New CJEU ruling on the borderline between medicinal products and medical devices: Key takeaways

The Case

The product concerned contains a substance used in urology, D-mannose. which has been marketed as medical device for the prevention and supportive treatment of cystitis and other urinary tract infections. D-mannose attaches in urine to an adhesin on Escherichia coli bacteria and thus prevents the bacteria from adhering to certain structures in the bladder wall. While the manufacturer argued that the product`s mechanism of action was purely mechanical/physical, the claimant, an industry association, however assumed a pharmacological effect, so that the product would qualify as a medicinal product by function and have to be authorized accordingly.

The Regional Court of Cologne and the Higher Regional Court of Cologne had decided that the product qualified as a medicinal product and could therefore not be marketed as a medical device. During the appeal proceedings, the German Federal Court of Justice referred the question of the product’s classification to the CJEU.

CJEU Judgment

Based on the guidance of the Medical Device Coordination Group (MDCG), MDCG 2022 – 5 Rev. 1 on borderline between medical devices and medicinal products, the concept of a ‘pharmacological action’ requires an “interaction between a substance or its metabolites and a constituent of the human body which results in initiation, enhancement, reduction or blockade of physiological functions or pathological processes”.

Constituent of the human body:

The CJEU states that an interaction with other (non-human) cellular constituents present within the user’s organism, such as bacteria, viruses or parasites, can be sufficient to assume a ‘pharmacological action’ (cf. Judgement of 6 September 2012, Chemische Fabrik Kreussler, Case C-308/11).

Interaction:

Furthermore, the CJEU argues that the interaction with the constituent within the human body (here: the bacteria) does not per se require the modification of the modular structure of the cellular constituent, so that a bonding by means of a hydrogen bond is sufficient. The CJEU stresses that the relevant provisions and guidance documents do not stipulate the requirement of an interaction in form of a permanent binding, so that also a reversible binding to a cellular constituent can be regarded as exerting a ‘pharmacological action’.

(Temporary) blockade of pathological processes:

Finally, the CJEU states that the substance causes a blockade of pathological processes, as it prevents the bacteria from adhering to certain structures in the bladder wall. Again, the CJEU argues that this does not require an irreversible binding.

Conclusion

While it might seem quite surprising that even a reversible binding only to bacteria is sufficient to be regarded as exerting a ‘pharmacological action’ and thus to qualify as a medicinal product, the ruling is in line with the general approach of the CJEU to interpret the definition of medicinal products broadly to ensure that the high safety standards from the medicinal products legislation apply. 

As an immediate consequence of the judgment, products containing D-mannose may no longer be sold as medical devices or food supplements and have to be withdrawn from the market. The ruling reinforces the general need for careful regulatory analysis in the classification of borderline products. Manufacturers and regulatory teams should (i) reassess the classification of borderline products on the market/ in development; (ii) ensure the technical documentation addresses the product´s mode of action in detail, (iii) be prepared for challenges of a product’s classification by industry associations or authorities. Furthermore, they should keep monitoring the regulatory developments and particularly the jurisdiction of the CJEU to evaluate any potential impact on the classification of their products leading to significant consequences for product approval, documentation and compliance requirements.