An Overview of Chemical Characterization of Medical Devices

Medical devices comprise any number of materials, typically a combination of metal, ceramic, and/or polymers. The exact composition depends primarily on the desired functionality. A tongue depressor, for example, is one of the simplest devices in a medical practitioner’s toolkit, typically comprising a single component–thus a single material. At the other end of the complexity scale would be a critical, multi-functional high-tech device, such as an artificial pancreas system.

High-functionality medical devices typically require greater design complexity. Part of the cost therein is additional scrutiny. Each material used in device construction undergoes processing and fabrication–potentially also synthesis–that impacts biostability and compatibility. These factors are vital in ensuring suitability. Robust chemical characterization is, thus, essential for ensuring patient safety and regulatory compliance. It involves identifying and quantifying chemical constituents to detect potential toxicological risks. This comprehensive analysis aids in mitigating adverse reactions, validating manufacturing processes, and enhancing the overall reliability and efficacy of medical devices.

Key Components of Chemical Characterization

ISO 10993 Standards

ISO 10993 is a series of international standards providing guidelines for the biological evaluation of medical devices. These standards are essential for ensuring that medical devices are safe for use. Key aspects of ISO 10993 include:

• Biocompatibility Testing: Ensuring that materials used in medical devices do not pose risks to human health.
• Extractables and Leachables Testing: Evaluating how much and how quickly compounds can be transferred from the device into the environment or the human body.

Extractables and Leachables (E&L) Testing

E&L testing is at the heart of chemical characterization. Extractables are compounds that can be extracted from a device under exaggerated conditions, while leachables migrate into the body under normal usage conditions. These tests help determine the level below which a substance is not expected to pose a risk to human health (threshold of toxicological concern) and  the potential for chemical release under extreme conditions to ensure safety margins.

Toxicological Risk Assessment

A comprehensive toxicological risk assessment involves several steps:

1. Hazard Identification: Identifying any compounds that may pose a risk, including their nature (e.g., carcinogenic or neurotoxic).
2. Dose-Response Assessment: Determining the levels of exposure that could cause a toxic response.
3. Exposure Assessment: Evaluating the population that might be exposed to the chemical.
4. Risk Characterization: Understanding the likelihood and severity of potential hazards.

Biological Equivalence

In the EU, establishing biological equivalence is essential for leveraging existing clinical data from equivalent devices. This involves demonstrating that devices:

• Use the same materials
• Are in contact with the same tissues or fluids
• Have similar release characteristics of substances.

Chemical characterization plays a crucial role in this process by providing a baseline for comparing devices.

Regulatory Compliance and Expert Involvement

Adhering to ISO 10993 standards and involving expert testers are crucial for interpreting biological evaluation data and designing necessary testing protocols. This helps in waiving certain tests when existing data is available and ensures new tests are performed as required.

Challenges and Considerations

Chemical characterization is not without its challenges. One significant challenge associated with chemical characterization is the complexity of accurately identifying and quantifying the wide range of potential extractables and leachables. This requires advanced analytical techniques and expertise in interpreting the data. Moreover, the evolving nature of regulatory requirements necessitates continuous updates to testing protocols and methodologies.

Furthermore, there is a growing need for more refined toxicological risk assessments that consider the latest scientific developments and emerging health concerns. This includes understanding the long-term effects of low-level exposures to certain chemicals and the potential for cumulative effects from multiple sources.

Explore RQM+'s Expertise in Chemical Characterization

At RQM+, we specialize in ensuring the safety and compliance of medical devices through rigorous chemical characterization. Our team of experts is equipped with the latest analytical techniques and extensive regulatory knowledge to help you navigate the complexities of ISO 10993 standards and toxicological risk assessments.

Why Choose RQM+?

• Unmatched Expertise: Our experienced professionals have deep knowledge in biocompatibility testing, extractables and leachables (E&L) testing, and toxicological risk assessments.
• Comprehensive Services: From hazard identification to risk characterization, we offer a full suite of services to ensure your medical devices meet regulatory requirements.
• Regulatory Insight: Stay ahead with our up-to-date understanding of evolving regulatory standards and best practices in chemical characterization.

Learn More About Our Services for Chemical Characterization

• Chemical characterization testing for medical devices
• Using chemical characterization to achieve biological equivalence
• Understanding ISO 10993 standards

Partner with RQM+ to ensure the safety and compliance of your medical devices. Visit our website to discover more about our lab services and how we can support your chemical characterization needs.

References

1. Chandrasekar V, Isayeva I, Liu J, Nahan K, Oktem B, Shin H, Sussman E, Wickramasekara S, Zheng J. Chemical Characterization and Non-targeted Analysis of Medical Device Extracts: A Review of Current Approaches, Gaps, and Emerging Practices. ACS Biomaterials Science & Engineering. 2022;8(3):939-963. doi:10.1021/acsbiomaterials.1c01119.
2. Materials and Chemical Characterization Program: Research on the Materials and Chemical Characterization of Medical Devices. U.S. Food & Drug Administration. https://www.fda.gov/medical-devices/medical-device-regulatory-science-research-programs-conducted-osel/materials-and-chemical-characterization-program-research-materials-and-chemical-characterization. Updated 30/01/2023. Accessed 30th July 2024.
3. Mark Anderson Jordi, Smriti Khera, Kevin Roland, Liuwei Jiang, Paige Solomon, Jenny Nelson, Syed Salman Lateef, James Woods, Leland Martin, Samantha Martin, Frankie Aiello, Nina Chen. Qualitative assessment of extractables from single-use components and the impact of reference standard selection. Journal of Pharmaceutical and Biomedical Analysis. Volume 150. 2018. https://doi.org/10.1016/j.jpba.2017.12.029.