Biological evaluation of medical devices. Tests for local effects after implantation. Subcutaneous implantation (UNE-EN ISO 10993-06: 2017).
Test with the Certificate of Good Laboratory Practices (GLPs).
The test sample should be implanted in the most suitable tissues according to the intended clinical use of the test material. In IVAMI, we perform subcutaneous implantation tests to evaluate the biological response of the subcutaneous tissue to an implanted material.
The animal species chosen for the test will be New Zealand albino rabbit, of known origin and with a defined microbiological health status. As many animals as necessary will be used to test a total of 10 replicates of the received sample and 10 controls, using at least 3 animals to evaluate the test product and another three for the controls.
The material must be manufactured, processed, contaminants removed and sterilized by the method provided for the final product, confirmed with adequate documentation that will be attached to the material.
For the implants, pieces of the material cut into discs of 10 - 12 mm in diameter and whose thickness is between 0.3 and 1 mm, supplied in this way by the manufacturer/client, will be used. Also, rods and cylinders of diameter 1.5 mm-2.0 mm and length between 5.0 to 10.0 mm can be supplied, with rounded ends. Non-solid samples (including powders) must be supplied in tubes of 1.5 mm diameter and 5.0 mm in length (for absorbable test materials the use of a localization marker is recommended). Other samples, with different anatomically compatible dimensions, are possible when the studies are conducted in conjunction with systemic toxicity studies.
The product sent by the customer will be implanted in subcutaneous tissue along the dorsal midline of the experimental animal.
The observation period after implantation should be determined by the probable clinical exposure time. For non-absorbable materials, short-term responses are typically evaluated with a test observation period of 1 to 4 weeks and long-term responses with test durations greater than 12 weeks. In IVAMI, the observation period after the implantation of permanent implantation devices will be 13 weeks.
For absorbable materials, the duration of the tests will depend on the estimated degradation of the product. Short, medium, or long-term tests should be carried out when there is minimal or no degradation, when degradation is taking place, or when the test material has already been absorbed, respectively.
Along the duration of the study, the test animals will be followed as indicated below:
Daily macroscopic observation of implantation sites.
After humanized euthanasia:
Recovery of the implant and surrounding tissue for histopathological evaluation.
If the gross pathology observed indicates it, extraction of lymph nodes that drain the implant region for histopathological evaluation.
The following histopathological evaluation will be performed:
Extent of fibrosis/fibrous capsule, layer thickness and extent of inflammation.
Cellular degeneration determined by changes in tissue morphology.
The number and distribution of inflammatory cell types, based on distance from the material/tissue interface.
Presence, extent and type of necrosis if observed.
Other tissue alterations such as fragmentation and/or the presence of detritus, the shape and location of the remains of the degraded material.
For absorbable and porous implant materials, the quality and quantity of tissue ingrowth.