COT statement on a toxicity study in the rat of a hydrogel filler for breast implants - September 2000

The Medical Devices Agency (MDA) had decided to review the safety data on a hydrogel pre-filled breast implant manufactured for Poly Implant Prostheses. The MDA had asked the Committee to consider the report of a study in the rat in which the animals had received subcutaneous injections of the filler material.

1. The Committee was informed that, because of concerns raised by clinicians about the safety of the fillers used in breast implants, the Medical Devices Agency (MDA) had decided to review the safety data on a hydrogel pre-filled breast implant manufactured for Poly Implant Prostheses. The MDA had asked the Committee to consider the report of a study in the rat in which the animals had received subcutaneous injections of the filler material and had then been observed for periods of up to 12 weeks.1

The implant

2. The filler comprises 92% of physiological saline gelled with 8% of a polysaccharide. It is understood that the polysaccharide is based on a cellulose derivative and forms long, linear chains linked by bridges. This gel is contained within a silicone elastomer shell.

The rat toxicity study

3. The Committee was advised that the only toxicity study of any duration was one in which groups of five rats were injected once subcutaneously on either flank with the gel filler material or with saline as a control. Groups of dosed and control rats were killed after 3 days, 4 weeks and 12 weeks. Limited observations were made during life and at necropsy. In the groups of rats that were killed at 4 and 12 weeks no abnormal clinical signs or differences in body weight were reported for either treated or control animals. However, in the treated animals residues of the gel and poorly characterised tissue damage were observed at the injection site. At these times there were histopathological changes in lymph nodes, livers and, to a lesser extent, the kidneys of the treated animals.

4. The Committee considered that, despite having been carried out in 1996, the study was unsatisfactory in its design, execution and reporting. It was the view of the Committee that the changes in the lymph nodes represented a real effect and were consistent with a chronic inflammatory response. These changes require further study, including investigation of lymph nodes close to and distant from the site of injection. In addition, there should be investigation of the lesions reported in the liver and kidney and of the reversibility of any changes observed.

Conclusions

i) The Committee considered that the conclusion of the study, namely that there were no pathological findings in the organs examined, was not supported by the limited experimental results provided, which were considered to be imprecise and inadequate.

ii) The Committee agreed that the findings from the study could not be discounted. The Committee was not able to exclude the possibility that the reported lesions were indicative of a toxic or immunologically-mediated response.

iii) The Committee considered that further testing should be undertaken involving the administration of single doses of the filler gel with longer-term follow-up and with more detailed reporting compatible with current guidelines for chronic toxicity tests.

September 2000
COT Statement 2000/09

Reference

1. Picard F C & Therin M (1996). Subacute toxicity in the rat on a gel (Hydrogel AQT 10-15) used in the filling of mammary prosthesis. Unpublished study No. 121E4041 carried out by BIOMATECH, Chasse sur Rhone, France. Submitted to the Medical Devices Agency by Poly Implant Prosthesis, ZAC les Playes Jean Monnet, 83500 La Seyne sur Mer, France.