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“Wine, Cheese and a Dash of Poison in the Forehead”:

Exploring the Evolution of the Injectable Filler Industry and the Consequent Implications for Regulatory Action

Angela Esther Kim

Class of 2006

Food and Drug Law

3L Paper

Professor Peter Barton Hutt

May 19, 2006

Abstract: Although the American pursuit of youth and beauty has long influenced female consumers, the recent introduction of injectable fillers has overwhelmed the country’s current capacity to regulate. Millions of American women annually receive a plethora of injections – some approved, some off-label, and others wholly unapproved. This paper examines the new challenges the Food and Drug Administration must confront as consumer obsession skyrockets, and manufacturers and physicians engage in questionable activity to meet the rising demand. The public’s increasingly casual attitude toward FDA approval of cosmetic uses has endangered an industry enamored, at all costs, with the pursuit of wrinkle-free, ageless beauty. This danger is compounded by the Internet’s creation of unprecedented marketing channels for manufacturers to inundate consumers with misleading information and sidestep FDA prohibitions. Through case studies of the four injectable fillers Botox, silicone, Radiesse and ArteFill, this paper addresses the obstacles the FDA must confront to adjust to a changing frontier.


“My original plan was to age like one of those fantastic French women--Juliette Binoche, Isabelle Adjani, Catherine Deneuve. But I waited in vain as my inner radiance refused to take over. Where lines and dark circles made those women look interesting, I just looked tired. So of course I was intrigued when I heard about a new procedure that could inject freshness and life into my face with less time and effort than a visit to the hairdresser. This supposedly miraculous treatment isn't available in the U.S., but I happened to know one of the doctors doing it in London...” [1]

... and so begins another article, in another fashion magazine, read by another intelligent, successful (yet unfailingly insecure) female consumer. She peers in the mirror to examine her frown lines, her smile lines, her crows’ feet... all lines that she has memorized, traced with her fingers, and wished away innumerable times before. But this time, she will be brave... she will accept the role that hundreds, thousands, millions of women have assumed before her; she will visit a dermatologist, a cosmetic surgeon, or maybe even just a Botox party, and inject one of a plethora of fillers available to her today.

While the pursuit of youth and beauty has both encouraged scientific research and tortured female consumers for ages, the cultural obsession with injectable fillers has overwhelmed the fields of cosmetic surgery and dermatology in recent years. Botox was the first to lure the American public with its promise of wrinkle relaxation; numerous other fillers – both approved and unapproved – have subsequently flooded the marketplace.

Charged with the responsibility of regulating medical devices, the Food and Drug Administration (“FDA”) assumes a frontline role in addressing the host of questions that accompany this rapidly expanding industry of cosmetic fillers. Even so, illegal uses are rampant and destructive, as black market fillers rage across the country, causing severe disfigurement and multiple fatalities.

While illegal fillers continue to ravage lives and communities, equally difficult questions require the FDA’s attention to the shades of gray – the potentially illegal marketing and dangerous use of legal devices. For example, with the rise of the Internet, manufacturers have discovered numerous methods to sidestep FDA regulations on advertising and promotion. These tactics render virtually obsolete the agency’s power to police the marketing of cosmetic off-label uses of devices. The FDA must acknowledge this evolution while refusing complicity with the status quo, and must adjust to accommodate the changing times that come with changing technology.

This paper seeks to illustrate the challenges confronting the FDA through case studies of four distinct devices and the types of harms accompanying them. The first study analyzes the transformation of Botox, derived from the toxin clostridium botulinum, otherwise known as “the world’s most poisonous poison.” Years of laboratory research have transformed the bacteria once responsible for fatal food poisoning into the much-desired fountain of youth. Once approved to treat uncontrollable blinking and misaligned eyes, Botox found fame in its off label use to reduce wrinkles. Upon approval, the floodgates opened – “Botox parties” and “Black market Botox” emerged as significant threats to consumer safety.

While Botox was approved for cosmetic use merely four years ago, avid consumers today have become unsatisfied with this basic, almost pedestrian , treatment. The second case study examines liquid silicone injections, a permanent alternative for facial contouring. Despite a long existence, silicone injections have gained massive popularity in recent years with silicone “pump parties” that combine the most dangerous features of Botox parties and Black market Botox. Cosmetic silicone injections currently constitute an off-label use, and rampant inappropriateness surrounding its application serves as a fierce warning to an administration seeking to protect the health and safety of consumers.

Impossible to ignore in an analysis of this filler craze is the paramount role of technological progress. The Internet creates unparalleled channels of communication between manufacturers and consumers, and consequently, unlimited opportunities for marketing. While the FDA prohibits the marketing of a device’s off-label uses to consumers, manufacturers easily transgress ethical and legal lines via the Internet. Physicians, too, reap benefits from this medium, as they market devices to consumers with misleading language. Exemplifying this phenomenon is the third case study, of the synthetic filler Radiesse. It is approved for oral/maxillofacial defects, vocal fold insufficiency and radiographic tissue marking, but it is used cosmetically as a contouring filler.

Lastly, this paper concludes with a case study of ArteFill, a device of Canadian origin expected to receive FDA approval for U.S. use in the near future. The potential for consumer harms is potentially more egregious, as Canadian physicians question the veracity and intentions of the manufacturer’s safety and health claims. For example, the device’s co-founder allegedly used the device illegally, disfigured a patient, and then attempted to exclude the results from clinical studies. This unfortunate incident illustrates the extent to which manufacturers attempting to meet the demands of an extraordinarily zealous public can (and will) mislead unsuspecting consumers in the process.

These case studies collectively illustrate an industry expanding at exponential rates, striving daily to reach a seemingly unlimited profit potential. In the crossfire, quite literally, are human faces, driven by the promise of youth and yet often blinded by their own vanity. With the rapid expansion of this industry and the pivotal changes introduced by technology, the FDA must embrace flexibility and adjust to confront the issues ushered in by this evolving frontier.

PART I. Exploring the Consumer’s Pursuit of Youth and Beauty

While the obsession with the newest injectable filler from other continents may be a modern development, the cultish pursuit of female beauty and youth is anything but. No matter how advanced or how primitive, every culture has engaged in the pursuit of the “perfect” female form. “Since Plato, feminine beauty has been idealized as representing moral or spiritual qualities.” [2] The “fair damsel” of medieval chivalry and the “female nude” during the Renaissance embody the divinity and desirability associated with feminine beauty.[3]

Along with such idealizations come the hordes of hungry females, eager to adjust, enhance and transform themselves at substantial cost The nineteenth century gave birth to corsets, which caused “breathlessness, fainting spells, and shifting organs,”[4] and the use of arsenic-coated paper to brighten the face. [5]

Regardless of the extensive history of the woman’s plight to adjust to societal pressures, the technology of today has ushered in a new era of transformation: “the twentieth century has produced an even more constraining corset – the woman’s own skin.”[6] In 2003, 2.8 million women received Botox injections in the United States;[7] in 2004, hundreds of thousands of women received injection of other fillers, including collagen, hyaluronic acid or calcium hydroxylapatite.[8]

Exploring the social, cultural, psychological causes “behind the craze”

Social scientists offer a plethora of reasons explaining this craze, this startling surge in the popularity of cosmetic enhancements. In HOPE OR HYPE: THE OBSESSION WITH MEDICAL ADVANCES AND THE HIGH COST OF FALSE PROMISES , Drs. Richard Deyo and Donald Patrick attribute the sudden rise in popularity to the national obsession with technology: “We’re a ‘techniconsumptive’ culture. We’re pulled irresistibly to new technology, often without recognizing the risks.” [9] Further, he contends that “[m]any Americans have a sense of entitlement – they feel that the latest medical advances are ‘owed’ to them.”[10] This shared mentality of seeking, desiring and “deserving” all that is newer, better and faster has created a cultural phenomenon of a nation of avid consumers, eagerly devouring whatever filler claims innovation and superiority.

In RESHAPING THE FEMALE BODY , Kathy Davis notes the allure of technology, but focuses additionally on the market model of medicine and the burgeoning consumer culture: “With the rise of medicine as a profession, medical cures and services become something which could be obtained for a fee. In an open market system, the patient is a consumer, and like consumers of other products, free to choose any treatment, provided it can be paid for.”[11] As a consequence, “[t]he body is no longer simply a dysfunctional object requiring medical intervention, but a commodity – not unlike ‘a car, a refrigerator, a house- which can be continuously upgraded and modified in accordance with new interests and greater resources.’ It can be endlessly manipulated – reshaped, restyled, and reconstructed to meet prevailing fashions and cultural values.”[12] Combined with a narcissistic culture,[13] this “disdain for material limits” and “intoxication with change” has made the possibilities both “desirable and endless.”[14]

These cultural influences of technology and consumerism have likely provided the groundwork for the increasing correlation that scholars note between the physical body and emotional happiness. Davis highlights the influence of the media, noting magazine articles describing women who just want “to feel a little better.” Through such portrayals, cosmetic enhancement “is presented as a relatively harmless way to improve appearance – an acceptable path toward happiness and well-being.”[15] Like Deyo and Patrick, Davis notes the integral role of today’s cultural sense of entitlement; in today’s world of immediate gratification, people “expect to be happy, to achieve a glamorous life style.”[16]

In CREATING BEAUTY TO CURE THE SOUL , Sander Gilman suggests a more direct link between the increasing social acceptability of physical enhancement and the psyche: “The decline of the stigma associated with aesthetic surgery is keyed to the change in the stigma associated with mental illness. Both illnesses were socially unacceptable as they reflected the pain and anguish of the ‘invisible’ psyche rather than the concrete body.”[17] Cosmetic surgery, he contends, has simply replaced psychotherapy as the popular means of seeking help for one’s emotional disturbances: “the acquisition of an idealized or imagined body type or physiognomy is a ‘cure’ for ‘unhappiness.’”[18]

This contention supports a novel understanding of the relationship between patient and surgeon:

“On the one hand, the patient hands over responsibility for his or her happiness to the surgeon. Rather than changing their bodies through diet or cosmetics or fashion, approaches that demand choices be made on the part of the individual, an ever growing number of people are turning this process over to those whom modern society empowers to deal with problems of physical and mental health, the physicians. Individual autonomy (with all of the limits on choice set by the world in which we live) seems to be replaced by the role of the dependent patient.”[19]

Though these scholars (Davis, Deyo and Patrick, and Gilman) identify unique causes behind the sudden national obsession with cosmetic enhancement, they commonly identify the same channels that made its cultivation possible: the media and the Internet. Deyo and Patrick explain how the media has dramatically increased accessibility to information and marketing, and has thus helped shape the pursuit of medical quick fixes:

“In a media age, innovations spread through mass marketing. The Internet also spreads news and creates demand through list serves, web sites, chat rooms and spam. Health news is a common topic for magazine articles and cocktail party conversation. What used to be sequestered in grandma’s medical book or in a medical library is now all around us: on paper, the radio, the Internet, and television.”[20]

In short, with mass marketing comes increased accessibility. Davis expands upon Deyo and Patrick’s contention by commenting on how this accessibility is constructed as desirable to the consumer: “the media constructs cosmetic surgery as an option which is not only available to everyone, but which bears the promise of an exalted life – one can partake in what was formerly available to the chosen few.[21] Thus, with the introduction of the Internet, marketers not only have access to the mass public, but individual consumers likewise gain access to a luxurious world defined by choice rather than by need.

Even so, boundless consumer choice inevitably leads to consumer confusion and, frequently, consumer harm. In this context, the Food and Drug Administration, in its regulatory capacity, plays a pivotal role in protecting consumers from dangerous devices.

PART II. Exploring the FDA’s Regulatory Role

As a division of the Department of Health and Human Services, the FDA seeks to “promote the public health by promptly and efficiently reviewing clinical research and taking appropriate action on the marketing of regulated products in a timely manner.”[22] The agency’s mission includes the goal to “protect the public health by ensuring that there is reasonable assurance of the safety and effectiveness of devices intended for human use.”[23]

A. Pre-Market Approval

New medical devices face different routes to FDA approval depending on their market familiarity. A manufacturer can seek approval through the § 510(k) process by proving “substantial equivalence” to a device in commercial distribution prior to the Medical Device Amendments of 1976 (“MDA”) to the Food, Drug and Cosmetics Act. This process requires the manufacturer to submit substantial premarket notifications including the device’s proposed labeling, the similarities and differences in design to the prior device, and other information useful for the FDA in determining substantial equivalence.[24]

Devices that cannot claim substantial equivalence must undergo the significantly more arduous “Premarket Approval” process. The applicant must file an application that contains “all information published or known to or which should reasonably be known to the applicant, concerning investigations which have been made to show whether or not such device is safe and effective;”[25] “statement of the components, ingredients, and properties and of the principle of operation, of such device;”[26] and “the methods used in, and the facilities and controls used for, the manufacture, processing, and when relevant, packing and installation of, such device.”[27] This application must include technical sections summarizing non-clinical laboratory studies and clinical investigations. The non-clinical laboratory studies section “includes information on microbiology, toxicology, immunology, biocompatibility, stress, wear, shelf life, and other laboratory animal tests.”[28] Alternatively, the clinical investigations section “includes study protocols, safety and effectiveness data, adverse reactions and complications, device failures and replacements, patient information, patient complaints, tabulations of data from all individual subjects, results of statistical analyses, and any other information from the clinical investigations.”[29] The purpose of submitting this information is to provide the FDA with “reasonable assurance” of the safety and affectiveness of the device.[30]

After the applicant submits the above information, the FDA has 180 days to grant or deny approval of the application. Throughout this process, “the Secretary shall rely on the conditions of use included in the proposed labeling as the basis for determining whether or not there is a reasonable assurance of safety and effectiveness, if the proposed label is neither false nor misleading.”[31]

B. Off-Label Use

Though the FDA regulates the commercial distribution and marketing of medical devices, it does not regulate the practice of medicine :

“As the law now stands, therefore, the Food and Drug Administration is charged with the responsibility of judging the safety and effectiveness of drugs and the truthfulness of their labeling. The physician is then responsible for making the final judgment as to which, if any, of the available drugs his patient will receive in the light of the information contained in their labeling and other adequate scientific data available to him.” [32]

Thus, physicians are granted tremendous discretion in using these devices according to an arguably abstract standard of care. The FDA provides the following vague advice: “Good medical practice and the best interests of the patient require that physicians use legally available drugs, biologics and devices according to their best knowledge and judgment.”[33]

Consequently, many physicians choose to prescribe drugs and use medical devices in manners not addressed by the approval process. This procedure is called “off-label use,” defined by the FDA as “use for indication, dosage form, dose regimen, population or other use parameter not mentioned in the approved labeling.”[34] In such cases, the FDA asks that physicians “be well informed about the product, ... base its use on firm scientific rationale and on sound medical evidence, and ... maintain records of the product's use and effects.”[35]

Not only is off-label use considered relatively common practice, the FDA largely condones the practice: In a 1982 issue of its Drug Bulletin , the FDA noted that

“The FD&C Act does not ... limit the manner in which a physician may use an approved drug. Once a product has been approved for marketing, a physician may prescribe it for uses or in treatment regimens or patient populations that are not included in approved labeling.”[36]

In 1993, when faced with questions regarding the off-label use of bone screws, the FDA reiterated in its Drug Bulletin its refusal to regulate off-label usage:

“[i]n practice, surgeons often use orthopedic screws which FDA has cleared for other purposes . . . as pedicle screws. Such use of medical devices for nonapproved purposes has traditionally been regulated by the hospitals in which the physicians practice and not by the FDA.” [37]

And in 1997, the FDA passed the Food and Drug Administration Modernization Act (“FDAMA”), in which it repeated its refusal to interfere with the practice of medicine:

“Nothing in this Act shall be construed to limit or interfere with the authority of a health care practitioner to prescribe or administer any legally marketed device to a patient for any condition or disease within a legitimate health care practitioner-patient relationship. This section shall not limit any existing authority of the Secretary to establish and enforce restrictions on the sale or distribution, or in the labeling, of a device that are part of a determination of substantial equivalence, established as a condition of approval, or promulgated through regulations. Further, this section shall not change any existing prohibition on the promotion of unapproved uses of legally marketed devices.”[38]

And currently the FDA notes on its website that “off-label use by prescribers is often appropriate and may represent the standard of care.”[39]

Such off-label use is rampant: an estimated 25% to 60% of all prescriptions are for unapproved uses.[40] Studies show that 56% of cancer patients and 81% of AIDS patients have used off-label drugs.[41] Nearly all pediatric patients have received off-label prescriptions, and antidepressants commonly treat the off-label uses of anxiety and alcoholism.[42]

Legally, off-label use has emerged relatively victorious in the courtroom:

“No court has held that a physician’s deviation from the officially approved labeling – whether directions for use, warnings, contraindications, or statements of relative efficacy – is per se negligence. The practitioner who departs from the manufacturer’s recommendations does not necessarily incur liability for any untoward effects which flow from a drug.”[43]

In Buckman Co. v. Plaintiffs’ Legal Comm ., the Supreme Court noted that “‘off-label’ usage of medical devices ... is an accepted and necessary corollary of the FDA’s mission to regulate in this area without directly interfering with the practice of medicine.”[44]

At the same time, courts have not entirely liberated the physician to use or prescribe any device or drug without limitation. For example, in Cabiroy v. Scipione , the Pennsylvania Superior Court affirmed the trial court’s decision to grant a new trial upon finding error in jury instructions declaring that the FDA lacked authority to regulate the practice of medicine.[45] Scipione had injected liquid silicone implants not yet approved by the FDA to cosmetically improve Cabiroy’s nasal deformity. Unfortunately, the silicone allegedly resulted in bumps in Cabiroy’s nasal area. In reviewing the jury charge, the Pennsylvania Superior Court found error, noting that “Doctors do not have sole and absolute discretion in treating their patients.”[46]

C. Marketing

Though doctors may use approved drugs in off-label uses; pharmaceutical manufacturers have significantly less discretion in marketing. According to the Food, Drug and Cosmetic Act, “a company must specify the intended uses of a product in its new drug application to the FDA. Once approved, the drug may not be marketed or promoted for so-called ‘off-label’ uses--any use not specified in an application and approved by the FDA.”[47]

With the FDAMA in 1997, the FDA’s marketing policy was amended to allow pharmaceutical companies to disseminate information on off-label uses to physicians, while still prohibiting them from marketing such uses to the public. Section 551 allows a manufacturer to disseminate to “(1) a health care practitioner; (2) a pharmacy benefit manager; (3) a health insurance issuer; (4) a group health plan; or (5) a Federal or State governmental agency; written information concerning the safety, effectiveness, or benefit of a use not described in the approved labeling of a drug or device.”[48] Sixty days before such dissemination, the manufacturer must submit to the Secretary “(A) a copy of the information to be disseminated; and any clinical trial information the manufacturer has relating to the safety or effectiveness of the new use, (B) any reports of clinical experience pertinent to the safety of the new use, and a summary of such information.”[49]

While the FDA has successfully applied its rules and regulations to protect the American public for years, the following case studies outlined in Part III illustrate additional issues that require regulatory attention. The studies demonstrate the insufficiency of the agency’s current tools in effectively mitigating the problems raised by injectable fillers and the evolving technology used to market them.

PART III. Case Studies

A. Botox

Within the world of non-surgical enhancement, one particular gateway to self-improvement revolutionized the industry; Botox, once a secret of Hollywood celebrities, is now accessible to housewives and movie stars alike. A pioneer of sorts, Botox laid the groundwork for the hordes of injectable fillers available today.

1. Early History: Botulism

Clostridium botulinum , an anaerobic bacterium, produces a number of neurotoxins universally regarded as the most potent of bacterial toxins.[50] Though the molecular events involved are not precisely known, “it appears that binding of the toxin is followed by a series of events that result in blocking the calcium-dependent fusion of synaptic vesicles with the presynaptic membrane and the subsequent release of acetylocholine.”[51] The effect is paralysis, “to kill nearby flesh, providing more oxygen-free living space for the bacteria.”[52]

Though botulism poisoning has likely infected humans since the beginning of time, the early 18th century marked its first documentation, as outbreaks of “sausage poisoning” struck Southern Germany.[53] Similar outbreaks struck in the 19th and 20th centuries before scientists discovered methods to inactivate clostridium botulinum spores. Though refined canning techniques have since drastically reduced outbreaks, the Center for Disease Control reports that approximately 110 cases of botulism poisoning are reported each year.[54] Twenty-five percent of those cases manifest as foodborne illness, usually a result of the improper canning of foods with low acid content. Infant and wound botulism account for the remainder.[55]

2. Responding to the Crisis through Warnings and Education

Throughout the 1900s, canneries adjusted with relative swiftness to prevent further outbreaks of botulism poisoning. However, the popularity of home-canning required substantial community effort to educate the domestic population. A 1935 article in Scientific Monthly warns households of the dangers of botulism poisoning (“It is probably the most dangerous of all”)[56] and educates homemakers on proper canning techniques:

“There are certain rules that every housewife should observe in order to avoid botulism. All home-canned, non-acid foods should be thoroughly boiled just before eating. This will destroy any poison present. Canned products should always be opened by an adult familiar with their normal appearance and odor. If there is the least trace of off-standard condition the product should be ruthlessly destroyed and never fed to animals or fowls. If there is no pressure cooker available in the home preserving of non-acid foods, it is safer to substitute drying, salting or pickling for canning.”[57]

Despite these efforts to educate home-canners and commercial canneries, the food industry did not remain immune to subsequent outbreak. In 1987, eight individuals suffered fatal consequences from ingesting clostridium bacterium spores, and investigations traced the poison to a dried white-fish, Kapchunka, produced in New York City. Despite sufficient levels of salt that met safety requirements for canning, the Kapchunka products nevertheless housed the deadly bacteria. As a result, the FDA issued a Class I Recall and prohibited the processing, distribution and sale of any Kapchunka products in the United States.[58]

In 1989, three individuals in Kingston, New York, suffered from botulism poisoning after ingesting a chopped garlic-in-oil bottled mix. As a result, the FDA prohibited companies from creating any such mixture, and also issued extensive warning guidelines to the public:

“The Food and Drug Administration today warned that consumers may risk potentially fatal botulism food poisoning from some commercial and homemade chopped garlic-and-oil mixes if they are left at room temperature instead of refrigerated. The warning follows an investigation of three hospitalizations in New York after use of such a product. ... The labels of non-preserved commercial products call for refrigeration, and FDA emphasized this means refrigeration from manufacturing to consumption. In particular, garlic-and-oil mixes containing little or no acidifying agent such as phosphoric or citric acid should be kept refrigerated at all times, FDA stressed.”[59]

3. Modern Uses of clostridium bacterium

Hoping to gain a better understanding of the toxin associated with food poisoning, scientists began to study clostridium bacterium in the early 1900s. Soon thereafter, botulism research shifted its focus to the bacterium’s injectability “because of the unique and specific muscle paralysis induced by minute amounts of the toxins. During the past 30 years of work on the use of the toxin for human treatment, selective procedures for the production, purification, and dispensing of the toxin have been developed to make it suitable for injection.”[60]

In the 1960s, researchers discovered that upon extraction, precipitation, purification and crystallization with ammonium sulfate, the toxin could safely be injected in ophthalmologic treatments.[61] In 1989, the FDA approved Botox to treat uncontrollable blinking (blepharospasm) and misaligned eyes (strabismus). [62] This much-awaited approval finally allowed Allergan to announce: “More than 100 years of research have expanded our knowledge of botulinum toxin type A from the identification of the bacterium Clostridium botulinum to the commercialization of botulinum toxin type A as BOTOX®.”[63]

In 2000, the FDA further approved the usage of Botox in treating cervical dystonia, a neurological movement disorder causing neck and shoulder contractions.[64] During this process, physicians at Columbia University witnessed a serendipitous side effect,[65] that “Botox softened the vertical frown (glabellar) lines between the eyebrows that tend to make people look tired, angry or displeased.”[66]

4. Off-Label Use: e.g., “Botox Parties”

“The world’s worst poison is becoming US’ first wonder drug for facial beauty.” [67]

Upon such discovery, the movement that followed was largely expected, but arguably farcical in its magnitude. In 1999, three years before Botox would receive FDA approval for cosmetic purposes, Beverly Hills plastic surgeon Larry Koplin reported to CNN that nearly all of his patients had received the treatment off-label.[68] In explaining his philosophy, Koplin shared: “I don't believe we are creating a generation of Dorian Grays, but rather than that, we're creating the ability for people to look the way they feel.”[69] It appears that Koplin referred to the age rather than the emotions of his patients – as Botox paralyzes facial lines, inhibiting facial expressions.

And even then, critics worried that

“the obsession with looks has gone too far. Sociologists say people don't need plastic surgery to have their looks reflect how they feel. ‘If we were to change our values towards aging ... we might find beauty in some of the characteristics we're trying to change,’ said Merrill Silverstein, professor of gerontology at the University of Southern California. Perhaps then we could learn to love our wrinkles instead of poisoning them.”[70]

Learn to love our wrinkles we did not, as over 1.6 million people received Botox injections in 2001, according to the American Society for Aesthetic Plastic Surgery.[71] Consequently, the FDA approved the use of Botox injections for the reduction of wrinkles between the brows in April, 2002, “satisfied by its review of studies indicating that Botox reduced the severity of frown lines for up to 120 days.”[72]

Although rampant off-label use of Botox to treat wrinkles pre-dated its approval for cosmetic purposes, “When the FDA recently approved Botox for cosmetic use, it opened the floodgates on what's rapidly becoming a billion-dollar business.” [73] Hotels in Las Vegas began offering Botox spa weekends; radio hosts offered free injections as giveaway prizes at the local mall.[74] And most interestingly, those floodgates burst open in convivial form, giving rise to a phenomenon known as “Botox Parties”: “No matter where you live, all you need is a little curiosity to snag an invitation to a Botox party, where there is plenty of food, drinks and a very compelling show.”[75] Botox parties are simply just that, parties with Botox, an unusual hybrid of wildly different offerings. Provide some hors d’oeuvres, combine with poison, and voila , the innovation of the 20th century: “The beautiful people. Not a frown line, crow's foot, or wrinkled brow in the room. While it looks like your typical wine and cheese party, there's a little chardonnay, [a] little brie, and botox.” [76] An explanation of the events at a typical party:

“Maria Brown's fete began at 7 p.m., when guests arrived at her four-bedroom home in Westchester, a tony neighborhood in Redmond, Wash. As the hors d'oeuvres circulated, Dr. David Stephens, a Bellevue, Wash., plastic surgeon, laid out a tray on the dining room table: sterilized needles and several vials of Botox, botulinum toxin type A -- a purified protein derived from bacteria that, when ingested, can cause botulism. Botox, when injected in the face, temporarily erases the signs of aging. After a 15-minute talk on how the procedure works and a bit of history about the drug, made by Allergan Inc., Dr. Stephens took questions about costs (discounted to $250 a pop for these special partygoers) and potential side effects, which can include paralysis of nearby muscles, headache, localized numbness, rash, bruising, local swelling, disorientation and double vision. Then, after each woman signed a consent form, the lineup began. With soft jazz playing in the background, the partyers chatted in the living room as each guest slipped away into the formal dining room for a quick procedure. Every time a patient emerged, post-Botox, the others offered a round of applause. Ms. Brown went last. She got five injections in her face: three between the eyebrows; one on each temple. Then she had a drink. Four days later, she says: ‘No frown, no frown lines.’”[77]

Though the phenomenon has been received with mixed reactions, individuals involved in the process extol its benefits. Particularly, they stress the psychological comfort of removing the procedure from a medical office setting. Dr. Stephens explains his thought process behind these events: “I started out with about five patients a week, then soon it was 15 to 20 a week, then a patient said, wouldn't this be great with a glass of champagne.”[78] Brown explains the attraction: “‘Ours was just so fabulous,’ says Ms. Brown, 32 years old, who held her first Botox party recently with 10 friends, over champagne, chocolate truffles and brie. [...] ‘The private setting makes it so relaxed -- it didn't feel so much like it was this big procedure.’”[79] Similarly, while on vacation in New York, Maureen Ingram accepted an invitation to a party, and “recalled how over drinks at Dr. Sachs's office, she got injections between her eyes. ‘Just amazing,’ is how she described the results. And the setting, she said, was ideal. ‘It takes away the whole doctor/patient feel.’”[80]

While some physicians welcomed the brilliant income-generating opportunity with open arms, others reacted with horror. The American Academy of Dermatology released a Patient Alert, warning consumers of the dangers present in Botox Parties.[81] Fred F. Castrow II, M.D., President of the American Academy of Dermatology declared: “A casual social activity for the purpose of administering botulinum toxin, such as a ‘Botox® Party,’ is an inappropriate and a potentially dangerous setting for performing medical procedures of any kind [...] Adding alcohol to the mix is a bad idea for a number of reasons, especially since bruising can be intensified.”[82] Further, the alert attempted to remind the public of a fact long forgotten amidst wine and cheese: “Botulinum toxin is a purified form of one of the most potent toxins in the world. In high doses, it can cause the clinical disease botulism.”[83]

Other prominent physicians voiced similar concerns. Dr. Patricia Wexler, dermatologist of many celebrities, commented, “As a doctor I feel it's inappropriate. It sends a wrong signal. It also trivializes the person doing the procedure. Privacy is important and these parties are a marketing tool.”[84] Dr. Richard Glogau, a clinical dermatologist at the University of California, San Francisco, agreed: "This is a medical procedure ... and I think it should remain one and I think it's wrong to trivialize it that way ... and... I don't think it's ever a good idea to mix alcohol with elective medicine.”[85]

Despite the detractors, Botox Parties still claim the support of many established physicians. However, the toxin’s surge in popularity has given rise to another far more harmful phenomenon, this one condemned by all: black market Botox. “With more and more Americans anxious to smooth their wrinkles, experts say black market Botox copycats are being produced around the world and marketed to doctors in the United States.” [86]

Though numbers and statistics are difficult to come by, black market Botox gained great publicity when it caused paralysis in a Floridian clinic. Dr. Bach McComb, an osteopathic physician, injected himself, his girlfriend and friends Bonnie and Eric Kaplan with botulinum toxin as a cheap alternative to Botox.[87] Each was afflicted by severe botulism as a result. The vials had contained potentially fatal amounts of the toxin and were obtained from a facility in Arizona, run by Dr.Chad Livdahl and Dr. Zarah Karim.[88] The physicians allegedly created vials from raw botulinum toxin meant for research purposes, and sold over 3,000 vials to 200 doctors nationwide.[89] More recently, in March 2006, a hairstylist from Salinas, California was arrested for allegedly injecting “bogus Botox” into numerous women. Unlicensed, she allegedly used cooking oil, and as a result one woman died.[90]

Not only are counterfeit vials available from laboratories; they can be purchased on the Internet: “Dermatologist Leslie Baumann, 37, does research for Botox's manufacturer and she uses it herself so she was shocked when she caught a Chinese company she'd never heard of fraudulently listing her as endorsing their product on a Web site.”[91] Black market Botox even began using the Botox seal; Allergan responded by adding a holographic prism to its packaging.

5. The FDA’s Role in the Botox Phenomenon

The transformation of botulinum toxin into commercially marketed Botox presents a unique study in the progression of the FDA’s role. In the 1980s, the FDA used its regulation powers to protect the public from the foodborne illness. As detailed above, the agency recalled products that facilitated death by botulism poisoning. In the 1990s, the FDA gave its approval for the use of that same toxin transformed into an injectable meant to cure blepharospasms, strabismus and cervical dystonia. And finally, after widespread off-label use, in 2002 the FDA approved “the world’s most poisonous poison” for cosmetic purposes.

One might expect a device’s pre-approval use to accompany significant hesitation, with post-approval use resulting in common, appropriate use. However, rather than follow this expected trajectory; Botox welcomed an expedited timeline. Before its approval, Botox was common practice. Millions of women used it, and whether the FDA had granted its approval seemed meaningless in practice.

Upon approval, the proverbial floodgates flew open, as Botox Parties and black market Botox hit the streets, the clinics and the social circuits. In response, the FDA issued the following statement: “The FDA is concerned that Botox has the potential for being abused. The ASAPS recently reported that unqualified people are dispensing Botox in salons, gyms, hotel rooms, home-based offices, and other retail venues. In such cases, people run the risks of improper technique, inappropriate dosages, and unsanitary conditions.”[92]

Whereas a simple warning may have been sufficient in educating housewives in proper home-canning, Botox has engaged a far more aggressive public. Beyond issuing statements, an FDA reaction must acknowledge how limited its control has been over the market effects of its own regulation. Approval in this case, is equated not to widespread appropriate use, but to a dangerous, potentially unmanageable national obsession. In whatever form, whether appropriate or legal, consumers and physicians alike are cutting costs and throwing safety to the wind.

And thus, whereas the agency may have successfully addressed botulinum toxin as a foodborne illness, monitoring the dangers associated with the cosmetic use of Botox provides new challenges. The potential harms associated with black market Botox and Botox Parties are real; they falsely eliminate any perceived risks associated with the medical procedure. And even if one finds these particular risks relatively harmless, the nation’s now-casual attitude toward banishing wrinkles has overwhelmed an entire industry. Botox is no longer the Holy Grail of treatments; rather, consumers are turning to a host of injectable fillers that further promise the elusive attainment of youth and beauty. And many of these treatments present even greater dangers than the Botox phenomenon.

B. Liquid Silicone Injections

Botox paved the way for the widespread social acceptance of reducing wrinkles; following an even more expedited trajectory of rampant use is liquid silicone. Though still used off-label, the dangerous uses of Botox that erupted post-approval have already affected/corrupted the application of injectable silicone. The accompanying dangers are terrifying: pain, disfigurement and fatalities.

1. The History of Silicone

“Silicone” is a term used to describe a “group of polymers based on the element Silicon that range in viscosity from fluids to solids.” [93] During World War II, silicone began its journey as an implant in increasing the breast size of Japanese prostitutes. According to Dr. Edward Kopf, a plastic surgeon and historian of silicone, “Japanese cosmetologists realized that American servicemen preferred women with larger breasts than were common among Japanese women. After experimenting with goats’ milk, paraffin and a variety of other substances, they tried silicone, injecting it directly into the breast.” [94] This practice was adopted by American plastic surgeons in the 1960s and 1970s; but even then, adverse physical reactions were dramatic and documented: “United States literature became littered with grotesque stories and pictures of women with lumpy, ulcerated breasts and scars and other problems in their abdomen, chest, arms and back from the drifting sticky bits of silicone. In a few cases in which the silicone migrated to the lungs, the result was death.”[95] In the 1970s, Dr. John Paul Heggers of the University of Texas medical campus at Galveston discovered that the immune system reacted problematically to the silicone in breast implants by developing antibodies.

As researchers sought innovative uses for silicone, studies illustrated a wide array of disconcerting results. Patients on kidney dialysis using silicone tubing had an unusually high rate of liver disease. Some died from the disease, and autopsies revealed a large amount of silicone in their livers.[96] In cardiac bypass surgery, researchers used silicone as an antifoam agent to oxygenate patients’ blood; silicone particles then blocked capillaries and caused tissue damage.[97]

Silicone use for breast augmentation persisted through the ‘60s and the ‘70s, and increased widely in popularity. However, in 1992, after numerous women reported health problems associated with the implants and their rupture, the FDA banned silicone implants for cosmetic breast augmentation. Adding to its controversy, this ban left unprohibited the use of silicone in clinical studies for reconstruction after mastectomy, correction of congenital deformities, or replacement of ruptured silicone gel-filled implants due to medical or surgical reasons.[98]

Nevertheless, liquid injectable silicone continued to be used illegally in the United States; one popular such use that emerged was to contour the face. In the early 1990s, the epidemic became so prevalent that the Department of Justice began filing injunctions on behalf of the FDA to prohibit physicians from injecting liquid silicone in patients.[99] FDA investigators attended a seminar held by Dr. James E. Fulton, and thus verified suspicions that he used and promoted injectable liquid silicone.[100] Soon thereafter, investigators inspected his clinics and confirmed its use.[101] Similarly, the Department of Justice filed injunctions against Drs. Norman and David Orentreich; inspections of their clinics revealed that they too used silicone injections to shape facial tissue.[102]

In 1994, the course of silicone use changed drastically as the FDA granted the pre-market approval of Adatosil 5000, a medical grade liquid injectable silicone device for use in the ophthalmologic procedure to tamponade retinal detachments. In 1997, Silikon 1000 was approved for the same use. Both agents contain polydimethylsiloxane polymers, composed of silicon, oxygen and methane molecules, varying in length and viscosity.[103]

Since the FDA allows for off-label use of approved devices (as exemplified by Botox, above), liquid injectable silicone regained popularity as a wrinkle filler. In 2000, the Orentreichs studied the “microdroplet serial puncture technique, which is applied at monthly treatment intervals until the desired cosmetic result is achieved. Small aliquots of .005-.01 ml liquid silicone are inserted in the skin at 2-10 mm intervals and is suggested to provide a safe, permanent, and consistent result for several cosmetic applications which include the filling of rhytides, scars, and dystrophies of varied depths and anatomic locations.”[104] In this procedure, the “mechanism of action” is thought to be the “combination of the displacement of the dermal connective tissue by silicone microdroplets and the production of thin-walled collagen capsules, which surrounds them.”[105]

Despite its growing popularity, medical opinions on the safety of injectable silicone differ. Dr. David Morrow, a plastic surgeon in Rancho Mirage, California, claims: “I’ve been using it for years. ... It's an excellent agent. The results are fabulous. There's nothing wrong with it.”[106] Others report a different experience.

“Minor adverse reactions that have been documented are very similar to those associated with other traditional filling agents and include pain upon injection, local and transient edema, dyschromia, and textural complaints. More concerning adverse reactions that appear to be more specific to liquid injectable silicone include granulomatous reactions, idiosyncratic inflammatory reaction, and reports of drifting. What appears most problematic about these reactions is that they have been reported to occur anywhere from 1 month to 25 years after initial treatment. In addition, because liquid injectable silicone is a permanent filler, any complication becomes compounded by the fact that the substance will not eventually be metabolized and the reaction can potentially persist despite treatment.”[107]

One issue of substantial concern is the relative dearth of information surrounding silicone’s long term consequences:

“the lack of long-term clinical data regarding the incubation period of a serious adverse reaction deems liquid injectable silicone a time bomb to its opponents. Unfortunately, we have a lack of long-term clinical data and reporting regarding the number of patients who have been treated properly or improperly and how many patients have had appropriate results or serious complications. These facts often cloud the ability of clinicians to appropriately weigh the risks and benefits of liquid silicone for use in soft tissue augmentation.”[108]

Regardless of the spectrum of medical opinions that surround silicone use, physicians agree that when used improperly, the adverse consequences can be disastrous. For example, Robert T. Rylee, chairman of the health care business for Dow Corning Wright, a major manufacturer of silicone products notes that “[i]n the wrong hands, injectable silicone is a disaster.” Specifically, “Dow strictly controls the distribution of its pure liquid silicone ... and does not market it for injection into people. Nevertheless ... unscrupulous people occasionally obtain the material and inject it into the breasts, buttocks and other body parts of people who cannot afford plastic surgery and who are not aware of the health risks involved.”[109] Furthermore, “[i]njectable silicone has been around the longest and, when used improperly, can maim or kill people. When injected freely into the body, it tends to travel to vital organs, causing severe toxic reactions. These include autoimmune diseases, blindness and death of tissue at the injection site.”[110]

2. “Pump Parties”

Examples of such improper use are most prominent in an extraordinarily dangerous setting called “pump parties,” a growing phenomenon within the transgender community. Just like “Botox parties,” “pumping parties” have gained in popularity as a relatively cost-effective way for individuals to receive injections. As the Miami-Dade County Healthy Department’s lead detective said: “cases of silicone parties are skyrocketing.” [111] These parties are often attended by transgender individuals who seek more feminine features, and “groups of patients typically receive silicone injections from an unlicensed, untrained person who is often using non-medical silicone.” [112] In fact, physicians have discovered that pump-party patients have been injected with “[i]ndustrial-grade silicone, floor products and sealers, and a host of contaminants including motor oil and paraffin.”[113]

The potential for harm is overwhelming:

“And so, transgendered people pay $200, $300, even $500 for a few injections of impure silicone, administered, usually, by someone with no medical training, no knowledge of human anatomy, no knowledge of sterile techniques, no idea of what to do if a medical emergency develops, and who may well be reusing needles without sterilizing them-- and this individual will more than likely have a very poor aesthetic sense. The result is Dangerous Curves-- what I sometimes refer to as Cheekbones from Hell-- body contours, especially lips and cheekbones, which just do not occur in nature. With repeated visits (and much money spent), the individual becomes a caricature, a cartoon, a person of exaggerated proportions. ... And the long term consequence is disfigurement.”[114]

One man in South Florida attended silicone pump parties for twelve years, first receiving the injections to eliminate wrinkles and creases, and finally in the buttocks. Now, his legs have become numb.[115] Even more disconcerting than disfigurement is the potential for fatalities; one woman in Miramar, Florida died after the silicone leaked into her bloodstream.[116] Three women died in Houston, and one more passed away in Georgia in 2003.[117] Also in 2003, two women in San Diego experienced severe respiratory arrest and were “near death” after being injected by unlicensed practitioners.[118]

According to Dr. Walter Bockting, coordinator of transgender health services at the University of Minnesota’s Center for Human Sexuality, transgendered individuals are particularly willing to forego safety costs in the pursuit of beauty: “Being beautiful and shapely is very important to certain segments of the transgender community — it’s a self-esteem builder for people who are feeling rejected by their families and communities.”[119]

Additionally, Mara Keistling, of the National Center for Transgender Equality in Washington, D.C., notes that transgendered individuals often face difficulty seeking treatment in more traditional forums: “Are you going to trust your best girlfriend or a doctor who may be rude to you and refuse to treat you or disrespect your reasons?”[120]

While pump parties are particularly popular within transgender communities, other groups of women have likewise picked up the trend. In South Florida, Enrique T. Torres, chief investigator for unlicensed activity with the state Health Department, describes the phenomenon with words commonly attributed to Botox Parties: “‘It's food, drink and injections ... . They gather, they eat, they drink, they have cash and everybody watches.’ He notes that ‘many of the procedures are taking place at in-home gatherings that resemble Tupperware parties or multilevel marketing meetings.’”[121] Women are lured in by a social setting created in a casual atmosphere: “A woman told state investigators she went to such an event in a Fort Lauderdale warehouse, where wine, low light and music set the mood.”[122] Additionally, “[r]ecently a group of freshly injected women were seen leaving a condo in the comfortable Miami suburb of Aventura. A local television crew spied them patting their numbed faces and studying their reflections in car windows.”[123]

The prevalence of these parties is overwhelming. As Torres noted: “This is in every corner, everywhere, because there's money to be made and people want to look good... If the state would be so kind as to give me 10 more investigators, they would be over-loaded the moment they started work.”[124] Mariano E. Busso, a dermatologist who teaches at the University of Miami shared that “[p]eople with problems from the injections show up almost daily” at his Coconut grove office.[125] Busso speaks of a woman he recently hospitalized who received silicone injections on her smile lines in 1993: “Eight years later, her face blew up like a balloon.”[126]

Investigators in South Florida take these accounts seriously, and have documented numerous disturbing cases. “One day in 1999, undercover investigators watched as a steady stream of people entered a small Miami apartment and waited in the cramped living room for the man they knew only as ‘Doctor David.’ In the suitcase he brought from Caracas, [Doctor David], who is not a doctor, always carried a crude brochure. Written in Spanish, it was a hand-drawn face with arrows connecting prices with body parts.” [127]

Angelina McCabe, 48, of Palm Beach County, used local beauty salons to network and get referrals for her silicone lip injection business. She had no authority to perform such injections, and was reported by a victim who “suffered pain, bleeding and swelling,” later suffering “a severe staph infection.”[128] Another salon worker reported “getting herpes from one of McCabe’s needles.” Upon searching her medical bag, investigators found $2,200 in cash and “used syringes and implements covered with dog hair.”[129]

The rampant use of liquid silicone illustrates a number of concerns. First, even when used by legitimate licensed physicians off-label, injectable silicone presents a host of potential harms. The dearth of information surrounding liquid silicone’s long term consequences creates cause for significant concern and more research.

Second, in the context of today’s cultural, obsessive pursuit of youth and beauty, the regulation of medical devices requires a fierce dedication to acknowledging illegal and black-market uses. Research and approval cannot focus solely on the effects of devices within the realm of legality, as the tragic consequences of black market Botox and silicone pump parties illustrate. Regulatory agencies must be flexible in adjusting to the demands of an obsessive consumer society; in these cases, the obsession has reached unacceptable extremes, as fatalities and permanent disfigurement occur frequently.

And thus, the FDA must acknowledge its experience with Botox in its consideration of silicone injections. If the agency chooses to grant the approval of liquid silicone for facial treatments, the FDA will elevate the injections from an off-label use to an approved use. Considering the expedited trajectory liquid silicone has already experienced, such floodgates will arguably create unprecedented danger.

C. Interlude

1. The Information Game: Analyzing the Growth of an Evolving Industry

Though the prescription of drugs and use of medical devices in unapproved manners remains fairly common in the practice of medicine, great controversy surrounds its applications in the cosmetic enhancement industry. The off-label use of approved devices and the rampant use of those yet unapproved have transformed the frontier – they have aggressively overwhelmed the fields of plastic surgery and dermatology.

2. ... Blame it on the Patient: the Shifting Role between Patient and Doctor

In its explanations for allowing off-label use, the FDA acknowledges that its authority falls short of regulating the practice of medicine. That discretion lies in the hands of physicians, individuals trained to apply a stringent standard of care to their patients. Such authority assumes that while patients exercise autonomy over which procedures are performed, doctors are the experts - the ones most capable of limiting options to the safe and effective. However, in recent years, the obsessive pursuit of youth and beauty has arguably shifted that delicate balance; physicians have substantially transferred decision-making powers to the patient. In many cases, the doctor’s role has receded sharply from expert advisor to mere facilitator. As NewYork Magazine reports:

“To hear some doctors tell it, client demand pushes physicians to experiment with unapproved treatments. ‘There’s a new kind of patient out there,’ says Stephen Bosniak, an ophthalmic plastic surgeon at New York Eye & Ear Infirmary. ‘They come in asking for these things. In this competitive market, people want to be the first to offer something new, because it is exciting.’”[130]

In New York City, physicians discuss the patient’s role in the use of Restylane, a dermal filler, prior to its approval:

“‘Three different patients came to me this summer with vials of Restylane in their purses and asked me to inject them with it,’ says a prominent Upper East Side plastic surgeon who asked not to be named. ‘I told them to go down the street to one of the dermatologists.’ To which dermatologist Soren White replies, ‘Plastic surgeons like to make our ethics or skills look questionable.’ White runs SkinKlinic, a spa that has long administered Botox and Restylane. ‘But my friends who are plastic surgeons are always asking me about the latest fillers.’”[131]

New York is not alone in witnessing this phenomenon; in San Francisco, patient interest and initiative is not dissimilar:

“Angelina Umansky, owner of a day spa in San Francisco, has observed plenty of trends in cosmetic procedures over the years, from breast implants to collagen injections to glycolic acid peels and, more recently, Botox. These days, she says, all she seems to hear from her clients is talk of the cosmetic fillers that are supposed to work faster on facial flaws and last longer than Botox ... ‘Safety is not a concern; they just want results.’”[132]

Likewise, in Chicago, Dr. Michael Byun, co-author of THE NON-SURGICAL FACELIFT BOOK, A GUIDE TO FACIAL REJUVENATION PROCEDURES and a Northbrook plastic surgeon, “doesn't object to unapproved medications — as long as a patient is fully informed about a substance's FDA status and the doctor's training background.”[133] His contemporary, Dr. Anthony Terrasse, harbors a bit more concern, but likewise notes: “it’s buyer beware.”[134]

3. The Information Game and the Modern Consumer’s Access

One reason behind this enormous shift in balance is undoubtedly the modern consumer’s unprecedented accessibility to information. As earlier noted, the Internet catapulted information previously held only by physicians and researchers to anyone and everyone’s fingertips. Whereas the average woman, years ago, may not have known about the existence of Restylane, let alone how to procure it – today, she can surf the web to discover, in mere seconds – in what countries said filler is available, and consequently, how to find its way to her purse and to her doctor’s office. For example, websites like “www.yestheyrefake.com” devote extensive space to providing such information.[135] Listed alphabetically, each segment includes a description of a different filler, including its ingredients, approximate cost, how to use it, cautions, what countries have approved it, and how to procure it. For example, the filler “Amazingel,” “a medical grade, hydrophilic polyacrylamide gel” can be found by contacting “Futian Dist. Shenzhen, China, Shenzhen, China, Guangdong (China) 518000.”[136] Phone and fax numbers are included.

With regards to whether Aquamid, an “injectable hydrophilic polyacrylamide gel (HPG, or PAAG) with 5 ppm residual unpolymerized acrylamide monomer” is available in the United States, the website states: “No, okay well not officially, but some physicians have brought it into the states or bought it from those who have and are offering it to their patients. This injectable is available throughout Europe, particularly in Germany, and also in Australia, Asia, Canada, Mexico, and more.”[137] Similarly, the filler Bioalcamid is obtainable though unapproved; the website states: “some patients have gotten it from their surgeons who have brought it into the country or bought it from those who have.  It is available in Mexico, and found in border cities.” Likewise, the silicone oil Biopolimero is said to be found “near border towns - this product is found in abundance in Mexico.”

And thus, it would seem, the modern woman is armed with far more information than her predecessors, and consequently, with far more knowledge to make well-informed decisions. However, such contention holds true only if the increase in volume presents accessibility to the entire spectrum of viewpoints. Unfortunately, while women today technically have access to varied medical opinions; the Internet bombards consumers less with an unbiased spectrum, and more with mass marketing.

The following case study illustrates the potential for consumers earnestly seeking information to be significantly deceived, as manufacturers and physicians alike skate ethical lines in their marketing approaches. Such deception requires the FDA to monitor promotional channels more substantially, and to adjust their current regulatory approach.

D. Radiance

1. Manufacturer Marketing

The FDA prohibits medical device manufacturers from marketing their products for off-label uses; however, the FDA does not prohibit non-manufacturers from discussing their benefits, and obviously cannot prohibit international marketing. This line is extraordinarily thin, as witnessed by the information available online for the product Radiance, otherwise known as Radiesse.

Radiesse is a synthetic filler composed of microspheres of calcium hydroxylapetite, a material similar to that found in teeth and bones. The FDA has approved i ts use for bladder neck augmentation for urinary incontinence, vocal cord augmentation for paresis, and periodontal defects.[138] However, the filler is also commonly used to treat wrinkles, most popularly marionette lines, nasiolabal folds and lip augmentation.

When entering the website for Radiesse, the viewer is presented with two options: “Radiesse USA” or “Radiesse Worldwide.”[139] Upon clicking the “USA” option, the consumer reads only that Radiesse has been cleared for “oral/maxillofacial defects, vocal fold insufficiency and radiographic tissue marking.”[140] Adjacent to the language, is a large button that reads “click here for Radiesse Worldwide.”

At this point, the consumer is presented with a far more sophisticated website, with numerous options allowing the viewer to pursue vast amounts of information. In bold, the opening page notes: “Radiesse is the newest non-surgical facial contouring filler that delivers an immediate, longer lasting result.”[141] The writing continues:

“Whether you’re longing to reverse the common signs of aging or address a health issue that otherwise would require an invasive treatment, you have more options in looking and feeling better with Radiesse. Developed with safety and longevity in mind, Radiesse is a new generation injectable filler that offers superior versatility for both cosmetic and reconstructive use without surgery. What sets Radiesse apart from other dermal fillers? The answer is in its durability, longevity, and versatility. The unique composition of Radiesse provides immediate visual improvement common with other fillers, along with the benefit of long-lasting results. This is because Radiesse is made of very tiny, smooth calcium hydroxylapatite (CaHA) microspheres. The microspheres (particles) form a scaffold through which your body’s own collagen grows, and this produces the desired long-term effect. These unique advantages make Radiesse the ideal choice for facial shaping and contouring – along with other therapeutic applications.”[142]

Accompanying such language is a rendering of a woman’s youthful face, wrinkle-free and with luscious, plump lips. The consumer can explore many more options by clicking on “treatment solutions,” “advantages,” “success stories,” “clinical effectiveness,” or “news and events.”[143]

The above documentation seeks to demonstrate the realistic implications of the prohibition on marketing placed by the FDA. Any consumer who discovers Radiesse’s website is highly likely to click on “Radiesse Worldwide,” after viewing the paltry information offered to those interested in “Radiesse USA.” One assumes that this technique is intentional on the part of the manufacturer. And thus, for all intensive purposes, the manufacturer has bypassed the FDA’s prohibition, and is directly marketing to the American consumer, while touting the filler’s off-label uses.

Radiesse was formerly known as “Radiance,” and one can discover a similar marketing loophole at www.radiancetreatment.com. The website is beautifully designed in muted purples and grays, and accompanied again by photographs of beautiful women with youthful skin and plump lips. At the page’s center, the engorged text reads: “Imagine a more vibrant you. Restore that youthful glow. Enhance your natural features. Radiance injection can smooth and revitalize key areas of your face.”[144] Again, the website presents the viewer with numerous options, including “Formula,” “Treatment,” “Before & After” and “Testimonials.” Upon clicking “Formula,” one is faced with: “The Ideal Solution.” Underneath, it reads:

“Finding a safe and lasting way to reverse the effects of aging on the face has been a longstanding search of medical science. The ideal approach would fill in the lines and creases that normally develop, and restore fullness to the lips and cheeks. It would be safe and totally compatible with the body. And it would last for many years. Until now, no treatment has met those high standards. Introducing Radiance, the first truly safe and enduring way to restore vitality to the face.”[145]

Again, for all intensive purposes, this website directly markets off-label uses to the consumer. In fact, one can even click a button to “find a Radiance Certified Aesthetic Center near you.”

However, in its attempt to avoid explicit violation of the FDA’s prohibition, one can peer closely to find the following shrunken text at the bottom of the page: “This website is maintained and operated by Aesthetic Communications, Inc. (ACI). ACI has no affiliation or relationship with the manufacturer of the Radiesse product, BioForm Medical, Inc. (BMI) or any other filler product manufacturer. The information contained herein has been obtained independently by ACI through interviews with physicians, patients and other medical research and market sources.”[146]

Whatever affiliation exists, explicit or not – the website arguably mirrors what a marketing website produced by the manufacturer, and aimed at the consumer would be. And thus, the manufacturers found a successful way to market the off-label uses of their product through whatever convoluted channels allowed them to escape affiliation, and thus, liability.

2. Physician Marketing

The websites discussed above illustrate just the beginning of the monumental amounts of information targeted at attracting consumers. An Internet search re: Radiesse results not in a predominance of scientific commentary, but rather, excess amounts of marketing. One such avenue is the physician’s website, plastered with advertising for various procedures, and often disguising important consumer information.

For example, the Metropolitan Institute of Plastic Surgery, located in Washington D.C., is a partnership of three plastic surgeons who advertise their practice through a website dedicating extensive space to Radiesse. Under the headline “Is Radiesse Safe?” the text reads, “Radiesse was approved by the Federal Food and Drug Administration (FDA) nearly a decade ago and since then has undergone continued testing in accordance with strict FDA requirements. Thousands of men and women have used Radiesse to safely and successfully smooth out deep facial wrinkles, creases, and folds.”[147] In response to “Where can Radiesse be used?” it is clear that the institute refers to off-label uses: “Radiesse is injected just below the surface of the skin, filling in the deep creases and folds that often form between the nose and mouth and on either side of the nose. It can also be used to enhance the area surrounding the lips and to minimize acne scars. The doctor will determine which areas to inject with Radiesse based on an evaluation of the skin on your face and neck.”[148]

Such advertisement is arguably deceptive, as the language implies that the FDA approved Radiesse for the uses outlined on the website. A consumer reading that the FDA approved Radiesse “nearly a decade ago,” and that Radiesse has been used on “thousands of men and women” safely, would have no reason to assume that approval had actually been granted for uses other than those described. Thus, this example demonstrates that while the modern consumer has far more access to information than her predecessors; such information is far from straightforward and unbiased. Those with the greatest financial investments tend to be the ones disseminating information on the Internet; and unfortunately, that leads to bias and deception.

The Metropolitan Institute is far from alone in its advertising spin. Dr. Douglas Hamilton skates around the issue of FDA approval by providing the following description of his experience with Radiesse on his website: “We have been treating patients with Radiesse™ since December 2002 in our Beverly Hills, Woodland Hills & Irvine offices for the above purposes and to also help introduce this procedure in the United States ... As of April 2006 we had treated over 400 patients with Radiesse.”[149] The “above purposes” refer to “lip enhancement” and “wrinkle removal,” described earlier in the entry.[150] With his language combined with his emphasis on the large number of patients treated, Hamilton gently sidesteps the issue of FDA approval; a consumer would only become aware of its off-label status if she knew enough to inquire about it.

Similarly deceptive is the advertising on the website for Dr. Jay Garcia of Florida. On his site (with the intriguing address www.beautyinaflash.com), Garcia poses the question: “Is Radiesse™ Radiance FN FDA approved?”[151] He responds: “Yes, it is currently being used in cosmetic procedures and also being safely injected for cosmetic purposes; Bioform is approved by the FDA for off-label use.”[152] The website’s claim of having received off-label approval is misleading. The FDA does not approve devices for their off-label uses; they approve them for very specific uses, and then doctors choose to use them off-label. The circuitous manner of the above response illustrates the physician’s attempt to manipulate the comfort levels of patients.

Yet another example is found on the website of Dr. Most, a cosmetic surgeon in Washington. He offers the following description of Radiesse: “Radiesse is an FDA-approved injectable filler material. It is gel-like material composed primarily of hydroxyapetite, an important component of our bone tissue. As a gel, however, it is soft (not like bone!). As a filler material, Radiesse is used to 'fill in' areas of wrinkles or other depressions that would benefit from 'filling out'.”[153] Again, though Radiesse is technically “an FDA-approved injectable filler material,” it is FDA approved for uses other than those for which Dr. Most promotes it. In fact, by following the above language immediately with: “As a filler material, Radiesse is used to ‘fill in’ areas of wrinkles,” the text suggests that these uses are exclusively those for which Radiesse was created, and consequently, the only uses for which the FDA could grant approval.

The above examples of advertisements on websites illustrate the majority of content available to consumers seeking information on Radiesse. Admittedly, with extensive searching, one can find alternate opinions. In an online article originally published in Town and Country Magazine , two dermatologists practicing in New York City note the risks involved with using Radiesse. Dr. Rhoda Narins comments: “You may get an immediate benefit but end up with a permanent problem, like granulomas, years later.”[154] Likewise, Dr. Howard Sobel notes: “I'm cautious about things that surface too quickly, like Artecoll and Radiance.”[155] Text at eMedicine.com under “Radiesse” reads: “Caution is advised when treating the lips, as a high risk of subcutaneous nodules has been noted when treating this area.” And furthermore, Health 24 reports “a small but significant risk of ‘granuloma,’ a localised skin reaction to a foreign body that can result in hardened, sometimes itchy bumps just under the skin. And, the problem can last months or even years, studies show. The lumps can also migrate to other parts of the body with a potential for complications that doctors know little about, according to the American Society of Plastic Surgeons.”[156]

However, despite the capacity of an Internet surfer to discover these cautionary opinions on Radiesse, the available information, to an overwhelming degree, can be found on the promotional websites examined above.

And thus, this case study of Radiesse demonstrates two distinct phenomena; first, consumers develop an arguably false sense of empowerment by their increased access to information, and second, the FDA regulations on the marketing of off-label uses are – for all practical purposes – completely useless.

In an age when the average consumer is capable of smuggling in illegal fillers from another country, the burdens of protecting the health and safety of patients complicate and increase. Years ago, consumers submitted to the medical degrees of their physicians; today, they provide doctors with the very tools shipped from abroad to perform their procedures. The modern patient seeking an injectable filler has visited the websites; she has read the “frequently asked questions” sections on physicians’ homepages. And thus, she feels no less knowledgeable than the caretaker she entrusts.

On one hand, this increased access to information represents the most powerful tool in a patient’s arsenal. No longer is she bound by the constraints of a single cosmetic surgeon’s consultation; she can surf the Internet and seek treatments that she finds most desirable, most appropriate.

On the other hand, that same access represents the greatest hindrance to an unbiased education. The naïve consumer fails to recognize that the majority of available information on the Internet seeks to manipulate, rather than educate. Manufacturers and cosmetic physicians have invested their finances, their livelihoods in the use of these fillers; and consequently, they construct the content of webpages accordingly.

And thus, when one discerningly examines the information available on the Internet, one realizes the astounding dysmmetry. A plethora of physicians skate around the issue of FDA approval, and only a few note the potentially serious side effects, focusing their content on luring in customers rather than educating the public. A patient might easily conclude that the use of Radiance to treat wrinkles is FDA approved, considering the deceptive language outlined above on physicians’ webpages.

The result is not the empowerment of the average consumer, but rather, deception. The patient feels empowered by her new knowledge, when in reality, she was the recipient of a multi-million dollar marketing campaign - not an education.

3. The FDA’s Approach to Off-Label Marketing

In examining the FDA’s role to protect the consumer, one considers the agency’s policies on marketing off-label uses of products. As demonstrated by the Radiesse case study, manufacturers have discovered numerous ways to sidestep the technicalities; despite the FDA’s prohibitions, consumers today are the direct recipients of off-label marketing by manufacturers.

On one hand, the government has taken the illegal marketing of drugs and devices very seriously. In 1996, the government brought criminal misbranding charges against Warner-Lambert for the off-label promotion of its drug Neurontin.[157] The case was settled in 2004, after the government alleged that Warner-Lambert “actively promoted Neurontin for off-label uses through its sales reps, medical liaisons, teleconferences, consultants’ meetings, and advisory boards.”[158] Warner-Lambert pled guilty to distribution of an unapproved new drug and distribution of a misbranded drug. Warner-Lambert settled the case by agreeing to pay $430 million in criminal fines and civil payments.[159]

Between 2000 and 2004, the federal government investigated the pharmaceutical company Serono for alleged violation of the False Claims Act for its illegal marketing of Serostim, a drug approved by the FDA to treat AIDS wasting. Serono allegedly expanded the definition of AIDS wasting to include loss of body cell mass, “despite an absence of objective weight loss.” Additionally, Serono illegally promoted the drug for lipodystrophy.[160]

In 2005, the federal government and Serono reached a settlement, in which Serono agreed to pay $704 million in criminal fines.[161]

These examples indicate that the government has successfully initiated investigations into illegal off-label promoting; thus providing some mechanism to tame the aggressive techniques of pharmaceutical marketers. However, while governmental regulation may target blatant, uncontroversial violations of the law; the most questionable territory involves the shades of gray. The evolution of the Internet has created marketing channels so expansive that pharmaceutical manufacturers face little difficulty bypassing FDA regulations to market off-label uses to consumers. For example, the above case study of Radiesse illustrates the ease with which pharmaceutical manufacturers can functionally achieve that which the FDA seeks to prohibit; while falling short of blatant illegality. First, Radiesse’s own promotional website fails to provide any substantial information regarding the product on its “USA” page, requiring customers to enter its far more engaging, “Radiesse Worldwide” page to obtain information. This transition is marketed by a large icon on the American site. The result is that American consumers receive direct promotional materials from the manufacturer itself on the off-label use of the device. Not even hidden, or earmarked as “off-label,” the description of this use occupies the entire front page and most of the site’s space. Additionally, websites embodying every attribute of a manufacturer’s promotional site can skate the line of liability by denying affiliation; the promotional website for Radiance claims no link to the actual manufacturer.

And unfortunately, while naïve consumers believe the information they gather from these websites increases their decision-making abilities, they are in fact recipients of limited and biased information: “Unfortunately, information presented by pharmaceutical companies is often a poor substitute for the substantial evidence presented to the FDA. As the Neurontin controversy shows, pharmaceutical companies are beholden to the interests of stakeholders and investors rather than the public, and simply do not adhere to the ethical guidelines outlined in Section 401 of the FDAMA.”[162]

These examples of marketing illustrate the ability of the pharmaceutical industry to sidestep technicalities, qualitatively deeming the FDA’s regulatory power useless. The Internet has simply revolutionized the industry, and provided direct access to consumer markets at an unprecedented level. Thus, marketing channels have transformed, and manufacturers have discovered a myriad of ways to bypass marketing prohibitions. In response, the FDA must adapt its guidelines and strengthen its positions to accommodate a technologically changing society; useless guidelines reflect a useless agency.

E. ArteFill

The case study of Radiesse illustrated questionable tactics used by a manufacturer to market an off-label use of a product, despite FDA prohibitions. A study of the injectable filler known by the names of Arteplast, Artecoll and ArteFill illustrates another example of such manipulation.

Arteplast was first used as an injectable filler in Europe between 1989 and 1994, “sieved from bone cement using a nylon mesh.”[163] Although the “rate of satisfaction was consistently high ... the rate of side effects was unacceptably high as well.”[164] In fact, researchers noted that “there are several reports from Europe of foreign body granuloma formation associated with Arteplast and other permanent filler substances.”[165] In a 1989 study conducted by the Ethical Commission of Frankfurt University, 15 subjects of 587 “developed foreign-body granulomas from 6 to 19 months after injection.”[166]

In response, researchers modified Arteplast by changing “the PMMA microsphere sieving procedure and use of collagen as a suspension medium.”[167] They labeled the result Artecoll, which “is composed of PMMA microspheres, 30 to 42 microns in size, suspended in a water based carrier gel composed of 3.5% bovine collagen, 96.5% buffered, isotonic water for injection including 0.3% lidocaine.”[168]

Artecoll is injected through a tunneling technique with a hypodermic needle: “The plunger is depressed and deposits the Artecoll while pulling out of the skin, leaving a small cylindrical mass of Artecoll. Each microbead is coated in bovine collagen to keep from clumping together; after the body gradually absorbs the collagen, it replaces it with its own collagen and causes a plumping up of the wrinkles or lips.” [169]

After conducting a one-year study of 117 women and 11 men, Artecoll’s manufacturer sought approval from the FDA in 2003. Though the FDA Advisory Panel recommended Artecoll, the FDA expressed concerns, and did not grant approval, but sent an “approvable letter” in 2004.

Even in the manufacturer’s study, within the first year – “16 percent of the 128 patients had complications, including persistent swelling, lumpiness, flu-like symptoms, and blurred vision.”[170] As Dr. Lowe notes, when questioned about Artecoll: “Still not approved for cosmetic use in the US. Problems can arise when granulomas develop around the remaining beads. The beads can also form crystals which can be felt beneath the skin.”[171]

After using Artecoll in their respective countries for years, doctors in Switzerland and Canada encountered problems with the device that support the FDA’s hesitance:

“Three Swiss medical societies issued a warning against its use in the face because of reports that it causes granulomas, which lead to unsightly bumps that usually have to be removed surgically. Many Canadian doctors disavow its use for lip augmentation for the same reasons. A large portion of the medical community believes Artecoll can cause inflammatory reactions that induce scar tissue, making removal of the beads nearly impossible without causing some lip disfigurement. In 2003, the Canadian company that sells Artecoll claimed that only 10 cases out of 8,000 patients worldwide have reported nodules within two years, but interviews with Canadian doctors indicate many more problems. Plastic surgeons explain that they don’t report lumpy lips because it doesn’t seem sufficiently important, but that means that there is no way to determine how many patients have experienced unattractive and sometimes disfiguring lumps and nodules.”[172]

As a result of the “large, unsightly bumps” that develop after a few years, the Swiss federal office of public health recommended that physicians halt their usage of permanent cosmetic fillers such as Artecoll. “Swiss authorities say complications, such as inflammation, can occur long after an injection and they say the cosmetic benefits of a permanent filler don't counterbalance those risks.” [173]

1. Conflicting Accounts of Incidences of Granuloma

Artecoll was approved for commerical use in Canada in 1988, where 10,000 syringes have been sold; and as many as 12,000 patients have been injected. [174] Artecoll’s manufacturer, Canderm, markets the product in pamphlets and on its website with the following claim: "Since Artecoll was introduced on the Canadian market in August, 1998, no incidences (of granuloma) have been reported."[175] In 2004, Dr. Stefan Lemperle, CEO of Artes Medical, made the following grand claims to Business Wire: “Many attempts have been made to develop a safe, partially synthetic material to permanently fill wrinkles and scars because the body absorbs all biological substances within one year. Previous synthetic products have been associated with negative side affects such as granulomas or late allergic reactions.”[176] However, “Artecoll has been specifically engineered to overcome these obstacles and provide safe, enduring results.”[177]

Despite Dr. Lemperle’s confident proclamations, other physicians deeply question the veracity of these claims: “at least three Toronto doctors each say they've found two granulomas associated with Artecoll and have told the company. A fourth doctor says he had seen and treated one of the lumps but didn't call Canderm. Among those finding granulomas was Toronto plastic surgeon Dr. Frank Beninger, who teaches Artecoll use on behalf of the firm and is paid for that service by Canderm.”[178] Beninger continues: “Both (cases) that I've seen were in the lip, [and] confirmed by a pathologist's analysis while the other precisely matched every characteristic of a granuloma, including disappearing with a steroid injection.”[179]

In 1999, four physicians published their discoveries of granuloma in three Artecoll patients in the American Journal of Surgical Pathology. The granuloma consisted of round vacuoles surrounding circumscribed, translucent, nonbirefringent foreign bodies. Their existence led to the excisions of the cosmetic implants in each patient.[180]

Dr. Stephen Mulholland, a cosmetic surgeon in Toronto, admits to having used “gallons” of Artecoll on his patients. However, he notes that “A lot of doctors are afraid to use it in the lips because you get those little nubbins... In about 50 per cent of (lip) patients you have lumps — no question about it. And patients need to know that.”[181]

Although bumps can also be caused by other types of injectable fillers, the permanence of Artecoll makes the bumps far more problematic: “long-term bumps are clearly a bigger problem with Artecoll,” as “Artecoll is an implant. You're putting solid material in there.”[182] Furthermore, as Canadian plastic surgeon Dr. Claudio De Lorenzi notes: “There's no way to remove this stuff except by cutting it out ... This is not acceptable for my patients.” De Lorenzi has since stopped offering Artecoll injections in his patients’ lips.[183] In fact, De Lorenzi felt so strongly, that he warned American doctors at the Aesthetic Meeting 2002 in Las Vegas: “It’s a part of our duty to tell others what our experience has been ... Instead of getting uniform enlargement, you get little tiny bits of gravel under the skin ... When the material coalesces together, you get a hard lump in the lip.”[184] While physicians have observed fewer problems when using Artecoll in other areas: “In what appeared to me as possibly its best possible use - lip enlargement, the material has failed miserably and unfortunately causes significant problems.”[185]

Largely as a result of De Lorenzi’s “warning,” Canadian doctors called for further clinical guidelines and additional research on adverse reactions to injections of Artecoll. Even patients themselves are issuing “warnings” to their peers; one patient posted the following on a public web discussion forum on lip augmentation:

“BE CAREFUL WITH THIS STUFF!!! Read my post earlier in the board. I am extreemely(sp) unhappy with my results. Raised scars now, wrinkled skin, uneven bumps and overcorrection (I now have labial folds when I did not before). Lips are probably safer areas, but scars and wrinkles and hollowed areas require exact and aesthetic injections. Unfortunately, my "technician" was inexperienced and inexact. I am now considering a facelift, dermabrasion, peels, implants and lipo for my face.”[186]

Even if Artecoll eventually receives FDA approval, Dr. Michelle Copeland, plastic surgeon in New York City and author of CHANGE YOUR LOOKS, CHANGE YOUR LIFE , expresses hesitation to use it on her patients. “My concern is even if it gets FDA approval, there's a chance you could have a problem with it and the correction can cause more irregularities in your tissues. Do you want to take that chance?”[187]

2. Accusations of Illegal Use and a Cover-Up Scam

And if the questionable veracity of the manufacturer’s health claims does not give rise to sufficient suspicion of Artes Medical’s integrity, the corporation has recently been accused of engaging in other severely misleading tactics. Whereas the above case studies involved false claims by unlicensed practitioners using bogus ingredients, at the center of this investigation is the manufacturer’s co-founder, Dr. Gottfried Lemperle.[188] Lemperle is attributed with the invention of Artefill, and maintains a license to practice dermatology in Germany. However, he remains unlicensed in the United States.[189]

Hairdresser Elizabeth Sandor, 40, alleged in May 2006 that Dr. Lemperle used Artefill as an injection to fill her facial wrinkes in 2002, when Artes Medical was still a small start-up company.[190] She alleges that Lemperle falsely convinced her that Artefill had received FDA approval, and that he never disclosed his lack of license in California.[191] Her claims detail suffering of pain and disfigurement: “[b]y March 2004, Sandor’s face was inflamed, she had scarring near the injection sites and had a fever and aches and pains, all of which she attributed to a negative reaction to Artefill.”[192] As a follow-up to her reactions, Sandor contends that Artes’ chief executive and Gottfried Lemperle’s son, Stefan Lemperle, convinced her to refrain from visiting a hospital, and referred her to dermatologist Steven Cohen. Sandor alleges that she was unaware that Cohen was the lead physician in the Artefill clinical trials, and an investor in Artes Medical. Despite the persistence of her negative reaction, Sandor claims that Cohen refrained from referring her to anyone else. Further, she alleges that the Lemperles and Cohen “sought to hide her negative reactions to Artefill so that it would not be included in the clinical trial results submitted to the FDA.”[193]

Although the Lemperles deny the accusations, attorneys say that emails verify Sandor’s story. Additionally, “[a]n internal investigation by Artes also determined that Gottfried Lemperle had used Artecoll, a predecessor product to Artefill that was sold outside the United States, on four people in this country, according to SEC documents.”[194] Meanwhile Stefan Lemperle had been publicly denouncing consumers who inappropriately sought injections in a practitioner’s home: “These people have money and could have chartered a plane, flown to Vancouver and had someone who is trained in using Artecoll do their work and avoid all these problems ... Instead they paid someone they didn’t know to do it in the bathroom.”[195]

These allegations create cause for substantial concern on the part of both consumers and regulators. The incentives of manufacturers and consumers are misaligned, and thus, consumers suffer as recipients of misleading information. The case study of Radiesse illustrates the new difficulties in policing off-label marketing that have arisen with the growth of technology. The case study of Artes Medical further demonstrates inappropriate techniques used by manufacturers in tending to the needs of a population crazed with desire for youth and beauty. While the government can and should be trusted to engage in criminal investigations, the magnitude and breadth of these improprieties are overwhelming. And unfortunately, the burden of confronting these barriers erected by a changing society is shared by the FDA; in its mission to protect the health and safety of the public, the regulatory agency must adapt to accommodate and preempt the cunning ways of the new frontier.


This paper has sought to illustrate the regulatory challenges and consumer risks that have accompanied the nation’s obsessive pursuit of the newest injectable filler. The promise of attaining youth and beauty has eluded cultures since Cleopatra, but the relatively novel potential to eliminate wrinkles and re-contour the face has lured more consumers than ever - from hairdressers to suburban housewives, from men to transgendered women. Researchers and pyschologists identify the causes of this phenomenon as rooted in technology, in consumption, and in the changing opinions of mental illness.

The first case study traced the incredible progress of the “world’s most poisonous poison” from its role in sausage poisoning and canning outbreaks, to its injection as a wrinkle-filler. Whereas the FDA successfully combated botulism and educated housewifes on proper home-canning techniques, the task of controlling the safety and appropriateness of injectable Botox has proven more difficult. Little hesitation accompanied off-label uses before the FDA approved cosmetic applications of Botox. Once the FDA granted its approval, the floodgates opened, and women across the nation now request a glass of white wine along with their potentially fatal poison. Even more disconcerting has been the emergence of widespread illegal use; black market Botox disfigures and kills, but has been embraced by unfortunate recipients as a cost-effective way to reduce wrinkles.

The next case study observed the even more dangerous phenomenon of liquid silicone injections. Banned by the FDA in 1992, then approved for ophthalmologic procedures in 1994, silicone injections are accompanied by an appropriately significant amount of hesitation by many in the medical community. Unfortunately, consumers are less afraid, and innumerable instances of disfigurement and fatalities have emerged as results of “pump parties.” Without a remote nod to the health risks involved in any type of injection, women, in the masses, have welcomed industrial-grade silicone into their bodies and faces – with disfigurement and death as common consequences. In contemplating its potential approval, the FDA ought to use the expedited trajectory of Botox as a warning; if pump parties are accepted practice within certain communities now – imagine what the floodgates will usher in upon approval.

In observing the cultural obsession with injectable fillers, it is impossible to ignore the pivotal role played by technology. As a result of the Internet, consumers have access to vast amounts of previously unattainable information – and manufacturers have unprecedented access to consumers. The FDA prohibits manufacturers from marketing the off-label uses of devices; however, the Internet provides innumerable ways for manufacturers to sidestep regulations. The third case study examined the filler Radiesse, and detailed the cunning ways the manufacturer marketed off-label uses. And manufacturers are not alone; physicians similarly lure online customers by describing devices with deceptive language. In particular, some physicians skate around the issue of FDA approval by using text that implies the approval of an off-label use. While not technically constituting blatant lies, much of this information is severely misleading.

And thus the emergence of the Internet as a massive marketing channel forces the FDA to confront changing times; new technology requires that the FDA recognize the obselete nature of its marketing guidelines. Perhaps the solution requires physicians to inform patients of a device’s FDA approval status. Regardless of its conclusions, the FDA must acknowledge the role played by technological evolution, and address it accordingly.

Lastly, the final case study examined the path of Arteplast/Artecoll/ArteFill. Perhaps more blatantly than the above examples, Artes Medical similarly crossed ethical lines by misrepresenting accounts of granulomas. Additionally, co-founder Gottfried Lemperle allegedly lied to a patient about the device’s approval status and attempted to exclude her negative reactions to the treatment from clinical studies. She suffered pain, disfigurement and massive deception, in this case not at the hands of a hairstylist masking as a practitioner, but from the chief scientist of a product likely to receive FDA approval. This behavior exemplifies the unfortunate ramifications of an industry crazed and overwhelmed in its attempt to meet the needs of a zealous public.

And thus, it seems, that most of the players involved in the industry have demonstrated great flexibility and cunningly quick, if not unethical, response to change. Psychotherapists have adjusted their musings on the pursuit of beauty to accommodate technology, rampant consumerism and the changing perceptions of mental illness. The result is in modified theories, which use the above factors to explain the cultural obsession with re-contouring faces and eliminating wrinkles. Likewise, the manufacturers have seamlessly integrated their marketing techniques with the rapid growth of the Internet; they have brilliantly used online channels of communication to mass market repeatedly and intensively to consumers. And finally, the last to change, the last to adapt: the government. Regulatory agencies must confront the changing times, must react to new developments with flexibility and creativity. Acknowledging the craze, identifying the factors that have caused consumer harm, and actively seeking change will allow the FDA to confront and manage the debacle created by injectable fillers, and ultimately fulfill its role of providing safety and protection to the American public.

[1] Ann Marie Gardner, Beyond Botox: Imagine Looking Younger in an Instant, with No Surgery and No Side Effects , HARPER’S BAZAAR, Apr. 1, 2002.


[3] Id . at 39.

[4] Id . at 41.


[6] DAVIS , supra note 2, at 41.

[7] Massachusetts Plastic Surgery Network, Plastic Surgery Statistics, http://www.plastic-surgery.net/plastic-surgery-statistics.html (last visited May 18, 2006).

[8] eBreastaug.com, ASAPS Statistics – Cosmetic Procedures, http://www.ebreastaug.com/breast-augmentation/asaps-statistics.html (last visited May 18, 2006).


[10] Id . at 17.

[11] DAVIS , supra note 2, at 17.

[12] Id .

[13] Id . at 18.

[14] Id . at 17.

[15] DAVIS , supra note 2, at 19.

[16] Id . at 47.


[18] Id . at 24.

[19] Id .

[20] DEYO & PATRICK , supra note 9, at 19.

[21] DAVIS , supra note 2, at 20.

[22] The Food and Drug Administration Modernization Act of 1997, Pub. L. No. 105-115, § 406(b)(1), 111 Stat. 2296 (codified at 21 U.S.C. §§ 301 et seq.).

[23] The Food and Drug Administration Modernization Act of 1997 § 406(b)(2).

[24] The Food and Drug Administration Modernization Act of 1997 § 205.

[25] 21 U.S.C. § 360e(c)(1)(A) (2000).

[26] 21 U.S.C. § 360e(c)(1)(B) (2000).

[27] 21 U.S.C. § 360e(c)(1)(C) (2000).

[28] Food and Drug Admin., Device Advice on Pre-Market Approvals , http://www.fda.gov/cdrh/devadvice/pma (last visited May 18, 2006).

[29] Id.

[30] See id.

[31] 21 U.S.C. §360e(d)(1)(A) (2000).

[32] Peter Barton Hutt & Richard A. Merrill, FOOD AND DRUG LAW: CASES AND MATERIALS 619 (2d ed. 1991).

[33] Food and Drug Admin., Guidance for Institutional Review Boards and Clinical Investigators 1988 Update: “Off-Label” and Investigational Use of Marketed Drugs, Biologics and Medical Devices , http://www.fda.gov/oc/ohrt/irbs/offlabel.html (last visited May 18, 2006).

[34] Id.

[35] Id.

[36] Food and Drug Admin., Use of Approved Drugs for Unlabeled Indications , 12 FDA DRUG BULLETIN 4 (April 1982).

[37] James Beck & Elizabeth Azari,FDA, Off-Label Use, and Informed Consent: Debunking Myths and Misconceptions , 53 FOOD & DRUG L.J. 71, 77 (1998).

[38] 21 U.S.C. § 396 (2000).

[39] Janet Woodcock, Presentation at DIA Montreal: A Shift in the Regulatory Approach (June 23, 1997), available at http://www.fda.gov/cder/present/diamontreal/regappr/sld005.htm (last visited May 18, 2006).

[40] Beck & Azari, supra note 37, at 80.

[41] Alexander T. Tabarrok, Assessing the FDA via the Anomaly of Off-Label Drug Prescribing , 5 THE INDEP. REV. 25, 26 (2000).

[42] See id .

[43] HUTT & MERRILL , supra note 32, at 630.

[44] 531 U.S. 341, 349 (2001).

[45] See 767 A.2d 1078, 1083 (Pa. Super. Ct. 2001).

[46] Id .

[47] Food and Drug Admin., Drug Maker to Pay $430 Million Fines, Civil Damages , FDA CONSUMER MAGAZINE , July-Aug. 2004, http://www.fda.gov/fdac/features/2004/404_wl.html.

[48] The Food and Drug Administration Modernization Act of 1997 § 551.

[49] The Food and Drug Administration Modernization Act of 1997 § 551.

[50] DAVIS , supra note 2, at 161.

[51] Id.

[52] MACINNIS , supra note 5, at 101.

[53] Center for Disease Control., Foodborne Botulism in the United states, 1990-2000 , 10 EMERGING INFECTIOUS DISEASES 1606 (Sep. 2004), available at http://www.cdc.gov/foodborneoutbreaks/pulication/2004/j_sobelBot_US_EID2004pdf.pdf.

[54] Center for Disease Control, Botulism, http://www.cdc.gov/ncidod/dbmd/diseaseinfo/botulism_g.htm (last visited May 19, 2006).

[55] Infant botulism results from the ingestion of clostridium bacterium spores, producing toxin in the intestinal tracts; it affects infants under 12 months of age. Infant botulism is often contracted through exposure to soil, dust and foods. Wound botulism results from the entry of clostridium bacterium into open wounds, and is often associated with intravenous drug users. See Food and Drug Admin., Foodborne Pathogenic Microorganisms and Natural Toxins Handbook: Clostridium botulinum, http://www.cfsan.fda.gov/~mow/chap2.html (last visited May 19, 2006).

[56] K.F. Meyer, Prevention of Food Poisoning , 40 SCI. MONTHLY 546 (1935).

[57] Id. at 565.

[58] See Food and Drug Admin., Foodborne Pathogenic Microorganisms and Natural Toxins Handbook: Clostridium botulinum, http://www.cfsan.fda.gov/~mow/chap2.html (last visited May 19, 2006).

[59] Id.

[60] WebMD, Botulinum Toxin (BOTOX), http://www.emedicine.com/neuro/topic585.htm (last visited May 19, 2006).

[61] See id.

[62] Carol Lewis, Botox Cosmetic: A Look at Looking Good , FDA CONSUMER MAGAZINE , July-Aug. 2002, http://www.fda.gov/fdac/features/2002/402_botox.html.

[63] http://www.botox.com.

[64] Lewis, supra note 62.

[65] Columbia University College of Physicians and Surgery, Botox Injections for Wrinkles, http://www.entcolumbia.org/botox.htm (last visited May 19, 2006).

[66] Lewis, supra note 62.

[67] Meena Shah, Botulinum Toxin’s Off-Label Uses: Poison for Beauty , EXPRESS PHARMA PULSE , May 9, 2002, http://www.expresspharmapulse.com/20020509/offbeat.shtml.

[68] Siobahn Darrow, Botulin Derivative New Poor Man’s Face Lift , CNN.COM , July 1, 1999, http://www.cnn.com/HEALTH/9907/01/botox.boom/.

[69] Id .

[70] Id .

[71] Lewis, supra note 62.

[72] Id .

[73] Tracy Smith, Throw a Botox Party? , CBS NEWS, June 7, 2002, http://www.cbsnews.com/stories/2002/06/06/earlyshow/contributors/tracysmith/main511360.shtml.

[74] Rand Richards Cooper, The Yyear in Ideas; Botox Parties , N.Y. TIMES, Dec. 15, 2002, available at http://query.nytimes.com/gst/fullpage.html?sec=health&res=9C00E4DE153AF936A25751C1A9649C8B63.

[75] Smith, supra note 73.

[76] KRON 4, Botox Parties , http://www.kron4.com/Global/story.asp?S=787444 (last visited May 19, 2006).

[77] Rachel Zimmerman, Old Business Model Adds a New Wrinkle , STARTUP J. , http://www.startupjournal.com/ideas/services/20020424-zimmerman.html (last visited May 19, 2006).

[78] Id .

[79] Id .

[80] Id .

[81] American Academy of Dermatology, Patient Alert: American Academy of Dermatology Stresses the Safe Use of Botulinum Toxin, Apr. 30, 2002, http://www.aad.org/public/News/NewsReleases/Press+Release+Archives/Cosmetic+Dermatology+-+Aging/BotoxParties.htm.

[82] Id .

[83] Id .

[84] Smith, supra note 73.

[85] Kron 4, supra note 76.

[86] CBS, Cracking Down On Bogus Botox , CBS NEWS , Jan. 3, 2005, http://www.cbsnews.com/stories/2005/01/03/eveningnews/main664518.shtml.

[87] Center for Infectious Disease Reasearch and Policy, Reports Blame Florida Botulism Cases on Misused Toxin , Dec. 15, 2004, http://www.cidrap.umn.edu/cidrap/content/bt/botulism/news/dec1504botulism.html.

[88] Peter Franceschina, S. Florida Botulism Victims Begin Therapy, Seek to Warn Others , SUN-SENTINEL Feb. 5, 2005, available at


[89] No Pundit Intended, Bootleg Botox Blues, http://www.nopunditintended.com/2005/02/bootleg_botox_blues.html (Feb. 3, 2005, 13:21 EST).

[90] Lilian Kim, Woman Dies After Bogus Botox Injection: Hair Stylist Has No Medical License , ABC NEWS KGO , Mar. 15, 2006, http://abclocal.go.com/kgo/story?section=local&id=3994596.

[91] CBS, supra note 86.

[92] Lewis, supra note 62.

[93] Lance H. Brown & Paul J. Frank, What's New in Fillers? , J. DRUGS DERMATOLOGY , June 2003, at 5, http://www.findarticles.com/p/articles/mi_m0PDG/is_3_2/ai_110808287/pg_5.

[94] Philip J. Hilts, Strange History of Silicone Held Many Warning Signs , N.Y. TIMES , Jan. 18, 1992, available at http://query.nytimes.com/gst/fullpage.html?res=9E0CEFD8153BF93BA25752C0A964958260.

[95] Id .

[96] See id .

[97] See id .

[98] Food and Drug Admin., FDA Breast Implant Consumer Handbook – 2004; Timeline Of Breast Implant Activities, http://www.fda.gov/cdrh/breastimplants/handbook2004/timeline.html (last visited May 19, 2006).

[99] Press Release, Food and Drug Admin., Physicians to Stop Injecting Silicone for Cosmetic Treatment of Wrinkles (Feb. 28, 1992), available at http://www.fda.gov/bbs/topics/NEWS/NEW00267.html.

[100] Id .

[101] Id .

[102] Id .

[103] Brown & Frank, supra note 93, at 5.

[104] Id . at 6.

[105] Id .

[106] Hilts, supra note 94.

[107] Brown & Frank, supra note 9394, at 6.

[108] Lance H. Brown & Paul Jarrod Frank, The Cosmetic Clinic: The Silicone Conundrum , 10 SKIN & AGING 15 (DEC. 2002) , available at http://www.skinandaging.com/sa/displayArticle.cfm?articleID=article1102.

[109] Sandra Blakeslee, Fighting Wrinkles with Fat; Other Remedies at Issue , N.Y. TIMES , July 24, 1991, http://query.nytimes.com/gst/fullpage.html?res=9D0CE3DA1430F937A15754C0A967958260.

[110] Id .

[111] Local 10.com, Silicone Injected At Parties In South Florida , http://www.local10.com/news/564792/detail.html (last visited May 19, 2006).

[112] Marty Graham, U.S. Experts Warn of Risky Silicone ‘Pump Parties’ , REUTERS, JULY 5, 2005 , available at http://www.msnbc.msn.com/id/8463413/.

[113] Id .

[114] Dallas Denny, Cheekbones from Hell, or Injectable Silicone: Bad News , GENDER.ORG , http://www.gender.org/resources/bad_news.html (last visited May 19, 2006).

[115] Local 10.com, supra note 1111.

[116] Id .

[117] Graham, supra note 1122.

[118] Id .

[119] Id .

[120] Id .

[121] Thomas C. Tobin, It's Food, Drink and Injections , ST. PETERSBURG TIMES , Apr. 18, 2001, http://www.sptimes.com/News/041801/State/_It_s_food__drink_and.shtml.

[122] Id .

[123] Id .

[124] Id .

[125] Id .

[126] Id .

[127] Id .

[128] Id .

[129] Id .

[130] Beth Landman, Beyond Botox , N.Y. MAG. , Oct. 6, 2003, http://newyorkmetro.com/nymetro/health/bestdoctors/cosmeticsurgery/2003/n_9281/ .

[131] Id .

[132] Sana Siwolop, Personal Business; Beyond Botox: An Industry's Quest for Smooth Skin , N.Y. TIMES , Mar. 9, 2003, http://query.nytimes.com/gst/fullpage.html?res=9806EFD7103FF93AA35750C0A9659C8B63.

[133] Judy Marcus, The Latest Wrinkle: Finding Eternal Youth Without Going Under the Knife , N. SHORE MAG. , http://www.northshoremag.com/cgi-bin/ns-article?article=/healthfam/02-04-healthfam-3.dat (last visited May 19, 2006).

[134] Id .

[135] Injectable Micro-implants, http://www.yestheyrefake.net/injectable_fillers_micro_implants.htm (last visited May 19, 2006).

[136] Id .

[137] Id .

[138] WebMD, Dermal Fillers, http://www.emedicine.com/derm/topic515.htm (last visited May 19, 2006).

[139] Radiesse, http://www.radiesse.com (last visited May 19, 2006).

[140] Radiesse-USA, http://www.radiesse.com/radiesse-usa.html (last visited May 19, 2006).

[141] Radiesse-Worldwide, http://www.radiesse.com/worldwide.html (last visited May 19, 2006).

[142] Id .

[143] Id .

[144] Radiance Treatment, http://www.radiancetreatment.com (last visited Apr. 20, 2006). The website has apparently since been discontinued.

[145] Id .

[146] Id .

[147] Metropolitan Institute of Plastic Surgery, Skin Care – Radiesse, http://www.metplasticsurgery.com/scare_rad.asp (last visited May 19, 2006).

[148] Id .

[149] Douglas Hamilton, M.D., Injectables, http://www.douglashamiltonmd.com/html/injectables.html (last visited May 19, 2006).

[150] Id .

[151] The Body Image Laser Institute, http://www.beautyinaflash.com/radiance.html (last visited May 19, 2006).

[152] Id .

[153] Sam P. Most, M.D., http://www.drmost.com/radies.html (last visited May 19, 2006).

[154] Janet Carlson Freed, The Latest Wrinkle-Fixers , TOWN & COUNTRY , Nov. 2003, http://magazines.ivillage.com/townandcountry/style/health/articles/0,,284694_602549,00.html.

[155] Id .

[156] Health24.com, A New Fountain of Youth? , July 21, 2003, http://www.health24.com/news/Plastic_surgery/1-938,23440.asp.

[157] Jack Cinquegrana & Diana K. Lloyd, Legal: Shifting Perspective on Off-Label Promotion , PHARMACEUTICAL EXECUTIVE , Jan. 1, 2006, http://pexec.adv100.com/pharmexec/article/articleDetail.jsp?id=282490&pageID=2.

[158] Id .

[159] See id .

[160] See id .

[161] Id .

[162] American Medical Student Association, Off-Label Marketing of Pharmaceuticals, http://www.amsa.org/hp/OffLabel.cfm (last visited May 19, 2006).

[163] Food and Drug Admin., Gen. and Plastic Surgery Devices Panel of the Med. Devices Advisory Comm. (Feb. 28, 2003), at 28, available at http://www.fda.gov/ohrms/dockets/ac/03/transcripts/3934t1-am%20session.doc.

[164] Id . at 29.

[165] Id .

[166] Steven R. Cohen & Ralph E. Holmes, Artecoll: A Long-Lasting Injectable Wrinkle Filler Material: Report of a Controlled, Randomized, Multicenter Clinical Trial of 251 Subjects , COSMETIC , Sep. 15, 2004, available at http://www.artesmedical.com/pdf_download/cohen_revd_proof.pdf.

[167] Food and Drug Admin.,Summary of Safety and Effectiveness Data: Artecoll , at 3, available at http://www.fda.gov/ohrms/dockets/ac/03/briefing/3934b1_01_SSE-artes.doc

[168] Id . at 1.


[170] Id .

[171] Alice Hart-Davies, Do You Really Want This in Your Face , EVENING STANDARD (LONDON) , Mar. 15, 2005, http://www.findarticles.com/p/articles/mi_qn4153/is_20050315/ai_n12942296/pg_4.

[172] ZUCKERMAN & NICHOLS , supra note 1699, at 3.

[173] Leslie Papp, Lumpy Lips a Danger with Canadian Substance, Artecoll , http://www.talksurgery.com/consumer/new/new00000103_6.html (last visited May 19, 2006).

[174] Mark Blanchard, Filler Material May Cause Nodules, Lumps in Lips , COSMETIC SURGERY TIMES , June 1, 2002, available at http://mediwire.mediwire.com/main/Default.aspx?P=Content&ArticleID=20543.

[175] Papp, supra note 1733.

[176] Landmark U.S. FDA Clinical Trial Results for First Permanent Injectable Wrinkle Filler Published in Journal of Plastic and Reconstructive Surgery , BUSINESS WIRE , Nov 9, 2004, http://www.findarticles.com/p/articles/mi_m0EIN/is_2004_Nov_9/ai_n6337543.

[177] Id .

[178] Papp, supra note 1733.

[179] Id .

[180] Christina M. Rudolph et al., Foreign Body Granulomas Due to Injectable Aesthetic Microimplants , 23 AM. J. SURGICAL PATHOLOGY 113 (1999) , available at http://www.ajsp.com/pt/re/ajsp/abstract.00000478-199901000-00013.htm;jsessionid=EYcjybXh3Yd4804PtCn4YU9UJYj4vZ0h21J8AaeBnX2zhz0e2Unz!-839643570!-949856144!9001!-1.

[181] Papp, supra note 1733.

[182] Id .

[183] Id .

[184] Blanchard, supra note 1744.

[185] Id .

[186] Posting of spoonman to Healthboards.com, http://www.healthboards.com/ubb/Forum36/HTML/000448.html (Dec. 31, 2001, 15:35 PM EST).

[187] Kristi Palma, Injecting Youth , EAGLE TRIBUNE , Mar. 10, 2003, http://www.eagletribune.com/news/stories/20030310/LI_001.htm.

[188] Terri Somers, Product Disfigured Her, Woman Says in Lawsuit , UNION TRIBUNE , May 13, 2006, available at http://www.signonsandiego.com/news/business/20060513-9999-1b13artes.html.

[189] Id .

[190] Id .

[191] Id .

[192] Id .

[193] Id .

[194] Id .

[195] Id .