Study-Beagle

March 28, 1978

To: JERRY HELMER

CC: D. SANDERS
M. HANSEN

FROM: W. STITH

SUBJECT: BEAGLE IMPLANT STUDIES

I have reviewed the material in the file on the Beagle Implant Studies performed by Industrial Bio-Test or Cape Laboratories. A summary of the studies performed
and also those in-progress is shown in Table 1. The animals implanted, the implant sites, and the type of implant are shown in Figures 1 - 19. No sheets are
available on animals 738H, 722H and 736H. A list of the materials implanted, implant size(where available), and material use is shown in Table 2.

My impression in going through the studies is that the majority of the implant studies concern materials that have, been discontinued, such as MEC 114 and MEC 127. These materials wire used for mammary prosthesis. The gel they contained, I understand, has also been discontinued. Interestingly, tissue inflammation was observed with the MEC 114 prosthesis but not with the
MEC 114 shell material. Some hemorrhage into the surrounding tissues also appeared to be present. No studies were performed to establish whether the
reaction was due to the gel material or the Dacron attachment on the back of the prosthesis intended for tissue in-growth.

Examination of other organs also revealed instances of possible pneumonia of the lung and hyperplasia of lymphoid tissue, in the large intestine. The cause and
significance of these findings were not discussed by the veterinary pathologists. The findings are further complicated by the presence of different materials in the same animal. One wouldn't be able to pin the effect to a specific material or whether the effect might have resulted from a combination or synergistic
effect of both materials.

* I submitted Dacron felt, presently in use as attachment to mammary prosthesis to North American Science Associates. They found the material to be toxic to cells in tissue culture. This may explain the inflammatory response seen in our studies. Smahel 1 examined the histology of 9 capsules around silicone implants from 7 patients. The implants were removed because of breast pain and constrictive fibrosis. He found chronic inflammatory infiltration of qreat1y varying intensity in areas surrounding he Dacron attachment.

Currently there are five animals St. Wedge Creek with MEC implants. These animals (Fig. 15-19) all contain more than one type of implanted material. This will
make interpretation of organ data difficult. Three of the animals (CC-74, 273 and 669M) also contain Plastigel. I met with L. Christensen and S. Aperavich and found that there is no traceability on this material. Both agree that it is probably GE material. As you know we now purchase Plastigel precursor material from Dow Corning.

I discussed our dog studies with R. Wallin, Scientific Director of North American Science Assoc. He was of the opinion that unless we had good material traceability, the study should be discontinued. He also stated that as much information could be gained from 90 day rabbit studies as from long-term dog
studies.

I feel that our present long-term beagle-study (5 animals) should be discontinued without histopathology examinations. My reasons are as follows:

1) No traceability on Plastigel samples in 3 animals. Other material used for implants in the animals has been discontinued.

2) The other 2 animals contain multiple materials—any deleterious effects couldn't be linked to a specific material.

3) The animals presently cost $425 month to maintain.

4) USP XIX calls out rabbits for evaluation of a plastic material in direct contact with living tissue. (Implant Studies)

5) According to R. Wallin, 90 day rabbit studies will give the information we need, in a shorter time and at a lower cost than the long-term beagle studies.

6) The data we have and will obtain from Industrial Bio-Test is questionable as you, the FDA and everyone else knows.

As you know, I have outlined testing procedures that I think should be performed on new materials and also additional lots of a previously tested material. I am
also looking at other implantable devices to see what testing has been performed on their component materials. I suspect that many of these materials will
also require implant studies. I would recommend that long-term dog studies not be performed on these materials and instead use 90 day rabbit implants. I
would also recommend not using different material in the same animal unless we only are interested in the local effect of the materials. In order to perform such a study, it would be necessary to separate imp1ant sites so as to preclude the possibility of cross-reactions occurring.

REFERENCES

Smahel, J., HISTOLOGY OF THE CAPSULES CAUSING
CONSTRICTIVE FIBROSIS
AROUND BREAST IMPLANTS. 8r~.t. Journal of Plastic
Surgery,
30:324-329, 1977.