ISO 10993 Biocompatibility Testing for Medical Device Coatings: Tests, Contact Categories, and 2025 Update

ISO 10993 is a series of international standards for the biological evaluation of medical devices, developed by ISO technical committee TC 194.

All medical devices that contact the human body must function as intended without causing harm. For inserted or implanted devices, manufacturers use medical device coatings to enhance safety. Such coatings, along with the medical device surfaces, are evaluated for biocompatibility according to ISO 10993 by analytical testing providers such as Hydromer®, who offer a range of testing services. 

ISO 10993 requires assessment of the finished device, including the coating, substrate, and post-sterilization state. The standard covers contact categorization, chemical characterization, toxicological risk assessment, and biological tests for cytotoxicity, sensitization, irritation, and hemocompatibility. The latest edition, ISO 10993-1:2025, shifts from a checklist approach to a risk-based process aligned with ISO 14971.¹

In this guide we review how ISO 10993 applies specifically to medical device coatings. We will focus on the contact categories, the biological effects that are evaluated, the test standards, and the role of chemical characterization. We also cover the latest changes introduced in the 2025 edition and the situations where a coating change calls for re-evaluation. Simply put, this article is a walkthrough of the testing process so biomedical engineers, regulatory affairs professionals, and medical device manufacturers can plan their coating biocompatibility work with confidence.

Key Takeaways

• ISO 10993 is a series of international standards for the biological evaluation of medical devices, developed by ISO technical committee TC 194.
• The latest edition, ISO 10993-1:2025, shifts from a checklist approach to a risk-based process aligned with ISO 14971.
• For a coated device, the coating shares the category of the surface it covers.
• Chemical characterization under ISO 10993-18 identifies what the coated device can release into the patient, and the 2025 edition of Part 1 makes it a prerequisite for every device.

What Is ISO 10993 Biocompatibility Testing?

ISO 10993 is a series of international standards developed by ISO technical committee TC 194 for the biological evaluation of medical devices.¹ Manufacturers, test laboratories, and regulators such as the US FDA use it to judge whether a device is safe for contact with the human body.² It is not a single pass-or-fail test. It is a process for identifying the biological risks of a device, deciding which of them need data, and generating that data in a consistent way.

Part 1 is the framework document of the series. Its sixth edition, ISO 10993-1:2025, treats biological evaluation as a risk management activity under ISO 14971 rather than a list of tests to complete.¹ The other parts describe how a specific biological effect is tested, how samples are prepared, and how the chemicals released by a device are identified and assessed.

How the ISO 10993 Series is Structured

The series is organized as a family of parts, and each part has a specific job.¹ Part 1 sets the evaluation process, the contact categories, and the biological effects to consider for each category. The test method parts each cover one biological effect, such as:

• Part 5 for in vitro cytotoxicity
• Part 10 for skin sensitization
• Part 23 for irritation
• Part 11 for systemic toxicity
• Part 4 for interactions with blood
• Part 6 for local effects after implantation
• Part 3 for genotoxicity

A third group of parts supports the testing itself. Part 12 covers sample preparation and reference materials, Part 18 covers chemical characterization, and Part 17 covers the toxicological risk assessment of the chemicals found. Part 7 deals with ethylene oxide sterilization residuals, and Parts 9 and 13 to 15 deal with degradation products. For a coated device, Parts 12, 17, and 18 usually carry as much weight as the biological tests, because the coating chemistry decides what can leach out.

What Changed in ISO 10993-1:2025 for Coated Devices

ISO 10993-1:2025 replaced the 2018 edition in November 2025.¹ Below are the changes that matter most for a coated medical device.

• Risk management first: Biological evaluation now sits inside the ISO 14971 process and runs through the device life cycle. The evaluation is a justified plan, not a checklist.¹
• Four contact tables: Table A.1 is gone. Devices are grouped by the tissue they contact, and each group has its own table of biological effects.¹
• Contact days: Repeated use is counted in contact days, so a coated device used daily on the same patient can move up a duration category.¹
• Reasonably foreseeable misuse: Predictable misuse that extends or changes the contact must now be part of the evaluation.¹
• Chemistry before biology: Material and chemical characterization come first, and in vitro methods are preferred over animal tests. This puts the coating formulation and its leachables at the front of the file.¹
• FDA position: The FDA recognized the 2025 edition in part on 25 May 2026 and accepts declarations to the 2018 edition until 1 July 2029.³

Key ISO 10993 Standards Relevant to Medical Device Coatings

A few parts of the series apply to every coated device, whatever tissue it contacts.¹ Below are the ones that shape the coating file. The parts tied to individual biological effects appear later with each effect.

• ISO 10993-1:2025: The framework document. It sets the contact categories, the biological effects to evaluate, and the records the evaluation must produce.¹
• ISO 10993-12:2021: Sample preparation. It defines how a coated device is extracted, including surface area to volume ratio, vehicle, and conditions.⁴
• ISO 10993-18:2020: Chemical characterization. It describes the extractables and leachables studies that show what a coating can release into the body.⁵
• ISO 10993-17:2023: Toxicological risk assessment. It turns the chemicals found under Part 18 into a safety judgment based on patient exposure.⁶
• ISO 10993-7:2026: Ethylene oxide residuals. It sets allowable limits for EO and ethylene chlorohydrin on sterilized devices, since polymer surfaces can retain EO.⁷

Contact Category and Contact Duration: The Starting Point for Coated Devices

The first step in any ISO 10993 evaluation is to place the device in a contact category and a duration category.

Under the 2025 edition, contact is classed by the tissue the device touches: intact skin, intact mucosal membranes, breached or compromised tissue or internal tissues other than blood, and circulating blood.¹

Duration is classed as limited (up to 24 hours), prolonged (more than 24 hours, up to 30 days), or long-term (over 30 days).¹

For a coated device, the coating shares the category of the surface it covers. A hydrophilic-coated guidewire is a blood-contacting device with limited exposure, while a coated indwelling urinary catheter contacts intact mucosal membranes for a prolonged or long-term period.² Note that repeated use on the same patient is counted as one total exposure period, measured in calendar days from first to last use.¹ When a device fits more than one category, the worst case decides the evaluation.¹

7 Essential ISO 10993 Tests for Coated Medical Devices

Once a coated device is categorized, the matching table in ISO 10993-1:2025 lists the biological effects to consider.¹ Below are the seven that come up most often for coated devices, and not every one ends in a test, as the next section shows.

1. Cytotoxicity (ISO 10993-5)

Cultured cells are exposed to an extract of the coated device, and a viability drop of more than 30% counts as a cytotoxic effect.⁸ It is the first screen for every coated device, and it is sensitive to uncured monomers, residual solvents, and photoinitiators left in the coating.

2. Sensitization (ISO 10993-10)

This test checks whether contact with the coating’s extractables can trigger an allergic skin response, through methods such as the guinea pig maximization test or the local lymph node assay.⁹ It applies across contact categories, and additives such as crosslinkers and photoinitiators are the usual sources of concern.

3. Irritation (ISO 10993-23)

Irritation is now assessed first on in vitro reconstructed human epidermis models, with animal methods such as the intracutaneous reactivity test kept for exposures the in vitro model cannot represent.¹⁰ For a coated urinary or airway catheter resting against mucosal membranes, this effect is a direct measure of local tolerance.

4. Systemic Toxicity (ISO 10993-11)

Extracts of the coated device are dosed into animals to look for effects away from the contact site, with the study length matched to the exposure duration.¹¹ This effect can often be addressed through chemical characterization and a toxicological risk assessment instead, which is where a well-documented coating formulation pays off.⁶

5. Hemocompatibility (ISO 10993-4)

Blood-contacting coatings are assessed for hemolysis, thrombosis, coagulation, platelet activation, and complement activation, with the test set chosen by the type and duration of blood contact.¹² Hydrophilic coatings on guidewires and catheters fall here, and a coating that sheds particles or leaches into blood shows up quickly.

6. Local Effects After Tissue Contact (ISO 10993-6)

Coated samples are placed in tissue and the local response, such as inflammation, fibrous capsule formation, and integration, is scored against a control material over time.¹³ The 2025 edition renamed this from implantation effects and applies it to any coated device in prolonged or long-term tissue contact, not only implants.¹

7. Genotoxicity (ISO 10993-3)

In vitro assays such as the bacterial reverse mutation test and a mammalian cell test check whether the coating’s extractables can damage DNA.¹⁴ Under the 2025 edition, this effect is considered for prolonged and long-term contact in every category except intact skin, a point the FDA has flagged for prolonged-contact devices.³

Chemical Characterization and Toxicological Risk Assessment of Coatings

Chemical characterization under ISO 10993-18 identifies what the coated device can release into the patient, and the 2025 edition of Part 1 makes it a prerequisite for every device.^1,5 The coating adds its own set of extractables on top of the substrate’s, so the formulation details from the coating supplier are the first input. See our guide to chemical characterization testing for how extractables and leachables studies are performed.

The toxicological risk assessment under ISO 10993-17 then compares the estimated patient exposure to each identified chemical against a tolerable exposure limit derived from toxicology data.⁶ When the margin is adequate, systemic toxicity, genotoxicity, and carcinogenicity can be addressed on paper rather than in animal studies.^2,6 This is the step that rewards a clean, well-documented coating formulation, and the step that may stall when the supplier cannot share its chemistry.

Testing the Coating vs. Testing the Finished Device

Coating-level data has its own place.

A supplier can screen a formulation on standard substrates for cytotoxicity and extractables. This helps with material selection and the information-gathering step of ISO 10993-18.⁵ That said, the results that support a submission come from the finished device: the coating on its actual substrate, cured through the production process, packaged, and sterilized.² A cure change, a new substrate, or a switch from ethylene oxide to gamma can change what the surface releases.

Supplier data can still reduce the test burden when the materials and processing are the same, though the 2025 edition sets a higher bar for claiming equivalence to an earlier device.¹ The biological evaluation plan is where these decisions are recorded: the categorization, the existing data, the gaps, and the tests to be run on the final sterilized product.¹ The biological evaluation report then closes the loop, pulling every result into one justified conclusion on biological safety.¹

Conclusion: Biocompatibility Testing for Hydrophilic Coatings

Hydrophilic coatings for medical devices raise the same ISO 10993 questions as any other material, plus two of their own:

• What the polymer network releases into the extract
• Whether the coating stays on the surface under use

Water-based formulations, controlled cure, and low-leaching chemistry help keep both in check. At Hydromer®, we have formulated hydrophilic coatings for over four decades, and we run ISO 10993 biocompatibility testing in-house at our FDA-registered, ISO 13485:2016 and ISO 9001:2015 certified facility.

This lets us support your biological evaluation from the first extractables screen on your own substrate to the data package for the final sterilized device. Contract coating, specialized analytical testing, formulation customization, and complementary PTFE tubing and liners are available as per your project.

Let us help you build a coating biocompatibility file that holds up under review. Please feel free to contact Hydromer® to discuss ISO 10993 testing for your coated device or to request samples.

FAQ

References

View All References (14 ISO & FDA Regulatory Sources)

1. International Organization for Standardization. ISO 10993-1:2025, Biological evaluation of medical devices, Part 1: Requirements and general principles for the evaluation of biological safety within a risk management process. Geneva: ISO; 2025. https://www.iso.org/standard/84512.html

2. U.S. Food and Drug Administration. Use of International Standard ISO 10993-1, Biological evaluation of medical devices, Part 1: Evaluation and testing within a risk management process: Guidance for Industry and Food and Drug Administration Staff. Silver Spring, MD: FDA; September 2023. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/use-international-standard-iso-10993-1-biological-evaluation-medical-devices-part-1-evaluation-and

3. U.S. Food and Drug Administration. Recognized Consensus Standards: Medical Devices, Recognition Number 2-313, ISO 10993-1 Sixth edition 2025-11. Silver Spring, MD: FDA; 2026. https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfstandards/detail.cfm?standard__identification_no=47116

4. International Organization for Standardization. ISO 10993-12:2021, Biological evaluation of medical devices, Part 12: Sample preparation and reference materials. Geneva: ISO; 2021. https://www.iso.org/standard/75769.html

5. International Organization for Standardization. ISO 10993-18:2020, Biological evaluation of medical devices, Part 18: Chemical characterization of medical device materials within a risk management process. Geneva: ISO; 2020. https://www.iso.org/standard/64750.html

6. International Organization for Standardization. ISO 10993-17:2023, Biological evaluation of medical devices, Part 17: Toxicological risk assessment of medical device constituents. Geneva: ISO; 2023. https://www.iso.org/standard/75323.html

7. International Organization for Standardization. ISO 10993-7:2026, Biological evaluation of medical devices, Part 7: Ethylene oxide sterilization residuals. Geneva: ISO; 2026. https://www.iso.org/standard/84824.html

8. International Organization for Standardization. ISO 10993-5:2009, Biological evaluation of medical devices, Part 5: Tests for in vitro cytotoxicity. Geneva: ISO; 2009. https://www.iso.org/standard/36406.html

9. International Organization for Standardization. ISO 10993-10:2021, Biological evaluation of medical devices, Part 10: Tests for skin sensitization. Geneva: ISO; 2021. https://www.iso.org/standard/75279.html

10. International Organization for Standardization. ISO 10993-23:2021, Biological evaluation of medical devices, Part 23: Tests for irritation. Geneva: ISO; 2021. https://www.iso.org/standard/74151.html

11. International Organization for Standardization. ISO 10993-11:2017, Biological evaluation of medical devices, Part 11: Tests for systemic toxicity. Geneva: ISO; 2017. https://www.iso.org/standard/68426.html

12. International Organization for Standardization. ISO 10993-4:2017, Biological evaluation of medical devices, Part 4: Selection of tests for interactions with blood. Geneva: ISO; 2017. https://www.iso.org/standard/63448.html

13. International Organization for Standardization. ISO 10993-6:2016, Biological evaluation of medical devices, Part 6: Tests for local effects after implantation. Geneva: ISO; 2016. https://www.iso.org/standard/61089.html

14. International Organization for Standardization. ISO 10993-3:2014, Biological evaluation of medical devices, Part 3: Tests for genotoxicity, carcinogenicity and reproductive toxicity. Geneva: ISO; 2014. https://www.iso.org/standard/55614.html