The guidance on the borderline between medical devices and medicinal products is now released in its final version. Its publication is very welcome as it replaces the old “borderline manual”, formally only applicable to MDD but practically, lacking alternatives, still used to unravel complex MDR classification issues.
Compared to the “borderline manual” the MDCG guidance is more detailed on the theory (legal basis) for classification and less on the examples. Which is possibly natural given the relatively limited experience we have with MDR classifications.
The document discusses extensively what are the aspects to consider for determining whether or not the combination of a medicinal substance with a medical device should be regulated under the Medicinal Product Directive or the MDR. This isn’t new or different from the MDD but the document includes useful guidance on what to take into account to prove and justify if the principal mode of action is achieved by pharmacological, immunological or metabolic means or not.
The document expands from the “borderline manual” on the topic of herbal medicinal products confirming that, when the principal mode of action cannot be defined, a combination-device should be regulated as a medicinal product. This approach of “in-doubt use the medicinal product directive” applies not only to devices incorporating herbal products but it is more likely to happen since herbal products are typically a mixture of several components often with unknown pharmacodynamics.
Useful is also the section related to substance-based devices. This is an area that, from a regulatory perspective, is still quite unexplored, therefore some definitions, clarifications and examples are very welcome.
The most surprising part though, is the section related to the removal of the wording “which is liable to act on the body” from rule 14. To trigger a class III classification and a drug authority consultation, the MDD required a device to incorporate a medicinal substance and this substance to be liable to act on the human body (ancillary action). This wording was removed from the text of the MDR and we have all (including Notified Bodies) been discussing how the intent of this was to make class III and subject to consultation any device incorporating a medicinal substance, whatever the amount and the effect on the patient. We have all been complaining that this draconian approach was impractical, not based on actual risk and would engulf competent authorities with lots of unnecessary consultations. Well, it appears we were wrong and were complaining and discussing about nothing: the concept of “liable to act” was sent out of the front door just to be brought back from the back door.
The explanation given in MDCG 2022-5 is that in the MDR wording “a substance which, if used separately, can be considered to be a medicinal product […] and that has an action ancillary to that of the devices” we need to focus on the verb “has”. Basically if you can prove that the medicinal substance, present in a device, does not have an action, then rule 14 is not applicable, the device is not automatically class III and a consultation is not required. The document goes even further explaining that the change of wording moves from a possibility (“liable to”) to a certainty (“has”); which potentially suggest the MDD being stricter as the simple possibility of a substance having an action triggered the extra requirements.
That is, I must admit, quite a surprise, although the draft version of the documents already gave some signs of the MDCG group heading this direction. And to be clear, it is a very good surprise. It takes away some unreasonable and unnecessary burden from certain devices that include a substance that is also a medicinal substance but it is not having any effects as such. Be aware, this is not a “get out of jail free” card: manufacturers have to prove and justify in a scientific manner that the substance has no action on the human body. It is not enough that the substance is not used for the pharmacological/immunological/metabolic action or it is not intended (or claimed) to have these types of action. It is not enough that the device is designed to keep the substance embedded and without direct contact with the body. It is not enough that the substance is present in minimal amount.
It must be positively demonstrated that it cannot leak into the body or that the amount is such that it does not have any effect on the patient or that, for any other reason, there is no pharmacological, immunological or metabolic action. It will definitely take some effort but it might be well worth it.
If your device might fall into the group of products incorporating a medicinal substance that has no action on the human body, you should start as soon as possible preparing your justification and collecting your evidence. The process might be long and require testing and the time to the end of the transition period is short, so there is no time to waste if you want to be ready in time. And if you need support with your strategy or justification, please get in touch with us at email@example.com. We will be more than happy to guide you and support you towards a positive result.