Nov. 2, 2012 -- Safety steps taken in the wake of the fungal meningitis outbreak have worsened drug shortages, raising questions about whether the U.S. must choose between the safety and the availability of crucial medicines.
Ameridose -- the sister firm of the NECC, the compounding pharmacy whose tainted products are at the heart of the outbreak -- has shut down, and at the FDA's urging recalled the more than 2,000 products it sold nationwide. The FDA yesterday admitted that these actions will worsen the ongoing shortage of six important drugs hospitals need to help critically ill patients.
Currently, 226 drugs are in short supply. Last year, 99% of U.S. hospitals reported drug shortages. And these are important drugs, says Joseph Hill, director of federal legislative affairs for the American Society of Health-System Pharmacists.
"In the last five years we have seen a significant spike in the number and severity of shortages," Hill says. "It is really alarming when you look at the classes of drugs involved: cancer drugs, heart drugs, pain drugs, and anesthetics. Imagine not being able to perform an emergency surgery."
Compounding pharmacies do not make most of the drugs that are in shortage. But they make an increasing number of them, says David Miller, RPh, CEO of the International Academy of Compounding Pharmacists (IACP).
"What we have seen is on a large scale, important drugs being in shortage -- and not for short periods, but in the months-to-years range," Miller says. "Compounding pharmacies help with that. Now, instead of filling short-term needs, compounding pharmacies are being looked to on a larger scale."
How many compounding pharmacies are doing this? The FDA does not know.
"We do not have this data," says FDA public information officer Sarah Clark-Lynn via email.
"It is important to note that compounded drugs can serve an important public health need if a patient has a particular medical need that cannot be met with an FDA-approved drug," Clark-Lynn says. "Compounded drugs that are prepared improperly pose potential health risks to the patients who take them. When such compounding occurs on a large scale, more patients are exposed to those risks."
Compounding Pharmacy Safety
It's impossible for a hospital running out of crucial drugs to know if a compounder is safe, says Michael Cohen, RPh, president of the Institute for Safe Medication Practices (ISMP).
"I cannot to this day clearly see anything that articulates what pharmacies are provided with the oversight to ensure that they're making these drugs safely and what pharmacies are not," Cohen testified before the FDA's September 2011 workshop on drug shortages.
A full year before the fungal meningitis outbreak, Cohen warned the panel that unsterile drugs made by compounders already had caused infections and deaths -- and that the oversight needed to prevent future disasters was "not happening."
Allen J. Vaida, PharmD, executive vice president of the ISMP, notes that compounding pharmacies are regulated by state boards of pharmacy. Those that also register as drug manufacturers, like Ameridose, are regulated by the FDA and, if they make controlled substances, by the Drug Enforcement Administration (DEA).
Many state boards of pharmacy require compounders to adhere to strict standards set by the U.S. Pharmacopeial Convention, a nonprofit scientific organization. But some do not, and states vary in how well they enforce these standards.
"With the advent of some of these compounding pharmacies getting more into the manufacturing realm -- actually making batches of pharmaceuticals, not specific patient prescriptions as is their traditional role -- they have more or less fallen through the cracks," Vaida says. "Issues now coming to light suggest there may not have been enough oversight. State boards are not equipped to do it, and the FDA is not equipped to do it on a mass basis."
Are New Laws Needed?
Drug shortages happen for many reasons. More than half occur when something goes wrong during commercial drug manufacture.
"When you're talking about a drug being sterile, you have to be 100% right, not 99% right," says Hill. "So manufacturers, if they identify a problem, they shut down the production line. And depending on how much of a drug they make, or if they are the only supplier, there is a shortage."
Drugmakers haven't always been quick to tell the FDA about such problems. That changed in October 2011, when President Obama issued an executive order requiring companies to immediately report production issues involving life-supporting drugs to the FDA.
With this kind of head start, the FDA can help relieve shortages by looking for other manufacturers who can make the drug. Or it can speed pending approvals for companies that already have asked to make the drug. In a news release, FDA Commissioner Margaret Hamburg, MD, says the FDA already has prevented 145 drug shortages this year.
Moreover, the July 2012 Food and Drug Administration Safety and Innovation Act established user fees for generic drugmakers that will allow the FDA to speed the approval process. It also expands the FDA's authority to inspect drug-making facilities.
But new legislation proposed by Rep. Edward Markey (D-Mass.) would vastly restrict what compounding pharmacies can manufacture and greatly increase FDA oversight.
Vaida says he's not sure additional legislation is needed.
"We haven't followed through or monitored compounding pharmacies as well as we could," he says. "Something has to come out of this [fungal meningitis outbreak]. Compounding pharmacies are going to have to be inspected, either by state boards -- given better resources and insisting on stricter requirements they have to follow -- or by the FDA if they are into drug manufacturing."
David Ball, a spokesman for the IACP trade group, agrees that changes are on the way.
"What the compounding profession hopes for is that whatever changes occur don't disrupt the legitimate care provided to patients," he says. "The hope is that compounders continue to be available to provide these services. ... What we want to see is that organizations operating outside their license, that are manufacturing drugs without a permit to do so, are dealt with. We want to make sure people in the profession are in compliance with the law."
Meanwhile, the toll from the fungal meningitis outbreak continues to mount. As of Nov. 2, the tainted drugs have caused 395 cases of fungal meningitis and nine cases of fungal joint infections. The injections have killed 29 of these people.