Phthalates Benefit-Risk Guidelines

The EU's Medical Devices Regulation (MDR) addresses requirements for using CMR and/or ED substances in Chapter II Section 10.4 of Annex I (MDR).

The commission’s Scientific Committee on Health, Environmental, and Emerging Risks (SCHEER) finalized its revised phthalates benefit-risk assessment guidelines on June 17, 2024. Under the MDR, these guidelines must be updated at least every five years.

SCHEER notes that phthalates are widely used as plasticizers of polymers or additives in various applications, including medical devices. "The interaction of phthalates with the polymers they are embedded is weak, so they may be released from the plastic product into the environment and the human body when exposure occurs”.

Intended for stakeholders including manufacturers, notified bodies, and regulatory bodies, the SCHEER guidelines offer a methodology for justifying the presence of phthalates classified as CMR 1A or 1B and/or ED in devices and/or parts or materials utilized at a percentage above 0.1% by weight, which otherwise are prohibited from use in medical devices under the MDR.

Additionally, they provide a methodology for evaluating potential alternatives to CMR/ED phthalates in devices, including alternative materials, designs, or medical treatments.

SCHEER notes, “The approach of these guidelines may also be used for a [benefit-risk analysis] of other CMR/ED substances in medical devices”.

Under the MDR, medical device manufacturers must justify using hazardous phthalates and other CMR or ED chemicals. The presence of those substances above de minimis levels must be communicated using a label on the device itself and/or on the packaging for each unit.

“The information labeled should be submitted using the Unique Device Identification (UDI) Database along with the UDI-DI. If the intended use of such medical devices includes treatment of special patient groups considered particularly vulnerable to such substances and/or materials, information on residual risks for those patient groups must be provided”.

The update includes minor changes to the preexisting document, mostly focusing on “the progress made in the last five years regarding the application, exposure, and toxicology of alternatives for the phthalate plasticizers in medical devices”, which is detailed in new annexes to the guidelines.

The final guidelines include three new annexes.

  • Annex 8 describes exposure to currently used CMR/ED phthalate alternatives,
  • Annex 9 describes the toxicology of currently used CMR/ED phthalate alternatives, 
  • Annex 10 describes progress in developing CMR/ED phthalate alternatives for use in blood bags.

Guidance for alternatives evaluation previously used wording pointing to “potentially relevant” candidates to consider as alternatives to CMR/ED phthalates; now the terminology has changed to “most relevant” candidates to help stakeholders avoid unnecessary alternatives review.

“While some alternatives might be available, the focus should be limited to the likely most relevant alternatives based on a preliminary evaluation of their suitability”, SCHEER says.

The committee recommends a minimum of three alternative evaluations and notes that less than three “needs to be justified by additional information”.

“However, risk is not the only parameter to consider: the impact of the possible alternatives on the functionality, performance, and the overall benefit-risk ratio of the medical device shall also be evaluated”, the committee says.

The guidelines include new information on regulation regarding ED hazard classification, including Category 1 comprising known or presumed EDs and Category 2 comprising suspected EDs for human health and the environment.

 

Summary

  • Phthalates classified as CMR 1A or 1B and/or endocrine-disrupting under EU chemical regulations are prohibited in medical devices above 0.1% by weight unless justified through alternatives assessment and risk-benefit analysis.
  • The EU increasingly focuses on identifying and regulating endocrine-disrupting substances as part of its Chemicals Strategy for Sustainability under the EU Green Deal.
  • To ensure compliance, stakeholders can use updated phthalates benefit-risk assessment guidelines (Annex 7) to approach all such regulated substances.

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