State inspections found lacking for pharmacies
Published: Sunday, December 22, 2013 at 6:01 a.m.
Last Modified: Saturday, December 21, 2013 at 6:29 p.m.
The deaths of 64 people injected with contaminated drugs created by the New England Compounding Center last year drew wide public attention because of the scale of the tragedy and the mistakes uncovered after the fact, but the incident was by no means isolated.
In 2007, three people died after being injected with a compounded drug made in a Texas pharmacy. Inspectors discovered that drugs were six times as potent as the labels indicated. Tougher state oversight would have prevented the deaths, critics say.
In 2005, a compounded medicine produced by a Maryland pharmacy for use in open-heart surgery caused severe infections and three deaths. Afterward, inspectors determined the drugs were contaminated.
In 2002, two died after being injected with tainted steroids produced by a South Carolina pharmacy. After the fact, South Carolina inspectors found the pharmacy unsanitary and its sterilization practices falling abysmally short.
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A year before the NECC deaths, nine people died when they received contaminated intravenous solutions from an Alabama pharmacy. The contaminating bacteria were typically found in water and sometimes bathrooms. Investigators after the fact found the same kind of bacteria at the pharmacy, including at a faucet that dispensed tap water.
In 2012, Franck's Compounding Lab in Ocala made sterile compounds it shipped to doctors in seven states for use during eye surgeries. The drugs were contaminated with mold. Thirty-three people lost some of their sight or needed additional surgeries to try and fix what the infections destroyed.
The common theme among these episodes was that, while investigations of the deadly mishaps revealed unsanitary or unsterile conditions, each compounding pharmacy had passed inspection by its state pharmacy board prior to the mishaps.
Florida Board of Pharmacy inspectors had visited Franck's before the incident, for example, and given it passing marks.
After the incident, federal inspectors found extensive sterility problems at the business. The Florida Department of Health, which oversees the pharmacy board, refused to release information about the issue to the Star-Banner, claiming it would violate privacy rules. It was Franck's second serious violation in three years.
State health officials would not say why their inspectors missed violations that federal inspectors later found.
And that, critics say, is the root of so many of the mistakes made by compounding pharmacies nationwide: State pharmacy regulators in Florida and elsewhere have long lacked the expertise, training and tools to do proper inspections of compounders who produce drugs from scratch and in large quantities.
Paul Doering, professor emeritus at the University of Florida School of Pharmacy and one of the leading pharmacy experts in the state, claims flatly that Florida and other states are simply not up to the task of ensuring the safety of compounded medications.
"NECC was the wake-up call ... and now the (Florida) Board of Pharmacy is being asked to do something at a level it's never been asked to do before," he said. "The states haven't done a very good job, don't have the technical know-how, the resources, and frankly, I don't think they have the motivation to do it."
A study by the U.S. House of Representatives this year reported that no state pharmacy board required its pharmacies to disclose how many sterile compounded drugs they made or how much they shipped to other states; 37 states didn't even require pharmacies to report whether they made sterile compounds.
The study found that almost half of state pharmacy boards did not even maintain inspection records well enough to identify which pharmacies had repeated violations.
After the NECC debacle, some states, including Florida, began taking a look at what their drug-making pharmacies were doing.
The picture wasn't pretty.
Nearly one in every five Florida pharmacies making sterile compounds had serious violations.
It was the first time Florida Board of Pharmacy inspectors even created a separate databank for pharmacies making riskier sterile products. Before that, inspectors treated neighborhood pharmacies and compounders the same.
The Florida Board of Pharmacy's inspection form was a single, one-side sheet of paper. Until 2012, inspectors used the same inspection forms for non-compounding pharmacies as they did for pharmacies making complex, sterile compounds.
But it wasn't just the paperwork. Pharmacy owners say the inspections themselves were cursory.
Sam Pratt, owner of Altamonte Springs Pharmacy Specialists, said before NECC, inspectors did little more than show up "and ask how are you doing today and then leave. Before (NECC), an inspection was a joke."
Pratt also said inspections rarely took more than two hours.
Pratt isn't alone. Other pharmacists, who asked not to be named, said Florida pharmacy inspectors sometimes didn't even open their inspection logs. One said the inspector talked about sports most of the time.
Another problem is that Florida has never performed random sampling of sterile compounded drugs. Two studies by the U.S. Food and Drug Administration suggest Florida compounded drugs may not be as safe as people think.
About a third of the compounded drug samples taken from various pharmacies across the country and studied by the FDA failed potency tests.
In Missouri, when a pharmacist pleaded guilty to watering down chemotherapy drugs, the state's pharmacy board in 2008 began sampling compounded drugs (in that state). One in four failed potency tests. In 2010, 15 percent failed.
Michele Weizer, a Florida Board of Pharmacy member, acknowledged that some of the oversight problems were the state's fault.
"Another part of our failure was we didn't enforce our rules," she said.
A Florida pharmacy inspector said so much of the information inspectors gather depends upon the honesty of the pharmacies.
"If they wanted to get it by me, I might not catch it," said inspector John Taylor.
And even if inspectors did enforce the rules strictly, Weizer said during a pharmacy board meeting this summer, they couldn't assure that the compounds created by pharmacies outside Florida were safe when they were shipped here.
"The problem we're having still exists," she said.
A fragmented approach
Howard Sklamberg, director of the FDA's office of compliance, said that pharmacy problems leading up to the NECC debacle were not surprising. They were bound to happen as pharmacies made more complex sterile compounds vulnerable to contamination, made them in bulk and shipped them across state lines.
Sklamberg said a significant problem is that the compounding industry is overseen by 50 state pharmacy boards, each with different compounding rules and no coordination or universal oversight.
Those pharmacy boards were never designed to regulate businesses making the kinds of complex sterile drugs they do now. Nor were pharmacy boards ever meant to regulate pharmacies that make large volumes of sterile compounds, sometimes in the thousands of doses, he said.
"States do not have the expertise and resources to inspect" (sterile compounding pharmacies)," he said.
Congress reached a similar conclusion in a study this year. The study revealed that 37 of the nation's 50 pharmacy boards failed to inspect all of their pharmacies during the previous 12 months. Some failed to even track the number of their inspections, and many failed to keep track of out-of-state pharmacies doing business in their states.
And, like Florida, most did not know until recently which pharmacies even compounded drugs, much less made complex, risky sterile compounds.
Ken Baker, an Arizona pharmacy lawyer and former executive at Pharmacists Mutual Companies, a company that insures pharmacies, said the sheer volume of drugs being compounded without strict oversight poses a problem.
"The larger your scale, the better (chance) you're going to have a good mixture," he said. "But if you make a mistake, you have 1,000 patients injured, not one, two or three."
There is no shortage of pharmacies making sterile drugs.
Among the 8,000 pharmacies in Florida, 946 reported producing sterile drugs. About a third of those are out-of-state pharmacies that are also licensed here in Florida but follow their own state production rules.
Of Florida's pharmacies, 314 reported that they produce sterile compounds in bulk and 95 say they make sterile drugs in bulk to sell to doctor's offices and other health care facilities.
What is driving the surge in compounding pharmacies is money.
Pratt, the owner of Altamonte Springs Pharmacy Specialists, said doctors contribute to the problem by pushing for lower prices and are willing to go to compounding pharmacists offering the lowest prices without regard for the safety of the items being produced.
"We have doctors come and doctors go because we're too expensive on some things," Pratt said.
One of Pratt's pharmacists, Terry Isler, considered making the same compounded steroid drug NECC made before the deaths but could not make it for anywhere near the price NECC charged.
Chris Schulte is the owner of Pensacola Apothecary compounding pharmacy. He is a member of the board of International Academy of Compounding Pharmacists.
Schulte said he had the same problem making sterile drugs at prices that could compete with other pharmacies that cut corners or did shoddy work.
"I lost several accounts in this area" when NECC offered the steroid "at roughly half the price." Schulte said.
Schulte said it was common for doctor's offices to ask for compounded, sterile drugs only to complain about the price and then buy it from pharmacies at cut-rate prices. Between 20 percent and 25 percent of Apothecary's prescriptions are for sterile compounds, but those prescriptions account for only about 2 percent of its revenue.
The pharmacy is accredited by the Pharmacy Compounding Accreditation Board. The organization also created the U.S. Pharmacopeia Standards for sterile compounded products referred to as USP 797.
Only about 2 percent of pharmacies are accredited by the board, and Schulte said they are at a competitive disadvantage against pharmacies that cut corners for profits. In addition, pharmacies following accreditation procedures have seen their costs to make safer drugs rise considerably, he said.
"It's hard to compete against non-accredited labs," he said.
Brian Kahan, a Boca Raton lawyer representing about 100 pharmacies, defends compounding as a necessary service. The need for customized, compounded medicines grew because patients wanted and needed them, he said.
Kahan said he thinks that one of the reasons companies like NECC grew wasn't because regulators allowed them to produce drugs unchecked but because they filled a niche when FDA-regulated manufacturers stopped making unprofitable drugs.
Pratt and Isler disagree. They said that about the time NECC was making its contaminated steroid batches, the steroid was readily available through FDA manufacturers.
Dr. Allan Vrable, who owns 13 pain clinics in North Florida, said he never ordered drugs from NECC and found all he needed for his pain clinics through commercial manufacturers.
"We don't use compounded drugs for injectables," Vrable said. "Without that (FDA) level of security, I wasn't comfortable with (compounded) injectables in the spine," he said.
Kahan said state regulators should not be judged too harshly.
"I would be very reluctant to condemn the process as it exists today," he said. "Regulation by its very nature is a compromise between a perfect system ... and a system with real people with real budgets with real limitations of time," he said.
But Kahan admits that the process had cracks.
"It became evident that while pharmacies were routinely inspected, there wasn't a specific focus on compounding pharmacies," he said. "For example, the (state) investigative services had a computer-generated evaluation inspection form that was on one sheet of paper."
The same inspection form was used for both compounding pharmacies and those that did not compound.
Kahan said the NECC problem might have been caught by Florida inspectors.
"Because that happened doesn't necessarily indicate that Florida's current system would have made the same errors in identifying such a substantial error in (compound drug) production," he said. "There are people who want to cut corners, but that is not reflective of a whole industry."
Schulte said he thinks that the problems that led to NECC and the 64 deaths aren't such an isolated incident. Much of the process and regulatory infrastructure that saw it happen is still in place.
Asked about the potential for a disaster like NECC in Florida, Schulte said only, "I wish I could say no," and shrugged.
Contact Fred Hiers at 867-4157 or firstname.lastname@example.org.
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