A confluence of forces is intensifying the pressure on and opening pathways to the reform of drug/device combination products regulation in Europe, with legislative changes and strategic priority needs at issue.
An underlying driver, impacting all regulators around the world, is the need to evolve regulatory processes to better accommodate the convergence of medicines, medical devices, and software and the sharing of expertise among stakeholders.
Having an immediate impact in the EU is its medical device regulation (MDR), which entered into full “application” on May 26, 2021.
The MDR introduces new responsibilities and procedures regarding drug/device combination products for the EMA and national medicines agencies as well as for manufacturers and notified bodies.
The proposed revision to the medical device legislation, initially published in September 2012, was finalized in May 2017 and scheduled to come into full force in May 2020. Due to the impact of COVID-19, the transition period was extended by one year. [See IPQ December 30, 2016, November 26, 2017, and July 26, 2019 for more on the MDR. A full, chronological listing of IPQ stories since 2010 that have focused on the dialogue and developments around the regulation of drug/biologic/device combination products, including those addressing the MDR, is provided below.]
The related in vitro diagnostic regulation (IVDR), also published in 2017, brings in even greater changes and more extensive requirements for diagnostic tests – including companion diagnostics – and is due to take full effect in May 2022.
The implications of the MDR and IVDR for the pharmaceutical industry are explained in a “medical devices” section of the EMA website (link provided below).
EMA references have included a Q&A that addresses procedural aspects of the MDR to combination product applications and a draft guidance on quality requirements, which were published in 2019 and discussed at an EMA multi-stakeholder webinar in late November 2020. At the meeting, it was explained that a task force had been convened, involving representatives from the device and drug units of the European Commission, EMA, and national regulatory agencies, to focus on finalizing the guidance.
On June 29, EMA published a revised and updated version of the 2019 Q&A on MDR/IVDR implementation, with extensive changes reflecting the input of the new task force. [Editor’s Note: The revised Q&A will be reviewed in a follow up IPQ story focused on MDR implementation and the implications of its Article 117, which addresses the notified body review of device constituent parts of “single integral products.”]
The EU “pharmaceutical strategy,” released by the European Commission (EC) in late 2020, calls for another round of legislative changes. A “roadmap” for the proposed revisions was open for comment through April 2021.
The roadmap notes that the current legislation “may not be fully equipped to respond quickly to innovation,” as it was developed at a time when certain technologies, such as genomic sequencing, genome editing and artificial intelligence (AI), did not exist or were in their infancy. It points out that “technological progress is leading to the development of complex combination products,” and that the current legislation should be adapted to cover “new scientific and technological developments and models.”
Meanwhile, the strategic priorities of the EMA, European Medicines Regulatory Network (EMRN) and individual member state agencies have been defined, which call for developing more flexible and adaptive approaches to support innovation.
At various venues over the past year, leading experts have been sharing their insights on the related strategies in development and on the cultural, structural and process changes required for the successful regulation of the medicines, medical devices and combination products of the future in Europe and globally.
The four-part story below explores the current dialogue on the drivers and pathways for a more collaborative, streamlined and globally-minded regulatory approach to combination products in Europe.
Part I: EU Pharma Strategy Roadmap, Comments from Industry, and Related Agency Strategies
The first part of the story focuses on the EU pharma strategy and its discussion of the “interplay” of medicines and medical devices. Reviewed are stakeholder comments on the proposals for handling combination products included in the initiatives for innovation and regulatory efficiency. Also reviewed are: ● combination product-related aspects of the EMA Regulatory Science Strategy and European Medicines Regulatory Network Strategy published in March 2020 and December 2020 respectively ● insights from Belgium FAMHP Christophe Lahorte on the evolving mandate of the EU Innovation Office Network, and ● a joint medicines and medical devices agencies initiative outlined in the June 2021 HMA procedures and governance update.
Part II: Culture/Structure/Process Change and Global Alignment
The second part further explores the increasing convergence between the worlds of medicines and medical devices and the importance of communication and collaboration – issues central to the discussions at a RAPS/TOPRA workshop on the global alignment of combination product regulation in June 2020. In focus is the discussion by former MHRA Devices head John Wilkinson of the changes needed, based on his experience in working with European and international regulators, policy makers, and industry leaders.
Part III: HPRA CEO Lorraine Nolan on HPRA and EMA Strategy
Part three offers insights from Ireland HPRA CEO and Vice-Chair of the EMA Management Board Lorraine Nolan on developing strategic plans for the agencies and dealing with the impact of Brexit and the COVID pandemic. Addressing a mid-2020 PDA Europe conference, Nolan discussed: ● the evolving regulatory role in enabling product access ● globalization, and ● the impact of the medtech sector.
Part IV: EMA’s Zaïde Frias and NB/Industry Perspectives on EU Regulatory Transformation
Continuing the discussion on regulatory transformation and European agency strategy developments, part four focuses on the keynote presentation by EMA’s Zaide Frias and the Q&A that followed at the October 2020 Medtech and Pharma Platform annual conference. Frias described the EMA regulatory science strategy and shared a vision of collaborative regulation for the complex, converging technologies and medicines that Europe’s regulatory system is facing. An integrated approach to combination product review was also espoused at a DIA Europe conference a few months earlier by notified body (NB) expert Bassil Akra and Zealand Pharma’s Lars Hyveled-Nielsen, who provided the small and medium-sized enterprise (SME) perspective.
[Editor’s Note: A companion story will follow providing an update on how FDA, with the help of its Office of Combination Products (OCP) and industry, is evolving its process for handling the combination product regulatory challenges.]
LINK: ● EMA Medical Devices