The EU Medical Device Regulation (MDR) introduces, as part of Annex I General Safety and Performance Requirements, new material and substance requirements for medical devices and device parts of single integral products. The aim of these new requirements is reducing as far as possible the risk posed by substances or particles from materials, degradation products and processing residues that may be release from the device.
Within section 10.4. Substances, section 10.4.1. Design and manufacture of devices indicates that invasive devices or components that come into direct contact with the body, or devices (re)administering, transporting or storing medicines or body liquids, shall only contain a concentration above 0.1 percent by weight of certain substances when justified according to section 10.4.2. Justification regarding the presence of CMR and/or endocrine disrupting substances. The substances of concern are those considered carcinogenic, mutagenic or toxic to reproduction substances (referred to as CMR) and substances with endocrine disrupting (referred to as ED) properties. If any of these substances are used and cannot be replaced or eliminated without affecting negatively the benefit-risk ratio, a justification for their use must be provided considering potential exposure of the patient or user, possible alternatives and suitability, relevant scientific committee guidelines, etc.
In the Medical Devices Directive (MDD) 93/42/EEC, material safety was already a topic of concern, included in Annex I Essential requirements, Section 7. Chemical, physical and biological properties. For example, Section 7.5. states that special attention shall be given to CMR substances when considering risks posed by substances leaking, and that phthalates classified as CMR must also be identified and labeled. However, in the Medical Devices Regulation (MDR) 2017/745, requirements are more stringent.CMR substances must be identified and justified when they are present in a concentration above 0,1%w/w in invasive devices or devices that are in contact with medicines or body fluids that are(re)administered into the body, regardless if such substances are leaking or not. MDR also introduces anew category: ED substances. Phthalates are specifically mentioned too, as in MDD, but only when they fall under CMR or ED categories.
Carcinogenic, mutagenic or toxic for reproduction substances (CMR)
“substances which are carcinogenic, mutagenic or toxic to reproduction (‘CMR’), of category1A or 1B, in accordance with Part 3 of Annex VI to Regulation (EC) No 1272/2008 of the European Parliament and of the Council (1)”- MDR Annex I 10.4.1.(a)
Part 3 of Annex VI to Regulation (EC) No 1272/2008 (CLP) consists of a List of harmonised classification and labeling of hazardous substances. This list is updated through an “Adaptation to Technical Progress(ATP)” issued yearly, which can be found on the European Chemical Agency (ECHA) website, “Table of harmonised entries in annex VI to CLP”
Endocrine disrupting substances (ED)
“substances having endocrine-disrupting properties for which there is scientific evidence of probable serious effects to human health and which are identified either in accordance with the procedure set out in Article 59 of Regulation (EC) No 1907/2006 of the European Parliament and of the Council (2) or, once a delegated act has been adopted by the commission pursuant to the first subparagraph of Article 5(3) of Regulation (EU) No528/2012 (Market and Use of Biocidal Products) of the European Parliament and the council (3), in accordance with the criteria that are relevant to human health amongst the criteria established therein.”- MDR Annex I 10.4.1.(b)
Article 59 of Regulation (EC) No 1907/2006 (REACH) defines a procedure that shall apply for the identification of substances of concern, including those with endocrine disrupting properties. For this purpose, a Candidate List for eventual inclusion in Annex XIV of REACH is established. Companies may have legal obligations resulting from the inclusion of substances in the Candidate List. Annex XIV includes the so-called “ Authorisation List ”, a list of substances that require authorisation.
The identification of substances of concern is an ongoing process. This means that the Candidate List and the Authorisation List can still be updated and should be checked periodically. In order to have an overview of the substances that may be included in these lists in the near future, the “RegulatoryManagement Option Analysis (RMOA)” list and the “Endocrine Disruption (ED) Assessment List” may also be useful.
Comparing to the MDD, the MDR has introduced new and more stringent requirements regarding materials and substances safety. The documentation for every invasive device or component that come into direct contact with the body or (re)administers, transports or stores medicines or body liquids, shall be updated in order to comply with these new requirements. The documentation for components or devices not meeting such conditions could also be updated to demonstrate the requirements are not applicable in that case.
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