Test for Chronic systemic toxicity (ISO 10993-11: 2017) and Tests for local effects after subcutaneous implantation (ISO 10993-06: 2016).
Test with the Certificate of Good Laboratory Practices (GLPs).
Chronic systemic toxicity is defined as adverse effects occurring after the repeated or continuous administration of a test sample for a major part of the life span. Because the inoculation route is subcutaneous implantation, the animal species chosen for the test will be an albino rabbit of the New Zealand breed, of known origin and with a defined microbiological health status. According to the ISO 10993-11 standard, for chronic toxicity the number of animals tested should be based on the minimum required to provide meaningful data, therefore, a consultation with a statistical expert is recommended. We offer the test with 10 animals, but the client must assure that this number is adequate for the test product. The 10 animals (5 males and 5 females) will be used to test a total of 10 replicas of the test sample. In addition, a group of 10 animals (5 males and 5 females) would be used as controls (implanted with the control device).
The material must be manufactured, processed, removed from contaminants and sterilized by the method intended for the final product, confirmed by appropriate documentation that will be attached to the material.
For the implants, pieces of the test material cut into 10-12 mm diameter discs will be used, with a thickness between 0.3 and 1 mm, supplied in this way by the manufacturer or client.
The test pieces sent by the client (test sample and control) will be implanted in subcutaneous tissue and the implantation will be carried out along the dorsal midline of the experimental animal.
The observation period for the experimental animals after implantation will be between 6 months to 12 months.
During the duration of the study, the test animals will be monitored as follows:
- Blood analysis 48 hours before implantation.
- Blood and urine analysis before humane slaughter of the animal.
- Measurement of the body weight of the animals 24 hours before implantation and then every week of observation.
- Macroscopic observation of the implantation sites daily.
- After humane slaughter:
- Recovery of the implant and surrounding tissue for histopathological evaluation.
- Extraction of lymph nodes draining the region histopathological evaluation.
- The following assessment will be performed:
- Extent of fibrosis/fibrous capsule, thickness of the cap and extent of inflammation.
- Cellular degeneration determined by changes in tissue morphology.
- Number and distribution of inflammatory cell types, as a function of distance from the material/tissue interface.
- Presence, extent and type of necrosis.
- Other tissue alterations such as fragmentation and/or presence of debris, shape and location of degraded material remnants.
- Complete macroscopic autopsy.
- Organ removal for weight and histopathological evaluation. The client must select the organs for study.
According to the ISO 10993-11 standard, the following organs should be weighed, with other organs weighed if scientifically appropriate: adrenals, brain, epididymis, heart, kidneys, liver, ovaries, spleen, testes, thymus and uterus.
ISO 10993-11 standard indicates a list for reduced histopathology for testing medical devices with commonly used composition. This list includes the following organs: heart, liver, adrenal glands, kidneys, skin, spleen, muscle, brain, ovaries, lungs and bronchial samples, bone (femur or sternum), bone marrow (from femur, rib or sternum).
Important information:
This information provides a general test, following the ISO 10993-11 standard. However, the test may require modifications depending on the medical device being tested and it is the client's responsibility to ensure that the test conditions comply with what the authorities will require for the registration of their product.