Lipodissolve

Editors-In-Chief: Martin I. Newman, M.D., FACS, Cleveland Clinic Florida, [mailto:Newmanm@ccf.org]; Michel C. Samson, M.D., FRCSC, FACS [mailto:samsonm1@ccf.org]

Overview
Lipo-dissolve or Lipodissolve, LipoShape or Lipostabil, also called injection lipolysis, is a controversial cosmetic procedure in which various non-FDA approved drug mixtures, often called PCDC, or phosphatidylcholine deoxycholate, are injected into patients to remove fat. This practice evolved from the initial intravenous use of PC-containing drug formulations to treat blood disorders. In 1966, investigators noted that the intravenous infusion of PC-containing solutions could remove fat emboli. Later, a drug formulation called LIPOSTABIL® containing 5% PC and 4.75% deoxycholate (DC) was approved in Germany and used in the treatment of fat embolism, dyslipidemia , and alcohol-induced liver cirrhosis. The first report of LIPOSTABIL® injection for fat removal demonstrated that infra-orbital (‘under the eyelid’) fat could be removed by LIPOSTABIL® injection. While no placebo-controlled studies have demonstrated the safety or efficacy of this therapy, numerous retrospective studies of LIPOSTABIL® injections have reported the efficacy of this unapproved practice. While the safety of Lipodissolve injections has yet to be proven in a prospective, placebo-controlled, double-blind clinical study, retrospective studies suggest that this practice does not present significant medical risk. The American Society for Aesthetic Plastic Surgery (ASAPS) received FDA authorization to initiate a double-blind, placebo-controlled 46-week study to experimentally examine the safety and efficacy of Lipodissolve injections. The mixture is injected directly into the subcutaneous fat through multiple microinjections administered over multiple treatment sessions. The desired end result is the removal of localized fat deposits.

The injection of Lipodissolve for fat removal remains somewhat controversial. In statements to the New York Times and USA Today, the FDA has taken the position that the injection of Lipodissolve mixtures for fat removal is an example of “unapproved drugs for unapproved uses.”  Despite that, multiple businesses have initiated commercialization of Lipodissolve by opening clinics that advertise and administer Lipodissolve injections for fat removal ,. One of these businesses states on its website that "Pharmacies are permitted to compound drugs pursuant to a valid patient/physician/pharmacist relationship - even if the drugs have not been approved by the FDA." The FDA has stated that it is “investigating and evaluating” the situation.

Lipodissolve regulation in the state of Kansas
On August 18, 2007, the Kansas State Board of Healing Arts voted unanimously to ban all commercial use of Lipodissolve and to allow the use of the drug only as part of FDA-sanctioned clinical trials under an Investigational New Drug Application. “We have to protect the public from the potentially disastrous effects of unproven drugs,” said Mark Stafford, the board’s general counsel, who noted that Lipodissolve is not approved for treating fat by the Food and Drug Administration. Stafford also stated that the board had received at least half a dozen complaints about the procedure, including side effects such as nodules, infections and nausea.

On August 31, fig. a company that manages or operates 15 medical body shaping centers offering the Lipodissolve procedure, filed a petition for a temporary restraining order in Shawnee, Kansas to prevent the ban from going into effect. .Fig states on their public website "Pharmacies are permitted to compound drugs pursuant to a valid patient/physician/pharmacist relationship - even if the drugs have not been approved by the FDA." . FDA spokesperson Karen Riley told USA Today on September 10, 2007 that FDA maintains a different view and considers injection of compounded Lipodissolve mixtures for fat removal as "unapproved drugs for unapproved uses" and noted that FDA is "investigating and evaluating" the situation.

On September 10, 2007 at a special meeting the Kansas State Board moved to "replace its permanent Lipodissolve ban with a temporary ban to allow public comment on the move, which could still begin Friday", according to Mark Stafford, general counsel of the healing arts board.

On September 13, 2007, Shawnee County District Judge David Bruns blocked the State Board's ban stating that the board erred by approving the ban without enough public input.

Health Warnings
Three medical associations have issued health warnings cautioning against the use of injection lypolysis, including the American Society of Plastic Surgeons (ASPS), the American Society of Aesthetic Plastic Surgery (ASAPS), and the American Society of Dermatologic Surgery (ASDS).


 * ASPS Health Warning:
 * ASAPS Health Warning:
 * ASDS Health Warning:
 * ASAL Responds to ASAPS Warnings:

International Regulation: Lipodissolve banned in Brazil.   Promotion of Lipodissolve curtailed in England and Canada
ANVISA (Agencia Nacional de Vigilancia), the governmental body regulating the manufacture and commercialization of drugs in Brazil, banned the manufacture, use, and sale of injection lipolysis agents containing phosphatidylcholine on December 30, 2002. The ANVISA statement justified the ban by stating that such agents were not approved for the removal of subcutaneous fat, and that the long term effects this unapproved therapy were unknown. For an English translation of the ANVISA statement, see. Health Canada issued a similar warning in 2004, though the drug is still being injected by various medspas. The MHRA (Medicines and Healthcare Products Regulatory Agency), the governmental body regulating the manufacture and commercialization of drugs in the United Kingdom, issued a similar warning to physicians considering the use of these substances for cosmetic purposes. The MHRA stated that these drugs "are being unlawfully advertised in the UK as a cosmetic product for the reduction of fat." The MHRA also pointed out that considerable safety concerns remain due to the fact that these agents have not been tested in controlled clinical trials. While British physicians can still inject Lipodissolve for fat removal, the drug cannot be promoted as a drug for that purpose. As of July, 2005, The Medical Protection Society, the organization that provides British doctors with legal advice and coverage against litigation costs and damages, ceased offering malpractice insurance for use of Lipodissolve because of safety concerns.

FDA currently investigating the marketing and distribution of 'Lipodissolve'
In September 2007, FDA spokesperson Karen Riley told USA Today, the New York Times , and KVBC News (Las Vegas) that FDA views injection of compounded Lipodissolve mixtures for fat removal as "unapproved drugs for unapproved uses" and noted that FDA is "investigating and evaluating" the situation. In June 2007, the FDA stated to NPR  and the Washington Post  that the Agency is investigating organizations marketing and/or distributing Lipodissolve. In 2003, the FDA sent a warning letter to a physician engaged in the unlawful marketing and distribution of Lipodissolve. The June 22, 2003 letter orders the physician to "immediately cease marketing and distributing this product." The letter uses the term 'Lipostabil' rather than 'Lipodissolve,' but these terms refer to mixtures with the same compositions. The letter also reiterated FDA's position that the product in question is a "new drug" per section 210(ff)(2)(A)(i) of the Federal Food, Drug, and Cosmetic Act, in that the product in an injectable agent that "alters the structure or function of the body." Both the route of administration (i.e., injection) and the claim that the agent alters "structure or function of the body" (i.e., it removes fat) qualifies the product as a "new drug" under the Federal Food, Drug, and Cosmetic Act and thus requires that a New Drug Application (NDA; section 505(a) of the Act) be filed with the FDA prior to marketing.

==FDA OASIS (Operational and Administrative System for Import Support) Refuses Delivery of Compounded PCDC mixtures for fat removal—declares the mixture as a “New Drug” Requiring Filing of NDA Prior to Commercialization== On June 18, 2007, the FDA OASIS (Operational and Administrative System for Import Support, see ) posted to its public access website that the Agency had refused to allow the delivery of PCDC mixtures prepared at a US-based compounding pharmacy. On its website, the FDA stated that the two reasons for the “refusal” were as follows:

1. Reason: DRUG GMPS

Section: 501(a)(2)(B), 801(a)(3); ADULTERATION

Charge: It appears that the methods used in or the facilities or controls used for manufacture, processing, packing, or holding do not conform to or are not operated or administered in conformity with current good manufacturing.

2. Reason: UNAPPROVED. Section: 505(a), 801(a)(3); UNAPPROVED NEW DRUG

Charge: The article appears to be a new drug without an approved new drug application.