The rising toll — 7 dead, 57 ill and thousands
potentially exposed — has cast a harsh light on the loose regulations that legal
experts say allowed a company to sell 17,676 vials of an unsafe drug to pain
clinics in 23 states. Federal health officials said Friday that all patients
injected with the steroid drug made by that company, the New England Compounding
Center in Framingham, Mass., which has a troubled history, needed to be tracked
down immediately and informed of the danger.
“This wasn’t some obscure procedure being done in some
obscure hospital,” said Tom Carroll, a close friend to the Lovelace family, and
their lawyer. “They had sought out a respected neurosurgeon who had been
referred by their
family
doctor, at a respected hospital,” he said, referring to the St. Thomas
Outpatient Neurosurgery Center. “How does this happen?”
The answer, at least in part, is that some doctors and
clinics have turned away from major drug manufacturers and have taken their
business to so-called compounding pharmacies, like New England Compounding,
which mix up batches of drugs on their own, often for much lower prices than
major manufacturers charge — and with little of the federal oversight of drug
safety and quality that is routine for the big companies.
“The
Food and Drug Administration has more regulatory
authority over a drug factory in China than over a compounding pharmacy in
Massachusetts,” said Kevin Outterson, an associate professor of law at Boston
University.
The outbreak has also brought new scrutiny to the
widely used procedure that Judge Lovelace and millions of Americans undergo each
year.
Patients most likely assumed there was strong evidence
that the procedure itself works. But the Cochrane Collaboration, an
international group of medical experts,
reviewed
the data last year and found there was “no strong evidence for or against”
the injections. Patients exposed to the drug in the current outbreak may have
risked their health or even their lives for an elusive goal.
A Large Demand
Over the past two decades, pain control has become a
growth industry, bolstered by the worn-out knees and aching backs of baby
boomers. Pain clinics began popping up around the country.
Starting in the 1990s, spinal injections for back
pain, known as lumbar epidural steroid injections, skyrocketed. They have since
leveled off, but the number remains high. In 2011, 2.5 million
Medicare
recipients had the injections, as did an equal number of younger people,
according to Dr. Ray Baker, president of the International Spine Intervention
Society.
Many people seek them in hopes of avoiding surgery.
The injections combine a steroid and a numbing drug in an effort to soothe
inflamed and irritated nerves. Patients are told they may get weeks, months or
even a year of relief.
The injections created a demand for steroids,
including
methylprednisolone
acetate, the drug that New England Compounding was making.
To be sure, many compounding pharmacies perform well,
producing formulations of drugs for specialized needs. Compounders have also
provided hospitals and doctors with cheaper alternatives to F.D.A.-approved
drugs.
For example, they are providing a far cheaper
alternative to a drug called
Makena, a new brand name version of an old
drug used to reduce the risk of premature births. Once the drug got F.D.A.
approval, the manufacturer of Makena began charging about a hundred times more
for the drug than compounders. Officials from the F.D.A. wanted to ban the
pharmacy-made versions on the grounds that Makena had met the agency’s rigorous
safety standards, but senior Obama administration officials, concerned about
Makena’s much higher price, stepped in to halt the ban.
In recent years, compounding pharmacies have sometimes
filled gaps left by shortages of drugs made by pharmaceutical companies.
“As drug shortages have become more complex and
common, pharmacies are turning to external compounding companies to help them,”
said Cynthia Reilly, of the
American Society of Health-System Pharmacists,
referring to hospital pharmacies.
Shortages may have played a role in the large
purchases of the injectable steroid now under suspicion from New England
Compounding. The two manufacturers of the generic version of the drug had
stopped making it.
Teva halted production in
2010 when it temporarily closed its Irvine, Calif., factory after receiving a
warning letter from the F.D.A. about manufacturing quality problems.
The other manufacturer,
Sandoz, stopped selling the product in the
United States this year, according to the company, which would not provide a
reason. Sandoz has also been reprimanded by the F.D.A. for manufacturing
problems.
While the F.D.A. says the drug is not in short supply,
the brand name product still available may have been considered too expensive,
prompting some medical practices to turn to compounding pharmacists.
PainCare, a medical practice with 12 locations
in New Hampshire, turned to New England Compounding for the injectable steroid
now under suspicion when its usual supplier ran out, said the company’s chief
executive, Dr. Michael J. O’Connell. The company’s two main locations alone do
more than 100 injections a week.
Dr. O’Connell said he preferred compounding pharmacies
because they could make the drug free of an alcohol often used as a preservative
in drugs manufactured by big companies that he worried could damage nerves.
In addition, Medicare and many private insurers
reimburse a fixed amount for the injections, about $300, giving doctors a
financial incentive to prefer the less costly compounded versions, he said. “If
you are using a more expensive product, there would be less left over,” Dr.
O’Connell said.
PainCare paid New England Compounding $25 for a vial
containing five 80-milligram doses, he said. A similar vial of the
Depo-Medrol
by Pfizer, with the alcohol preservative, costs about $40 to $46, according to
the Web site of
Clint
Pharmaceuticals, a distributor.
About 186 of PainCare’s patients were injected with
the suspect product. About two dozen have had symptoms that could indicate
meningitis and have come in for spinal taps. The lab results are not back, Dr.
O’Connell said, but the fluid samples were clear, rather than cloudy, as they
would be if infected by a fungus.
Questions of Origins
Some physicians who work in big hospitals may not even
know whether the drug they use is from a compounder.
Dr. Anders Cohen, the chief of
neurosurgery
and spine surgery at the
Brooklyn Hospital Center, said: “We ask for the
medication, it’s in stock, we use it. I don’t know if it’s coming from A, B or
C. This is kind of a wake-up call about where your stuff is coming from.”
Because of the outbreak, Dr. Cohen has stopped
performing spinal injections for now, and he was planning to declare a
moratorium on them at his hospital until he was certain all the medicine was
clean, even though his hospital is not on the
list of
facilities that received the potentially contaminated drug.
The size of New England Compounding appears to have
reassured some doctors, who thought dealing with a large company might be safer
than buying from a mom-and-pop compounder.
One pain specialist said he had heard from colleagues
that the company had a good reputation and that even prestigious hospitals had
used it. His practice did not buy the steroid medicine from New England
Compounding but a contrast agent, a type of dye used for imaging. After he first
contacted the Massachusetts company, it flew in a sales representative to meet
him.
“We were impressed,” said the doctor, who spoke on the
condition of anonymity because he had not yet consulted his malpractice insurer
about whether he should publicly identify himself as having bought products from
New England Compounding. “It seemed like big time.” The representative “assured
me that all standards are being met.”
But all the dye the doctor bought from New England
Compounding has had to be thrown out on the chance that it also might be
contaminated, he said.
And the Massachusetts company itself has a troubled
past. A series of complaints had been lodged against New England Compounding
over the past decade. The State Health Department inspected in 2006. According
to a warning letter sent by the F.D.A. from that year, the company was accused
of illegally producing a standardized anesthetic topical cream, inappropriately
repackaging a drug, and telling doctors that using an office staff member’s name
was enough to put in an order, even though rules require a prescription for a
particular patient.
Issues of Law
Meningitis can be caused by viruses, bacteria or
fungi. Doctors say that the fungal type is the hardest to treat and devastating
to patients because it can cause strokes. And indeed, some of the patients in
the current outbreak have suffered strokes.
Federal inspectors last week removed samples of the
suspect drug from New England Compounding to test for fungal contamination. The
center, which takes in about $2.2 million a year, according to its corporate
filings, is housed in a two-story brick building.
The company’s offices in suburban Boston were locked
Friday, with a “no soliciting” sign on the door. The company did not respond to
repeated requests for comment last week. Before it went offline, the company’s
Web site said New England Compounding was licensed in all 50 states. State and
federal officials said it had shipped out a prodigious amount of the potentially
contaminated medicine to 75 pain clinics in 23 states.
Traditionally, the law meant compounding to be a local
service in which pharmacists could tailor-make
prescriptions
for patients with special needs. Compounding pharmacies were not supposed to
become miniature drug companies.
It is not clear how much large-scale compounding
actually goes on. David G. Miller, executive vice president of the
International Academy
of Compounding Pharmacists, estimated that large-scale compounders
represented about 10 percent of all compounding pharmacies, but he could not say
what percentage of compounded medicines they made.
As state and federal authorities pored over
information about New England Compounding last week, there was little agreement
among experts on whether the company broke the law by making products in bulk
and shipping them around the country.
Compounding falls in a legal no man’s land, between
the federal government and the states. The F.D.A. regulates manufacturers, but
compounders register as pharmacies, putting them under a patchwork of state
rules. The F.D.A. did develop a clear set of rules for compounding, but
subsequent litigation that culminated in a Supreme Court decision in 2002 struck
them down, and Congress never re-established the agency’s clear authority,
Professor Outterson said.
Jeff Gibbs, a lawyer in Washington who has represented
compounders and drug companies, said it was unusual for a compounding pharmacy
to produce large quantities of a drug that is commercially available. Policies
of the F.D.A. were more concerned about compounders’ making drugs that are
already approved and on the market, and not so much about compounders’ producing
large volumes of medicine, he said.
But Sheldon T. Bradshaw, a lawyer in Washington who
was chief counsel for the F.D.A. from 2005 to 2007, said large-scale compounders
often behave like manufacturers, complete with sales teams that market their
products to doctors. And they do not have to abide by the F.D.A.’s regulations,
which require that problems with products be reported to the agency. In effect,
he said, the companies are circumventing the regulatory process.
He contended that the F.D.A. could invoke the
Food,
Drug and Cosmetic Act of 1938, which makes it a criminal act “to introduce
into interstate commerce an unapproved drug.” That is what New England
Compounding’s products would most likely be considered because the company was
doing more than traditional compounding, yet had not obtained a new drug
approval, something that large drug makers spend millions of dollars and years
to get. He said the agency has often sent letters to producers telling them to
stop, and they usually comply, knowing there might be criminal charges if they
do not.
“Some of these companies are just setting up big
manufacturing shops in the guise of traditional compounding and making drugs
that are, for the most part, commercially available,” Mr. Bradshaw said.
“Instead of making fake Rolexes, they are making fake drugs.”
Jess Bidgood and Sheelagh McNeill contributed
reporting.
