Understanding ISO 10993-1:2025: The Risk-Based Framework for Medical Device Biocompatibility

ISO 10993-1 sits at the center of how regulators expect you to think about biological safety. It is the international standard for biological evaluation of medical devices, and Part 1 provides the framework for structuring your entire biocompatibility strategy within a risk management process.

The 2025 edition, represents the most significant change to biocompatibility evaluation in decades. The familiar endpoint matrix that guided testing decisions for over 30 years has been replaced with a systematic biological risk assessment framework that fundamentally changes how manufacturers approach biocompatibility evaluation.

If you are a manufacturer, consultant, or CRO, you're navigating this transition now. You must interpret ISO 10993-1:2025 correctly, reconcile it with existing FDA guidance that references the old matrix approach, connect it to ISO 14971 risk management, and maintain timelines and budgets while ensuring biological safety. At the same time, you cannot over-test, under-test, or ignore material and process changes that shift your biological risk profile.

This article walks through ISO 10993-1:2025 as it applies to real regulatory strategies in 2026, helping you move from "What tests do we run?" to "What biological risks do we have, and how do we justify our approach in a way regulators accept?"

Key Principles and Structure of ISO 10993-1:2025

ISO 10993-1:2025 provides a structured framework for biological evaluation, but the approach has fundamentally changed from previous editions.

The Risk-Based Biological Evaluation Framework

The core principle remains: you identify how your device contacts the body, assess biological risks, then justify your evaluation approach through testing, chemical characterization, existing data, or combination thereof. However, how you do this has changed dramatically.

What's different in ISO 10993-1:2025:

The endpoint matrix is gone. Device contact type and duration no longer automatically dictate which biological tests are required. Instead, you must conduct systematic biological risk assessment to determine what information is needed.

Information gathering comes first. The standard prioritizes gathering existing information—material data, literature, chemical characterization, post-market surveillance—before conducting new biological testing.

Animal welfare requirements are strengthened. The standard explicitly states that in vivo testing shall not be conducted where valid information on released constituents and degradation products has been addressed by other means and constituents have known and acceptable toxicity profiles.

Scientific justification is mandatory. Every decision—to test, not to test, or to use alternative approaches—requires clear scientific rationale documented in your biological evaluation plan and report.

Device Characterization and Contact Categorization

While the matrix is gone, device characterization remains essential.

Contact categorization still matters for framing biological risk assessment:

• Contact type: surface, external communicating, or implant

• Contact location: skin, mucosal membrane, breached surface, blood path, tissue, bone

• Contact frequency and duration: limited (≤24 hours), prolonged (>24 hours to 30 days), permanent (>30 days)

However, this categorization informs your biological risk assessment rather than prescribing specific tests.

Device characteristics requiring evaluation include:

• Materials of construction and their chemical composition

• Physical characteristics (porosity, particle size, surface morphology)

• Manufacturing process impacts (passivation, laser marking, sterilization)

• Constituents available on device surface or released during use

• Potential degradation products

• Interactions with other devices or medicines

The Biological Risk Assessment Process

ISO 10993-1:2025 requires a systematic process:

1. Identify biological hazards based on device characteristics, materials, and intended use

2. Estimate biological risks using available information from multiple sources

3. Evaluate risk acceptability against defined criteria

4. Determine information needs - what additional data (if any) is required

5. Plan evaluation activities - testing, chemical characterization, or other assessments

6. Conduct evaluations and integrate results

7. Draw safety conclusions with scientific justification

This process must be documented in your biological evaluation plan and executed systematically, not treated as a checklist exercise.

Applying FDA Guidance with ISO 10993-1:2025

FDA uses ISO 10993-1 as a recognized consensus standard, but current FDA guidance predates the 2025 revision and still references the endpoint matrix approach. This creates a practical challenge manufacturers must navigate.

Reconciling FDA Guidance with ISO 10993-1:2025

FDA's biocompatibility guidance (issued before ISO 10993-1:2025) includes a modified biological endpoint matrix that looks similar to the old ISO 10993-1:2018 table. FDA adjusts certain endpoints, timing, and expectations based on review experience.

The practical approach for 2026:

Start with ISO 10993-1:2025 risk-based evaluation. Conduct systematic biological risk assessment identifying hazards, estimating risks, and determining what information is needed.

Consider FDA's endpoint guidance as input. Use FDA's matrix as one factor informing which biological effects warrant evaluation, but don't treat it as an automatic testing requirement.

Provide clear scientific justification. Document why your risk-based approach adequately addresses biological safety, referencing both ISO 10993-1:2025 principles and FDA's endpoint expectations.

Expect FDA questions during transition. Reviewers familiar with the matrix approach may question decisions not to conduct certain tests. Prepare strong scientific rationales explaining how you addressed those biological risks through alternative means.

What FDA Expects in Submissions

Regardless of the standard revision, FDA fundamentally cares about:

Biological risk assessment documentation. Clear identification of biological hazards, risk estimation, and determination of information needs based on device characteristics and intended use.

Test article preparation. When testing is conducted, clear description of worst-case configurations, processing, sterilization, and extraction conditions that represent clinical use.

Chemical characterization. For devices where chemical constituents drive biological risk, robust analytical methods, detection limits, and traceable toxicological risk assessment—not generic "no concern" statements.

Scientific justification. Clear rationale for all decisions, including decisions not to conduct specific tests when existing information is sufficient.

Documentation quality. A structured biological evaluation plan followed by a comprehensive report that integrates all information sources and ties conclusions back to identified risks.

If you build your biocompatibility strategy using ISO 10993-1:2025's risk-based framework while addressing FDA's endpoint expectations through scientific justification, you reduce review questions and maintain submission timeline control.

Overview of the ISO 10993 Series as an Integrated System

ISO 10993 is not a single document—it's a toolbox. Part 1 provides the framework for biological evaluation planning; the rest of the series provides methods and guidance for generating and interpreting the data your plan requires.

The series can be organized into four groups:

Biological test methods: Cytotoxicity (Part 5), sensitization (Part 10), irritation (Part 10), systemic toxicity (Part 11), genotoxicity (Part 3), implantation (Part 6), and similar endpoints.

Chemistry and toxicology: Chemical characterization (Part 18), identification and quantification of degradation products from polymers (Part 13), ceramics (Part 14), and metals (Part 15), toxicological risk assessment (Part 17), and toxicokinetic study design (Part 16).

Special situations: Degradation products (Part 9), interactions with blood (Part 4), and specific tissue or organ interactions.

Guidance and support: Sample preparation (Part 12), animal welfare (Part 2), and general principles (Part 1).

Using the Series Systematically

Build your biological evaluation plan from ISO 10993-1:2025, conducting systematic biological risk assessment to determine what information is needed.

Map information needs to relevant parts of the series. If chemical characterization is needed, use Part 18. If toxicological risk assessment is required, apply Part 17. If biological testing is necessary, select appropriate test methods from Parts 3-6, 10-11.

Align methods with risk assessment under ISO 14971, ensuring your evaluation approach addresses identified biological hazards and risks.

Document clear connections between biological risks, information sources (existing data, literature, chemical characterization, testing), evaluation methods, and safety conclusions.

This systematic approach transforms the ISO 10993 series from a collection of test methods into a coherent biological risk management system aligned with ISO 10993-1:2025's framework.

Practical Considerations and Best Practices

You can treat ISO 10993-1:2025 as a checklist, or you can use it as a strategic tool for efficient biological evaluation. The second approach saves time, money, and regulatory friction.

Get Device Characterization Right Early

Lock device description and contact categorization early. Define contact type, location, frequency, and duration in plain language. Identify all materials with direct or indirect patient contact.

Align characterization across teams. Ensure design, clinical, labeling, and regulatory teams describe the device consistently. Inconsistencies create regulatory questions.

Reconfirm when changes occur. Reassess device characterization and contact categorization when design modifications, indication changes, or use scenarios evolve.

Build Risk-Based Evaluation Strategy

Start with biological risk assessment, not the test matrix. Identify biological hazards based on device characteristics, estimate risks using available information, then determine what additional data is needed.

Gather existing information systematically. Review material supplier data, published literature, similar device information, and post-market data before planning new testing or chemical characterization.

Use chemical characterization strategically. For systemic biological endpoints (systemic toxicity, genotoxicity, carcinogenicity), chemical characterization with toxicological risk assessment often addresses risks more efficiently than animal testing.

Recognize when biological testing is necessary. Local tissue effects (cytotoxicity, sensitization, irritation, implantation) typically require biological testing even when comprehensive chemical data are available.

Document scientific justification clearly. For each biological effect, document the risk, information sources considered, evaluation approach selected, and rationale for that approach.

Treat Documentation as Strategic Asset

Maintain a living biological evaluation plan and report. Update these documents when new information becomes available, changes occur, or post-market data emerges.

Standardize report structure. Use consistent organization across products so reviewers know where to find key information.

Create clear traceability. Link device characteristics to biological hazards to evaluation activities to safety conclusions in a way reviewers can follow.

Stay Current with Evolving Expectations

Monitor regulatory communications. Track FDA guidance updates, warning letters, and industry communications about ISO 10993-1:2025 implementation.

Participate in industry forums. Engage with professional organizations sharing experiences with the new standard and regulatory interactions.

Conduct periodic gap assessments. Evaluate your current approach against ISO 10993-1:2025 requirements and evolving regulatory expectations at defined intervals.

Prioritize high-impact updates. Focus on areas drawing the most regulatory questions—chemical characterization strategy, toxicological risk assessment quality, and scientific justification for testing decisions.

ISO 10993-1:2025 fundamentally changes biocompatibility evaluation from a matrix-driven testing exercise to a systematic biological risk assessment process. This shift aligns with modern risk management principles, emphasizes animal welfare, and recognizes that chemical characterization with toxicological expertise often provides more relevant safety information than routine biological testing.

Success under ISO 10993-1:2025 requires understanding the risk-based framework, gathering existing information before planning new studies, providing clear scientific justification for all decisions, and integrating biological evaluation with design controls and risk management throughout the device lifecycle.

Manufacturers, consultants, and CROs who embrace this approach—rather than trying to force the old matrix thinking into the new framework—will find more efficient paths to demonstrating biological safety while meeting regulatory expectations in 2026 and beyond.

Expert Guidance for ISO 10993-1:2025 Implementation

Successfully navigating ISO 10993-1:2025's risk-based biological evaluation framework requires deep toxicological expertise and understanding of both the standard's requirements and regulatory expectations.

At JL Tox Consulting, we help medical device manufacturers, consultants, and CROs implement ISO 10993-1:2025 requirements while maintaining efficient product development and regulatory approval timelines.

Our ISO 10993-1:2025 implementation services include:

• Biological evaluation planning using systematic risk assessment frameworks

• Chemical characterization strategy for extractables and leachables per ISO 10993-18

• Toxicological risk assessment of chemical constituents per ISO 10993-17

• Scientific justification documentation for testing decisions and safety conclusions

• Biological evaluation report preparation integrating all information sources

• FDA submission support reconciling ISO 10993-1:2025 with FDA guidance expectations

• Training and knowledge transfer on risk-based biological evaluation principles

Contact JL Tox Consulting to implement ISO 10993-1:2025 effectively:

Email: info@JLTox.com

Phone: (877) 899-6568