GLP Research Unit – Implantation – Subcutaneous implantation ISO 10993-6

The implantation test presented in the PN-EN ISO 10996-6 standard is intended to assess medical devices, including the materials included in them, in terms of the potential to cause local effects as a result of placing the tested material in an animal model.

The size of the medical device being tested, the place of subcutaneous implantation and the duration of the experiment determine the choice of animal species. Small laboratory animals such as mice, rats, and domestic animals are usually used.

The tested material is implanted in a place and in an animal species appropriate to assess the biological safety of the medical device. These are usually places along the back line and around the neck.

The biological assessment of a medical device for the implantation of a test material in accordance with ISO 10995 part 6 is based on the local reaction of the animal’s tissue caused by the test material compared to the control material.

The exposure time/implantation period should be determined based on the probable clinical exposure time of the test material (medical device), or the test is continued until stabilization in terms of the biological reaction is achieved, or longer.

The subcutaneous implantation method is appropriate for testing:

• solid, non-absorbable or absorbable/degradable materials;
• non-solid materials (porous, liquids, gels, pastes, solid particles), non-absorbable or absorbable/degradable.

The local effects of the test material are assessed by comparing the tissue reaction induced by the test material with the reaction induced by control materials used in medical devices whose clinical acceptability and biocompatibility characteristics have been established. The aim of the method is to characterize the development of tissue reactions after implantation of a medical device/biomaterial, including the final integration or absorption/degradation of the material.

Particularly in the case of degradable/absorbable materials, the degradation characteristics of the material and the resulting tissue response are determined.

In the case of absorbable materials, the implantation site should be marked in a manner appropriate to identify the site after the exposure time has ended. The use of a neutral, permanent skin marker is only recommended for short-term testing periods. For long-term study periods, a composite marker may be used to identify the implant site with an appropriate non-absorbable negative control (e.g. HDPE, PP suture, gold band, clips). Implantation location markers should be removed prior to histological evaluation.

For non-absorbable materials, short-term reactions should be assessed within 1 week to 4 weeks and long-term reactions beyond 12 weeks.

The local biological response to implanted materials depends both on the properties of these materials and on the response to the surgical procedure itself. Each case of tissue reaction, such as hematoma, swelling or halo, is recorded along with information about the size of the affected area. After implantation, animals are also observed to check whether they have returned to normal eating and drinking habits and to check for any questionable behavior.

Please contact us directly to select the appropriate test method for your medical device.

Our laboratory has a Good Laboratory Practice certificate in the biocompatibility section (scope 9) for the biological assessment of medical devices for in vitro and in vivo tests.