A New Era for Medical Devices
Current Regulatory Issues

Sandra Blumenrath
DIA Science Writer

n the last year, large-molecule (biologics) submissions to the Food and Drug Administration (FDA) and other regulatory agencies far outnumbered submissions for small-molecule therapies. Since nearly all of these biological products require a device to administer the drug, approval applications for combination products (or drug-device combinations) are on the rise as well, receiving increased scrutiny for example by the FDA’s Center of Devices and Radiological Health (CDRH). Sessions in this topic area focused on changes and challenges in the regulatory landscape for drug-device combinations.

Key Takeaways

• Differences in terminology in the US and EU (“combination products” versus “drug-device combinations”) complicate the issue of medical devices from both a regulatory and a GMP perspective.
• The EU Medical Device Regulation (MDR), which entered into force in May 2017 and governs market access to devices, sets new legal requirements to meet the high quality and safety standards for medical devices and address common safety concerns. The regulation applies to all new devices, but it’s still unclear to what extent older devices will be affected.
• In Europe, submissions of a drug-device combination (DDC) need to be accompanied by a statement from the Notified Body, which assesses conformity under the respective EU Directive. Although the content of the statement is described in the MDR, its precise extent and length remain unclear.
• The growing number of guidelines published by regulatory bodies across the globe, and the different ways combination products are defined, make it increasingly difficult to harmonize the regulatory expectations for these products.

Why this is important: In light of the constantly evolving global regulatory environment, it is increasingly challenging to prepare effective combination product submissions. To incentivize the development of DDCs and accelerate the approval process, we need clearer instructions for obtaining Notified Body statements as well as a clear overview of regulatory expectations. Diverging regulatory expectations slow down the global development of DDCs. Therefore, our efforts have to focus on harmonization.

The Issue of Terminology

For manufacturers of medical devices, the first challenge begins with terminology. The US term “combination products” refers to four different types of devices, whereas “drug-device combinations” the term used in Europe – describes only one of them. Consistent definitions would simplify the submission process and compliance with GMPs.

Placing Devices on the Market under Europe’s New MDR

The EU Medical Device Regulation will take full effect in all EU Member States on May 26, 2020, which will have given manufacturers a transition time of three years to meet the requirements of the updated MDR. There is contradictory information on whether currently approved medical devices are exempt from the new regulation, or if they will have to be re-approved. The MDR seems to require manufacturers to obtain Notified Body (NB) approval for any product that is already on the market, although some sources suggest that already approved devices only have to be grandfathered in if updates are made to these products. It is crucial for medical device manufacturers to stay current on the progress of the MDR and other changes that may impact them.

Furthermore, all marketing applications for a DDC product have to include a statement from the Notified Body about the compliance of the device, but the precise submission content, the extent of the statement, and the NB’s involvement in general remain unclear. All of these open questions present a significant degree of regulatory uncertainty.

Speed of Scientific Developments versus Regulatory Guidelines

In the medical devices area, scientific developments have progressed much faster than the development of regulatory guidelines to accompany them. In an effort to catch up, several countries have issued guidelines, resulting in a number of diverging requirements that are difficult to reconcile. Regulatory gaps also remain. What’s more, more than 15 countries now have definitions of combination products, several of which are quite different. These issues present significant roadblocks to keeping up with the scientific advancements and delivering safe, cutting-edge products to patients.

As science advances, DDCs (or combination products) will become increasingly common and complicated. To be appropriately prepared, there is a need for a globally consistent regulation and definition of these products. It is therefore important to engage with both regulators and industry, including the International Organization for Standardization (ISO) and the International Council for Harmonisation (ICH), to harmonize regulatory requirements.

This article summarizes key takeaways from sessions in “Topic G: A New Era for Medical Devices and Diagnostics. How Is The Impact?”