In late April 2022, the long-awaited Medical Device Coordination Group (MDCG) guidance on borderline devices under the Medical Device Regulation (MDR) was published. This document, MDCG 2022-5: “Guidance on borderline between medical devices and medicinal products under Regulation (EU) 2017/745 on medical devices,” may be found by clicking here.
In this newly-released guidance, the MDCG essentially replaces the borderline guidance in MEDDEV 2.1/3 Rev3, originally written for the EU Medical Device Directive (MDD). It provides guidance and clarification with a focus on the differences between the MDD and MDR, as well as new requirements introduced with the MDR such as substance-based devices (rule 21).
In all, four areas are addressed:
- The borderline between medical devices and medicinal products
- Herbal products
- Substance-based medical devices
- Medical device and medicinal product combinations
Section 1: The Borderline Between Medical Devices and Medicinal Products
This is by far the largest section and addresses several issues that are critical for manufacturers attempting to classify borderline devices under the MDR.
First, it provides definitions of the critical terms needed to establish the mode of action of a medical device, including definitions for “pharmacological means,” “immunological means” and “metabolic means.” Examples of the types of action which fall under these definitions and those that don’t are also provided.
The borderline for diagnostics is clarified based on intended use. Products used to distinguish between healthy and pathological tissue meet the definition of “medical diagnosis” and are regulated as drugs (i.e., x-ray contrast media); while products whose purpose is to visualise an area for surgery do not meet the definition and are regulated as devices (i.e., endoscopic tattoo).
The second key area addresses the impact on the classification of devices as a result of the removal of the phrase “liable to act upon the body” from the definition of a medical device with ancillary action in the MDR. Guidance is provided on the concepts of “a substance which if used separately may be considered to be a medicinal product” and “action ancillary to that of the device.” Notably:
- The action of the substance (is it a medicinal product?) and whether or not its action is ancillary to that of the device must both be based on scientific evidence.
- The manufacturers intention, the quantity of the substance in the device and the route of administration are not relevant for determining the action of the substance.
- The quantity of the substance available to the human body is relevant when considering whether the action is ancillary to the device (flavourings, colorants, antioxidants or chelating agents are given as examples which may be excluded based on quantity).
Lastly, section 1 includes specific examples of medical devices, accessories and medicinal products.
Section 2: Herbal Products
The guidance draws together relevant definitions and concepts from the legislation on herbal medicines. The principles that apply to “conventional ”medicinal substances” also apply to plant-based or herbal substances when determining whether a product can be a medical device and if rule 14 applies.
A list of examples of products, which should generally be considered herbal medicines, is provided. Section 4 of the guidance also includes a list of herbal substances considered as medicinal products, and are therefore likely to lead to the application of rule 14 if incorporated in a medical device with ancillary action.
Section 3: Substance-Based Medical Devices
This short section highlights rule 3 and rule 21 as specific rules for substance-based devices. A list of examples of devices under rule 21 is provided which is identical to the list in the classification guidance: MDCG 2021-24. Arguably, the key statement of this section is that all applicable rules must be considered so that if the substance in question is a medicinal substance with ancillary action, then rule 14 also applies.
Section 4: Medical Device and Medicinal Product Combinations
This section addresses different combination scenarios and the regulatory status of products with the aid of a flow chart. It highlights the new requirement in the MDR for the Notified Body review of products, such as prefilled syringes, which incorporate medical devices, but are regulated as medicines. Examples of each of the different combination scenarios are also provided. In most cases, this list is consistent with what is found in MEDDEV 2.1/3 Rev 3; however, it is worth noting that blood bags containing a medicinal substance are included as medical devices incorporating a medicinal substance as an integral part. These devices previously classified as IIb under the MDD are now class III under rule 14.
This MDCG is essential reading for manufacturers with borderline products whether transitioning to the MDR or accessing the EU market for the first time. It provides greater detail and a “principles-based” rather than “list-based” approach, together with flow charts, to help steer manufactures and regulators through this complex area.
MDCG 2022-5 does not cover the consultation process for devices classified under rule 14 (this was included in the MEDDEV guidance). Manufacturers, therefore, currently have to rely on guidance from individual Notified Bodies and medicines agencies such as the EMA guidance which references MEDDEV 2.1/3 Rev3. Intriguingly, MDCG 2022-5 does make reference to MDGC guidance on the consultation procedures for rule 14 and rule 21, so presumably this will be published soon, although not currently included in the list of MDCG under development.
How Can NAMSA Help?
- Do you have devices that incorporate a medicinal substance?
- Do you have products which sit on the borderline between devices and drugs?
- Are you unsure whether rule 14 or rule 21 applies to your device?
- Has your Notified Body told you that rule 14 applies to your legacy device?
- Do you have a legacy device which now falls under rule 14 and needs a medicines agency review?
At NAMSA, our European regulatory team can help guide you through this complex regulatory environment and help determine the correct regulatory pathway for your product. Our experts have extensive experience in compiling consultation dossiers for devices incorporating medicinal substances with ancillary action. Combined with our biological safety, clinical research and Clinical Evaluation Report (CER) writing expertise, NAMSA is uniquely placed to help you generate the necessary data to support your consultation submission.
To learn about NAMSA’s full suite of Regulatory and Quality services and solutions, including MDR compliance planning, please visit: https://namsa.com/services/regulatory-and-quality-consulting. Or, if you’re ready to set up a complimentary consultation, get in touch with one of our experts here: https://namsa.com/namsa-expertise/subject-matter-experts.
Jane Arnold-Round has 30 years’ experience in the medical device industry working with a broad range of medical device technologies and organisations from start-ups to multinationals. She was a Notified Body reviewer for over 15 years having worked for BSI as a medical device product specialist with particular responsibility for the wound care sector, device-drug combinations medical device utilising animal tissues. A regulatory consultant for 17 years, she joined the medical device consulting team at NAMSA in 2018 and currently serves as a Senior Principal Regulatory Consultant.