Background note: pharmaceutical package provisional agreement elements 

Regulatory data and market protection periods

Regulatory data protection period: 8 years

Regulatory market protection period: 1 year

Additional regulatory market protection periods

The regulatory data market protection period (...) 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;

or

• for medicinal products containing a new active substance, fulfilling a combination of conditions on comparative clinical trials, clinical trials in several member states and the obligation to apply for market authorisation within 90 days after the submission of the application for the first marketing authorisation outside the Union

The regulatory market protection period shall be extended by an additional year if, during the regulatory data protection period (...), the marketing authorisation holder obtains an authorisation for one or more new therapeutic indications which, during the scientific evaluation prior to their authorisation and based on supporting data submitted by the marketing authorisation holder, are held to bring a significant clinical benefit in comparison with existing therapies. (DIR 81.2a)

Cap on total possible regulatory protection: 11 years

BOLAR exemption

The protection provided by patent rights, or supplementary protection certificates of medicinal products shall not be regarded as infringed when the necessary studies, trials and other activities are conducted for the purposes of:

• obtaining a marketing authorisation of medicinal products, in particular of generic, biosimilar, hybrid or bio-hybrid medicinal products and for subsequent variations;
• conducting health technology assessment (...)
• obtaining pricing and reimbursement. approval
• complying with subsequent practical requirements associated with activities referred (above)
• submitting an application on procurement tenders, in compliance with Union and national law, to the extent that it does not entail the sale or offering for sale or marketing of the medicinal product concerned during the protection period provided by patent rights or supplementary protection certificate

(DIR Art 85)

Orphan medicinal products

A medicinal product that is intended for the diagnosis, prevention or treatment of a life-threatening or chronically debilitating condition shall be granted an orphan designation where the orphan medicinal product sponsor can demonstrate that the following requirements are met:

(a) the condition affects not more than five in 10 000 persons in the Union when the application for an orphan designation is submitted and

(b) there exists no satisfactory method of diagnosis, prevention or treatment of the condition in question that has been authorised in the Union or, where such method exists, that the medicinal product would be of significant benefit to those affected by that condition. (REG Art 63)

The register of designated orphan medicinal products shall list all designated orphan medicinal products. It shall be set up and managed by the Agency and be publicly available. (REG Art 67)

Breakthrough orphan medicinal products = orphan medicinal products addressing a disease with no current available medicinal treatment, where it fulfils the following requirements:

• there is no medicinal product authorised in the Union for the orphan condition; and
• the use of the orphan medicinal product results in a clinically relevant reduction in disease morbidity or mortality for the relevant patient population.

Market exclusivity following an orphan marketing authorisation

The duration of market exclusivity shall be as follows:

• nine years for orphan medicinal products other than those referred to in points (b) and (c);
• eleven years for orphan medicinal products addressing a high unmet medical need as referred to in Article 70;
• four years for orphan medicinal products which have been authorised in accordance with Article 13 of [revised Directive 2001/83/EC].

(REG Art 71)

Paediatrics

Obligation to have a paediatric investigation plan (PIP)

(Paediatric provisions both in REG Chapter VII and in DIR Section 7 - Art. 48)

EMA (Committee for Medicinal Products for Human Use) responsible for agreeing PIP, (REG Art 77, 86 & DIR Art 48)

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Monitoring and management of shortages and critical shortages

Obligation on marketing authorisations holder (MAH) – ensure appropriate and continued supplies of that medicinal product to wholesale distributors, pharmacies or persons authorised to supply medicinal products (DIR Art 56.3)

Obligations on MAHs to notify market cessations, withdrawals, temporary suspensions and temporary disruptions and submit additional information (REG Art 116, Annex IV)

For temporary disruptions notification:

(d) a temporary disruption in supply of a medicinal product in a given Member State, of an expected duration of in excess of two weeks based on the demand forecast of the marketing authorisation holder, as soon as possible and in any event no less than six months before the start of such temporary disruption of supply. (REG Art 116.1d)

Shortage prevention plans to be put in place and updated by MAHs for medicinal products subject to prescription and medicinal products that would require a shortage prevention plan identified by the Commission (through delegated acts). (REG Art 117)

Monitoring of expected and actual shortages by both national competent authorities (for nationally and centrally authorised medicines) and EMA (for centrally authorised medicines), based on MAH notifications (REG Art 118)

The Agency (...) shall establish and update a list of critical shortages of Union concern (...) (REG Art 122)

In order to mitigate critical shortages of medicinal products, Member States may, on a voluntary basis and as a last resort, request to the MSSG the activation of the Voluntary Solidarity Mechanism for Medicines. The Voluntary Solidarity Mechanism for Medicines shall be coordinated by the MSSG and supported by the Agency.

The Voluntary Solidarity Mechanism for Medicines referred to in paragraph 1 may be activated by the MSSG on behalf of a requesting Member State where the following conditions are met:

1. a) The Agency has been notified of the critical shortage in accordance with Article 121(1)(c), and the shortage has been brought to the attention of the single point of contact working party referred to in Article 3(6) of Regulation (EU) 2022/123;
2. b) There are no or insufficient therapeutic alternatives available in the Member State concerned;
3. c) There are insufficient quantities of the medicinal product available in the Member State concerned to treat critical indications;
4. d) Import of stocks from third countries or other short-term measures do not provide a solution in a timely manner or in sufficient quantities;
5. e) There is a concrete risk of stockout in the Member State concerned within one month or less. (...)

(REG, new article)

Security of supply and the Union list of critical medicines

The competent authority of the Member State shall, after consultation with healthcare professionals and patient organisations, identify critical medicinal products in that Member State (...) REG, Art 127

EMA shall, in collaboration with the Medicine Shortages Steering Group (MSSG) and the Commission, ensure the following:

1. a) develop a common methodology to identify critical medicinal products (...) REG, Art 128

(...) MSSG shall propose a Union list of critical medicinal products authorised to be placed on the market of a Member State (...) and for which the coordinated Union level action foreseen in this chapter is necessary (“the Union list of critical medicinal products”).

The MSSG shall propose updates to the Union list of critical medicinal products to the Commission, where necessary, in particular taking into account the progress of vulnerability evaluation. REG, Art 131

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Transparency on public funding

The marketing authorisation holder shall declare to the public any direct financial support received from any public authority, publicly funded body, philanthropic organisation, or not-for-profit organisation or fund, irrespective of its geographic location, 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. (DIR Art. 57.1)

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Regulatory framework

Improved clarity on the interplay between EU legislative frameworks for medicines and for other health technologies (e.g. medical devices, substances of human origin)

DIR CHAPTER I. REG CHAPT. V

Regulatory sandboxes to test new and innovative therapies

The Commission may set up on a case-by-case basis a regulatory sandbox (...), where all of the following conditions are met:

(a) it is not possible to develop and authorise the medicinal product or category of medicinal products in full compliance with the requirements applicable to medicinal products set out in this Regulation and [revised Directive 2001/83/EC] due methods related to the medicinal product or due to the scientific or technical characteristics inherent to the medicinal product, for which certain targeted and technical adaptations to the requirements laid down in this Regulation and [revised Directive 2001/83/EC] are considered indispensable;

(b) the characteristics or methods referred to in point (a) are likely to, based on available scientific evidence, positively and distinctively contribute to the quality, safety or efficacy of the medicinal product or category of medicinal products in an at least equivalent manner to the standards set out in this Regulation [and revised Directive 2001/83/EC] or provide a major contribution to patient access to prevention, diagnosis, treatment, or patient care.

(REG Art 113)

Optimising EMA’s structure and simplifying regulatory procedures

Objectives and tasks of the Agency REG, Art 138

Administrative and management structure REG, Art 142

The Agency shall ensure that the opinion of the Committee for Medicinal Products for Human Use is given within 180 days after receipt of a valid application. (REG, Art 6.6)

Electronic submission of applications

In order to obtain a marketing authorisation, an electronic marketing authorisation application shall be submitted to the competent authority concerned in a common format. The Agency shall make available such format after consultation with the Member States. (DIR Art. 6.1, REG Art. 5.3, Art. 6.1)

Unlimited validity for marketing authorisation renewal as default

(...) A marketing authorisation for a medicinal product shall be valid for an unlimited period - (...) the Commission may decide when granting an authorisation, on the basis of a scientific opinion by the Agency concerning the safety of the medicinal product, to limit the validity of the marketing authorisation to five years (REG Art. 17).

Electronic product information

A package leaflet shall be mandatory for medicinal products. The package leaflet shall be made available by the marketing authorisation holder in the packaging in paper format and electronically in accordance with the specifications, standards and format specified by the implementing act (...) (DIR Art 63.1)

(...) Member States may decide that the package leaflet shall only be made available electronically by the marketing authorisation holder for specific categories of medicinal products or for all medicinal products, following a consultation of patients, healthcare professionals and other relevant stakeholders. It shall be ensured that the information in digital format is easily accessible to all patients. Where the package leaflet is only made available electronically, the patient’s right to a printed copy of the package leaflet shall be guaranteed upon request and free of charge. (...) (DIR Art 63.3)

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Prudent use of antimicrobials - additional measures

The marketing authorisation holder shall ensure, where the pack is intended for direct dispensing to patients, that the pack size of the antimicrobial corresponds to the usual posology and duration of treatment. (DIR Art. 17.3)

Antimicrobial stewardship plan

Where the application for a marketing authorisation concerns an antimicrobial, the application shall also contain a) an antimicrobial stewardship plan as referred to in Annex I and b) a description of the special information requirements outlined in Article 69 and listed in Annex I. (DIR Art. 17.1; Annex I)

Information requirements

Where Member States decide that the package leaflet is made available in the electronic format only(...), the information referred to in the previous subparagraph shall also be made available to patients in paper format (“awareness card”). The awareness card shall be presented in a distinct and immediately visible way. (...) (DIR Art. 69.2)

Special ERA for antimicrobials

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. (DIR Art. 22.4)

Compulsory prescription status

A medicinal product shall be subject to medical prescription where it (...) (e) is an antimicrobial (...). (DIR Art. 51.1)

Member States may set the following additional conditions on the prescription of antimicrobials (...):

(a) limiting the quantities prescribed to the amount required for the treatment or therapy concerned, or

(b) restricting the validity of medical prescription, or

(c) submitting certain antimicrobial medicinal products to special medical prescription or restricted prescription. (DIR Art 51.2)

Transferable data exclusivity vouchers

Following a request by the applicant when applying for a marketing authorisation, the Commission may, by means of implementing acts, grant a transferable data exclusivity voucher to a ‘priority antimicrobial’ (...)

[The voucher] shall give the right to its holder to an additional 12 months of data protection (...) for one authorised medicinal product.

(REG Art 40)

A voucher may be used to add 12 months of data protection (...) of the priority antimicrobial or another medicinal product authorised in accordance with this Regulation of the same or different marketing authorisation holder.

A voucher may used once only and in relation to a single centrally authorised medicinal product.

In case of a medicinal product other than the priority antimicrobial concerned, the use of the voucher can take place only in the fifth or sixth year of the regulatory data protection period and if the marketing authorisation holder demonstrates that the annual gross sales of that medicinal product in the Union during any of the preceding first four years after the granting of the marketing authorisation have not exceeded 490 million euros.

(REG Art 41)

Voluntary subscription model for the joint procurement of antimicrobials

1. Contracting authorities from different Member States may act jointly in the award of public contracts pursuant to Article 39 of Directive 2014/24/EU with a view to purchasing antimicrobials. (...)
2. The contract to be awarded shall take the form of a multi-year subscription and include at least the following conditions:

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

(b) arrangements regarding criteria to support continuous and sufficient supply and receive in pre-agreed quantities;

1. (...) the Commission shall, in consultation with Member States and relevant parties, draw up guidelines to identify the relevant components for a subscription model system, including the methodology for valuing and remunerating products to ensure economic viability of their supply, and incentives to encourage investment in priority antimicrobial product development.

(REG, new article)

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Strengthening the environmental risk assessment (ERA) in the marketing authorisation procedure

ERA means the evaluation of the risks to the environment, or risks to public health, posed by the release of the medicinal product in the environment from the use and disposal of the medicinal product and the identification of risk prevention, limitation and mitigation measures (...) (DIR Art 4.1.33)

Obligation to submit the ERA (DIR Art.6.2, Art. 22, Annex I.4)

ERA must indicate whether product/ingredients include any of the following: persistent, bioaccumulative and toxic (PBT); very persistent and very bioaccumulative (vPvB); persistent, mobile and toxic (PMT), very persistent and very mobile (vPvM); endocrine active agents. (DIR Art 22.2)

The marketing authorisation shall be refused if (...) (d) the environmental risk assessment is incomplete or insufficiently substantiated by the applicant or if the risks identified in the environmental risk assessment have not been sufficiently addressed (...) REG Art 15.1d

By 5 years from the date of application of this Directive, the Commission shall present a report to the European Parliament and the Council on the application of Article 22 and the impact of the Environmental Risk Assessment of medicinal products on the protection of human health and the environment. (...) The Commission shall, if appropriate, present legislative proposals based on that assessment in order to amend this Directive or make further proposals, including on expanding the scope of ERA to the manufacturing phase for all medicinal products. (DIR, new article)