NEW YORK (AP) — Was it some moldy ceiling tiles? The dusty shoes of a
careless employee? Or did the contamination ride in on one of the
ingredients?
There are lots of ways fungus could have gotten
inside the Massachusetts compounding pharmacy whose steroid medication
has been linked to a lethal outbreak of a rare fungal form of
meningitis.
The outbreak has killed at least 15 people and
sickened more than 200 others in 15 states. Nearly all the victims had
received steroid injections for back pain.
Federal and state
investigators have been tightlipped about any problems they may have
seen at the New England Compounding Center or whether they have
pinpointed the source of the contamination. They did disclose last week
that they found fungus in more than 50 vials from the pharmacy.
Company
spokesman Andrew Paven said by email that criminal investigators from
the Food and Drug Administration were at the pharmacy in Framingham,
Mass., on Tuesday. The visit was part of a broad federal and state
investigation of the outbreak, FDA spokesman Steven Immergut said in an
email.
New England Compounding has not commented on its production
process or what might have gone wrong, so outside experts can only
speculate. But the betting money seems to be on dirty conditions, faulty
sterilizing equipment, tainted ingredients or sloppiness on the part of
employees.
The drug at the center of the investigation is made
without preservative, meaning there's no alcohol or other solution in it
to kill germs such as a fungus. So it's very important that it be made
under highly sterile conditions, experts said.
Compounding
pharmacies aren't as tightly regulated as drug company plants, but they
are supposed to follow certain rules: Clean the floors and other
surfaces daily; monitor air in "clean rooms" where drugs are made;
require employees to wear gloves and gowns; test samples from each lot.
The
rules are in the U.S. Pharmacopeia, a kind of national standards book
for compounding medicines that's written by a nonprofit scientific
organization. Most inspections, though, are handled by state boards of
pharmacy. Massachusetts last inspected New England Compounding in March
in response to a complaint unrelated to the outbreak; the results have
not been released.
High-volume production of the sort that went on
at New England Compounding also raises the chances of contamination,
experts said.
Traditionally, compounding pharmacies fill special
orders placed by doctors for individual patients, turning out maybe five
or six vials. But many medical practices and hospitals place large
orders to have the medicines on hand for their patients. That's allowed
in at least 40 states but not under Massachusetts regulations.
Last
month, New England Compounding recalled three lots of steroids made
since May that totaled 17,676 single-dose vials of medicine — roughly
equivalent to 20 gallons.
"I don't see it as appropriate for a
community pharmacy to do a batch of something preservative-free in
numbers in the thousands" of doses, said Lou Diorio, a New Jersey-based
consultant to compounding pharmacies. Diorio, who has no connection to
the investigation or the company, said it is harder to keep everything
sterile when working with large amounts.
To make the steroid, a
chemical powder from a supplier is mixed with a liquid, sterilized
through heating, then pumped into vials, according to Eric Kastango,
another consultant from New Jersey who helps compounding pharmacies deal
with contamination problems. He is not connected to the company either.
Perhaps
the powder was contaminated, either at New England Compounding or
another location. Maybe the fungus was in the liquid, some experts said.
Kastango
offered additional possible scenarios, related to the large volume
produced: Making thousands of doses at a time can take many hours or
days. It's possible that a batch could sit for hours or even a day or so
before being placed in vials, making it vulnerable to contamination, he
said.
It's also likely a pharmacy worker would take a break to
get a snack or cup of coffee, to go to the bathroom or to step outside
for a smoke, Kastango explained. If the person hurried back and didn't
properly wash up or put on new gowns, masks and other safety garb, that
could introduce contamination.
Faulty or misused sterilizing
equipment is also a possibility. After a 2002 fungal meningitis outbreak
linked to a South Carolina compounding pharmacy, investigators
discovered that a piece of sterilizing equipment called an autoclave had
been improperly used by the staff.
The types of fungus in the
latest outbreak are ubiquitous: The first to be identified was
Aspergillus, commonly found indoors and outdoors. As more testing of
patients was completed, it became clear that another fungus — a black
mold called Exserohilum — caused most of the illnesses. Exserohilum is
common in dirt and grasses.
Most people do not get sick from
ordinary exposure to these kinds of fungus, but spinal injections can
provide them a pathway into the brain. Doctors are generally leery of
using spinal steroid injections that contain preservatives because of
fears the preservatives themselves can cause side effects.
Whatever happened at New England Compounding, it probably wasn't unique.
Just
last year, there were at least three apparently similar incidents: At
least 33 patients suffered fungal eye infections traced to products made
by a compounding pharmacy in Ocala, Fla.; at least a dozen Florida
patients were blinded or damaged in an outbreak linked to a compounder
in Hollywood, Fla.; and the deaths of nine Alabama patients were
attributed to tainted intravenous nutritional supplement provided by a
compounder in Birmingham.
"These events have been happening once
or twice a year for the last 15 years," Kastango said. "We wouldn't
tolerate this if a plane crashed once or twice a year. But in health
care, we've grown desensitized to these kinds of problems."