Can Biological Tests Be Waived? What a Defensible Rationale Requires

Why Test Waivers Are Often Misunderstood

Waivers are often treated like loopholes or shortcuts. In practice, a good waiver requires more thinking than ordering a test. You need to show why the endpoint is already addressed through device-specific evidence such as material characterization, published literature, prior testing, chemistry data, equivalence, or toxicological risk assessment.

When a Test Waiver Is Appropriate

A no-new-testing rationale may be appropriate when the total evidence is sufficient to address the endpoint for the device and intended market. First use the biological endpoint selection guide to identify the question and available evidence routes. The examples below are possible starting points for evaluation, not automatic waivers:

• Cytotoxicity: relevant prior evidence, material and process history, and finished-device comparability may contribute to a rationale after changes and remaining uncertainty are assessed.
• Sensitization: constituent knowledge, prior evidence and finished-device representation may contribute, but a material declaration or absence of a known sensitizer is not sufficient by itself.
• Genotoxicity: chemical characterization and toxicological analysis can contribute to the endpoint-specific weight of evidence under ISO 10993-3 and the applicable market framework. The absence of detected compounds above selected thresholds does not, by itself, establish that the endpoint is addressed.
• Carcinogenicity: long-term exposure, genotoxicity, constituents, degradation and other relevant evidence require an endpoint-specific evaluation. A TRA conclusion is one input, not an automatic waiver.

What a Valid Waiver Justification Needs

A waiver is not a checkbox. It is a written scientific argument. A strong justification usually contains:

• The endpoint being waived: clearly identify what is not being tested.
• The evidence used: literature, test reports, chemistry data, material specifications, predicate/equivalence logic, or TRA outputs.
• Device relevance: explain why that evidence actually applies to the finished device, its materials, its contact type, and its contact duration.
• A conclusion: state clearly that the endpoint is adequately addressed without additional testing and why.

What Weak Waiver Rationale Looks Like

This is where many submissions fail. Reviewers often push back when the file says "not applicable" or "covered by existing data" without showing the logical bridge from the evidence to the endpoint conclusion.

• Generic language: the rationale is not tied to the actual device or patient-contacting materials.
• No finished-device representation: the evidence is based on raw material data, not the final processed and sterilized device.
• No chemistry bridge: extractables or material characterization exist, but the file does not explain how they support the endpoint conclusion.
• No link to duration or contact type: the waiver ignores one of the core drivers of endpoint applicability.

Why ISO 10993-1:2025 Matters

The 2025 revision strengthens the role of evidence-led no-new-testing decisions. It makes clear that new biological tests should not be performed when existing evidence is already sufficient. That is good science and better animal-use ethics, but it does not create an automatic entitlement to omit a test: evidence sufficiency and the remaining uncertainty still need to be documented for the endpoint, device and applicable market framework.

Where Chemistry and TRA Become Critical

For prolonged-contact and permanent-contact devices, a no-new-testing rationale may rely substantially on ISO 10993-18 chemical characterization and ISO 10993-17 toxicological risk assessment. These inputs can support endpoint conclusions, but they do not automatically replace the endpoint evaluation. ISO 10993-3:2026 addresses evaluation of genotoxicity, carcinogenicity, reproductive toxicity and developmental toxicity after the need for those evaluations has been established under ISO 10993-1.

Practical Rule for BEP and BER

The BEP should state the intended waiver strategy and the evidence path that will be used. The BER should present the actual evidence and the final waiver conclusion. When the plan and report align, the waiver reads as part of a controlled scientific process rather than a last-minute omission.