Understanding ASTM Tests in Medical Device Biocompatibility: Scope, Application, and Limitations

In the world of medical device development, ensuring the biocompatibility and safety of materials is crucial. ASTM (American Society for Testing and Materials) standards play a key role in establishing testing protocols for a wide variety of materials, but they aren’t universally applicable to all medical devices. For manufacturers and developers, it’s important to understand which ASTM tests are relevant, why some devices may fall outside their scope, and how they intersect with other regulatory frameworks like ISO and FDA requirements.

This article will explore the different ASTM tests used in medical device biocompatibility, their applicability, and why their use is limited in some instances.

1. What Are ASTM Tests, and How Do They Relate to Medical Devices?

ASTM is an internationally recognized standards organization that develops testing protocols across various industries, including medical devices. ASTM standards outline specific material properties testing procedures, including mechanical strength, chemical composition, and biocompatibility.

For medical devices, ASTM tests are often used to assess:

• Mechanical and Physical Properties: Tensile strength, elasticity, durability, and resistance to environmental factors.
• Chemical Properties: Composition, degradation, and leachables that could impact biocompatibility.
• Biological Responses: Cytotoxicity, sensitization, irritation, and more.

These tests help ensure that materials used in medical devices perform safely and predictably under intended use conditions. However, ASTM standards often focus on the material properties rather than the entire device’s performance, which means they might not fully address biocompatibility concerns for complex devices.

2. Common ASTM Tests in Medical Device Biocompatibility

While there are numerous ASTM standards, here are some commonly referenced in the medical device industry:

1. Mechanical Testing Standards

• ASTM F382: Standard for assessing the mechanical properties of metallic bone plates. This test evaluates the strength and durability of materials used in orthopedic implants, ensuring they can withstand bodily stresses.
• ASTM D638: A tensile test standard used to measure plastics’ tensile strength and elongation, often applicable for medical device housings or components exposed to tensile forces.

1. Biological Testing Standards

• ASTM F748: Guidelines for selecting appropriate biological test methods for medical materials and devices based on their intended use. It offers a general framework for evaluating biocompatibility, focusing on testing protocols like pyrogen testing, while not covering chemical assessments.

• ASTM F895: Standard associated with the Agar Diffusion Cell Culture Screening Test for cytotoxicity in materials used for medical devices. This method involves applying material extracts to cell cultures in an agar medium to assess potential cell damage or toxicity.
• ASTM F2148: Standard test method for assessing skin sensitization potential of medical devices using the Local Lymph Node Assay (LLNA). This test evaluates the allergic response triggered by a device material when it comes into contact with the skin. It is primarily used for devices that may have direct skin exposure, ensuring they do not cause harmful allergic reactions.

These standards provide methods to test for specific properties that are crucial in certain medical devices, but many lack the comprehensive biological assessment required for devices with direct or prolonged human contact.

3. Why ASTM Tests Are Not Universally Applicable to All Medical Devices

ASTM standards primarily focus on performance testing or very specific interactions, such as material strength or surface properties, which may not address the broader biological safety and regulatory needs of medical devices. While these tests are valuable for evaluating particular characteristics, they may not cover all aspects required by regulatory bodies, especially for complex or high-risk devices. Here’s why ASTM tests are not universally applicable:

1. Focus on Material Properties, Not Whole Devices

ASTM tests often target individual materials rather than entire devices. In contrast, regulatory bodies such as the FDA and ISO require testing of the device in its final form, including any potential interactions between materials or effects of manufacturing processes.

• Example: A catheter made of multiple materials may pass individual ASTM tests on component materials but could fail comprehensive ISO biocompatibility tests due to interactions between materials or degradation over time.

1. Limited Scope of Biological Evaluation

ASTM norms and ISO 10993 biocompatibility norms differ primarily in their scope, approach, and focus. ASTM standards, developed in the United States, concentrate on detailed methodologies for specific material properties and tests, such as cytotoxicity or hemocompatibility. They are often material-specific and are widely referenced by the FDA for compliance in the U.S. In contrast, ISO 10993, developed internationally, provides a comprehensive framework for the biological evaluation of medical devices, emphasizing device-level safety rather than just material characteristics. It incorporates a risk-based approach, guiding manufacturers through a systematic assessment of biocompatibility based on device classification, exposure duration, and patient impact. While ASTM offers highly detailed test protocols, ISO 10993 focuses on global regulatory alignment, offering a broader strategy for ensuring biological safety across international markets. Both are complementary, with ASTM often providing specific test methods that can fulfill the broader requirements outlined in ISO 10993.

• Example: For implantable devices like heart valves or stents, a broad range of biological evaluations (beyond ASTM’s scope) are required to assess long-term tissue compatibility, which is fully covered under ISO 10993 standards.

1. Regional Regulatory Preferences

The FDA and other regulatory agencies often refer to ISO standards for medical device biocompatibility testing because ISO standards have global acceptance. While ASTM standards are widely respected in the U.S., they may not be recognized internationally, making them less ideal for devices marketed globally.

• Example: A medical device manufacturer planning to sell in both the U.S. and European markets would likely prioritize ISO 10993 compliance over ASTM biocompatibility tests due to ISO’s broader acceptance and applicability.

1. Differences in Test Methodologies and Endpoints

ASTM and ISO tests sometimes measure the same properties but use different methodologies or test endpoints. As a result, ASTM tests may not always meet regulatory standards for medical devices, especially if an ISO equivalent test specifies additional or stricter requirements.

• Example: ASTM F756 provides a very specific protocol for measuring hemolysis (red blood cell damage), which is not defined in such detail in ISO 10993-4. While it offers valuable insights into hemolysis testing, ASTM F756 alone may not provide a comprehensive assessment of all biocompatibility concerns. Therefore, combining it with ISO 10993-4 ensures a more robust evaluation of hemocompatibility, with ASTM F756 offering precise testing details that complement the broader framework provided by ISO 10993-4. 

4. When ASTM Tests Are Applicable in Medical Device Testing

Despite their limitations, ASTM tests are essential in certain stages of medical device development and regulatory submission, particularly when it comes to material selection and preliminary evaluations.

• Material Screening: ASTM standards are frequently used in the early stages to select suitable materials for a device. For example, ASTM F1980’s accelerated aging can help screen materials for stability.
• Mechanical Testing: ASTM standards such as D638 are ideal for testing the mechanical properties of components that do not interact with tissues directly, like plastic housings or external devices.
• Supplemental Testing: For certain device types, ASTM tests are used in addition to ISO tests. For example, ASTM F2255 provides a standardized method to evaluate the adhesive strength of tissue adhesives, offering a valuable way to compare adhesives or bonding processes in terms of susceptibility to fatigue and environmental changes. This serves as an additional and complementary check alongside ISO guidelines for biocompatibility and performance.

5. Navigating Regulatory Requirements: When to Use ASTM and ISO Standards

For most medical device biocompatibility testing, ISO 10993 standards are the primary requirement for regulatory bodies such as the FDA and EU Notified Bodies. However, ASTM tests may complement ISO testing in the following scenarios:

• FDA 510(k) Submissions: The FDA may accept ASTM tests as part of a premarket notification (510(k)) submission for low-to-moderate risk devices, particularly if they demonstrate specific material properties.
• Supplementary Data for Risk Management: ASTM tests can provide additional data for the device’s risk management file, which can be helpful in identifying and mitigating potential risks that may not be addressed through ISO alone.

Conclusion

ASTM standards play a valuable role in medical device testing, particularly in material selection and preliminary testing of individual properties. However, they are not a comprehensive substitute for biocompatibility testing, especially for devices requiring holistic biological evaluations. For medical devices that involve complex biological interactions, ISO 10993 standards remain the primary reference, offering more extensive coverage for regulatory acceptance worldwide.

For medical device manufacturers, understanding the unique strengths and limitations of ASTM standards allows for a strategic approach to testing that balances compliance with material performance, ultimately supporting the safe and effective use of devices in healthcare settings.

About the Author: Prof. Łukasz Szymański

Prof. Łukasz Szymański is an expert in medical device biocompatibility testing, serving as the Chief Scientific Officer (CSO) of the ISO 17025-accredited and GLP-certified North American Biomedical Institute (NABI) and European Biomedical Institute (EBI). As a dedicated researcher and a key contributor to advancing safety standards in the biomedical field, Prof. Szymański plays an integral role in shaping scientific innovations and regulatory compliance within the industry.