On September 9, 2026, FDA’s Center for Devices and Radiological Health (CDRH) hosted the first of three town halls focused on biocompatibility and medical devices. This first session focused on recent updates to ISO 10993-1:2025, risk assessment approaches for evaluating biocompatibility endpoints, and examples where risk-based assessments may be appropriate in lieu of certain biological or chemical testing.

For medical device and combination product teams, the message was clear: biocompatibility is a clear risk management activity that should be supported by material knowledge, manufacturing information, and solid documentation.

What FDA clarified about ISO 10993-1:2025

FDA partially recognized ISO 10993-1:2025 in May 2026. The updated standard realigns biological evaluation with risk management principles consistent with ISO 14971:2019, which FDA fully recognizes.

However, FDA noted that Clause 6.9, Biological Risk Estimation, in the 2025 version lacks enough implementation specificity and is not fully aligned with ISO 14971. At this time, FDA does not generally request biological risk estimation under Clause 6.9 to be included in marketing submissions.

FDA also stated that it will continue to follow its existing 2023 Biocompatibility Guidance, and currently does not plan to update that guidance. Importanty, FDA emphasized that its expectations for biocompatibility testing are not being increased simply because ISO 10993-1 was updated.

Transition period: 2018 version still acceptable

FDA will accept declarations of conformity to ISO 10993-1:2018 in premarket submissions until July 1, 2029. During the transition period, manufacturers may make declarations of conformity to either the fifth edition or sixth edition.

This matters because teams do not need to panic-shift every file overnight. But they should understand the differences between the 2018 and 2025 versions and be prepared to justify their approach.

Risk-based assessment: when testing may not be necessary

A major theme of the town hall was that testing is not always the only way to address biocompatibility endpoints.

FDA explained that sponsors may use a combination of:

• Nonclinical testing
• Clinical information
• Material and chemical information
• Manufacturing process information
• Similar device experience
• Literature or prior knowledge
• Master files
• Conformity to recognized standards

When the risk and uncertainty are low, a well-supported risk-based assessment may be sufficient for some biological or chemical testing.

Examples include devices made from well-known, standardized materials; materials supported by an applicable master file; or devices with strong similarity to a legally marketed device with the same or worse-case tissue contact & duration.

Material-mediated pyrogenicity: assessment may replace RPT in some cases

FDA also spent significant time discussing material-mediated pyrogenicity (MMP). While MMP was removed from the ISO 10993-1:2025 tables, FDA clarified that it is still addressed under “Other biological effects” in the standard and remains relevant for submissions.

FDA explained that the traditional Rabbit Pyrogen Test (RPT) may be most appropriate in specific circumstances, such as:

• Devices with absorbable or degradable materials that are not well characterized
• Devices with biologically derived materials lacking a history of safe use
• Devices made from materials with no history of safe use in similar or worse-case contact
•  Devices labeled as “non-pyrogenic”

For other devices, FDA indicated that an MMP assessment based on material and manufacturing evaluation may be acceptable in lieu of RPT.

This is important for manufacturers because it supports a least-burdensome approach while still requiring a clear, evidence-based rationale.

Systemic endpoints: material and process knowledge matter

FDA also discussed risk-based assessment for systemic endpoints, including:

• Acute systemic toxicity
• Subacute, subchronic, and chronic toxicity
• Genotoxicity
• Carcinogenicity
• Reproductive and developmental toxicity

For well-characterized materials and controlled manufacturing processes, FDA provided examples where risk assessment may be acceptable in lieu of additional testing.

Examples included bare metal stents made from standardized metals, PEEK orthopedic implants supported by a master file, manufacturing changes involving a validated cleaning process, and molding equipment changes where material properties and processing conditions remain well understood.

The practical takeaway: the stronger your material characterization and manufacturing understanding, the more defensible your risk-based approach becomes.

Supply chain changes still require biocompatibility thinking

One question addressed whether a risk-based approach can support material changes caused by supply chain constraints.

FDA’s answer was yes, depending on the specific endpoint and the information available. However, FDA emphasized that the level of information needed depends on the material type, intended use, type and duration of contact, and whether differences exist in manufacturing process, impurity profile, or trace constituents.

For manufacturers, this is a reminder that supplier or material changes cannot be treated as simple procurement substitutions. They need to be evaluated through quality, regulatory, risk management  and biocompatibility lenses.

What device teams should do now

Based on FDA’s town hall, manufacturers should consider the following:

1) Revisit the biological evaluation strategy

Confirm whether the current biocompatibility plan is based on actual risk, material knowledge, tissue contact, duration, manufacturing processes, and available prior information.

2) Strengthen material and manufacturing documentation

Risk-based assessments depend on good inputs. Teams should ensure supplier information, material specifications, manufacturing aids, cleaning processes, sterilization details, coatings, additives, and residuals are documented and controlled.

3) Use testing when uncertainty is high

Testing may still be appropriate for novel materials, poorly characterized materials, absorbable/ degradable components, biologically derived materials, unexpected toxicity signals, or manufacturing processes that introduce new uncertainty.

4) Document the rationale clearly

If a team chooses a risk-based assessment instead of testing, the rationale should be easy for FDA to follow. The file should explain why the endpoint is addressed, what evidence supports the conclusion, and why additional testing is not necessary.

5) Consider Q-Sub for specific approaches

FDA encouraged sponsors to use the Q-Submission program for specific proposed approaches, especially when the strategy is novel, complex, or may differ from standard expectations.

Bottom line

FDA’s first biocompatibility town hall reinforced a practical message: biocompatibility is not simply a checklist of tests. It is a risk-based evaluation supported by material characterization, manufacturing knowledge, prior evidence, and clear documentation.

For device and combination product teams, this creates an opportunity to reduce unnecessary testing when risk and uncertainty are low. But it also raises the bar for having a well-organized biological evaluation strategy that can stand up to FDA review.

If your team is preparing a new submission, evaluating a material or supplier change, or updating a biological evaluation plan, QSN can help pressure-test the risk assessment, documentation, and submission strategy before questions arise during review.