Implant Veterans of Toxic Exposure

Document #451
02/02/87
TESTING
TISSUE REACTION

Rasmussen's monthly report for February, 1987, to Ruhr reporting the deaths of ten more animals due to moribund condition in the Two-Year Gel Implant Study - M8518-0, bringing the total number of deaths to 48. Also, "thirteen animals are presently living out of a total of 21 which are or have exhibited masses associated with the gel implant."
CITE: KMM 315219 - 315221

Document # 452
02/09/87
TESTING
SILICA
TISSUE REACTION

Siddiqui reports to Dow Corning regarding a 1987 study of anal leakage when rats are subjected to polydimethylsiloxane fluids. The test materials are Dow Corning 1500 antifoam, a 50/56 mixture of Dow Corning 200 fluid and Dow Corning 112 compound. The positive control is 50 cs of Dow Corning 200 fluid. Siddiqui observes 1) a definite loss in body weights with all treated animal, 2) mushy. light-green stools in the animals treated with the mixture of Dow Corning 200 fluid and Dow Corning 112 compound at 5 or 8 gl kg/day doses and 3) soft and oily feces in the animals treated with Dow Corning 1500 antifoam at 5 and 8 kg/day doses. The rats showed gastric endemic and slight intestinal irritation. The report concludes that the material containing small amounts of silica in polydimethylsiloxane fluids does not significantly improve the results of anal leakage previously obtained in the laboratory.
CITE: T 34186 - 34323.

Document #453
02/23/87
ACKNOWLEDGEMENT OF NEED FOR TESTING
COHESIVENESS - LIQUID COMPONENT OF GEL
CONCEALING FROM FDA
FRAUD/MISREPRESENTATION
GEL MIGRATION
KNOWLEDGE OF SYSTEMIC DISEASE
MISCELLANEOUS - RECKLESS/CONSCIOUS DISREGARD
SHELL DEGRADATION
TESTING
TISSUE REACTION

Robert LeVier, Dow Corning, memo to Hayes, Rylee, Stark, Thiess, Weyenberg, and Yerrick regarding the "Medtox Project Final Report." Seven numbered copies of the Medtox Report were issued to the seven individuals
listed above. The final report replaces the 12/31/86 interim report. Levier asks each of the recipients to "Please discard the interim report dated December 31, 1986. (KMM 298339).

The purpose of the Medtox project was to formulate a consolidated understanding of all internally funded safety studies of silicone material relevant to the Health Care Business and to relate the findings to current safety issues as presented in the literature, by the physician community and in litigation. LeVier reviewed four sources of information: the Corporate Toxicology File 1949 - present, the DC 360 Fluid NDA 2702 file 1974, the Medical Research Report File 1980 - present, and the Corporate Mainframe Reference List 1957 - present. The report will generate a database for Dow Corning to search and will be available to the Legal Department. The first and earliest report LeVier noted was a 1949 publication. He also located and identified in the appendix 110 reports. The studies through 1963 were primarily related to antifoam compounds and emulsions used in antigas formulations. Thereafter, the studies were conducted to qualify materials. "Studies in the 1980 - 1986 period are primarily directed toward requalification of materials that have been in use for some time."

Levier concludes that the reaction at the implantation site is an acute inflammation progressing to chronic inflammation characteristic of a mild foreign body response and that there is no evidence of systemic toxicity.

LeVier does note, however, that:

Two studies indicate that PDMS injected S.Q. or I.P. in very large quantities (5 to 62 ml/animal) in mice and rats is disseminated broadly and polymer is microscopically visible as deposits in tissue. It is likely that these deposits are the end-stage result of phagocytic transport and aggregation of polymer....

Several teratology studies in rats and rabbits have shown a positive but low incidence of skeletal defects and increased fetal resorptions.

LeVier acknowledges that silicone fluid and silicone elastomers can be found in macrophages and multinucleated giant cells. "The greater incidence of macrophages and giant cells is more characteristic of a chronic inflammatory state than usually seen around elastomer implants in the absence of abrasion particles." He notes that the silicone fluid migrates and is transported to regional lymph nodes. Further, LeVier concludes that:

The implantation site reaction to silicone gel, particularly in the form of a fabricated mammary prosthesis, is similar to that produced by fluid polymer. In the case of free silicone gel the distribution compared to fluid polymer resides in the cohesiveness of the gel.... In the case of free gel, progressive gel subdivision by connective tissue septa is superimposed on encapsulation of the entire gel mass.

The analyses of the internal studies indicates that there are notable deficiencies among the reports. LeVier classifies these as "Nuisance Issues" and "Substantive Issues." The nuisance issues include that the study designs are outdated, the studies are of limited utility, the variety of systemic histopathologic findings is broad, and the majority of the studies were conducted by IBT and FDRL. "Both of these companies are known to have falsified data in the time period relevant to the studies conducted for Dow Corning." He does not think it likely that any of Dow Corning's studies were falsified, but he does not state the basis for this belief.

Regarding the substantive issues, LeVier states:

There are two specific deficiencies of importance that tend to limit the utility of the long-term studies in particular.

1. The histopathology of the reticuleondothelial system (RES) including liver, spleen, lungs, lymph nodes and bone marrow was not examined carefully or systematically in any long-term study. Therefore, little information is available from these studies with regard to migration of implanted materials nor with regard to target tissue effects. Such an examination is rarely part of a formal toxicity study but the absence of such an evaluation is often cited as a criticism.

2. None of the studies incorporate a critical assessment of physiologic effects induced by the local inflammatory reaction. Nor is the nature of the local reaction assessed in detail. Thus, no information is available with regard to effects on the immune system, for example.

In discussing the limitations of the prior studies, LeVier admits that there are no studies in which the inflammatory reactions were described and classified according to "criteria employed by researchers expert in the study of inflammation nor have any studies been designed to detect the range of systemic effects that could attend a chronic inflammatory state.... Presently, there are insufficient data to effectively understand cause and effect relationships or to defend silicones against the broadening claims of HAD stimulation.:

In discussing what corrective measures should be taken. LeVier recommends that Dow Corning should not replicate any of the studies that were flawed and outdated. He states:

Replication of existing studies for the sole purpose of correcting nuisance problems would be very costly and would consume several years before results could be available. Some problems such as too few animal per group and too many implants per animal could be corrected but it is improbable that the spectrum of unrelated pathologic events could be materially influenced. It is such pathologic events that are used to claim systemic toxicity caused by silicone implants. The course of action (corrective measure) that is recommended is to develop sound arguments in support of the validity of existing studies.

(emphasis added). LeVier also discusses the immunopotentiation of silicone and notes that "if immunopotentiation is prolonged in response to PDMS, then the probability may be increased that silicone has an adjuvant like effect of sufficient duration to promote development of auto-antibodies in susceptible individuals."
CITE: KMM 298296 - 298339. NOTE? The interim Medtox report is dated 12/31/86. NOTE: Includes LeVier memo sending attached Medtox report to D. Hayes, R. Rylee, F. Stark, G. Thiess, D. Weyenberg and K. Yerrick.

Document #454
02/24/87
COHESIVENESS - LIQUID COMPONENT OF GEL

Bruce A. Reuter, International Marketing Manager at "Dow Corning Wright, responds to Charles A. Vinnik, M.D.'s letter of 01/16/87 regarding gel biodegradability and problems with gel cohesivity. He states, "Biodegradability implies a change in chemical make-up as opposed to physical change. Using this definition, it can be said, categorically, that silicone does not biodegrade as a result of contact with body tissues. We do know that silicone gel can be physically broken down into smaller particles either mechanically or by manipulation in the presence of water or body fluids.: Thus, "It is the combination of gel in contact with body fluids and manipulation which causes the physical breakdown.

With regard to gel cohesivity, Reuter states that the gel undergoes a physical change when it is in contact with body fluids. It becomes less cohesive. Reuter disagrees with Dr. Vinnik's contention that Dow Corning Wright's "quality assurance testing is more rigorous than the exercises" Vinnik prescribes. "Our quality assurance testing is a single episode under controlled conditions as opposed to a daily manipulation which varies in force from patient to patient.... There is no quantitative clinical data to determine how much concentrated stress an implant can take in a confined space before fatigue occurs, nor are there any currently accepted scientific methodologies to test this phenomenon in situ."

In response to the clinical trials on the Silastic II that Dr. Vinnik participated in, Dow Corning Wright has decided not to computerize and analyze the data. The study is considered closed. Dow Corning Wright is also developing a thick gel high profile teardrop prosthesis but "no formal evaluation is planned."
CITE: M 420161 - 420166.

Document #455
02/24/87
CONCEALING FROM FDA
KNOWLEDGE OF SYSTEMIC DISEASE
FRAID/MISREPRESENTATION

Steinberg, Dow Corning counsel, submits information to the FDA regarding the Two-Year Gel Implant Study of Dow Corning 360 Fluid and the findings of malignant lymphoma.
CITE: KMM 491863 - 491912.

Document #456
03/24/87
ACKNOWLEDGEMENT OF NEED FOR TESTING
KNOWLEDGE OF SYSTEMIC DISEASE

W. Boley, Dow Corning Wright, memo to Brodhagen, Frisch, Jakubczak, and others regarding "Summary of H.E.S. Testing Activities In Support Of Health Care Businesses For February." The first immunotoxicology testing by Dow Corning is scheduled to begin on April 27. 1987 (25 years after Dow Corning first sold breast implants). The protocol was sent to Dow Corning for approval.
CITE: M 170187 - 170191.

Document 457
04/01/87
ACKNOWLEDGEMENT OF NEED FOR TESTING
COHESIVENESS - LIQUID COMPONENT OF GEL
KNOWLEDGE OF GEL BLEED

Dow Corning Quality Assurance Department Report 0058 by Sharon McCoy entitled "Factors Affecting The Integrity And Stability Of Q72159A Mammary Gel And Intermediates." The objectives of the study were to identify causes of gel penetration drift, identify causes of gel depolymerization and determine feasibility of using SiH to vinyl ratios to predict final gel penetration values. (OOT 41655) On the issue of depolymerization of the gel, she states that "Potassium in Ql-0043 appears to cause depolymerization in the finished product Q7-2159A when levels exceed 1.75 ppm, taking test repeatability into account" (Id.)
CITE: Hancock Deposition, Exhibit to Olson Deposition, and Exhibit to Isquith Deposition. OOT 41654 - 41676, Exhibit to Harris County Burda Deposition, Exhibit to Petraitis Deposition, Exhibits 11 and 27A

Document 458
04/10/87
TESTING
FRAUD/MISREPRESENTATION
MISCELLANEOUS - PRODUCT LABELLING

I.G. Hignite, Dow Corning, records the minutes of the "Health Care Businesses Board Meeting Minutes - 04/07 - 08/87" The Board decided to proceed on Talmadge Holmes' proposal to acquire 1,250 case histories from Dr. Ben Gregory. Dow Corning plans to computerize the data and publish a paper on the findings. Also, LeVier presented the results of his Medtox final report which showed that "there can be acute to chronic inflammation and mild foreign bold reaction" from silicone breast implants. He claims there was no indication of systemic reaction. The immunotoxicology testing is now to begin in September 1987. LeVier noted that Dow Corning has "not been able to define how to design experiments that measure antibody formation from silicones." Also, the Health Care Board reported that legal counsel recommended that Dow Corning settle the Stern case because of "incomplete information on our implant package inserts...." Dow Corning recommends a review of all other package inserts to bring them up to date.
CITE: F 817 - 822.

Document #459
04/13/87
ACKNOWLEDGEMENT OF NEED FOR TESTING
KNOWDEDGE OF SYSTEMIC DISEASE

John Ludington, Dow Corning, memo to Gene Jakubczak. Ludington states:

It has recently come to the attention of Executive Management of Dow Corning Corporation that preliminary indications from a current study, indicate adverse effects of Dow Corning medical grade silicone gels placed into the body of highly sensitive test rats. Our scientific assessment is that this does not represent a human health concern....

A committee is formed comprised of Reed, who will be the President and Chairman, Jenkins who will be the legal counsel to the committee, Rylee, and Stark. He directs the committee to "make appropriate recommendation for future action in light of Dow Corning's legal and ethical responsibilities. This investigation is a top priority matter." Ludington cautions persons not to speculate about these matters with anyone else.
CITE: KMM 302536 - 302537, Exhibit to Ludington Deposition, Exhibit to Reed Deposition, Exhibit to Stark Deposition, Exhibit 23 to McKennon Deposition, and Exhibit 26 to Zimmer Deposition.

Document #460 & 461
06/11-12/87
ACKNOWLEDGEMENT OF NEED FOR TESTING
TESTING
TISSUE REACTION

An expert panel was convened at the request of Dow Corning Corporation to review and discuss the chemical and biological data base on silicone gel products along with the relevant medical data. The purposes of the panel were to provide an opinion as to whether any of the information reviewed indicate a significant risk to human health and suggest additional work which could be undertaken to further support the safety of these gel products.

The panel expressed the opinion that the findings of sarcomas at the implant was predictable and consistent with the mechanism of foreign body tumorigenesis. The panel found that the study finding increased malignant lymphoma was flawed in terms of conduct, diagnosis and reporting. "Because of these problems, the panel determined that no definitive conclusions could be reached on the basis of the study. The panel members did, however, recommend that additional safety data in the form of a chronic bioassay in a non-rodent species ... and further studies to elucidate the mechanism of solid state tumorigenesis in rodents should be undertaken." Specifically, the panel recommended that Dow Corning conduct a seven-year dog study. The panel recommended that the tissue be re-examined by another pathologist and that the data from this study be re-evaluated after this work is completed.
CITE: KMM 362273 - 362277 and DCC 267360013 - 267360331 and DCC 267420044- 267420289, Exhibit 8 to Zimmer Deposition (draft). NOTE: Dow Corning never did the seven-year dog study suggested by the panel. DUPLICATE: KMM451887: KMM 366396 - 366712.

Document 462
07/06/87
COHESIVENESS - LIQUID COMPONENT OF GEL
GEL MIGRATION

Dr. Charles Vinnik writes to Robert Rylee, Dow Corning, concerning recurrent problems with gel cohesivity and "runny" gel in Dow Corning implants. Gene Jakubczak promised Dr. Vinnik that Dow Corning would compare gel specifications on implants returned for evaluation. "Sadly, despite the fact that I had sent a number of patients' samples back ... there has never been any description of comparison of the returned gel samples with the original gel standards that were supposedly retained by your company.... The problem either emanates from the top, or that people under you are operating contrary to our explicit agreement...." He continues, "I can only draw the conclusion that there is a deliberate attempt at evasion with respect to the level of cohesivity of the gels used in the original silastic prostheses dating from approximately 1077. I might further add that the cohesivity of the Silastic II prosthesis is not as good as I would like it to be ... compared with one of your competitors.... The safety factor in terms of patients not having problems associated with migratory gel and all of those legal implications to you from that problem is enormous."
CITE: M 490090 - 490091.

Document #463
07/06/87
ACKNOWLEDGEMENT OF NEED FOR TESTING
MISCELLANEOUS - ORGANIZATIONAL SURVEY
TESTING

Weyenberg and Gehring letter to Shilling regarding joint research agreement for identification of agricultural chemicals - modification of item 10 (changing agreement from 3 years to 4) and amendment specifying subsidiaries of the parties may receive info exchanged under their agreement and may be employed to conduct work on the program.
CITE: DCC 2001190 - 2001191.

Document #464
08/05/87
TESTING
KNOWLEDGE OF SYSTEMIC DISEASE

Dow Corning summarizes data concerning a Two Year Gel Implant Study in rats conducted by Industrial Bio-Test Laboratories using the old gel - MDF 0193, and responsive gel - Q7-2159A. Dow Corning claims there were deficiencies in the original report such as improper tabulation and evaluation of tumor findings including malignant lymphomas. Hughes Research and Development was asked to review the data and tissue samples and, in their second report, found a treatment-related increase in the incidence of malignant lymphoma. Dow Corning refuted this conclusion claiming that the increase in lymphoma was "stress related viral induced but no basis to substantiate our opinion." Dow Corning subsequently conducted an internal study. An independent panel of experts convened by Dow Corning reviews all data and finds that the implant site sarcomas identified in the studies are predictable due to "solid state" carcinogenesis in rats, a phenomena which allegedly poses no significant risk to human health.
CITE: KMM 491869 - 491881.

Document #465
08/13/87
SHELL STRENGTH - THICKNESS
RUPTURE - CLOSED CAPSULOTOMY
ACKNOWLEDGEMENT OF NEED FOR TESTING
KNOWLEDGE OF SYSTEMIC DISEASE
GEL MIGRATION
TISSUE REACTION

Jakubczak, Dow Corning, sends Dr. Muller a lengthy response to his questions about implant rupture. He states that a hypothetical cause of rupture which may be possible but about which he does not have direct knowledge of is "Excessive force created when closed capsulotomy is being performed." Also, in the event of an implant rupture, gel can migrate and complications include "enlarged lymph nodes, scar formation, inflammation, granulomatous foreign body reaction, presence of foamy histiocytes, silicone mastopathy, nodule formation, or other difficulties.... The long term physiological effects of uncontained gel are not completely known."

Jakubczak states that Dow Corning has been tracking the rate of ruptures since the gel-filled implants were introduced to the market. "The rate (Of rupture) is less than ).1% for gel filled product. The gel-saline product is slightly less than that for gel product. The SILASTIC II mammary implant, to the best of our knowledge, is in the ballpark or slightly less. For the specific time period of the last 1970's our data indicates that the rate of rupture was the same."
CITE: M 460204. DUPLICATE: KKH 75863 - 75871. NOTE: Jakubczak did have direct knowledge of ruptures occurring with closed capsulotomies. Also, Dow Corning did not track rupture rates like he represents in this letter.

Document #466
09/21/87
ACKNOWLEDGEMENT OF NEED FOR TESTING
TESTING
TISSUE REACTION

Talmadge Holmes, epidemiologist at Dow Corning, memo to Dillon, Hobbs, Jenkins, LeVier, Ruhr, Rylee, Stark, Steinberg and Zimmer regarding an epidemiological study on the relationship of cancer and silicone breast implants. Holmes notes that the Deapen study "was limited in that there were only 6.2 average years of follow-up per person and no data were collected regarding known breast cancer risk factors." A proposal for additional epidemiologic investigation into the relationship between silicone gel used in mammary implants and cancer is attached.
CITE: KMM 387394 - 387397, Exhibit 29 to Zimmer Deposition.

Document #467
09/24/87
ACKNOWLEDGEMENT OF NEED FOR TESTING

Eldon Frisch, Dow Corning, memo to Hayes, Dillon, LeVier, and Thiess regarding a proposal from Nir Kossovsky to study noninfectious inflammatory reactions in human tissues collected at autopsy from patients with all types of implants. Frisch notes that Kossovsky has testified as an expert for plaintiffs in silicone implant litigation and states, "In my opinion, the study he wishes to conduct would be highly worthwhile from a scientific standpoint, and may confirm that there are problems with all types of implant materials, but I am uncertain of its value to Dow Corning and thus have had a problem identifying just why Dow Corning should fund this work."
CITE: DCC 240001004, Exhibit to Dillon Deposition, Exhibit to Frisch Deposition, Exhibit to LeVier Deposition, and Exhibit 5 to Harris County Burchiel Deposition.

Document #468
11/03/87
KNOWLEDGE OF LIQUID SILICONE DANGERS
GEL MIGRATION
KNOWLEDGE OF SYSTEMIC DISEASE

Dan Hayes, Dow Corning, memo to Frisch, Hobbs, LeVier, Steinberg, the DCW Business Board, Rylee, and Stark regarding the Dow Corning Wright Keratosis Program. Hayes asks, "What is the best approach to deal with silicone migration in this application? How do we approach the immunology issues that have been raised in literature in recent years?"
CITE: DCC 251000386 - 251000387

Document #469
11/17/87
TISSUE REACTION
KNOWLEDGE OF SYSTEMIC DISEASE

Complaint Report MW 2030 submitted to Dow Corning regarding a Silastic implant. The patient developed "bronchospastic asthma of allergic nature" related to the silicone. The patient has leakage from her nipples which is suspected to contain silicone. Dow Corning agrees to devise a test to detect whether the discharge was silicone. CITE: KKH 72651

Document #470
12/15/87
DOCUMENT DESTRUCTION
FRAUD/MISREPRESENTATION

Note from Winton, Dow Corning, regarding conversation he had with Don Linkert about the falsification of cure oven charts. He quotes Linkert as saying that they had gotten low on inventory and there was pressure to get product out the door. Winton claims that Linkert told him that there was some discussion about the problem and the QA department's hassling over atypical situations such as oven cycles. Winton quotes Linkert as saying that he was aware that a second chart could be run with nothing in the oven and substitute that chart for the original. Winton claims that Linkert responded to this suggestion by saying: "do what you have to, but I don't want to know about it." Mike Mitchell was fired earlier in the year for falsification of documents.
CITE: DCC 80062087 - 80062088. DUPLICATE: DCC 17015132

Document #471
12/31/87
ACKNOWLEDGEMENT OF NEED FOR TESTING
KNOWLEDGE OF SYSTEMIC DESEASE

Eldon Frisch, Dow Corning, outlines the "Keratosis Program" and the biological tests needed. Biological assay data is needed for "defense against litigation.... Because of the findings from silicone gel implant studies, both internal and regulatory requirements for assurance of the biological safety of subdermal silicone fluid will be particularly critical and demanding."

Frisch states that the "must time-consuming and expensive study will be an assay of carcinogenic potential" as will reproductive and developmental toxicity assays. "Prior studies will not suffice" since they were inconclusive. Both studies showed increases in skeletal deformities and increased in utero mortality rates in animal reproduction studies. Also, the Dow Corning internal study, Frisch claims, is "distrusted scientifically and was of questionable statistical design."
CITE: KMM 407480 - 407482.

Document #472
00/00/88
SHELL STRENGTH - THICKNESS
MISCELLANEOUS - PRODUCT LABELLING

Dow Corning Territory Strategy Sheet by Bill Fargie states that, "I need to increase anxiety level of surgeons re: litigation and broken shells. Most of board certified (surgeons) in my territory are beginning to see alarming number of implants with 'loss of shell integrity'...I need label revision on all Plastic packaging - everything confusing and difficult." CITE: KAA 64021.

Document #473
01/00/88
KNOWLEDGE OF SYSTEMIC DISEASE
FRAUD/MISREPRESENTATION

Hayes, Dow Corning, writes Dear Doctor letter regarding immunological reactions to silicone. He encloses a position paper. The position paper criticizes the research done by the Japanese by claiming that fluids used were often adulterated and by claiming that the adjuvant concept is broadly misunderstood. The paper gives a brief description of the research that has been done on the problem and then states:

Unfortunately, all animal studies reported to date have been founded upon incomplete experimental designs, and interpretations and speculations that extend well beyond the support that can be provided by the data.
CITE: KMM 122710 - 122712. DUPLICATE: MD 145633 - 145635.

Document #474
01/22/88
KNOWLEDGE OF LIQUID SILICONE DANGERS
ACKNOWLEDGEMENT OF NEED FOR TESTING
KNOWLEDGE OF SYSTEMIC DISEASE

Frisch, Hobbs, LeVier, and Steinberg, Dow Corning, author a report "keratosis Program Team Report." One of the issues this team has identified is to negotiate an IDE program with the FDA that would allow Dow Corning to do only short-term evaluations of silicone fluid injections for keratosis" without the requirement for extensive clinical and laboratory studies." The silicone to be injected is Dow Corning 360 Fluid. The team assumes that, "Prior studies sponsored by Dow Corning (carcinogenic, reproductive and developmental) will not suffice. The protocols and designs of prior studies were not adequate by today's standards, and in some studies the findings left unanswered questions."

The team notes that bioassays which must be addressed include carcinogenic, pharmacokinetic and immunologic. "Immunologic studies are not on the FDA general list and are not included in projected costs, but because of the current flurry of publications alleging immunogenic reactions to silicones FDA may want these studies done. Internally, evaluation of the immunogenic potential of silicone fluids is currently being planned, and it is believed these data would apply to 360 fluid even if the fluid involved in the study were 200 fluid."

Furthermore, the team states:

FDA will probably require adequate data to assure safety prior to allowing the clinical investigation to proceed. FDA's concerns will most likely center on carcinogenicity and reproductive/developmental toxicity issues. Dow Corning currently has neither human nor animal data to address these issues in a statistically valid, scientific fashion. The reproductive/developmental toxicity issue could perhaps be temporarily waived by not including women who may have children, but this still leaves the carcinogenicity issue unresolved.

CITE: KMM 407502 - 407540.

Document #475
02/01/88
ACKNOWLEDGEMENT OF NEED FOR TESTING
RUPTURE
SHELL STRENGTH - THICKNESS

Letter from Franklin Wilder, The Hartford, to Greg Thiess, Senior Managing Attorney at Dow Corning, about a woman who struck her breast when slipping at a grocery store, allegedly causing one or both implants to rupture. Wilder questions, "Is there a standard for rupture force? The reason for this question is that it is foreseeable that a woman may hit her breast, or suffer some trauma and this force imparted to the implant. (sic) Has Dow Corning performed any studies along these lines?"
CITE: KKM 42522. Note: See 02/04/88 response

Document #476
02/04/88
DOCUMENT DESTRUCTION
FRAUD/MISREPRESENTATION
CONCEALING FROM FDA

Harvey Steinberg, in-house legal counsel for Dow Corning, memo to the File regarding the "GMP Records Review." This document is the basis for Griffin Bell's finding in his October 12, 1992 report that Dow Corning falsified oven temperature charts, and has a typed note at the top: "Attachment I, APPROVED FOR PUBLIC DISSEMINATION ON OCTOBER 12, 1992." Steinberg writes that"

In late Fall, 1987, Sandy Brondstetter, a sister of a mammary area employee, advised her supervisor,

Ken Montague, that dummy over (sic) cure charts were being made in the mammary area. Brondstetter and Montague investigated and found, under a desk blotter in the mammary area, an actual chart evidencing an interim oven shutdown for a lot where a chart for a cycle not exhibiting any such shutdown had been submitted with the lot history record....On December 1, at a meeting with T. Bartolo, Boone and Winter were advised that Bartolo were completely unaware of any problems with the cure ovens that would lead to anybody even having a need to be concerned about charts, at least since the new controllers and recorders were installed in late 1986 or early 1987. He admitted that with the old equipment there were a number of problems with the recorders with the result that a substantial number of problems with the recorders with the result that a substantial number of the curing charts evidenced atypical curing cycles and required management review and clearance. Bartolo admitted that he had personally prepared mocked-up charts to submit in place of the actual charts where, based on his technical knowledge of the limits of the cure cycle, he could conclude that the product had actually been cured a fully sufficient amount of time even if outside of the SOP/specs for the product. His knowledge of cure cycle was based upon his co-authoring the TS&D reports documenting that intermediate interruptions do not interfere with the proper cure of the silicone materials where the total cycle time, at the specified cycle temperature, is achieved. He repeated that, to the best of his knowledge, this practice stopped with the installation of the new equipment.

*** The investigation reasonably established that the cure ovens would kick off in the middle of a cycle an average of about once a week (four times a month) whereas an actual review of the mammary charts showed only 3 out of 104 lots as anything other than a perfect. non-interrupted cycle. Of those 3, none represented a substantial intermittent downtime (e.g. overnight) as did the chart discovered hiding under the desk blotter. A subsequent review of an additional 84 mammary chart turned up only 2 less than perfect samples. In contrast, a review of cured non-mammary silicones showed about 20% of cure runs evidencing over shutdowns, a number consistent with the once-a-week expectation.

The memo also states that Les Schnoll reviewed the lot history records for 1985-1987 and that all lots passed the test evidencing proper gel cure. Schnoll also reviewed the complaint trends and found no unusual events or activities. " Based on the above, it was concluded that all product fully met quality standards and the issue was merely a personnel and documentation concern." Dow Corning suspended for 30 days all implicated individuals and supervisors and gave them stern warnings and lectures on the importance of documentation.
CITE: DCC 105000001 - 105000003.

Document #477
02/04/88
ACKNOWLEDGEMENT OF NEED FOR TESTING
RUPTURE
SHELL STRENGTH - THICKNESS

Greg Thiess, Senior Managing Attorney at Dow Corning, Letter to Frank Wilder, The Hartford, about a breast implant case filed against Dow Corning. Thiess states, "With respect to your question concerning any Dow Corning studies on the force that a mammary implant could withstand once placed inside of the female breast, Dow Corning has done no such studies."
CITE: KMM 42521. Note: See 02/01/88 entry.

Document #478
03/25/88
ACKNOWLEDGEMENT OF NEED FOR TESTING
KNOWLEDGE OF SYSTEMIC DISEASE
TESTING

Board of Directors' meeting showing a report that early test results show that D4 has a toxic effect on daphnia in low concentrations and that further testing is planned.
CITE: DCC 101003623 - 101003626, Exhibit 10 to McKennon Deposition, and Exhibit to Weyenberg Deposition.

Document #479
05/02/88
MISCELLANEOUS - ORGANIZATIONAL SURVEY

"Dow Corning Organizational Survey." "Our manufacturing technology lags 10 years behind state-of-the-art with regard to control and automation. This is especially apparent if you compare the Midland plant (oldest DC plant) with some of the European plants." With regard to Dow Corning's commitment to quality, the comment is made that, "Managers say 'improve quality,' but don't show any interest. They need to 'walk the talk.;" Also, "We should emphasize permanent fixes rather than temporary ones ... usually the emphasis is to do things as quickly as possible, especially when it comes to changing over the use of equipment."

A comment from Production and Manufacturing was, "Good quality programs, but NO follow-up. We've made the same suggestions for fixing problems for the past two years and we see nothing being done to fix the problem.... Dow Corning does not accept the fact that quality costs money...." A criticism voiced is the "over-emphasis on profitability," the constant emphasis on sale/profits/results," the pressure for quantity over quality, and an emphasis on "political savvy" instead of qualifications to get ahead.

Also, employees complain about "Ineffective decision-making process: bureaucratic, with blurred responsibilities, CYA ('cover your ass') effect. Politics, game-playing, 'good old boy' network."

"SOPs ... are outdated, never been written or written by people who do not do the work. Lack of quality standards for products, which results in different interpretation of what is a good product and what isn't. Often engineering and lab do not agree so it is left up to the operator to take responsibility and make a judgment call about continuing to run the line."

On the topic of Dow Corning's reactive, short term focus, the RDE&S Professionals write, "We have too much short-term thinking and fire-fighting, especially from TS&D and marketing. This detracts from long-term, fundamental research."
CITE: KMM 247952 - 247965.

Document #480
05/11/88
TESTING DOCUMENT DESTRUCTION
FRAUD/MISREPRESENTATION

Eldon Frisch, Dow Corning, memo to Bauer regarding "Animal Implant Reactions To Breast Prostheses." He encloses the 11/29/68 study in dogs conducted by Food and Drug Research Laboratories which he has redacted
Frisch states:

A large number of materials were tested in this single study. Thus, when information pertinent to all materials and all animals is considered the report is rather confusing, difficult to interpret, and can easily be misrepresented to a jury as happened in the Stern case. Accordingly, all data not pertinent to the four dogs who received SILASTIC 372 elastomer (the envelope material) and the miniature breast implants and the control animals have been removed. Data were deleted by covering the copy with paper or tape, and nothing has been added.

CITE: KMM 200817 - 200862.

Document #481
05/23/88
TESTING
TISSUE REACTION

PATHCO Inc. reports to Dow Corning on a "Two-Year Gel Implant Study (B7811) In Sprague Dawley Rats." Gels MDL 0193 and Q7-2159A were implanted subcutaneously in rats at Industrial Bio-Test Laboratories.

Microslides were prepared by Hughes Research and Development. The study was evaluated histopathologically by Hughes R&D. At the request of Mark Zimmer, Dow Corning, PATHCO Conducted a complete wet tissue audit and histopathologic evaluation of the study.

Evidence of toxicity/carcinogenicity for all four silicone gels tested was restricted to the implant site. All four gels were associated with the presence of mesenchymal neoplasms in at least on sex. Gel 1208 was associated with neoplasms in both sexes, Gel 1209 with neoplasms in males only and Gels 1210 and 1211 with neoplasm in females only. Dysplasia of the capsule of the implant, and apparent preneoplastic lesion, was seen with all four gels in females and with Gel 1208, 1209, and 1210 in males. Other lesions associated with all four gels were fibrosis of the capsule, the presence of extracapsular gel, and inflammatory changes both within the capsule and in the immediate extracapsular tissues.
CITE: R 14267 - 144314.

Document #482
07/25/88
ACKNOWLEDGEMENT OF NEED FOR TESTING
MISCELLANEOUS - ORGANIZATIONAL SURVEY
TESTING

Letter agreement between Dow Corning (signed by Weyenberg) and Dow Chemical (signed by Perry Gehring) regarding the 08/01/84 Joint Research Agreement for Identification of Agricultural Chemicals. Dow Corning proposes this agreement be extended and additional 3 years.
CITE: DCC 2001192.

Document #483
07/25/88
GEL MIGRATION
TESTING
TISSUE REACTION

FDA: An internal FDA review of the epidemiological study involving 3,000 women in California by Dr. Dennis Deapen and his colleagues, Pike, Casagrande, and Brody, to determine if breast implants increase the chance of developing cancer, concludes there were "numerous sources of errors, biases and methodological limitations." Also:

"this study has not contributed greatly to our understanding of the relationship between breast implants and the risk of breast cancer. Furthermore, it is known that silicone can migrate to other body sites away from the site of implantation. Even with all the biases inherent in the study design, the authors did note a higher number of observed cases of cancers at other sites than expected (24 observed versus 15.8 expected). Based on these results and the fact that silicone can migrate to other sites, the authors should have addressed this issue by including cancers at other sites, instead of limiting their study to only breast cancer.
CITE: M 780066 - 780069; Attachment 3 to Staff Report prepared by the Human Resources and Intergovernmental Relations Subcommittee on Government Operations, December, 1992, p. 9. NOTE: See 05/10/89 ENTRY. See 00/00/00 (M 780074 - 780078), 00/00/87 (M780070 - 780073), 08/17/89 (M 780079 - 780090) and 08/03/88 (M 780056 -780063 entries; possible attachments to this document. DUPLICATE: M790025 - 790029

Document #484
08/09/88
TESTING
CONCEALING FROM FDA
KNOWLDEDGE OF SYSTEMIC DISEASE

FDA: M. Stratmeyer, Acting Chief, Health Sciences Branch of FDA to Director, office of Science and Technology, memo with attached report regarding analysis of Dow Corning data on carcinogenicity of silicone gels. "As you will see, the conclusion of this report is that silicone can cause cancer in rats; there is no direct proof that silicone causes cancers in humans; however, there is considerable reason to suspect that silicone can do so." The FDA Reviewer finds that patients were studied for an average of 6.2 years which is "probably too short to detect breast cancer... considering that the latency period for foreign body carcinogenesis in humans appears to be in the range of 20-30 years."
CITE" M 780055. DUPLICATE: FDA 29449 - 29457.

Document #485
09/23/88
TESTING
KNOWLEDGE OF SYSTEMIC DISEASE
TISSUE REACTION

Dr. Selwyn, Statistics Unlimited, Inc., prepares a "Statistical Analysis for Two-Year Gel-Implant Study of Q7-2159A and MDF-0193 in Sprague Dawley Rats (M8518-0)" for Dow Corning which concludes that "Carcinogenesis is noted in mammary gels in significant amounts." (KMM 388066 - 388150: KMM 2726331 - 272637). Histopathological analysis demonstrated "increased incidences of fibrosarcomas at the implant site which were highly significant for both the Q7-2159A group and the MDF-0193 group, and in both sexes." Incidences of non-neoplastic findings were statistically greater in the Q7-2159A group males than in the control group for the following: "chronic capsular inflammation, implant site dysplasia, fibrous capsule at the implant site, implant site necrosis, extracapsular gel, acute and chronic pyelitis, necrosis in the liver, seminal vesicle secretion (reduced or absent), stomach necrosis, and thymic region hemorrhage."
CITE: KMM 388067 - 388150. DUPLICATE: KMM 272631 - 272637.

Document #486
10/21/88
TESTING
TISSUE REACTION

Dow Corning Report 153 concerning "A Two Year Gel Implant Study Of Dow Corning Q7-2159A and Dow Corning MDF-0193 In Rats." "Implantation site-associated mesenchymal tumors (i.e., sarcomas) were seen in both silicone gel treatment groups at an incidence of 23-24%. The sarcomas were associated with the connective tissue capsule of the implanted materials and the majority were fibrosarcomas." The study also found "depressed" survival rated among male rats implanted with Q7-2159A and those implanted with MDF-0193. "The biologic relevance of the observation is unknown." Dow Corning claims the sarcomas are explained by the "Oppenheimer effect" - solid state carcinogenesis.
CITE: P 17215 - 17390. NOTE: See 03/00/88 and 08/15/88 entries. Silicone gel does not have the same smooth characteristics as the implants used in the tests which gave rise to the "Oppenheimer effect" theory. DUPLICATE: KKP 136919 - 13626; T 15805 - 15926.

Document #487
11/28/88
ACKNOWLEDGEMENT OF NEED FOR TESTING
MISCELLANEOUS - COMPLICATIONS
SHELL DETERIORATION
SHELL STRENGTH - THICKNESS
TESTING
TISSUE REACTION

LeVier, Dow Corning, memo to Hayes, Rylee, Rusk and Stark regarding gel tox studies. LeVier states that the following actions should be taken:

Large volume studies designed to evaluate a possible chemical tumorigenesis effect but solid state tumore will not necessarily be seen in this study because of the large volumes doses used. Envelope studies designed to obtain 2-year implantation data in the rat on both components of the Silastic II shell.

Threshold determination and material comparison studies designed to estimate the gel volume/surface area threshold for initiation of the solid state effect of non- silicone materials under state of the art experimental conditions.

LeVier also gives dosage parameters for rats and mice.
CITE: DCC 267420828 - 267420829.

Document #488
12/14/88
TESTING
TISSUE REACTION
KNOWLEDGE OF SYSTEMIC DISEASE
ACKNOWLEDGEMENT OF NEED FOR TESTING
SILICA

John Yan, Mentor, reports on his trip to Dow Corning. He notes that Dow Corning uses the Statistical Process Control Method to assure product reliance. Mark Zimmer, Dow Corning's veterinarian, presents Dow Corning's

internal study on the two-year rat study. (No reference is made to IBT's or Hughes Research findings nor to other "expert" panel and their recommendations.) "Dow Corning found the test animals to develop dysplasia, chondrosarcoma, fibrosarcoma, and sarcoma.... (T)hey found a 52% incidence of site related tumor formation with the rats and 24% incidence with the female rats." Yan notes that Dow Corning purchases all of its fumed silica from Cab-o-Sil.

Yan also notes that, "At present, teratogenicity, immunological, and pharmacokinetic studies have not been initiated on the gel." (emphasis added). Dow Corning did not share with Mentor the Master File for the Gel.
CITE: MMD 167731 - 167733.

Document #489
01/06/89
MISCELLANEOUS - SALES

Weigel and Thiess, Dow Corning, author "Facts You Should Know About Product Liability And Dow Corning Corporation." The document states:

OVERRIDING IMPACT: PRODUCT LIABILITY IS A COST OF QUALITY WHICH HAS A SIGNIFICANT EFFECT ON THE COMPANY'S PROFITABILITY.

PRODUCT LIABILITY COSTS ARE INCREASING...AND WE HAVE INDICATIONS THAT OUR LIABILITY COSTS ARE HIGHER THAN OTHER COMPANIES IN SIMILAR BUSINESSES.

THE PRODUCT LIABILITY TREND IS DIRECTLY CONTRARY TO DOW CORNING'S EXPERIENCE WITH WORKERS COMPENSATION AND PROPERTY INSURANCE COSTS WHERE OUR STRONG PREVENTION PROGRAMS HAVE LED TO COSTS WELL BELOW INDUSTRY AVERAGES.

SINCE 1978, DOW CORNING'S GLOBAL SALES HAVE INCREASED 174%; PROFITS HAVE INCREASED 141% AND PRODUCT LIABILITY PREMIUMS INCREASED 571%. IN THE U.S. AREA IN 1988 IT TOOK $57M IN SALES AT CURRENT ROS TO PAY ITS SHARE OF THE PREMIUM.

IN 1978, TOTAL PRODUCT LIABILITY PREMIUMS PAID GLOBALLY BY DOW CORNING WERE $1.4M (40% OF THE TOTAL INSURANCE PREMIUMS PAID). PRODUCT LIABILITY PREMIUMS IN 1987 WERE $8.0M, WHICH REPRESENTS 59% OF THE TOTAL PREMIUM....

SINCE 1978, INTERPRETATION OF THE U.S. STANDARD OF STRICT LIABILITY HAS BECOME INCREASINGLY LIBERAL; THUS, PUNITIVE DAMAGE AWARDS HAVE RAPIDLY ESCALATED. IN RECENT YEARS JURIES HAVE INCREASINGLY FOUND ALMOST ANY FAILURE IN A PRODUCT TO CONSTITUTE A DEFECT FOR WHICH DAMAGES CAN BE AWARDED. FAILURE TO WARN HAS BECOME A MAJOR SOURCE OF LIABILITY FOR ALL BUSINESSES.

CITE: KKA 41392 - 41393.

Document #490
03/01/89
TESTING
TISSUE REACTION
DNOWLEDGE OF SYSTEMIC DISEASE

Siddiqui, Kolesar, Zimmer, and Hobbs, Dow Corning, report on "A 90-Day Sub-Chronic Inhalation Toxicity Study Of Octamethylcyclotetrasiloxane (D4) In The Rat." Exposure resulted in slight growth retardation and lower food consumption in females. There was also an increase in liver weights that was statistically significant, leading the authors to conclude that "these data indicate that D4 has an effect on the liver."
CITE: T 40150 - 40276, Exhibit 34 to Zimmer Deposition. DUPLICATE: KKP 15029 - 12155.

Document #491
03/27/89
TESTING

Eldon Frisch, Dow Corning, responds to the request by Emanuel Horowitz of the Johns Hopkins University for industry technical data and standards on medical grade, implantable silicone.

There is no general agreement on the standards for implant grades of silicone elastomers, nor for other applications. Unfortunately, other than allowing everyone to say a standard has been written,

ASTM F604 "Silicone Elastomers Used in Medical Applications" is hardly worth the paper it is printed on. I would like to see it revised, and believe I improved the language of Section 1.4 on biocompatibility when it was last reviewed, but I also know that attempting to make the major revision needed would create a lot of controversy, many negatives, and approval would be difficult.

CITE: DCC 17043724 - 17043727

Document #492
04/17/89
ACKNOWLEDGEMENT OF NEED FOR TESTINGMISCELLANEOUS COMPLICATIONS
TESTING
TISSUE REACTION

Dow Corning Report 82 by H.M. Mehendale entitled "Evaluation of the liver Microsomal Enzyme Induction Potential of D-5." In the University of Mississippi Medical Center study, sponsored by Dow Corning, D5 was administered orally to 24 female rats. "D5 was found to induce hepatomegaly with recovery after cessation of dosing. The enlargement appeared to be due to a net enlargement in liver mass. D5 was found to be an inducer of drug metabolizing microsomal enzymes and to resemble phenobarbital in this regard. However, D5 differed from phenobarbital in that it decreased the P-450 hemoprotein content of the microsomes."

CITE: P 15182, Exhibit to Isquith Deposition. DUPLICATE: F 433 - 460.

Document #493
05/22/89
SILICA
KNOWLEDGE OF SYSTEMIC DISEASE
MISCELLANEOUS - RECKLESS/CONSCIOUS DISREGARD

LeVier, Dow Corning, memo to Birdsall, Steinberg and Groh regarding "Risk Assessment: Carcinogenic Potential Of Silicone RTV Elastomers And Foams Containing Celite Super Floss Or Celite 315 Fillers." Attached is the first draft of a risk assessment overview necessitated by the recent discovery that the supplier of silica had been using cristobalite and other crystalline silicas in materials that comprise the elastomer. LeVier states:

"The majority of health care elastomer products employ amorphous silica as the reinforcing filler. These fumed amorphous fillers have been shown by X-ray defraction analysis to contain no crystalline fraction. However, RTV's in the form of elastomers and foams are based on older tin catalyzed formulations that use Manville Celite Super Floss (CAN#: 68855-54-9) or Cilite 315 (CAN#:61780-53/2) as the reinforcing filler (MSDS's attached). These silicas are generically classified as flux calcinated diatomaceous earth. It has recently been learned from the silica manufacturer that Celite Super Floss contains up to 63% cristobalite and Celite 315 contains up to 23% cristobalite. Cristobalite and other crystalline silicas have been classified by the International Agency for Research on Cancer (IARC) as probably carcinogenic for humans." (emphasis added)."

The products affected by this discovery include 382 Medical Grade Elastomer which was discontinued in 1987:
"for economic reasons related to additional safety testing required to investigate the availability and effects of stannous octoate catalyst degradation products (the subject of a 1987 Risk Assessment).... This product was sold to many other manufacturers and individual physicians.... Dow Corning has also recently licensed the 382 technology to the World Health Organization (WHO) for the purpose of manufacturing and selling a contraceptive vaginal ring. Dow Corning's supply position in the later application has not yet been fully defined. The cristobalite component in these materials ranges from about 10 weight percent to 30 weight percent. The highest concentration of crystalline silica occurs in 382 Medical Grade Elastomer."

LeVier reviews the Dow Corning data on stannous octoate RTV formulations and concludes that "there are no long-term animal implantation data available." The human data from inhalation studies of silica show that "crystalline silica can increase the incidence of lung cancer.... There is sufficient evidence for carcinogenicity of crystalline silica to experimental animals. There is limited evidence for the carcinogenicity of crystalline silica to humans." LeViers risk assessment conclusions are that:

1) Unmodified crystalline silicas including cristobalite-containing silicas are probably carcinogenic for humans via inhalation exposure. The probability that crystalline silicas are carcinogenic for humans via parenteral exposure is less certain but existing animal data indicates that such silicas administered parenterally may be carcinogenic for humans....

4) The effect of in situ plasticizer treatment of Celite silicas on their possible carcinogenicity is unknown except on a theoretical basis. Theoretical considerations lead to the prediction that treated crystalline silicas could be less carcinogenic than unmodified crystalline silicas....

6) "An (sic) life-time rat study of the potential carcinogenicity of treated Celite silicas cannot provide unequivocal proof that such silicas cannot be carcinogenic for humans.
CITE: KKA 1601 - 1608

Document #494
09/08/89
CONCEALING FROM FDA
FRAUD/MISREPRESENTATION
MISCELLANEOUS - RECKLESS/CONSCIOUS DISREGARD

Patricia Lang, a consulting toxicologist, writes to Birdsall, Dow Corning, with copies to Stark, Ovsenik, Frith and Benson enclosing her assessment of Dow Corning's toxicology laboratory and its efforts to comply with Good Laboratory Practices (GLP). Lang states:

"In the last two weeks it has become apparent that though some actions are being implemented to bring HES into compliance, the general feeling within the lab is one of chaos. This can be explained, at least in part, by the fact that there is no management with a full understanding of laboratory function to give direction, and get things implemented. Until now, the three consultants you hired, Charles Frith, Barry Benson and myself, have been trying to take the place of management, with very limited success. The only real progress to date has been in educating some of the personnel in general theory behind Good Laboratory Practice regulations. This does not mean that these people are trained, just educated to some degree.... With the pressures put on the already-too-few people to generate SOP's in the past two weeks (especially the ones for Zybion), I was hearing many comments indicating that these documents will be generated haphazardly, without respect to whether they are accurate or not. Because the department has so much breadth and so little depth, there are not natural double-check systems to assure that either bad science or poorly thought out procedures (let alone poorly written sets of instructions) do not get put into place.... Since there is so much work to be done to bring the lab into compliance, any SOP's which get approved in the new system, will have to be followed for a long time before anyone has time to rewrite them. They should be correct and complete the first time." (DCC 80112044)

Under the "Personnel" section, Lang notes that:

"The consultants you hired were TRYING to take the place of a manager of toxicology. Because they were not part of the group, and only had the ear of Brian Hobbs (who apparently was given the authority to make decisions which should not have been his to make), they were not able to do the job that is needed to be done. As stated several months ago, IT IS ESSENTIAL THAT A GOOD MANAGER OF TOXICOLOGY BE HIRED IMMEDIATELY. The Dow Corning management style is not conducive to running even an adequate toxicology laboratory." (DCC 80112045) She goes on to note that Dow Corning's toxicology department has serious problems working its Xybion computer system, that it hasn't been maintained and that inexperienced persons are operating it. (Id.) Further, she notes many problems with formulation of policies on scientific issues:

"At the present time, the WRONG people are making decisions (in some cases the WRONG decisions) which impact upon the science being performed. The policies which I am addressing include, BUT ARE NOT LIMITED TO, use of Room Log Books for entry of study information, secondary review of raw data or calculations, assurance of room conditions (light cycle, temperature and humidity), health check by veterinarian prior to study assignment, proper anesthetization procedures for animals, training procedures for various tasks (as necropsy, weighing organs, ect.), supervision of weekend activity, and authority of study directors to assure proper study conduct. This list is far from complete." (DCC 80112045 - 80112046) Lang notes that the pathology procedures need a "complete overhaul."

She states"

"Documentation is extremely poor at present, and no one in HES fully understands the requirements in this area.... A plan must be written to bring this group up to industry standard as soon as possible. Just getting this department into compliance will take several months...." (DCC 80112046)

CITE: DCC 80112043 - 80112071, Exhibit to Isquith Deposition (used by Dow Corning).

Document #495
11/15/89
KNOWLEDGE OF LIQUID SILICONE DANGERS

E. Frisch, Dow Corning, memo to B. Lipscomb regarding the "keratosis IDE" and the information necessary to convince the FDA that the material is safe. He notes that the FDA's position is that animal studies are useful for safety while clinical studies are only useful for efficacy. Frisch acknowledges that Dow Corning's "primary focus has been on efficacy," even with the clinical studies. "Safety data ... are scant and based on superficial external examination of the injection site" that does not include any detail or blood chemistries, urine analysis, liver function studies, or examination for lymph node enlargement. Key studies needed are carcinogenesis pharmacokinetics, developmental and reproductive toxicology, and immune response. Frisch notes that LeVier has a copy of a 9 page letter from the FDA to the Ortho division of J&J rejecting their IDE application for cosmetic uses of silicone fluid. CITE: KMM 407633 - 407634.

Document #496
12/04/89
CONCEALING FROM FDA
ACKNOWLEDGEMENT OF NEED FOR TESTING
KNOWLEDGE OF SYSTEMIC DISEASE

515(B): Dr. Jack Fisher (ASPRS) informs "All Members of BIRAC, Old and New" about progress report since ASPRS convention in San Francisco. He notes four concerns of the PSEF Board of Directors and those of BIRAC: 1) that manufacturers had written the RFP and they thought Colton was going to do this; 2) concerned that all southern California bidders would be excluded; 3) concerned that one manufacturer stated that it would only fund two issues from a longer list that PSEF wanted studies; and 4) concerned and "disappointed that the study does not address the connective tissue issue.... Based on our very best clinical judgment and scientific understanding, we believe that CT disease issue will forever loom until we meet it head on." (emphasis added). PSEF is also deeply concerned about the reporting requirements - the potential delays in notification of study results. PSEF believes "these restrictions to be an infringement of academic freedom and a potential embarrassment to foundation (PSEF)."
CITE: KKA 43763 - 43769A

Document #497
01/31/90
TESTING
TISSUE REACTION
KNOWLEDGE OF SYSTEMIC DISEASE

Crofoot, Stanton, Siddiqui, and Zimmer, Dow Corning, report on "A 14 - Day Subchronic Oral Gavage Study With Hexamethylcyclotrisiloxane In Rats." Oral administration of the test material, D3, "may produce increases in liver weight at dose levels as low as 100 mg/kg and perhaps as low as 25/kg in the male rat...." The authors state that the "toxicologic significance of the liver weight increases cannot be made."
CITE: T 37322 - 37409, exhibit 36 to Zimmer Deposition.
DUPLICATE: T 37447 - 37490.

Document #498.
02/08/90
SHELL STRENGTH - THICKNESS
MISCELLANEOUS - RECKLESS/CONSCIOUS DISREGARD

Jim Curtis memo to John Dillingham, both of Dow Corning, regarding deficiencies in the stocking and shipping process at the Arlington plant. He states:

"I can tell you that the stock here in Arlington is mixture of old and new units. Eight year old SILASTIC II units are in a bin with 2 month old units. And the people that pull the implants from the bins to fill orders tell me that they will pull any, with no attention to the lot number (production date). When I asked why we had eight year old implants, I was told that many implants are returned from territory stock and mixed in the bins with the new implants.... If the system goes unchanged, the customer will develop the perception that our implant quality is very inconsistent.

CITE: KKA 5640. NOTE: A listing of the useable life and shelf life for Dow Corning products is located at KKA 097708 - 097710.

Document #499
02/08/90
MISCELLANEOUS
MISCELLANEOUS - ORGANIZATIONAL SURVEY
SILICA

Burda, Dow Corning, prepares a "Product Structure Of Silastic Mammary Implant (1964 To The Present)" in which he lists all of the products Dow Corning has manufactured and their component parts. Contains charts that show silica content and corporate and manufacturing organization.
CITE: DCC 17007927 - 17007993.

Document #500
02/19/90
CONCEALING FROM FDA

515(b) Lois Duel writes to other manufacturers suggesting that the epidemiology studies be funded only by manufacturers, and that ASPRS be excluded. She claims the basis for this position is the "need to preserve the confidential nature of the study content as its supports PMA submissions by sponsoring manufacturers." Duel further suggests that ASPRS and PSEF play a modified role such as PR efforts.
CITE: MEX 28736 - 28738.

Document #501
07/331/90
KNOWLEDGE OF LIQUID SILICONE DANGERS
CONCEALING FROM FDA
ACKNOWLEDGEMENT OF NEED FOR TESTING

Dow Corning's "Summary of Pre-clinical Testing Relevant To The Keratosis Project And Indications For Additional Studies." There is no testing of extracts, hemolysis, mutagenicity for 360 Fluid (although the author notes that this should have been done since "such testing is brief and inexpensive"), skin irritation for DC 360 Fluid, Sensitization, 90-Day implantation study of 360 Fluid, and no long term studies. The author also reviews the chronic exposure toxicology files and states:

"A series of five studies (1968-1976) in the rat and dog involve the injection of relatively large volumes of DC 360 Fluid, 350 cs at subcutaneous, sublantar and intramuscular sites for periods of one to two years. These studies provide evidence of a limited local inflammatory reaction and instances of fatty necrosis at the injection sites. These findings are expected. Unfortunately, none of these studies conform to GLP regulations and, more seriously, none of the wet tissues, blocks or slide preparations have been retained. There is another series of reports of fluid injection experiments conducted by Dr. Ashley and by Dr. Rees (1964-1972). These latter studies are of virtually no utility. They suffer from the same deficiencies as the other long-term studies and, in addition, no protocols or in-life data can be retrieved.

On at least two occasions the FDA has indicated that existing chronic data are insufficient to support the use of PDMS in small volume injection applications. Most recently (April, 1988), the FDA informed Ortho Pharmaceutical that a rat carcinogenicity study must be completed before initiating clinical trials related to the treatment of facial wrinkles with injected PDMS. The bottom line is that there are no specific long-term pre-clinical safety studies conforming to GLP's to support development of a product to treat keratosis.

A 2-year study in the rat has not yet been requested. Such a study cannot be started in HES until about April 1991. The objective of a life-time rat study is to assess the long-term local reaction as well as systemic toxicity including carcinogenicity."

With regard to special testing on polymer distribution, nine in vivo distribution studies of PDMS have been conducted between 1956 - 1985. "All of the animal studies tend to show a low level ubiquitous distribution with the highest concentrations found in lymphatic tissue."

With regard to immunotoxicity, the author states:

"A study was done in 1974 to look at the immune adjuvant activity of a number of organosilicone compounds and polymers including several viscosities of DC 200 Fluid.... This is not a well-structured nor GLP-conforming study but it is unlikely that a repeat will be needed."

With regard to teratology and reproductive effects studies, the author claims that there are no adverse effects from PDMS on reproductive capacity in the rat or primate. The summary also lists a cost estimate for conducting additional studies and a list of the present studies in the Toxicology Files.
CITE: KMM 407282 - 407282.

Document # 502
08/13/90
CONCEALING FROM FDA
KNOWLEDGE OF SYSTEMIC DISEASE
DOCUMENT DESTRUCTION

FDA: B. Levier, Dow Corning, memo to R. Dieck and L. Duel regarding Statistical Analysis of Neoplasm Data from 2 Year Gel-Implant Study of Q7-2159A and MDF-0193 in rats stating, "but the sum of hepatocellular adenomas and carcinomas is within only one or two tumors of being statistically significant.... Our argument... may still be plausible but it is weakened by these findings... (and) I think it would be imprudent to test this issue with the FDA." A handwritten note at the bottom of the memo states "Please discard this memo after reading
CITE: KMM 451517 - 451525.

Document #503
08/20/90
CONCEALING FROM FDA

Woodbury, Dow Corning, memo to R. Dieck, C. Dillon, L. Duel, R. LeVier, H. Steinberg, regarding comment by Roscoe Moore, FDA, at the 1990 Data users Conferences that manufacturers purposely overestimate device prevalence because it allows them to underestimate complication rates.
CITE: KMM 402702, Exhibit to Dillon Deposition, Exhibit 13 to Woodbury Deposition.

Document #504
09/06/90
DOCUMENT DESTRUCTION
CONCEALING FROM FDA

FDA: W.L. Miller, Dow Corning Wright Marketing, telex to Lutz and Schmitz regarding the MSI Questionnaire during the period of 01/01/90 to 03/27/91. He states that, "The FDA continues to exert tremendous influence on the ways in which we manage our business. As a result, the questionnaire which we developed would be required to be included in the submission package when MSI is presented for P.M.A. review by the FDA. Even if the results of our evaluation are very product/D.C. positive such a document could raise many questions and potentially impact our successful completion of the PMA process. THEREFORE I MUST ASK YOU TO DESTROY ALL COPIES OF THIS DOCUMENT WHICH CURRENTLY EXIST IN YOUR FILES. A NEW DOCUMENT HAS BEEN CREATED, AND HAS ALREADY BEEN SENT TO DUSSELDORF VIA FAX FOR DISTRIBUTION."
CITE: KKE 1315.

Document #505
10/09/90
SHELL STRENGTH - THICKNESS
FRAUD/MISREPRESENTATION

Dr. Flowers sends a letter to Doris Michelson, Dow Corning, regarding complaint Report MW 3416. Dow Corning claimed that a slit developed in the implant "in response to wear and stresses that were greater than the implant's design limits." Dr. Flowers believes it is the same fold flaw phenomenon as that which caused near 100% deflation rates in McGhan implants between 1977 and 1979. He believes the deflation problem is caused by folding, which in turn causes fiber fatigue and later fracture and slits. He blames inadequate pre-market testing and is distressed about Dow Corning's complaint analysis process. He states that, "What alarms me most of all, and that which I find totally unacceptable is the identical 'finding' which contains two fairly lengthy sentences, word for word identical with the earlier patient. This obviously is a company approved 'finding' that is 'rubber stamped' in an effort to decrease company liability and conceal the true significance of the findings."
CITE: KMM 498693 - 498696.

Document #506
10/17/90
SHELL STRENGTH - THICKNESS
MISCELLANEOUS - RECKLESS/ONSCIOUS DISREGARD

Dave Kinne memo to Glenn Dennis, both of Dow Corning, regarding an inspection of the dipping process for making envelopes. For the week of October 8, 1990, "49% to 87% of the units inspected and passed may actually be non-conforming" and should not have been accepted. Kinne states:

"These statistics are disturbing at best and give further weight to arguments in favor of shutting down and addressing our problems. At the very least they should serve to get the actions that have been recommended for the past several months executed and provide some tangible support to my quality efforts.
CITE: KKA 19032 - 19036.

Document #507
12/06/90
CONCEALING FROM FDA
KNOWLEDGE OF SYSTEMIC DISEASE

Robert Rylee, Vice President and General Manager of the Health Care Business of Dow Corning, sends a "Dear Doctor" letter. Rylee states that Dow Corning "voluntarily" submitted information to the FDA including a "summary list of 750 bio-safety studies and full reports of more than 30 toxicology studies.... The list included all of our studies; none were withheld." Rylee discusses recent media attention and a 11/27/90 decision by a district court in Washington D.C. ordering Dow Corning to make public this bio-safety data.

Dow Corning cites the need for confidentiality as the reason it is appealing the district court's order.

Rylee also states that there have been recent reports of immunological responses to silicone breast implants. "Suspected immunological response is a controversial subject because there are so few cases available for study. A review of the global literature indicates that out of more than two million women with silicone mammary implants, only about 40 have been reported to have a form of rheumatic/connective tissue disease. Some form of scleroderma has been reported in 14 implanted women with a latency of about 10 years, and so-called human adjuvant disease HAD) has been reported in 13 implanted women with a latency of about 7 years." He concludes by states that based on Dow Corning's 25 years of experience in silicone breast implants has demonstrated the "reasonable safety and efficacy of these devices."
CITE: M 370276 - 370277, Exhibit to MDL Rathjen Deposition. DUPLICATE: M 690014 - 690014A.

Document #508
12/10/90
FRAUD/MISREPRESENTATION
DOCUMENT DESTRUCTION

Woodbury and Delongchamp, Dow Corning, memo to various Dow Corning employees regarding U.S. breast implant prevalence. The "figure of 2,000,000 women in the U.S. with breast implant does not appear to be supportable or reliable." Woodbury and Delongchamp claim that the prevalence rates are "roughly 250,00 to 800,000. These figures translate to a prevalence rate of about 4 to 8 per 1000 adult white women in the United States."
CITE: KMM 403370, Exhibit 2 to Woodbury Deposition. DUPLICATE: KMM 489617.

Document #509
12/12/90
FRAUD/MISREPRESENTATION
ACKNOWLEDGEMENT OF NEED FOR TESTING
CONCEALING FROM FDA

Dow Corning "Epidemiology Update" on post-surgical complications in breast augmentation notes that internal customer complaints based on Dow Corning Wright data probably "substantially underestimates true incidence rates. The number of complaints reported underestimates the true number. And, product sales, used as a denominator in rate calculations, likely overestimates the number of women who have been implanted."
CITE (KKA 1971: KMM 396712).
CITE: KKA 10971 - 10972, Exhibit to Dillon Deposition, and Exhibit 4 to Woodbury Deposition. DUPLICATE: KMM 396712; KKA 155318 - 155322. NOTE: Regarding the Micro Surfaced Implant (MSI), the report notes the principal outcome of the clinical trial in progress is "excessive capsular contracture."

Document #510
12/12/90
DOCUMENT DESTRUCTION
FRAUD/MISREPRESENTATION

Woodbury and Delongchamp, Dow Corning's Medical Research Services, memo concerning the National Center for Health Statistics, 1988 Device Survey, Attached materials provide findings based on 142 documents from the FDA funded Device Supplement to the National Center for Health Statistics (NCHS) 1988 National Health Interview Survey. Woodbury and Delongchamp conclude that in the U.S. there are 544,000 implanted breast devices and 320,000 women with breast implants (4.2 per 1000 adult white population). Also, 25.9% of the devices had some problems, equaling 30.3% of the women. Within 5 years of implantation, 13% of sampled women had a replacement, with 17% having a replacement by 10 years. Device defect, failure or malfunction was reported for 11% of the women, and defect or malfunction being the reason for replacement in 30% of replaced devices.
CITE: DCC 80011571 - 80011597, Exhibit to Dillon Deposition, Exhibit to LeVier Deposition, Exhibit to Harris County Rylee Deposition, and Exhibit 3 to Woodbury Deposition. DUPLICATE: KMM 333323 - 333349. NOTE: This is the document that Rylee and Thiess are alleged to have requested Dillon and Woodbury to destroy because it would be damaging to Dow Corning.

Document #511
12/14/90
COHESIVENESS - LIQUID COMPONENT OF GEL
KNOWLEDGE OF SYSTEMIC DISEASE
MISCELLANEOUS - COMPLICATIONS

Hazleton memo to various personnel regarding the establishment of a Steering committee Team to manage the evolving issues and communications surrounding the biosafety of D4 and other small molecule dimethyl materials. The team will be comprised of Bill Cavanaugh, Barie Carmichael, Chuck Dillon, Deb Zellner, Doug Wernecke, Mark Zimmer and Jack Pulley.
CITE: No Bates Number; Exhibit 3 to Boley Deposition, and Exhibit 33 to Zimmer Deposition.

Document #512
12/20/90
DOCUMENT DESTRUCTION

Dillon, Dow Corning Corporate Medical Director, memo to Swanson, Dow Corning Corporate Ethics Committee, stating:

"I am writing to report a recent incident and to request a formal review by the DC Corporate Committee on Ethics. I make this request because I feel that this episode represents a violation of corporate, professional, and commonly accepted business ethics.

The specific incident occurred on Friday, December 14th at 5:15 PM. Greg Thiess, a senior litigation attorney in the corporate legal department approached Mary Ann Woodbury, a research scientist of my staff in her DC-1 office. He asked that she destroy all copies of a memo she circulated two days previously. The memo contained a data analysis of a recent National Center for Health Statistics Survey of Surgical Device complication rates, and the overheads for a presentation to the Reed Committee on mammary implant issues that summarized the overall scope and current status of Epidemiology projects for the Health Care Business's (sic) mammary implant products.

Mary Ann asked me to join them in her office and Greg repeated his request to both of us. Greg stated to us that he was acting at the specific request of Robert Rylee II, Vice President and General Manager of the Health Care Business who was very angry with the memos, and that he had spoken with Mr. Rylee on this subject earlier by telephone. He also stated that from his personal viewpoint, the information contained in the memos would compromise projects that he was then working on in Dow Corning product liability litigation and be adverse to the company if publicly revealed. I directed Mary Ann not comply with the request and stated to Greg that to do so would in my opinion be unethical conduct.

I feel that this is a serious example of misconduct requiring formal review. I am concerned that these documents may be sought out and destroyed. Also, I am concerned that the incident, if not amended, may lead to others that would threaten the integrity of my department, its employees, their ability to provide valid scientific evaluations to management, as well as their careers in the company.
CITE: DCC 80090119, Exhibit to Dillon Deposition, Exhibit to Duel Deposition, Exhibit to Freeman Deposition, and Exhibit 5 to Woodbury Deposition. DUPLICATE: DCC 80090589.

Document #513
01/11/91
DOCUMENT DESTRUCTION

Yerrick, Dow Corning, memo to Dillon and Woodbury regarding the Code of Conduct meeting. Yerrick states:

"I hope you feel your concerns were heard and understood; and more importantly they will be acted upon in a sincere manner. You have my commitment to do so. I understand that you may have some skepticism about the outcome but that's OK because we need that to determine our success.

I, and others, appreciate your candor in bringing forward the issue as a generic problem to be evaluated. It was the right thing to do."
CITE: KMM 486118, Exhibit 8 to Woodbury Deposition.

Document #514
01/16/91
FRAUD/MISREPRESENTATION
DOCUMENT DESTRUCTION

Woodbury, Dow Corning, responds to Yerrick's memo of 01/14/91 stating, "I have just returned from being off sick. I tend to still be skeptical, as a result of other things that I know Bob Rylee has done."
CITE: KMM 486119, Exhibit 9 to Woodbury Deposition.

Document #515
01/22/91
CONCEALING FROM FDA
DOCUMENT DESTRUCTION

Lois Duel, Dow Corning, memo to Bailey Lipscomb and others regarding the "January, 1991 Monthly Report." Under the heading of "Technical Communications," Duel notes that she "spent MANY days reviewing, filing and/or trashing retained documents in my files. Major progress was made, but there is more to do."
CITE: KKA 37643 - 37646.

Document #516
01/22/91
FRAUD/MISREPRESENTATION
TESTING

515(B): Dr. Cherup sends a letter to ASAPS returning a research grant. She reports that she did not get any cooperation from Dow Corning and Mentor and that they "more or less told me that they did not want their textured silicone implants involved in any studies over which they were unable to have direct control. They explained to me that they had other studies ongoing with other researchers characterizing their implants, but they admitted to me that they had direct control over these studies." She states that she does not want to add to the "the mound of already existing information wrought by studies which are biased as being supported by one company or product or another."
CITE: MD 120461 - 120463.

Document #517
01/28/91
ACKNOWLEDGEMENT OF NEED FOR TESTING
KNOWLEDGE OF SYSTEMIC DISEASE
TESTING

Zimmer, Dow Corning, memo to Co-Producers Technical Committee and Co-Producers Steering Committee regarding documents to review for February technical committee meeting. Zimmer states that the draft reports of the previous morphometrics and DNA studies indicate that it is fair to say that D4 causes hepatocellular hyperplasia and that no evidence of hypertrophy was evident. He also enclosed morphometrics and DNA assay protocols for a 2-year rat bioassay and for cell replication studies.
CITE: DCC 260000566, Exhibit 39 to Zimmer Deposition.

Document #518
01/29/91
COHESIVENESS - LIQUID COMPONENT OF GEL
FRAUD/MISREPRESENTATION
KNOWLEDGE OF GEL BLEED

FDA: Department of Health and Human Services pharmacologist, Hoan My Do Luu, letter to Dow Corning and Dan McGunagle of the Breast Implant Task Force regarding Appendix A and B, supplements to PMA P910039A (Silastic II H.P.) and P910040A (Silastic MSI single lumen silicone gel-filled mammary implants). The letter deals with the summary of extraction data for Dow Corning Silastic shells, gels and patches. Luu states that "the reporting of low amount of cyclics (less than 2% wt) in the summary report is misleading because the company selectively reported only two of the 17 cyclics found in the components' extracts. The firm selectively reported the amount recovered for cyclic tetrameter (D4) and pentameter (D5) as total volatile cycles. Other shortcomings were found in the methodology protocols used such as incomplete extraction in ethanol, ethanol: CH2CL2 and saline, lack of controls and validation of the methodology.... The reporting of no detectable siloxane residues in saline extracts was questionable." See original document for additional questions regarding Dow Corning's reporting.
CITE: FDA 12281 - 12290. NOTE: See entries of 12/20/91, 02/05/92, 02/06/92 and 03/13/92.

Document #519
02/28/91
CONCEALING FROM FDA
DOCUMENT DESTRUCTION

FDA: Eldon Frisch, Dow Corning, memo to Garry Brody, M.D. regarding letters from the FDA on the use of silicone fluid on hypodermic needles. Frisch states;

"I have found the letters from FDA that have served as a basis for the use of silicone fluid on hypodermic needles and syringes for many years. I have removed all references to Dow Corning just in case these letters somehow find their way back to FDA. I have been asked by some of the individuals at FDA about the basis for silicone fluid being used on syringes and needles, and have never produced these letters. There are some who believe that if FDA cannot identify how it came about that fluids were allowed on syringes and needles then it is difficult for them to rescind the approval."

(emphasis added). Attached are two documents - a letter from Philip Sheeler, FDA, in which all names of individuals and companies have been redacted, and a second letter from William Jester, FDA, in which all names have also been redacted.

CITE: DCC 17037526 - 17037528.

Document #520
03/12/91
ACKNOWLEDGEMENT OF NEED FOR TESTING
KNOWLEDGE OF SYSTEMIC DISEASE
TESTING
TISSUE REACTION

Stark, Dow Corning, memo to Lentz regarding the proposed modification of future D4 testing programs. Stark states that the morphometric and DNA studies are technically sound and correctly interpreted, the ovary weight issue must be resolved, pharmocohinetics and additional metabolism data are imperative before we embark on reproduction, teratology, and chronic studies, and cell replication studies must precede chronic studies. Stark encloses an outline of the proposed D4 research plan.
CITE: DCC 260000706 - 260000716, Exhibit 42 to Zimmer Deposition.

Document #521
03/15/91
FRAUD/MISREPRESENTATION
CONCEALING FROM FDA
KNOWLEDGE OF SYSTEMIC DISEASE

Woodbury, Dow Corning, letter to Gary Brody, M.D., regarding National Health Statistics Survey. Woodbury states:

Factors which may influence the accuracy of prevalence estimates:

--Primary data collection methodology.
--Statistical design of sampling plan.
--Specific data collection methodology within a given primary data
collection method.
--Survey participation bias.
--Completeness or representativeness of data upon which estimates are based.
--Analysis Method.
--Willingness of respondent to disclose information or knowledge and illingness to disclose for a proxy respondent.
--Device replacement rates and frequency of replacement.
--Permanent removal rates.
--Mortality patterns for implanted patients.
--Device inventory and wastage for marketing based estimates.
--Subjective estimates of surgery rates by surgeons within surgeon surveys.

The letter includes an attachment containing a comments by R. Delongchamp, Dow Corning, stating:

"The observation of serious disease among women with cosmetic implants is expected simply because all women eventfully die whether or not they have an implant. As the numbers of women with implants increases, this fact makes it inevitable that at least one woman with an implant will succumb to even the rarest of diseases. An assessment that the implant caused the disease is unwarranted."

The letter also includes attachments presenting survey data.
CITE: KMM 403500 - 403530, Exhibit to Harris County Rylee Deposition, Exhibit 17 to Woodbury Deposition. DUPLICATE: KKA 102860 - 102880.

Document #522
05/01/91
ACKNOWLEDGEMTN OF NED FOR TESTING
KNOWLEDGE OF SYSTEMIC DISEASE
MISCELLANEOUS - COMPLICATIONS
TESTING
TISSUE REACTION

Study by Ruhr and Hoffman titled "Progress Report: A Chronic Implant Study In Rats With Dow Corning Q7-2423 and Q7-2551 Elastomers," Dow Corning Tox file 3810-10 and 5194-8. These silicone elastomeric materials comprise the envelope for the Silastic II and silastic MSI mammary prostheses.

Four groups of 60 male and 60 female rats each are incorporated into the study design. There is a sham operated control group, a U.S.P. polyethylene control group, and one group for each of the elastomers.

Statistical analysis will be performed on body weight and food consumption data; organ weight; and appropriate clinical pathology data.
CITE: P 19120 - 19163, Exhibit 21 to Zimmer Deposition, Exhibit 5 to Bejarano Deposition, Exhibit 1 to Bey Deposition, and Exhibit 36 to McKennon Deposition.

Document #523
06/04/91
CONCEALING FROM FDA
FRAUD/MISREPRESENTATION
MISCELLANEOUS - PRODUCT LABELING
TESTING

J Curtis sends a telex to L. Duel, Dow Corning, regarding animal study data for the PMA submission, "I was not privileged to its duration and discovered its incompleteness during preparation for the PMA.... Is LeVier's response not a problem for us. Doesn't John Gauger utilize some of the data from these 'incomplete' studies as the basis for product claims in 'labeling' (i.e. product advertising)?"
CITE: KAA 57.

Document #524
06/19/91
KNOWLEDGE OF GEL BLEED
TESTING

Varaprath, Dow Corning, report on internal Dow Corning Wright study entitled "Composition(al) Analysis of Mammary (Implant) Gel Bleed." Analysis states:

"Silicone gel bleed was collected from mammary implants fabricated with and without a fluorosilicone barrier interlayer using accelerating conditions to collect significant quantities via a short period of time (not in in-vivo simulation). The -prostheses used in the test were 1) Low Profile Round (LPR) Design High Performance (H.P.) Mammary Prosthesis with no fluorosilicone barrier, and 20 SILASTIC II LPR H.P. Mammary prosthesis which contain fluorosilicone barrier interlayers. The test method for gel bleed collection is documented by the author. The fluorosilicone barrier was shown to reduce the amount of gel bleed by approximately a factor of 20 (i.e., 837.3 + or - 64.9 mg. without barrier vs. 44.3 + or - 5.6 mg. barrier). After collection, the gel bleed was analyzed using different spectrochemical techniques to determine its composition (i.e., sivinyl and Si-H were detected by infrared spectroscopy, platinum by atomic absorption spectroscopy, and molecular distribution by gel permeation chromatography). The molecular weight distribution of the LPR samples was relatively close to the reference material, Q7-2317, while the SILASTIC II samples exhibited significantly lower molecular weight distribution that the reference. The Sivinyl content of the LPR samples averaged 156. + or - 13.5 ppm; SILASTIC II samples averaged 100.0 + or - 7.0 ppm; and Q7-2317 was 9.8 + or - 7.4 ppm. Infrared and atomic absorption spectroscopy did not detect Si-H or platinum."

Adverse effects are listed as N/A.
CITE: FDA 33559 - 33569.

Document #525
06/24/91
FRAUD/MISREPRESENTATION


Hall, Dow Corning, memo to Gary Anderson, Campbell, Carmichael, Biggs, LeVier, and Jenkins regarding the "DCC Committee." Hall states:

It has been two weeks since we had the great session with the BOD at which time they pointed out some of the problems we were facing and suggested ways we might get beyond them. This communication is intended to simply summarize where I feel we are.

The issue of cover-up is going well from a long-term perspective. We are moving rapidly ahead on our press conference, and all things appear to be in place for that with the exception of the University of Michigan study being finalized....

The number one issue in my mind is the establishment of networks. I believe we have made no progress in the two weeks. Obviously, this is the largest single issue on our platter because it affects not only the next 2-3 years profitability of DCC, but also ultimately has a big impact on the long-term ethics and believability issues. If we do not win this one, or at least minimize the financial impact that people are able to achieve, you can forget about whether we have done all these other things correctly....

It has become obvious to me that what is at risk here is somewhere between $50 million and $500 million. Right now, I think we are losing the time race badly in this critical area, and I believe that the amount of money we are going to lose is increasingly rapidly since we are not going to be in a position to divert the opposing forces into the directions we want soon....

The place we have the biggest hole still missing and two weeks behind from the time we got the word from Keith McKennan (sic), is in this whole arena of getting a patient grass roots movement going.
CITE: KKA 332805 - 32806.

Document #526
09/13/91
KNOWLEDGE OF GEL BLEED
RUPTURE
SHELL DEGRADATION
SHELL STRENGTH - THICKNESS
TESTING
TISSUE REACTION

FDA: Letter from the FDA to B. Lipscomb, Director of Clinical and Regulatory Affairs for Dow Corning Wright. Dow Corning Wright submitted 229 studies to the FDA in its PMA for the Silastic II Mammary Implant H.P. and the MSI Mammary Implant H.P. but the FDA states, "we believe that the PMA lacks information needed to show that there is reasonable assurance that the device is safe and effective for its intended use." The FDA then lists "major deficiencies" in the PMA including lack of specific data on rupture testing, tear resistance testing, abrasion resistance, gel bleed performance testing, pharmacokinetic/biodegradation studies, mutagenicity testing, manufacturing information, and clinical and non-clinical investigations.
CITE: m 780258 - 780265. DUPLICATE: M 780092 - 780100: M 780101 -780103; KKA 178597 - 178604.

Document #527
10/09/91
COHESIVENESS - LIQUID COMPONENT OF GEL
KNOWLEDGE OF GEL BLEED
TESTING

FDA: FDA Materials Research Engineer, Lawrence D. Coyne, Ph.D., issues a memorandum titled "Dow Corning single and Double Lumen Silastic II and Silastic MSI Breast Prothesis: In-Depth Review of Gel Bleed Testing." He reviews eight Dow Corning reports of gel bleed permeation testing, two of which provide useful information:

"The bleed consists of approximately 80% compounds of low molecular weight (=5300) in the range of, although lower than, the linear (i.e., uncross-linked) polydimethylsiloxane compound found in the original gel fill. Approximately 4% is composed of components of very low molecular weight (=525) which may correspond to unreacted or deliberately added dimethylcyclosiloxanes. The remainder, approximately 16%, is of much higher molecular weight (=245,000) and probably arises from unreacted or degraded parts of the cross-linked material found in either the gel or the shell material. It is vital that a thorough and adequate extraction of the original gel fill and shell be performed so as to resolve the origin of these detected bleed products!"

Also noted is that for simulating in vivo gel bleed, use of mineral oil rather than saline as solvent in testing is better and proper, since it: "represents more realistically the in vivo state in which large concentration gradients outside the shell are maintained by the turnover and replenishment of body fluids possibly with the assistance of some active transport process. These conditions do not exist in a static in vitro experiment employing a very poor solvent such as saline."

The writer particularly criticizes a Dow Corning bleed study due to:

"the complete lack of chemical or molecular weight distribution analysis of the bleed product. The importance of determining the identity of the bleed product, in addition to its total accumulated weight, cannot be overstated. The barrier layers of these "low-bleed" devices may in reality be much more efficient at retarding the passage of components of higher molecular weight, but be relatively permeable toward potentially more hazardous low molecular weight linear and cyclical molecules. The chemical analysis of this study is not nearly thorough enough. Concentrations of unreacted functionalities as a useful quantity, but even more important is the complete identification of the lower molecular components, which would be expected to pose the most significant health risk." CITE: DCC 241000088 - 241000101.

Document #528
10/27/91
DOCUMENT DESTRUCTION
SHELL STRENGTH - THICKNESS

Morris, Dow Corning, memo to Kinne regarding the monthly report. "Mandrel repair has maintained a 50% success rate. There are now approximately 500 Mandrels in the repair loop. The number is continuously growing! The mandrel repair team cannot keep up with the rate of damage." She also states that she is a member of recently formed "Document Investigation and Review Team (D.I.R.T.)... All documentation and paperwork is being created/edited." She also reports that:

"there were several major losses this month. Some of the most significant were 98 units lost due to lack of final cure, 16 units were rejected because of rotocoat malfunction, 71 envelopes were lost due to a high fill level in the tank, and 27 envelopes were dipped on the wrong profile.
CITE: KKA 22700.

Document #529
12/20/91
COHESIVENESS - LIQUID COMPONENT OF GEL
KNOWLEDGE OF GEL BLEED
RUPTURE
SHELL STRENGTH - THICKNESS
TESTING

FDA: Lawrence Coyne, Material Research Engineer for the FDA, provides an in-depth review of Gel Bleed and Mechanical Testing submitted in Dow Corning's 12/13/91 Amendment (Volume 1) concerning Single and Double Lumen Silastic II and Silastic MSI Breast Prostheses, PMAs P910039A and P910040A. One notable deficiency in the testing is "the absence of any reported values for the total energy to rupture." Also:

a. Tensile Strength Testing
Coyne's "examination of the raw data for ultimate elongation reveals that a number of inordinately low elongation values were simply disregarded in calculating average values of this property." As such, Dow Corning's calculations were artificially high, within ASTM F703 guideline; however, inclusion of all data would have brought the mean average down to "a clearly unacceptably small and highly fluctuating value." Coyne attributes the low values to poor manufacturing quality control leading to "chemical differences within the shells."

b. Patch/Valve Tensile Testing

Significantly lower values of ultimate elongation and tensile strength in the patch material and the shell material in the vicinity of the patch would appear to indicate the higher probability of device rupture in these areas.

Finally, Coyne finds Dow Corning's gel bleed study unacceptable, as it "does not include any chemical or molecular weight characterization of the gel bleed products.... Also, contrary to what might be expected, the bleed rates were higher in terms of a weight basis for the firm gel as opposed to the soft or responsive gel."
CITE: FDA 12423 - 12431.

Document #530
12/30/91
FRAUD/MISREPRESENTATION

FDA: FDA sends a Warning Letter to Dow Corning Wright instructing them to take immediate action to eliminate dissemination of false and/or misleading information concerning the safety of breast implants. Examples of false statements made regarding the following subjects are:

1) Implant Safety - "Scientific data and research show that breast implants are 100% safe.... After thirty years of study conducted with patients, there have never been health problems with implants or silicone.... Breast implants are safe."

2) Gel Bleed - "a minute amount of gel, less than half a teaspoon, which doesn't go anywhere."

3) Rupture - "...results from a traumatic incident... such as being hit in the chest with a two by four.... It (rupture) has happened less than 1% in 2 million women."

4) Migration - "It is not possible for the silicone to go to the internal organs because it is not specifically possible for the silicone to get into your spleen, kidneys, etc."

5) Autoimmune disease - "It must be a genetic glitch... Silicone breast implants have never been linked to autoimmune or connective tissue disease in any studies ever done."

6) Cancer - "There is no increase in breast cancer from implants, if anything it is less."

7) Capsular Contracture Complications. - "But remember, you can have complications when you have a baby, yet people do it all the time."

CITE: M 780626 - 780628. DUPLICATE: KKA 39985 - 29987; FDA 16233; FDA 50509 - 50512; DCC 242061180 - 242061182; DCC 242010055 -242010057; DCC 242051629 -242051631: M 780626 - 780628: DCC 17006751 -17006753; DCC 242031792 - 242031794.

Document #531
01/08/92
KNOWLEDGE OF LIQUID SILICONE DANGERS
EMBOLISM

FDA: Hoan-My Do Luu summarized the adverse effects associated with the use of injectable liquid silicone fluid. The short term effects are swelling, erythema, pain, edema, pigmentation, slight rubbery of the skin, discoloration of the skin and embolism. Long term effects are severe inflammation, granuloma, dermal and subcutaneous atrophy, pain, migration or disappearance of the injected material, lymph node hypertrophy, dermatitis, calcification, human adjuvant disease and breast cancer.
CITE: FDA 12449

Document # 532
01/27/92
TESTING
FRAUD/MISREPRESENTATION
KNOWLEDGE OF LIQUID SILICONE DANGERS

M. Zimmer memo to the "substantial Risk Evaluation Committee" regarding his conclusions reached after reviewing some of the previous teratology studies on Dow Corning silicones. His conclusions differ from the conclusions reached in the initial reports.

In some studies, after reevaluation of the data, it has been determined that the original interpretation of the data was incorrect.

First, he notes increased skeletal defects which "may be due to a direct effect of the test material. This conclusion differs from that on the report...." Second, "an increase in dead fetuses and a decrease in live births were seen at all doses of 360 fluid.... This conclusion differs from that in the report.... The finding of dead fetuses in the treated groups were related to treatment." Third, "There is evidence of material toxicity based on maternal body weights" in albino rats. "The study demonstrates material effect at 1000 mg/kg but has no fetotoxic or teratologic effect at any dose."

Zimmer also notes that the conclusions in File No. 1059-5 that polydimethylsilozane does not cause adverse reproductive teratologic and mutagenic effects is incorrect. (emphasis added).
CITE" KMM 452794 - 452802.

Document #533
02/11/92
FRAUD/MISREPRESENTATION
KNOWLEDGE OF SYSTEMIC DISEASE
MISCELLANEOUS - COMPLICATIONS
MISCELLANEOUS LOBBYING

Zellner, Lutz, McClintick, Rothhaar and Clary, Dow Corning, memo to Parr, Yerrick and Anderson regarding D4 issue definition and actions. The authors present an overall communication plan that is split into two phases. Phase I is to disseminate the most recent information regarding the orally administered, range-finding study on rabbits. Phase II is to assure a state of DC preparedness to effectively meet any/all future D4-related events and provide a mechanism for periodically updating customers regarding D4 study plans and results. The authors enclose a schedule for each phase.
CITE: DCC 260000852 - 260000854, Exhibit 43 to Zimmer Deposition.

Document #534
02/12/92
DOCUMENT DESTRUCTION
CONCEALING FROM FDA

Greg Thiess, Dow Corning, memo to Jim Jenkins regarding Dillon's memo regarding document destruction. Thiess does not want memo released publicly to the FDA for a number of reason. He states:

"First, it is difficult to understand how Dillon's complaint could be relevant in any way to the FDA's investigation or its further inquiries, primarily because the document R. Rylee sought to be withdrawn or destroyed as inaccurate was not, in fact, withdrawn or destroyed. The request initiated by Rylee and transmitted by me was, simply stated, refused....

Second, I do not wish for my character to once again be drawn into question by the release of such an irrelevant document, particularly where the facts of the incident (in my opinion) showed that I was the victim of an apparent long simmering dispute between Messrs. Rylee and Dillon and a childish unwillingness or refusal of them to communicate about needed epidemiological studies, creation of internal documents, etc. Moreover, if the unfounded allegation of Dillon is released, how am I to answer the charge without, in effect, releasing confidential communications to me by a representative (Rylee) of my client, made to another representative of my client (Dillon)?

Third, I remain as concerned today as after the Committee meeting that the Committee never actually reached a decision about the supposed improper conduct. As I said at the meeting of my conduct, or that of R. Rylee for that matter, did not breach any DCC code of conduct or any applicable rule of professional conduct for lawyers."
CITE: DCC 80021872, Exhibit to Dillon Deposition, Exhibit to Reed Deposition, and Exhibit 15 to Woodbury Deposition.

Document #535
02/13/92
ACKNOWLEDGEMENT OF NEED FOR TESTING
KNOWLEDGE OF SYSTEMIC DISEASE
TISSUE REACTION

Klykken, Dow Corning, memo concerning "Differentiation Of Foreign Body Reactions And Immune Granulomas." Klykken gives a brief overview of foreign body reactions - which he claims are a "normal wound healing response" - and immune reactions to the implant which could range from "mild, fleeting symptoms to severe disruption of immunoregulatory functions and premature removal of the medical device." He claims that Dow Corning scientists "have failed to demonstrate any linkage between these implant materials and immunological sensitization."
CITE: M 850018. NOTE: Eldon Frisch, Dow Corning, admitted in memos dated 11/15/89 that Dow Corning had not done any immunological testing but needed to do so.

Document #536
02/24/92
CONCEALING FROM FDA
FRAUD/MISREPRESENTATION
KNOWLEDGE OF SYSTEMIC DISEASE
MISCELLANEOUS - COMPLICATIONS
TESTING

Joan Hatfield, Dow Corning Australia, fax attaching several documents, notably:

a. Dow Corning 02/10/92 press release announcing the release of "15 reports of scientific studies and 94 internal, non-scientific company documents.' In the release, Rylee admits implants are not risk-free. Tylee quotes Dr. Calman of the United Kingdom Department of Health stating: "There is little evidence on links between silicone gel implants and autoimmune disease."

b. McKennon 02/11/92 letter expressing regret that the "10 or so most painful memos" to be used against Dow were taken out of context, "to discredit Dow Corning," often without concern for any responsive documents or memos. Also, McKennon feels that "many of Dow Corning's critics are applying 1990's standards to 1970's memos and studies." McKennon also states that he has been assured that all of the information known to Dow Corning which might be relevant to their deliberations has already been provided to the FDA.

CITE: DCC 267010007 - 267010014.

Document #537
03/02/92
CONCEALING FROM FDA
FRAUD/MISREPRESENTATION
KNOWLEDGE OF GEL BLEED
MISCELLANEOUS - COMPLICATIONS
RUPTURE
SHELL DEGRADATION
SHELL STRENGTH - THICKNESS
STERILIZATION/CONTAMINATION
TESTING
TISSUE REACTION

FDA: FDA inspects Dow Corning Wright's plant from January 13 to March 2 and finds various examples of MDR reportable silicone breast implant complaints that were not reported to the Food and Drug Administration.

Examples include leaking mammary envelopes, ruptured mammary implants, implant deflations, capsular contracture complaints, inflammatory reactions, infections, gel bleed, an inadequate program in place for monitoring and controlling the levels of microbial and particulate matter in the controlled rooms, improper validation of the envelope curing oven, inadequate calibration program and MDR reports not filed in a timely manner.
CITE: M 780802 - 780813.

Document #538
03/09/92
COHESIVENESS - LIQUID COMPONENT OF GEL
FRAUD/MISREPRESENTATION
KNOWLEDGE OF GEL BLEED
KNOWLEDGE OF SYSTEMIC DISEASE
TISSUE REACTION

Lutz, Dow Corning, memo to Clary, McClintick, Klykken, Rigas, Roghhaar and Zellner regarding position statement on gel bleed and D4 - review and comments. Comments regarding bleed include bleed of silicone fluid is commonly associated with mammary implants and has long been recognized by surgeons as a characteristic of silicone gel-filled breast implants. The amount of bleed is largely dependent on the molecular weight of the silicone material. The comments regarding D4 include that it is contained in minute quantities in the silicone gel-filled mammary implant and Dow Corning and other manufacturers believe D4 is safe for use in its intended applications and in no way affects the safety of silicone mammary implants.
CITE: KMM 452997 - 453002, Exhibit 44 to Zimmer Deposition.

Document #539
03/13/92
COHESIVENESS - LIQUID COMPONENT OF GEL
KNOWLEDGE OF SYSTEMIC DISEASE
MISCELLANEOUS - COMPLICATIONS
TESTING
TISSUE REACTION

Memos updating latest D4 study results. One study showed that pregnant rabbits will stop eating and show a significant weight loss. Non-pregnant rabbits will do the same. Another study has shown that there are effects on certain internal organs, organ effects can be expected whenever there is significant weight loss. It is believed that Dow Corning's exposure guidelines and work practices for D4 continue to provide adequate protection for all employees.
CITE: DCC 17030046 - 17030047, Exhibit 15 to Zimmer Deposition, and Exhibit 4 to Boley Deposition.

Document #540
03/13/92
COHESIVENESS - LIQUID COMPONENT OF GEL
KNOWLEDGE OF GEL BLEED
RUPTURE
SHELL STRENGTH - THICKNESS
TESTING

FDA: The FDA cites deficiencies in Dow Corning, Mentor and McGhan's PMA test data on chemical extraction studies, in-vitro gel cohesivity, valve competence, joint integrity, tear resistance, and tensile strength. Include internal FDA memos dated 03/13/92 and 03/18/92 from Lawrence Coyne explaining in detail the reasons for the PMA denials.
CITE: FDA 12567 - 12607. NOTE/ FDA 12519 - 12535 may be an attachment to this document.

Document #541
02/13/92
COHESIVENESS - LIQUID COMPONENT OF GEL
KNOWLEDGE OF GEL BLEED
RUPTURE
SHELL STRENGTH - THICKNESS
TESTING

FDA: The FDA, in a summary of safety and effectiveness data, cites deficiencies in Dow Corning's, Mentor's, and McGhan's PMA test data on chemical extraction studies, in-vitro gel cohesivity, valve competence, joint integrity, tear resistance, and tensile strength.
CITE: FDA 12519 - 12535. NOTE: May be an attachment to FDA 12567 -12607.

Document #542
03/13/92
COHESIVENESS - LIQUID COMPONENT OF GEL
KNOWLEDGE OF SYSTEMIC DISEASE
MISCELLANEOUS - COMPLICATIONS
TESTING
TISSUE REACTION

Harrison memo to S&T plant personnel regarding an update of D4 study findings.
CITE: DCC 17030046 - 17030047, Exhibit 15 to Zimmer Deposition.

Document #543
04/24/92
COHESIVENESS - LIQUID COMPONENT OF GEL
KNOWLEDGE OF SYSTEMIC DISEASE
MISCELLANEOUS - COMPLICATIONS
MISCELLANEOUS - PRODUCT LABELING
TESTING
TISSUE REACTION

Rothhaar, Dow Corning, memo to Product Safety and Regulatory Compliance Staff regarding D4 material safety data sheets and labels. Rothhaar states that there is a moratorium on changes to material safety data sheets and labels for products containing D4 and D5. The reason for this moratorium is because the increased liver seen in some test animals exposed to D4 is believed to be an adaptive response rather than a true toxic effect and it is appropriate to retain the current 10 ppm industrial hygiene exposure guideline.

New products will not show D4 listed in the MSDS unless the D4 contributes to the product being a physical hazard and if not listed, no statements regarding the liver effect information and no mention of the IHG will be included in the MSDS but will be listed if it is determined to be hazardous. In any case the label for the product will not include any health hazard warnings relating to D4. There will be no potential liver effect statement on the label.
CITE: DCC 260000772 - 260000774, Exhibit 53 to Zimmer Deposition.

Document #544
06/24/92
CONCEALING FROM FDA
FRAUD/MISREPRESENTATION
MISCELLANEOUS - RECKLESS/CONSCIOUS DISREGARD
TESTING

McGunagle memo to Johnson and Kalins regarding the significance of Dow Corning studies omitted from their PMA's.
CITE: FDA 30537 - 30539, Exhibit to LeVier Deposition, Exhibit 21 to McKennon Deposition, Exhibit 10 to Harris County LeVier Deposition, and Exhibit to Issquith Deposition.

Document #545
06/24/92
CONCEALING FROM FDA
FRAUD/MISREPRESENTATION
MISCELLANEOUS - RECKLESS/CONSCIOUS DISREGARD
TESTING

FDA: Daniel S. McGunagle, Task Leader for the FDAs Breast Prosthesis PMA Review Team, memo stating that studies were omitted from Dow Corning's PMA. Dow Corning's PMA does not contain information significant to the determination of the safety and effectiveness of breast implants. McGunagle lists eleven specific studies that Dow Corning had failed to Mention or submit. These provide a factual basis for the FDA's concern regarding silicone-filled breast implants. Further, he notes that:

"The content of the withheld documents can be said to show a pattern. Intelligent people, familiar with this material, and anxious to obtain agency approval would recognize that these studies would draw more inquiry and justify further investigation into the safety of these devices. It is reasonable to assume that such people would not want this to happen and, being in a position to control the content of the PMAs, would leave these studies out to improve the chances for PMA approval."

CITE: FDA 51245 - 51247.

Document #546
07/14/92
ACKNOWLEDGEMENT OF NEED FOR TESTING
COHESIVENESS - LIQUID COMPONENT OF GEL
KNOWLEDGE OF SYSTEMIC DISEASE
TESTING

Memo from Forrest Stark to the Environment, Health & Safety (EHS) Board which consists of Gary Anderson, Bey, Crossman, Foglesong, Harrison, Lacefield, LeVier, Pulley, Weyenberg and Yerrick. Copies of the memo were sent to D. Anderson, Bassani, Birdsall, Churchfield, Dover, Frye, Grupp, Haberer, Hayes, Hazleton, Hoover, Jenkins, Kabbe, Ludington, Marciniak, McCormick, Nishio, Parr, Pfuehler, Reed, Rothhaar, Skinner, Snedeker, Steinhoff, Ziarno, Roth, Zimmer and Groh. The memo discusses "Environment, Health & Safety Board Meeting Minutes Meeting Held June 30, 1992."
CITE: DCC 17003795 - 17003829, Exhibit 18 to Zimmer Deposition. NOTE: This contains overhead presentations on D4 which are very interesting.

Document #547
09/07/92
ACKNOWLEDGEMENT OF NEED FOR TESTING
KNOWLEDGE OF SYSTEMIC DISEASE

Dow Corning lists "Clinical Immunology Proposals...and finds worthy of serious consideration:

1. Barrett Noones's silicone as an antigen and =/-presence of specific antibodies; specific T-cell stimulation; Dow Corning states that this "becomes important in the light of the recent Goldblum article";

2. Walter Peter's cytokines in implanted individuals. He has already started screening individuals and Myron Harrison, Dow Corning, has asked him to combine this clinical study with Laurence Rubin's proposal on serologies on implanted women to look for markers of autoimmune disease.

3. James Sanger's proposal to study the presence or absence of humoral antibodies contiguous to implants or in case of rupture.

4. Kimber White's (study on the potential immunogenicity of silicone elastomers and elicitation of humoral or cell-mediated responses.

5. Daniel Ladin's and David Fivenson's study hyupothesis that T cell activation occurs at the site of capsular formation and that peripheral blood lymphocytes have the same oligocloanality.

6. Howard Smith's study on indiciduals who are being explanted and claims to be seeing differences in some biomarkers levels.

7. Marianne Frieri"s clinical immunology focusing on cytokine and growth factor assessment in breast implant patients.

8. Robert Winchester's and Jane Morse's characterization on the clinical features, auto-antibody profile, lymphocyte phenotypes, and HLA groups of women who are symptomatic post implant.

9. Nemecek Young's clinical research with emphasis on immunology and genetics.

10. Sudha Agarwal's and Marc Liang's study on immune response to silicone implants.

11. John Varga's clinical studies.

12. Jeffrey Brown's rupture detection via MRI.

13. M.A. Atassi's clinical immunology and animal studies of the immune system.

CITE: DCC 267011492 - 267011512.

Document #548
10/19/92
ACKNOWLEDGEMETN OF NEED FOR TESTING
COHESIVENESS - LIQUID COMPONENT OF GEL
KNOWLEDGE OF SYSTEMIC DISEASE
TESTING

Minutes of the Substantial Risk Evaluation committee Meeting. The committee considered the risk associated with D4 and determined that the single high dose had a toxic effect on the tested animals and therefore the other observations are not necessarily indicative of an immune system effect, insufficient data is available to determine a dose-response relationship but there is no reason to suspect that actual exposure to D4 would cause the effects noted, the method of exposure in this study is not expected in real-world situations so the risk of these results being seen in actual exposed populations is slight, and even if people exposed to D4 had similar effects as noted in the study there is no substantial risk because the effects would be transient or reversible and not result in serious effects.

CITE: DCC 281061443 - 281061450, Exhibit 47 to Zimmer Deposition.

Document #549
12/31/92
ACKNOWLEDGEMENT OF NEED FOR TESTING
CONCEALING FROM FDA
FRAUD/MISREPRESENTATION
GEL MIGRATION
KNOWLEDGE OF GEL BLEED
KNOWLEDGE OF LIQUID SILICONE DANGERS
KNOWLEDGE OF SYSTEMIC DISEASE
MISCELLANEOUS
MISCELLANEOUS - LOBBYING
RUPTURE
TESTING
TISSUE REACTION

The Committee on Government Operations (John Coyners, Chairman, Henry Waxman, et al.) writes a report which includes a scathing critique of the FDA's failed regulation of silicone breast implants while ignoring their own scientists recommendations and the manufacturers' failure to do any long term safety studies. Silicone breast implants should have been banned due to lack of safety evidence in all manufacturers PMA's. The article covers all areas of this issue.
CITE: PSSC Medical Articles CD, J 3968 - 4022.

Document #550
12/09/92
COHESIVENESS - LIQUID COMPONENT OF GEL
KNOWLEDGE OF SYSTEMIC DISEASE
MISCELLANEOUS - ORGANIZATIONAL SURVEY

Bey memo regarding industry associations, silicone health council (SHC) history, SHC/GSPA meeting objectives - D4 program, Dow Corning position SCH/GSPA meeting November 9012, 1992 - D4 program, global silicone producers association - committee chairs and current members, and SCH/GSPA meeting results - D4 program.

The Silicone Health Council was founded in the mid-1970's by Dow Corning, General Electric and Union Carbide. It was managed via the Industrial Health Foundation at the University of Pittsburgh. Wacker Silicones and Rhone Poulenc joined SHC in the 1970's. In the 1980's, SHC was affiliated with SOCMA, Wm. Smock, Director. In the 1990's, Shin-Etsu Chemical, PCR, Huls, and Goldschmidt joined SHC.
CITE: DCC 17003711 - 17003719

Document #551
01/07/93
COHESIVENESS - LIQUID COMPONENT OF GEL
KNOWLEDGE OF SYSTEMIC DISEASE
MISCELLANEIOUS - COMPLICATIONS
TESTING

Zellner, Dow Corning, memo to Area S&T Directors regarding updates on D4 studies. Zellner states that studies indicate that D4 is safe for the use as a cosmetic ingredient, D4 has a very low toxicity level and that Dow Corning retain the Industrial Hygiene Guideline of 10 ppm for D4 and D5. Zellner insists that these studies were conducted by an independent group of scientists.
CITE: DCC 17005456 - 17005457,

Document #552
03/09/93
TESTING

Paul Klykken, Galbraith, Woodhiser, Duwe, Mudgett, Nash and Malczewski, Dow Corning, report which duplicates an original study performed by Dr. John O. Naim of University of Rochester. Both studies show that silicone is not biologically inert and therefore can cause autoimmune response.
CITE: DCC 267010511 - 2670010530. DUPLICATE: DCC 260000234 - 260000251.

Document #553
03/22/93
TESTING
KNOWLEDGE OF SYSTEMIC DISEASE

FDA: An FDA Talk Paper references two studies that show silicone gel can act as an antibody adjuvant. This supports the causal relationship between silicone gel-filled breast implants and autoimmune disorders.
CITE: BMS 68289 - 68291

Document #554
04/21/93
CONCEALING FROM FDA

Jim Jenkins, general counsel to Dow Corning, letter to Dr. Charles Vinnik agreeing to indemnify him whenever you are named as a defendant in lawsuits related to Dow Corning's silicone gel-filled breast implants, except for claims of malpractice arising from surgery.... We are extending this indemnification to you because of the historical role you have played with respect to our products. In turn, you have agreed to cooperate and work together with us in defending this litigation."
CITE: DCC 80071933 - 80071934, Exhibit to Duel Deposition, Exhibit 116 to Burda Deposition, and Exhibit to MDL Rathjen Deposition.

Document #555
06/14/93
ACKNOWLEDGEMENT OF NEED FOR TESTING
KNOWLEDGE OF SYSTEMIC DISEASE
MISCELLANEOUS - COMPLICATIONS
TESTING
TISSUE REACTION

Study by Crofoot, Kolesar and Evans regarding an acute and repeated dose inhalation toxicity study with Dow Corning Z-6228 silane in albino rats.

The results of this study indicate that Dow Corning Z-6228 most likely will not present a significant acute inhalation hazard. However, repeated exposures may cause injury of respiratory tract under the conditions of this study. It is recommended that further toxicological studies be conducted to investigate the effects of long-term exposure. CITE: DCC 411000178 - 411000230 (Temporary Dow Corning Bates Number 178 -230); Exhibit 7 to Bejarano Deposition; Exhibit 6 to Bey Deposition, and Exhibit 22 to Zimmer Deposition.

Document #556
07/20/93
ACKNOWLEDGEMENT OF NEED FOR TESTING
KNOWLEDGE OF SYSTEMIC DISEASE
MISCELLANEOUS - COMPLICATIONS
TESTING
TISSUE REACTION

Study by Kolesar, Hoffman, Crofoot, Kowalski. Siddiqui, Evans and Groh regarding a two-week repeated dose inhalation toxicity study of hydrogen chloride and selected chlorosilanes in albino rats.

The results of this study showed no differences between gaseous hydrogen chloride and Me3SiC1, Me3SiC13, and MeSiC13. However, microscopic examination revealed mineralization in the kidneys of females exposed to HSiC13. Whether or not this lesion represents an earlier age-related predisposition to development is not known.
CITE DCC 411000141 - 411000157; Exhibit 6 to Bejarano Deposition; Exhibit 7 to Bey Deposition, and Exhibit 23 to Zimmer Deposition.

Document #557
09/01/93
TESTING
KNOWLEDGE OF GEL BLEED
KNOWLEDGE OF SYSTEMIC DISEASE

Malczewski, Woolhiser, Mudget, Duwe, Galbraith, Nash and Klykken, Dow Corning, report on "A Humoral Adjuvancy Study In The Rat Of Dow Corning Silicone Gel (Q7-2159a) Preparations And Mammary Gel Bleed." All three sheared mammary gel/BSA preparations demonstrated comparable antibody responses to the positive FCA/BSA control and were significantly greater than that of the non-adjuvant control at 4, 6, and 8 weeks post-immunization. The ability of sheared silicone gel preparations to elicit an adjuvant response does not appear to be a preparation-dependent phenomenon under the conditions of this assay. The adjuvancy potential of mammary gel may not be primarily dependent on the preparation technique. Mammary gel bleed did not elicit an adjuvant response following i.m. administration. The antibody levels generated from this group were equivalent to the non-adjuvant control at all time points measured.
CITE: OOT 48639 - 48655, Exhibit 9 to Klykken deposition in Harris County.

Document #558
11/24/93
CONCEALING FROM FDA
FRAUD/MISREPRESENTATION
MISCELLANEOUS - RECKLESS/CONSCIOUS DISREGARD
TESTING

Study by Busey titled "Audit Report For Dow Corning Corporation Project Number 7088 - A Life-time Implant Study With Dow Corning Q7-2159A In Rats." The raw data did not appear to have been reviewed in a timely fashion. Deficiencies were detected in the accountability and identification of the animals on study. Raw data was deleted for no apparent reason. Records for the receipt, distribution and archiving of the control article were not present or were incomplete. Records for the transfer of samples, namely blood samples, within the laboratory were not present. Some of the maintenance records for the balances used on this study were not present. The printed protocol and its amendments were incomplete with regard to identifying personnel assigned to the study, specifically the current study director and pathologist.
CITE: DCC 411000615 - 411000765, Exhibit 10 to Bey Deposition, Exhibit 45 to Zimmer Deposition.

Document #559
01/25/94
CONCEALING FROM FDA
FRAUD/MISREPRESENTATION
MISCELLANEOUS - RECKLESS/CONSCIOUS DISREGARD
TESTING

Study by Busey titled "Audit report For Dow Corning corporation Master Schedule Number M8616-0 EPL Project Number 287-005-Biodurability And Tissue Compatibility Of Optimized 55- and 70- durometer H.P. Elastomers."

No data were present documenting how or where the control samples of each test material were selected and stored control samples were inconsistently used. Some samples were not tested within 48 hours of implant retrieval as specified by the protocol. The test material receipt log does not document the receipt of the DeMattia Bars. There are no precise test article accountability records. There were several inconsistencies among the daily observations, veterinary records and material removed records concerning the loss and re-implantation of implants. The animal daily observation records indicate that daily observations were not recorded after 9/16/87 as specified by the protocol. No dogs were sacrificed at the 6 month interval. There were no environmental records. There were no raw data documenting the histologic preparation of the capsule tissue collected at necropsy. No raw data were present documenting the collection or preparation of the tissue samples for transmission electron microscopy. CITE: DCC 411000580 - 411000614, Exhibit 11 to Bey Deposition, Exhibit 46 to Zimmer Deposition.

Document #560
05/25/94
TESTING
TISSUE REACTION

Study by Kolesar, Evans, Hoffman, Siddiqui and Heffel regarding a 14 day repeated dose inhalation toxicity study of Dow Corning X1-6145A additive in albino rats.

No apparent treatment-related clinical signs were observed in animals exposed to 50 ppb of the test material. Statistically significant decreases in body weight were observed in body weight were observed in males exposed to 100 and 200 ppb and females exposed to 200 ppb. Relative liver, kidney, and adrenal weights were increased in males in the 200 ppb group. Also, relative liver weights were increased in females in the 200 ppb group. All lesions in the lung and other organs examined microscopically were considered agonal or spontaneous and unrelated to test article exposure.
CITE: DCC 411000001 - 41000140; Exhibit 8 to Bey Deposition, Exhibit 8 to Bejarano Deposition, and Exhibit 24 to Zimmer Deposition.

Document # 561
06/29/94
FRAUD/MISREPRESENTATION
MISCELLANEOUS - RECKLESS/CONSCIOUS DISREGARD
TESTING

Mast, letter to Bejarano regarding the inappropriate actions he took in connection with his responsibilities in Dow Corning's Health and Environmental Sciences Laboratory; four animal studies; tissue taken from one particular animal and characterized the tissue as being taken from other animals. Bejarano's early retirement has effectively positioned him to avoid the severe disciplinary actions warranted by his misconduct. Dow Corning cannot overlook the harm that has been done to it and people who depend upon it.
CITE: BEJ 393, Exhibit 15 to Bejarano Deposition

Document #562
08/15/94
CONCEALING FROM FDA
FRAUD/MISREPRESENTATION
TESTING

Dow Corning study titled "A Chronic Implant Study in Rats with Dow Corning Q7-2423 and Q7-2551 Elastomers: Audit of Pathology Materials" by Experimental Pathology Laboratories, Inc. The report states:

"The results of the initial slide/block comparison of 20% of the animals revealed several identification discrepancies between the slides and blocks and several slides with missing blocks."

"This audit revealed several discrepancies in the conduct of the histology phase of the study."

"The detailed findings from the audit of the blocks and slides and supporting documentation are presented in Appendix A. In addition to the cutting of duplicate slides, a variety of other discrepancies were noted in the identification and histologic preparation of the slides on this study.
CITE: DCC 411000769 - 411000965, Exhibit 4 to Bey Deposition

All documents may be ordered from the National Breast Implant Depository in Birmingham, Alabama.