Medical devices: management of hazardous substances during the transition to regulation (EU) 2017/745

Protecting human health and the environment from the risks that chemicals can pose has always been a priority for Europe. In 2007, the REACH Regulation (Regulation (EC) No 1907/2006) was adopted with the aim of making the manufacture and use of chemicals safer in European industry. The main aims are to identify, assess and control chemicals that are manufactured, imported and placed on the European market.

The entry into force of Regulation (EU) 2017/745 of the European Parliament on medical devices is accompanied by new requirements for medical device manufacturers regarding the use of certain substances. The new general safety and performance requirement is Requirement 10.4 in Annex I of this Regulation. This safety requirement is related to the chemicals used in the manufacture of medical devices and is strongly inspired by the REACH Regulation.

However, application of this requirement under Regulation (EU) 2017/745 shall not replace the application of the REACH Regulation. These two regulations are therefore complementary but have their own specific features. It is therefore important to clearly define the scope of each regulation.

In order to correctly apply this new specific requirement on medical devices, it is important to understand it.

What are the substances concerned?

• Substances that are carcinogenic, mutagenic or toxic to reproduction, category 1A or 1B, according to Annex VI, Part 3 of Regulation (EC) No 1272/2008 (CLP Regulation on classification, labelling and packaging of substances and mixtures) of the European Parliament and of the Council:
  • Carcinogenic (C): substances and mixtures which, if inhaled, ingested or absorbed through the skin, may cause cancer or increase its incidence.
  • Mutagenic (M) or genotoxic: substances and mixtures which, if inhaled, ingested or absorbed through the skin, may cause genetic defects or increase their incidence.
  • Toxic to reproduction (R) or reprotoxic: substances and mixtures which, if inhaled, ingested or absorbed through the skin, may cause or increase the incidence of non-heritable adverse effects in the offspring or impair reproductive functions or capacities.
• Substances with endocrine disrupting properties, for which there is scientific evidence that they may have serious effects on human health and which have been identified either in accordance with the procedure laid down in Article 59 of Regulation (EC) No 1907/2006 (REACH) of the European Parliament and of the Council or according to Regulation (EU) No 528/2012 for biocidal products.

The list of CMR and ED substances is regularly updated on the ECHA website and is based on the criteria of the REACH Regulation.

What devices are concerned and what are the impacts?

It is stipulated that devices that are invasive and/or intended to administer or transport biological fluids or substances (medicinal or otherwise) may not contain a concentration of CMR substances or endocrine disruptors greater than 0.1% (by mass fraction), unless justified in accordance with Sub-section 10.4.2 which lists the evidence to be included for justification. This requires extensive work by your Research & Development and Regulatory Departments to justify the use of these hazardous substances in medical devices. It requires an assessment of the benefits/risks of their use, after having evaluated alternative solutions. The notion of benefit/risk ratio is essential to demonstrate that the use of such a substance is indispensable to achieve the desired level of benefit. If this is not the case, an alternative solution must be considered. This justification must be submitted to your notified body. In addition, you will have to comply with the applicable labelling requirements as mentioned in Sub-section 10.4.5.

This new requirement has a major impact on the labelling of devices and also on the justifications to be provided in your technical dossier. Your package insert, your biological assessment, your labels and also your design dossier are all affected.

For example, with the update to the status of cobalt as a CMR substance, many manufacturers of implantable medical devices containing chromium-cobalt will have to rule on these different points. Similarly, manufacturers using plasticisers that are known to be endocrine disruptors and may be in indirect contact with patients will have to initiate and develop this type of approach until they find alternative solutions to produce their medical devices.

What support do we offer?

This process of identifying, measuring and justifying the presence of substances through a risk management approach involves collegial work between design teams and regulatory affairs, as well as in-depth knowledge of the applicable guides and regulations.

Feel free to ask Efor consultants to provide you with scientific and regulatory expertise to ensure a smooth transition to the new Regulation (EU) 2017/745.