What Is Systemic Toxicity — ISO 10993-11?
The systemic toxicity assessment examines whether substances released from the device have an effect beyond the contact site, throughout the body. It is divided by exposure duration into acute, subacute, subchronic and chronic; which category is required depends on the device's contact duration.
Purpose of Systemic Toxicity — ISO 10993-11
The purpose is to determine whether substances released over the device's period of use lead to a systemic toxic effect. The assessment is primarily carried out through chemical characterisation and toxicological risk assessment.
Which Products Is Systemic Toxicity — ISO 10993-11 Applied To?
- Long-term implants
- Blood-contacting devices
- Dialysis and infusion sets
- Absorbable materials
- Long-term indwelling catheters
In Which Sectors Is Systemic Toxicity — ISO 10993-11 Used?
Standards Related to Systemic Toxicity — ISO 10993-11
- ISO 10993-11sistemik toksisite test
Systemic Toxicity — ISO 10993-11 Conditions
- Category
- Acute, subacute, subchronic or chronic, according to the device's contact duration
- Priority
- Chemical characterisation (ISO 10993-18) and toxicological risk assessment
- Extraction
- Per ISO 10993-12; representing the worst case of clinical use
- Assessment
- Comparing the amount of substance released against the permitted exposure level
Equipment for Systemic Toxicity — ISO 10993-11
- Extraction and sample preparation setup
- GC-MS, LC-MS and ICP-MS systems (leachable substance determination)
- Access to toxicological databases
- Controlled environment and recording systems
Sample Requirements for Systemic Toxicity — ISO 10993-11
- The specimen must be supplied in its final state, having gone through all series-production processes (including sterilisation).
- The surface area and mass of the device in patient contact must be provided.
- Material composition, manufacturing aids and coating information, if any, must be shared.
- The specimen quantity needed for extraction is calculated from the surface area; this must be confirmed before shipping.
- Packaging integrity must be maintained for sterile products.
Duration of Systemic Toxicity — ISO 10993-11
Chemical characterisation and toxicological assessment take several weeks. If a test under the chronic category is required, duration is much longer and separately planned.
Systemic Toxicity — ISO 10993-11 Procedure
- 1The device's contact duration and category are determined.
- 2The material is chemically characterised per ISO 10993-18.
- 3Leachable and extractable substances are determined.
- 4The toxicological threshold and permitted exposure are assessed for each substance.
- 5If the risk cannot be closed with chemical data, a suitable test is planned.
- 6Findings are assessed with the ISO 10993-17 approach.
- 7The result is carried into the biological evaluation report.
Systemic Toxicity — ISO 10993-11 Acceptance Criteria
The acceptance criterion is selected from the relevant section of the standard according to the device's contact type (surface, externally communicating, implant), contact duration and intended use. The assessment relies not on a single test result but on the biological evaluation plan carried out under ISO 10993-1; this page therefore gives no fixed limit.
Evaluation of Results
The assessment relies on whether the amount of substance the patient is exposed to stays below the toxicologically acceptable level. Where the margin is insufficient, the material, manufacturing process or cleaning step is reviewed.
Systemic Toxicity — ISO 10993-11 Report
- Device identification, model and lot number, if any
- Device contact type, duration and intended use
- Standard and section applied
- Extraction or sample preparation conditions
- Cell line, test system or test rig used
- Controls and their results
- Observations, measurement results and assessment
- A statement that the result applies only to the specimen submitted for testing
Accreditation
EUROLAB holds internationally recognised accreditation obtained from accreditation bodies party to the IAF and ILAC multilateral recognition arrangements, under ISO/IEC 17025 for laboratory testing, ISO/IEC 17020 for inspection and surveillance, and ISO/IEC 17021-1 and ISO/IEC 17065 for system and product certification. This chain ensures the reports and certificates issued are accepted worldwide.
Whether this test can be offered within accredited scope depends on your product and the standard applied; since accreditation is method-based, the scope is confirmed in writing at the quotation stage.
Scope and authorisationsRelated Regulations
- EU 2017/745 Medical Device Regulation (MDR)
- Medical Device Regulation (Türkiye)
- ISO 14971 (risk management for medical devices)
- ISO 13485 (medical devices — quality management system)
Medikal Cihaz Testleri — What Does This Testing Field Cover?
The section below describes the field that the Systemic Toxicity test belongs to; the conditions and acceptance criteria of this particular test are given in the sections above. The scope specific to your product is confirmed in writing at the quotation stage.
Medical device testing shows that a device is safe for the patient and the user and maintains its intended performance. In this family safety is not only about avoiding harm; a device failing to perform its expected function is also treated as a risk. A monitor missing an alarm or a pump delivering the wrong dose is directly a patient safety event.
At the centre of the field is RISK MANAGEMENT, and this is what sets medical apart from other sectors. The risk management process run under ISO 14971 also determines which tests are required. The test list is not copied from a table of standards; it is derived and justified from the device's intended use, the nature and duration of patient contact, the use environment and foreseeable misuse.
Assessment consists of several separate bodies of work, each with its own set of standards. Biocompatibility runs through the ISO 10993 series, electrical device safety through the IEC 60601 series, sterilisation through ISO 11135/11137/17665, packaging through ISO 11607, software through IEC 62304 and usability through IEC 62366. The quality system (ISO 13485) is the framework that binds these together.
Which tests are required is determined by the device's CLASS and its MODE OF CONTACT WITH THE BODY. A product in brief contact with skin and an implant entering the bloodstream do not go through the same test set; the scope is set by a biological evaluation plan prepared under ISO 10993-1. That plan justifies in writing which endpoints are required and why the others are not.
Packaging and sterilisation are taken as seriously as the device itself in this field. For a sterile device the packaging is not a transport container but the barrier that maintains sterility; if the barrier is breached, the device is no longer sterile. Packaging processes are therefore validated and shelf life is supported by real-time ageing data.
For devices containing software, assessment shifts from testing towards PROCESS assurance. IEC 62304 defines which development and verification steps must be followed according to the safety class of the software; the evidence is the traceability of the development process. Testing software does not make it safe — the process record does.
The clinical side is a separate column of the technical file. Test reports show that the device is technically safe; clinical evaluation establishes that the device delivers the intended clinical benefit and that the benefit-risk balance is acceptable. Neither replaces the other.
Method groups in this field
Biocompatibility
Cytotoxicity, irritation, skin sensitisation, systemic toxicity, haemocompatibility, genotoxicity and local effects after implantation. The required endpoints are set by the ISO 10993-1 plan.
Electrical device safety
IEC 60601-1 basic safety and essential performance; EMC, alarm, usability and environmental requirements through the collateral standards.
Sterilisation validation
Validation of sterilisation processes by ethylene oxide, radiation or moist heat; bioburden and sterility assurance level studies.
Packaging
Integrity of the sterile barrier system, seal strength, distribution simulation and shelf-life studies.
Microbiological tests
Bioburden determination, sterility testing, bacterial endotoxin and, where required, carrier validation studies.
Software and usability
IEC 62304 life cycle evidence and use-error focused evaluation under IEC 62366.
Commonly confused in this field
- Cytotoxicity alone is not evidence of biocompatibility; the required set of endpoints is determined and justified according to ISO 10993-1.
- An ISO 13485 certificate does not confer CE marking; classification under the MDR, the technical file and the notified body process run separately.
- Accelerated ageing does not replace real-time ageing; a shelf life claim is supported by real-time data.
- A change of material (supplier, pigment, sterilisation method) may require the biological evaluation to be repeated; it is not a silent change.
- An assessment made without the collateral and particular standards for IEC 60601-1 is incomplete; which -1-x and -2-x standards were applied must appear in the report.
- In vitro diagnostic devices fall under the IVDR rather than the MDR, and laboratory equipment is often on the IEC 61010-1 side.
Which decisions these results support
- MDR/IVDR technical file and notified body assessment
- Completing the biological evaluation plan
- Sterilisation and packaging validation
- Determining shelf life and storage conditions
- Determining the scope of reassessment after a design change
Related Tests
Frequently Asked Questions About Systemic Toxicity — ISO 10993-11
Is systemic toxicity testing required for every device?
No. ISO 10993-1 ties the requirement to contact type and duration; in most cases, chemical characterisation and toxicological risk assessment close the endpoint.
What is the difference between extractable and leachable substances?
Extractables are substances that can come out of the material under exaggerated conditions; leachables are those that come out under real clinical use conditions. The risk assessment uses both together.