Earlier this week, in a plenary vote, the EU Parliament endorsed the texts of the Regulation on Medical Devices (the “Regulation”—latest version available here) and the parallel Regulation on In-Vitro Diagnostic Medical Devices (the “IVD Regulation”—latest version available here).  This presents a good opportunity to have a closer look at one of the essential questions of the revision of the medical device rules, namely, whether the scope of the Regulation changes in comparison to that of the main Medical Devices Directive 93/42/EEC (the “Directive”).  We examine below the changes to the definition of a medical device and whether the Regulation affects borderline determinations.

As discussed in our earlier post, the borderline between medical devices, medicinal products, cosmetics and foods or food supplements is often blurred.  The Regulation sheds some additional light on the definition of a medical device and strengthens the Commission’s power in relation to the borderline issues.  Nevertheless, important questions continue to exist, for instance in relation to the pharmacological versus physical (or purely chemical) mode of action of a product.

Broader Scope

The Regulation somewhat widens the definition of a medical device, compared to the Directive.  Below we copy the definition of a medical device of Article 2(1) of the Regulation, identifying with bolded and underlined text where it differs from the Directive:

“any instrument, apparatus, appliance, software, implant, reagent, material or other article, whether  intended by the manufacturer to be used, alone or in combination, including software intended by tis manufacturer to be used specifically for diagnostic and/or therapeutic purposes and necessary for its proper application, intended by the manufacturer to be used for human beings for one or more of the following specific medical purposes of:

• diagnosis, prevention, monitoring, prediction, prognosis, treatment or alleviation of disease,
• diagnosis, monitoring, treatment, alleviation of, or compensation for, an injury or handicap disability,
• investigation, replacement or modification of the anatomy or of a physiological or pathological process or state,
• providing information by means of in vitro examination of specimens derived from the human body, including organ, blood and tissue donations,
• control of conception

and which does not achieve its principal intended action in or on the human body by pharmacological, immunological or metabolic means, in or on the human body, but which may be assisted in its function by such means.”

The additions to the definition (e.g., reagent, the manufacturer’s intent, medical purpose, prediction, etc.) are expected to answer at least some of the qualification questions that exist today.  The Regulation also specifies—in a separate subparagraph of Article 2(1)—that products intended for cleaning, disinfecting and sterilising medical devices and devices for the control and support of conception are “deemed to be” medical devices.

Besides containing a broader definition, the Regulation also subjects some products without medical purpose to the new rules.  They are listed in Annex XVI and are regulated because they have a risk profile that is similar to that of medical devices.  For example, coloured contact lenses, which are only used for aesthetic purposes, would be required to comply with the Regulation.  Other “non-medical” devices include liposuction equipment and equipment intended for brain stimulation.  On the other hand, the Regulation clarifies that products utilising viable biological materials or viable organisms such as bacteria or fungi are not covered by the medical devices regulatory regime.

Borderline Determinations

New Procedure for Borderline Determinations

Borderline issues arise when the regulatory qualification of a product—for instance as a medicine, a food (supplement), a cosmetic or a medical device—is not clear.  For example, an “antiseptic” or “antibacterial” mouthwash can be qualified as a biocidal, cosmetic or medicinal product.  Currently, borderline determinations are made almost exclusively at the Member State level.

The Directive adopts a system that allows the European Commission to decide whether a product falls within the definition of a medical device, but only on a “duly substantiated” request from a Member State.  In practice, this procedure is very rarely used (Article 13(1)(d)).  To date, there has been only one instance when it was used; at the request of France, the Commission prepared a draft decision that “products whose principal intended action, depending on proanthocyanidins (PAC) present in cranberry (Vaccinium Macrocarpon), is to prevent or treat cystitis” are not medical devices (see our earlier post).  We understand that there is no final decision yet.

Because of the strong focus on national decision-making, the same product can qualify as a medical device in one Member State, and as a food, cosmetic or medicine in the other (as confirmed by the European Court of Justice in case C-109/12).  It is hard to predict to what extent the new regulatory regime will affect this lack of harmonisation.  Interestingly, the Regulation strengthens the powers of the Commission to ensure a more consistent qualification of the borderline products across the EU.  The new procedure (outlined in Article 4 of the Regulation) builds on Article 13 of the Directive, and gives the Commission power to decide about the product qualification not only at a Member State request, but also at its own initiative.  It is important, therefore, that  during its deliberations, the Commission consult the Medical Device Coordination Group (MDCG) and/or the relevant agencies (i.e., the European Medicines Agency, the European Chemical Agency and the European Food Safety Authority) to ensure an appropriate level of scientific expertise.

Continuing Confusion About the Mode of Action?

One of the key issues in determining the regulatory classification of a product is its principal mode of action.  More specifically, a product only qualifies as a medical device when it does not achieve its principal intended action by pharmacological, immunological or metabolic means (see the definition in Article 2(1) of the Regulation above).  In other words, the product must have a primarily physical or chemical mode of action.  The Directive and the Regulation do not provide definitions of these modes of action.  Instead, the European Commission guidance on the borderline between medical devices and medicines (“the MEDDEV Guidance”) provides the following definitions: 

• pharmacological mode of action: “an interaction between the molecules of the substance in question and a cellular constituent, usually referred to as a receptor, which either results in a direct response, or which blocks the response to another agent. Although not a completely reliable criterion, the presence of a dose-response correlation is indicative of a pharmacological effect.”  We note the European Court of Justice confirmed (see case C-308/11) that, while not legally binding, guidelines on borderline issues may be taken into account “in order to apply the term ‘pharmacological action.’”

• immunological mode of action: “an action in or on the body by stimulation and/or mobilisation of cells and/or products involved in a specific immune reaction.”

• metabolic mode of action: “an action which involves an alteration, including stopping, starting or changing the speed of the normal chemical processes participating in, and available for, normal body function.”

These definitions still leave many questions unanswered, and do not always allow a clear-cut borderline determination.  The Regulation seems to take account of this reality as it underscores the need to consult with the relevant EU agencies when deciding about the qualification of the product.

In addition, these definitions also seem to be moving targets.  For instance, in relation to the qualification of the cranberry capsules (mentioned above), the European Medicines Agency’s scientific committee (CHMP) issued an opinion using broader definitions of pharmacological, immunological and metabolic modes of actions than the MEDDEV Guidance:

1. The CHMP’s view is that a pharmacological mode of action means

“a direct interaction between, or an indirect effect of, the molecules of the substance in question or its metabolites, and a constituent of the human body (including any of its parts, or an organism or other pathogens within or on the body) through any type of chemical binding which results in initiation, enhancement, mitigation or blockade of physiological or pathological characteristics. Although not a completely reliable criterion, the presence of a dose-response correlation is indicative of a pharmacological effect.”

This definition differs from the MEDDEV Guidance definition quoted above.  The addition “including any of its parts, or an organism or other pathogens within or on the body”, for instance, reflects the reasoning of the European Court of Justice in case C-308/11.  Indeed, the Court considered that “the molecules of which do not interact with a human cellular constituent may nevertheless, by means of its interaction with other cellular constituents present within the user’s organism, such as bacteria, viruses or parasites, have the effect of restoring, correcting or modifying physiological functions in human beings.”

2. With respect to the definition of immunological mode of action, the CHMP included “replacement” as an example of exerted action by immunocompetent cells.

3. The metabolic mode of action as considered by the CHMP not only refers to the alternation of the speed of the chemical process—now defined as normal and pathological one—but also to the change of its extent and nature.

It seems that, despite the Regulation’s clarifications of the medical device definition and the elaborated procedure on borderline decisions, complex qualification questions are likely to persist.  It is, for instance, not hard to imagine that different definitions of principal modes of actions may lead to different borderline determinations.  Therefore, under the Regulation, as under the Directive, manufactures will need to continue paying close attention when determining the regulatory classifications of their products.

Following the Parliament endorsement in plenary, the texts of the Regulation and the IVD Regulation will be published in the EU Official Journal, probably in May.  Both texts will start applying, respectively, three and five years after their publication and companies will need to plan very carefully their compliance with the new rules.

Anna Wawrzyniak, PhD, contributed to this post.