The use of CMR fabrics is rigorously regulated. The MDR also regulates the CMR fabrics and places rigorous requirements for producers of medical devices.

This article helps to meet these requirements.

1. CMR fabrics: the challenges

Cmr stands for:

• CAncerogeno (cancer, cancer)
• MUtagen (genetic modification)
• RAnd -Oxic Productor (reproductive stoxical)

CMR fabrics are demanding for medical devices manufacturers:

• CMR fabrics have particularly negative effects on patient safety.
• However, the consequences for patients can only be recognized in the long term and mostly not covered by post-market surveillance.
• It is not immediately clear which tissues are considered CMR (carcinogen, mutagene or reproductive oxic).
• The legal requirements are (therefore) particularly extensive.
• The proof of the absence of CMR fabrics and therefore compliance is difficult.

The following chapters help to face these challenges.

2. Classification as CMR fabric

Manufacturers must know which fabrics contain their products and release. You must also know if these tissues are considered cancer, mutagen or reproductive oxic.

Databases help with this division.

A. Toxicological database

Toxicological databases also contain data In vitro– AND In-vivo-The attempts that provide information on the fact that it is a carcinogenic, mutage or reproductive oxide substance.

Examples of toxicological database are:

B. Appendix of the CLP regulation

In Table 3 of Appendix VI, the CLP regulation contains a list of CMR fabrics with its official classification.

The official title of the ordinance is “Regulation (EC) n. 1272/2008 of the European Parliament and the Council of 16 December 2008 on the classification, labeling and packaging of fabrics and blends”.

C. List of the EU Commission

The EU has published an overview of the CMR substances, which, however, focuses on cosmetics. However, these substances can also be found in medical devices and are therefore relevant.

D. Kmr-Liste of IFA

The Professional Security and Professional Security Institute of the German Insurance of Legal Accidents (IFA) has published a Kmr list. This complete list contains classified fabrics such as CMR and is regularly updated.

And

On the EU website there is a list of IARC (International Agency for Cancer Research).

3. Origin of CMR fabrics in medical devices

There are many different ways for how CMR substances can be brought to products. The origin cannot always be clearly clarified. The possibilities are:

• CMR fabrics already contained in the starting material
• The fabrics are residues of chemicals of process.
• CMR fabrics arise during production, e.g. B. When heated or through reactions with other materials.

4. Cmr fabric tests

The tests and evaluation of the CMR fabrics are performed in several steps.

Step 1: Check data cards

In the first step, producers should control the data of the starting materials and guarantee the suitability of the material during a material qualification. The same goes for the sheets of data of the process chemicals.

Step 2: perform chemical analyzes

The chemical analysis eventually clarifies if the final product releases CMR fabrics. This should always be part of the tests necessary for biocompatibility in accordance with ISO 10993-18. The results should be evaluated by an expert with toxicological competence.

Step 3: Tossicological risk analysis and other tests

On the basis of chemical characterization, a toxicological evaluation can take place. Compared to the relevant limit values, this clarifies how the risk must be evaluated by a possible release of CMR substances and if further tests are needed (for example exams on genexicity, carcinogenicity and reproductive toxicity in accordance with ISO 10993-3).

5. Regulatory requirements

A. MDR requirements

MDR, Capitel II, 10.4.1

Invasive products or interact directly with the body to give, remove or store drugs or body fluids can contain CMR fabrics in a concentration of over 0.1 % of mass content if it is justified.

MDR, Capitel II, 10.4.2

The justification of the CMR fabrics must contain:

• An analysis of potential exposure
• The survey on available alternatives, including revisions and scientific studies
• A reason why alternatives could be inappropriate taking into account the functionality of the product and the relationship at risk of benefits
• The consideration of groups of special patients (children, pregnant women, breastfeeding).

If available, current guidelines should be used.

B. ISO 10993 family

As part of the evaluation of biological security according to ISO 10993-1, the genotoxicity of endpoints (includes the potential mutagens of substances) are to face carcinogenicity, reproductive and development toxicity.

As part of the toxicological risk assessment, 10993-17 provides information on the risk assessment of carcinogenic substances. These reviews should always be conducted by experts with appropriate toxicological skills.

C. Further requirements for CMR fabrics

Further regulations have an indirect effect: the regulation of the flow regulates the management of particularly worrying substances (SVHC), which include many CMR fabrics. CLP regulation regulates the classification, labeling and packaging of chemicals. National regulations must also be observed (for example, a legislation on professional safety and the ordinance on dangerous substances).

If you cannot avoid the CMR fabrics in your product, pay attention to the adaptation of the documentation (label, IFU).

6. Tips to meet the CMR fabric requirements

Tip 1: pay attention to the fabrics without cmr from the beginning

Use only starting materials for which significant data cards are obtained. Check and evaluate the substances in of its cited and avoid the output materials that are or contain CMR fabrics.

On this basis, make a material qualification and documents because the material is suitable. Consult experts at this point.

For all production phases, select only materials without CMR fabrics.

If the substances are not avoidable, they strive to ensure that their concentration remains at the limit of 0.1 %. If you cannot adhere to this limit, have an assessment of the exposure and an analysis of the risk of risk conducted by an expert with toxicological competence.

Tip 2: Perform the exams at the beginning of the project

Too often, the producers of medical devices create the topic of the CMR “on the back” and perform only the necessary exams at the end of the development of the product. This limits the options for action and often brings with it high rectification and default costs of the project.

Early knowledge of substances often allows a redesign of the product to avoid or reduce the release of CMR substances from the final product.

Tip 3: Follow the ISO 10993 family

Check, as stated by ISO 10993, the biocompatibility on the final product. This also includes a detailed chemical characterization.

Evaluate the results and carry out a toxicological risk assessment if necessary.

Tip 4: Make sure the experience

Pay attention to the documented experience of the people responsible for this. These must also meet toxicological details and Z. B. can evaluate the exposure and effects on the groups of critical patients.

7. Conclusion and summary

It is understandable that legislators set particularly rigorous requirements for carcinogenic, mutagenic and reproductive and reproductive -oxious substances.

Therefore, manufacturers should avoid these substances in their medical devices in the best possible way and the evidence that the CMR fabrics remain below the toxicologically applicable limit values. However, a toxicological risk assessment is needed and highlights the responsibility for competence for those responsible.

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