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European Commission Updates Chemical Classification and Labeling

On 11 July 2023, and once more on 5 January 2024, the European Commission updated its list of harmonized classification and labeling of chemicals. Regulation (EC) No 1272/2008 on classification, labeling and packaging of substances and mixtures (a.k.a CLP Regulation), particularly Annex VI (list of harmonized classification and labeling of hazardous substances), has been amended by the two following Regulations:

  • Commission Delegated Regulation (EU) 2023/1435 of 2 May 2023 (20th Adaptation to Technical Progress [ATP]): 4 entries were revised. The new classifications will apply as of 1 February 2025.
  • Commission Delegated Regulation (EU) 2024/197 of 19 October 2023 (21st ATP): 28 entries were added, and 24 entries were revised. The new classifications will apply as of 1 September 2025.

The scientific assessment for these substances was done in collaboration between the European Chemicals Agency (ECHA), its Committee for Risk Assessment (RAC) and Member State authorities for decision-making at the Commission.

Among substances with updated or new CLP classification, some could be found in medical devices, such as 2-ethylhexanoic acid (CAS No. 149-57-5) which is used as a catalyst promoter in the manufacture of polyester products (including low-density polyethylene). This substance and its salts are now classified as Reprotoxic category 1B.

The ECHA has prepared an Excel table containing all updates to the harmonized classification and labeling of hazardous substances, which are available in Table 3 of Annex VI to the CLP Regulation. The table is available on the ECHA website: https://echa.europa.eu/fr/information-on-chemicals/annex-vi-to-clp. Currently, only the 20th ATP has been included in the Excel table. Although not legally binding, this tool is useful to check the classification of a medical device constituent per the latest revision of CLP Regulation.

On 23 January 2024, ECHA announced the addition of the following hazardous chemicals to the Candidate List of substances of very high concern (SVHC):

  • Oligomerisation and alkylation reaction products of 2-phenylpropene and phenol
  • Bumetrizole (UV-326) (CAS No. 3896-11-5)
  • 2-(dimethylamino)-2-[(4-methylphenyl)methyl]-1-[4-(morpholin-4-yl)phenyl]butan-1-one (CAS No. 119344-86-4)
  • 2-(2H-benzotriazol-2-yl)-4-(1,1,3,3-tetramethylbutyl)phenol (UV-329) (CAS No. 3147-75-9)
  • 2,4,6-tri-tert-butylphenol (CAS No. 732-26-3)

Among these five substances, three have been recognized as toxic for the environment, and two have been listed for health hazard properties (toxic for reproduction), i.e. 2-(dimethylamino)-2-[(4-methylphenyl)methyl]-1-[4-(morpholin-4-yl)phenyl]butan-1-one and 2,4,6-tri-tert-butylphenol.

While the first compound is not expected to be present in medical devices, 2,4,6-tri-tert-butylphenol is used as a stabilizer and antioxidant in lubricating oils, as well as in elastomeric and thermoplastic polymers, and could therefore be present in medical devices made from such materials.

The Candidate List now contains 240 entries for chemicals that can harm people or the environment. The complete list can be consulted on the ECHA website: https://echa.europa.eu/fr/candidate-list-table.

Substances identified as carcinogenic, mutagenic or toxic to reproduction (‘CMR’) in the CLP, and those having endocrine-disrupting properties (ED) identified in the REACH regulations, have strict requirements under General Safety and Performance Requirements (GSPR) 10.4.1 of the EU Medical Device Regulation (2017/745). These requirements include providing a rationale and justification of the presence of such substances with a concentration of above 0.1% w/w, as well as specific labeling requirements and, where applicable, communication of precautionary measures for vulnerable patient groups. Notwithstanding the requirements under the Medical Device Regulation (MDR), avoiding the use of CMR/ED substances in medical device design and manufacture is a critical risk mitigation step for the biocompatibility of a device.

NAMSA recommends you regularly verify the impact of CLP and SVHC list updates on your devices, as chemicals’ classifications can evolve over time while new scientific and toxicological data are made available.

How Can NAMSA Help?

NAMSA is the pioneer of the medical device testing industry and the industry leader in driving successful regulatory outcomes through effective, daily interactions with the FDA, Notified Bodies and other global Competent Authorities.

We understand the confidence you require in your biocompatibility testing partner to deliver high-quality, accurate results on your way to commercialization. Our global team of medical device experts, including 14 accredited toxicologists (DABT and ERT), can advise on device biocompatibility and help you navigate the pathway to successfully launching your product in the U.S., EU and Japan.

If you are interested in speaking with us about how we can support your product development needs, please Contact Us or learn more about our experts at namsa.com/subject-matter-experts.

Valériane Levelut

Valériane Levelut is a EUROTOX (ERT) certified Toxicological Pharmacist, with a rich experience as a safety assessor in many sectors. Before joining NAMSA she led the toxicological evaluation of medical devices, biocidal products, cosmetic products and food supplements at other organisations. Her role at NAMSA focuses on conducting biological evaluations and toxicological risk assessments in accordance with ISO 10993-1 and other medical device requirements, as well as assisting sponsors by addressing a wide range of issues related to biocompatibility and regulatory compliance.