MDR: Innovations and Implications for Medical Devices Based on Substances
Regulation (EU) 2017/745 has introduced significant innovations in the field of medical devices, particularly those composed of substances. However, the distinction between these and medicines can be blurred, leading to lengthy and complex discussions. The European Commission’s MDCG 2022-5 guide aims to clarify these contentious issues to guide the product qualification process.
This article will discuss some controversial aspects in this field in order to clarify the product qualification process.
Regulation (EU) 2017/745, fully applicable since May 2021, has introduced several innovations in the medical devices sector; among these, medical devices (MD) composed of substances deserve special mention.
The definition of MD in Regulation (EU) 2017/745 (MDR) states that the use for which medicinal products (MP) and medical devices are intended is very similar, with the only difference being the mechanism of action, which is pharmacological, immunological, or metabolic for MPs.
Medical devices composed of substances have a medical purpose and are available in a presentation similar to medicinal products, such as eye drops, creams, syrups, capsules, yet they do not fall under the definition of drugs because the mechanism of action responsible for the intended main action is non-pharmacological, non-immunological, or non-metabolic, but physical (e.g., mechanical action, physical barrier, lubrication, etc.).
Evolution of Medical Devices Based on Substances
In the last 20 years, many substance-based products have been classified as medical devices under Directive 93/42/EEC, although they were not originally contemplated. The term “material” has been translated as “substance,” paving the way for this category. However, the lack of specific rules has led to lengthy discussions on their safety and classification.
Regulation (EU) 2017/745: Further Steps Forward
The MDR has finally recognized medical devices composed of substances as a defined category. The final version of the regulation introduced specific requirements and classification rules to address safety concerns.
In order to obtain a risk-based classification of devices composed of substances, specific classification rules have been introduced, taking into account the site where the device acts in the human body, whether it is introduced or applied, and whether there is systemic absorption of substances.
Based on these considerations, the legislator introduced an ad hoc classification rule in the MDR, Rule 21 (Annex VIII), as well as specific essential requirements.
Rule 21: Classification and Specific Risks of Medical Devices Composed of Substances
Rule 21 takes into account specific risks for medical devices based on substances, precisely in relation to the fact that they are intended to be introduced into the human body (through an orifice or to be applied on the skin) and, above all, considering that substances are absorbed by the human body or locally dispersed in it. The risk class depends on the route of administration and any systemic absorption.
Unlike the previous regulatory framework, medical devices composed of substances can no longer be classified as Class I, so all conformity assessment procedures involve the intervention of a notified body.
Furthermore, for the first time, the concept of local dispersion is mentioned in the MDR and defined in MDCG Guide 2021-24 as “the condition in which substances remain at a specific site without being distributed throughout the body through the circulatory and/or lymphatic system.”
Guidance on the Borderline between Medical Devices and Medicinal Products under the MDR (MDCG 2022-5)
The recent publication of MDCG Guide 2022-5 represents a crucial document in the context of qualifying products at the borderline between medical devices and medicinal products. An important starting point is the definition of “substance,” which is not specified in the MDR but is referred to in Directive 2001/83/EC.
The guide focuses on the importance of distinguishing between the intended use of a medical device and the mechanism of action that determines its therapeutic effect. While the intended use may resemble that of a medicinal product, it is the mechanism of action that delineates the difference between the two.
The pharmacological mechanism of action, as defined by MEDDEV Guide 2.1/3 rev.3, involves two steps: an interaction between the substance and the human body followed by an event that produces a conformational change. This subsequent event is essential to determine the therapeutic effect.
Conversely, medical devices are based on a simpler mechanism of action, producing a therapeutic effect without requiring a subsequent event. The interactions described in medicinal products are primarily pharmacological, as they lead to a subsequent event targeted at a specific site of action.
In summary, MDCG Guide 2022-5 provides clarity on the distinction between medical devices and medicinal products, highlighting the importance of the mechanism of action in determining this distinction.
Medical Devices Composed of Herbal Substances
Qualifying medical devices containing herbs is particularly complex. Herbal mixtures have multiple mechanisms of action, making it difficult to identify the principal one for the correct qualification of the product.
Directive 2001/83/EC, as amended by Directive 2004/24/EC, provides a simplified registration for traditional herbal medicinal products (THMP). However, challenges in identifying the mechanism of action may lead to a lack of description in the Pharmacodynamics section of the summary of product characteristics (SmPC), as required by the directive.
EMA’s THMP monographs specify the intended use and route of administration for products with recognized traditional use, establishing criteria for safety and efficacy. This standard of evidence is lower than that required for medical devices composed of substances under the MDR.
Data Required by Regulation (EU) 2017/745 for Devices Based on Substances
The MDR establishes specific standards for the safety and performance of medical devices composed of substances. These devices must comply with the general safety and performance requirements of Annex I, Section 12.2. Additionally, they must be assessed for absorption, distribution, metabolism, excretion, local tolerance, toxicity, and interactions with other devices or substances, following the guidelines of Directive 2001/83/EC.
For devices that are absorbed into the body to achieve their purpose, the MDR provides for a consultation procedure with a competent authority for medicinal products or the EMA. This opinion is not binding but is part of the notified body’s conformity assessment. The notified body must carefully consider this opinion and communicate its final decision to the consulted authority.
Annex II provides additional information necessary for specific cases, such as absorption studies, distribution, metabolism, interactions, local tolerability, and toxicity. If such studies are not available, adequate justification is required.
The MDR establishes that the qualification of a product as a medical device is the responsibility of the manufacturer, in consultation with the notified body, and must comply with relevant regulatory requirements. The data in the technical file must be robust, scientifically valid, and state-of-the-art.
To ensure consistent decisions among Member States, the Commission may decide whether a product, category, or group of products falls within the scope of the MDR, consulting the EMA, ECHA, and EFSA.
The MDR has overcome the idea that a product qualified as medicinal was automatically safer than one qualified as a medical device. Now, for medical devices composed of substances, comparable data to those for medicinal products are required. This raises the standard of evidence needed and promotes the safety and effectiveness of medical devices composed of substances, even though they may present additional challenges in terms of innovation and development.
Need guidance to comply with the MDR? We are here to guide you through the regulatory process and ensure compliance of your medical device.
With determination, Gruppo FarmaImpresa has embraced the complex certification process according to the MDR, keeping safety and quality at the heart of its corporate mission.
The first certifications obtained concern emulsions containing simethicone in six different variants. Furthermore, we have acquired MDR certification for intra-articular syringes based on high molecular weight hyaluronic acid, further enriching our portfolio of CE certifications within the MDR context.
Source: Leone Maria Grazia, Medical Devices Made of Substances: A New Challenge, Frontiers in Drug Safety and Regulation, VOL.2, 2022, 10.3389/fdsfr.2022.952013.
