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RULE 21 – New Requirement under MDR for medical devices that are composed of substances or combinations of substances

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An update to MDR EU 2017 / 745

Medical Device Regulation EU 2017/745 has introduced a new rule for classification of the devices and relates to the devices that are composed of substances or of combinations of substances that are intended to be introduced into the human body via a body orifice or applied to the skin and that are absorbed by or locally dispersed in the human body.

Body orifice is defined as any external opening in the body of an animal. In a typical mammalian body such as the human body, the body orifices are: nostrils, eyes, mouth, ear canals, anus, urethra, vagina, orifices of nipples, orifices of sweat glands, and navel.

Manufacturers of substances-based devices should provide clear information supporting the mode of action through which the substance achieves the intended specific medical purpose as a basis for the application of this rule.

The classification takes into account:

  • The site of application of the medical device,
  • The site where the medical device performs its action, in or on the human body.
    For the purpose of this rule, nails are also considered as falling under “skin”.

The definition of the word “substance” according to the MDR is any matter that is part of the medical device, including those according to the definition of “substance” in Article 1(3) of Directive 2001/83/EC.

In addition, if the principal intended action of such substance-based medical devices is achieved or supported by pharmacological, immunological, or metabolic means, Directive 2001/83/EC or Regulation (EC) No 746/2004 Rule 14 has to be applied to the product, respectively.

Relevant requirements of MDR and Annex I of Directive 2001/83/EC for the evaluation of substance-based devices are:

  • Absorption, distribution, metabolism, and excretion of each substance contained in the device.
  • Local tolerance of each substance and also for the whole device.
  • Toxicity profile for each substance.
  • Possible interactions with other devices, medicinal products, or other substances.
  • Any potential for an adverse reaction.

In order for the manufacturer to assess the above endpoints, they should consider the below:
✓ If toxicokinetic studies should be considered or the data collected from the literature is enough to prove the ADME of each substance separately, relating to the site of application.
✓ If a physical and chemical characterization according to ISO 10993-18 is appropriate for the medical device characterization.
✓ Identification of the active substances and in vitro models demonstrating the mode of action.
✓ If biocompatibility studies are necessary to be performed or the data collected from the literature are enough to prove the safety of the product, relating on the contact duration of the device with the user/patient, the ingredients’ toxicological profile, the ADME of each ingredient and possible antagonistic or synergistic effect, and the site of application (for instance, intact skin or breached).

If your company needs any further guidance on how to assess the above endpoints, we can support you. Contact us today to learn more about our services: