One of the big changes in EU MDR 2017/745 in contrast to the MDD are the clear requirements on the handling of substances which are carcinogenic, mutagenic or toxic to reproduction (‘CMR’).

Fortunately, manufacturers are not meant to define by themselves which substances are considered CMR. REGULATION (EC) No 1272/2008, Annex VI, part 3 provides a list of known CMR and classifies them into two main categories. According to MDR only CMR of category I need to be taken into account. These are substances known to be human carcinogen, mutagen or reproductive toxicant based on evidence from either human epidemiological studies (Category IA) or animal studies (Category IB).

Manufacturer shall not only gather information on the amount of CMR in raw materials used but also be aware of any potential contamination along the process route for example through auxiliary materials, cleaning or sterilization agents.

In a first step it is always advisable to contact every single supplier to see if they have any information on potential presence or even on the actual concentration of CMR in the products they are supplying. Given an actual concentration, the concentration in the finished medical device can easily be calculated. If no or too little information is given on a material the manufacturer shall do a characterization according to EN ISO 10993-18:2009 to either screen for potential CMR or use a targeted approach to quantify any CMR known to be present. If the concentration of any CMR in a medical device exceeds 0.1% weight by weight (w/w) the manufacturer is obliged to justify its presence based on:

• analysis and estimation of potential patient or user exposure to the substance. This includes a biological evaluation and testing of the device within a risk management process according to (EN) ISO 10993-1.

  
  

• analysis of possible alternative substances, materials, or designs. This shall also include, where available, information about independent research, peer-reviewed studies and scientific opinions.

  
  

• argumentation why possible alternatives are not feasible in regards to functionality, performance and the benefit-risk ratio of the product.

If applicable and available, the latest relevant scientific committee guidelines. Additionally, every CMR present in a concentration above 0.1% (w/w) shall be referenced in the labelling. If the intended population includes children, pregnant or breast-feeding women or other groups considered vulnerable to such substances, information on residual risks and possible precautionary measures shall be given in the instructions for use.