Biocompatibility Testing of Medical Devices
Ensuring Material Safety and Regulatory Compliance with New Approach Methodologies
This article provides a quick overview of biocompatibility testing, a critical component of the broader biological evaluation for medical devices. It covers the regulatory landscape, key test endpoints, and the increasing importance of New Approach Methodologies (NAMs). We also highlight GARD®skin Medical Device, an ethical and scientifically robust alternative to traditional animal-based sensitization testing.
Key takeaways
- Understanding biocompatibility: What it is and why it’s a non-negotiable part of medical device development.
- The regulatory framework: ISO 10993 standard series and global requirements.
- The “big three” endpoints: Cytotoxicity, Irritation, and Sensitization.
- In vitro biocompatibility testing: A cost-efficient, human-relevant and ethical alternative.
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What is biocompatibility testing and why does it matter?
Any medical device that comes into contact with the human body requires a biological evaluation to ensure patient safety. This is a comprehensive process guided by a risk-based approach.
Biocompatibility testing is a critical component of this evaluation. It involves a series of scientific assessments to determine if a device interacts safely with biological systems without causing harmful local or systemic effects.
Biocompatibility testing is a critical step in ensuring the safety of medical devices. It helps manufacturers to:
- Demonstrate that a device is safe for its intended use.
- Comply with regulatory requirements.
- Identify and address potential biological risks early in product development.
- Reduce the risk of costly delays during the market approval process.
Regulatory framework: ISO standards and global requirements
The biological evaluation of medical devices is primarily guided by the ISO 10993 series, a set of internationally recognized standards that provide a structured framework for assessing biological safety. These standards are used in conjunction with ISO 14971 for risk management throughout a device’s lifecycle.
ISO 10993: The global foundation of biological evaluation
- ISO 10993-1 establishes the framework for biological evaluation, including how to select appropriate biocompatibility test endpoints based on the device’s nature, contact type, and duration of exposure.
- It advocates for a risk-based approach, emphasizing that a thorough chemical characterization and toxicological assessment should be completed before initiating new experimentation.
- Supporting standards such as ISO 10993-5, -10, -17, and -23 provide detailed guidance on specific test endpoints.
Regional regulatory frameworks
While ISO 10993 provides a harmonized foundation, implementation and expectations for biocompatibility testing can vary significantly across regions.
European Union
- The EU Medical Device Regulation (MDR 2017/745) is the overarching regulation for medical device safety.
- The MDR aligns with ISO 10993 and use ISO 10993-1 as a key framework for demonstrating the biocompatibility of medical devices, while adding its own requirements for risk management, documentation, and post-market surveillance.
- EU Notified Bodies often require thorough chemical characterization and scientific justification for test strategies.
United States
- The U.S. Food and Drug Administration (FDA) recognizes ISO 10993-1 but supplements it with its own guidance: “Use of International Standard ISO 10993-1” (2020).
- FDA strongly promotes a biological risk assessment approach, leveraging chemical characterization data to reduce or waive unnecessary animal testing.
- FDA also provides detailed device-specific recommendations through various device guidance documents and recognized consensus standards.
Japan
- The Pharmaceuticals and Medical Devices Agency (PMDA) bases its evaluations on ISO 10993, supplemented by national regulations.
China
- The National Medical Products Administration (NMPA) follows the Chinese national guidelines for medical device safety, which aligns with ISO 10993 standards and includes additional detailed requirements for extractables/leachables testing and selection of test methods.
- NMPA requires local testing at accredited Chinese laboratories for many endpoints, even if testing has been conducted overseas.
South Korea
- The Ministry of Food and Drug Safety (MFDS) recognizes ISO 10993 and has its own guidelines for biocompatibility evaluation.
- Korean regulations emphasize the use of GLP-certified laboratories and may request additional testing depending on the device class and materials.
The “big three” biocompatibility tests: Cytotoxicity, Irritation, and Sensitization
According to ISO 10993-1, a biological risk assessment determines which endpoints need to be tested. For most devices, the following three are considered fundamental:
Cytotoxicity (ISO 10993-5)
This test assesses whether a material or its extract is toxic to cells. Conducted in vitro using cultured mammalian cells, it measures cell viability after exposure. As a cost-effective and rapid assay, it is widely used during early development to screen for potential material issues.
Skin Irritation (ISO 10993-23)
This test evaluates whether a material causes localized skin or mucosal inflammation. While traditionally assessed in animals, this endpoint can now be reliably evaluated using validated in vitro models such as Reconstructed Human Epidermis (RhE).
Skin Sensitization (ISO 10993-10)
This test assesses whether repeated exposure to a material may trigger an allergic skin reaction. Traditionally, this was evaluated using animal models like the Local Lymph Node Assay (LLNA) or the Guinea Pig Maximization Test (GPMT).
Since 2021, New Approach Methodologies (NAMs) included in the OECD Test Guideline 442 have been recognized in Annex C of ISO 10993-10 as in vitro alternatives. Ongoing efforts aim to fully integrate some of these NAMs, such as GARD®skin Medical Device, into the normative sections of the standard, further supporting their use in regulatory safety assessments.
Learn more about how GARD®skin Medical Device enables direct testing of medical device extracts, supporting both polar and non-polar extraction vehicles as recommended in ISO 10993-12.
In vitro biocompatibility testing: A cost-efficient, human-relevant and ethical alternative
Historically, biocompatibility testing relied heavily on animal models. Today, however, a combination of ethical imperatives, scientific innovation, and increasing regulatory acceptance is accelerating the shift toward non-animal methods, known as New Approach Methodologies (NAMs).
What’s driving the transition to NAMs?
Several global developments are supporting the move toward in vitro biocompatibility testing:
- Ethical mandates: Including the EU’s Directive 2010/63/EU and the U.S. FDA Modernization Act 2.0, which promote the use of non-animal testing.
- Scientific Innovation: Advances in human-relevant science are providing more predictive and biologically relevant results than traditional animal models.
- The 3Rs initiatives: Global efforts promoting the Replacement, Reduction, and Refinement of animal use in testing
Benefits of New Approach Methodologies
In vitro methods offer significant advantages for both safety assessments and product development:
- Greater biological relevance to human health.
- Shorter turnaround times, supporting accelerated development timelines.
- Enhanced reproducibility and consistency.
- Fewer ethical concerns.
- Improved mechanistic understanding of toxicological effects.
Increasing Regulatory Recognition
The international regulatory landscape is actively evolving to support the use of in vitro data:
- ISO 10993-23 (2021) formally recognizes in vitro irritation testing using Reconstructed Human Epidermis (RhE) models.
- ISO 10993-10 includes several OECD-approved in vitro skin sensitization assays, such as GARD®, in its Annex C.
- Regulatory bodies like the FDA, EU Notified Bodies, PMDA (Japan), and NMPA (China) are increasingly open to validated NAMs, especially when supported by a strong risk assessment and robust data.
In summary, the growing availability of validated in vitro assays, coupled with regulatory alignment and scientific progress, is fundamentally transforming how biocompatibility testing is conducted.
For medical device manufacturers, adopting in vitro strategies not only aligns with ethical and regulatory expectations but also offers faster, more human-relevant, and cost-effective safety evaluations. It’s a forward-looking approach that enhances both compliance and competitiveness in the global market.
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Ready to integrate non-animal methods into your biocompatibility testing? Get a Quote or Contact Our Experts to explore more about our Medical Device services.
