Out of focus: EC proposals for changes in the European pharmaceutical legislation that went unnoticed – Part I

16 May 2023

On 26 April 2023, the European Commission presented its long-awaited proposal for a comprehensive reform of the European pharmaceutical legislation. The reform aims to replace Directive 2001/83/EC on the Community code relating to medicinal products for human use with a new Directive (“the Directive”) and the integration into a new general regulation (“the Regulation”) of the Regulations establishing the European Medicines Agency and the centralised procedure for the authorisation of medicinal products (Regulation No 726/2004), orphan medicinal products (Regulation No 141/2000), advanced therapy medicinal products (Regulation No 1394/2007) and medicinal products for paediatric use (Regulation No 1901/2006). The idea for codification of European pharmaceutical legislation aims not only to make it easier to work with the legislative acts, but to implement several key EU policies that the European Commission considers have not enjoyed satisfactory progress thus far. The focus is on equal access to innovative medicines in all EU Member States, the fight against antimicrobial resistance, and measures to address the shortage of key medicinal products on the European market, etc.

All these priorities of the European Commission should also be key priorities of the Bulgarian state, which, according to publicly available data, has access to only about 30% of recently authorised medicines in the EU, where the use of antibiotics (and therefore antimicrobial resistance) is at alarmingly high levels, and the shortage of key medicines is a daily topic in the media and an unpleasant fact in the life of us all. According to EFPIA data, as of 5 January 2023, out of 168 new therapies approved for the entire EU, Bulgaria has access to only 56.

Due to the importance of the topic, as well as the multitude of information and support materials of the European Commission accompanying the proposed overhaul, the reform of the European pharmaceutical legislation found leading coverage in most Bulgarian media, including those that do not specialize in medical or legal topics.

At the same time, due to the volume of the legislative acts proposed by the European Commission and the huge number of changes envisaged by them, the majority of attention was paid to a limited part of the changes envisaged by the proposals for new Regulation and Directive – those concerning the reduced regulatory data protection periods and the various incentives to increase them, including incentives to develop new antimicrobial medicines, as well as measures to address drug shortages.

Overshadowed by the aforementioned, many other key changes in the two pieces of legislation remained “under the radar” of media attention. With this article we would like to draw attention to these changes, many of which are of comparably important for pharmaceutical companies and the European healthcare sector, as a whole.

I. Introduction of new sub-types of medicinal products

The proposal for a European Commission Directive introduces definitions and specific rules for many new sub-types of medicinal products, including:

  • hybrid medicinal products (Art. 10 of the Directive)and bio-hybrid medicinal products (Art. 12 of the Directive)– medicinal products similar to generics that do not meet the definition of a generic medicinal product due to changes in the strength, pharmaceutical form, route of administration or therapeutic indications, compared to the reference medicinal product. Regarding these medicinal products, the draft Directive stipulates that the marketing authorisation applicant shall submit results of non-clinical tests or clinical studies to the extent necessary to establish a scientific bridge between the hybrid medicinal product and the reference medicinal/biological product, specified in the application. This enables the applicant to benefit from the clinical and preclinical data submitted during the registration procedure of the reference product;
  • antimicrobial medicinal products (Article 17 of the Directive) – The European Commission is elevating antimicrobial medicinal products to a separate category of medicinal products, since under the proposal they will be subject to additional requirements before their authorisation, including a requirement to attach to the application an antimicrobial stewardship plan, that shall outline the mitigation measures to address antimicrobial resistance that is expected to gradually arise as a result of the prescription and use of the medicinal product;
  • integral combinations of medicinal products and medical devices (Article 18 of the Directive), medicinal products in exclusive use with medical devices (Article 19 of the Directive) and combinations of medicinal products with products other than medical devices (Article 20 of the Directive) – in the procedure for their marketing authorisation, the applicant shall submit, together with data on the safety of the medicinal product and the medical device/products other than medical devices, when used separately, safety data for their combined use as a single product;

II. Changes to the authorisation procedure for medicinal products

The drafts of the new Directive and Regulation provide for comprehensive changes in the procedure for the authorisation of medicinal products in all its phases – the preliminary phase (while clinical trials are being carried out and the application is being prepared), types of applications and marketing authorisations (“MAs“), examination of the application, issuance and validity of the MA, etc.:

  • The draft Regulation provides that the European Medicines Agency (“EMA”) may provide scientific and regulatory support to pharmaceutical companies as early as the development phase of their new medicinal products – in parallel with the scientific support provided to developers under Regulation (EU) 2021/2282 of the European Parliament and of the Council of 15 December 2021 on health technology assessment (more information about the content of this Regulation can be found here).
  • The Regulation significantly expands the categories of medicinal products subject to a centralised marketing authorisation procedure by the EMA (essentially taking away further powers from national drug authorities). In addition to the categories of products subject to the centralised procedure under Regulation (EC) No 726/2004, centralised MA shall also receive:
    • all medicinal products whose active substance was not authorised in the European Union on 20 May 2004 (the current regime provides for the issuance of centralized MA only for medicinal products with a new active substance for AIDS, cancer, diabetes, neurodegenerative disorders, auto-immune and viral diseases, while for other new active substances the centralized procedure is optional);
    • medicinal products with a paediatric use marketing authorisation (a new type of marketing authorisation introduced by the Regulation for medicinal products intended exclusively to be used by children);
    • priority antimicrobials under Article 40 of the Regulation;
  • Although the Directive and the Regulation do not provide for any major changes to the currently well-established mutual recognition procedure and decentralised procedure for issuing MAs, the draft Directive introduces the possibility for a Member State to opt-in on its own initiative in an applicant-initiated mutual recognition procedure or a decentralised procedure for issuing MA. This change transfers control over the matter where a medicinal product will be authorised from the applicant to the Member States with all the positive and negative consequences thereof – improved patient access, especially in Eastern European countries, but also regulatory and financial risk for pharmaceutical companies that do not have sufficient financial and administrative resources for the successful completion of the administrative procedure in more countries than originally planned;
  • The Regulation introduces a new type of marketing authorisation granted by the EMA – temporary emergency marketing authorisation (“TEMA”). The introduction of the TEMA is the result of the lessons learned by the Commission from the COVID-19 pandemic, during which it was established that there was no legal instrument of Union pharmaceutical legislation for emergency response to pandemics and health crises (the result of which was that the UK and USA issued authorised coronavirus vaccines significantly faster than EMA). It is envisaged that the TEMA will be issued through the most simplified procedure possible, in the event of a public health emergency at Union level and only for the duration of that emergency. Should the marketing authorisation holder (“MAH”) elect to continue the use of the medicinal product beyond the end of the health emergency, the MAH should apply for issuance of one of the standard MAs.
  • The draft Directive introduces several additional conditions that can be included in the national MAs, namely: that the medicinal product is authorised for use, subject to an obligation to carry out: (i) post-authorisation studies to substantiate the clinical benefit; (ii) post-authorisation environmental risk assessment studies (“ERA“); (iii) post-authorisation studies to improve the safe and effective use of the medicinal product; (iv) a medicinal product-specific validation studies to replace animal-based control methods with non-animal-based control methods;
  • A significant shortening of the deadlines for authorisation of the use of a medicinal product is envisaged: the deadline for issuing a centralized MA is reduced from 277 days to 226 days, while the deadline under the national procedure is reduced from 210 days to 180 days.
  • The Directive and the Regulation introduce new grounds for refusal to issue a MA – if the ERA enclosed to the MA application is incomplete, insufficiently substantiated or does not sufficiently address the identified environmental risks, and if the labels and package leaflet do not comply with the applicable requirements;
  • If the proposed changes are adopted, the issued MA will be valid for an unlimited period (under the current legal framework the term of validity of the initial MA is 5 years). It remains possible, for reasons based on the safety of the medicinal product, for EMA or Member States to consider that the initial marketing authorisation should be granted for a period of 5 years.

III. Better market access for generic medicinal products

  • With certain exceptions, the requirement to enclose a risk management plan to the application for the issuance of a МА for generics and biosimilar medicinal products is abolished;
  • The Directive and the Regulation extend the so-called “bolar exemption” – the rule transposed into Аrt. 33 of the Bulgarian Medicinal Products in Human Medicine Act (“MPHMA“) that the conduct of the necessary studies in order to prepare marketing authorisation documentation and subsequent practical requirements in relation to the MA of the generic medicinal product does not constitute an infringement of the patent or the supplementary protection certificate of the reference medicinal product. In this revised and extended version of the exemption, the following are added amongst the authorised activities: activities relating to health technology assessment, price registration and reimbursement procedures, as well as actions related to the above administrative procedures, including the offer, manufacture, sale, supply, storage, import, use and purchase of patented medicinal products or processes, including by third party suppliers and service providers. By extending this exemption, the Commission aims to facilitate the release of generic medicinal products to the European market at the earliest possible moment after the expiry of patent protection of the original product (in Bulgaria, pricing and reimbursement procedures may take more than a year).

In the next article, which will be published soon on our website, we will review in-depth additional changes outlined in the Commission’s proposals for a new Directive and Regulation – changes to the advertising of medicinal products, new measures and requirements for environmental protection, changes to the legal regime concerning orphan medicines, advanced therapy medicinal products and medicinal products for pediatric use and other significant changes that will affect the pharmaceutical market in the European Union.

This article has an informative purpose and is not representative of detailed legal advice. If you are interested in receiving advice in the context of a certain situation, we can happily assist you. The law firm is not responsible for any harm caused by acts or omissions undertaken due to this text.


For further information, please contact:

Eleonora Mateina
Principal Associate
T: +359 2 439 07 07

Philip Kiossev
Principal Associate
T: +359 2 439 07 07