The European Commission’s proposal to amend the EU’s general pharmaceutical legislation includes a new draft directive replacing Directive 2001/83/EC (the draft Directive) and a new draft regulation replacing Regulation (EC) No 726/2004, which will also incorporate the EU’s amended paediatric and orphan medicine rules (the draft Regulation).

Whilst the proposal maintains the dual legislative system of a Regulation and Directive, it introduces some significant changes to streamline the EU’s regulatory procedures to promote innovation, increase access to medicines and reduce administrative burden.  Below we have highlighted some key points for marketing authorisations (MAs).

Simplification of EMA’s Scientific Committees

The proposal provides for the simplification and reduction in the number of European Medicines Agency (EMA) scientific committees, leaving only the two main committees for medicinal products for human use: the Committee on Medicinal Products for Human Use (CHMP); and the Pharmacovigilance Risk Assessment Committee (PRAC).  The expertise of the other committees, such as the Committee for Advanced Therapies (CAT), Committee for Orphan Medicinal Products (COMP), the Paediatric Committee (PDCO) and Committee on Herbal Medicinal Products, will be retained and reorganised in the form of working groups, working parties and a pool of experts.

The CHMP and PRAC may rely on scientific working parties to perform certain tasks, but the committees will be ultimately responsible for any assessment or scientific opinion.  This should avoid the complexities associated with a divergence of opinion in the scientific assessment of products that has occurred occasionally in the past.  Accordingly, the remit of the CHMP is expanded to reflect it will now regulate all medicinal products, including advanced therapy medicinal products, orphans and paediatric medicines.

Marketing Authorisations

The proposal maintains the current flexibility for applicants to submit marketing authorisation applications (MAAs) either centrally, purely nationally or through the decentralised or mutual recognition procedures.  The mandatory scope of the centralised procedure, however, will be extended to include priority antimicrobial medicinal products and products seeking a paediatric use marketing authorisation. 

Other key changes that will be introduced include:

Duplicates restricted to IP protection and co-marketing reasons

Under the centralised procedure, the same MA applicant can in principle be granted only one MA for a specific medicinal product.  As a derogation, the Commission may grant a duplicate MA in exceptional circumstances.  Under the draft Regulation, these circumstances will now be limited to the protection of intellectual property rights (IPR) or for co-marketing reasons.  In other words, it will no longer be possible to seek a duplicate MA on public health grounds linked to the availability of medicines. 

Specifically, the draft Regulation limits the grounds for a duplicate MA to:

  • where one of the medicinal product’s “indications or pharmaceutical forms is protected by a patent or a supplementary protection certificate in one or more Member States”; or
  • “for reasons of co-marketing with a different undertaking not belonging to the same group as the marketing authorisation holder of the medicinal product.”

Where a duplicate MA is granted to protect IPR, the draft Regulation requires that the initial or duplicate MA is withdrawn once the relevant IPR expires. Although the proposed changes expressly restrict the potential grounds for a duplicate MA, in essence, they reflect the Commission’s current policy on duplicates.  The Commission applies a very restrictive interpretation of the current public health ground and what constitutes “objective verifiable reasons relating to public health regardingthe availability of medicinal products to health-care professionals and/or patients.”  The Commission seems only to accept that the availability of a product would clearly be increased where a duplicate MA is granted for fewer indications due to IPRs.  It follows that in recent years the Commission tends to grant duplicate MAs only for intellectual property protection or co-marketing reasons.

MAs may be subject to post-authorisation conditions

Competent authorities will have greater scope to grant a MA subject to post-authorisation conditions.  For example, the draft Directive will empower authorities to grant a MA subject to one or more of the following new conditions:

  • a post-authorisation obligation to substantiate the clinical benefit;
  • to conduct post-authorisation environmental risk assessment studies; and

to conduct post-authorisation studies to improve the safe and effective use of the product.

MA under exceptional circumstances and conditional MAs for new indications

The Commission and national competent authorities will have the flexibility to grant a MA under exceptional circumstances for “a new therapeutic indication of an existing [standard] marketing authorisation.”  Also, the Commission will be able to grant a conditional MA “for a new indication for an existing [centrally approved] marketing authorisation.”  These provisions are designed to promote innovation and increase access to medicines that treat unmet medical needs.

Duration

Notably, standard marketing authorisations (MAs) will be granted for an indefinite period, unless there are grounds relating to safety that justify the MA should be subject to renewal after 5 years.  This should ease the regulatory burden of renewals. 

However, MAs granted under exceptional circumstances will still be subject to renewal and in addition, will be re-assessed after an initial two years and thereafter based on the associated risks.  Conditional MAs granted via the centralised procedure will be valid for an initial one year, on a renewable basis for the first three years and thereafter every two years.

Electronic dossier and additional data requirements

MAAs will need to be submitted electronically and include additional information, in particular:

  • an environmental risk assessment (ERA) plan that assesses the risks to the environment and public health, including antimicrobial resistance, that may arise from the manufacture of the product.  Also, the ERA should include risk mitigation measures (see our blog here for more information on ERA requirements);
  • the results of paediatric trials conducted in accordance with an agreed paediatric investigation plan (PIP) for new products or for certain variation applications, unless a waiver or deferral has been granted (see our blog here on the proposed changes to the paediatric rules); and
  • for an antimicrobial product, an antimicrobial stewardship plan and special information, such as educational material for healthcare professionals and an awareness card for patients with information on antimicrobial resistance.

Reliance on an ASMF Certificate or Additional Quality Master Files

For a chemical active substance, MA applicants will be able to rely on an active substance master file (ASMF) certificate granted by the EMA or an AMSF (where no ASMF certificate exists) to replace all the information required on the active substance under Annex II of the draft Directive.  As is the case currently, the ASMF concept does not apply to biological medicinal products.  However, for data on “an active substance other than a chemical active substance, or on other substances present or used in the manufacture of a medicinal product” that is required under Annex II, MA applicants can rely on additional quality master files.  The broad wording of the provision suggests that biological medicinal products could fall within the scope of additional quality master files.  However, recital 93 of the draft Directive indicates otherwise and that additional quality master files will be limited to “novel excipients, adjuvants, radiopharmaceutical precursors and active substance intermediates, when the intermediate is a chemical active substance by itself or used in conjugation with a biological substance.”

The ASMF/additional quality certificate holder will be responsible for keeping the certificate up to date and in the case of an ASMF, submit to inspections.  Where the certificate holder breaches its legal obligations, competent authorities may suspend or revoke the certificate, but also may suspend or revoke a MA relying on the certificate.  In addition, competent authorities will have a broad power to “take measures to prohibit the supply of the medicinal product relying on that certificate.”  The draft Directive makes clear that a marketing authorisation holder (MAH) relying on an ASMF or additional quality certificate will be ultimately responsible for its medicinal product, including its constituent parts.

Extended grounds for refusal

Competent authorities will be able to refuse a MAA not only on quality, safety or efficacy grounds, but also on environmental risk grounds or if the proposed labelling and package leaflet does not comply with the legal requirements.

Rewards and incentives

The potential regulatory protections for an innovative product granted a MA will be shortened.  The current standard 8 years data exclusivity, followed by 2 years of market exclusivity (“8+2”), will become a “6+2”-year period (see our blog here on the proposed changes to regulatory protections for further details). 

The draft Regulation also envisages shortening the standard 10-year period of orphan exclusivity to 9 years ( or 5 years for orphan medicines approved on the basis of bibliographic data).  The new rules will allow competitors to file 2 years before the expiry of orphan exclusivity, which they currently cannot do (see our blog here on the proposed changes to the orphan rules for further details).   

This blog is based on the wording of the EU’s proposal published on 26 April 2023.  This wording could significantly change during the legislative process.  Our Dublin, Brussels, Frankfurt and London teams will continue to monitor this legislation.  We will be hosting a webinar to discuss the impact on 9 May.  To sign up for the webinar please click here.

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Photo of Marie Doyle-Rossi Marie Doyle-Rossi

Marie Doyle-Rossi is an Irish and UK qualified lawyer with a Ph.D. in biology. Her practice focuses on life sciences regulatory, commercial and administrative law matters. She has specialized experience in GxP matters and navigating the regulation of complex technologies, including advanced therapeutics…

Marie Doyle-Rossi is an Irish and UK qualified lawyer with a Ph.D. in biology. Her practice focuses on life sciences regulatory, commercial and administrative law matters. She has specialized experience in GxP matters and navigating the regulation of complex technologies, including advanced therapeutics, biologics, combination products, digital health and personalized medicine.

Marie provides strategic, policy and regulatory advice on biologics, orphans, human tissue and cells, market and data exclusivity, clinical trials, pricing and reimbursement, product life-cycle management, data privacy and compliance issues.

She has developed considerable expertise in GxP, including adverse event reporting, quality systems and manufacturing, supply chains and recalls. She regularly counsels clients on “Brexit” related issues from both a UK, EU and Irish perspective.

Marie also advises on, and performs regulatory due diligence for, corporate/commercial transactions including acquisitions, public offerings and clinical trial agreements.

She is associate co-chair of Covington’s Food, Drug, and Device Rapid Response team during the COVID-19 pandemic.

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Photo of Grant Castle Grant Castle

Grant Castle is a partner in London, Brussels, and Dublin practicing in the areas of EU, UK, and Irish life sciences regulatory law. He supports innovative pharmaceutical, biotech, medical device and diagnostics manufacturers on regulatory, compliance, legislative, policy, market access and public law…

Grant Castle is a partner in London, Brussels, and Dublin practicing in the areas of EU, UK, and Irish life sciences regulatory law. He supports innovative pharmaceutical, biotech, medical device and diagnostics manufacturers on regulatory, compliance, legislative, policy, market access and public law litigation matters in the EU, UK, and Irish Courts.

He is one of the Co-chairs of Covington’s Life Sciences Industry Group and is Head of Covington’s European Life Sciences Regulatory Practice.

Grant regularly advises on:

  • EU and UK regulatory pathways to market for pharmaceuticals and medical devices, including in vitro diagnostics and on associated product life cycle management;
  • Pharmaceutical GxPs, including those governing pharmacovigilance, manufacturing, the supply chain and both clinical and non-clinical research;
  • Medical device CE and UKCA marking, quality systems, device vigilance and rules governing clinical investigations and performance evaluations of medical devices and in vitro diagnostics;
  • Advertising and promotion of both pharmaceuticals and medical devices; and
  • Pricing, reimbursement and market access for both pharmaceuticals and medical devices.

Grant also handles procedural matters before EU, UK and Irish regulators and UK and Irish market access bodies, where necessary bringing judicial reviews for his life sciences clients before the EU, UK and Irish Courts.

Chambers UK has ranked Grant in Band 1 for Life Sciences Regulatory for the last 21 years. He is recognized by Chambers UK, Life Sciences as “excellent,” “a knowledgeable lawyer with a strong presence in the industry,” who provides “absolutely first-rate regulatory advice,” according to sources, who also describe him as “one of the key players in that area,” whilst Chambers Global sources report that “he worked in the sector for many years, and has a thorough understanding of how the industry ticks.” He is praised by clients for his “absolutely first-rate” European regulatory practice. Legal 500 UK notes that he is “highly competent in understanding legal and technical biological issues.”

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