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Updated ISO Guideline Emphasizes Toxicological Assessment of Extractables and Leachables

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The revised International Organization for Standardization (ISO) 10993-17 guideline, published in 2023, focuses on the toxicological assessment of extractable and leachable (E&L) in medical devices. This updated standard outlines the process and requirements for assessing the toxicological risk associated with the constituents of medical devices, particularly extractables and leachables. It also provides methods and criteria for determining whether exposure to these constituents poses appreciable harm.

The ISO emphasizes that this guideline is particularly relevant to chemical characterization, including extractable and leachable data, gathered following ISO 10993-18. It is crucial when a toxicological risk assessment is required to determine whether the risks related to the constituents are negligible or tolerable.

Toxicological Assessment of Medical Devices: Ensuring Safety and Compliance

  1. Constituents (excluding a cohort of concern or excluded chemicals) present in or extracted from a medical device at an amount representative of patient exposure below a relevant, toxicologically-based reporting threshold.
  2. When a new or changed medical device has established chemical or biological equivalence with an existing biocompatible or clinically established medical device.
  3. In vitro diagnostics medical device constituents.
  4. Biological risks associated with physical interactions of the medical device with the body (e.g., application of mechanical forces, energy, or surface morphology), provided that chemical exposure is not changed.
  5. Active pharmaceutical ingredients (APIs) of device-drug combination products or biologic components of device-biologic combination products, as additional regulatory considerations can apply.
  6. Exposure to a specific constituent is obtained from sources other than the device, such as food, water, or air.

Toxicological assessment of extractable and leachable is crucial for ensuring the safety of medical devices and combination products. The ISO guideline provides a structured approach to evaluating the potential risks associated with these constituents, helping manufacturers and regulatory authorities make informed decisions about product safety.

Toxicological Assessment

Elevating Medical Device Safety: Enhanced VOC Analysis for Toxicological Assessment

In addition to the ISO guideline, a study conducted by the US Food and Drug Administration (FDA) sheds light on the assessment of volatile organic compounds (VOCs) released by medical devices during clinical use. The study, published in Biomedical Materials & Devices, discusses the use of Dynamic Headspace (DHS) methods for VOC analysis, comparing them to traditional Static Headspace (SHS) and Stir Bar Sorptive Extraction (SBSE) gas chromatography-mass spectrometry (GC–MS) methods.

ISO 10993-18:2020 introduces the Analytical Evaluation Threshold (AET) as a method for determining the necessary analytical sensitivity for detecting volatile extractables. Compounds at or above the AET must be reported for toxicological assessment. While SHS analysis has been a supplementary technique for volatile analysis, it has limitations in terms of signal response and sensitivity.

The study found that DHS GC–MS analysis achieved over a tenfold increase in sensitivity compared to conventional VOC analysis methods. This enhanced sensitivity allows for a more robust toxicological risk assessment of volatile compounds from medical devices. DHS methods are considered valuable tools for VOC analysis due to their optimized conditions and robust data.

In conclusion, the revised ISO 10993-17 guideline emphasizes the importance of toxicological evaluation of extractable and leachable in medical devices. It provides a structured approach to assess the risks associated with these constituents, ensuring product safety. Additionally, the use of DHS methods for VOC analysis enhances the sensitivity of toxicological assessments, further contributing to the safety evaluation of medical devices and combination products.


Resource: European Pharmaceutical Review, January 29, 2024

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