Toxicological evaluation of leachable substances according to ISO 10993-17

A medical device toxicology assessment involves evaluating the potential health risks associated with the materials and chemicals used in the device following the ISO 10993-17 norm. Several methods are used to perform a comprehensive toxicology assessment, including:

• Extractables and Leachables (E&L) Testing: This involves identifying and quantifying the chemical compounds that could be released from the medical device during its use. Analytical techniques such as gas chromatography-mass spectrometry (GC-MS), liquid chromatography-mass spectrometry (LC-MS), and inductively coupled plasma-mass spectrometry (ICP-MS) are commonly used for E&L testing.
• Biocompatibility Testing: This includes a series of in vitro and in vivo tests to determine the biological response of the medical device materials when in contact with living tissues. Common tests include cytotoxicity, sensitization, irritation, genotoxicity, and systemic toxicity assessments.

• Physicochemical Testing: This involves evaluating the physical and chemical properties of the medical device materials, such as surface chemistry, degradation products, and mechanical properties, which could impact their safety and biocompatibility.

• Computational Toxicology: In silico methods, such as quantitative structure-activity relationship (QSAR) modeling, can be used to predict the toxicological properties of chemicals based on their molecular structures. This approach can help prioritize substances for further testing and provide preliminary risk assessments.

• Toxicological Risk Assessment: Based on the data obtained from E&L testing, biocompatibility testing, physicochemical testing, and computational toxicology, a toxicological risk assessment is performed to evaluate the potential health risks associated with the identified substances. This may involve comparing the exposure levels with established safety thresholds or conducting additional toxicological studies if necessary.

• Weight of Evidence Approach: This involves integrating data from various sources (e.g., E&L testing, biocompatibility testing, computational toxicology, and literature) to make a comprehensive assessment of the potential health risks associated with the medical device materials.

By employing these methods in a systematic and integrated manner, a thorough medical device toxicology assessment can be performed, ensuring that the device is safe for its intended use and compliant with regulatory requirements.

ISO 10993-17, titled "Biological evaluation of medical devices - Part 17: Establishment of allowable limits for leachable substances," is a standard that provides guidance for evaluating the potential toxicological risks of leachable substances in medical devices. The main requirements specified by ISO 10993-17 include:

• Risk assessment: Conduct a risk assessment to identify potential sources of leachable substances and their possible health effects. This should take into consideration the materials used, manufacturing processes, storage conditions, and intended use of the medical device.

• Identification of toxicologically relevant substances: Identify the leachable substances that may be present in the medical device and have toxicological relevance. This can be based on the results of extractables and leachables testing or other relevant information, such as material safety data sheets or known impurities in the materials used.

• Establishment of allowable limits: Determine the allowable limits for the identified toxicologically relevant substances based on their potential health risks. These limits should be derived from established toxicological data or calculated using appropriate methods, such as dose-response relationships or safety factors.

• Comparison with exposure levels: Compare the actual exposure levels of the leachable substances in the medical device (obtained from E&L testing) with the established allowable limits. This comparison helps assess the potential toxicological risks associated with the device's use.

• Toxicological risk assessment: Perform a toxicological risk assessment to evaluate the potential health risks associated with the identified leachable substances. This may involve comparing the concentrations of the detected compounds with the established allowable limits or conducting additional toxicological studies if necessary.

• Documentation and reporting: Maintain thorough documentation of the risk assessment process, including the identification of toxicologically relevant substances, establishment of allowable limits, comparison with exposure levels, and toxicological risk assessment. Prepare a comprehensive report detailing the findings and conclusions of the ISO 10993-17 assessment.

By following the requirements specified by ISO 10993-17, manufacturers can effectively evaluate the potential toxicological risks of leachable substances in their medical devices, ensuring compliance with regulatory requirements and safeguarding patient safety.

Choosing an ISO 10993-17 accredited laboratory such as FILAB for your toxicological risk assessment on medical devices offers several advantages, ensuring that the assessment is performed according to the highest quality standards and industry best practices. Some of the main reasons include:

• Compliance with international standards: An ISO 10993-17 accredited laboratory follows the guidelines and requirements outlined in the ISO 10993-17 standard, ensuring that the toxicological risk assessment is conducted according to internationally recognized best practices.

• Technical expertise: Accredited laboratories have demonstrated their technical competence in performing toxicological risk assessments, ensuring that they have the necessary knowledge, skills, and experience to provide accurate and reliable results.

• Quality assurance: ISO 10993-17 accreditation requires laboratories to implement a robust quality management system, which includes regular audits, internal reviews, method validation, and proficiency testing. This ensures that the laboratory maintains a high level of quality and consistency in its services.

• Traceability and transparency: Accredited laboratories are required to maintain detailed documentation of their processes, procedures, and results, ensuring traceability and transparency throughout the toxicological risk assessment process.

• Confidence and credibility: Choosing an ISO 10993-17 accredited laboratory provides confidence in the accuracy and reliability of the toxicological risk assessment, as the laboratory has been independently assessed and certified by an accreditation body.

• Regulatory compliance: Many regulatory authorities and organizations require or recommend the use of accredited laboratories for toxicological risk assessments, ensuring that the assessment meets requirements and helps facilitate the approval process for medical devices.