The 12 patients who died and the 137 patients sickened so far from a Massachusetts compounding pharmacy's fungus-infected steroid should put more than a few hospital executives on edge.
Many providers in recent years have grown to depend on these companies for some of their products.
But organizations impacted by this especially tragic story of medical harm shouldn't be surprised by it. There have been several eerily similar incidents over the years that should have been plenty of warning.
Ten years ago, a similar fungus contaminated the same injectable product, methylprednisolone acetate. It was also administered to patients to alleviate pain. And it caused the same acute meningitis as in the current outbreak. In the 2002 event, at least five patients were sickened and one died in North Carolina.
The December 2002 Morbidity and Mortality Weekly Report on the contaminated steroids said a South Carolina company referred to as compounding pharmacy "A," "had been supplying the compounded product to hospitals and pain management clinics in five states after a proprietary form of methylprednisolone acetate injectable suspension...became difficult to obtain from the manufacturer."
An investigation by the state's Board of Pharmacy "found improper performance of an autoclave with no written procedures for autoclave operation, no testing for sterility or appropriate checking of quality indicators, and inadequate clean-room practices as outlined in the American Society of Health-System Pharmacists (ASPH) guidance for pharmacy prepared sterile products."
History repeats itself
And earlier this year, federal charges were filed against an unaccredited Texas pharmacy for killing patients far away in Washington and Oregon with a gout treatment it shipped, called colchicine. Its potency levels were allegedly far stronger than appropriate.
"As we all start peeling back the layers of this onion, it turns out this has been an issue that any number of people have been quite aware of for some time," says Vanderbilt University Medical Center's William Schaffner, MD, past president of the National Foundation for Infectious Diseases. "It's just that nothing's been done about it. And it's not because harmful contamination issues have not occurred. They have."
Lawmakers and regulators, for whatever reasons, haven't wanted to tackle it, he says. Maybe it has been considered a state's rights issue, or maybe these compounding companies were seen as too small, or their operations too benign to cause much damage.
But here we have a major problem: Deaths and illness and panic in 10 states where 13,000 people have been exposed. Only now do the headlines say lawmakers are starting to take notice.
A patchwork of regulations
This scandal has exposed huge regulatory loopholes—a patchwork of widely varying state regulations, combined with unclear definitions for when a compounding pharmacy becomes a "manufacturer"—that have allowed these suppliers to escape U.S. Food and Drug Administration oversight.
Manufacturers do have to register with and meet requirements of the FDA, but compounding pharmacies do not, leaving unclear what propels a mere compounding pharmacy to manufacturer status.
The latest episode prompts Cynthia Reilly, of the American Society of Health System Pharmacists, to warn hospitals and other providers, "in most situations, you're really dealing with something that's 'buyer beware.'" Hospitals should now be working hard to check where their drug supplies are coming from because more hospitals are relying on these pharmacies for products.
"In the last decade, we do see more hospital pharmacies contracting out some of their services, maybe because particular products are hard to compound or [because they] may be high risk products, or because of drug shortages that's the only way to get them," Reilly says.
Her organization offers tools for providers to double-check their suppliers for certain quality criteria.
The 5% Rule
Hospitals and other purchasers looking to buy these supplies might go by one standard, Reilly says, which is that "if more than 5% of the product that they're making is for an undetermined patient—that is, it's not pursuant to a prescription that's either available or anticipated—then we suggest in those instances, if they're making more than 5% for an unknown patient, then they should be dealing with a manufacturer."
Hospital trade groups have been uncharacteristically quiet on this issue. Marie Watteau of the American Hospital Association responded to questions by e-mail saying that anecdotally, compounding pharmacies are not the first place to which hospitals turn when they need a drug. "But in a severe shortage, compounding pharmacies may be the only source for a drug their patients need."
Schaffner says that in addition to acquiring critical drugs during shortages, hospitals and doctors have reached out to compounding pharmacies because traditional source products often "contain preservatives that some physicians thought impaired the drug's function—like alcohol with a steroid might produce more root nerve irritation."
Additionally, some providers may not need the large quantities of some drugs that traditional suppliers require them to buy, he says.
Professional pharmacy organizations know something must be done, but they're not sure what. One possibility is greater emphasis on accreditation.
According to Joe Cabaleiro, executive director of the Pharmacy Compounding Accreditation Board, only 162 of the 5,000 to 7,500 compounding pharmacies in the nation meet their credentials. The pharmacy implicated in the current meningitis outbreak, the New England Compounding Center in Framingham, isn't one of them.
Need for tighter regulation is up for debate
If regulators severely tighten restrictions, "it could have a bad impact on the ability (of providers) to meet certain patients' needs when they're completely reliant on these compounded medications. Whatever regulation comes—and no doubt it appears that something is necessary—regulators cannot afford to completely eliminate compounding pharmacies. We just need to have something that draws the line between compounding and manufacturing."
David Miller, chief executive officer of the International Academy of Compounding Pharmacists, worries that those who cry for greater regulation may be overlooking the fact that existing laws would have prevented the current event if they had been followed.
"This pharmacy had been disciplined by the Massachusetts Board of Pharmacy. And in addition, the FDA has the statutory authority to inspect any pharmacy at any time," Miller says.
Except that in this case, the laws and regulations didn't work because apparently, the discipline didn't prevent this from happening,
In the time it took me to write this column, the death toll increased by from 11 to 12, the number of people infected from 119 to 137, and the number of people who may have been exposed is now at 13,000 in 10 states.
I note that in the 2002 MMWR report, federal disease investigators cautioned: "Some health system pharmacists might not realize that they are purchasing injectables prepared through compounding." The agency urged purchasers to check that "supplies are provided through a compounding pharmacy that is licensed in their state and that follows appropriate measures."
And there was this line: "In most states, compounding pharmacies are not required to report adverse events associated with their products to state or federal agencies," however, reporting to the FDA is required for "manufacturing companies."
Even though the unused steroid products are being recalled, it's obvious to me that the issue has legs this time, even if last time it was quickly forgotten. Lawmakers and regulators will have to step in. I think they should give the FDA authority to take a much greater role to prevent this from happening again.
Vanderbilt's Schaffner put it a different way: "I think we're going to have to rub the Congress's nose in this, because this is not the sort of thing it likes to get into."