Laser Hair Removal Deaths

Student's Death Sparks Concerns About Compounded Preparations

[March 1, 2005, AJHP News]

BETHESDA, MD, 14 February 2005 — Pharmacy compounding came under the spotlight in North Carolina in January when a 22-year-old college student died after having an adverse reaction to a potent anesthetic gel prepared by a pharmacy and sold to a so-called medical spa, which resold the product to the patient without a prescription.

Shiri Berg had a seizure in her car on December 28, 2004, after applying a topical gel containing 10% lidocaine, 10% tetracaine, and an unknown amount of phenylephrine, said Gail Campbell, a nurse employed by Kirby & Holt, a Raleigh law firm founded by former Senator John Edwards.

The student, she said, lapsed into a coma and never regained consciousness before dying on January 5.

The law firm is investigating Berg's death on behalf of her family.

A February 2 autopsy report indicated that Berg died of anoxic brain injury due to lidocaine toxicity, said Kirby & Holt lawyer Laurie Armstrong.

She said Berg bought two 30-g tubes of the anesthetic gel on December 27, 2004, for $40 each from Premier Body, a medical spa in Raleigh where the student planned to have a laser hair removal procedure the next day.

Berg did not have a prescription for the compounded medication, Campbell said.

North Carolina forbids the resale of compounded formulations, even if a licensed physician, physician assistant, or nurse practitioner has a permit from the board of pharmacy to dispense prescription drugs. However, licensed health professionals in the state may obtain compounded preparations to administer in their offices to patients.

Neither Premier Body nor two physicians identified by the medical spa's attorney as past and current medical directors held a permit to dispense prescription drug products, said David R. Work, executive director of the North Carolina Board of Pharmacy, which is conducting a joint investigation with the state's medical board and FDA about the circumstances surrounding Berg's death.

Premier Body reportedly closed its operation on January 31.

The product sold to Berg, labeled as Lasergel Plus 10/10 Gel, was prepared by Triangle Compounding Pharmacy of Cary, North Carolina.

An attorney representing the pharmacy, David Duke of Young, Moore & Henderson in Raleigh, said his client is "cooperating 100%" with investigators.

Triangle Compounding reportedly ceased making the anesthetic gel until the board of pharmacy has completed its investigation.

Work said that investigators are examining whether the pharmacy was compounding within the scope of practice or illegally manufacturing products.

He said that investigators obtained a sample of Berg's gel to determine its potency and whether the ingredients were in fact those stated on the label. However, he said he could not comment on the board's findings during an ongoing investigation.

The preparation's label stated the three active ingredients, lot number, storage temperature, beyond-use date, and the pharmacy's name and address, Armstrong said, adding that the label clearly stated that the product was intended "for office use only."

Some states require pharmacies that sell compounded formulations to licensed health professionals to indicate on the label that a product is for administration to patients in the professional's place of practice only and not for resale. However, North Carolina does not require such a statement on a formulation's label, Work said.

Written information. Berg received no written patient information about the product, Armstrong said.

"Nothing was found in her car or at her residence that would indicate she got anything of that nature," she maintained.

Armstrong said her firm had received calls from other Premier Body clients claiming that they also had not received written patient information with the anesthetic gel they bought from the medical spa.

Triangle Compounding, Duke said, issues written product information with each formulation it sells.

Armstrong acknowledged that it was "possible that the compounding pharmacy provided Premier with some sort of insert" that came with the order for the compounded lidocaine preparation.

But, she added, compounding pharmacies may mistakenly assume that the written information gets passed on to patients.

Campbell questioned why Premier Body would sell patients a product that had 10% lidocaine.

Many medical spa Web sites suggest using a less potent product to numb skin before undergoing laser hair removal, such as Emla, AstraZeneca's topical anesthetic, which contains 2.5% lidocaine and 2.5% prilocaine.

Work noted that a study conducted by a pharmacy student completing an experiential rotation at the board of pharmacy found that most drug-related deaths in the state were due to commonly prescribed medications, including lidocaine, rather than drugs that are often abused, such as oxycodone or so-called "street drugs."

"But no one ever hears about those deaths from common drugs until it hits the media, as in [the Berg] case," he said.

Counseling. Armstrong said her firm found no indication in medical records that Berg had consulted with a physician or other licensed health care professional at the medical spa about use of the lidocaine preparation.

"There is no evidence that a [Premier Body] doctor saw her," Armstrong contended, adding that the other Premier Body clients who contacted the law firm also stated that no health care professional had counseled them about the use of the compounded medication or potential adverse effects.

Campbell said that a review of records also found no indication that Berg had been counseled by a pharmacist at Triangle Compounding or any other pharmacist.

She said she hoped Berg's death would generate more oversight of the dispensing of compounded formulations by the board of pharmacy.

Nonetheless, Armstrong added, compounding pharmacies need to be more aware of the types of organizations and health care providers that they take as clients.

She questioned whether pharmacies are doing enough to ensure, "for their own protection," that the health care professionals to whom they sell compounded formulations are properly administering the preparations in their offices and not reselling the products to patients and that patients are being counseled about use of the medications and warned about potential adverse effects.

Warning information. "There was no warning on the label," Campbell said about the compounded lidocaine gel that Berg bought.

Most states do not require pharmacies to include warnings and precautions for patients on the labels of compounded formulations.

Many states' compounding regulations call for only the preparation and beyond-use dates, lot number, and active ingredients on labels.

Iowa recently implemented requirements for labels on compounded formulations to include instructions for use and precautions to be observed.

North Carolina's Work said his board may consider adopting similar requirements for labels. However, he acknowledged that there has not been any official proposal to do so.

Without such warnings on the labels of compounded preparations, said Sarah L. Sellers, a former member of FDA's defunct advisory committee on pharmacy compounding, a medication's risks and benefits are not communicated to patients and their health care providers.

Plus, she added, a lack of warning information on the labels of compounded formulations prevents a prescriber, when administering a product in an office, from having the opportunity to fulfill his or her obligation of disclosing to a patient the potential risks associated with the use of the medication.

"Without warnings in the labeling, both docs and patients are assuming the risks while pharmacies are making the profits," Sellers said.

Premier Body's Web site and brochures indicate that laser hair removal is performed by nurses at the medical spa.

Kevin Prakke, a partner with Wyrick, Robbins, Yates & Ponton, the Raleigh law firm representing Premier Body, said he could not confirm whether a physician is present during all laser hair removal procedures. But, he said, the medical spa "does have a medical director and did have one at the time" of Berg's death.

He referred questions to Bob Clay at Patterson, Dilthy, Clay, & Bryson, a Raleigh firm representing the company that insures Premier Body. Calls to Clay were unreturned.

The medical board is mulling over whether it should consider laser hair removal procedures a practice of medicine.

The board plans to meet for three days in mid-March, at which time it could decide whether to regulate the procedure, said Dale Breaden, public affairs director for the board. However, he noted, a violation of practicing medicine without a license in North Carolina is a misdemeanor offense.

FDA's involvement. Although states govern the practice of pharmacy compounding, Sellers said she expects FDA to be more aggressive about investigating compounding pharmacies that violate state and federal regulations.

Indeed, the agency has issued several warning letters to compounding pharmacies within the past six months.

This past September, FDA warned a Mississippi compounding pharmacy for failing to have labeling on formulations that provided adequate directions for use, which, the agency maintained, constitutes the misbranding of drug products under Section 502 of the Food, Drug, and Cosmetic Act.

Regulators charged in a warning letter to Delta Pharma Inc., of Ripley, Mississippi, that the compounding pharmacy was running an operation that was "more consistent in size and production volume with a drug manufacturer."

On December 20, 2004, FDA warned RespiCare Group in Puerto Rico about labeling and manufacturing violations, calling the company's inhalation solutions misbranded and adulterated.

Also in December, the agency accused a Clearwater, Florida, compounding pharmacy, Lincare Inc., and its sister company, Reliant Pharmacy Services, of engaging in drug manufacturing.

"While FDA recognizes some pharmacists extemporaneously compound reasonable quantities of human drugs upon receipt of valid prescriptions for individual patients, your firm produces enormous amounts of what are essentially copies of commercially available drugs," the agency stated in its warning letter.

Regulating compounding. According to federal regulators, all compounded preparations could technically be considered under the law as unapproved new drugs because they differ from the approved formulation of the drug.

Literal application of the Food, Drug, and Cosmetic Act's sections 201(g), 501, 502, and 505, could mean that virtually all compounded drugs violate the law, said Steven K. Galson, acting director of FDA's Center for Drug Evaluation and Research, during his October 2003 testimony before the Senate Committee on Health, Education, Labor, and Pensions.

However, regulators have stated in testimony, warning letters, and court documents that FDA has exercised its enforcement discretion in allowing the legitimate preparation of compounded formulations, as regulated by state boards of pharmacy.

Galson noted that while federal officials defer to state boards of pharmacy in regulating compounding, the agency believes it has an important role to play in addressing dangerous practices.

Pharmacy compounding regulations vary widely from state to state.

While some states have clearly defined rules, others lack guidance about the practice of pharmacy compounding.

Randomized testing. Only one state, Missouri, has implemented a randomized testing program for compounded products.

Kevin Kinkade, executive director of Missouri's board of pharmacy, said that a preliminary review of data collected from late 2003 to fall 2004 found that 17 of 92 compounded formulations from 13 pharmacies were either subpotent or superpotent.

A test of a pharmacy's formulation of metronidazole suspension 100 mg/mL found that the preparation contained 135% of the active ingredient, he said.

But investigators detected no active ingredient in a formulation of progesterone 10 mg, Kinkade said.

Most of the products tested were either capsules or oral liquids, he noted.

Only one topical cream was tested for potency, he said.

Investigators examined three inhalation solutions and one ophthalmic preparation for sterility.

Missouri's board of pharmacy purchased all of the products that it tested, Kinkade said, spending $2,550.

The laboratory costs for testing the compounded formulations were substantially greater, at $27,500.

The board of pharmacy plans to issue a report within the year, Kinkade said.

Fred Richman, acting deputy director of FDA's Division of New Drugs and Labeling Compliance, said that the agency encourages states to conduct randomized testing of compounded drug preparations as part of the regulatory process.

Investigators examined three inhalation solutions and one ophthalmic preparation for sterility.

Missouri's board of pharmacy purchased all of the products that it tested, Kinkade said, spending $2,550.

The laboratory costs for testing the compounded formulations were substantially greater, at $27,500.

The board of pharmacy plans to issue a report within the year, Kinkade said.

Fred Richman, acting deputy director of FDA's Division of New Drugs and Labeling Compliance, said that the agency encourages states to conduct randomized testing of compounded drug preparations as part of the regulatory process.