When silicone medical devices were under attack: A regulatory leviathan

A quarter century has passed since CBS News correspondent Connie Chung opened her broadcast of Face to Face with Connie Chung with these words: “Most of us know very little about breast implants; we don’t know anything about the dangers.”1 The report that followed sent a wave of fear throughout the nation. Plastic surgeons and their patients were primarily affected, but so was every surgical specialty that used silicone devices. How could breast implant toxicity be the subject of a national news program without focusing on other silicone devices that have provided patient benefits for decades?

In fact, a media focus on breast implants had preceded the December 1990 CBS broadcast by two years. In October 1988, Sidney M. Wolfe, MD, co-founder and then-director of Public Citizen’s Health Research Group, a consumer and health care lobbying organization, predicted a looming epidemic of breast cancers occurring in women with breast implants.2 Dr. Wolfe issued this warning at the same time as the American College of Surgeons (ACS) 1988 Clinical Congress was taking place, October 23–28 in Chicago, IL, so journalists were primed to feature news from the surgical specialties. In reality, little evidence was available to support the assertion that an epidemic was likely, and a 1986 epidemiologic study had, in fact, already demonstrated a modest decrease in breast cancer incidence among women with breast implants.3

This article reviews the history of the use of silicone in medicine and surgery, the debate over the potential risks of silicone breast implants, the U.S. Food and Drug Administration’s (FDA’s) regulatory response, and how increasing government regulation has had a stifling effect on innovation.

History of silicone devices

Silicone polymers were first synthesized in the U.K. in the 1890s and then rediscovered in the 1930s by Corning Glass chemist J. Franklin Hyde, PhD. Because of their remarkable stability at extreme temperatures, the silicones served an essential military role as miracle lubricants permitting aircraft to fly at required altitudes and submarines to reach the depths necessary for survival. Scientists at newly established Dow Corning Corporation stood proud; their handiwork helped make it possible to win World War II within four years.4

Soon after, toxicological studies confirmed that the human body was able to tolerate silicone remarkably well.5 Additional testing showed negligible influence on immune function.6 Peacetime uses began to appear, and, in time, medical applications proliferated. Health care professionals found that syringes and IV tubing coated with silicone functioned better. Implanted silicone catheters remained patent, allowing neurosurgeons to insert a shunt that spared the brains of hydrocephalic infants.7 Today, silicone is ubiquitous throughout the health care environment.

Silicone devices, unlike plastics, display their properties without the need for catalytic activators. Their physical structure varies according to molecular chain length, ranging from liquids to oils to flexible solids. In 1962 a cohesive gel was introduced that permitted the development of mammary implants. This innovation was developed by two Houston, TX, plastic surgeons—Thomas Cronin, MD, and Frank Gerow, MD—and transformed both reconstructive and cosmetic breast surgery.8 Subsequently, silicone gel was used in further medical advances, including testicular implants and non-adherent wound dressings.9

The FDA steps in

The FDA was not assigned jurisdiction over medical devices until the Medical Device Amendments of 1976 to the Federal Food, Drug, and Cosmetic Act were passed. Previously unbeholden to the medical profession, the agency was now required to establish advisory panels responsible for designating risk categories for every device in use. The General and Plastic Surgery Advisory Panel functioned effectively under the chairmanship of the late J. B. Lynch, MD, FACS, then-chair of the department of plastic surgery at Vanderbilt University Hospital and Clinic, Nashville, TN. Dr. Lynch held this position until 1988 when, in the face of increasing allegations of silicone-related disorders, the agency replaced him with Norman Anderson, MD, an internist without surgical experience with implantable devices. Under Dr. Anderson’s leadership, a panel previously dominated by surgeons was expanded to include consumer advocates and industry critics. Trial attorneys sitting in on hearings were encouraged by Dr. Anderson to voice their opinions.10 In a meeting I had with Dr. Lynch soon after these events, he indicated that he believed that what he had witnessed while attending his final hearing was an event that the FDA deliberately staged to send a new message regarding breast implants and, by implication, other silicone devices.

By this time, in addition to the persisting cancer scare, reports of autoimmune diseases occurring in women with breast implants were surfacing. The scene was now set for a major media focus on the issue, commonly believed to be orchestrated by Dr. Wolfe and assisted by Fenton Communications, a public relations firm. On the evening of December 2, 1990, viewers of Face to Face with Connie Chung listened to the experiences of four women with silicone breast implants voice complaints ranging from fatigue to hair loss, total body pain to mouth ulcers. Such was the problem of defining the putative “silicone disease,” but diagnostic criteria were not discussed in any detail in the broadcast.1 Disease claims were confirmed by two “experts”—Canadian chemist Pierre Blais and Tennessee pathologist Douglas Shanklin, MD—both of whom lacked any clinical training or device experience.1 Although CBS producers accepted their testimony at face value, both were later disqualified from providing testimony in American courts.11

Trained as both a physician and a lawyer, FDA Commissioner David A. Kessler, MD, JD, understood the difference between legal and scientific evidence. Attorneys emphasize the evidence that supports their client’s position, whereas scientists must consider all available evidence. Disregarding the recommendations of his own advisory panel and relying on trial testimony that yielded a $7.3 million judgment against Dow Corning, on January 6, 1992, Dr. Kessler called for a moratorium on the use of silicone gel breast implants.12

Dr. Kessler acknowledged during an afternoon television broadcast two days later that very few women were at risk for disease from breast implants. His call for a moratorium elicited an unprecedented rebuke of his agency’s integrity.13 Meanwhile, doubt was effectively cast on the safety of several hundred silicone devices in use at the time. Trial attorneys promptly filed thousands of suits against implant manufacturers. By year’s end, most plastic surgeons in the nation had been named in one or more lawsuits. Plaintiff attorneys were positioned to reap 30 percent to 40 percent of every award declared by a jury or issued in a settlement conference.14

Professional organizations rallied in support of the medical device industry, among them the ACS; the American College of Radiology; the American College of Rheumatology; the American College of Clinical Oncology; the American College of Pathology; and the American Psychiatric Association, whose members recognized an emotional benefit from breast reconstruction surgery. All such pleadings fell on deaf agency ears.

At an FDA hearing soon after the moratorium on silicone breast implants was announced, U.S. Representative Marilyn Lloyd (D-TN), a member of the House Science Committee, asked Dr. Kessler, “How scientific is the FDA’s decision that no woman should have implants put in and no woman should have them taken out?” A breast cancer victim herself, she reminded the commissioner that he had placed unjustified limits on the choices her surgeon, a practicing professional, could offer her for reconstruction.15

Speaking on behalf of the College, ACS Regent Maurice Jurkiewicz, MD, FACS, a plastic and reconstructive surgeon and professor of surgery at Emory University, Atlanta, GA, cautioned the panel not to restrict the benefits of silicone devices for reconstructive surgery, especially for patients who had undergone a full mastectomy. Dr. Jurkiewicz further voiced the College’s strong objection to removing voting rights from the panel’s qualified surgeons who had more experience with implanted medical devices than any of the panelists.16 Meanwhile, manufacturers who had protested the continued chairmanship of Dr. Anderson learned he would be replaced by a distinguished gynecologist, Elizabeth Connell, MD, FACOG. Not until 1999 would silicone devices and, in particular, breast implants receive a full pardon—not from the FDA but instead from the Institute of Medicine (IOM). A panel of 13 medical scientists declared all claims of carcinogenic, teratogenic, mutagenic, and immunologic influence as invalid. Instead the panel affirmed the original toxicology findings that had been discounted by the FDA.17

Regrettably, the IOM’s reprieve came too late for some manufacturers who by then had expended billions of dollars to preserve their commercial viability and appease the demands of America’s litigation industry. Dow Corning was forced into bankruptcy, while several other manufacturers discontinued their medical product lines.18 Implantable device innovation in the U.S. nearly came to a standstill, and for the first time, silicone product development gained traction in Europe and Asia.

The evolution of a leviathan

I had the privilege of serving as a spokesperson for the Plastic Surgery Education Foundation and its ad hoc breast implant research committee during our most intense battles with regulators regarding the safety of silicone breast implants. Consequently, I developed a deep interest in the growth of regulatory power in America, with a specific focus on the role of the FDA. The FDA started as the Bureau of Chemistry in 1906 when it first gained legislative backing in the form of the Pure Food and Drugs Act, but, in time, the agency became an evolving leviathan, controlling access to products worth $1 trillion dollars annually.19

Silicone on TrialFollowing retirement from academic surgical practice, I formalized my interest with a period of graduate study in U.S. political and economic history. One important lesson learned: government regulation is a political process and not a scientific one, even when a product is based on technology.

Given the reality that some people are inherently risk-averse while others are remarkably tolerant of potential danger, whose perception of risk should take precedence? The challenge for policymakers and regulators is to find a balance between risk estimates and statutory limits, product innovation and market barriers, and between unanticipated outcomes and rational compensation for avoidable hazards. Meanwhile, no one should be surprised by the inevitable conflicts that arise between risk-taking innovators and regulators who are mandated by the electorate to avoid risk.

Regulatory power has grown in the U.S. in response to isolated events featuring, at times, negative outcomes. A 1938 revision of the original Pure Food and Drugs Act immediately followed the elixir sulfanilamide tragedy when a small company inexcusably blended the compound with a toxic glycol instead of a harmless glycerol, resulting in the death of 107 children. After several major pharmaceutical houses declined to lease a new German sedative because of inadequate testing, a little-known company known for its medicated salves elected to bring thalidomide to the U.S. market, resulting in 17 deformed newborns. Amendments to the 1938 law soon followed, replacing required premarket notification with mandated premarket approval of all drugs. And because of a single unethical surgeon and his business partners who lied about the safety of their intrauterine device, efforts to pass medical device amendments advanced quickly to become law in 1976.20

Impact on surgical innovation

Today’s surgical innovator must be prepared for an encounter with regulators. Whether it be an improved procedure, a new device, or an untested treatment regimen, regulatory approval will require justification based on measured outcomes. Surgeons of all stripes, including residents in training, are advised to learn more about the origins and expanding power of regulation, how the FDA is organized and what it requires from innovators, and why significant change may not come quickly or easily—certainly not without new legislation to support it.

To this day, the FDA has yet to accept the conclusions of the IOM panel. In fact, its website continues to list autoimmune disease as a possible risk of breast implants, even though the number of epidemiologic studies that disprove any disease linkage now exceeds 30.21 It took seven more years of filing applications, conducting studies, monitoring results, responding to demands for more data, resolving deficiency reports, testifying at hearings, receiving denials, resubmitting applications, gaining advisory panel support, negotiating label requirements, and accepting limitations on product use before the two remaining manufacturers received conditional approval to market a full line of devices for reconstructive and cosmetic surgery in November 2006.22

Regulation does not have to function in this manner. The evaluation and approval of medical devices in Europe does not involve government regulators directly. Instead, “notified bodies” test and certify according to established standards. Silicone devices in Europe now benefit from polymer innovations a decade ahead of the U.S., where a polymer change requires a new filing that starts the approval clock ticking all over again. The European Medicines Agency (EMA) is considered lean and efficient by the drug industry. Furthermore, unlike the FDA, the EMA maintains a close liaison with medical professionals and draws willingly from their clinical expertise.23

There is no shortage of inventive proposals for correcting the problems that plague the FDA, many of them coming from the agency’s previous leadership.24 For example, former FDA Commissioner Andrew von Eschenbach, MD, makes a strong case for accelerated drug approvals based on safety trials alone, reserving efficacy determination for post-market monitoring of the same test subjects.25 For devices, Henry I. Miller MD, MSc, founding Director of the FDA Office of Biotechnology, urges adoption of the nationally recognized and proven testing laboratory model, best exemplified by the highly successful Underwriters Laboratory, Inc.26

But these revisions cannot become reality without congressional action. Consider, for example, a bill now under debate, the Promise for Antibiotics and Therapeutics for Health (PATH) Act. With bipartisan sponsorship, it provides for accelerated approval of new antibiotics for an emerging class of resistant organisms. Any endeavor that promises new antibiotics is a noble cause but there are outspoken critics of the measure. Readers of this article are now primed to monitor the bill’s progress and learn who supports and who opposes the legislation.27

Meanwhile, surgical specialty organizations are free to maintain their preferred relationship with regulators. The American Academy of Orthopaedic Surgeons represents a model for sustaining a productive liaison with the FDA, and plastic surgeons have learned to pursue a more proactive stance with the agency. Expanding on the advisory panel format, the American Society of Plastic Surgeons and its foundation, The Plastic Surgery Foundation, remain vigilant regarding problems involving the use of devices. These entities seek advice from their own advisory panels and, on their own initiative, forward relevant information to the FDA.

One such problem is the risk that never seems to go away—cancer following breast implantation. Beginning in 1998, reports of a lymphoma developing in the fibrous capsule surrounding breast implants first appeared.28 None are cancers involving the breast gland itself but instead anaplastic large cell lymphoma (ALCL). Without an exact number of women with implants worldwide (estimates range from 10 million to 20 million), an incidence rate cannot be precisely determined. The FDA places the risk of ALCL at two or three per million.29

Fortunately, the FDA has taken a more measured view than its 1991 reaction to unsubstantiated breast implant linked diseases by stating, “The FDA believes that women with breast implants may have a very low but increased risk of developing ALCL adjacent to the breast implant.”30 Because these tumors are believed to be a manifestation of chronic inflammation and not specific to silicone, it is not unreasonable to expect they might arise in capsules known to form around any implanted device, so there is ample motivation for all surgical specialties to monitor the problem and maintain a liaison with the FDA.31

In the face of power, we are advised to speak truth. When the opponent is a government agency, success requires a listener willing to act on the basis of scientific principle, not political bias. James Madison said it another way: “In framing a government to be administered by men over men, first enable the government to control the governed; then oblige it to control itself.32

Note

For more information, see Silicone on Trial: Breast Implants and the Politics of Risk, by Jack C. Fisher, The Sager Group, La Jolla CA, 2015.

Residency program directors wanting their residents to learn more about regulation in America including policies for drug and device approval should contact Dr. Fisher for access to discounted copies at Jfisher37@icloud.com.


References

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  2. Reinberg S. FDA panel’s breast implant ruling puzzles, pleases. HealthDay News. April 2005. Available at: http://consumer.healthday.com/public-health-information-30/food-and-drug-administration-news-315/fda-panel-s-breast-implant-ruling-puzzles-pleases-525160.html. Accessed October 16, 2015.
  3. Deapen DM, Pike MC, Casagrande JT,Brody GS. The relationship between breast cancer and augmentation mammaplasty: An epidemiologic study. Plast Reconstr Surg. 1986;77(3):361-368.
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  6. Bradley SG, White KL Jr., McCay JA, et al. Immunotoxicity of 180 day exposure to polydimethylsiloxane (silicone) fluid, gel and elastomer and polyurethane disks in female B6C3F1 mice. Drug Chem Toxicol.1994;17(3):221-269.
  7. LaFay HA. A father’s last-chance invention saves his son. Reader’s Digest. January 1957:29-32.
  8. Cronin TD, Gerow FJ. Augmentation mammoplasty: A new “natural feel” prosthesis. Transections of the Third International Congress of Plastic Surgery, Amsterdam. Excerpta Medical. 1964:41-49.
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  10. Transcript of proceedings, FDA Advisory Panel for General and Plastic Devices, November 22, 1988.
  11. Casetext Inc. Hall v. Baxter Healthcare Corp. Available at: https://casetext.com/case/hall-v-baxter-healthcare-corp. Accessed October 16, 2015.
  12. Kessler DA. Food and Drug Administration. U.S. Department of Health and Human Services. HHS News. No. P92-11. Statement on Silicone Gel Breast Implants. 1992.
  13. Transcript of Diane Rehm Show, interview of David Kessler on Jan. 8, 1992. Diversified Reporting Services, Washington, DC.
  14. Nocera J. Fatal Litigation. Fortune. October 16, 1995, 137-140.
  15. Cimons M. Silicone implant maker proposes study: Human trials to answer safety questions could forestall ban on the device. Los Angeles Times. February 20, 1992. Available at: http://articles.latimes.com/1992-02-20/news/mn-3560_1_silicone-implant. Accessed October 16, 2015.
  16. Statement of ACS Regent Maurice J. Jurkiewicz before FDA Advisory Panel for General and Plastic Surgery Devices, November 12, 1991.
  17. Institute of Medicine (US);Grigg M, Bondurant S, Ernster VL, Herdman R, editors. Information for Women About the Safety of Silicone Breast Implants. Washington , DC: National Academies Press; 2000.
  18. Nocera J. Dow Corning succumbs. Fortune. October 30, 1995, 154-155.
  19. Miller HI. Sick Process. Hoover Digest. 1999. Available at: www.hoover.org/research/sick-process. Accessed October 23, 2015.
  20. Bernstein DE. Review: The breast implant fiasco. California Law Rev. 1999;87(2):457-510.
  21. Medical Device Amendments of 1976. 94th Congress. May 28, 1976. Available at: www.gpo.gov/fdsys/pkg/STATUTE-90/pdf/STATUTE-90-Pg539.pdf. Accessed October 16, 2015.
  22. S. Food and Drug Administration. 2006 Device Approvals. Available at: www.fda.gov/MedicalDevices/ProductsandMedicalProcedures/DeviceApprovalsandClearances/Recently-ApprovedDevices/ucm073317.htm. Accessed October 23, 2015.
  23. Perkins LL, Clark BD,Klein PJ, Cook RR. A meta-analysis of breast implants and connective tissue disease. Ann Plast Surg. 1995;35(6):561-570.
  24. Fisher JC. Silicone on Trial: Breast Implants and the Politics of Risk. New York, NY: The Sager Group; 2015.
  25. von Eschenbach A. Medical innovation: How the U.S. can retain its lead. Wall Street Journal. February 14, 2012. Available at: www.wsj.com/articles/SB10001424052970203646004577215403399350874. Accessed October 16, 2015.
  26. Miller H. To America’s Health: A Proposal to Reform the Food and Drug Administration. Stanford, CA: Hoover Institution Press; 2000.
  27. Promise for Antibiotics and Therapeutics for Health (PATH) Act S. 185, 114th Congress. 2015. Available at: www.congress.gov/bill/114th-congress/senate-bill/185/text/. Accessed October 16, 2015.
  28. The Plastic Surgery Foundation. PROFILE: Investigating Breast Implant Associated ALCL. Available at: www.thepsf.org/research/clinical-impact/profile-investigating-breast-implant-associated-alcl.htm. Accessed October 23, 2015.
  29. S. Food and Drug Administration. Anaplastic Large Cell Lymphoma (ALCL). Available at: www.fda.gov/medicaldevices/productsandmedicalprocedures/implantsandprosthetics/breastimplants/ucm239995.htm. Accessed October 26, 2015.
  30. Keech JA Jr., Creech BJ. Anaplastic T-cell lymphoma in proximity to a saline-filled breast implant. Plast Reconstr Surg. 1997;100(2):554-555.
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  32. Madison J. The Federalist no. 51, 1787.

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