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Extractables & Leachables Testing (Materials Characterization)

ISO 10993 Part 18 In accordance with final guidance from ISO 10993 in 2020, materials characterizations should be considered for every device. Extractable/leachable studies are conducted to get a full characterization of all chemicals, which is then used to create an accurate assessment of risk.
Extractables and leachables are materials that migrate from packaging system components, such as container and closure systems, and may contaminate the drug product. A comprehensive approach is required to analyze for the variety of possible extractable and leachable materials.

  • Extractable and Leachable Study Design

    Extractables and leachables studies are designed to be optimized and customized for the pharmaceutical container or closure under investigation, such as materials and their compatibility with extraction solvents, type of container, type of contact between the container and the medicinal product, storage conditions, specific administration or reconstitution procedures, type of medicinal product, route of administration, dosing regimen, and associated threshold requirements.

    Exhaustive extractions using solvents with a range of polarity (polar, non-polar, mid-range) may be conducted to identify extractable materials These extractable materials will be referenced against known target compounds from material and container preparation and processing. Leachable materials may be extracted using model solvent system comparable to end use applications.

    • ISO 10993-17 Toxicological Evaluation

      With our experts and certified toxicologists we can provide toxicological evaluation of medical device and combination product based on data received from the clients or using data coming from direct testing activities.
      Medical devices that come into direct or indirect contact with the human body must be biocompatible. The ISO 10993 series of standards provides an internationally harmonized system for assessing the biocompatibility of medical devices.
      Toxicological risk assessment is an integral part of the overall evaluation of medical devices.
      Chemical characterization of materials will improve safety assessment Chemical characterization is an important step.

      - Leachable substances can be identified
      - Semi-quantitative or quantitative profile can allow for worst-case exposure estimates
      - Literature reviews can be leveraged for data-rich compounds
      - In silico tools can be used to predict toxicity

      Toxicological risk assessments are performed in four primary steps in a scientific attempt to identify and estimate the true risks of a medical device, in line with ISO 14971 Medical Devices - Application of risk management to medical devices. These primary steps are:

      * Hazard Identification
      * Hazard Characterization
      * Exposure Assessment
      * Risk Characterization

      ISO 10993-17 does not prescriptively define a procedure to complete these four steps. Instead, ISO 10993-17 provides a systematic method for assessing the wealth of complex toxicological data that varies widely in quantity and quality, in order to adequately address these four steps.

      As outlined in ISO 10993-17, risks associated with exposure to identified leachables are managed by quantifying the associated risks and limiting exposure within tolerable levels. The process of establishing these tolerable levels can be broken down into the following key steps:
      - Conduct comprehensive literature searches the critical health endpoint
      - Determine a point-of-departure (usually a NOAEL)
      - Derive a Tolerable Intake (TI), specific for the route of entry and duration of exposure
      - Calculate the Tolerable Exposure (TE) for the target patient subgroups
      - If appropriate, modify the initial TE to account for utilisation, benefit etc
      - Compare the final TE with the estimated worst-case exposure of the potential leachable and calculate a Margin of Safety (MOS).

    • ISO 10993 Part 18

      Designing an extractables/leachables study for your device requires an understanding of the materials and manufacturing process. Even commonly used materials can have different extractables/leachables results based on impurities and processing. Our team of chemists and toxicologists will meet with customers to develop an appropriate test plan that aligns with current regulatory expectations.

      • Analytical Techniques

        -Organic analysis by GC, GC/MS, HPLC, LC/MS, LC/MS/MS
        -Elemental analysis by ICP, GFAA and cold vapor AA
        -FTIR and UV/Vis Spectroscopy
        -pH and Total Organic Carbon (TOC) provide non-specific indications of chemical migration
        -Ion chromatography
        -Particle sizing analysis
        -Karl Fischer

      • Extractables Leachables Capabilities

        -OINDPs (pMDI, DPI, Nasal Sprays...)
        -Dermal and Topical Applications
        -Biodisposables / Single Use Systems
        -Medical Devices
        -Label/Ink Migration
        -Drug Delivery Systems
        -Primary/Secondary Container Closure Systems
        -Raw Material/Polymers
        -Material Characterization
        -Material Comparison
        -Residual Analysis

    If you have additional questions about the test, or would like to consult with the experts at Biolink, ASK OUR EXPERT
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