1. Breast Implants Historical Origins Dow legal case Materials Design Evolution Structural Analysis Regulatory Issues State of the Art

2. Historical Origins 1890: paraffin wax injections 1920: fat transplants from abdomen, buttocks 1940: Japanese prostitutes use silicone injections 1950: polyvinyl sponge implants 1962: first silicone implant 1962-1964: clinical trials 1964: Dow Corning publicly markets implants 1973: 2 nd generation implants –Thin shells, thin gel 1985: 3 rd generation implants –Thick textured shell w/ barrier layer www.mentorcorp.com

3. Breast implants on trial http://www.pbs.org/wgbh/pages/frontline/implants/cron.html 1960s First silicone breast implants are developed by plastic surgeons 1962 First silicone implant is implanted FDA enacts the Medical Devices act-- but silicone implants are grandfathered in as medical devices 1977 First lawsuit involving silicone implants. Woman receives $170,000 from Dow Corning- the case receives little publicity

4. 1980s Ralph Nader's Public Citizen Health Research Group, Washington, D.C. sends out warning signals that silicone breast implants cause cancer. January 1982 FDA proposes to classify silicone breast implants into a Class III category which would require manufacturers to prove their safety in order to keep them on the market. 1984 Stern vs Dow Corning, San Francisco. Case wins on many internal Dow Corning documents that had been discovered in a Dow storage area by attorney Dan Bolton. Maria Stern's systemic autoimmune disease is found by a jury to be caused by her silicone breast implants. Bolton introduces the silicone-induced problems for the first time in court, with "experts" that theorize the silicone-immune system connection. After a monthlong trial, the jury awards Maria Stern $211,000 in compensatory damages and $1.5 million in punitive damages. The evidence is sealed by a court order. June 1988 Six years after the 1982 proposal, FDA classifies the implants into Class III. Premarket Approval Applications from silicone breast implant manufacturers are due by July 1991. The PMA's must prove affirmatively, with valid scientific data evaluated by the FDA, that their devices are safe and effective. After the PMA's are submitted by the manufacturers, the FDA has 180 days to evaluate the safety data.

5. 1990-1991 December 1990 Program on the dangers of silicone breast implants airs on "Face to Face with Connie Chung. ” Congressional hearing headed by Representative Ted Weiss deals with the safety of silicone breast implants. This hearing also discusses the fact that not all the information that the manufacturers have are available for public scrutiny due to a court order from the Stern verdict. July 1991 Dow Corning releases 329 studies to FDA. Toole vs Baxter, Alabama. Jury awards the largest settlement so far, $5.4 million, to Brenda Toole. Toole, who shows only preliminary symptoms of systemic autoimmune problems, nevertheless had silicone in her lymphatic system according to plaintiffs' witnesses and thus an increased risk of developing an autoimmune disease. September-November 1991 FDA concludes that the silicone breast implant manufacturers' safety data does not prove the devices are safe or harmful. The FDA brings together its General and Plastic Surgery Devices Panel to review all of the safety data from the manufacturers. The panel is to advise FDA as to what to tell the public about the safety and effectiveness of the silicone breast implants based on the PMA's. The panel is composed of a broad range of experts, including representatives from the fields of plastic surgery, oncology, epidemiology, immunology, radiology, pathology, gynecology, toxicology, sociology, biomaterials, psychology... The panel hearing rejects the data from Dow Corning, Mentor, McGhan, and Bioplasty, concluding there is not sufficient data about the risks and benefits of the devices. The panel recommends the devices stay on the market temporarily and with limited access. The need for more safety data is stressed.

6. 1991- 1992 December 1991 Hopkins vs Dow Corning, San Francisco. The largest award yet, $7.3 million, is given to Mariann Hopkins whose mixed connective- tissue disease is linked to her ruptured silicone breast implants. The lawyer for the case, Dan Bolton, wins the suit with the help of internal memos and studies from the Stern lawsuit, in addition to new studies he recently obtained from Dow. Mr. Bolton gives several of the internal documents to the FDA which has never seen the documents before. 137 individual lawsuits have been filed against Dow. January 1992 FDA Commissioner, David Kessler, calls for a voluntary moratorium on the distribution or implantation of silicone breast implants until the FDA and the advisory panel have an opportunity to consider newly available information. The manufacturers agree. February 1992 The class action lawsuit is filed in Cincinnati by Stan Chesley. The hope is to compensate women at a faster rate than filing individual lawsuits. Dow Corning CEO, Lawrence Reed, is replaced by Keith McKennon. The General and Plastic Surgery Devices Panel reconvenes to review the new information regarding the safety of silicone breast implants. The panel recommends that the further use of implants be limited for reconstruction only and that women receiving the implants participate in scientific protocols and that epidemiologic studies be conducted to assess the risk of autoimmune disease. The panel concludes that no causal link has been established between autoimmune disease and silicone breast implants. Many of the Dow Corning internal memos are released to the public.

7. 1992-1993 March 1992 Dow Corning leaves the silicone breast implant business as do Bristol-Myers Squibb and Bioplasty. McGhan and Mentor will still manufacture breast implants. Dow sets up a fund for further research into the safety of breast implants. April 1992 Dr. Kessler lifts the moratorium on silicone breast implants. The only women allowed to receive implant surgery are those undergoing breast reconstruction. All of the implant recipients must become part of a scientific protocol. December 1992 Johnson vs Bristol-Myers Squibb, Houston. Pamela Jean Johnson wins $25 million, $5 million actual damages and $20 million punitive damages in a case argued by Texas attorney John O'Quinn. A jury finds Ms. Johnson's ruptured silicone implants were linked to her mixed connective tissue disease, auto-immune responses, chronic fatigue, muscle pain, joint pain, headaches, and dizziness. Expert witnesses and lawyers admit her symptoms amount to "a bad flu.” To date 3,558 individual lawsuits have been filed against Dow Corning. June 1993 Dick Hazleton becomes CEO. By year's end 12,359 individual lawsuits have been filed against Dow Corning.

8. 1994 March 1994 A Houston jury awards three women a total of $27.9 million against 3M, $15 million in punitive, $12 million in compensatory damages for illness. The lawyer arguing the case against 3M is John O'Quinn. The three women suffered from either atypical lupus, neurological impairment, and a "silicone induced" autoimmune problem. The class action suit is finalized by manufacturers with Dow Corning being the largest contributor. The other contributors include Baxter, Bristol-Myers Squibb/MEC, 3M. It is the largest class action settlement in history. Manufacturers claim there is no scientific evidence linking silicone breast implants with autoimmune diseases. There are set monetary amounts that will be awarded to women with specific medical conditions. No requirements are needed to prove implants are the cause of their ailments. Women will be allowed to drop out of the settlement. Companies can also opt out if too few women register claims. April 1994 Preliminary approval to class action by Judge Pointer. Clears the way for women to start applying for claims in the settlement. Final approval of class action/global settlement from Judge Pointer in September. June 1994 The Mayo Clinic study is published in the New England Journal of Medicine, which finds no increased risk of connective-tissue disease or other disorders that were studied in women with silicone implants. December 1994 By this date 19,092 individual lawsuits have been filed against Dow Corning.

9. 1995 1995: The American College of Rheumatology issues a statement saying the evidence is "compelling" that implants did not cause systemic disease. May 1995 Dow Corning files for Chapter 11 bankruptcy. Dow is facing 20,000 lawsuits, some with multiple plaintiffs and about 410,000 potential claims that have been filed in the global settlement. The bankruptcy essentially halts all litigation. June 1995 About 440,000 women have registered in the global settlement. About 70,000 can be immediately compensated. The Harvard Nurses Epidemiologic Study is published in the New England Journal of Medicine. This finds no increased risk of connective-tissue disease or certain signs and symptoms of connective-tissue disease in women with silicone implants. October 1995 Mahlum vs Dow Chemical, Reno. This is the first case where Dow Chemical, the parent company of Dow Corning, is the sole defendant. Charlotte Mahlum is awarded $3.9 million in compensatory damages and $10 million in punitive damages. About 13,000 breast implant lawsuits are pending against Dow Chemical. December 1995 More than 20 (non-case report) studies and abstracts have come out in the U.S. and internationally, all failing to support a causal relationship between silicone implants and a variety of auto-immune related illnesses.

10. 1996-1997 April 1996 Two Federal judges in New York appoint an impartial, expert panel to review the scientific issues involved in breast implant lawsuits. This rare move will influence judges throughout the country. September 1996 The California Court of Appeal upholds a decision dismissing Dow Chemical and Dow Corning from 1,800 breast-implant lawsuits. December 1996 Oregon Federal Judge Robert E. Jones, after input from a panel of impartial scientists, rules that plaintiffs' lawyers cannot present evidence that silicone implants caused disease because it is scientifically invalid. He dismisses 70 claims, shocking the litigation community. Sam C. Pointer, the Alabama judge overseeing all federal implant cases, appoints his own panel of scientific experts who are not connected to implant litigation. January 1997 The American Academy of Neurology reviews existing silicone implant studies and reports that "existing research shows no link between silicone breast implants and neurological disorders.” March 1997 A judge in Michigan rules that the Dow Chemical Company is not liable for the medical problems of hundreds of women in the state. Thus far, some state appellate courts have upheld Dow Chemical's liability and others have not.

11. August 1997 The New York Times reports that implant manufacturers have been winning 80% of cases against them. Nevertheless, a state jury in the first class-action suit finds that Dow Chemical knowingly deceived women by hiding safety information about the silicone in their implants. September 1997 The Journal of the National Cancer Institute publishes a review of scores of medical studies that concludes breast implants do not cause breast cancer. The researchers described the evidence for linking implants to any other disease as "borderline." April 1998 Two large Scandinavian studies fail to show that silicone implants are linked to neurological disease. July 1998 Plaintiffs agree to Dow Corning's offer of $3.2 billion to settle tens of thousands of claims of injury from silicone breast implants. The agreement will let the plaintiffs receive money within a year and also enable Dow Corning to emerge from bankruptcy proceedings. After being asked by the British minister of health to review the safety of silicone implants, a seven-member panel of scientists report no convincing evidence that they cause disease. (The U.K. has never removed silicone implants from the market.) 1997-1998

12. 1998-1999 November 1998 Dow Corning files for bankruptcy reorganization, which includes the $3.2 billion previously agreed-to settlement and offers claimants several payout options. Those who want to cash-out immediately and not file a disease claim will be paid $2,000. This figure can also be combined with $5,000 for implant removal surgery and $20,000 for a ruptured implant. Those who have already filed a disease claim will receive between $10,000 and $250,000 plus any compensation claimed for removal or ruptures. December 1998 After two years and $800,000, a panel of four independent experts appointed by Judge Sam C. Pointer, overseer of implant lawsuits in the Federal courts, concludes that scientific evidence so far has failed to show that silicone breast implants cause disease. Nevada Supreme Court upholds a compensatory damage award of $41 million against Dow Chemical to Charlotte Mahlum for her multiple-sclerosis-like symptoms. Dow Chemical was earlier found liable for helping Dow Corning conceal evidence about the harmful effects of silicone. The court, however, overturns a $10 million punitive award. January 1999 A jury in a Washington Federal court awards $10 million in compensatory damages against Bristol-Myers Squibb Co. to an attorney who claimed her implants caused scleroderma.

13. 1999-2006 Spring 1999 Silicone-gel-filled implants remain off the market in the U.S. pending manufacturer safety studies. They are available only to women who have had or will have breast surgery for a medical condition or have other complications from existing implants, and only if they agree to be part of a scientific protocol, or study. June 1999 The Institute of Medicine releases a 400-page report prepared by an independent committee of 13 scientists. They conclude that although silicone breast implants may be responsible for localized problems such as hardening or scarring of breast tissue, implants do not cause any major diseases such as lupus or rheumatoid arthritis. The Institute of Medicine is part of the National Academy of Sciences, the nation's most prestigious scientific organization. Congress had asked the Institute to set up the committee. The committee did not conduct any original research; they examined past research and other materials, and conducted public hearings to hear all sides of the issue. 2000- Saline breast implants remain on the market with some known risks (http://www.fda.gov/fdac/features/2000/400_implant.html)http://www.fda.gov/fdac/features/2000/400_implant.html 2004- FDA releases handbook on risks associated with breast implants. Silicone gel-filled breast implant must be PMA-approved to be sold on the market. At this time no manufacturer had a PMA to sell silicone implants. (http://www.fda.gov/cdrh/breastimplants/indexbip.html)

14. Silicone Chemistry Silicones –Broad class –Base structure, polydimethylsiloxane –R 1 and R 2 can be methyl, vinyl, hydrogen or hydroxy groups –n = 3 - 100

15. Gel Structure 10-20% crosslinked silicone –Silicone oil swells silicone shells Lowers shell tensile strength Increases “bleeding”

16. Device Chemistry Silicone Gel –Vary viscosity via crosslinking –Peroxide based crosslinking agent –Dow Silastic II: trimethyl end-blocked dimethyl and methylvinyl polysiloxane Elastomer Shell –contains amorphous silica as reinforcing agent –Barrier coating-silicone copolymer

17. Evolution of Implant Design 1st Generation Implants –1963-1972 –Thick shell wall, viscous gel and Dacron patches –capsular contracture lead to second generation

18. Evolution of Implant Design 2nd Generation Implant –Thin wall and less viscous gel –Low tear strength –Capsular contracture

19. Evolution of Implant Design 3rd Generation Implant –Stronger, thicker shell, more viscous gel and barrier layer Other gel implants –240 styles of breast implants manufactured

20. Requirements Biological Aspects –Toxicology studies –Example-Shell Compatibility between filler and shell Effects of shell surface texture on surrounding tissues Integrity points tested for appropriate resistance to failure Test for: static rupture, fatigue rupture, static impact Mechanical Properties –Cohesiveness of Silicone Gel –Rupture rate of shell –Abrasion properties of shell

21. Structural Analysis of Shell Minimum thickness (pressure vessel) Leak-before-break condition Abrasive Wear

22. Minimum Shell Thickness Spherical pressure vessel (Thin-walled approximation) = 6.2 MPa P = 150 KPa r = 30mm t =.35mm

23. Leak Before Break Condition a c >t Flaw due to injection or suture K IC =1 a c =0.4mm t = 0.35mm Leak before break condition achieved

24. FDA Approval Process 1963: Dow Corning begins selling implants w/o regulation –FDA does not have authority over medical devices yet May 1976: Medical Device Amendments gave FDA control over devices –Implants can remain on market Jun. 1976: breast implants classified as class II device Jun. 1988: breast implants reclassfied as class III device Apr. 1991: FDA requires manufacturer PMAs by July 9, 1991 Jan. 1992: FDA recommends voluntary moratorium to await data –Implants only allowed for FDA studies, not augmentation 1999: FDA finalizes the type of safety data wanted from companies Mar. 2000: approval of Mentor Corporation, McGhan Medical Corporation PMAs

25. Biocompatibility Studies 1992: IEAG – Department of Health, UK –Animal studies show silicones do not affect immune responses –No evidence of increased risk of connective tissue disease 1997: IRG – Independent Review Group, UK –No evidence of abnormal immune response –No link b/t breast implants and connective tissue disease –Claim diseases caused by other factors 2000: Department of Health& Human Services, US –Lack evidence to establish silicone implants cause autoimmune disease –Local complications such as rupture, pain, capsular contracture, disfigurement, infection lead to multiple surgeries and are the primary safety issue

26. Legal issues 1984: jury finds patient ’ s autoimmune disease caused by silicone implants, Dow Corning loses case and pays ~ $2 million 1991: a jury links connective tissue disease to ruptured implants, Dow Corning loses case and pays ~ $7.3 million in damages 1994: largest class action law suit in history against Dow Corning, Medical Engineering Corporation, Baxter

27. What are your thoughts? Are silicone implants safe? Did Dow misinform the public? Should Dow have been bankrupted by class action lawsuit?