Written and maintained by CASRAI Editorial Board
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This guide is general product and standards information for lab, clinic and supply staff. It is not medical advice and does not describe any test procedure.
Short answer
ISO 10993-11 (also written “ISO 10993 11”) is the part of the ISO 10993 biological-evaluation series that covers tests for systemic toxicity: effects that appear away from the point where a device or material touches the body. FDA lists it among recognized standards and accepts two of its methods, acute systemic toxicity and material-mediated pyrogenicity, under its ASCA program for biocompatibility testing.
Definition and scope
ISO 10993-1 sets out the overall framework for evaluating a device’s biological safety, and the other parts supply the individual test methods. Part 11 is titled “Tests for systemic toxicity”. FDA’s biocompatibility guidance and its ASCA guidance both refer to it by that title. For how the framework as a whole is applied in a premarket file, see our guide to FDA guidance on biocompatibility; for what counts as a device in the first place, see what is a medical device. This page stays on the systemic-toxicity question only.
How systemic toxicity evidence fits a device file
FDA’s guidance on using ISO 10993-1 (issued September 8, 2023) groups devices by body contact and by duration of contact, and its endpoint table (Table A.1) lists the biological endpoints to consider for each group. The systemic endpoints named there are acute systemic toxicity, material-mediated pyrogenicity, subacute/subchronic toxicity and chronic toxicity.
| FDA contact-duration category | Definition in FDA’s Table A.1 |
|---|---|
| A, limited | Contact of less than 24 hours |
| B, prolonged | More than 24 hours up to 30 days |
| C, long term | More than 30 days |
The table is a matrix: its body-contact rows are marked against these duration categories and against the endpoint columns, so the expected systemic endpoints are read off the row that matches the device’s contact type and duration.
The same FDA text adds a duration rule: a device used for more than 14 days should not be assessed with a 14-day test.
Acute systemic toxicity versus pyrogenicity
FDA notes that ISO 10993-1:2018 identifies material-mediated pyrogenicity as a subset of acute systemic toxicity. It then adds a practical limit: acute systemic toxicity or implantation data may not stand in for a separate pyrogenicity evaluation if the study lacked periodic temperature measurements or was not run in an appropriate model. A supplier that offers one acute study as covering both questions should be asked to show those temperature records.
FDA also says a pyrogenicity test may be unnecessary when chemical characterization of the extract and prior information show that all patient-contacting components are adequately assessed. Otherwise it expects an extract of the device material (prepared as ISO 10993-12 describes) tested by the USP <151> rabbit test or an equivalent validated method.
What a systemic toxicity test report should show
FDA’s ASCA guidance gives example summary test reports (Appendices G and H) and states the points the report must flag. These make a concrete checklist for anyone reading a supplier’s document.
| Item to look for | What FDA’s ASCA guidance says |
|---|---|
| Control animals, acute systemic toxicity | Acceptance requires saline and oil control animals with no adverse clinical findings, no body-weight decrease above 10% per animal and no deaths |
| Flags in the report, acute systemic toxicity | The report must flag any test or control animal that died or had adverse clinical findings, and any test animal that lost more than 10% of its body weight |
| Flags in the report, pyrogenicity | The report must flag any rabbit with a baseline temperature above 39.8 °C or a temperature rise of 0.5 °C or more; the guidance sets no predefined control criteria |
| Sample preparation | Test article preparation follows ISO 10993-12; the example report records the extraction solvent (for instance 0.9% sodium chloride or a vegetable oil) and any deviations |
When a chemical risk assessment can replace testing
FDA states that if extractables and leachables data show exposure below the derived tolerable intake for a chemical (or the threshold of toxicological concern when no tolerable intake can be derived), further toxicological assessment is unnecessary for some endpoints, systemic toxicity among them. FDA also says the no-observed-adverse-effect level (NOAEL) or lowest-observed-adverse-effect level (LOAEL) from a systemic toxicity study can often address acute, subchronic or chronic systemic toxicity endpoints. Background on extractables work is in extractables and leachables in single-use systems, and the toxicology vocabulary is in what is toxicology.
Where it matters for labs, clinics and supply decisions
Systemic toxicity data usually reaches buyers as a line in a supplier’s biocompatibility summary. Reading it against the checklist above shows whether the document states the test, the extraction, the controls and the flags. Related material-level claims are covered in USP Class VI certification, and a product-level example is in FDA-compliant nitrile gloves. Quality-system context is in ISO 13485.
Common misunderstandings
- “One acute study always covers pyrogenicity.” Only if it had the periodic temperature measurements and an appropriate model, per FDA.
- “A short test can cover any duration.” FDA says devices used for more than 14 days should not be assessed with a 14-day test.
- “Testing is always required.” FDA accepts a toxicological risk assessment in some cases, as described above.
FAQ
What is ISO 10993-11?
It is Part 11 of the ISO 10993 series, “Tests for systemic toxicity”, the part FDA recognizes for acute systemic toxicity and material-mediated pyrogenicity testing.
Is “ISO 10993 11” the same as ISO 10993-11?
Yes. The two spellings refer to the same standard part.
Does ISO 10993-11 cover pyrogenicity?
FDA’s ASCA program lists “ISO 10993-11 and USP 151” as the material-mediated pyrogenicity method, and FDA describes pyrogenicity as a subset of acute systemic toxicity in ISO 10993-1:2018.
How do contact type and duration relate to systemic toxicity endpoints?
FDA’s Table A.1 in its ISO 10993-1 guidance sets out the systemic endpoints for each body-contact and duration group; see the category table above.
Sources
- FDA, Use of International Standard ISO 10993-1, Biological evaluation of medical devices, Part 1 (https://www.fda.gov/media/142959/download) (issued September 8, 2023), checked 2026-11-01.
- FDA, Accreditation Scheme for Conformity Assessment (ASCA) Program: Biocompatibility Testing of Medical Devices (https://www.fda.gov/media/142388/download) (issued September 25, 2020), checked 2026-11-01.
