The European Commission’s proposal to amend the current pharmaceutical regulatory framework includes a draft Directive on medicines for human use (the “Proposed Directive”) and a draft Regulation on the central authorisation and supervision of medicines (the “Proposed Regulation”, together the “Proposal”).  In this blog, we provide an overview of the potential impact of the Proposal on pharmacovigilance.

No Major Changes to the Pharmacovigilance Regulatory Framework

Overall, the Proposal introduces only limited changes to the current EU pharmacovigilance provisions of the Directive 2001/83/EC and Regulation (EC) 726/2004.  Therefore, the core pharmacovigilance obligations of a marketing authorisation holder (“MAH”) (i.e., establishing a pharmacovigilance system, reporting and recording suspected adverse reactions, and submitting Periodic Safety Update Reports, etc.) still apply.  Likewise, the Proposal maintains the structure and powers of entities responsible for pharmacovigilance supervision at Member State and EU levels (e.g., the involvement of the Pharmacovigilance Risk Assessment Committee and enforcement by national competent authorities, subject to potential financial penalties infringement proceedings by the Commission), and the use of the EudraVigilance database.  This will be a relief for companies and should not come as a surprise in light of the extensive reforms of the pharmacovigilance rules in 2010, which entered into force in 2012. 

New Provisions on Risk Management for Generics and Biosimilars

The Proposal introduces one main change to a MAH’s pharmacovigilance obligations in respect of risk management plans (“RMPs”) for certain products.  Currently, under Article 95(4) of Directive 2001/83/EC, a MAH must, as part of its pharmacovigilance system, operate and update a risk management system (“RMS”) for each new medicinal product authorised.  As part of its marketing authorisation application (“MAA”) an applicant must submit a RMP, which details the RMS.   

Article 21 of the Proposed Directive maintains this obligation, but carves-out generic and biosimilar products if: (i) no additional risk minimisation measures exist for the reference product; and (ii) the marketing authorisation (“MA”) for the reference product has not been withdrawn prior to the submission of the generic or biosimilar MAA.

However, under Article 91(1) of the Proposed Directive, a MAH of an authorised generic or biosimilar product will still need to submit a RMP to the relevant competent authority in two scenarios: 

  • When the MA for the reference product is withdrawn, but the MA for the generic or biosimilar is maintained.  The RMP must be submitted within 60 days of the MA withdrawal for the reference product.
  • When requested by the competent authority.  Such a request may be made where: (i) additional risk minimisation measures have been imposed on the reference product, in which case the RMP should be aligned with the reference product’s RMP; or (ii) it is “justified on pharmacovigilance grounds.”  The Proposal does not provide further details on what constitutes “pharmacovigilance grounds” and therefore the provision leaves a lot of flexibility to competent authorities to impose a RMP.   

The Proposed Regulation includes similar provisions for centrally-authorised products. 

The proposed carve-out for applicants submitting a MAA for a generic or biosimilar product from the RMP requirement should ultimately facilitate the earlier entry into the market of these products.

Clarification of the Obligation to Record and Report Pharmacovigilance Information

Currently, under Article 107 of Directive 2001/83/EC, MAHs must record all suspected adverse reactions in the EU or third countries that are brought to their attention.  A MAH must then report valid reports to the EudraVigilance database within the specified time periods, following the day on which the MAH gained knowledge about the reaction.

Article 105(1) of the Proposed Directive expressly requires that MAHs record and report suspected adverse reactions “including data relating to off-label use of the product.”  The additional wording concerning off-label data reflects current EU Good Pharmacovigilance Practice (“GVP”) Guidance that requires MAHs to collect and report instances of off-label use that lead to suspected adverse reactions, but this is now a legal requirement. In addition, Article 101 of the Proposed Regulation provides that the EudraVigilance database may include, in justified cases, pharmacovigilance information with regard to medicines used under compassionate use or early access schemes.  Again, this additional wording reflects current EU GVPs on recording and reporting pharmacovigilance information.   

Pharmacovigilance Obligations Imposed on Certain Undertakings

Currently, the EU pharmacovigilance rules are strictly speaking only imposed on MAHs.  Pursuant to Article 105(6) of the Proposed Directive certain undertakings will also be subject to the reporting and recording obligations that apply to MAHs.  In this context, “undertakings” refer to persons that supply medicines under Article 3 of the Proposed Directive, either:

  • pursuant to an exemption granted by a Member State, to fulfil special needs, in response to a bona fide unsolicited order formulated in accordance with the specifications of an authorised healthcare professional, and for use by an individual patient under their direct personal responsibility (i.e., named patient supply); or
  • pursuant to a temporary authorisation from a Member State, in response to the suspected or confirmed spread of pathogenic agents, toxins, chemical agents or nuclear radiation, any of which could cause harm (i.e., temporary emergency use authorisation).

This is echoed in the obligations imposed on Member States, which must report all suspected adverse reactions that occur in their territory, including those reported in relation to named patient use (see Article 106(1) of the Proposed Directive).  While this should ensure that relevant pharmacovigilance information related to use of medicines in specific scenarios is recorded and reported effectively, it also requires concerned undertakings to have the infrastructure and expertise needed to comply with these obligations. 

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 Grant Castle Grant Castle

Grant Castle is a partner in London 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…

Grant Castle is a partner in London 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 18 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.”

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.

Photo of Anna Wawrzyniak Anna Wawrzyniak

Anna Wawrzyniak is a senior scientific and regulatory advisor in the Life Sciences team. As a non-lawyer with a Ph.D. in biomedical sciences, Anna provides detailed scientific and regulatory advice to the firm’s pharmaceutical, food and feed clients. She draws on her technical…

Anna Wawrzyniak is a senior scientific and regulatory advisor in the Life Sciences team. As a non-lawyer with a Ph.D. in biomedical sciences, Anna provides detailed scientific and regulatory advice to the firm’s pharmaceutical, food and feed clients. She draws on her technical and regulatory expertise to help clients in strategic planning and in navigating regulatory proceedings, especially in areas where a deep understanding of the underlying science is important. In particular, she advises pharmaceutical clients on regulatory issues relating to product classification, biologics, advanced therapies, orphans, paediatrics, market and data exclusivities.

Anna has deep expertise in the following areas:

  • The development and approval of medicinal products;
  • Strategies for obtaining and maintaining regulatory exclusivities, including orphan market exclusivities, regulatory data exclusivities (new active substance status) and paediatric incentives;
  • Support to high stake litigation on regulatory aspects;
  • PRIME, accelerated approvals, conditional and exceptional marketing authorisations;
  • Advanced therapies, biologic and substances of human origin;
  • Borderline classification;
  • Regulatory due diligence;
  • Novel foods and food supplements; and
  • Feed.
Photo of Valeria Sturla Valeria Sturla

Valeria Sturla is a Legal Intern in the Life Sciences Practice Group.

Valeria completed a double degree in Law at the Universities of Milan (Università Statale di Milano), and Toulouse (Université Toulouse 1 Capitole). Valeria also completed the LL.M in European Legal Studies…

Valeria Sturla is a Legal Intern in the Life Sciences Practice Group.

Valeria completed a double degree in Law at the Universities of Milan (Università Statale di Milano), and Toulouse (Université Toulouse 1 Capitole). Valeria also completed the LL.M in European Legal Studies at the College of Europe of Bruges.

She is a native Italian speaker and fluent in English and French.