The Impact of Medicinal Substance Levels on Medical Devices and Borderline Product Classification in the EU

This blog will help you to understand how medicinal substance levels may affect borderline product classification and, more specifically,medical devices incorporating a medicinal substance with an ancillary action.

The status of many products on the “borderline” between medicinal products and food supplements, biocides, cosmetic products or medical devices can be difficult to determine.

These cases are decided after considering the manufacturer’s intended purpose for the product taking into account the way it is presented and the method by which the principal mode of action is achieved. In the case of a medical device, the principal mode of action is typically fulfilled by physical means (including mechanical action, physical barrier, replacement of, or support to, organs or body functions).

Medical devices may be assisted in their function by non-mechanical action

Medical devices may be assisted in their function by pharmacological, immunological or metabolic means as long as this is not defined as their principal mode of action. Accordingly, where a product achieves its principal intended action by pharmacological, immunological or metabolic means, it is a medicinal product.

Medical devices incorporating, as an integral part, a medicinal substance with an ancillary action

The Medical Device Directive (MDD) and the Active Implantable Medical Devices Directive (AIMDD) specify the definition of medical devices incorporating, as an integral part, a medicinal substance with ancillary action.

This definition relates to a device that incorporates, as an integral part, a substance which, if used separately, may be considered to be a medicinal product within the meaning of Article 1 of the Medicinal Product Directive (MPD) and which is liable to act upon the body with action that is ancillary to that of the device.

Thus, the substance incorporated in the device must meet all three of the following conditions:

• The substance, if used separately, may be considered to be a medicinal product
• The substance is liable to act upon the human body
• The action of this substance is ancillary to that of the device

Let’s focus on the first condition, to understand when the substance, if used separately, may be considered to be a medicinal product.

Article 1 of Directive 2001/83/EC as amended defines a “medicinal product” as:

• “Any substance or combination of substances presented as having properties for treating or preventing disease in human beings (first limb);
• Any substance or combination of substances which may be used in, or administered to, human beings, either with a view to restoring, correcting or modifying physiological functions by exerting a pharmacological, immunological or metabolic action, or to making a medical diagnosis (second limb)”

However, regulatory guidance documents give no definition for the terms “illness” or “disease”. The only possible definitions for these terms are therefore those most commonly accepted on the basis of scientific knowledge.

In European Court Case C-369/88 Delattre, “disease” is defined as “any injury, ailment or adverse condition, whether of body or mind”.

The importance of medicinal substance levels in the medical device product – regulatory practice

In other to treat or prevent disease or exert a significant effect on the actual functioning of the body, the amount of the medicinal substance plays a very important role. This scientific fact is also reflected in EU regulatory practice.

EU guidance about borderline products and medical devices which incorporate anancillary medicinalsubstance (MEDDEV 2. 1/3 rev 3) reads that “The definition of medicinal product must be applied case by case and must be read in accordance with the case law of the European Court of Justice.”

EU court cases in the impact of medicinal substance levels on product classification

We present here several EU Court Cases which stress the importance of recommended dosage or medicinal substance levels when an evaluation of the borderline products is undertaken.

Court Case (C-140/07) Hecht-Pharma GmbH v StaatlichesGewerbeaufsichtsamtLüneburg states that “it would be necessary for the competent national authorities also to have to base their assessment on the dosage recommended by the manufacturer, since the manner in which the product is to be used can be seen from the recommended dosage”.

Important conclusions may be drawn from the case-law of the Court on the classification of vitamin preparations.

In the Van Bennekom case, the Court held that vitamins may not, as a general rule, be regarded as medicinal products since they are only consumed in small quantities. However, the Court then emphasized that vitamin or multi-vitamin preparations are sometimes used, generally in large doses, for therapeutic purposes in combating certain diseases other than those for which the morbid cause is a vitamin deficiency.

On the basis of this argument, in Commission v Germany, the Court ruled, in contrast with Community Law, a national administrative practice under which vitamin preparations which were legally manufactured or placed on the market in other Member States as food supplements were automatically classified as medicinal products if they exceeded three times the daily amount recommended by the Deutsche Gesellschaft fürErnährung (German Food Association).

In relation to this finding, it was decided that the three-fold rule would be automatically applied by the national authorities, without any assessment being made on a case-by-case basis by reference to the different vitamins added or to the risk associated with taking them.

The Court Case (C-140/07) concludes that . . . “it is not possible to draw scientifically accurate conclusions in relation to a product’s characteristics as a medicinal product without taking into account the respective intended dosage”.

What does literature say about intended dosage of medicinal substances?

A similar standpoint on medicinal substance dosage is discussed in the relevant literature.

Dettling, H. U (2007),refers to the fact that in many substances and preparations derived from substances, different effects may be produced depending on the dosage. In his opinion, in order for a product to be considered a medicinal product, its useful modifying effect on bodily functions, in the actual dosage, combination, pharmaceutical form and application, had to be the main effect of the substance or the preparation made from substances.

Similarly, Büttner, T (2006), states that the dosage of a substance is decisive. Büttner writes that it is true that a number of vitamins, minerals and other substances have authorizations as medicinal products. However, from this it cannot be concluded that, as a matter of principle, a therapeutic purpose and a pharmacological effect have to be assumed. On the contrary, he argues that an exact differentiation must be made according to the dosage from which authorization as a medicinal product was granted.

Finally, Kraft, F (2006), states that the mere fact that a substance is contained in an authorized medicinal product is not in itself sufficient to justify the assumption that, as a matter of principle, a food supplement containing this substance has pharmacological effects. This applies in particular to ‘dual-use’ substances, which, depending on the dose administered, could be used for either nutritional-physiological or medicinal purposes.

So, in order to satisfy the second limb of the medicinal product definition, one would have to prove or disprove that the substance under discussion has the ability, usually based on extensively available and published scientific data, to modify physiology through pharmacological means at the dosage level used.

Therefore, the manufacturer of a medical device which includes a substance potentially defined as medicinal should analyse scientific literature on the substance and common regulatory practice relating toproducts which include these substances.

Specifically, the company should have knowledge about the concentration of the substance included in the product and its total levels based on the recommended dosage.

The resultofsuchanalysis could have far-reaching consequencesfor the commercial success of the company.

In the case where the incorporated medicinal substance with an ancillary action is considered to be a medicinal product, the medical device will be classified as Class III, based on Rule 13.

If this is not the case, such product could be classified as Class II or even Class I in the EU.

The costs and approval times for Class III productsare significantly greater compared to Class I or Class II devices and therefore theclassification may have a major impact on the company’s success.

BioRegards,

Daniel

References

Dettling, H. U., (‘Physiologische, pharmakologische und toxikologischeWirkung – Ein BeitragzurAbgrenzung von Lebensmitteln, Arzneimitteln und gefährlichenStoffen (Teil 1)’, Lebensmittel&Recht, 2007, part 1, p. 8).

Büttner, T., (‘Die Zweifelsregelungenthebtnicht der Prüfung, obein Medicinal product vorliegt’, Zeitschriftfür das gesamteLebensmittelrecht, 2006, part 6, p. 762).

Kraft, F. (KlareWortezurZweifelsregelung“, Zeitschriftfür das gesamteLebensmittelrecht, 2006, part 6, p. 751).