What are the Biggest Regulatory Challenges for Combination Products? Device Perspective

Interview with Educo Life Sciences expert Richard Young

A combination product refers to a medical device that contains an element of a pharmaceutical. Recognising this and understanding which regulations need to be met is essential to ensure the successful marketing of your product.

Educo Life Sciences caught up with Richard Young, who explained some common challenges when navigating the regulatory landscape for combination products and what you can do to successfully ensure market approval.

You can watch or read the interview below.

For those who might be new to this industry – what exactly do we mean by combination products and why are they important?

Combination products are an interesting and growing part of today’s medical solutions. They combine elements of medical devices with pharmaceutical agents, and these combinations can be regulated as either drugs or medical devices. It’s important to recognise and properly regulate these combinations, considering the product’s design and understanding each element’s contribution and features. This is an exciting and rapidly growing area, especially in drug delivery.


What are some of the biggest challenges people face when navigating the regulatory landscape for combination products?

Considering the regulatory pathway, if you’re a medical device manufacturer, adding a pharmaceutical product to your design introduces new complications. This addition brings challenges you haven’t previously encountered.

A typical drug-device combination might be a drug-eluting stent, where a coronary stent introduced to the heart includes a drug that has a secondary effect to the stent itself. Generally, this is classified as a medical device.

However, once we introduce the pharmaceutical component, we must consider pharmaceutical regulations. We need to determine how to incorporate the product and ensure enhanced communication with our notified body in Europe to agree on whether the product is classified as a medical device or a pharmaceutical. This classification is documented in a decision letter from the notified body. For products classified as medical devices, they typically fall under class three, the highest risk classification.
The requirements for the pharmaceutical and medical device components remain the same, regardless of the regulator. We still need to design the medical device with all standard design considerations and acceptance criteria. The difference lies in directing the product to different sets of reviewers for final assessment before market clearance. The FDA in the US has a specific Office of Combination Products to advise manufacturers on classification and market routes. The regulatory approach differs slightly between America and Europe, but there are many commonalities in their methodologies.


Does the medical device portion of the combination product need to meet state of the art with regards to design?

Absolutely. The medical devices regulation in Europe specifically modifies pharmaceutical regulation. Essentially, it states that we are not CE marking the product as we would for a medical device. Instead, we are complying with Annex I of the regulation. For those unfamiliar with medical devices, Annex I outlines the general safety and performance requirements, including state-of-the-art standards, biocompatibility, and sterilisation, which apply to the design and testing of medical devices.
Compliance with these general safety and performance requirements is still necessary. The product must meet state-of-the-art standards, and this information will be part of the pharmaceutical submission. Even if the product is regulated as a pharmaceutical, the same information required for a medical device must be provided.

Plus the additional complications and interactions between the device and the pharmaceutical, for drug delivery device, we want to make sure they go together. We’re also now interested in things like drug delivery rights, possible contamination, all these things, stuff that we’re going to have to take into account, and cover in the design and development for the product and its design history file, that documentation that comes with it.

It’s the same just a little bit more complicated.


Can you explain the principal mode of action?

Yes, certainly. The principal mode of action is your basic starting point as a developer or manufacturer to determine the potential regulatory pathway for your product, though this can be quite nuanced. For example, a drug-eluting stent catheter is classified as a medical device because its primary mode of action is mechanical—it holds the coronary artery open. The drug component is secondary. Conversely, a prefilled syringe with a COVID-19 vaccine is regulated as a pharmaceutical because the primary mode of action is to deliver the vaccine into the body, with the syringe merely serving as the delivery mechanism.

It’s important to assess what the medical device contributes compared to the pharmaceutical component. This can sometimes be nuanced. For instance, consider bandages for ulcerated leg wounds that contain pharmaceutical products. One could argue it’s a medical device providing a physical barrier, or that it’s a pharmaceutical vehicle delivering drugs to the ulcer. These are borderline cases, resolved through discussions with notified bodies and consulting the borderlines manual by the Medical Device Coordination Group. If unresolved, the competent authorities of Europe vote on the classification.

In the United States, the Office of Combination Products regulates combination products without needing to distinguish which component takes the lead, as all regulatory functions are consolidated. Understanding the primary mode of action is crucial for developers, but it’s important to recognise when the pharmaceutical component drives the product’s function, requiring a different regulatory approach.

How will the course Regulatory Affairs for Combination Products help delegates tackle the regulatory landscape for combination products?

This course, presented by myself and my colleague Andrew Willis, offers delegates the chance to discuss product development, design issues, and regulatory challenges from both perspectives. You’ll have the opportunity to approach these problems with consultants who have extensive experience in different areas.
My perspective focuses on the development of medical devices, including the rules, state-of-the-art practices, and their application. Andrew’s viewpoint centres on pharmaceutical development and the documentation requirements from that angle.
Interestingly, these perspectives are not in conflict. By explaining both sides coherently, we help participants understand the common ground and approaches that aid in project planning, identifying pitfalls, and successfully bringing a product to market. This course is particularly beneficial for pharmacists or pharmaceutical company employees new to medical device development and designers unfamiliar with pharmaceutical development or regulation.
It’s a unique opportunity to see the whole picture, receive comprehensive training, and engage in discussions and consultations with experts from both fields. The course offers great value for money, with free consultations over lunch!


Watch the interview below:



Richard teaches the following courses:

Regulatory Affairs for Combination Products (Drug/Device and Device/Drug)

Fundamentals of the EU IVD Regulation (IVDR)

Labelling and UDI for Medical Devices and IVDs

Medical Device Design and Development for New and Legacy Products



To view all our medical device and IVD courses follow the link below.

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