There are products with substances, among the so-called ‘borderline’ substances, for which the identification of the correct legal context is not straightforward.

These products could fall within the scope of the Medicinal Products Directive MPD 2001/83/EC because they are classifiable as medicinal products; otherwise, they could fall within the scope of the MDR (EU) 2017/745 as they have the characteristics of substance-based Medical Devices. Therefore, it is first necessary to assess the product category according to the respective definitions of medical device (according to MDR) and medicinal product (according to MPD).

In this article, we focus on drug-supported Medical Devices with an ancillary function, to understand their characteristics and requirements to be demonstrated to fall within the framework of the MDR (EU) 2017/745 Medical Device Regulation.

MDR (EU) 2017/745 introduced several novelties for substance-based Medical Devices (medicinal and non-medicinal), in response to the need for a more adequate risk assessment related to the use of substance-based products (invasive products and/or products that can be absorbed), as well as revising the classification rules.

Medical Devices Supported by a Drug with an Ancillary Function

Substance-based Medical Devices are included in the definition of a medical device in the MDR (EU) 2017/75, i.e. a product with a specific medical purpose that does not exert in or on the human body the principal action for which it is intended by pharmacological, immunological or metabolic means, but whose function may be assisted by such means. Substance-based Medical Devices consist, for example, of solutions, ointments, sprays, tablets, and drops containing substances permitted by MDR (EU) 2017/745 and which are applied to or introduced into the human body.

A substance-based medical device differs from a medicinal product, which is any substance or combination of substances, which may be administered to human beings to make a medical diagnosis or to restore, correct or modify physiological functions by exerting a pharmacological, immunological or metabolic action, or to making a medical diagnosis.

In particular, substance-based Medical Devices using pharmaceuticals with an ancillary function are specifically regulated by the MDR (EU) 2017/745, starting with the classification in Rule 14 (Anx. VIII) and ending with hybrid testing to demonstrate compliance of these products.

A medical device with an ancillary function is defined as a device whose main action is not achieved through a medicinal substance but may include a pharmaceutical component that plays an ancillary or secondary role, e.g. gauze soaked in a fungal substance. In other words, if the substances incorporated in the device exert a pharmacological, immunological or metabolic action, but this action is ancillary to the main mechanism of action by which the device achieves its medical purpose, then the device must be evaluated and authorised under the MDR, and follow the classification rules of Annex VIII.

In these cases, the substance’s quality, safety and efficacy are verified by analogy with the methods in Annex I of Directive 2001/83/EC – MPD.

Mechanism of Action and Demonstration of the Ancillary Function of the Medicinal Substance

The decisive demarcation criterion for the distinction between Medical Devices and medicinal products is the so-called ‘principal mode of action’, i.e. the product’s mechanism of action.
The mechanism of action represents the principal means by which the product achieves its intended use, i.e. a physical/mechanical mechanism in the case of Medical Devices and a pharmacological, immunological or metabolic mechanism in the case of medicinal products.

Examples of typical main mechanisms of action of Medical Devices are the formation of a physical barrier such as a film, lubrication, heat transfer, radiation, ultrasound, hydration or dehydration and pH modification.

It is important to emphasise that the determination of the nature of the substance, i.e. whether it should be ‘considered a medicine’ or not, is independent of the manufacturer’s intention, its quantity in the device and the route of administration.

On the contrary, the ancillary action of the substance must be scientifically objective and demonstrable and take into account its biocompatibility with the human body.
It is therefore up to the manufacturer to prove whether the substance has an ancillary action, based on objective scientific data up to date with the state of the art.

Qualification, Product Classification According to MDR

For the demonstration of ancillary drug action, specifications concerning test or study protocols, methods of analysis and data synthesis, and conclusions on ADME testing must be included in the technical documentation. Studies that are not submitted must always be accompanied by a justification with a scientific basis.

To be covered by the MDR, a product must meet the definition of a medical device (Article 2(1)) and must not be excluded from its scope of application (Article 1(6)):

• Device description;
• Intended Use;
• Mechanism of Action;
• Contact with the patient.

Currently, substance-based devices can no longer be sold on a self-certification basis as per the previous Directive, but fall from Class II to Class III depending on the cases expressed in Rule 14 and Rule 21 of the MDR (EU) 2017/745. Therefore, each substance-based device will have to be verified by a Notified Body, with possible joint consultation with other authorities as appropriate, such as EMA and EFSA.

With the Borderline service, THEMA, in synergy with the other companies of the Complife Group, can offer integrated and comprehensive support for regulatory compliance and quality management in the substance-based device market. Furthermore, in collaboration with other Complife Group companies, Thema can provide support in the planning and execution of biocompatibility tests, ADME tests and mechanism of action demonstration.

 

Contact us: sales@thema-med.com.