Compounding pharmacies under fresh scrutiny amid meningitis outbreak
Published: Sunday, October 14, 2012 at 6:01 a.m.
Last Modified: Sunday, October 14, 2012 at 12:24 a.m.
Revelations that the national meningitis scare was caused by a Massachusetts drug compounder who shipped tainted steroids to doctors across the U.S. has a familiar ring to Ocala residents who watched a local compounding pharmacy dissolve under the weight of its costly and deadly mistakes in recent years.
By now, the Franck's Compounding Lab saga is well known: In 2009, the company incorrectly mixed a supplement that killed two dozen prized polo horses. Then last year, tainted ophthalmic solutions the company shipped to eye doctors blinded some patients, health officials said.
The mistakes made by Franck's raised fresh questions about why compounding pharmacies aren't subject to the same regulation and oversight as major pharmaceutical companies.
But at least one expert thinks the meningitis outbreak, which has afflicted nearly 200 people in 12 states and killed 15, could be the tipping point that finally brings about changes in the laws that govern the practice of compounding.
"I think this case, because the size of it and costs of human life, is certainly going to throw gasoline on the fire. It's going to take this debate from a two-alarm fire to a four-alarm fire," said Paul Doering, professor emeritus at the University of Florida School of Pharmacy.
Compounding pharmacies make medications and other medical preparations from scratch. They cannot make copies of commercially available medications and can only make medications when they are ordered by a doctor.
But the Food and Drug Administration, which is tasked with ensuring the safety of drugs in the nation, has limited oversight of compounding pharmacies because of the way the law establishing the agency was drawn up in the 1930s. Each state regulates compounders and pharmacists, but oversight and regulations differ from state to state.
Many compounders do what is known as "anticipatory compounding," preparing large quantities of drugs to fill future orders.
The contaminated steroid preparation at the heart of the meningitis outbreak, made by New England Compounding Center near Boston, was a run of more than 17,000 doses.
The FDA believes that producing drugs in large quantities constitutes manufacturing, which they are charged with regulating. The compounding industry argues size does not matter as long as the drugs or preparations are backed by doctors' prescriptions.
Doering thinks the Massachusetts firm crossed the line into manufacturing.
"The 17,000 doses had to be produced on an industrial scale," he said. "From all appearances, what they were doing, on such a large scale, I don't think that falls under the compounding label."
The FDA has advocated the regulation of large-volume compounders for years, but courts have struck down such attempts.
In 1997, Congress passed a law that, in part, tried to require large-volume compounders to get approval from the FDA for new drugs.
The law also restricted compounding pharmacies from advertising the compounding of any particular drug. The U.S. Supreme Court found that part of the law unconstitutional, saying it violated the protections of commercial speech.
Critics point to some very public compounding mistakes as proof that the practice needs to be regulated the same as pharmaceutical companies. Two of those mistakes occurred in Ocala.
After Franck's Compounding Lab incorrectly mixed a vitamin supplement that killed two dozen prized polo horses in 2009, the FDA sued to stop the lab from making any more veterinary compounds. The agency argued that Franck's was operating outside the limits of a compounding lab by producing compounds from bulk ingredients.
A federal judge in Ocala disagreed and ruled in favor of the lab.
While that case was focused on a single incident, the FDA's true goal, according to Jeffrey Gibbs, director of Washington law firm Hyman, Phelps & McNamara, was to try and get wider regulatory powers over compounders.
All compounding labs buy their ingredients in bulk to create compounds. Had the FDA prevailed, it would have abolished compounding as a separate practice from pharmaceutical manufacturing, Gibbs said.
"The FDA's essentially arguing that all compounding is illegal and is asserting its authority to regulate these businesses," Gibbs said in a June interview.
Then in May of this year, Franck's issued a recall of all its sterile products after ophthalmic preparations it made were found to be contaminated.
The preparations were injected directly into patients' eyes. Of the 33 people affected, most suffered vision loss and required additional eye surgery, according to a Centers for Disease Control and Prevention report.
In the wake of a continuing investigation, Franck's was sold in July to Wells Pharmacy Network, a Wellington-based company. Franck's Compounding Lab was one of the largest compounding labs in the country.
At the root of the issue is the historic role of compounding in pharmacology.
Compounding was the way most people got their prescription medicines for many generations. As recently as the 1960s pharmacists routinely ground and mixed compounds in their stores to make the medicines prescribed by local doctors. "Before, you'd give the pharmacist a piece of paper from your doctor. He'd look at it, scratch his head, go to the back, do some magic and he'd come back out with your dose," Doering said.
That started to change after pharmaceutical companies began producing drugs in volume. Eventually, the need for routine compounding mostly disappeared.
Today, compounding, in the historic sense, is a small part of the industry. Most pharmacy schools require students to spend less and less time compounding in a classroom setting.
"If you went to your average pharmacy and asked if they could compound, they would probably say they are not set up for it, but really the person behind the counter is probably not skilled enough to do it," Doering said.
He said most pharmacists interested in compounding take courses after graduation.But the recent boom in compounding is not an effort to return to bygone days of mixing medicines or preparations for a local clientele, but rather to join the growing number of high-volume compounders.
"Compounding, historically, is not something that happens in large volume," Doering said. "These compounding pharmacies, in a polite way, have developed a niche."
The danger, Doering says, is that quality control at compounding labs is not as stringent as at pharmaceutical companies.
The FDA illustrated this point in testimony before Congress in 2003.
"Concerns have been raised by the FDA and others that some pharmacies are going beyond traditional drug compounding for individual patients by, for example, compounding and selling large quantities of drugs without meeting safety and quality and other requirements for new manufactured drugs," said Janet Heinrich, then FDA director of health care and public health issues.
The agency re-emphasized the point in a report to Congress in 2007.
"Not all pharmacists have the same level of skills and equipment," wrote Rear Admiral Steven K. Galson, director of the Center for Drug Evaluation and Research at the FDA. "In some cases, compounders may lack sufficient controls (equipment, training, testing or facilities) to ensure product quality or to compound complex products such as sterile or modified release drugs. The quality of the drugs that these pharmacists compound is uncertain, and these drugs pose potential risks to the patients who take them."
David Miller, the executive vice president for the International Academy of Compounding Pharmacies, an advocacy group for the industry, disagrees.
"Size does not make you a manufacturer," Miller said. "The difference between a pharmacy and a manufacturer is, (the compounders) know about how much (they) need of a certain compound because (they) have had a history of prescriptions. Manufacturers produce their finished product first and then go out and persuade doctors to write prescriptions for them."