Smoke Fire Documents 501

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.” (emphasis added).

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. Dow Corning Trial Exhibit List Abstracts

PENDLETON/PSC Attorney Work Product/Privileged & Confidential

----------------------------

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.” (emphasis added).

CITE: KMM 451517 - 451525. Dow Corning Trial Exhibit List Abstracts

PENDLETON/PSC Attorney Work Product/Privileged & Confidential

----------------------------

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. Dow Corning Trial Exhibit List Abstracts

PENDLETON/PSC Attorney Work Product/Privileged & Confidential

----------------------------

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.” (emphasis added).

CITE: KKE 1315. Dow Corning Trial Exhibit List Abstracts

PENDLETON/PSC Attorney Work Product/Privileged & Confidential

----------------------------

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. Dow Corning Trial Exhibit List Abstracts

PENDLETON/PSC Attorney Work Product/Privileged & Confidential

----------------------------

Document #506

10/17/90

SHELL STRENGTH - THICKNESS

MISCELLANEOUS - RECKLESS/CONSCIOUS 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. Dow Corning Trial Exhibit List Abstracts

PENDLETON/PSC Attorney Work Product/Privileged & Confidential

----------------------------

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. Dow Corning Trial Exhibit List Abstracts

PENDLETON/PSC Attorney Work Product/Privileged & Confidential

----------------------------

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. Dow Corning Trial Exhibit List Abstracts

PENDLETON/PSC Attorney Work Product/Privileged & Confidential

----------------------------

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.” (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.” Dow Corning Trial Exhibit List Abstracts

PENDLETON/PSC Attorney Work Product/Privileged & Confidential

----------------------------

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. Dow Corning Trial Exhibit List

Abstracts

PENDLETON/PSC Attorney Work Product/Privileged & Confidential

----------------------------

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. Dow Corning Trial Exhibit List Abstracts

PENDLETON/PSC Attorney Work Product/Privileged & Confidential

----------------------------

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 14^th 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. Dow Corning Trial Exhibit List Abstracts

PENDLETON/PSC Attorney Work Product/Privileged & Confidential

----------------------------

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. Dow Corning Trial Exhibit List Abstracts

PENDLETON/PSC Attorney Work Product/Privileged & Confidential

----------------------------

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. Dow Corning Trial Exhibit List Abstracts

PENDLETON/PSC Attorney Work Product/Privileged & Confidential

----------------------------

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. Dow Corning Trial Exhibit List Abstracts

PENDLETON/PSC Attorney Work Product/Privileged & Confidential

----------------------------

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. Dow Corning Trial Exhibit List Abstracts

PENDLETON/PSC Attorney Work Product/Privileged & Confidential

----------------------------

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. Dow Corning Trial Exhibit List Abstracts

PENDLETON/PSC Attorney Work Product/Privileged & Confidential

----------------------------

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. Dow Corning Trial Exhibit List Abstracts

PENDLETON/PSC Attorney Work Product/Privileged & Confidential

----------------------------

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. Dow Corning Trial List Exhibit List Abstracts

PENDLETON/PSC Attorney Work Product /Privileged & Confidential

----------------------------

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. Dow Corning Trial Exhibit List Abstracts

PENDLETON/PSC Attorney Work Product/Privileged & Confidential

----------------------------

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. Dow Corning Trial Exhibit List Abstracts

PENDLETON/PSC Attorney Work Product/Privileged & Confidential

----------------------------

Document #522

05/01/91

ACKNOWLEDGEMENT OF NEED 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. Dow Corning Trial Exhibit List Abstracts

PENDLETON/PSC Attorney Work Product/Privileged & Confidential

----------------------------

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. Dow Corning Trial Exhibit List Abstracts

PENDLETON/PSC Attorney Work Product/Privileged & Confidential

----------------------------

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. Dow Corning Trial Exhibit List Abstracts

PENDLETON/PSC Attorney Work Product/Privileged & Confidential

----------------------------

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. Dow Corning Trial Exhibit List Abstracts

PENDLETON/PSC Attorney Work Product/Privileged & Confidential

----------------------------

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. Dow Corning Trial Exhibit List Abstracts

PENDLETON/PSC Attorney Work Product/Privileged & Confidential

----------------------------

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. Dow Corning Trial Exhibit List Abstracts

PENDLETON/PSC Attorney Work Product/Privileged & Confidential

----------------------------

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. Dow Corning Trial Exhibit List Abstracts

PENDLETON/PSC Attorney Work Product/Privileged & Confidential

----------------------------

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. Dow Corning Trial Exhibit List Abstracts

PENDLETON/PSC Attorney Work Product/Privileged & Confidential

----------------------------

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. Dow Corning Trial Exhibit List Abstracts

PENDLETON/PSC Attorney Work Product/Privileged & Confidential

----------------------------

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 Dow Corning Trial Exhibit List Abstracts

PENDLETON/PSC Attorney Work Product/Privileged & Confidential

----------------------------

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 Dow Corning Trial Exhibit List Abstracts

PENDLETON/PSC Attorney Work Product/Privileged & Confidential

----------------------------

Document #533

02/11/92