“1. A voucher may be used to extend the data protection for a period of 12, 9 or 6 months of the priority antimicrobial or another medicinal product authorised in accordance with this Regulation of the same or different marketing authorisation holder. (Art.41.1)

A voucher shall only be used once and in relation to a single centrally authorised medicinal product and only if that product is within its first four years of regulatory data protection. The voucher shall not be used for a product which already benefited from maximum regulatory data protection period as set in Article 81 of [revised Directive 2001/83/EC]” (Art.41.1)

A voucher may be transferred to another marketing authorisation holder once and shall not be transferred further.

European Health Emergency Preparedness and Response Authority

• The Health Emergency Preparedness and Response Authority (hereafter ‘HERA’ or ‘the Authority’) is hereby established as a separate structure under the legal personality of the European Centre for Disease Prevention and Control (ECDC).

1. The Authority shall be responsible for creating, coordinating and implementing of the long-term European portfolio of biomedical research and development agenda for medical countermeasures against current and emerging public health threats as well as the, production, procurement, stockpiling and distribution capacity of medical countermeasures and other priority medical products in the EU. (...) (Article 175a new)

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DIRECTIVE

General

• New definitions for “platform technology”, “type 1 gene therapy medicinal product”, “type 2 gene therapy medicinal product”

Environmental risk assessment

• ERA 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 these effluents leave the manufacturing sites.” (Art. 22.3)
• “By ... [12 months after the date of entry into force of this Directive], the Commission shall, after having consulted the Agency, the European Environmental Agency (EEA), and the ECDC, issue guidelines on how to conduct the ERA for antimicrobials other than antibiotics.” (Art. 22.4a new)
• “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 or, as appropriate, by the competent authority of the Member State.” (Art. 22.7a new)
• “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 they can be identified as potentially harmful to the environment.” (Art. 47.1d new)

Marketing authorisation

• “Additional platform technology master files”

“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’).” (...) (Art. 26a new

Medicinal products subject to medical prescription (antimicrobials)

• Clarification: “is an antibiotic or any other antimicrobial for which there is an identified risk of antimicrobial resistance;” (Art. 51(e)) and “The Commission shall adopt implementing acts in accordance with the examination procedure referred to in Article 214(2) to add further antimicrobial products that shall be subject to prescription status where the Agency has identified a risk of antimicrobial resistance.” (Art. 51.1a new)
• “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 case a diagnostic test has not been performed, a justification shall be required.” (Art. 51.2a new)

Product information and labelling

• “Member States may decide that for individual products, categories of products or for all products, the package leaflet shall be made available both in paper format and electronically or electronically only. In the latter case, this decision shall be made only following a consultation of patients, carers and other relevant stakeholders.” (...) (Art. 63.3)
• “If a Member State has decided that the package leaflet is only to be made available electronically, patients shall be made aware of their right to a printed copy of the package leaflet.” (Art. 63.3a)
• “Each single dose of the blister pack shall include the following labelling particulars: (a) the name of the medicinal product followed by its strength and pharmaceutical form; (b) a data matrix code in which the following information is encoded: (i) the Global Trading Index Number (GTIN); (ii) the expiry date; (iii) the batch number.” (Art.66.2a new)
• “Members States shall introduce appropriate disposal systems for antimicrobials in the community setting, and inform the general public on the correct disposal methods for antimicrobial.” (Art. 69.3.1 new)

Regulatory data protection

• “The regulatory data protection period shall be seven years and six months from the date when the marketing authorisation for that medicinal product was granted in accordance with Article 6(2).” (...) (Art. 81.1)

(Subject to a scientific evaluation by the relevant competent authority, the data protection period referred to in paragraph 1 shall be prolonged by:)

• “12 months, where the marketing authorisation applicant demonstrates at the time of the initial marketing authorisation application that the medicinal product addresses an unmet medical need as referred to in Article 83;” (Art. 81.1)
• “six months, for medicinal products containing a new active substance, where the clinical trials supporting the initial marketing authorisation application use a relevant and evidence-based comparator in accordance with scientific advice provided by the Agency;” (Art. 81.1)
• six months, where the marketing authorisation holder demonstrates that a significant share of research and development, including preclinical and clinical, related to the medicinal product has been done within the Union and at least in part in collaboration with public entities, including University Hospital Institutes, centres of excellence or bioclusters in the Union. (Art. 81.1 - new)

“The regulatory protection referred to in paragraphs 1 and 2 shall not exceed eight years and six months.” (Art. 81.4 - new)

Market protection

• “2. A medicinal product concerned by a subsequent marketing authorisation referred to in paragraph 1 shall not be placed on the market for a period of two years after the expiry of the relevant regulatory data protection periods referred to in Article 81.” (Art.80.2 - Commission proposal)

2 a. The period referred in paragraph 2 shall be extended by an additional period of one year, where the marketing authorization holder obtains, during the data protection period referred to in Article 81, an authorisation for an additional therapeutic indication , provided that significant clinical benefit in comparison with existing therapies has been demonstrated by the marketing authorisation holder with supporting data. This extension may only be granted once. (Art. 80.2a new)

Pricing and reimbursement

• “Obligation to submit an application for pricing and reimbursement in all Member States”: “1. The marketing authorisation holder shall, upon request by a Member State in which the marketing authorisation is valid, in good faith and within the limits of its responsibilities submit an application for pricing and reimbursement for the medicinal product and, where relevant, negotiate. In case of a positive decision to permit the marketing of the medicinal product according to Directive 89/105/EEC, the obligation in article 56(3) to ensure appropriate and continued supply to cover the needs of patients in that Member State shall apply.” (...) (Art. 58a new)
• “EU Access to Medicines Notification System”

“1. The Commission shall set up and maintain an electronic notification system for the notification of compliance with the obligations set out in Article 58a. The EU Access to Medicines Notification System shall be interoperable with other relevant Union-wide data repositories for medicinal products.

The marketing authorisation holder shall use the EU Access to Medicines Notification System to notify their compliance with the obligations set out in Article 58a. In the Member States where the marketing authorisation is valid, the national competent authority shall use the EU Access to Medicines Notification System to indicate that the marketing authorisation holder has fulfilled its obligations set out in Article 58a.” (Art. 58b new)

Reporting on access to medicinal products

• “1. The Commission, in collaboration with the Member States, shall develop indicators to measure access to medicinal products within the EU. These indicators shall be evidence-based, measurable, and regularly reviewed to reflect the evolving healthcare landscape within the EU.

The Commission shall publish a report assessing access to medicinal products and barriers to improving access in each Member State as well as on an aggregated Union level. The report shall be publically available.

Based on the report, the Commission shall create a dedicated website with easily accessible information on the access indicators and access to medicinal products in the Union, intended for the general public and relevant stakeholders.” (Art. 86a new)

Member State pharmacovigilance system

• Additional responsibility: “(e a) facilitate the protection of patients in relation to adverse events through the development and implementation of plans for safe administration and handling of medicinal products, which may include the use of digital medication safety systems in hospitals and ambulatory care settings.” (Art. 97.1.ea new)

National medicines web-portal

• Additional information to be provided on portal (Art. 102.1)

“(b b) The outcome of the assessment of the ERA, including the data submitted by the marketing authorisation holder, in accordance with Article 22(7a new) and Article 29 (4a (new));

(d a) Where relevant, information related to antimicrobials, in accordance with Article 17(2) and Article 29 (4a (new));

(d b) Where relevant, the awareness card with information on antimicrobial resistance and the appropriate use and disposal of antimicrobials;

(d c) periodic safety update reports;

(d d) information on the shortage status of medicinal products as referred to in Article 121(1)(b) of [revised Regulation (EC) No 726/2004];”