Systemic Toxicity Testing (ISO 10993-11)
Systemic toxicity studies evaluate the potential generalized effects of a medical device’s leachable substances on organs and tissues away from the point of contact. Unlike local irritation, systemic toxicity focuses on the health of the entire organism, including the cardiovascular, endocrine, and nervous systems.
At EBI, we perform a full range of systemic evaluations as defined by ISO 10993-11, categorized by the duration of exposure.
Acute Systemic Toxicity
Single-dose exposure evaluation.
This study determines whether a single, short-term exposure to a medical device extract poses an immediate health risk. It is a fundamental requirement for nearly all medical device categories.
- Methodology: The device is extracted in both polar (saline) and non-polar (cottonseed oil) vehicles.
- Procedure: Extracts are administered via intravenous or intraperitoneal injection in mice.
- Observation: Animals are monitored at 24h, 48h, and 72h for any signs of biological reactivity, weight loss, or clinical distress.
- Pass Criteria: The test is negative if no significant biological reaction occurs compared to the control group.
- Turnaround Time: 6 weeks.
Subacute Toxicity
Repeated exposure over 14 to 28 days.
Subacute studies evaluate the effects of repeated or continuous exposure over a period that represents a transition from short-term to long-term use.
- Species: Wistar Rats (Rattus norvegicus).
- Evaluation: Includes daily clinical observations and detailed body weight tracking.
- Clinical Pathology: At the study’s conclusion, we perform a comprehensive screen, including 17 biochemistry parameters, 9 urine parameters, and 6 hematology parameters.
- Turnaround Time: 12 weeks.
Subacute & Subchronic & Chronic Toxicity (Combined with Implantation)
Long-term safety evaluation for permanent and prolonged-contact devices.
For devices intended for long-term use, ISO 10993-11 requires subacute (up to 28 days) subchronic (up to 90 days) or chronic (over 180 days) evaluations. EBI specializes in combined studies, where we evaluate both systemic toxicity (ISO 10993-11) and local effects after implantation (ISO 10993-6) in a single study.
Subacute Studies (28 Days)
- Goal: To evaluate systemic and local effects after 28 days of subcutaneous implantation in rats.
- Clinical Pathology: Full terminal screening (Urine, Biochemistry, Hematology) and comprehensive gross necropsy.
- Histopathology: Evaluation of 40 different tissues by a certified histopathologist.
- Turnaround Time: 20 weeks.
Subchronic Studies (90 Days)
- Goal: To evaluate systemic and local effects after 90 days of subcutaneous implantation in rats.
- Clinical Pathology: Full terminal screening (Urine, Biochemistry, Hematology) and comprehensive gross necropsy.
- Histopathology: Evaluation of 40 different tissues by a certified histopathologist.
- Turnaround Time: 20 weeks.
Chronic Studies (180+ Days)
- Goal: To assess the long-term biological safety and degradation profile of the material.
- Duration: 180 days (or longer depending on the clinical life of the device).
- Clinical Pathology: Full terminal screening (Urine, Biochemistry, Hematology) and comprehensive gross necropsy.
- Turnaround Time: 32 weeks.
Technical Specifications
| Test Category | Duration | Route of Administration | Animal Quantity | Turnaround |
|---|---|---|---|---|
| Acute Systemic | 72 Hours | IV / IP Injection | 20 Mice | 6 Weeks |
| Subacute | 14 Days | IV / IP Injection | 24 Rats | 12 Weeks |
| Subacute | 28 Days | Implantation | 20 Rats | TAT do uzupełnienia |
| Subchronic | 90 Days | Implantation | 40 Rats | 20 Weeks |
| Chronic | 180 Days | Implantation | 60 Rats | 32 Weeks |
Sample Requirements for Toxicity Testing
Due to the length and complexity of systemic studies, sample requirements are calculated individually based on the device surface area and the planned number of replicates.
- Acute Toxicity: 120 cm² (thickness <0.5mm) or 60 cm² (thickness ≥0.5mm).
- Subacute/Subchronic/Chronic: To be determined after a technical review of the test plan.
Standards & Regulatory Framework
Our toxicity testing protocols follow the most stringent international guidelines:
- ISO 10993-11: Tests for systemic toxicity.
- ISO 10993-6: Tests for local effects after implantation (for combined studies).
- ISO 10993-12: Sample preparation and reference materials.
- FDA & MHLW Guidelines: For US and Japanese market submissions.
How We Work
Discovery & Insight
We begin with an in-depth consultation to understand your needs, challenges, and objectives. This helps us define the right strategy and scientific approach for your project.
Design & Development
Our experts translate your vision into actionable plans — combining innovative research, data, and technology to build precise and reliable solutions.
Delivery & Support
We implement the solution with full transparency and ongoing communication. After delivery, we stay involved — supporting you with optimization, updates, and future improvements.
FAQ: Systemic Toxicity Strategies
Can I combine Systemic Toxicity with an Implantation study?
Yes. In fact, ISO 10993-11 and ISO 10993-6 encourage combining these tests to reduce the number of animals used and to provide a more holistic view of how the device interacts with the body. EBI regularly performs these combined protocols.
When is Chronic Toxicity testing mandatory?
Chronic testing is typically required for permanent implants or devices that have long-term (more than 30 days) contact with internal tissues, the cardiovascular system, or the skeletal system.
Why is the turnaround time for Chronic Toxicity 32 weeks?
The 32-week timeframe includes the 180-day (approx. 26 weeks) in-life phase, followed by weeks of intensive laboratory work: processing dozens of tissue types for histopathology, analyzing clinical pathology data, and drafting the final expert report.
Can I combine Systemic Toxicity with an Implantation study?
Yes. In fact, ISO 10993-11 and ISO 10993-6 encourage combining these tests to reduce the number of animals used and to provide a more holistic view of how the device interacts with the body. EBI regularly performs these combined protocols.
When is Chronic Toxicity testing mandatory?
Chronic testing is typically required for permanent implants or devices that have long-term (more than 30 days) contact with internal tissues, the cardiovascular system, or the skeletal system.
Why is the turnaround time for Chronic Toxicity 32 weeks?
The 32-week timeframe includes the 180-day (approx. 26 weeks) in-life phase, followed by weeks of intensive laboratory work: processing dozens of tissue types for histopathology, analyzing clinical pathology data, and drafting the final expert report.
Contact with us
We’re open to collaboration and research partnerships. Fill out the form — our team will respond as soon as possible.
Location:
Europejski Instytut Biomedyczny sp. z o.o.
ul. Bartycka 63A lok. 6, 00-716 Warszawa
Mail:
contact@ebi.bio
Phone:
+48 22 780 06 32
Get in touch
