nderstanding, collaboration, and a one-point-of-contact model were a few of the “asks” from the experts representing regulatory agencies, competent authorities, notified bodies, and industry organizations at the 2024 Combination Products in the EU Summit jointly presented by DIA and the Regulatory Affairs Professionals Society (RAPS) in January 2024 in Brussels.

This first-ever collaboration between DIA and RAPS convened representatives from all stakeholders who must work together to solve the regulatory requirements for combination products in the EU and aimed to find answers to many unresolved questions surrounding the regulatory requirements for combination products.

“It is great to have all the actors come together to drill a bit more for changes so that it can be better understood across the factions,” said Cristelle Bouygues (European Medicines Agency). “We need to get a picture of what is coming, not maybe in the next two years, but in the future.”

Many attendees sought answers to their daily workplace challenges. Kay McGrath (Advanced Medical Solutions) said that she wanted to “understand the opportunities for cross-pollination, especially in situations where device-lead combination products do things a certain way, could really help solve some of the issues for drug-lead combination products and vice versa.”

Underpinning the current state is that “There is no legal definition of ‘combination product.’ In Europe, you are either a medicinal product or a medical device,” noted Tim Chesworth (AstraZeneca). He added that combination products are increasingly important and increasingly complex, “leading to increased pressure on the current regulatory frameworks. How can the current frameworks cope with the additional volume that is coming but also the additional complexity?”

Impacts of MDR and GPL

Panel discussions included exploration of the challenges associated with Article 117 of the EU Medical Device Regulation (MDR), which requires a manufacturer of an integral drug-device combination product to get a notified body opinion (NBOp) that confirms the device portion is compliant with MDR’s general safety and performance requirements. Although an NBOp adds an important layer of protection, it can also lengthen approval times and increase costs for smaller manufacturers.

Another key topic was the impact of the pending EU General Pharmaceutical Legislation (GPL) on the development and marketing of combination products.

According to Lilia Luchianov, policy officer at the European Commission Directorate-General for Health and Food Safety (DG-SANTE), the draft legislation has six key political objectives. It aims to:

• Eliminate single market access
• Ensure the availability and security of the supply chain
• Improve affordability
• Create a competitive regulatory framework
• Support environmental sustainability
• Combat antimicrobial resistance.

The legislation also clarifies the interplay between other EU legislative frameworks, including those for medical devices and substances of human origin. “This is where we talk about combination products because that was one of the areas where we really had to look closer and to see what can be done to improve the situation,” Luchianov explained.

Presentations were augmented by parallel roundtable discussions on these same topics, where small groups of delegates collaborated with officials from National Competent Authorities, Notified Bodies, and EU bodies to examine specific issues in great depth and then discuss potential, pragmatic strategies and solutions to them.

Consensus and Solutions

The summit’s consensus is that new multilateral collaboration pathways engaging all the players must be created to ensure Europe’s competitive position in the combination products space. Strengthening the communication pathways between regulatory agencies and notified bodies and replacing sequential assessments of the medicinal and device components of a product with a simultaneous and coordinated assessment would also shorten approval timelines.

One possible ideal solution—and a long-term aspiration—would be to create one legislation that encompasses all medical products, whether devices or pharmaceuticals. The new EU GPL, the first pharmaceutical legislation update since 2004, may provide an example and opportunity for similar legislative change in the coming decades.

Until then, several pragmatic solutions (many of which are already in motion) could be implemented:

• Parallel or joint review processes between notified bodies and competent authorities, which would result in significantly shorter timelines.
• Developing a framework that would allow notified bodies to offer consultations and scientific advice.
• Inclusion of delegated acts at the interfaces between legislations to alleviate the work of legislators by bridging gaps between legislations that govern specific products.

Summit participants said that they could foresee positive outcomes from the two-day meeting. “We have been discussing these problems for years and always saying we need to bring all the stakeholders together,” said Stephan Affolter (Ypsomed AG). “So, it is really good to see not only industry and notified bodies but also national competent authorities, the EMA, and also the European Commission here.”